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Sample records for brain tumour model

  1. A reproducible brain tumour model established from human glioblastoma biopsies

    International Nuclear Information System (INIS)

    Wang, Jian; Chekenya, Martha; Bjerkvig, Rolf; Enger, Per Ø; Miletic, Hrvoje; Sakariassen, Per Ø; Huszthy, Peter C; Jacobsen, Hege; Brekkå, Narve; Li, Xingang; Zhao, Peng; Mørk, Sverre

    2009-01-01

    Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression

  2. A reproducible brain tumour model established from human glioblastoma biopsies

    Directory of Open Access Journals (Sweden)

    Li Xingang

    2009-12-01

    Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

  3. of brain tumours

    African Journals Online (AJOL)

    outline of the important clinical issues related to brain tumours and psychiatry. ... Left-sided, frontal tumours also seem to be associated with higher rates of depression, while those in the frontal lobe of the right .... Oxford: Blackwell Science,.

  4. Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture

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    Maria Angeles Marques-Torrejon

    2018-02-01

    Full Text Available Glioblastoma multiforme (GBM is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as glioma stem cells (GSCs. Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human. Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring live cell behaviours. Here, we explored whole adult brain coronal organotypic slices as an alternative model. Mouse adult brain slices remain viable in a serum-free basal medium for several weeks. GSCs can be easily microinjected into specific anatomical sites ex vivo, and we demonstrate distinct responses of engrafted GSCs to diverse microenvironments in the brain tissue. Within the subependymal zone – one of the adult neural stem cell niches – injected tumour cells could effectively engraft and respond to endothelial niche signals. Tumour-transplanted slices were treated with the antimitotic drug temozolomide as proof of principle of the utility in modelling responses to existing treatments. Engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices therefore provides a simplified, yet flexible, experimental model. This will help to increase the precision and throughput of modelling GSC-host brain interactions and complements ongoing in vivo studies. This article has an associated First Person interview with the first author of the paper.

  5. A novel technique of serial biopsy in mouse brain tumour models.

    Directory of Open Access Journals (Sweden)

    Sasha Rogers

    Full Text Available Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804 is a tyrosine kinase inhibitor (TKI, which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4 are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used. Immunodeficient mice received cortical implants of the human glioblastoma cell line, U87MG, modified to express the constitutively-active EGFR mutant, EGFRvIII, GFP and luciferase. Tumour growth was monitored using bioluminescence imaging. Upon attainment of a moderate tumour size, free-hand biopsy was performed on a subgroup of animals. Animal monitoring using a neurological severity score (NSS showed that all mice survived the procedure with minimal perioperative morbidity and recovered to similar levels as controls over a period of five days. The technique was used to evaluate dacomitinib-mediated inhibition of EGFRvIII two hours after drug administration. We show that serial tissue samples can be obtained, that the samples retain histological features of the tumour, and are of sufficient quality to determine response to treatment. This approach represents a significant advance in murine brain surgery that may be applicable to other brain tumour models. Importantly, the methodology has the potential to accelerate the preclinical in vivo drug screening process.

  6. Imaging brain tumour microstructure.

    Science.gov (United States)

    Nilsson, Markus; Englund, Elisabet; Szczepankiewicz, Filip; van Westen, Danielle; Sundgren, Pia C

    2018-05-08

    Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called 'microstructure imaging'. The promise of microstructure imaging is one of 'virtual biopsy' with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging. Copyright © 2018. Published by Elsevier Inc.

  7. Tumours of the brain

    International Nuclear Information System (INIS)

    Bleehen, N.M.

    1986-01-01

    This volume is the last in a series of publications containing the edited texts of the clinical oncology symposia patronaged by the Royal College of Radiologists. The topics included essentially cover the pathology, imaging, diagnosis, and treatment of common and uncommon tumors of the brain. Only malignant tumors are discussed in any detail. A short introductory chapter summarized the pathology of brain tumors and the still-prevailing confusion of classification of gliomas. Two interesting chapters deal with immunologic techniques: one for characterizing tumors with immunocytochemical methods; the other, for localization and imaging by means of radiolabeled antibodies. Conventional radiologic methods of imaging, with emphasis on computed tomography, are covered in a comprehensive chapter summarizing what is known today of the accuracy of these methods in the detection, characterization, and grading of tumors of the brain. Two chapters are devoted to more recent developments in imaging, namely, magnetic resonance (MR) imaging and positron emission tomography

  8. The negative brain scintiscan in brain tumours

    International Nuclear Information System (INIS)

    Dalke, K.G.

    1978-01-01

    On the basis of 53 histologically verified and two histologically unidentified brain tumours, the author examined the reasons for these wrongly negative scintiscans. EEGs and angiographies carried out at about the same time were taken into account and compared with the scintigraphic findings. (orig.) [de

  9. [Awake craniotomy for brain tumours].

    Science.gov (United States)

    Milos, Peter; Metcalf, Kerstin; Vigren, Patrick; Lindehammar, Hans; Nilsson, Malin; Boström, Sverre

    2016-10-11

    Awake craniotomy for brain tumours  Awake neurosurgery is a useful method in lesions near eloquent brain areas, particularly low-grade gliomas.The aim is to maximise tumour resection and preserve neurological function. We performed 40 primary awake surgeries and 8 residual surgeries. Patients were operated awake throughout the procedure or with a laryngeal mask and general anaesthesia during the opening stage and then awake during intracerebral surgery. Language and motor function were mapped with direct cortical stimulation, motor evoked potential and standardised neurological testing. Radiologically, complete resection was achieved in 18 out of 40 patients in the primary surgeries. Full neurological recovery at three months was observed in 29 patients. Of the 11 patients with persisting neurological deficits at three months, symptoms were present preoperatively in 9 patients. We conclude that awake surgery, combined with intraoperative neurophysiological methods, is a safe method to improve treatment for low-grade gliomas.

  10. Radiopharmaceutical therapy of brain tumours

    International Nuclear Information System (INIS)

    Riva, P.; Franceschi, G.; Frattarelli, M.; Casi, M.; Santimaria, M.; Cremonini, A.M.; Guiducci, G.; Riva, N.

    1999-01-01

    Full text: The loco-regional radioimmunotherapy (RIT) of high-grade malignant glioma may represent a further favourable therapeutic approach, able to ameliorate the ominous prognosis of these diseases. The anti-tenascin monoclonal antibodies (MAbs) are directly injected in the tumoral bed after the operation. In the first pilot study, 81 glioblastoma patients received the MAbs (BC2 and BC4) labelled with 131 I (mean dose 2035 MBq). The toxicity was absent. The median survival was prolonged up to 25 months and the response rate (PR + CR + NED: no evidence of disease in cases with minimal lesions after customary treatments) was 44%. More recently, 90 Y instead of 131 I was employed. The benzyl-DTPA chelator was utilized for 90 Y conjugation. A phase I study was performed in 20 glioblastoma patients, who previously received all conventional regimens, but with progressive tumour. They were intralesionally given escalating 90 Y doses (185, 370, 555, 740, 925 MBq), 4 cases were included in each incremental level. No change in haematology, liver and renal parameters were encountered. The brain MTD was 925 MBq. The radiopharmaceutical remained in high amount only in the neoplastic area and did not diffuse in normal brain region nor in normal organs. The radiation dose to the tumour was, on average, 0.54 Gy per MBq of 90 Y administered (about 4 times higher in comparison to 131 I). Now a phase II study has been initiated. 30 evaluable patients (23 glioblastoma and 7 anaplastic astrocytoma; 8 newly diagnosed and 22 recurrent tumours) who have been already treated with surgery and radiotherapy, underwent loco-regional RIT, by administering a mean 90 Y dose of 740 MBq; in many cases multiple cycles were given. The median survival of patients who had the antibody infusion when their tumour burden was reduced was 28 months. The objective response consisted of 8 PD, 5 SD, 11 PR, 1 CR and 4 NED. The global response rate (PR + CR + NED) was 53.3% (47.8% in glioblastoma and 75.7% in

  11. Neurofibromatosis type 1: brain stem tumours

    International Nuclear Information System (INIS)

    Bilaniuk, L.T.; Molloy, P.T.; Zimmerman, R.A.; Phillips, P.C.; Vaughan, S.N.; Liu, G.T.; Sutton, L.N.; Needle, M.

    1997-01-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs

  12. Treatment Of Brain Tumours In Childhood

    International Nuclear Information System (INIS)

    Stancokova, T.

    2007-01-01

    Children tumours are the second most common oncologic diseases in childhood (20 %) with highest incidence of mortality in children oncology. Brain tumours form a heterogenous group of tumours with their classification,diagnostic criteria and therapeutic modalities. General principles of treatment involve neurosurgery, which is a prognostic factor, its radicality depends on localization. Radiotherapy has limitations in children until 3 years for possible late effects. Chemotherapy is effective in tumours with high growing rate. These days challenge is to improve therapeutic outcomes and minimalize toxicity of therapy. (author)

  13. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model.

    Directory of Open Access Journals (Sweden)

    Habib Baghirov

    Full Text Available The treatment of brain diseases is hindered by the blood-brain barrier (BBB preventing most drugs from entering the brain. Focused ultrasound (FUS with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.

  14. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

    Science.gov (United States)

    Baghirov, Habib; Snipstad, Sofie; Sulheim, Einar; Berg, Sigrid; Hansen, Rune; Thorsen, Frits; Mørch, Yrr; Åslund, Andreas K. O.

    2018-01-01

    The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma. PMID:29338016

  15. Primary brain tumours, meningiomas and brain metastases in pregnancy

    DEFF Research Database (Denmark)

    Verheecke, Magali; Halaska, Michael J; Lok, Christianne A

    2014-01-01

    to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS: We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973......, respectively. Eight patients (30%) underwent brain surgery, seven patients (26%) had radiotherapy and in three patients (11%) chemotherapy was administered during gestation. Two patients died during pregnancy and four pregnancies were terminated. In 16 (59%) patients elective caesarean section was performed...... were reassuring. CONCLUSION: Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery....

  16. EVALUATION OF BRAIN TUMOURS USING COMPUTED TOMOGRAPHY

    Directory of Open Access Journals (Sweden)

    B. Vinod Kumar

    2016-07-01

    Full Text Available BACKGROUND The brain is basically formed by the neurons and the supporting cells. Tumours arising of neurons are almost impossible because the neurons never divide. Tumours arising from the supporting cells are almost frequently seen. The tumour characteristics depend upon the cell of origin. The brain is covered by meninges and the vascular tissue supplies the essential nutrients to all these components of the brain. Unfortunately, the brain is placed in a rigid box called as neurocranium. According to Monro–Kellie principle, if any of the one component increases in a rigid box, the other components will be compensated. So in a limited space if any of the catastrophes occur i.e. space occupying lesions, then the other components will be compensated and as a result the effects will be seen in a very small amount of time. A sincere effort has been put in this study to understand and evaluate the Brain Tumours using a CT scan. This study is intended to be useful to the diagnosing radiologists, internal medicine practitioners and general practitioners and surgeons. METHODS The aim of the study is to evaluate the brain tumours using CT and to confirm the diagnosis by sending to the Histopathology Department. The study is a cross-sectional study and is done in the Department of Radiology, Fathima Medical College, Kadapa, Andhra Pradesh. The study was done from December 2014 to May 2016. The study was done using thirty cases who were believed to have brain tumour and were studied in the Department of Radiology after initial clinical evaluation. First, the plain CT was done and was checked for the location, size, characteristics of the lesion and the surrounding characteristics were observed. RESULT In the present study, the most common of all tumours were those of the neuroepithelial groups. Next in frequency were the tumours of meninges of all intracranial tumours. This was followed by tumours of cranial nerves, metastatic tumour, one lymphoma case

  17. Aqp 9 and Brain Tumour Stem Cells

    Directory of Open Access Journals (Sweden)

    Guri Fossdal

    2012-01-01

    Full Text Available Several studies have implicated the aquaporins (aqp 1, 4, and 9 in the pathogenesis of malignant brain tumours, suggesting that they contribute to motility, invasiveness, and oedema formation and facilitate metabolism in tumour cells under hypoxic conditions. We have studied the expression of aqp1, 4, and 9 in biopsies from glioblastomas, isolated tumour stem cells grown in a tumoursphere assay and analyzed the progenitor and differentiated cells from these cultures. We have compared these to the situation in normal rat brain, its stem cells, and differentiated cells derived thereof. In short, qPCR in tumour tissue showed presence of aqp1, 4, and 9. In the tumour progenitor population, aqp9 was markedly more highly expressed, whilst in tumour-derived differentiated cells, aqp4 was downregulated. However, immunostaining did not reveal increased protein expression of aqp9 in the tumourspheres containing progenitor cells; in contrast, its expression (both mRNA and protein was high in differentiated cultures. We, therefore, propose that aquaporin 9 may have a central role in the tumorigenesis of glioblastoma.

  18. Phase congruency map driven brain tumour segmentation

    Science.gov (United States)

    Szilágyi, Tünde; Brady, Michael; Berényi, Ervin

    2015-03-01

    Computer Aided Diagnostic (CAD) systems are already of proven value in healthcare, especially for surgical planning, nevertheless much remains to be done. Gliomas are the most common brain tumours (70%) in adults, with a survival time of just 2-3 months if detected at WHO grades III or higher. Such tumours are extremely variable, necessitating multi-modal Magnetic Resonance Images (MRI). The use of Gadolinium-based contrast agents is only relevant at later stages of the disease where it highlights the enhancing rim of the tumour. Currently, there is no single accepted method that can be used as a reference. There are three main challenges with such images: to decide whether there is tumour present and is so localize it; to construct a mask that separates healthy and diseased tissue; and to differentiate between the tumour core and the surrounding oedema. This paper presents two contributions. First, we develop tumour seed selection based on multiscale multi-modal texture feature vectors. Second, we develop a method based on a local phase congruency based feature map to drive level-set segmentation. The segmentations achieved with our method are more accurate than previously presented methods, particularly for challenging low grade tumours.

  19. 2-d spectroscopic imaging of brain tumours

    International Nuclear Information System (INIS)

    Ferris, N.J.; Brotchie, P.R.

    2002-01-01

    Full text: This poster illustrates the use of two-dimensional spectroscopic imaging (2-D SI) in the characterisation of brain tumours, and the monitoring of subsequent treatment. After conventional contrast-enhanced MR imaging of patients with known or suspected brain tumours, 2-D SI is performed at a single axial level. The level is chosen to include the maximum volume of abnormal enhancement, or, in non-enhancing lesions. The most extensive T2 signal abnormality. Two different MR systems have been used (Marconi Edge and GE Signa LX); at each site, a PRESS localisation sequence is employed with TE 128-144 ms. Automated software is used to generate spectral arrays, metabolite maps, and metabolite ratio maps from the spectroscopic data. Colour overlays of the maps onto anatomical images are produced using manufacturer software or the Medex imaging data analysis package. High grade gliomas showed choline levels higher than those in apparently normal brain, with decreases in NAA and creatine. Some lesions showed spectral abnormality extending into otherwise normal appearing brain. This was also seen in a case of CNS lymphoma. Lowgrade lesions showed choline levels similar to normal brain, but with decreased NAA. Only a small number of metastases have been studied, but to date no metastasis has shown spectral abnormality beyond the margins suggested by conventional imaging. Follow-up studies generally show spectral heterogeneity. Regions with choline levels higher than those in normal-appearing brain are considered to represent recurrent high-grade tumour. Some regions show choline to be the dominant metabolite, but its level is not greater than that seen in normal brain. These regions are considered suspicious for residual / recurrent tumour when the choline / creatine ratio exceeds 2 (lower ratios may represent treatment effect). 2-D SI improves the initial assessment of brain tumours, and has potential for influencing the radiotherapy treatment strategy. 2-D SI also

  20. Prophylactic Anticonvulsants in patients with brain tumour

    International Nuclear Information System (INIS)

    Forsyth, P.A.; Weaver, S.; Fulton, D.

    2003-01-01

    We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need ≥900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

  1. Prophylactic Anticonvulsants in patients with brain tumour

    Energy Technology Data Exchange (ETDEWEB)

    Forsyth, P.A. [Depts. of Oncology and Clinical Neurosciences, Univ. of Calgary, Calgary, Alberta (Canada); Tom Baker Cancer Centre, Calgary, Alberta (Canada); Weaver, S. [Depts. of Neurology and Medicine, Albany Medical College, Albany, New York (United States); Fulton, D. [Dept. of Radiation Oncology, Cross Cancer Institute and Dept. of Medicine/Neurology, Univ. of Alberta, Edmonton, Alberta (Canada)

    2003-05-01

    We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need {>=}900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

  2. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

    2015-04-01

    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  3. Monte Carlo dosimetry for synchrotron stereotactic radiotherapy of brain tumours

    International Nuclear Information System (INIS)

    Boudou, Caroline; Balosso, Jacques; Esteve, Francois; Elleaume, Helene

    2005-01-01

    A radiation dose enhancement can be obtained in brain tumours after infusion of an iodinated contrast agent and irradiation with kilovoltage x-rays in tomography mode. The aim of this study was to assess dosimetric properties of the synchrotron stereotactic radiotherapy technique applied to humans (SSR) for preparing clinical trials. We designed an interface for dose computation based on a Monte Carlo code (MCNPX). A patient head was constructed from computed tomography (CT) data and a tumour volume was modelled. Dose distributions were calculated in SSR configuration for various energy beam and iodine content in the target volume. From the calculations, it appears that the iodine-filled target (10 mg ml -1 ) can be efficiently irradiated by a monochromatic beam of energy ranging from 50 to 85 keV. This paper demonstrates the feasibility of stereotactic radiotherapy for treating deep-seated brain tumours with monoenergetic x-rays from a synchrotron

  4. The feasibility of a brain tumour website

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Juhler, M

    2015-01-01

    PURPOSE: Patients with a high-grade glioma (HGG) and their caregivers have imminent and changing informational and supportive care needs. The purpose of this study was to investigate the feasibility and safety of a Danish brain tumour website (BTW) in patients with HGG and their caregivers. We...... one overarching theme 'challenges and barriers'. Being newly diagnosed, patients described a chaotic and overwhelming life situation and had difficulties in identifying with their new and changed role. When using the BTW, some patients and caregivers experienced technological challenges, while...

  5. Osteopenia in children surviving brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Whitton, A.C.; Eves, M. [Children' s Hospital at Chedoke-McMaster, Room 3N27B, Health Sciences Centre, McMaster University, 1200 Main Street West, Hamilton, Ontario (Canada); Hay, J. [Brock University, St. Catharines, Ontario (Canada); Gill, G.J.; Webber, C.E. [Faculty of Health Sciences, McMaster University (Canada); Simpson, T. [Hamilton Regional Cancer Centre, Hamilton, Ontario (Canada); Barr, R.D. [Children' s Hospital at Chedoke-McMaster, Room 3N27B, Health Sciences Centre, McMaster University, 1200 Main Street West, Hamilton, Ontario (Canada)

    1998-05-01

    Osteopenia has been reported in children surviving acute lymphoblastic leukaemia, apparently as a consequence of therapy. It has been suggested that cranial irradiation may play a crucial role in this disorder. To explore that possibility, survivors of brain tumours in childhood, all of whom had received radiotherapy, were examined for evidence of bone mineral loss. 19 children were assessed, on average at 7 years after treatment. Measurements of growth velocities, plain radiography of the skeleton, bone densitometry, health-related quality of life and physical activity were undertaken. Growth hormone (GH) deficiency had been detected in 6 children and 5 had received GH replacement, for a minimum of more than 3 years. 9 children were radiographically osteopenic (including the 5 who had received GH). Z scores for bone mineral density (BMD) were negative in the majority of children. Health-related quality of life was less and pain more frequent in those with low BMD scores. Pain was correlated negatively with both free-time activity and seasonal activity (P<0.01). Osteopenia is a common sequel of therapy in children with brain tumours. Those with osteopenia have more pain and more compromised, health-related quality of life than those who are not osteopenic, and pain significantly limits physical activity. The pathogenesis of osteopenia in these children is still uncertain, but is likely to be multifactorial. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  6. Residential Radon and Brain Tumour Incidence in a Danish Cohort

    DEFF Research Database (Denmark)

    Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus Erik

    2013-01-01

    Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect of expo...... significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies.......Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect...... of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods: During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced...

  7. Discrimination of paediatric brain tumours using apparent diffusion coefficient histograms

    International Nuclear Information System (INIS)

    Bull, Jonathan G.; Clark, Christopher A.; Saunders, Dawn E.

    2012-01-01

    To determine if histograms of apparent diffusion coefficients (ADC) can be used to differentiate paediatric brain tumours. Imaging of histologically confirmed tumours with pre-operative ADC maps were reviewed (54 cases, 32 male, mean age 6.1 years; range 0.1-15.8 years) comprising 6 groups. Whole tumour ADC histograms were calculated; normalised for volume. Stepwise logistic regression analysis was used to differentiate tumour types using histogram metrics, initially for all groups and then for specific subsets. All 6 groups (5 dysembryoplastic neuroectodermal tumours, 22 primitive neuroectodermal tumours (PNET), 5 ependymomas, 7 choroid plexus papillomas, 4 atypical teratoid rhabdoid tumours (ATRT) and 9 juvenile pilocytic astrocytomas (JPA)) were compared. 74% (40/54) were correctly classified using logistic regression of ADC histogram parameters. In the analysis of posterior fossa tumours, 80% of ependymomas, 100% of astrocytomas and 94% of PNET-medulloblastoma were classified correctly. All PNETs were discriminated from ATRTs (22 PNET and 4 supratentorial ATRTs) (100%). ADC histograms are useful in differentiating paediatric brain tumours, in particular, the common posterior fossa tumours of childhood. PNETs were differentiated from supratentorial ATRTs, in all cases, which has important implications in terms of clinical management. (orig.)

  8. Incidence of Brain Tumours at an Academic Centre in Western ...

    African Journals Online (AJOL)

    Objective: To determine the incidence of brain tumours at King AbdulAziz University Hospital (KAUH) in Jeddah, Saudi Arabia, over eight year period. Design: Retrospective study. Sitting: King Abdul Aziz University Hospital in Jeddah Saudi Arabia. Subjects: Patients with intracranial tumours. Results: The overall average ...

  9. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...

  10. Results of irradiating brain tumours (1959-1969)

    Energy Technology Data Exchange (ETDEWEB)

    Zu Eulenburg, G

    1973-01-01

    The results of the radiation treatment of brain tumours were evaluated for 78 patients. The calculated average survival times, as well as the shape of survival curves show, as compared to numerous other authors, that there is no great deviation for any tumour group. The interpretation of the ratio of an amnesis to survival time shows that with fast growing brain tumours as with glioblastoma, the success of radiotherapy is very small. Radiotherapy was well successful in almost all cases of patients with a longer than average anamnesis.

  11. The role of choline (Cho) in the diagnostics and differentiation of brain tumours with HMRS technique

    International Nuclear Information System (INIS)

    Sobiecka, B.; Urbanik, A.

    2009-01-01

    Background: The aim of the research was a comprehensive analysis of Cho concentration and Cho/Cr, NAA/Cho, NAA/Cho+Cr ratios for the purposes of the diagnostics and differentiation of brain tumours (the type of the pathological lesion in patients with brain tumours) with the use of HMRS technique. Material/Methods: The HMRS examinations were performed with the use of the MRI Signa Excite 1.5 T system, in PRESS technique (TR = 1500 ms, TE = 35 ms) and involved 100 patients with brain tumours (age range: 18 to 81 yrs, mean age 50.61). Spectra were taken from three different locations: tumour centre, the tumour edge and contralateral unchanged cerebral tissue. All patients underwent surgery followed by histopathological analysis, on the basis of which two groups were separated (benign tumours, malignant tumours - 50 cases each). Additionally, 30 healthy volunteers in the age of 20 to 79 years (mean age 40.8) were examined. Results: The comparison of the examined patients with the control group revealed significantly higher Cho concentrations in patients with brain tumours. The analysis of Cho concentration was also performed with consideration of the age factor (under and over 60 years of age). Significantly lower mean Cho concentrations were discovered in a group of patients under 60 years of age. The analysis of Cho concentrations and Cho/Cr ratios reveled statistical significance for two factors: voxel location factor and the type of the pathological lesion. The average of Cho concentration and Cho/Cr ratios were higher in the group of patients with malignant tumours. The highest Cho concentrations and Cho/Cr ratios were observed in the tumour centre. The relative NAA/Cho and NAA/Cho+Cr ratios were statistically significant when taking into consideration the voxel location factor only. The results received from contralateral normal cerebral tissue (the internal model) were compared with control group (the external model). Mean values of Cho concentration were

  12. Analysis of clonogenic human brain tumour cells: preliminary results of tumour sensitivity testing with BCNU

    Energy Technology Data Exchange (ETDEWEB)

    Rosenblum, M L; Dougherty, D A; Deen, D F; Hoshino, T; Wilson, C B [California Univ., San Francisco (USA). Dept. of Neurology

    1980-04-01

    Biopsies from 6 patients with glioblastoma multiforme were disaggregated and single cells were treated in vitro with various concentrations of 1,3-bis(2-chloroethyl)-1-nitroso urea (BCNU) and plated for cell survival. One patient's cells were sensitive to BCNU in vitro; after a single dose of BCNU her brain scan reverted to normal and she was clinically well. Five tumours demonstrated resistance in vitro. Three of these tumours progressed during the first course of chemotherapy with a nitrosourea and the patients died at 21/2, 4 and 81/2 months after operation. Two patients who showed dramatic responses to radiation therapy were considered unchanged after the first course of nitrosourea therapy (although one demonstrated tumour enlargement on brain scan). The correlation of in vitro testing of tumour cell sensitivity with actual patient response is encouraging enough to warrant further work to determine whether such tests should weigh in decisions on patient therapy.

  13. Emotional and personality changes following brain tumour resection.

    Science.gov (United States)

    Jenkins, Lisanne M; Drummond, Katharine J; Andrewes, David G

    2016-07-01

    Psychological distress has a high prevalence in brain tumour patients, and understanding the emotional and personality changes that may follow neurosurgery is important for clinical management of these patients. We aimed to characterise these emotional and personality changes using subjective, observer-rated and clinical measures. We examined subjective changes in emotional experience and observer-rated changes to personality disturbances following neurosurgery for brain tumours (n=44), compared to a control group that had undergone spinal surgery (n=26). Participants completed the Hospital Anxiety and Depression Scale and a Subjective Emotional Change Questionnaire. Observers who knew the patients well also completed the Iowa Rating Scale of Personality Change. Compared to controls, patients with tumours reported significantly more changes to their subjective experience of emotions following neurosurgery, particularly anger, disgust and sadness. For the observer-ratings, tumour patients were described as having significant changes in the personality disturbances of irritability, impulsivity, moodiness, inflexibility, and being easily overwhelmed. Anxiety and depression were not significantly different between groups. Neurosurgical resection of a brain tumour is a major life event that changes patients' subjective experiences of different emotions, and leads to observer-rated changes in personality. In this study, these changes were not accompanied by increases in anxiety or depression. We conclude with a discussion of biological and psychosocial mechanisms that can impact emotional functioning and personality in patients with brain tumours. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A rare metastasis from a rare brain tumour

    DEFF Research Database (Denmark)

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

    This case report presents the story of a patient with an oligodendroglioma metastasizing to the bone marrow and to lymph nodes of the neck. The patient had undergone primary brain surgery 13 years prior to the discovery of metastases and radiotherapy directed at the brain tumour two months prior........ Oligodendroglioma are rare primary brain tumours of which extraneural metastasis is even more rare. The incidence of cases like this may be increasing because of better treatment and thus longer survival of patients with oligodendroglioma....

  15. New MR sequences (diffusion, perfusion, spectroscopy) in brain tumours

    International Nuclear Information System (INIS)

    Rossi, Andrea; Gandolfo, Carlo; Morana, Giovanni; Severino, Mariasavina; Garre, Maria Luisa; Cama, Armando

    2010-01-01

    While MRI has been instrumental in significantly improving care in children harbouring brain tumours, conventional sequences lack information regarding functional parameters including cellularity, haemodynamics and metabolism. Advanced MR imaging modalities, such as diffusion (including diffusion tensor imaging and fibre tractography), perfusion and spectroscopy have significantly improved our understanding of the physiopathology of brain tumours and have provided invaluable additional information for treatment planning and monitoring of treatment results. The contribution of these methods to the characterization of brain neoplasms in children is the focus of the present manuscript. (orig.)

  16. Cognitive deficits in adult patients with brain tumours.

    NARCIS (Netherlands)

    Taphoorn, M.J.B.; Klein, M.

    2004-01-01

    Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient's clinical situation and adverse treatment effects. Radiotherapy has been regarded as the

  17. Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours.

    Science.gov (United States)

    Wilson, Martin; Cummins, Carole L; Macpherson, Lesley; Sun, Yu; Natarajan, Kal; Grundy, Richard G; Arvanitis, Theodoros N; Kauppinen, Risto A; Peet, Andrew C

    2013-01-01

    Brain tumours cause the highest mortality and morbidity rate of all childhood tumour groups and new methods are required to improve clinical management. (1)H magnetic resonance spectroscopy (MRS) allows non-invasive concentration measurements of small molecules present in tumour tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to investigate whether MRS detectable molecules can predict the survival of paediatric brain tumour patients. Short echo time (30ms) single voxel (1)H MRS was performed on children attending Birmingham Children's Hospital with a suspected brain tumour and 115 patients were included in the survival analysis. Patients were followed-up for a median period of 35 months and Cox-Regression was used to establish the prognostic value of individual MRS detectable molecules. A multivariate model of survival was also investigated to improve prognostic power. Lipids and scyllo-inositol predicted poor survival whilst glutamine and N-acetyl aspartate predicted improved survival (pmodel of survival based on three MRS biomarkers predicted survival with a similar accuracy to histologic grading (p5e-5). A negative correlation between lipids and glutamine was found, suggesting a functional link between these molecules. MRS detectable biomolecules have been identified that predict survival of paediatric brain tumour patients across a range of tumour types. The evaluation of these biomarkers in large prospective studies of specific tumour types should be undertaken. The correlation between lipids and glutamine provides new insight into paediatric brain tumour metabolism that may present novel targets for therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. The significance of brain scintiscanning with Te-99m in the diagnosis of brain tumours

    International Nuclear Information System (INIS)

    Spengel, F.

    1973-01-01

    The author gives a short introduction to the technology and methods of brain scintiscanning and states his reasons for using the γ source 99 m Tc as test substance. The pathophysiological causes of the accumulation of this nuclide in tumour tissue are discussed, and the normal brain scan is illustrated by models. After this, the scintiscans with tu1our diagnosis obtained in the 2nd university clinic for internal diseases in the period between 1968 and 1970 are listed. 11 of these cases are treated in detail in a casuistics, and the findings are discussed. (orig.) [de

  19. Over-all accuracy of sup(99m)Tc-pertechnetate brain scanning for brain tumours

    International Nuclear Information System (INIS)

    Bjoernsson, O.G.; Petursson, E.; Sigurbjoernsson, B.; Davidsson, D.

    1978-01-01

    A 3-year follow-up and re-evaluation of all scans on all patients referred for brain scanning in Iceland during 1 year was performed in order to assess the diagnostic reliability of radioisotope scanning for brain tumours. The study included 471 patients. Of these 25 had primary brain tumours and 7 brain metastases. Scans were positive and correctly interpreted in 68% of the patients with primary brain tumours and in 3 of the 7 patients with metastases. The over-all accuracy of brain scanning for brain tumours defined as the total number of correct positive scans and correct negative scans versus total number of scans examined was 96%, this figure being mainly influenced by the high number of true negative scans. (orig.) [de

  20. Study of bantam miRNA expression in brain tumour resulted due to ...

    Indian Academy of Sciences (India)

    ANIMESH BANERJEE

    2017-06-19

    Jun 19, 2017 ... these genes lead to an inappropriate segregation of cell fate determinants ... ground could possibly be a consequence of brain tumour resulting ... Expression of bantam miRNA in Drosophila brain tumour. Figure 1. Bantam is ...

  1. Predicting parenting stress in caregivers of children with brain tumours.

    Science.gov (United States)

    Bennett, Emily; English, Martin William; Rennoldson, Michael; Starza-Smith, Arleta

    2013-03-01

    The purpose of the study was to identify factors that contribute to parenting stress in caregivers of children diagnosed with brain tumours. The study was cross-sectional and recruited 37 participants from a clinical database at a specialist children's hospital. Parents were sent questionnaires, which were used to measure factors related to stress in caregivers of children diagnosed with a brain tumour. Stress levels were measured using the Parenting Stress Index-Short Form (PSI/SF). Correlation analysis and multiple linear regression were used to examine the associations between parenting stress and coping styles, locus of control, parent-perceived child disability and time since diagnosis. Results revealed that 51% of parents were experiencing clinically significant levels of stress. The mean stress level of parents in the study was significantly higher than the PSI/SF norms (t = 4.7, p parenting stress. Other styles of coping, child behaviour problems and the amount of time since diagnosis were not found to be predictive of levels of parenting stress. There was a high prevalence of parenting stress in caregivers of children with a brain tumour. An external locus of control and coping by accepting responsibility increased the likelihood of elevated levels of stress. Results emphasised the importance of ongoing support for parents of children with brain tumours. Intervention might helpfully be centred on strategies to increase parents' internal locus of control. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Psychiatric manifestations of brain tumours: a review | Magoha | East ...

    African Journals Online (AJOL)

    Clinicians must have high index of suspicion when managing psychiatric symptoms that are atypical, new-onset, anxiety, or with poor response and resistance to known and efficacious psychopharmaco-therapy treatment regimes, as there may be an underlying brain tumour responsible for the symptomatology. This must ...

  3. Ten years summary: FDG-PET on irradiated brain tumour

    International Nuclear Information System (INIS)

    Wang Shuxia; Boethius, J.

    2004-01-01

    Purpose: To retrospectively evaluate FDG-PET in differentiation of post-radiotherapy status: recurrence, radiation necrosis, malignant regression of low grade primary brain tumour, and to evaluate PET in terms of survival prediction. Material and methods: 117 irradiated patients (156 PET) were consecutively included. PET results were judged by a set of rigid follow-up standards. Brain metastases from lung carcinoma were further studied. Survival time was analysed with Kaplan-Meier method. Results: There were 61 true-positive, 2 false-positive, 15 false-negative, 51 true-negative PET; leaving 5 positive and 22 negative PET results indeterminate. PET positive predictive value was 96% in all and 100% in brain metastasis from lung carcinoma. PET negative predictive value was 55.6% among surgically selected cases. Survival time was significantly longer in patient's with negative PET, both brain metastasis and primary brain tumour. Conclusions: FDG-PET was a good method to pick up tumour recurrence from radiation necrosis, especially metastasis from lung carcinoma. FDG uptake could be used as a non-invasive parameter to predict patient's prognosis. (authors)

  4. Mobile phone use and risk of brain tumours

    International Nuclear Information System (INIS)

    Lahkola, A.

    2010-05-01

    Mobile phone use has increased rapidly worldwide since the 1990's. As mobile telephones are used close to the head, the exposure to the radiofrequency radiation emitted by mobile phones has been suggested as a possible risk factor for brain tumours. The effect of mobile phone use on risk of brain tumours, particularly gliomas and meningiomas as well as acoustic neuromas, was evaluated using both a case-control approach and a meta-analysis. In addition, one of the most important sources of error in a case-control study, selection bias due to differential participation, was assessed in a subset of the case-control data. The risk of glioma and meningioma in relation to mobile phone use was investigated in population-based case-control studies conducted in five North European countries. All these countries used a common protocol and were included in a multinational study on mobile phone use and brain tumours, the INTERPHONE study, coordinated by the International Agency for Research on Cancer (IARC). Cases (1,521 gliomas and 1,209 meningiomas) were identified mostly from hospitals and controls (3,299) from national population registers or general practitioners' patient lists. Detailed history of mobile phone use was obtained in personal interviews. Mobile phone use was assessed using several exposure indicators, such as regular use (phone use at least once a week for at least six months), duration of use as well as cumulative number of hours and calls. To comprehensively evaluate the effect of mobile phone use on risk of brain tumours, the existing evidence from the epidemiological studies published on the issue was combined using meta-analysis. In the analysis, a pooled estimate was calculated for all brain tumours combined, and also separately for the three most common tumour types, glioma, meningioma and acoustic neuroma using inverse variance-weighted method. Pooled estimate was also obtained for different telephone types (NMT and GSM) and by the location of the

  5. Radiation-induced brain tumours: potential late complications of radiation therapy for brain tumours

    International Nuclear Information System (INIS)

    Nishio, S.; Morioka, T.; Inamura, T.; Takeshita, I.; Fukui, M.; Sasaki, M.; Nakamura, K.; Wakisaka, S.

    1998-01-01

    The development of neoplasms subsequent to therapeutic cranial irradiation is a rare but serious and potentially fatal complication. In this study, we retrospectively reviewed the clinical and pathological aspects of 11 patients who underwent cranial irradiation (range, 24-110 cGy) to treat their primary disease and thereafter developed secondary tumours within a span of 13 years. All tumours arose within the previous radiation fields, and satisfied the widely used criteria for the definition of radiation-induced neoplasms. There was no sex predominance (M: 5, F: 6) and the patients tended to be young at irradiation (1.3 - 42 years; median age: 22 years). The median latency period before the detection of the secondary tumour was 14.5 years (range: 6.5 - 24 years). Meningiomas developed in 5 patients, sarcomas in 4, and malignant gliomas in 2. A pre-operative diagnosis of a secondary tumour was correctly obtained in 10 patients based on the neuro-imaging as well as nuclear medicine findings. All patients underwent a surgical removal of the secondary tumour, 3 underwent additional chemotherapy, and one received stereotactic secondary irradiation therapy. During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). Based on these data, the clinicopathological characteristics and possible role of treatment for secondary tumours are briefly discussed. (author)

  6. Combined radiotherapy and chemotherapy for high-grade brain tumours

    Science.gov (United States)

    Barazzuol, Lara

    Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

  7. CT-stereotactic interstitial Curie-therapy using iodine-125 seeds in inoperable brain tumours

    International Nuclear Information System (INIS)

    Mundinger, F.

    1985-01-01

    Iodine-125 seeds are a new radio-drug featuring favourable physical, biological and radiation protection characteristics and available for interstitial (local) irradiation (Curie-therapy) of non-resectable brain tumours as such (cerebral tumours) or of tumours of the interior of the neuro-cranium (extracerebral tumours). Emitters are inserted right into the tumour or tumour recurrence by means of computerized-tomography stereotaxy either permanently or temporarily with dose release being largely restricted to the tumour and the surrounding brain tissue being spared. (orig.) [de

  8. Evaluation of brain tumours by positron emission tomography

    International Nuclear Information System (INIS)

    Schober, O.; Meyer, G.J.

    1992-01-01

    The clinical application of positron emission tomography (PET) for the evaluation of brain tumours has proved clinically valuable. Amino acid and FDG-glucose PET provide information on the degree of malignancy and the prognosis during the initial evaluation. After therapy, the residual tumour can be visualized and recurrence can be differentiated from necrosis. Amino acids have advantages over FDG for these clinical applications. Blood flow, oxygen extraction and metabolism and blood-brain barrier permeability are of minor relevance in clinical situations. Comparison of PET with MRI and MRS will provide new data. The quantitative information of the unique information yielded by PET will lead to a more important clinical role, as will the extrapolation of this experience to the SPECT technique. (orig.) [de

  9. Scintigraphic assessment of vascularity and blood-tissue barrier of human brain tumours

    International Nuclear Information System (INIS)

    Front, D.

    1978-01-01

    Assessment of vascularity and blood-tissue barrier was performed by sequential scintigraphy in 43 patients with brain tumours. The blood-tumour barrier was evaluated by use of sup(99m)Tc-pertechnetate, and vascularity using sup(99m)Tc-labelled red blood cells. Three groups of tumours were found: tumours with low vascularity and permeable barrier, tumours with high vascularity and permeable barrier, and tumours with low vascularity and relatively impermeable barrier. The first group indicates that when vessels are permeable, there may be a rapid penetration of large amounts of pertechnetate into the tumour even when vascularity is not increased. In the other two groups penetration of pertechnetate into the tumour is affected by vascularity, as it determines the total area where passage of the radiopharmaceutical takes place. It is suggested that the permeability of the blood-tumour barrier and the amount of vascularity may have an effect on the success of chemotherapy in brain tumours. (author)

  10. Modelling of tumour repopulation after chemotherapy

    International Nuclear Information System (INIS)

    Marcu, Loredana; Bezak, Eva

    2010-01-01

    Full text: While repopulation is a clinically observed phe nomenon after radiotherapy, repopulation of tumour cells between cycles of chemotherapy is usually a neglected factor in cancer treatment. As the effect of both radiotherapy and chemotherapy on tumour cells is the same (attack on cancer cells), the response of the tumour to injury and cell loss from the two treatment methods should be similar, including repopulation. Cell recruitment is known to be a possible mechanism responsible for tumour regrowth after radio therapy. The literature data regarding mechanisms of repopulation after chemotherapy is very limited. The current paper employs a Monte Carlo modelling approach to implement the pharmacokinetics of a widely used drug (cisplatin) into a previously developed vit1ual head and neck tumour and to study the effect of cisplatin on tumour regres sion and regrowth during treatment. The mechanism of cell recruitment was modelled by releasing various percentages (5-50%) of quiescent cells into the mitotic cycle after each chemotherapy cell kill. The onset of repopulation was also simulated, with both immediate onset and late onset of cell recruitment. Repopulation during chemotherapy, if occu ring, is a highly potent phenomenon, similar to drug resis tance, therefore it should not be neglected during treatment.

  11. Tumour resistance to cisplatin: a modelling approach

    International Nuclear Information System (INIS)

    Marcu, L; Bezak, E; Olver, I; Doorn, T van

    2005-01-01

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

  12. Tumour resistance to cisplatin: a modelling approach

    Energy Technology Data Exchange (ETDEWEB)

    Marcu, L [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Bezak, E [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Olver, I [Faculty of Medicine, University of Adelaide, North Terrace, SA 5000 (Australia); Doorn, T van [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia)

    2005-01-07

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

  13. Brain tumour stem cells: implications for cancer therapy and regenerative medicine.

    Science.gov (United States)

    Sanchez-Martin, Manuel

    2008-09-01

    The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.

  14. Narrative skills of children treated for brain tumours: The impact of tumour and treatment related variables on microstructure and macrostructure.

    Science.gov (United States)

    Docking, Kimberley; Munro, Natalie; Marshall, Tara; Togher, Leanne

    2016-01-01

    The narrative skills of children with brain tumours were examined. Influence of tumour location, radiotherapy, time post-treatment and presence of hydrocephalus was also investigated, as well as associations between narrative and language abilities. Seventeen children (aged 5;6-14;11) treated for brain tumour and their matched controls completed a narrative assessment and comprehensive language testing. Audio recorded narratives were analysed for microstructure and macrostructure elements. Between-group comparisons were conducted. Narrative elements were explored in association with tumour and treatment-related variables. Correlation analysis examined relationships between narrative scores and language test performance. While significant differences were not found between two groups of children across narrative elements, sub-group comparisons revealed marginal differences in macrostructure related to tumour location and hydrocephalus. Children treated with methods other than radiotherapy showed a significant increase in number of mazes in their narratives compared to children who received radiotherapy. Strong positive correlations also existed between narrative elements and language performance. Preliminary findings highlight the importance of investigating narrative abilities as part of a comprehensive language assessment. Macrostructure should be routinely examined where children are diagnosed with either posterior fossa tumour or hydrocephalus or have undergone surgery and/or chemotherapy for brain tumour.

  15. Incidence of brain tumours in rats exposed to an aerosol of 239PuO2

    International Nuclear Information System (INIS)

    Sanders, C.L.; Dagle, G.E.; Mahaffey, J.A.

    1992-01-01

    Incidence of brain tumours was investigated in 3390 female and male Wistar rats exposed to an aerosol of 239 PuO 2 , or as sham-exposed controls. Lung doses ranged from 0.05 to 22 Gy. In females, six brain tumours were found in 1058 control rats (incidence, 0.6%) and 24 brain tumours in 2134 rats exposed to Pu (incidence, 1.1%); the survival-adjusted level of significance was p = 0.29 for comparing control with exposed females. In males, two brain tumours were found in 60 control rats (incidence, 3.3%) and seven brain tumours in 138 rats exposed to Pu (incidence, 5.1%); the survival-adjusted level of significance was p = 0.33. Brain tumour incidence was about five times greater in male than in female rats (p = 0.0001), a highly significant sex difference in brain tumour incidence. Tumour types were distributed similarly among control and Pu-exposed groups of both sexes; most were astrocytomas. Mean lifespans for rats with brain tumours were not significantly different between control and Pu-exposed rats. (author)

  16. A Systematic Overview of Radiation Therapy Effects in Brain Tumours

    International Nuclear Information System (INIS)

    Berg, Gertrud; Blomquist, Erik; Cavallin-Staahl, Eva

    2003-01-01

    A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for brain tumours is based on data from 9 randomized trials and 1 meta-analysis. Moreover, data from 2 prospective studies, 3 retrospective studies and 4 other articles were used. In total, 19 scientific articles are included, involving 4,266 patients. The results were compared with those of a similar overview from 1996 including 11,252 patients. The conclusions reached can be summarized as follows: The conclusion from SBU 129/2 that curative treatment is not available for patients with high-grade malignant glioma (grade III and IV) is still valid. The survival benefit from postoperative radiotherapy compared to supportive care only or chemotherapy is about 3-4 months, as demonstrated in earlier randomized studies. Quality of life is now currently estimated and considered to be of major importance when reporting the outcome of treatment for patients with brain tumours. There is no scientific evidence that radiotherapy using hyper- and hypofractionation leads to longer survival for patients with high-grade malignant glioma than conventional radiotherapy. There is large documentation, but only one randomized study. There is some documentation to support the view that patients with grade IV glioma and poor prognosis can be treated with hypofractionation and with an outcome similar to that after conventional fractionation. A shorter treatment time should be convenient for the patient. Documentation of the benefit of a radiotherapy boost with brachytherapy is limited and no conclusion can be drawn. There is no scientific evidence that radiotherapy prolongs life for patients with low-grade glioma. There are some data supporting that radiotherapy can be used to treat symptoms in

  17. New technologies to combat malignant tumours of the brain.

    Science.gov (United States)

    Heppner, F

    1982-01-01

    1. The primary problem in an effective treatment of a glioblastoma is the prevention of a recurrence. 2. For that purpose were the following therapeutical procedures undertaken: (a) Temporary implantation of radio cobalt in the brain itself (1957): (b) Clostridium butyricum M 55 was used to render the centre of the tumour fluid (1967): (c) Podophyllin was used to destroy the border of the tumour (1980); (d) The CO2 Laser beam (1975); (e) The electromagnetic heat induction deep in the brain (1973-1978). 3. In order to make the operation and postoperative phase safer for the patient, the following precautions were drawn upon or employed: (a) Hyperbaric oxygenisation in the pressure chamber (1971); (b) The anti-G-suit (1974); (c) the computer controlled automatic infusion pump (1980), and (d) the telemetric measurement of intra-cranial pressure (1975). 4. Apart from the pressure chamber, the mentioned devices were all supervised and developed in the department of the author. 5. The first successful means in the prevention of the recurrence of a glioblastoma multiform seems to be the telethermic method mentioned in 2 (e) above.

  18. Radiation-induced brain disorders in patients with pituitary tumours

    International Nuclear Information System (INIS)

    Bhansali, A.; Chanda, A.; Dash, R.J.; Banerjee, A.K.; Singh, P.; Sharma, S.C.; Mathuriya, S.N.

    2004-01-01

    Radiation-induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post-surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non-functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 ± 8.3; median, 36) with a follow-up period of 696 months (mean, 18.3 ± 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 ± 13.4; median, 45), which was given in 1530 fractions (mean, 18.6 ± 5.0; median, 15) with 2.8 ± 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 ± 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 ± 57.0; median, 57). The clinical spectrum of RIBD included new-onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic

  19. Neuro-ophthalmic and clinical characteristics of brain tumours in a ...

    African Journals Online (AJOL)

    Background: Anecdotally, increasing number of patients are seen at Korle Bu Teaching Hospital (KBTH) with brain tumour. Neuro-ophthalmic symptoms and signs may help in timely diagnosis and intervention. Objective: To evaluate the neuro-ophthalmic and clinical characteristics of brain tumour in patients presenting at a ...

  20. A PROSPECTIVE HISTOPATHOLOGICAL-BASED STUDY OF BRAIN TUMOURS IN A REFERRAL CENTRE

    Directory of Open Access Journals (Sweden)

    Prathima Gujjaru

    2016-07-01

    Full Text Available BACKGROUND Brain neoplasms occur at all ages and account for around 2-3 percent of all deaths in adults. In children, the frequency increases to more than twenty percent. In children, it forms the second most common type of malignancy. Most of the tumours encountered are not related to any identifiable risk factors except for irradiation and some hereditary syndromes like subependymal giant cell astrocytoma, glioblastoma multiforme, cerebellar haemangioblastoma, meningioma, Schwannoma of 7 th cranial nerve. Gliomas constitute fifty percent of the brain tumours and sixty percent of all gliomas are glioblastoma multiforme. Meningiomas constitute twenty percent and cerebral metastasis is seen in fifteen percent of the cases. Seventy percent of supratentorial tumours are found in adults and seventy percent of brain tumours in children are infratentorial. The three common tumours of cerebellum are medulloblastoma, haemangioblastoma and juvenile pilocytic astrocytoma. Brain tumours are space occupying lesions and cause compression and destruction of adjacent structures, brain oedema (Peritumoural tissue, infarction and ischaemia of brain by compressing/infiltrating cerebral blood vessels, obstruction of CSF flow causing hydrocephalus, and rise in intracranial pressure with herniations. Tumours can undergo ischaemic necrosis and necrotic tumours tend to bleed. Brain tumours generally do not metastasise. Schwannoma and meningioma are benign tumours. Medulloblastoma of childhood may have drop metastasis via CSF. A sincere effort has been put in this study to identify the incidence of each variety of brain tumour among the fifty confirmed and identified cases of brain tumours. METHODS The age range of the cases in present study was 5-72 years with a mean age of occurrence of 44.11 years and the peak age group affected were in the 3 rd and 4 th decades. Cerebral hemisphere was the commonest site for intracranial tumours. RESULT In the present study, fifty

  1. Thallium uptake and biological behaviour in childhood brain tumours

    International Nuclear Information System (INIS)

    Bernard, E.J.; Howman-Giles, R.; Kellie, S.; Uren, R.F.

    1998-01-01

    Full text: The histopathological grade and radiological appearance of the diverse cerebral neoplasms in childhood frequently poorly reflect their biological behaviour. We examined thallium accumulation prior to treatment (and in several cases, at intervals there after) in 13 children to determine its usefulness as a tumour marker. 23 SPECT studies were acquired 20 minutes after the injection of 1-3 mCi of 201 TI. Thallium index (TI), the ratio of counts in tumour/normal brain, was calculated. No uptake was seen in two patients (pts) with a Grade 1 cerebellar astrocytomas (disease free at 4/12 f/u). Three pts with medulloblastomas were studied. One pt showed intense uptake (Tl =12). His tumour (proliferative antigen stain Ki67 = 50%) recurred early after debulking surgery (Tl +ve prior to CT or MRI changes). The second pt was imaged at relapse Ki67 = 60%) and showed intense uptake, Tl = 17. The third pt showed lower level uptake (Tl = 2), Ki67 = 5%, and is disease-free at 5/12 (as per 201 TI and MRI). One pt with a Grade 1 brainstem glioma showed Tl = 5 and has progressed rapidly despite low grade histology. Four pts with chiasmatic-hypothalamic gliomas have been studied. Although these neoplasms are usually low grade histologically, their growth properties vary greatly. Two pts with Tl 3.5 and have required aggressive treatment for rapid disease progression. One pt with a large pilocytic astrocytoma of the optic chiasm showed Tl = 9.5. Active treatment was not undertaken. One pt with a pineal germ cell tumour showed avid 201 TI uptake (Tl not performed) and has had two normal studies, and is clinically well, since BMT. Avid 201 TI uptake also seen in one pt with cerebral neuroblastoma. (Died at 8/12 after Dx.) Thus, 201 TI accumulates in histologically diverse paediatric neoplasms. The Tl appears to reflect biological behaviour in the limited number of medulloblastoma and optic gliomas pts studied. Whilst promising, further patient studies and longer follow-up is

  2. Three-dimensional textural features of conventional MRI improve diagnostic classification of childhood brain tumours.

    Science.gov (United States)

    Fetit, Ahmed E; Novak, Jan; Peet, Andrew C; Arvanitits, Theodoros N

    2015-09-01

    The aim of this study was to assess the efficacy of three-dimensional texture analysis (3D TA) of conventional MR images for the classification of childhood brain tumours in a quantitative manner. The dataset comprised pre-contrast T1 - and T2-weighted MRI series obtained from 48 children diagnosed with brain tumours (medulloblastoma, pilocytic astrocytoma and ependymoma). 3D and 2D TA were carried out on the images using first-, second- and higher order statistical methods. Six supervised classification algorithms were trained with the most influential 3D and 2D textural features, and their performances in the classification of tumour types, using the two feature sets, were compared. Model validation was carried out using the leave-one-out cross-validation (LOOCV) approach, as well as stratified 10-fold cross-validation, in order to provide additional reassurance. McNemar's test was used to test the statistical significance of any improvements demonstrated by 3D-trained classifiers. Supervised learning models trained with 3D textural features showed improved classification performances to those trained with conventional 2D features. For instance, a neural network classifier showed 12% improvement in area under the receiver operator characteristics curve (AUC) and 19% in overall classification accuracy. These improvements were statistically significant for four of the tested classifiers, as per McNemar's tests. This study shows that 3D textural features extracted from conventional T1 - and T2-weighted images can improve the diagnostic classification of childhood brain tumours. Long-term benefits of accurate, yet non-invasive, diagnostic aids include a reduction in surgical procedures, improvement in surgical and therapy planning, and support of discussions with patients' families. It remains necessary, however, to extend the analysis to a multicentre cohort in order to assess the scalability of the techniques used. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Treatment planning figures of merit in thermal and epithermal boron capture therapy of brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, S.A.; Mathur, J.N. (Wollongong Univ., NSW (Australia)); Allen, B.J. (Ansto PMB 1 Menai, NSW (Australia). Biomedicine and Health)

    1994-05-01

    The boron neutron capture therapy (BNCT) figures of merit of advantage depth, therapeutic depth, modified advantage depth and maximum therapeutic depth have been studied as functions of [sup 10]B tumour to blood ratios and absolute levels. These relationships were examined using the Monte Carlo neutron photon transport code, MCNP, with an ideal 18.4 cm diameter neutron beam incident laterally upon an ellipsoidal neutron photon brain-equivalent model. Mono-energetic beams of 0.025 eV (thermal) and 35 eV (epithermal) were simulated. Increasing the tumour to blood [sup 10]B ratio predictably increases all figures of merit. [sup 10]B concentration was also shown to have a strong bearing on the figures of merit when low levels were present in the system. This is the result of a non-[sup 10]B dependent background dose. At higher levels however, the concentration of [sup 10]B has a diminishing influence. For boron sulphydryl (BSH), little advantage is gained by extending the blood [sup 10]B level beyond 30 ppm, whilst for D, L,-p-boronophenylalanine (BPA) this limit is 10 ppm. Applying the epithermal beam under identical conditions, the therapeutic depth reaches the brain mid-line with a tumour to blood [sup 10]B ratio of only 5.7 for BPA. For BSH, the maximum therapeutic depth reaches the brain mid-line with a tumour to blood ratio of only 1.9 with 30 ppm in the blood. Human data for these compounds are very close to these requirements. (author).

  4. In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

    Science.gov (United States)

    Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

    2016-09-01

    During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery.

  5. Time sequential single photon emission computed tomography studies in brain tumour using thallium-201

    International Nuclear Information System (INIS)

    Ueda, Takashi; Kaji, Yasuhiro; Wakisaka, Shinichiro; Watanabe, Katsushi; Hoshi, Hiroaki; Jinnouchi, Seishi; Futami, Shigemi

    1993-01-01

    Time sequential single photon emission computed tomography (SPECT) studies using thallium-201 were performed in 25 patients with brain tumours to evaluate the kinetics of thallium in the tumour and the biological malignancy grade preoperatively. After acquisition and reconstruction of SPECT data from 1 min post injection to 48 h (1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 15-20 min, followed by 4-6, 24 and 48 h), the thallium uptake ratio in the tumour versus the homologous contralateral area of the brain was calculated and compared with findings of X-ray CT, magnetic resonance imaging, cerebral angiography and histological investigations. Early uptake of thallium in tumours was related to tumour vascularity and the disruption of the blood-brain barrier. High and rapid uptake and slow reduction of thallium indicated a hypervascular malignant tumour; however, high and rapid uptake but rapid reduction of thallium indicated a hypervascular benign tumour, such as meningioma. Hypovascular and benign tumours tended to show low uptake and slow reduction of thallium. Long-lasting retention or uptake of thallium indicates tumour malignancy. (orig.)

  6. Pentavalent 99Tcm - DMSA SPECT in primary brain tumours of glial cell origin

    International Nuclear Information System (INIS)

    Chung, D.K.; Evans, S.G.; Larcos, G.; Gruenewald, S.; Kumar, V.; Barton, M.

    1999-01-01

    Full text: 99 Tc m (V)-DMSA [DMSA(V)] has shown promise in brain tumour imaging. This study aimed to assess the role of DMSA(V) brain SPET in glioma for: (1) predicting the histopathological grade of malignancy, (2) monitoring response to therapy and (3) discriminating recurrent tumour from post-radiotherapy necrosis. Twenty-three patients (pts) (14 men, 9 women) of mean age 57 years (range 20-79) were referred with a lesion on CT/MRI (14 new presentations, 5 known and 4 suspected tumour recurrence). Up to 555 MBq of 99 Tc m (V)DMSA were administered and SPET was acquired at 3 h. Tumour uptake ratio (UR) was calculated by the ratio of activity in the tumour to a region in the contralateral brain. All 19 pts with known tumour showed DMSA(V) uptake. The 14 pts with new tumours (10 grade IV, I grade III, 2 grade II and 1 necrotic tumour) had a pre-therapy mean UR of 7.7 (range 2.8-13.6). The 3 lower-grade tumours were scattered widely within this range. Four pts completed radiotherapy and returned for a post-therapy scan, where the UR was less than the pre-therapy UR in 2, unchanged in 1 and greater in 1. The 5 known recurrent tumours had a mean UR of 13.5 (range 7.3-24.9). In the 4 pts with suspected recurrence, the DMSA(V) scan result agreed with clinical course or PET in 3 but was falsely positive in 1. In summary, 99 Tc m (V)-DMSA: (1) showed uptake in all known glial cell tumours in this series, however the UR did not correlate with the histopathological grade; (2) may be useful for discriminating tumour recurrence from post-radiotherapy necrosis; and (3) may have a role in predicting post-therapy prognosis

  7. Medical exposure to ionising radiation and the risk of brain tumours

    DEFF Research Database (Denmark)

    Blettner, Maria; Schlehofer, Brigitte; Samkange-Zeeb, Florence

    2007-01-01

    BACKGROUND: The role of exposure to low doses of ionising radiation in the aetiology of brain tumours has yet to be clarified. The objective of this study was to investigate the association between medically or occupationally related exposure to ionising radiation and brain tumours. METHODS: We...... used self-reported medical and occupational data collected during the German part of a multinational case-control study on mobile phone use and the risk of brain tumours (Interphone study) for the analyses. RESULTS: For any exposure to medical ionising radiation we found odds ratios (ORs) of 0.63 (95...... regions. CONCLUSION: We did not find any significant increased risk of brain tumours for exposure to medical ionising radiation....

  8. Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours

    DEFF Research Database (Denmark)

    Poulsen, H.S.; Grunnet, K.; Sorensen, M.

    2009-01-01

    MATERIAL AND METHODS: We retrospectively determined the efficacy and safety of a combination of bevacizumab and irinotecan in a consecutive series of 52 heavily pre-treated patients with recurrent high-grade brain tumours. Patients received bevacizumab (10 mg/kg) and irinotecan [340 mg/m(2...... acceptable safety and is a clinically relevant choice of therapy in heavily pre-treated patients with recurrent high-grade brain tumours Udgivelsesdato: 2009...

  9. Comparison of contrast in brightness mode and strain ultrasonography of glial brain tumours

    International Nuclear Information System (INIS)

    Selbekk, Tormod; Brekken, Reidar; Indergaard, Marit; Solheim, Ole; Unsgård, Geirmund

    2012-01-01

    Image contrast between normal tissue and brain tumours may sometimes appear to be low in intraoperative ultrasound. Ultrasound imaging of strain is an image modality that has been recently explored for intraoperative imaging of the brain. This study aims to investigate differences in image contrast between ultrasound brightness mode (B-mode) images and ultrasound strain magnitude images of brain tumours. Ultrasound radiofrequency (RF) data was acquired during surgery in 15 patients with glial tumours. The data were subsequently processed to provide strain magnitude images. The contrast in the B-mode images and the strain images was determined in assumed normal brain tissue and tumour tissue at selected regions of interest (ROI). Three measurements of contrast were done in the ultrasound data for each patient. The B-mode and strain contrasts measurements were compared using the paired samples t- test. The statistical analysis of a total of 45 measurements shows that the contrasts in the strain magnitude images are significantly higher than in the conventional ultrasound B-mode images (P < 0.0001). The results indicate that ultrasound strain imaging provides better discrimination between normal brain tissue and glial tumour tissue than conventional ultrasound B-mode imaging. Ultrasound imaging of tissue strain therefore holds the potential of becoming a valuable adjunct to conventional intraoperative ultrasound imaging in brain tumour surgery

  10. Proton magnetic resonance spectroscopy (1H-MRS) for the evaluation of treatment of brain tumours

    International Nuclear Information System (INIS)

    Houkin, K.; Kamada, K.; Sawamura, Y.; Iwasaki, Y.; Abe, H.; Kashiwaba, T.

    1995-01-01

    We investigated metabolic changes in brain tumours following treatment, using proton magnetic resonance spectroscopy. In meningiomas, effective therapeutic embolisation led to an acute increase in lactate. In radiosensitive tumours such as malignant lymphoma, a decrease in lactate and in increase in N-acetyl-aspartate occurred after radiotherapy, which preceded changes observed on magnetic resonance imaging. On the other hand, no significant changes in spectral patterns were observed in malignant gliomas resistant to therapy. Tissue characterisation of brain tumours by spectral patterns on proton magnetic resonance spectroscopy remains controversial. However, we have shown it to be sensitive to metabolic changes following treatment, which may reflect the efficacy of the therapy. (orig.)

  11. Tumour model with intrusive morphology, progressive phenotypical heterogeneity and memory

    Science.gov (United States)

    Atangana, Abdon; Alqahtani, Rubayyi T.

    2018-03-01

    The model of a tumour, taking into account invasive morphology, progressive phenotypical heterogeneity and also memory, is developed and analyzed in this paper. Three models are investigated: first we consider the model describing the proliferation concentrates in proximity of tumour boundaries, in which the oxygen levels are pronounced. Then we consider the model where the oxygen around the tumour is considered to be unchanged by the vascular system. Finally, we investigate the model of growth of tumours using the concept of non-local operators with the Mittag-Leffler kernel. We provide the numerical solution using the extended 3/8 Simpson method for the new trends of fractional integration for the proliferation concentrates in the proximity of the tumour model. Then we provide the exact solutions of the Gompertz model with three different fractional differentiations involving power law, exponential decay law and the Mittag-Leffler law.

  12. 3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

    KAUST Repository

    Perfahl, H.

    2012-11-01

    We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

  13. 3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

    KAUST Repository

    Perfahl, H.; Byrne, H. M.; Chen, T.; Estrella, V.; Alarcó n, T.; Lapin, A.; Gatenby, R. A.; Gillies, R. J.; Lloyd, M. C.; Maini, P. K.; Reuss, M.; Owen, M. R.

    2012-01-01

    We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

  14. Quantitative MR imaging and spectroscopy of brain tumours: a step forward?

    Energy Technology Data Exchange (ETDEWEB)

    Wagnerova, Dita; Herynek, Vit; Dezortova, Monika; Jiru, Filip; Skoch, Antonin; Hajek, Milan [Institute for Clinical and Experimental Medicine, Department of Diagnostic and Interventional Radiology, Prague (Czech Republic); Malucelli, Alberto; Bartos, Robert; Sames, Martin [JE Purkyne University and Masaryk Hospital, Department of Neurosurgery, Usti nad Labem (Czech Republic); Vymazal, Josef [Na Homolce Hospital, Department of Radiology, Prague (Czech Republic); Urgosik, Dusan [Na Homolce Hospital, Stereotactic and Radiation Neurosurgery, Prague (Czech Republic); Syrucek, Martin [Na Homolce Hospital, Department of Pathology, Prague (Czech Republic)

    2012-11-15

    A prospective quantitative MR study of brain tumours was performed to show the potential of combining different MR techniques to distinguish various disease processes in routine clinical practice. Twenty-three patients with various intracranial tumours before treatment (diagnosis confirmed by a biopsy) and 59 healthy subjects were examined on a 3-T system by conventional MR imaging, 1H spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Metabolic concentrations and their ratios, T2 relaxation times and mean diffusivities were calculated and correlated on a pixel-by-pixel basis and compared to control data. Different tumour types and different localisations revealed specific patterns of correlations between metabolic concentrations and mean diffusivity or T2 relaxation times. The patterns distinguish given tissue states in the examined area: healthy tissue, tissue infiltrated by tumour, active tumour, oedema infiltrated by tumour, oedema, etc. This method is able to describe the complexity of a highly heterogeneous tissue in the tumour and its vicinity, and determines crucial parameters for tissue differentiation. A combination of different MR parameters on a pixel-by-pixel basis in individual patients enables better identification of the tumour type, direction of proliferation and assessment of the tumour extension. (orig.)

  15. A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures

    DEFF Research Database (Denmark)

    Vienneau, Danielle; Infanger, Denis; Feychting, Maria

    2016-01-01

    supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were...... complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain...... during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents....

  16. Known glioma risk loci are associated with glioma with a family history of brain tumours

    DEFF Research Database (Denmark)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika

    2013-01-01

    significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk...... family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies...... and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain...

  17. Differential Equations Related to the Williams-Bjerknes Tumour Model

    Indian Academy of Sciences (India)

    Bjerknes tumour model for a cancer which spreads through an epithelial basal layer modeled on ⊂ 2. The solution of this problem is a family =(()), where each () could be considered as an approximation to the probability that the ...

  18. Short term outcomes following surgery in brain tumours sans neuronavigation.

    Science.gov (United States)

    Rashid, Mamoon Ur; Junaid, Muhammad; Bukhari, Syed Sarmad; Afsheen, Afeera

    2018-02-01

    To determine the presentation and frequency of various intracranial neoplasms and assess outcomes for patients who underwent surgery without neuronavigation. This retrospective study was conducted at Combined Military Hospital, Peshawar, Pakistan, and comprised medical records related to the period from August 2011 to July 2014. Patient histories, examination reports and preoperative and post-operative radiological scans were reviewed and extent of excision was determined based on these coupled with recurrence rates. Intraoperatively, tumour excision was determined largely by the experience of the surgeon and preoperative planning using bony landmarks and radiological scans as an objective guide to resection. SPSS 21 was used for data analysis. Of the 143 patients, 83(57.9%) were males and 60(42.1%)were females. Gliomas were the most common tumours, occurring in 20(33.3%) females and 35(42.2%) males. One-year survival rate for grade 4 astrocytomas was poor (39.4%) and was excellent for meningiomas (100%) and pituitary tumours (100%). Time-tested methods of careful neurological examination and knowledge of neuroanatomy can allow a surgeon with limited resources to plan and accommodate for accurate tumour resection with adequate margins.

  19. Generating prior probabilities for classifiers of brain tumours using belief networks

    Directory of Open Access Journals (Sweden)

    Arvanitis Theodoros N

    2007-09-01

    Full Text Available Abstract Background Numerous methods for classifying brain tumours based on magnetic resonance spectra and imaging have been presented in the last 15 years. Generally, these methods use supervised machine learning to develop a classifier from a database of cases for which the diagnosis is already known. However, little has been published on developing classifiers based on mixed modalities, e.g. combining imaging information with spectroscopy. In this work a method of generating probabilities of tumour class from anatomical location is presented. Methods The method of "belief networks" is introduced as a means of generating probabilities that a tumour is any given type. The belief networks are constructed using a database of paediatric tumour cases consisting of data collected over five decades; the problems associated with using this data are discussed. To verify the usefulness of the networks, an application of the method is presented in which prior probabilities were generated and combined with a classification of tumours based solely on MRS data. Results Belief networks were constructed from a database of over 1300 cases. These can be used to generate a probability that a tumour is any given type. Networks are presented for astrocytoma grades I and II, astrocytoma grades III and IV, ependymoma, pineoblastoma, primitive neuroectodermal tumour (PNET, germinoma, medulloblastoma, craniopharyngioma and a group representing rare tumours, "other". Using the network to generate prior probabilities for classification improves the accuracy when compared with generating prior probabilities based on class prevalence. Conclusion Bayesian belief networks are a simple way of using discrete clinical information to generate probabilities usable in classification. The belief network method can be robust to incomplete datasets. Inclusion of a priori knowledge is an effective way of improving classification of brain tumours by non-invasive methods.

  20. High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours

    International Nuclear Information System (INIS)

    Jalali, Rakesh; Budrukkar, Ashwini; Sarin, Rajiv; Sharma, Dayananda S.

    2005-01-01

    Background and purpose: To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. Materials and methods: Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV + 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3-9 conformal fixed fields to a median dose of 54 Gy/30 fractions. Results: The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12-47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. Conclusion: High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7-10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data

  1. Multiphase modelling of vascular tumour growth in two spatial dimensions

    KAUST Repository

    Hubbard, M.E.

    2013-01-01

    In this paper we present a continuum mathematical model of vascular tumour growth which is based on a multiphase framework in which the tissue is decomposed into four distinct phases and the principles of conservation of mass and momentum are applied to the normal/healthy cells, tumour cells, blood vessels and extracellular material. The inclusion of a diffusible nutrient, supplied by the blood vessels, allows the vasculature to have a nonlocal influence on the other phases. Two-dimensional computational simulations are carried out on unstructured, triangular meshes to allow a natural treatment of irregular geometries, and the tumour boundary is captured as a diffuse interface on this mesh, thereby obviating the need to explicitly track the (potentially highly irregular and ill-defined) tumour boundary. A hybrid finite volume/finite element algorithm is used to discretise the continuum model: the application of a conservative, upwind, finite volume scheme to the hyperbolic mass balance equations and a finite element scheme with a stable element pair to the generalised Stokes equations derived from momentum balance, leads to a robust algorithm which does not use any form of artificial stabilisation. The use of a matrix-free Newton iteration with a finite element scheme for the nutrient reaction-diffusion equations allows full nonlinearity in the source terms of the mathematical model.Numerical simulations reveal that this four-phase model reproduces the characteristic pattern of tumour growth in which a necrotic core forms behind an expanding rim of well-vascularised proliferating tumour cells. The simulations consistently predict linear tumour growth rates. The dependence of both the speed with which the tumour grows and the irregularity of the invading tumour front on the model parameters is investigated. © 2012 Elsevier Ltd.

  2. Active video gaming improves body coordination in survivors of childhood brain tumours

    DEFF Research Database (Denmark)

    Sabel, M.; Sjölund, A.; Broeren, J.

    2016-01-01

    Purpose: We investigated whether active video gaming (AVG) could bring about regular, enjoyable, physical exercise in children treated for brain tumours, what level of physical activity could be reached and if the children’s physical functioning improved. Methods: Thirteen children, aged 7–17 years...... compared to their healthy peers. Active video gaming (AVG), supported by Internet coaching, is a feasible home-based intervention in children treated for brain tumours, promoting enjoyable, regular physical exercise of moderate intensity. In this pilot study, AVG with Nintendo Wii improved Body...

  3. Multiphase modelling of vascular tumour growth in two spatial dimensions

    KAUST Repository

    Hubbard, M.E.; Byrne, H.M.

    2013-01-01

    the (potentially highly irregular and ill-defined) tumour boundary. A hybrid finite volume/finite element algorithm is used to discretise the continuum model: the application of a conservative, upwind, finite volume scheme to the hyperbolic mass balance equations

  4. Fractionated afterloading therapy in inoperable malignant tumours of the brain

    International Nuclear Information System (INIS)

    Sparenberg, A.

    1987-01-01

    With the advent of the method of afterloading the range of uses for fractionated interstitial brady-therapy could be broadened to include malignant cerebral tumours. The mean survival time of 33 female patients was calculated to be 8.3 months for the entire group and 11.3 months for cases not otherwise pretreated. Even though the age, tumour volume, target dose and Karnofsky index obviously tended to influence the survival time, such relationships could not be confirmed statistically. Using the method by Kaplan-Meier it was determined that 65% of the total study group were likely to survive beyond six months and 32% to survive for one year. A separate analysis of patients receiving no previous treatment showed these chances to be 75% and 44%, respectively. The advantages of this therapy are discussed on a comparative basis. (VHE) [de

  5. Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

    Science.gov (United States)

    Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

    Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

  6. Preclinical studies for increasing radiation response of malignant brain tumours

    International Nuclear Information System (INIS)

    Kalia, Vijay K.; Kumari, Kalyani; Sai Shyam; George, Jennifer; Shobha, A.G.; Chandrasekhar Sagar, B.K.; Lal, Jagath

    2013-01-01

    Malignant gliomas are the most common among the CNS cancers. Standard treatment for these tumours - comprises of surgery, followed by Radiotherapy (RT). Combination of Temozolomide (TMZ) increases survival, but hematological toxicities are also increased as compared to RT alone. The median survival depends on grade and location of tumour, as well as the age of the patient. Grade IV gliomas (GSMs) are third leading cause of cancer induced death in the age group of 15 to 34 years. Therefore, it is important to carry out further preclinical studies to develop more effective treatment of malignant gliomas. The present studies were carried out on different established malignant glioma cell lines. (U373MG) as well as primary monolayer cultures derived from biopsies obtained from patients with malignant gliomas. Exponentially growing cells were exposed to TMZ, Lonidamine (LND) (in 0.1% DMSO), or 2-Deoxy-D-Glucose (2-DG, aqueous solution) - with or without 60 Co-Gamma-rays (1- 2 Gy). The drugs were removed 4 hours after irradiation and the cultures were processed further for different assays of damage. Short term (4 h) treatments with TMZ 20 μM, LND 100 μM or their combination; did not induce micronuclei formation in the unirradiated cultures of U373MG cells. However, radiation (2 Gy) induced micronuclei was significantly increased by drug treatments. In primary cultures from different tumours, TMZ (≤ 10 μM) or 2-DG (1 mM), or gamma-irradiation (1-2 Gy) induced micronuclei and/ or apoptosis. The effects, however, varied in different tumours. These data show that clinically achievable, very low concentrations of these drugs could induce cellular damage and death; and increase radiosensitivity of malignant gliomas. Therefore, adjuvants like Lonidamine and 2-DG, with non-overlapping toxicities, could optimize treatment of malignant gliomas, by reducing the side effects of radio-chemotherapy. (author)

  7. Occupational exposure to extremely low frequency magnetic fields and brain tumour risks in the INTEROCC study

    Science.gov (United States)

    Turner, Michelle C; Benke, Geza; Bowman, Joseph D; Figuerola, Jordi; Fleming, Sarah; Hours, Martine; Kincl, Laurel; Krewski, Daniel; McLean, Dave; Parent, Marie-Elise; Richardson, Lesley; Sadetzki, Siegal; Schlaefer, Klaus; Schlehofer, Brigitte; Schüz, Joachim; Siemiatycki, Jack; van Tongeren, Martie; Cardis, Elisabeth

    2014-01-01

    Background Occupational exposure to extremely low frequency magnetic fields (ELF) is a suspected risk factor for brain tumours, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumours. This study examines the association between ELF and brain tumours in the large-scale INTEROCC study. Methods Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1–4, 5–9, and 10+ years prior to the diagnosis/reference date. Results There were 3,761 included brain tumour cases (1,939 glioma, 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1–4 years prior to the diagnosis/reference date and glioma (odds ratio (OR) ≥ 90th percentile vs Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumourigenesis. PMID:24935666

  8. In vivo magnetic resonance imaging and 31P spectroscopy of large human brain tumours at 1.5 tesla

    DEFF Research Database (Denmark)

    Thomsen, C; Jensen, K E; Achten, E

    1988-01-01

    31P MR spectroscopy of human brain tumours is one feature of magnetic resonance imaging. Eight patients with large superficial brain tumours and eight healthy volunteers were examined with 31P spectroscopy using an 8 cm surface coil for volume selection. Seven frequencies were resolved in our spe...

  9. Modelling breast cancer tumour growth for a stable disease population.

    Science.gov (United States)

    Isheden, Gabriel; Humphreys, Keith

    2017-01-01

    Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.

  10. A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.

    Science.gov (United States)

    Vienneau, Danielle; Infanger, Denis; Feychting, Maria; Schüz, Joachim; Schmidt, Lisbeth Samsø; Poulsen, Aslak Harbo; Tettamanti, Giorgio; Klæboe, Lars; Kuehni, Claudia E; Tynes, Tore; Von der Weid, Nicolas; Lannering, Birgitta; Röösli, Martin

    2016-02-01

    Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight, length, maternal age), birth characteristics (e.g. vacuum extraction, preterm delivery, birth order) and exposures during pregnancy (e.g. maternal: smoking, working, dietary supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain tumour risk. Agreement between interview and birth registry data ranged from moderate (Kappa=0.54; worked during pregnancy) to almost perfect (Kappa=0.98; birth weight). Neither anthropogenic factors nor birth characteristics were associated with childhood brain tumour risk. Maternal vitamin intake during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade.

    Directory of Open Access Journals (Sweden)

    Sylwia Libard

    Full Text Available Human cytomegalovirus (HCMV has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.

  12. Adapting MR-BrainPET scans for comparison with conventional PET: experiences with dynamic FET-PET in brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lohmann, Philipp; Herzog, Hans; Kops, Elena Rota; Stoffels, Gabriele; Filss, Christian [Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Juelich, Juelich (Germany); Galldiks, Norbert [Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Juelich, Juelich (Germany); Department of Neurology, University of Cologne, Cologne (Germany); Coenen, Heinrich H; Shah, N Jon; Langen, Karl-Josef [Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Juelich, Juelich (Germany)

    2014-07-29

    Imaging results from subsequent measurements (preclinical 3T MR-BrainPET, HR+) are compared. O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine (FET) may exhibit non-uniform tracer uptake in gliomas. The aim was to analyse and adapt the physical properties of the scanners and study variations of biological tumour volume (BTV) in early and late FET-PET.

  13. neuro-ophthalmic and clinical characteristics of brain tumours in a ...

    African Journals Online (AJOL)

    2015-09-01

    Sep 1, 2015 ... Ophthalmology, Neurosurgery and Endocrine units of. KBTH, Ghana. All patients had clinical diagnosis of brain tumour with confirmation by computerized to- mography (CT) or magnetic resonance imaging (MRI). Thirteen patients had histological confirmation of di- agnosis. Outcome measures: Presenting ...

  14. Changes in Cognition and Decision Making Capacity Following Brain Tumour Resection: Illustrated with Two Cases.

    Science.gov (United States)

    Veretennikoff, Katie; Walker, David; Biggs, Vivien; Robinson, Gail

    2017-09-24

    Changes in cognition, behaviour and emotion frequently occur in patients with primary and secondary brain tumours. This impacts the ability to make considered decisions, especially following surgical resection, which is often overlooked in the management of patients. Moreover, the impact of cognitive deficits on decision making ability affects activities of daily living and functional independence. The assessment process to ascertain decision making capacity remains a matter of debate. One avenue for evaluating a patient's ability to make informed decisions in the context of brain tumour resection is neuropsychological assessment. This involves the assessment of a wide range of cognitive abilities on standard measurement tools, providing a robust approach to ascertaining capacity. Evidence has shown that a comprehensive and tailored neuropsychological assessment has greater sensitivity than brief cognitive screening tools to detect subtle and/or specific cognitive deficits in brain tumours. It is the precise nature and severity of any cognitive deficits that determines any implications for decision making capacity. This paper focuses on cognitive deficits and decision making capacity following surgical resection of both benign and malignant, and primary and secondary brain tumours in adult patients, and the implications for patients' ability to consent to future medical treatment and make decisions related to everyday activities.

  15. Validation of brain tumour imaging with p-[123I]iodo-l-phenylalanine and SPECT

    International Nuclear Information System (INIS)

    Hellwig, Dirk; Sell, Nadja; Schaefer, Andrea; Kirsch, Carl-Martin; Samnick, Samuel; Ketter, Ralf; Moringlane, Jean R.; Romeike, Bernd F.M.

    2005-01-01

    The aims of this prospective study were to validate single-photon emission computed tomography (SPECT) with p-[ 123 I]iodo-l-phenylalanine (IPA) in brain tumours and to evaluate its potential for the characterisation of indeterminate brain lesions. In 45 patients with indeterminate brain lesions or suspected progression of glioma, amino acid uptake was studied using IPA-SPECT and compared with the final diagnosis established by biopsy or serial imaging. After image fusion of IPA-SPECT and magnetic resonance imaging, the presence of tumour was visually determined by two independent observers. IPA uptake was quantified as the ratio between maximum uptake in the suspicious lesion and mean uptake in unaffected brain. Primary brain tumours were present in 35 cases (12 low-grade and 23 high-grade gliomas). Non-neoplastic brain lesions were confirmed in seven cases (three dysplasias, three inflammatory lesions, one lesion after effective therapy). Visual analysis showed a high concordance between the two observers (kappa=0.90, p<0.001), with sensitivity and specificity of 86% and 100% for the discrimination of primary brain tumours and non-neoplastic lesions. At 30 min p.i., IPA uptake in primary brain tumours was higher than that in non-neoplastic lesions (1.70±0.36 vs 1.14±0.18, p<0.05). Brain metastases showed no increased uptake (1.13±0.22, n=3). The persistent retention of IPA in low-grade gliomas without disruption of the blood-brain barrier was visualised up to 24 h p.i. Low-grade and high-grade gliomas showed equivalent IPA uptake (1.72±0.37 vs 1.67±0.36 at 30 min, p=0.745). IPA shows long and specific retention in gliomas. IPA is a promising and safe radiopharmaceutical for the visualisation of gliomas and the characterisation of indeterminate brain lesions. (orig.)

  16. 1H MR spectroscopy of human brain tumours: a practical approach

    International Nuclear Information System (INIS)

    Callot, Virginie; Galanaud, Damien; Le Fur, Yann; Confort-Gouny, Sylviane; Ranjeva, Jean-Philippe; Cozzone, Patrick J.

    2008-01-01

    Magnetic resonance spectroscopy (MRS) is proposed in addition to magnetic resonance imaging (MRI) to help in the characterization of brain tumours by detecting metabolic alterations that may be indicative of the tumour class. MRS can be routinely performed on clinical magnets, within a reasonable acquisition time and if performed under adequate conditions, MRS is reproducible and thus can be used for longitudinal follow-up of treatment. MRS can also be performed in clinical practice to guide the neurosurgeon into the most aggressive part of the lesions or to avoid unnecessary surgery, which may furthermore decrease the risk of surgical morbidity

  17. {sup 1}H MR spectroscopy of human brain tumours: a practical approach

    Energy Technology Data Exchange (ETDEWEB)

    Callot, Virginie [Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612, CNRS - Universite de la Mediterranee, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05 (France)], E-mail: virginie.callot@univmed.fr; Galanaud, Damien [Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612, CNRS - Universite de la Mediterranee, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05 (France); Departement de Neuroradiologie, Hopital La Pitie-Salpetriere, Paris (France); Le Fur, Yann; Confort-Gouny, Sylviane; Ranjeva, Jean-Philippe; Cozzone, Patrick J. [Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612, CNRS - Universite de la Mediterranee, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05 (France)

    2008-08-15

    Magnetic resonance spectroscopy (MRS) is proposed in addition to magnetic resonance imaging (MRI) to help in the characterization of brain tumours by detecting metabolic alterations that may be indicative of the tumour class. MRS can be routinely performed on clinical magnets, within a reasonable acquisition time and if performed under adequate conditions, MRS is reproducible and thus can be used for longitudinal follow-up of treatment. MRS can also be performed in clinical practice to guide the neurosurgeon into the most aggressive part of the lesions or to avoid unnecessary surgery, which may furthermore decrease the risk of surgical morbidity.

  18. Neuro-ophthalmic and clinical characteristics of brain tumours in a tertiary hospital in Ghana

    International Nuclear Information System (INIS)

    Tagoe, N. N.; Essuman, V. A.; Fordjuor, G.; Akpalu, J.; Bankah, P.; Ndanu, T.

    2015-01-01

    Anecdotally, increasing number of patients are seen at Korle Bu Teaching Hospital (KBTH) with brain tumour. Neuro-ophthalmic symptoms and signs may help in timely diagnosis and intervention. The objective of this study is to evaluate the neuro-ophthalmic and clinical characteristics of brain tumour in patients presenting at a tertiary hospital in Ghana. The study design involved a prospective case series involving 36 consecutive patients newly diagnosed with brain tumour from November 2010 to October 2011, at the Ophthalmology, Neurosurgery and Endocrine units of KBTH, Ghana. All patients had clinical diagnosis of brain tumour with confirmation by computerized tomography (CT) or magnetic resonance imaging (MRI). Thirteen patients had histological confirmation of diagnosis. The outcome measures of the study include presenting visual acuity, colour vision, visual fields and cranial nerve deficits. Data of 36 patients were analysed. The results of the study showed that ages ranged from 3 to 69 years, mean (SD) 42.56(±16.6 years). Twenty-six (72%) were females. Tumours included pituitary adenoma (20, 55.5%), meningioma (10, 27.8%), choroid plexus tumour (1, 2.8%), medulloblastom (1, 2.8%), craniopharyngioma (1, 2.8%), haemangioblastoma (1, 2.8%), thalamic tumour (1, 2.8%) and haemangioma (1, 2.8%). Histologically confirmed tumours included pituitary adenoma (9, 69.2%), meningioma (3, 23.1%), craniopharyngioma (1, 7.7%). One patient had both a pituitary adenoma and meningioma. Blurred vision (30, 83.3%), headache (28, 77.8%) and photophobia (13, 36.1%) were predominant symptoms. Commonest neuro-ophthalmic signs were impaired colour vision (62 eyes, 88.6%), optic atrophy (26, 74.3%), unilateral or bitemporal hemianopia (15, 41.5%) and relative afferent pupillary defect (12, 34.3%). Seven (19.4%) patients were visually impaired and nine (25%) blind. Thirty-three of 72(45.8%) eyes had monocular blindness. Common neuro-ophthalmic characteristics were blurred vision

  19. Intra-operative 3-T MRI for paediatric brain tumours: challenges and perspectives

    International Nuclear Information System (INIS)

    Abernethy, L.J.; Avula, S.; Hughes, G.M.; Wright, E.J.; Mallucci, C.L.

    2012-01-01

    MRI is the ideal modality for imaging intracranial tumours. Intraoperative MRI (ioMRI) makes it possible to obtain scans during a neurosurgical operation that can aid complete macroscopic tumour resection - a major prognostic factor in the majority of brain tumours in children. Intra-operative MRI can also help limit damage to normal brain tissue. It therefore has the potential to improve the survival of children with brain tumours and to minimise morbidity, including neurological deficits. The use of ioMRI is also likely to reduce the need for second look surgery, and may reduce the need for chemotherapy and radiotherapy. High-field MRI systems provide better anatomical information and also enable effective utilisation of advanced MRI techniques such as perfusion imaging, diffusion tensor imaging, and magnetic resonance spectroscopy. However, high-field ioMRI facilities require substantial capital investment, and careful planning is required for optimal benefit. Safe ioMRI requires meticulous attention to detail and rigorous application of magnetic field safety precautions. Interpretation of ioMRI can be challenging and requires experience and understanding of artefacts that are common in the intra-operative setting. (orig.)

  20. MR imaging-guided cryoablation of metastatic brain tumours: initial experience in six patients

    International Nuclear Information System (INIS)

    Li, Chengli; Wu, Lebin; Song, Jiqing; Liu, Ming; Lv, Yubo; Sequeiros, Roberto Blanco

    2010-01-01

    The objective was to evaluate the initial experience and safety of magnetic resonance imaging (MRI)-guided transcranial cryoablation in cystic metastatic brain tumours. Seven cystic metastatic brain tumours in six patients were treated with cryoablation. The approval from the local ethics committee and individual patient consent were acquired before the study. Before the procedure the tumours were detected with conventional CT or MRI. The procedure was performed under local anaesthesia and conscious sedation. A 0.23-T open MRI system with optical tracking was used for procedural planning, instrument guidance and procedural monitoring of the ice ball formation. An MR-compatible, argon-based cryoablation system was used. The schedule of follow-up imaging ranged from 12 days to 12 months. Seven treatment sessions were performed. All the cryoprobes were successfully inserted into the target with one pass. All the patients tolerated the procedure well without experiencing any neurological deficits during the treatment phase or during the immediate post-treatment period. One patient died 12 days after cryoablation. MR-guided and monitored metastasis brain tumour cryoablation is technically feasible and may represent an alternative treatment in selected patients. (orig.)

  1. First experience of brain tumour scintigraphy with 99mTc-MIBI before and after surgery

    International Nuclear Information System (INIS)

    Jurkiene, N.; Kulakiene, I.; Aleksandrovas, D.; Tamasauskas, A.

    2004-01-01

    Full text: Morphological imaging techniques like computed tomography and magnetic resonance imaging are routinely used to localize tumours. However, their use for prediction of histopathological diagnosis and tumour changes after treatment is difficult. Functional imaging using positron emission tomography and single photon emission computed tomography (SPECT) were introduced as non-invasive methods for the differentiation and evaluation of brain tumours, especially for their follow-up. The purpose of present study was to investigate the uptake of 99mTc-MIBI in case of malignant brain tumours before and after surgery. 25 patients (13 males and 12 females; age range 21-75 years; average age 48.76±17.25 years) with brain tumours were investigated. The histological diagnoses of the tumours were confirmed from surgical specimens. None of the patients had received any treatment before enrolment for the study. 99mTc-MIBI brain SPECT was performed 3.88±2.85 days before surgery and 9.88±2.24 days after surgery in all cases. SPECT scans were acquired in 64 projections over 360 deg. using a dual-head gamma camera (Siemens E.Cam) coupled with low energy collimator, 15 minutes after intravenous injection of 550 MBq 99mTc-MIBI. Data were recorded in a 64x64 matrix at a zoom factor of 1.78. SPECT images were reconstructed and analysed in the transversal, axial and coronal planes. The study results are presented in the table. Of the 25 tumors, only 19, majority glioblastoma (11) showed avid uptake in the pre- surgery scan. Tumors, II0 astrocytoma (1), oligoasrtrocytoma (1), III0 astrocytoma (3) were missed in the pre surgery scan. Comparison of pre- and postoperative images showed the reduction of 99mTc-MIBI uptake post-operatively except in one case of gliosarcoma where the uptake increased after surgery. In one case of III deg. astrocytoma the 99mTc-MIBI uptakes was observed only after the surgery. All post-operative images showed more intensive uptake in the scalp (zone of

  2. Using R2* values to evaluate brain tumours on magnetic resonance imaging: Preliminary results

    International Nuclear Information System (INIS)

    Liu, Zhenghua; Liao, Haibo; Yin, Jianhua; Li, Yanfang

    2014-01-01

    To determine the usefulness of the R2* value in assessing the histopathological grade of glioma at magnetic resonance imaging and differentiating various brain tumours. Sixty-four patients with brain tumours underwent R2* mapping and diffusion-weighted imaging examinations. ANOVA was performed to analyse R2* values among four groups of glioma and among high-grade gliomas (grades III and IV), low-grade gliomas (grades I and II), meningiomas, and brain metastasis. Spearman's correlation coefficients were used to determine the relationships between the R2* values or apparent diffusion coefficient (ADC) and the histopathological grade of gliomas. R2* values of low- and high-grade gliomas were analysed with the receiver-operator characteristic curve. R2* values were significantly different among high-grade gliomas, low-grade gliomas, meningiomas, and brain metastasis, but not between grade I and grade II or between grade III and grade IV. The R2* value (18.73) of high-grade gliomas provided a very high sensitivity and specificity for differentiating low-grade gliomas. A strong correlation existed between the R2* value and the pathological grade of gliomas. R2* mapping is a useful sequence for determining grade of gliomas and in distinguishing benign from malignant tumours. R2* values are better than ADC for characterising gliomas. (orig.)

  3. In vivo proton magnetic resonance spectroscopy of intraventricular tumours of the brain

    International Nuclear Information System (INIS)

    Majos, Carles; Aguilera, Carles; Cos, Monica; Camins, Angels; Samitier, Alex; Castaner, Sara; Sanchez, Juan J.; Candiota, Ana P.; Delgado-Goni, Teresa; Mato, David; Acebes, Juan J.; Arus, Carles

    2009-01-01

    The aim of this study was to assess the usefulness of proton MR spectroscopy in the diagnosis of intraventricular tumours. Fifty-two intraventricular tumours pertaining to 16 different tumour types were derived from our database. All cases had single-voxel proton MR spectroscopy performed at TE at both 30 and 136 ms at 1.5 T. The Mann-Whitney U test was used to search for the most discriminative datapoints each tumour type. Characteristic trends were found for some groups: high Glx and Ala in meningiomas (p<0.001 and p<0.01, respectively), high mobile lipids in metastasis (p<0.001), high Cho in PNET (p<0.001), high mI+Gly in ependymoma (p<0.001), high NAC (p<0.01) in the absence of the normal brain parenchyma pattern in colloid cysts, and high mI/Gly and Ala in central neurocytoma. Proton MR spectroscopy provides additional metabolic information that could be useful in the diagnosis of intraventricular brain tumors. (orig.)

  4. In vivo proton magnetic resonance spectroscopy of intraventricular tumours of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Majos, Carles; Aguilera, Carles [Hospital Universitari de Bellvitge, Institut de Diagnostic per la Imatge (IDI). Centre Bellvitge, L' Hospitalet de Llobregat, Barcelona (Spain); Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain); Cos, Monica; Camins, Angels; Samitier, Alex; Castaner, Sara; Sanchez, Juan J. [Hospital Universitari de Bellvitge, Institut de Diagnostic per la Imatge (IDI). Centre Bellvitge, L' Hospitalet de Llobregat, Barcelona (Spain); Candiota, Ana P.; Delgado-Goni, Teresa [Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain); Unitat de Bioquimica de Biociencies, Department de Bioquimica i Biologia Molecular, Cerdanyola del Valles (Spain); Mato, David [Hospital Universitari de Bellvitge, Department of Neurosurgery, L' Hospitalet de Llobregat, Barcelona (Spain); Acebes, Juan J. [Hospital Universitari de Bellvitge, Department of Neurosurgery, L' Hospitalet de Llobregat, Barcelona (Spain); Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain); Arus, Carles [Unitat de Bioquimica de Biociencies, Department de Bioquimica i Biologia Molecular, Cerdanyola del Valles (Spain); Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain)

    2009-08-15

    The aim of this study was to assess the usefulness of proton MR spectroscopy in the diagnosis of intraventricular tumours. Fifty-two intraventricular tumours pertaining to 16 different tumour types were derived from our database. All cases had single-voxel proton MR spectroscopy performed at TE at both 30 and 136 ms at 1.5 T. The Mann-Whitney U test was used to search for the most discriminative datapoints each tumour type. Characteristic trends were found for some groups: high Glx and Ala in meningiomas (p<0.001 and p<0.01, respectively), high mobile lipids in metastasis (p<0.001), high Cho in PNET (p<0.001), high mI+Gly in ependymoma (p<0.001), high NAC (p<0.01) in the absence of the normal brain parenchyma pattern in colloid cysts, and high mI/Gly and Ala in central neurocytoma. Proton MR spectroscopy provides additional metabolic information that could be useful in the diagnosis of intraventricular brain tumors. (orig.)

  5. Stochastic modelling of avascular tumour growth and therapy

    International Nuclear Information System (INIS)

    Sahoo, S; Sahoo, A; Shearer, S F C

    2011-01-01

    In this paper, a generalized stochastic model for the growth of avascular tumours is presented. This model captures the dynamical evolution of avascular tumour cell subpopulations by incorporating Gaussian white noise into the growth rate of the mitotic function. This work generalizes the deterministic model proposed by Sherratt and Chaplain (2001 J. Math. Biol. 43 291) where they formulated a tumour model in an in vivo setting, in terms of continuum densities of proliferating, quiescent and necrotic cells. Detailed simulations of our model show that the inclusion of Gaussian noise in the original model of Sherratt and Chaplain substantially distorts the overall structure of the density profiles in addition to reducing the speed of tumour growth. Within this stochastic carcinogenesis framework the action of therapy is also investigated by replacing Gaussian white noise with a therapy term. We compare a constant therapy protocol with a logarithmic time-dependent protocol. Our results predict that a logarithmic therapy is more effective than the constant therapy protocol.

  6. Role of 99mTc labelled GHA in post treatment evaluation of brain tumours

    International Nuclear Information System (INIS)

    Choudhury, P.

    2003-01-01

    Full text: Introduction: Biochemical investigations have a major role to play in the management of primary brain tumours. It is well known that major biochemical changes occur during cancerous transformation including changes in the energy metabolism of the cell. Changes take place in terms of utilization of glucose and other substrates, protein synthesis and expression of antigens and receptors. Changes also take place in disruption of transport mechanisms across cell membranes and other physiological boundaries like blood brain barrier. In the management of primary brain tumours positron emitting tracers have an undisputed role and the role of cationic tracers like Thallium-201, 99m-Tc MIBI and 99m-Tc tetrofosmin has been cited as an alternative to positron tracers in neuro oncology. It must be borne in mind that the cationic tracers are expensive to procure and facilities for positron emission tomography are not available in most of the developing countries. Tc-99m GHA Brain Imaging: Keeping in view the above, a cheaper alternative for PET radio tracers was evaluated. We have so far conducted more than 100 brain SPECT studies, using Tc-99m Glucoheptonic acid (GHA), in 60 patients of brain tumour, both at the time of their diagnosis, as well as after treatment during the follow-up period. Tc-99m Glucoheptonic acid (GHA) is a chemical glucose analogue. Avid concentration of the radiopharmaceutical was noted in viable tumor tissue in the SPECT images done one hour after injection of 740 MBq of 99m-Tc GHA. This was subsequently confirmed by histopathological examination in patients undergoing re-surgery for residual disease or follow up and clinical correlation in patients under remission. Avid tracer concentration was also well demonstrated in recurrent disease (proven by clinical examination, histopathology and/or magnetic resonance imaging (MRI). No significant tracer uptake was seen in areas of radiation induced necrosis. Non-specific uptake in the tumor bed was

  7. Target volumes in radiation therapy of childhood brain tumours

    International Nuclear Information System (INIS)

    Habrand, J.L.; Abdulkarim, B.; Beaudre, A.; El Khouri, M.; Kalifa, C.

    2001-01-01

    Pediatric tumors have enjoyed considerable improvements for the past 30 years. This is mainly due to the extensive use of combined therapeutical modalities in which chemotherapy plays a prominent role. In many children, local treatment including radiotherapy, can nowadays be adapted in terms of target volume and dose to the 'response' to an initial course of chemotherapy almost on a case by case basis. This makes precise recommendation on local therapy highly difficult in this age group. We will concentrate in this paper on brain tumors in which chemotherapy is of limited value and radiotherapy still plays a key-role. (authors)

  8. Comparison of metastatic disease after local tumour treatment with radiotherapy or surgery in various tumour models

    International Nuclear Information System (INIS)

    Ruiter, J. de; Cramer, S.J.; Lelieveld, P.; Putten, L.M. van

    1982-01-01

    Spontaneous metastases in lymph nodes and/or the lung were obtained after tumour cell inoculation of four mouse tumours and one rat tumour into the foot-pads of syngeneic animals or their F 1 hybrids. Following local radiotherapy with doses of 45-80 Gy, significantly more mice died with metastases than following local amputation of the tumour-bearing foot when the 2661 carcinoma was involved. No significant difference was observed after these treatments for the other tumours. The enhancement of metastatic growth after local radiotherapy in the 2661 carcinoma seems not to be due to incomplete killing of tumour cells in the foot. The presence of irradiated normal structures and tumour tissue after radiotherapy promoted the outgrowth of 2661 carcinoma cells which were outside the radiation field at the time of treatment. Evidently, even under similar experimental conditions, radiotherapy may enhance the growth of metastases from some tumours and not from others. (author)

  9. Malignancy assessment of brain tumours with magnetic resonance spectroscopy and dynamic susceptibility contrast MRI

    Energy Technology Data Exchange (ETDEWEB)

    Fayed, Nicolas; Davila, Jorge; Medrano, Jaime [Diagnostic Radiology Department, Clinica Quiron, Zaragoza (Spain); Olmos, Salvador [Instituto de Investigacion en Ingenieria de Aragon, Zaragoza (Spain)], E-mail: olmos@unizar.es

    2008-09-15

    Magnetic resonance imaging (MRI) is the most common and well-established imaging modality for evaluation of intracerebral neoplasms, but there are still some incompletely solved challenges, such as reliable distinction between high- and low-grade tumours, exact delineation of tumour extension, and discrimination between recurrent tumour and radiation necrosis. The aim of this study was to evaluate the contribution of two MRI techniques to non-invasively estimate brain tumour grade. Twenty-four patients referred to MRI examination were analyzed and diagnosed with single intra-axial brain tumour. Lastly, histopathological analysis was performed to verify tumour type. Ten patients presented low-grade gliomas, while the remaining patients showed high-grade tumours, including glioblastomas in eight cases, isolated metastases in four patients and two cases with anaplastic gliomas. MRI examinations were performed on a 1.5-T scanner (Signa, General Electric). The acquisition protocol included the following sequences: saggital T1-weighted localizer, axial T1- and T2-weighted MRI, single-voxel magnetic resonance spectroscopy (MRS), dynamic susceptibility contrast (DSC) MRI and contrast-enhanced T1-weighted MRI. MRS data was analyzed with standard software provided by the scanner manufacturer. The metabolite ratio with the largest significant difference between tumour grades was the choline/creatine (Ch/Cr) ratio with elevated values in high-grade gliomas and metastases. A Ch/Cr ratio equal or larger than 1.55 predicted malignancy grade with 92% sensitivity and 80% specificity. The area under the ROC curve was 0.92 (CI: 95%; 0.81-1). Regarding to perfusion parameters, relative cerebral blood volume (rCBV) maps were estimated from the MR signal intensity time series during bolus passage with two commercial software packages. Two different regions of interest (ROI) were used to evaluate rCBV: lesion centre and perilesional region. All rCBV values were normalized to CBV in a

  10. Malignancy assessment of brain tumours with magnetic resonance spectroscopy and dynamic susceptibility contrast MRI

    International Nuclear Information System (INIS)

    Fayed, Nicolas; Davila, Jorge; Medrano, Jaime; Olmos, Salvador

    2008-01-01

    Magnetic resonance imaging (MRI) is the most common and well-established imaging modality for evaluation of intracerebral neoplasms, but there are still some incompletely solved challenges, such as reliable distinction between high- and low-grade tumours, exact delineation of tumour extension, and discrimination between recurrent tumour and radiation necrosis. The aim of this study was to evaluate the contribution of two MRI techniques to non-invasively estimate brain tumour grade. Twenty-four patients referred to MRI examination were analyzed and diagnosed with single intra-axial brain tumour. Lastly, histopathological analysis was performed to verify tumour type. Ten patients presented low-grade gliomas, while the remaining patients showed high-grade tumours, including glioblastomas in eight cases, isolated metastases in four patients and two cases with anaplastic gliomas. MRI examinations were performed on a 1.5-T scanner (Signa, General Electric). The acquisition protocol included the following sequences: saggital T1-weighted localizer, axial T1- and T2-weighted MRI, single-voxel magnetic resonance spectroscopy (MRS), dynamic susceptibility contrast (DSC) MRI and contrast-enhanced T1-weighted MRI. MRS data was analyzed with standard software provided by the scanner manufacturer. The metabolite ratio with the largest significant difference between tumour grades was the choline/creatine (Ch/Cr) ratio with elevated values in high-grade gliomas and metastases. A Ch/Cr ratio equal or larger than 1.55 predicted malignancy grade with 92% sensitivity and 80% specificity. The area under the ROC curve was 0.92 (CI: 95%; 0.81-1). Regarding to perfusion parameters, relative cerebral blood volume (rCBV) maps were estimated from the MR signal intensity time series during bolus passage with two commercial software packages. Two different regions of interest (ROI) were used to evaluate rCBV: lesion centre and perilesional region. All rCBV values were normalized to CBV in a

  11. Information needs and requirements in patients with brain tumours and their relatives.

    Science.gov (United States)

    Reinert, Christiane; Rathberger, Katharina; Klinkhammer-Schalke, Monika; Kölbl, Oliver; Proescholdt, Martin; Riemenschneider, Markus J; Schuierer, Gerhard; Hutterer, Markus; Gerken, Michael; Hau, Peter

    2018-06-01

    Patients with brain tumours face a number of medical and social challenges. Previous studies have shown that these patients and their relatives need a high level of patient-oriented information and counselling. However, these needs are often underestimated. In this single-centre cross-sectional study, we evaluated, for the first time, the information needs of patients with brain tumours and their relatives depending on diagnosis, age and level of education. The participants were interviewed using pre-specified questionnaires. Answers were evaluated descriptively using standard statistical methods. A total of 888 questionnaires were sent out. The return rate was 50.7%. The majority of patients (nP = 103; 59.9%) and a higher proportion of relatives (nR = 103; 72.5%; p = 0.019) wished to receive a maximum of information. The majority (79.7% of patients; 83.1% of relatives) also stated that they preferred a personal, face-to-face meeting as primary source of information. The need for information increased with education (p = 0.015), and decreased with tumour grade (p = 0.025) and age (p = 0.118). Our data indicate that patients with brain tumours and their relatives have high information needs throughout their disease and continuously require information and counselling. Optimal provision of information is based on personal preferences, which needs to be evaluated appropriately. Patient-oriented information and counselling are parts of a successful communication strategy that can improve cancer care significantly.

  12. Double-labelling immunohistochemistry for MGMT and a “cocktail” of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours

    OpenAIRE

    Burke, Elinor; Grobler, Mariana; Elderfield, Kay; Bond, Frances; Crocker, Matthew; Taylor, Rohan; Bridges, Leslie R

    2013-01-01

    Background Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT an...

  13. Intraoperative probe detecting β{sup −} decays in brain tumour radio-guided surgery

    Energy Technology Data Exchange (ETDEWEB)

    Solfaroli Camillocci, E., E-mail: elena.solfaroli@roma1.infn.it [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Bocci, V.; Chiodi, G. [INFN Sezione di Roma, Roma (Italy); Collamati, F. [INFN Sezione di Roma, Roma (Italy); Dip. Scienze di Base e Applicate per l' Ingegneria, Sapienza Univ. di Roma, Roma (Italy); Donnarumma, R.; Faccini, R.; Mancini Terracciano, C. [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Marafini, M. [INFN Sezione di Roma, Roma (Italy); Museo Storico della Fisica e Centro Studi e Ricerche ‘E. Fermi’, Roma (Italy); Mattei, I.; Muraro, S. [Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma (Italy); Recchia, L. [INFN Sezione di Roma, Roma (Italy); Rucinski, A. [INFN Sezione di Roma, Roma (Italy); Dip. Scienze di Base e Applicate per l' Ingegneria, Sapienza Univ. di Roma, Roma (Italy); Russomando, A. [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma (Italy); Toppi, M. [Laboratori Nazionali di Frascati dell' INFN, Frascati (Italy); Traini, G. [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Morganti, S. [INFN Sezione di Roma, Roma (Italy)

    2017-02-11

    Radio-guided surgery (RGS) is a technique to intraoperatively detect tumour remnants, favouring a radical resection. Exploiting β{sup −} emitting tracers provides a higher signal to background ratio compared to the established technique with γ radiation, allowing the extension of the RGS applicability range. We developed and tested a detector based on para-terphenyl scintillator with high sensitivity to low energy electrons and almost transparent to γs to be used as intraoperative probe for RGS with β{sup −} emitting tracer. Portable read out electronics was customised to match the surgeon needs. This probe was used for preclinical test on specific phantoms and a test on “ex vivo” specimens from patients affected by meningioma showing very promising results for the application of this new technique on brain tumours. In this paper, the prototype of the intraoperative probe and the tests are discussed; then, the results on meningioma are used to make predictions on the performance of the probe detecting residuals of a more challenging and more interesting brain tumour: the glioma.

  14. Early medical rehabilitation after neurosurgical treatment of malignant brain tumours in Slovenia.

    Science.gov (United States)

    Kos, Natasa; Kos, Boris; Benedicic, Mitja

    2016-06-01

    The number of patients with malignant brain tumours is on the rise, but due to the novel treatment methods the survival rates are higher. Despite increased survival the consequences of tumour properties and treatment can have a significant negative effect on the patients' quality of life. Providing timely and appropriate rehabilitation interventions is an important aspect of patient treatment and should be started immediately after surgery. The most important goal of rehabilitation is to prevent complications that could have a negative effect on the patients' ability to function. By using individually tailored early rehabilitation it is often possible to achieve the patients' independence in mobility as well as in performing daily tasks before leaving the hospital. A more precise evaluation of the patients' functional state after completing additional oncologic therapy should be performed to stratify the patients who should be directed to complex rehabilitation treatment. The chances of a good functional outcome in patients with malignant brain tumours could be increased with good early medical rehabilitation treatment.

  15. Long-term exposure to ambient air pollution and incidence of brain tumours: The Danish Nurse Cohort

    DEFF Research Database (Denmark)

    Jørgensen, Jeanette Therming; Johansen, Martin Søes; Ravnskjær, Line

    2016-01-01

    -reported information on lifestyle was collected. We obtained data on the incidence of brain tumours until 2013 from the Danish Cancer Register, and estimated annual mean concentrations of particulate matter with diameterPM2.5), particulate matter with diameter... positive association between total brain tumours and PM2.5 (1.06; 0.80-1.40 per 3.37μg/m(3)), NO2 (1.09; 0.91-1.29) per 7.5μg/m(3), and NOx (1.02; 0.93-1.12 per 10.22μg/m(3)), and none with PM10 (0.93; 0.70-1.23 per 3.31μg/m(3)). Associations with PM2.5 and NO2 were stronger for tumours located in meninges...... than in brain, and for benign than for malignant tumours. Finally, association of total brain tumours with PM2.5 was modified by BMI, and was statistically significantly enhanced in obese women (2.03; 1.35-3.05). CONCLUSION: We found weak evidence for association between risk of brain tumours and long...

  16. Role of diffusion-weighted echo-planar MRI in distinguishing between brain abscess and tumour: a preliminary report

    International Nuclear Information System (INIS)

    Noguchi, K.; Watanabe, N.; Nagayoshi, T.; Kanazawa, T.; Toyoshima, S.; Shimizu, M.; Seto, H.

    1999-01-01

    Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in differentiating between brain abscess and tumour. We examined two patients with surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two different b values (20 and 1200 s/mm 2 ). All capsule-stage brain abscesses (4 lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI as markedly high-signal areas of decreased ADC (range, 0.58-0.70 [(10-3 mm 2 /s; mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20-3.20 [(10-3 mm 2 /s; mean, 2.70)]). Solid, contrast-enhancing portions of brain tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of sightly decreased or increased ADC (range, 0.77-1.29 [(10-3 mm 2 /s; mean, 0.94)]). Our preliminary results indicate that DW echo-planar MRI be used for distinguishing between brain abscess and tumour. (orig.) (orig.)

  17. Mathematical models of tumour and normal tissue response

    International Nuclear Information System (INIS)

    Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

    1999-01-01

    The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

  18. Tumour-cell killing by X-rays and immunity quantitated in a mouse model system

    International Nuclear Information System (INIS)

    Porteous, D.D.; Porteous, K.M.; Hughes, M.J.

    1979-01-01

    As part of an investigation of the interaction of X-rays and immune cytotoxicity in tumour control, an experimental mouse model system has been used in which quantitative anti-tumour immunity was raised in prospective recipients of tumour-cell suspensions exposed to varying doses of X-rays in vitro before injection. Findings reported here indicate that, whilst X-rays kill a proportion of cells, induced immunity deals with a fixed number dependent upon the immune status of the host, and that X-rays and anti-tumour immunity do not act synergistically in tumour-cell killing. The tumour used was the ascites sarcoma BP8. (author)

  19. Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis

    DEFF Research Database (Denmark)

    Kaemmerer, Elke; Schneider, Ursula; Klaus, Christina

    2012-01-01

    Kaemmerer E, Schneider U, Klaus C, Plum P, Reinartz A, Adolf M, Renner M, Wolfs T G A M, Kramer B W, Wagner N, Mollenhauer J & Gassler N (2012) Histopathology Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis Aims:  Deleted in malignant brain...

  20. Pre- and post-operative values of serum CRP in patients undergoing surgery for brain tumour

    International Nuclear Information System (INIS)

    Syeda, T.; Rizvi, H.A.; Hashim, A.S.

    2014-01-01

    Objective: To determine the concentration of C-reactive protein in pre- and post-operative serum samples of brain tumour patients in order to detect the potential risks of post-operative infections. Methods: Serum C-reactive protein was measured on pre- and post-operative Day 1, Day 2 and Day 7 in 18 patients who underwent surgery for brain tumours. The study was performed at the Neurosurgical Ward, Jinnah Postgraduate Medical Centre, Karachi, from May 2007 to April 2008. Mean pre-operative patients and control values were compared using Mann-Whitney or Wilcoxon tests for comparing between pre- and post-operative values. P-value was considered significant at 5.0mg/L but no statistically significant difference was found when compared with healthy controls, with mean 4.4+-6.6 and 0.9+-0.7, respectively. Significantly raised serum concentrations were observed in all post-operative samples when compared with pre-operative samples. Serum CRP concentrations significantly increased post-operatively on Day 1, with mean value of 102.9+-82.0mg/L (p<0.0005), and further increased on Day 2 with mean value of 166.9+-128.1mg/L (p<0.0005), but declined on Day 7, with mean value of 42.7+-63.6mg/L (p<0.005). Conclusion: Pre-operative serum C-reactive protein concentrations of 28% of the patients were elevated, suggesting an association with brain tumours. Post-operative serum concentrations were significantly higher than those noted before the surgery. Absence of a fall of concentration from peak value on post-operative Day 2 or a secondary rise from post-operative Day 7 could be alarming for inter-current infection. (author)

  1. Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection

    DEFF Research Database (Denmark)

    Müller, H; End, C; Weiss, C

    2007-01-01

    .0179). An increase of respiratory DMBT1 levels was detected in neonatal infections (P ...Deleted in Malignant Brain Tumours 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds and aggregates various bacteria and viruses in vitro. Studies in adults have shown that DMBT1 is expressed mainly by mucosal epithelia and glands, in particular within the respiratory...... tract, and plays a role in innate immune defence. We hypothesized that respiratory DMBT1 levels may be influenced by various developmental and clinical factors such as maturity, age and bacterial infection. DMBT1 levels were studied in 205 tracheal aspirate samples of 82 ventilated preterm and full...

  2. Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.

    Science.gov (United States)

    Ciezka, Magdalena; Acosta, Milena; Herranz, Cristina; Canals, Josep M; Pumarola, Martí; Candiota, Ana Paula; Arús, Carles

    2016-08-01

    The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

  3. Childhood brain tumours and use of mobile phones: comparison of a case–control study with incidence data

    Directory of Open Access Journals (Sweden)

    Aydin Denis

    2012-05-01

    Full Text Available Abstract The first case–control study on mobile phone use and brain tumour risk among children and adolescents (CEFALO study has recently been published. In a commentary published in Environmental Health, Söderqvist and colleagues argued that CEFALO suggests an increased brain tumour risk in relation to wireless phone use. In this article, we respond and show why consistency checks of case–control study results with observed time trends of incidence rates are essential, given the well described limitations of case–control studies and the steep increase of mobile phone use among children and adolescents during the last decade. There is no plausible explanation of how a notably increased risk from use of wireless phones would correspond to the relatively stable incidence time trends for brain tumours among children and adolescents observed in the Nordic countries. Nevertheless, an increased risk restricted to heavy mobile phone use, to very early life exposure, or to rare subtypes of brain tumours may be compatible with stable incidence trends at this time and thus further monitoring of childhood brain tumour incidence rate time trends is warranted.

  4. The importance of radiotherapy in paediatric atypical teratoid rhabdoid tumour of the brain

    International Nuclear Information System (INIS)

    Korab - Chrzanowska, E.; Bartoszewska, J.; Drogosiewicz, M.; Kwiatkowski, S.; Skowronska-Gardas, A.

    2009-01-01

    Background: Atypical teratoid rhabdoid tumours (ATRT) are very rare children cancers. Approximately 200 cases of ATRT located in the central nervous system have been described in the literature up till now. Aim: The aim of this report was to analyze the results of treatment of 8 children with these very rare neoplasms of the central nervous system, who were treated according to the Polish Paediatric Brain Tumour Group protocol. Material And Methods: Eight children aged from 4 months to 22 years, 5 girls, 3 boys with ATRT of the central nervous system are presented. All children have been operated on and received multidrug chemotherapy; 5 children received radiotherapy as well. In all craniospinal irradiation was applied, in doses of 35 Gy to the whole axis and 55 Gy to tumour boost. Results: Five patients died and 3 children are still alive. The progression-free survival of all 8 patients was 3 to 73 months. The overall survival was 5 to 73 months. All living children received radiotherapy. Two of them had total surgical resection and one partial. Conclusions: We conclude that radiotherapy prolonged survival in ATRT and should be incorporated in all treatment protocols for patients with this diagnosis. (authors)

  5. Spatio-temporal tumour model for analysis and mechanism of action ...

    Indian Academy of Sciences (India)

    We have developed a one-dimensional tumour simulator to describe the biodistribution of chemotherapeutic drugs to a tumoral lesion and the tumour cell's response to therapy. A three-compartment model is used for drug dynamics within the tumour. The first compartment represents the extracellular space in which cells ...

  6. Use of the Graded Prognostic Assessment (GPA) score in patients with brain metastases from primary tumours not represented in the diagnosis-specific GPA studies

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, C. [Nordland Hospital, Bodoe (Norway). Dept. of Oncology and Palliative Medicine; Tromsoe Univ. (Norway). Inst. of Clinical Medicine; Andratschke, N.H. [University Hospital Rostock (Germany). Dept. of Radiation Oncology; Geinitz, H. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Grosu, A.L. [University Hospital Freiburg (Germany). Dept. of Radiation Oncology

    2012-08-15

    Background and purpose: Assessment of prognostic factors might influence treatment decisions in patients with brain metastases. Based on large studies, the diagnosis-specific graded prognostic assessment (GPA) score is a useful tool. However, patients with unknown or rare primary tumours are not represented in this model. A pragmatic approach might be use of the first GPA version which is not limited to specific primary tumours. Patients and methods: This retrospective analysis examines for the first time whether the GPA is a valid score in patients not eligible for the diagnosis-specific GPA. It includes 71 patients with unknown primary tumour, bladder cancer, ovarian cancer, thyroid cancer or other uncommon primaries. Survival was evaluated in uni- and multivariate tests. Results: The GPA significantly predicted survival. Moreover, improved survival was seen in patients treated with surgical resection or radiosurgery (SRS) for brain metastases. The older recursive partitioning analysis (RPA) score was significant in univariate analysis. However, the multivariate model with RPA, GPA and surgery or SRS versus none showed that only GPA and type of treatment were independent predictors of survival. Conclusion: Ideally, cooperative research efforts would lead to development of diagnosis-specific scores also for patients with rare or unknown primary tumours. In the meantime, a pragmatic approach of using the general GPA score appears reasonable. (orig.)

  7. Use of the Graded Prognostic Assessment (GPA) score in patients with brain metastases from primary tumours not represented in the diagnosis-specific GPA studies

    International Nuclear Information System (INIS)

    Nieder, C.; Tromsoe Univ.; Andratschke, N.H.; Geinitz, H.; Grosu, A.L.

    2012-01-01

    Background and purpose: Assessment of prognostic factors might influence treatment decisions in patients with brain metastases. Based on large studies, the diagnosis-specific graded prognostic assessment (GPA) score is a useful tool. However, patients with unknown or rare primary tumours are not represented in this model. A pragmatic approach might be use of the first GPA version which is not limited to specific primary tumours. Patients and methods: This retrospective analysis examines for the first time whether the GPA is a valid score in patients not eligible for the diagnosis-specific GPA. It includes 71 patients with unknown primary tumour, bladder cancer, ovarian cancer, thyroid cancer or other uncommon primaries. Survival was evaluated in uni- and multivariate tests. Results: The GPA significantly predicted survival. Moreover, improved survival was seen in patients treated with surgical resection or radiosurgery (SRS) for brain metastases. The older recursive partitioning analysis (RPA) score was significant in univariate analysis. However, the multivariate model with RPA, GPA and surgery or SRS versus none showed that only GPA and type of treatment were independent predictors of survival. Conclusion: Ideally, cooperative research efforts would lead to development of diagnosis-specific scores also for patients with rare or unknown primary tumours. In the meantime, a pragmatic approach of using the general GPA score appears reasonable. (orig.)

  8. Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours

    DEFF Research Database (Denmark)

    Koch, Klaus Ulrik; Tietze, Anna; Aanerud, Joel

    2017-01-01

    extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured. ETHICS AND DISSEMINATION: This study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer......INTRODUCTION: During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after......, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60 mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood...

  9. Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells

    DEFF Research Database (Denmark)

    Cheng, Chang; Edin, Nina F Jeppesen; Lauritzen, Knut H

    2012-01-01

    Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours...

  10. Intra-operative neurophysiological mapping and monitoring during brain tumour surgery in children: an update.

    Science.gov (United States)

    Coppola, Angela; Tramontano, Vincenzo; Basaldella, Federica; Arcaro, Chiara; Squintani, Giovanna; Sala, Francesco

    2016-10-01

    Over the past decade, the reluctance to operate in eloquent brain areas has been reconsidered in the light of the advent of new peri-operative functional neuroimaging techniques and new evidence from neuro-oncology. To maximise tumour resection while minimising morbidity should be the goal of brain surgery in children as much as it is in adults, and preservation of brain functions is critical in the light of the increased survival and the expectations in terms of quality of life. Intra-operative neurophysiology is the gold standard to localise and preserve brain functions during surgery and is increasingly used in paediatric neurosurgery. Yet, the developing nervous system has peculiar characteristics in terms of anatomical and physiological maturation, and some technical aspects need to be tailored for its use in children, especially in infants. This paper will review the most recent advances in the field of intra-operative neurophysiology (ION) techniques during brain surgery, focussing on those aspects that are relevant to the paediatric neurosurgery practice.

  11. Functional Magnetic Resonance Imaging for Preoperative Planning in Brain Tumour Surgery.

    Science.gov (United States)

    Lau, Jonathan C; Kosteniuk, Suzanne E; Bihari, Frank; Megyesi, Joseph F

    2017-01-01

    Functional magnetic resonance imaging (fMRI) is being increasingly used for the preoperative evaluation of patients with brain tumours. The study is a retrospective chart review investigating the use of clinical fMRI from 2002 through 2013 in the preoperative evaluation of brain tumour patients. Baseline demographic and clinical data were collected. The specific fMRI protocols used for each patient were recorded. Sixty patients were identified over the 12-year period. The tumour types most commonly investigated were high-grade glioma (World Health Organization grade III or IV), low-grade glioma (World Health Organization grade II), and meningioma. Most common presenting symptoms were seizures (69.6%), language deficits (23.2%), and headache (19.6%). There was a predominance of left hemispheric lesions investigated with fMRI (76.8% vs 23.2% for right). The most commonly involved lobes were frontal (64.3%), temporal (33.9%), parietal (21.4%), and insular (7.1%). The most common fMRI paradigms were language (83.9%), motor (75.0%), sensory (16.1%), and memory (10.7%). The majority of patients ultimately underwent a craniotomy (75.0%), whereas smaller groups underwent stereotactic biopsy (8.9%) and nonsurgical management (16.1%). Time from request for fMRI to actual fMRI acquisition was 3.1±2.3 weeks. Time from fMRI acquisition to intervention was 4.9±5.5 weeks. We have characterized patient demographics in a retrospective single-surgeon cohort undergoing preoperative clinical fMRI at a Canadian centre. Our experience suggests an acceptable wait time from scan request to scan completion/analysis and from scan to intervention.

  12. Frequency, clinical correlates and rating of behavioural changes in primary brain tumour patients: A preliminary investigation.

    Directory of Open Access Journals (Sweden)

    Grahame K Simpson

    2015-04-01

    Full Text Available PurposeFew studies have addressed the specific behavioural changes associated with primary brain tumour (PBT. This paper will report on the frequency and demographic/clinical correlates of such behaviours, and the reliability of rating such behaviours amongst people with PBT, family informants and clinicians. The association of behavioural changes and patient functional status will also be discussed.MethodsA total of 57 patients with 37 family informants were recruited from two large Australian metropolitan hospitals. Each completed three neuro-behavioural self-report measures. Patients also completed a depression symptom measure. Functional status was defined by clinician-rated Karnofsky Performance Status.ResultsPatients were on average 52 years old, a median of four months (range 1-82 post-diagnosis, with high grade (39%, low grade (22% or benign tumours (39%. Patients reported frequency rates of 7-40% across various behavioural domains including anger, inappropriate behaviour, apathy, inertia and executive impairment. The presence of epileptic seizures was associated with significantly higher levels of behavioural changes. Notably, behaviour did not correlate with tumour grade or treatment modality. There was moderate agreement between patients and relatives on the presence or absence of behavioural changes, and substantial agreement between relative and clinician ratings. Depressed patients did not generally report more changes than non-depressed patients. Increases in the relative and clinician-rated behaviour scores were significantly correlated with decreasing functional status in the patient.ConclusionsBehavioural changes were a common sequela of both benign and malignant PBT. Larger scale studies are required to confirm these results. The results suggest the importance of including behaviour in brain cancer psychosocial assessments and the need to develop interventions to treat these patients and reduce the burden of care on families.

  13. Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours

    International Nuclear Information System (INIS)

    Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-ichi; Maruhashi, Akira

    2006-01-01

    Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger

  14. Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours

    Science.gov (United States)

    Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-ichi; Maruhashi, Akira

    2006-03-01

    Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

  15. Metastatic disease of the brain: extra-axial metastases (skull, dura, leptomeningeal) and tumour spread

    Energy Technology Data Exchange (ETDEWEB)

    Maroldi, Roberto; Ambrosi, Claudia; Farina, Davide [University of Brescia, Department of Radiology, Brescia, BS (Italy)

    2005-03-01

    Extra-axial intracranial metastases may arise through several situations. Hematogenous spread to the meninges is the most frequent cause. Direct extension from contiguous extra-cranial neoplasms, secondary invasion of the meninges by calvarium and skull base metastases, and migration along perineural or perivascular structures are less common. Leptomeningeal invasion gives rise to tumour cell dissemination by the cerebrospinal fluid (CSF), eventually leading to neoplastic coating of brain surfaces. Contrast-enhanced magnetic resonance (MR) imaging is complementary to CSF examinations and can be invaluable, detecting up to 50% of false-negative lumbar punctures. MR findings range from diffuse linear leptomeningeal enhancement to multiple enhancing extra-axial nodules, obstructive communicating and non-communicating hydrocephalus. Both calvarial and epidural metastases infrequently transgress the dura, which acts as a barrier against tumour spread. Radionuclide bone studies are still a valuable screening test to detect bone metastases. With computed tomography (CT) and MR, bone metastases extending intracranially and primary dural metastases show the characteristic biconvex shape, usually associated with brain displacement away from the inner table. Although CT is better in detecting skull base erosion, MR is more sensitive and provides more detailed information about dural involvement. Perineural and perivascular spread from head and neck neoplasms require thin-section contrast-enhanced MR. (orig.)

  16. Diffusion tensor imaging of brain tumours at 3 T: A potential tool for assessing White matter tract invasion?

    Energy Technology Data Exchange (ETDEWEB)

    Price, S.J.; Burnet, N.G.; Donovan, T.; Green, H.A.L.; Pena, A.; Antoun, N.M.; Pickard, J.D.; Carpenter, T.A.; Gillard, J.H. E-mail: jhg21@cam.ac.uk

    2003-06-01

    AIM: To determine whether diffusion tensor imaging (DTI) of brain tumours can demonstrate abnormalities distal to hyperintensities on T2-weighted images, and possibly relate these to tumour grade. MATERIALS AND METHODS: Twenty patients with histologically confirmed supratentorial tumours, both gliomas (high and low grade) and metastases, were imaged at 3 T using T2-weighted and DTI sequences. Regions of interest (ROI) were drawn within the tumour, in white matter at various distances from the tumour and in areas of abnormality on DTI that appeared normal on T2-weighted images. The relative anisotropy index (RAI)--a measure of white matter organization, was calculated for these ROI. RESULTS: The abnormality on DTI was larger than that seen on T2-weighted images in 10/13 patients (77%) with high-grade gliomas. New abnormalities were seen in the contralateral white matter in 4/13 (30%) of these cases. In these high-grade tumours the RAI in areas of white matter disruption with normal appearance on T2-weighted images was reduced (0.19{+-}0.04). Even excluding patients with previous radiotherapy this difference remains significant. In all non high-grade tumours (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to the abnormalities shown on T2-weighted imaging and RAI measurements were not reduced (0.3{+-}0.04). CONCLUSIONS: Subtle white matter disruption can be identified using DTI in patients with high-grade gliomas. Such disruption is not identified in association with metastases or low-grade gliomas despite these tumours producing significant mass effect and oedema. We suggest the changes in DTI may be due to tumour infiltration and that the DTI may provide a useful method of detecting occult white matter invasion by gliomas.

  17. Diffusion tensor imaging of brain tumours at 3 T: A potential tool for assessing White matter tract invasion?

    International Nuclear Information System (INIS)

    Price, S.J.; Burnet, N.G.; Donovan, T.; Green, H.A.L.; Pena, A.; Antoun, N.M.; Pickard, J.D.; Carpenter, T.A.; Gillard, J.H.

    2003-01-01

    AIM: To determine whether diffusion tensor imaging (DTI) of brain tumours can demonstrate abnormalities distal to hyperintensities on T2-weighted images, and possibly relate these to tumour grade. MATERIALS AND METHODS: Twenty patients with histologically confirmed supratentorial tumours, both gliomas (high and low grade) and metastases, were imaged at 3 T using T2-weighted and DTI sequences. Regions of interest (ROI) were drawn within the tumour, in white matter at various distances from the tumour and in areas of abnormality on DTI that appeared normal on T2-weighted images. The relative anisotropy index (RAI)--a measure of white matter organization, was calculated for these ROI. RESULTS: The abnormality on DTI was larger than that seen on T2-weighted images in 10/13 patients (77%) with high-grade gliomas. New abnormalities were seen in the contralateral white matter in 4/13 (30%) of these cases. In these high-grade tumours the RAI in areas of white matter disruption with normal appearance on T2-weighted images was reduced (0.19±0.04). Even excluding patients with previous radiotherapy this difference remains significant. In all non high-grade tumours (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to the abnormalities shown on T2-weighted imaging and RAI measurements were not reduced (0.3±0.04). CONCLUSIONS: Subtle white matter disruption can be identified using DTI in patients with high-grade gliomas. Such disruption is not identified in association with metastases or low-grade gliomas despite these tumours producing significant mass effect and oedema. We suggest the changes in DTI may be due to tumour infiltration and that the DTI may provide a useful method of detecting occult white matter invasion by gliomas

  18. Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model

    Directory of Open Access Journals (Sweden)

    Carole eGrasso

    2014-12-01

    Full Text Available Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM, is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy of radiation combined with a one hour exposure to ascorbate (5 mM sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant.

  19. Brain Network Modelling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther

    Three main topics are presented in this thesis. The first and largest topic concerns network modelling of functional Magnetic Resonance Imaging (fMRI) and Diffusion Weighted Imaging (DWI). In particular nonparametric Bayesian methods are used to model brain networks derived from resting state f...... for their ability to reproduce node clustering and predict unseen data. Comparing the models on whole brain networks, BCD and IRM showed better reproducibility and predictability than IDM, suggesting that resting state networks exhibit community structure. This also points to the importance of using models, which...... allow for complex interactions between all pairs of clusters. In addition, it is demonstrated how the IRM can be used for segmenting brain structures into functionally coherent clusters. A new nonparametric Bayesian network model is presented. The model builds upon the IRM and can be used to infer...

  20. Mathematical modeling of liver metastases tumour growth and control with radiotherapy

    International Nuclear Information System (INIS)

    Campbell, Adrienne; Sivakumaran, Thiru; Wong, Eugene; Davidson, Melanie; Lock, Michael

    2008-01-01

    Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumour sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian-Exponential growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof of concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.52% per day; the fractional radiation cell kill for the prescribed dose (60 Gy in 15 fractions) was 42% per day, and the tumour repopulation rate was 2.9% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

  1. Analysis of the interaction between two nitrosourea compounds and X-irradiation in rat brain tumour cells

    Energy Technology Data Exchange (ETDEWEB)

    Leenhouts, H P; Chadwick, K H [Association Euratom-ITAL, Wageningen (Netherlands); Deen, D F [California Univ., San Francisco (USA). Dept. of Neurology

    1980-02-01

    Experimental measurements have shown that both BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) and CCNU (1-(2-choroethyl)-3-cyclohexyl-1-nitrosourea) are toxic in rat 9L brain tumour cells and also sensitize these cells to the action of ionizing radiation. The interaction of BCNU and CCNU with radiation has been interpreted using a recently developed extension of the molecular theory of cell survival. The experimental results are shown to be compatible with the mathematical equations predicted by the model and the analysis indicates that the sensitizing effect is caused by a synergistic interaction between sublethal damage caused by the nitrosourea compound and the radiation at the molecular level. The analysis of the dependence of the interaction on the time between nitrosourea treatment and radiation indicates that the optimal interaction occurs with a 5 hour interval.

  2. An analysis of the interaction between two nitrosourea compounds and X-irradiation in rat brain tumour cells

    International Nuclear Information System (INIS)

    Leenhouts, H.P.; Chadwick, K.H.; Deen, D.F.

    1980-01-01

    Experimental measurements have shown that both BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and CCNU [1-(2-choroethyl)-3-cyclohexyl-1-nitrosourea] are toxic in rat 9L brain tumour cells and also sensitize these cells to the action of ionizing radiation. The interaction of BCNU and CCNU with radiation has been interpreted using a recently developed extension of the molecular theory of cell survival. The experimental results are shown to be compatible with the mathematical equations predicted by the model and the analysis indicates that the sensitizing effect is caused by a synergistic interaction between sublethal damage caused by the nitrosourea compound and the radiation at the molecular level. The analysis of the dependence of the interaction on the time between nitrosourea treatment and radiation indicates that the optimal interaction occurs with a 5 hour interval. (Author)

  3. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  4. Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

    Science.gov (United States)

    Ali, Selman A; Ahmad, Murrium; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Choolun, Esther; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

    2004-09-09

    OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.

  5. Dose-response models for the radiation-induction of skin tumours in mice

    International Nuclear Information System (INIS)

    Papworth, D.G.; Hulse, E.V.

    1983-01-01

    Extensive data on radiation-induced skin tumours in mice were examined using 8 models, all based on the concept that incidences of radiation-induced tumours depend on a combination of two radiation effects: a tumour induction process and the loss of reproductive integrity by the potential tumour cells. Models with and without a threshold were used, in spite of theoretical objections to threshold models. No model fitted well both the epidermal and the dermal tumour data and models which proved to be statistically satisfactory for some of the data were rejected for biological reasons. It is concluded that, for skin tumours, dose-response curves depending on a combination of cancer induction and loss of cellular reproductive integrity are distorted by some special, relatively radio-resistant, factor which we have previously postulated as being involved in radiation skin carcinogenesis. (author)

  6. Automated Measurement Of The Density Of Vessels On Whole Slide Images Of Paediatric Brain Tumours

    Directory of Open Access Journals (Sweden)

    Christophe Deroulers

    2016-06-01

    Only a few parameters have to be chosen, once and for all samples (e.g., the minimal acceptable size of a blood vessel fragment, which makes the method more robust than assessment by a (panel of human expert(s. The automatic calibration steps enable one to deal with a heterogeneous set of slides (e.g., slight differences in background colour and staining. The method uses only open-source software. It is easy to extend or improve and not tight to a single immunomarker. We applied the method to 129 paediatric brain tumours of 8 different types and 3 locations (posterior fossa, thalamus, hemispheres — 185 samples in total. For each patient, the density of microvessels in the sample is compared to the cerebral blood flow as assessed by preoperative perfusion-weighted-imaging using arterial-spin-labeling. We find a good correlation between microvascular density, MRI data and tumour grading. The microvascular density is broadly distributed among the samples. Visualisation in a web browser is slightly more fluid when images are uploaded in the DeepZoom format rather than as pyramidal TIFF images, but the former consumes roughly 20 times more disk space and needs the transfer of a very large number of files after each modification, which is less tractable.

  7. Initial psycho-oncological counselling in neuro-oncology: analysis of topics and needs of brain tumour patients.

    Science.gov (United States)

    Schipmann, Stephanie; Suero Molina, Eric; Frasch, Anna; Stummer, Walter; Wiewrodt, Dorothee

    2018-02-01

    Diagnosis of a brain tumour is associated with a tremendous disruption of emotional, physical and social well-being. Due to the complexity of the disease and the affection of the central organ, the brain, brain tumour patients differ from other cancer patients. The purpose of this study was to evaluate the concerns and burdens presented by brain tumour patients during their initial psycho-oncological consultation. We performed a retrospective analysis of 53 patients with the diagnosis of either benign or malignant brain tumour, seeking counsel by a neurosurgeon specialised in psycho-oncology. We performed a thematic analysis of the interviews at first consultation identifying themes and patterns and created thematic categories. The main concerns of the patients presented during the first consultations were psychological problems, reported by 40 patients (75.5%). Death and dying was mentioned by more than half of the patients (n = 30, 56.6%). In addition, 62.3% of the patients (n = 33) asked for information regarding the medical treatment and diagnosis. With our study, we created greater awareness of the psychological needs of brain tumour patients in order to define treatment strategies for this important aspect of disease. We showed that there is a need for patients to talk about death even during the initial consultation. Psycho-oncologist in a neuro-oncological setting should be prepared for topics like that and should have a neurosurgical background or collaborate with members of the surgical team in order to provide the patients with medical details and to better understand the impact of the disease.

  8. Perfusion MRI of brain tumours: a comparative study of pseudo-continuous arterial spin labelling and dynamic susceptibility contrast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jaernum, Hanna; Steffensen, Elena G.; Simonsen, Carsten Wiberg; Jensen, Finn Taagehoej [Aalborg Hospital/Aarhus University Hospital, Department of Radiology, Aalborg (Denmark); Knutsson, Linda [Lund University, Department of Medical Radiation Physics, Lund (Sweden); Fruend, Ernst-Torben [Aalborg Hospital/Aarhus University Hospital, Department of Radiology, Aalborg (Denmark); GE Healthcare - Applied Science Lab Europe, Aalborg (Denmark); Lundbye-Christensen, Soeren [Aalborg Hospital/Aarhus University Hospital, Department of Cardiology, Center for Cardiovascular Research, Aalborg (Denmark); Shankaranarayanan, Ajit [Global Applied Science Lab, GE Healthcare, Menlo Park, CA (United States); Alsop, David C. [Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (United States); Larsson, Elna-Marie [Aalborg Hospital/Aarhus University Hospital, Department of Radiology, Aalborg (Denmark); Uppsala University Hospital, Department of Radiology, Uppsala (Sweden)

    2010-04-15

    The purpose of this study was to compare the non-invasive 3D pseudo-continuous arterial spin labelling (PC ASL) technique with the clinically established dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI) for evaluation of brain tumours. A prospective study of 28 patients with contrast-enhancing brain tumours was performed at 3 T using DSC-MRI and PC ASL with whole-brain coverage. The visual qualitative evaluation of signal enhancement in tumour was scored from 0 to 3 (0 = no signal enhancement compared with white matter, 3 = pronounced signal enhancement with equal or higher signal intensity than in grey matter/basal ganglia). The extent of susceptibility artefacts in the tumour was scored from 0 to 2 (0 = no susceptibility artefacts and 2 = extensive susceptibility artefacts (maximum diameter > 2 cm)). A quantitative analysis was performed with normalised tumour blood flow values (ASL nTBF, DSC nTBF): mean value for region of interest (ROI) in an area with maximum signal enhancement/the mean value for ROIs in cerebellum. There was no difference in total visual score for signal enhancement between PC ASL and DSC relative cerebral blood flow (p = 0.12). ASL had a lower susceptibility-artefact score than DSC-MRI (p = 0.03). There was good correlation between DSC nTBF and ASL nTBF values with a correlation coefficient of 0.82. PC ASL is an alternative to DSC-MRI for the evaluation of perfusion in brain tumours. The method has fewer susceptibility artefacts than DSC-MRI and can be used in patients with renal failure because no contrast injection is needed. (orig.)

  9. Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study

    International Nuclear Information System (INIS)

    Spoudeas, H.A.; Hindmarsh, P.C.; Brook, C.G.D.; Matthews, D.R.

    1996-01-01

    To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1.5-11.8 years, with brain tumours in the posterior foss (n = 25) or cerebral hemispheres (n 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR 9n 9); Group 2: ≥ 30 Gy DXR only (n = 22); Group 3: ≥ 30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children. (author)

  10. Dosimetric and geometric evaluation of an open low-field magnetic resonance simulator for radiotherapy treatment planning of brain tumours

    DEFF Research Database (Denmark)

    Kristensen, B.H.; Laursen, F.J.; Logager, V.

    2008-01-01

    Background and purpose: Magnetic resonance (MR) imaging is superior to computed tomography (CT) in radiotherapy of brain tumours. In this study an open low-field MR-simulator is evaluated in order to eliminate the cost of and time spent on additional CT scanning. Materials and methods: Eleven...

  11. Intra-arterial and intra-venous chemotherapy combined with radiation in the treatment of brain tumours

    International Nuclear Information System (INIS)

    Watne, K.

    1992-01-01

    The present investigations were undertaken to study the effect of combining different modalities of chemotherapy with radiation in post-operative treatment of brain tumours. The conclusions and clinical implication of the investigations are as follows: The combination of combined intra-arterial chemotherapy followed by radiation leads to an increased median survival with more long term survivors in patients with anaplastic astrocytomas and in patients older than 40 years with astrocytomas. In patients with glioblastoma multiforme, this modality of treatment do not improve median survival, but an increased number of long-term survivors may be seen. Patients younger than 40 years with astrocytomas do not benefit from this modality of treatment. A parallelism exists between sensitivity to chemotherapy and response to radiotherapy. Patients who will benefit from the treatment may be selected early, normally two months after treatment start. Combining intra-arterial chemotherapy and radiation does not lead to an increased incidence of adverse CNS reactions. Specific transient abnormalities in the brain may occur during the first year after treatment and may be misinterpreted as tumour recurrence. EEG may be valuable in predicting adverse CNS reactions following treatment. Nuclear brain scan may be of valuable in selecting the patients who are in danger of developing adverse CNS reactions. Intra-arterial chemotherapy does have an effect in patients with brain tumours who have recurrent tumour after radiation. The most important prognostic factors are age, corticosteroid dependency at treatment start, performance status, histology and frontal lobe location. 103 refs., 2 tabs

  12. Thallium brain SPECT and MRI correlation in the evaluation of tumour recurrence versus radiation necrosis

    International Nuclear Information System (INIS)

    Robins, P.D.; Mahoney, D.S.; Mullan, B.P.

    2000-01-01

    Full text: This study compares different methods of determining thallium tumour uptake indices. Correlation with MR was performed to evaluate features that may affect the thallium index (TI) and to improve specificity for differentiation of recurrent tumor from radiation necrosis. 23 patients who had received radiotherapy for a brain neoplasm were included. The TI was determined using three different methods including large and small regions-of-interest (ROI). The concordance between the thallium SPECT and MRI was assessed. The effect of central necrosis on the different thallium indices derived was evaluated. 18 patients were determined to have recurrent tumor and five had inactive disease. The optimal TI cut-off values was statistically delivered and sensitivity and specificity was 78-94% and 80% respectively for cut-off values between 2.0 and 2.6 depending on the method used to calculate the TI. When compared with MRI, the majority of SPECT abnormalities correlated well with location and degree of uptake and enhancement. Seven cases showed central necrosis and the degree of necrosis had less effect on the TI when a small ROI was used in these cases. In conclusion thallium brain SPECT is a sensitive technique for detecting recurrent tumour. When performing semi-quantitative assessment of thallium uptake, a smaller ROI over the most intense area of uptake will reduce the underestimation of the TI in the presence of necrosis and a Tl cut-off value of 2.6 gave optimal accuracy using this method. Correlation with MRI aids in localization, particularly where there is anatomic distortion and enables more accurate analysis of these lesions by avoiding areas of necrosis. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  13. Brain tumour imaging with PET: a comparison between [{sup 18}F]fluorodopa and [{sup 11}C]methionine

    Energy Technology Data Exchange (ETDEWEB)

    Becherer, Alexander; Karanikas, Georgios; Szabo, Monica; Zettinig, Georg; Wadsak, Wolfgang; Kletter, Kurt [Department of Nuclear Medicine, Medical School, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Asenbaum, Susanne [Department of Neurology, Medical School, University of Vienna, Vienna (Austria); Marosi, Christine [Department of Oncology, Medical School, University of Vienna, Vienna (Austria); Henk, Christine; Wunderbaldinger, Patrick [Department of Radiology, Medical School, University of Vienna, Vienna (Austria); Czech, Thomas [Department of Neurosurgery, Medical School, University of Vienna, Vienna (Austria)

    2003-11-01

    Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[{sup 18}F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean{+-}SD), were 2.05{+-}0.91 for MET and 2.04{+-}0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of {sup 18}F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. (orig.)

  14. High field strength magnetic resonance imaging in paediatric brain tumour surgery--its role in prevention of early repeat resections.

    Science.gov (United States)

    Avula, Shivaram; Pettorini, Benedetta; Abernethy, Laurence; Pizer, Barry; Williams, Dawn; Mallucci, Conor

    2013-10-01

    The purpose of this study is to compare the surgical and imaging outcome in children who underwent brain tumour surgery with intention of complete tumour resection, prior to and following the start of intra-operative MRI (ioMRI) service. ioMRI service for brain tumour resection commenced in October 2009. A cohort of patients operated between June 2007 and September 2009 with a pre-surgical intention of complete tumour resection were selected (Group A). A similar number of consecutive cases were selected from a prospective database of patients undergoing ioMRI (Group B). The demographics, imaging, pathology and surgical outcome of both groups were compared. Thirty-six of 47 cases from Group A met the inclusion criterion and 36 cases were selected from Group B; 7 of the 36 cases in Group A had unequivocal evidence of residual tumour on the post-operative scan; 5 (14%) of them underwent repeat resection within 6 months post-surgery. In Group B, ioMRI revealed unequivocal evidence of residual tumour in 11 of the 36 cases following initial resection. In 10 of these 11 cases, repeat resections were performed during the same surgical episode and none of these 11 cases required repeat surgery in the following 6 months. Early repeat resection rate was significantly different between both groups (p = 0.003). Following the advent of ioMRI at our institution, the need for repeat resection within 6 months has been prevented in cases where ioMRI revealed unequivocal evidence of residual tumour.

  15. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model

    International Nuclear Information System (INIS)

    Marques, Ines J; Bagowski, Christoph P; Weiss, Frank Ulrich; Vlecken, Danielle H; Nitsche, Claudia; Bakkers, Jeroen; Lagendijk, Anne K; Partecke, Lars Ivo; Heidecke, Claus-Dieter; Lerch, Markus M

    2009-01-01

    Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For primary human tumours we establish here a simple, fast, sensitive and cost-effective in vivo model to analyse tumour invasion and metastatic behaviour. We fluorescently labelled small explants from gastrointestinal human tumours and investigated their metastatic behaviour after transplantation into zebrafish embryos and larvae. The transparency of the zebrafish embryos allows to follow invasion, migration and micrometastasis formation in real-time. High resolution imaging was achieved through laser scanning confocal microscopy of live zebrafish. In the transparent zebrafish embryos invasion, circulation of tumour cells in blood vessels, migration and micrometastasis formation can be followed in real-time. Xenografts of primary human tumours showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumour tissue was implanted. Furthermore, primary human tumour cells, when organotopically implanted in the zebrafish liver, demonstrated invasiveness and metastatic behaviour, whereas primary control cells remained in the liver. Pancreatic tumour cells showed no metastatic behaviour when injected into cloche mutant embryos, which lack a functional vasculature. Our results show that the zebrafish is a useful in vivo animal model for rapid analysis of invasion and metastatic behaviour of primary human tumour specimen

  16. Texture analysis in quantitative MR imaging. Tissue characterisation of normal brain and intracranial tumours at 1.5 T

    DEFF Research Database (Denmark)

    Kjaer, L; Ring, P; Thomsen, C

    1995-01-01

    The diagnostic potential of texture analysis in quantitative tissue characterisation by MR imaging at 1.5 T was evaluated in the brain of 6 healthy volunteers and in 88 patients with intracranial tumours. Texture images were computed from calculated T1 and T2 parameter images by applying groups o...... to be successful in some cases of clinical importance. However, no discrimination between benign and malignant tumour growth was possible. Much texture information seems to be contained in MR images, which may prove useful for classification and image segmentation....

  17. Challenges in providing culturally-competent care to patients with metastatic brain tumours and their families.

    Science.gov (United States)

    Longo, Lianne; Slater, Serena

    2014-01-01

    Being diagnosed with a metastatic brain tumour can be devastating as it is characterized by very low cure rates, as well as significant morbidity and mortality. Given the poor life expectancy and progressive disability that ensues, patients and family members experience much turmoil, which includes losses that bring about changes to family roles, routines and relationships. Crisis and conflict are common during such major disruptions to a family system, as individual members attempt to make sense of the illness experience based on cultural and spiritual beliefs, past experiences and personal philosophies. It is imperative health care providers strive towards increased awareness and knowledge of how culture affects the overall experience of illness and death in order to help create a mutually satisfactory care plan. Providing culturally-competent care entails the use of proper communication skills to facilitate the exploration of patient and family perspectives and allows for mutual decision making. A case study will illustrate the challenges encountered in providing culturally-competent care to a woman with brain cancer and her family. As the patient's health declined, the family entered into a state of crisis where communication between family members and health care professionals was strained; leading to conflict and sub-optimal outcomes. This paper will address the ethical dilemma of providing culturally-competent care when a patient's safety is at risk, and the nursing implications of upholding best practices in the context of differing beliefs and priorities.

  18. Increasing Rates of Brain Tumours in the Swedish National Inpatient Register and the Causes of Death Register

    Directory of Open Access Journals (Sweden)

    Lennart Hardell

    2015-04-01

    Full Text Available Radiofrequency emissions in the frequency range 30 kHz–300 GHz were evaluated to be Group 2B, i.e., “possibly”, carcinogenic to humans by the International Agency for Research on Cancer (IARC at WHO in May 2011. The Swedish Cancer Register has not shown increasing incidence of brain tumours in recent years and has been used to dismiss epidemiological evidence on a risk. In this study we used the Swedish National Inpatient Register (IPR and Causes of Death Register (CDR to further study the incidence comparing with the Cancer Register data for the time period 1998–2013 using joinpoint regression analysis. In the IPR we found a joinpoint in 2007 with Annual Percentage Change (APC +4.25%, 95% CI +1.98, +6.57% during 2007–2013 for tumours of unknown type in the brain or CNS. In the CDR joinpoint regression found one joinpoint in 2008 with APC during 2008–2013 +22.60%, 95% CI +9.68, +37.03%. These tumour diagnoses would be based on clinical examination, mainly CT and/or MRI, but without histopathology or cytology. No statistically significant increasing incidence was found in the Swedish Cancer Register during these years. We postulate that a large part of brain tumours of unknown type are never reported to the Cancer Register. Furthermore, the frequency of diagnosis based on autopsy has declined substantially due to a general decline of autopsies in Sweden adding further to missing cases. We conclude that the Swedish Cancer Register is not reliable to be used to dismiss results in epidemiological studies on the use of wireless phones and brain tumour risk.

  19. Hybrid MR-PET of brain tumours using amino acid PET and chemical exchange saturation transfer MRI.

    Science.gov (United States)

    da Silva, N A; Lohmann, P; Fairney, J; Magill, A W; Oros Peusquens, A-M; Choi, C-H; Stirnberg, R; Stoffels, G; Galldiks, N; Golay, X; Langen, K-J; Jon Shah, N

    2018-06-01

    PET using radiolabelled amino acids has become a promising tool in the diagnostics of gliomas and brain metastasis. Current research is focused on the evaluation of amide proton transfer (APT) chemical exchange saturation transfer (CEST) MR imaging for brain tumour imaging. In this hybrid MR-PET study, brain tumours were compared using 3D data derived from APT-CEST MRI and amino acid PET using O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET). Eight patients with gliomas were investigated simultaneously with 18 F-FET PET and APT-CEST MRI using a 3-T MR-BrainPET scanner. CEST imaging was based on a steady-state approach using a B 1 average power of 1μT. B 0 field inhomogeneities were corrected a Prametric images of magnetisation transfer ratio asymmetry (MTR asym ) and differences to the extrapolated semi-solid magnetisation transfer reference method, APT# and nuclear Overhauser effect (NOE#), were calculated. Statistical analysis of the tumour-to-brain ratio of the CEST data was performed against PET data using the non-parametric Wilcoxon test. A tumour-to-brain ratio derived from APT# and 18 F-FET presented no significant differences, and no correlation was found between APT# and 18 F-FET PET data. The distance between local hot spot APT# and 18 F-FET were different (average 20 ± 13 mm, range 4-45 mm). For the first time, CEST images were compared with 18 F-FET in a simultaneous MR-PET measurement. Imaging findings derived from 18 F-FET PET and APT CEST MRI seem to provide different biological information. The validation of these imaging findings by histological confirmation is necessary, ideally using stereotactic biopsy.

  20. Predictive model for functional consequences of oral cavity tumour resections

    NARCIS (Netherlands)

    van Alphen, M.J.A.; Hageman, T.A.G.; Hageman, Tijmen Antoon Geert; Smeele, L.E.; Balm, Alfonsus Jacobus Maria; Balm, A.J.M.; van der Heijden, Ferdinand; Lemke, H.U.

    2013-01-01

    The prediction of functional consequences after treatment of large oral cavity tumours is mainly based on the size and location of the tumour. However, patient specific factors play an important role in the functional outcome, making the current predictions unreliable and subjective. An objective

  1. International Case-Control Study of Adult Brain, Head and Neck Tumours: Results of the Feasibility Study (invited paper)

    International Nuclear Information System (INIS)

    Cardis, E.; Kilkenny, M.

    1999-01-01

    The objectives of the feasibility study were to collect and analyse the information necessary to assess the feasibility of a multi-centric study of adult head and neck tumours (including brain tumours) and mobile telephones. Information was obtained on the availability and accessibility of records from companies, the prevalence of mobile telephone use over time and the expected number of tumour cases in the proposed study regions. The conclusion is that it is feasible to develop a study of the relation between mobile telephone use and brain cancer risk. The feasibility of a study of the relation between radiofrequency exposure and cancer risk is, however, unclear at present. It is unknown whether a sufficiently accurate and precise RF exposure gradient can be derived to classify adequately each subject in the proposed study. A study of the relation between mobile telephone use and risk of salivary gland tumours and acoustic neurinomas is probably feasible, but more information is required about the logistic difficulties of ascertaining these cases in the study regions. Two subcommittees have been formed to develop the exposure measurement and epidemiological aspect of the study. (author)

  2. Pre-surgical planning and MR-tractography utility in brain tumour resection

    Energy Technology Data Exchange (ETDEWEB)

    Romano, A.; Fantozzi, L.M.; Bozzao, A. [University Sapienza, Department of Neuroradiology, S. Andrea Hospital, Rome (Italy); D' Andrea, G.; Mastronardi, L.; Ferrante, L. [University Sapienza, Department of Neurosurgery, S. Andrea Hospital, Rome (Italy); Minniti, G. [University Sapienza, Department of Radiotherapy, S. Andrea Hospital, Rome (Italy)

    2009-12-15

    The purposes of this study were (1) to evaluate the possible identification of trajectories of fibre tracts, (2) to examine the useful of a neuronavigation system for pre-surgical planning, (3) to assess pre- and post-surgery patients' clinical condition and (4) to evaluate the impact of this information on surgical planning and procedure. Twenty-eight right-handed patients were prospectively and consecutively studied. All the patients were clinically assessed by a neurologist in both pre- and post-surgical phases. Separately the pyramidal tract, optic radiation and arcuate fasciculus were reconstructed. The trajectories were considered suitable for surgical planning if there were no interruptions of any of the layers at the level of the lesion. Dedicated software 'merged' the acquired images with the tractographic processing, and the whole dataset was sent to the neuronavigation system. The assessment of the 37 visualised trajectories close to the tumour resulted in a modification of the surgical approach to corticotomy in six patients (21%); the impact on the definition of the resection margins during surgery was 64% (18 cases). The overall impact percentage on the surgical procedure was 82%. In 27 cases, the symptoms had not changed. MR-tractography provides the neurosurgeon with a new anatomical view that has an impact on the surgical resection planning for brain neoplasms. (orig.)

  3. Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood

    International Nuclear Information System (INIS)

    Shalet, S.M.; Beardwell, C.G.; MacFarlane, I.A.; Morris Jones, P.H.; Pearson, D.

    1977-01-01

    Hypothalamic-pituitary function was assessed in 20 adult subjects who were treated with cerebral irradiation for brain tumours during childhood between 8 and 32 years earlier. Nine patients showed impaired growth hormone (GH) responses to hypoglycaemia, of whom, 7 are below the third centile for standing height. All GH deficient subjects recieved more than 2950 rads to the hypothalamic-pituitary axis with a maximum dose of approximately 5000 rads being used in one case. Three subjects have an elevated basal serum thyroid stimulating hormone (TSH) level and 2 of these show an exaggerated TSH response to thyrotrophin releasing hormone (TRH) but no patient was clinically or biochemically hypothyroid. The rest of hypothalamic-pituitary function was essentially normal. This study shows that multiple pituitary hormone deficiencies do not develop with time when the radiation dose is below a critical level. Thus it appears that there is a gradation of radiation damage to the hypothalamic-pituitary axis which is dependent primarily on the dose received rather than the time interval after radiotherapy. (auth.)

  4. Growth and growth hormone secretion in children following treatment of brain tumours with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Darendeliler, F.; Livesey, E.A.; Hindmarsh, P.C.; Brook, C.G.D. (Endocrine Unit, The Middlesex Hospital, London (UK))

    1990-01-01

    We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n=20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n=36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whome were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m{sup 2}/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. (authors).

  5. Growth and growth hormone secretion in children following treatment of brain tumours with radiotherapy

    International Nuclear Information System (INIS)

    Darendeliler, F.; Livesey, E.A.; Hindmarsh, P.C.; Brook, C.G.D.

    1990-01-01

    We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n=20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n=36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whome were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m 2 /week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. (authors)

  6. Pre-surgical planning and MR-tractography utility in brain tumour resection

    International Nuclear Information System (INIS)

    Romano, A.; Fantozzi, L.M.; Bozzao, A.; D'Andrea, G.; Mastronardi, L.; Ferrante, L.; Minniti, G.

    2009-01-01

    The purposes of this study were (1) to evaluate the possible identification of trajectories of fibre tracts, (2) to examine the useful of a neuronavigation system for pre-surgical planning, (3) to assess pre- and post-surgery patients' clinical condition and (4) to evaluate the impact of this information on surgical planning and procedure. Twenty-eight right-handed patients were prospectively and consecutively studied. All the patients were clinically assessed by a neurologist in both pre- and post-surgical phases. Separately the pyramidal tract, optic radiation and arcuate fasciculus were reconstructed. The trajectories were considered suitable for surgical planning if there were no interruptions of any of the layers at the level of the lesion. Dedicated software 'merged' the acquired images with the tractographic processing, and the whole dataset was sent to the neuronavigation system. The assessment of the 37 visualised trajectories close to the tumour resulted in a modification of the surgical approach to corticotomy in six patients (21%); the impact on the definition of the resection margins during surgery was 64% (18 cases). The overall impact percentage on the surgical procedure was 82%. In 27 cases, the symptoms had not changed. MR-tractography provides the neurosurgeon with a new anatomical view that has an impact on the surgical resection planning for brain neoplasms. (orig.)

  7. A case series discussing the anaesthetic management of pregnant patients with brain tumours [v2; ref status: indexed, http://f1000r.es/2hn

    Directory of Open Access Journals (Sweden)

    Alaa A Abd-Elsayed

    2013-12-01

    Full Text Available Pregnancy may aggravate the natural history of an intracranial tumour, and may even unmask a previously unknown diagnosis. Here we present a series of seven patients who had brain tumours during pregnancy. The aim of this case series is to characterize the current perioperative management and to suggest evidence based guidelines for the anaesthetic management of pregnant females with brain tumours. This is a retrospective study. Information on pregnant patients diagnosed with brain tumours that underwent caesarean section (CS and/or brain tumour resection from May 2003 through June 2008 was obtained from the Department of General Anaesthesia and the Rose Ella Burkhardt Brain Tumour & Neuro-Oncology Centre (BBTC at the Cleveland Clinic, OH, USA. The mean age was 34.5 years (range 29-40 years old. Six patients had glioma, two of whom had concomitant craniotomy and CS. Six cases had the tumour in the frontal lobe. Four cases were operated on under general anaesthesia and three underwent awake craniotomy. The neonatal outcomes of the six patients with elective or emergent delivery were six viable infants with normal Apgar scores. Pregnancy was terminated in the 7th patient. In conclusion, good knowledge of the variable anesthetic agents and their effects on the fetus is very important in managing those patients.

  8. Preoperative mapping of cortical language areas in adult brain tumour patients using PET and individual non-normalised SPM analyses

    International Nuclear Information System (INIS)

    Meyer, Philipp T.; Sturz, Laszlo; Schreckenberger, Mathias; Setani, Keyvan S.; Buell, Udalrich; Spetzger, Uwe; Meyer, Georg F.; Sabri, Osama

    2003-01-01

    In patients scheduled for the resection of perisylvian brain tumours, knowledge of the cortical topography of language functions is crucial in order to avoid neurological deficits. We investigated the applicability of statistical parametric mapping (SPM) without stereotactic normalisation for individual preoperative language function brain mapping using positron emission tomography (PET). Seven right-handed adult patients with left-sided brain tumours (six frontal and one temporal) underwent 12 oxygen-15 labelled water PET scans during overt verb generation and rest. Individual activation maps were calculated for P<0.005 and P<0.001 without anatomical normalisation and overlaid onto the individuals' magnetic resonance images for preoperative planning. Activations corresponding to Broca's and Wernicke's areas were found in five and six cases, respectively, for P<0.005 and in three and six cases, respectively, for P<0.001. One patient with a glioma located in the classical Broca's area without aphasic symptoms presented an activation of the adjacent inferior frontal cortex and of a right-sided area homologous to Broca's area. Four additional patients with left frontal tumours also presented activations of the right-sided Broca's homologue; two of these showed aphasic symptoms and two only a weak or no activation of Broca's area. Other frequently observed activations included bilaterally the superior temporal gyri, prefrontal cortices, anterior insulae, motor areas and the cerebellum. The middle and inferior temporal gyri were activated predominantly on the left. An SPM group analysis (P<0.05, corrected) in patients with left frontal tumours confirmed the activation pattern shown by the individual analyses. We conclude that SPM analyses without stereotactic normalisation offer a promising alternative for analysing individual preoperative language function brain mapping studies. The observed right frontal activations agree with proposed reorganisation processes, but

  9. A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.

    OpenAIRE

    Vienneau Danielle; Infanger Denis; Feychting Maria; Schüz Joachim; Schmidt Lisbeth Samsø; Poulsen Aslak Harbo; Tettamanti Giorgio; Klæboe Lars; Kuehni Claudia E; Tynes Tore; Von der Weid Nicolas; Lannering Birgitta; Röösli Martin

    2016-01-01

    Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight length maternal age) birth characteristics (e.g. vacuum extraction preterm delivery birth order) and exposures during pregnancy (e.g. maternal: smoking working dietary supplement intake) in relation to risk of brain tumour diagnosis among 7 19 year olds. The multinational case control study in Denmark Sweden Norway and Switzerland (CEFALO) included interviews with 352 (particip...

  10. Double-labelling immunohistochemistry for MGMT and a “cocktail” of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours

    Science.gov (United States)

    2013-01-01

    Background Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA, a recognised molecular genetic technique which we applied as the gold-standard for the methylation status). Results Double-labelling immunohistochemistry for MGMT produced a visual separation of tumourous and non-tumourous elements on the same histological slide, making it quick and easy to determine whether tumour cell nuclei were MGMT-positive or MGMT-negative (and thereby infer the methylation status of the tumour). We found good agreement between observers (kappa 0.76) and within observer (kappa 0.84). Furthermore, double-labelling showed good specificity (80%), sensitivity (73.33%), positive predictive value (PPV, 83.33%) and negative predictive value (NPV, 68.75%) compared to MS-MLPA. Double-labelling was quicker and easier to assess than single-labelling and it outperformed quantitative computerised image analysis of MGMT single-labelling in terms of sensitivity, specificity, PPV and NPV. Conclusions Double-labelling immunohistochemistry for MGMT and a cocktail of non-tumourous elements provides a "one look" method for determining whether tumour cell nuclei are MGMT-positive or MGMT-negative. This can be used to infer the methylation status of the tumour. There is good observer agreement and good specificity, sensitivity, PPV and NPV compared to a molecular gold-standard. PMID:24252243

  11. Double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours.

    Science.gov (United States)

    Burke, Elinor; Grobler, Mariana; Elderfield, Kay; Bond, Frances; Crocker, Matthew; Taylor, Rohan; Bridges, Leslie R

    2013-06-10

    Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA, a recognised molecular genetic technique which we applied as the gold-standard for the methylation status). Double-labelling immunohistochemistry for MGMT produced a visual separation of tumourous and non-tumourous elements on the same histological slide, making it quick and easy to determine whether tumour cell nuclei were MGMT-positive or MGMT-negative (and thereby infer the methylation status of the tumour). We found good agreement between observers (kappa 0.76) and within observer (kappa 0.84). Furthermore, double-labelling showed good specificity (80%), sensitivity (73.33%), positive predictive value (PPV, 83.33%) and negative predictive value (NPV, 68.75%) compared to MS-MLPA. Double-labelling was quicker and easier to assess than single-labelling and it outperformed quantitative computerised image analysis of MGMT single-labelling in terms of sensitivity, specificity, PPV and NPV. Double-labelling immunohistochemistry for MGMT and a cocktail of non-tumourous elements provides a "one look" method for determining whether tumour cell nuclei are MGMT-positive or MGMT-negative. This can be used to infer the methylation status of the tumour. There is good observer agreement and good specificity, sensitivity, PPV and NPV compared to a molecular gold-standard.

  12. Precise modelling of the eye for proton therapy of intra-ocular tumours

    Energy Technology Data Exchange (ETDEWEB)

    Dobler, B.; Bendl, R. [Medizinische Physik, Deutsches Krebsforschungszentrum, INF 280, 69120 Heidelberg (Germany)]. E-mails: b.dobler@dkfz-heidelberg.de; barbara.dobler@gmx.de; r.bendl@dkfz-heidelberg.de

    2002-02-21

    A new method is described that allows precise modelling of organs at risk and target volume for radiation therapy of intra-ocular tumours. The aim is to optimize the dose distribution and thus to reduce normal tissue complication probability. A geometrical 3D model based on elliptic shapes was developed that can be used for multimodal model-based segmentation of 3D patient data. The tumour volume cannot be clearly identified in CT and MR data, whereas the tumour outline can be discriminated very precisely in fundus photographs. Therefore, a multimodal 2D fundus diagram was developed, which allows us to correlate and display simultaneously information extracted from the eye model, 3D data and the fundus photograph. Thus, the connection of fundus diagram and 3D data is well-defined and the 3D volume can be calculated directly from the tumour outline drawn onto the fundus photograph and the tumour height measured by ultrasound. The method allows the calculation of a precise 3D eye model of the patient, including the different structures of the eye as well as the tumour volume. The method was developed as part of the new 3D treatment planning system OCTOPUS for proton therapy of ocular tumours within a national research project together with the Hahn-Meitner-Institut Berlin. (author)

  13. Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine

    International Nuclear Information System (INIS)

    Becherer, Alexander; Karanikas, Georgios; Szabo, Monica; Zettinig, Georg; Wadsak, Wolfgang; Kletter, Kurt; Asenbaum, Susanne; Marosi, Christine; Henk, Christine; Wunderbaldinger, Patrick; Czech, Thomas

    2003-01-01

    Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[ 18 F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean±SD), were 2.05±0.91 for MET and 2.04±0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of 18 F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. (orig.)

  14. Contribution of sup(99m)Tc pertechnetate brain scintigraphy in the diagnosis of tumours of posterior fossa

    International Nuclear Information System (INIS)

    Sergent, Aline.

    1976-01-01

    The present work concerns 38 posterior cranial fossa tumour cases subjected to sup(99m)Tc pertechnetate brain scintigraphy between May 1974 and June 1976. 33 of these patients have undergone an anatomical check while for the remaining 5, the existence of a posterior fossa tumour is established from the conjunction of clinical signs and other paraclinical examinations. The procedure was the same for all these 38 patients: after a 300 μC/kg injection of tracer, an immediate angioscintigraphic period, an early set of pictures (half an hour after the tracer injection) then delayed set (4 to 5 hours later) taken from 4 angles: front, back and two profiles. The examination was performed with an OHIO NUCLEAR SIEMENS gamma camera and sometimes a conventional scanner as well (the latter giving no better a diagnosis than the former). In 75% of the cases a hyperfixation of the injected tracer was observed and its site located quite accurately in the posterior fossa tumour. The etiology of the lesion could be diagnosed in 'most probable' or 'least probable' terms. Examination of work by other authors, who obtained similar results, leads to the conclusion that this method is very helpful in the diagnosis of posterior fossa tumours when used as a means of early detection, before the undertaking of more complex neuroradiological explorations [fr

  15. Oscillatory dynamics in a model of vascular tumour growth - implications for chemotherapy

    Directory of Open Access Journals (Sweden)

    Maini PK

    2010-04-01

    Full Text Available Abstract Background Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth. Results By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls. Conclusions We have developed a mathematical model of vascular tumour growth formulated as a system of partial

  16. Noninvasive quantification of 18F-FLT human brain PET for the assessment of tumour proliferation in patients with high-grade glioma

    International Nuclear Information System (INIS)

    Backes, Heiko; Ullrich, Roland; Neumaier, Bernd; Kracht, Lutz; Wienhard, Klaus; Jacobs, Andreas H.

    2009-01-01

    Compartmental modelling of 3 ' -deoxy-3 ' -[ 18 F]-fluorothymidine ( 18 F-FLT) PET-derived kinetics provides a method for noninvasive assessment of the proliferation rate of gliomas. Such analyses, however, require an input function generally derived by serial blood sampling and counting. In the current study, 18 F-FLT kinetic parameters obtained from image-derived input functions were compared with those from input functions derived from arterialized blood samples. Based on the analysis of 11 patients with glioma (WHO grade II-IV) a procedure for the automated extraction of an input function from 18 F-FLT brain PET data was derived. The time-activity curve of the volume of interest with the maximum difference in 18 F-FLT uptake during the first 5 min after injection and the period from 60 to 90 min was corrected for partial-volume effects and in vivo metabolism of 18 F-FLT. For each patient a two-compartment kinetic model was applied to the tumour tissue using the image-derived input function. The resulting kinetic rate constants K 1 (transport across the blood-brain barrier) and K i (metabolic rate constant or net influx constant) were compared with those obtained from the same data using the input function derived from blood samples. Additionally, the metabolic rate constant was correlated with the frequency of tumour cells stained with Ki-67, a widely used immunohistochemical marker of cell proliferation. The rate constants from kinetic modelling were comparable when the blood sample-derived input functions were replaced by the image-derived functions (K 1,img and K 1,sample , r = 0.95, p -5 ; K i,img and K i,sample , r = 0.86, p 1,img and K 1,sample , p = 0.20; K i,img and K i,sample , p = 0.92). Furthermore, a significant correlation between K i,img and the percentage of Ki-67-positive cells was observed (r = 0.73, p = 0.01). Kinetic modelling of 18 F-FLT brain PET data using image-derived input functions extracted from human brain PET data with the practical

  17. DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours

    DEFF Research Database (Denmark)

    Mollenhauer, J; Wiemann, S; Scheurlen, W

    1997-01-01

    Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80% of the tumo......Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80....... Intragenic homozygous deletions has been detected in 2/20 medulloblastomas and in 9/39 glioblastomas multiformes. Lack of DMBT1 expression has been demonstrated in 4/5 brain-tumour cell lines. We suggest that DMBT1 is a putative tumour-suppressor gene implicated in the carcinogenesis of medulloblastoma...

  18. Tumour size measurement in a mouse model using high resolution MRI

    International Nuclear Information System (INIS)

    Montelius, Mikael; Ljungberg, Maria; Horn, Michael; Forssell-Aronsson, Eva

    2012-01-01

    Animal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (10 −2 –10 −1 g). The aim of this study was to assess the accuracy of MRI based tumour size measurements of small tumours on mice. 2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1 g/cm 3 , using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis. Strong correlations were demonstrated between MRI- and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2 g) tumours were assessed for inter- and intraobserver variation. In 3D images, the voxel sizes could be increased from 160 3 μm 3 to 240 3 μm 3 without affecting the results significantly, thus reducing acquisition time substantially. 2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2 g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session

  19. Constrained customization of non-coplanar beam orientations in radiotherapy of brain tumours

    International Nuclear Information System (INIS)

    Rowbottom, C.G.; Oldham, M.; Webb, S.

    1999-01-01

    A methodology for the constrained customization of non-coplanar beam orientations in radiotherapy treatment planning has been developed and tested on a cohort of five patients with tumours of the brain. The methodology employed a combination of single and multibeam cost functions to produce customized beam orientations. The single-beam cost function was used to reduce the search space for the multibeam cost function, which was minimized using a fast simulated annealing algorithm. The scheme aims to produce well-spaced, customized beam orientations for each patient that produce low dose to organs at risk (OARs). The customized plans were compared with standard plans containing the number and orientation of beams chosen by a human planner. The beam orientation constraint-customized plans employed the same number of treatment beams as the standard plan but with beam orientations chosen by the constrained-customization scheme. Improvements from beam orientation constraint-customization were studied in isolation by customizing the beam weights of both plans using a dose-based downhill simplex algorithm. The results show that beam orientation constraint-customization reduced the maximum dose to the orbits by an average of 18.8 (±3.8, 1SD)% and to the optic nerves by 11.4 (±4.8, 1SD)% with no degradation of the planning target volume (PTV) dose distribution. The mean doses, averaged over the patient cohort, were reduced by 4.2 (±1.1, 1SD)% and 12.4 (±3.1 1SD)% for the orbits and optic nerves respectively. In conclusion, the beam orientation constraint-customization can reduce the dose to OARs, for few-beam treatment plans, when compared with standard treatment plans developed by a human planner. (author)

  20. Classification of brain tumours using short echo time 1H MR spectra

    Science.gov (United States)

    Devos, A.; Lukas, L.; Suykens, J. A. K.; Vanhamme, L.; Tate, A. R.; Howe, F. A.; Majós, C.; Moreno-Torres, A.; van der Graaf, M.; Arús, C.; Van Huffel, S.

    2004-09-01

    The purpose was to objectively compare the application of several techniques and the use of several input features for brain tumour classification using Magnetic Resonance Spectroscopy (MRS). Short echo time 1H MRS signals from patients with glioblastomas ( n = 87), meningiomas ( n = 57), metastases ( n = 39), and astrocytomas grade II ( n = 22) were provided by six centres in the European Union funded INTERPRET project. Linear discriminant analysis, least squares support vector machines (LS-SVM) with a linear kernel and LS-SVM with radial basis function kernel were applied and evaluated over 100 stratified random splittings of the dataset into training and test sets. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of binary classifiers, while the percentage of correct classifications was used to evaluate the multiclass classifiers. The influence of several factors on the classification performance has been tested: L2- vs. water normalization, magnitude vs. real spectra and baseline correction. The effect of input feature reduction was also investigated by using only the selected frequency regions containing the most discriminatory information, and peak integrated values. Using L2-normalized complete spectra the automated binary classifiers reached a mean test AUC of more than 0.95, except for glioblastomas vs. metastases. Similar results were obtained for all classification techniques and input features except for water normalized spectra, where classification performance was lower. This indicates that data acquisition and processing can be simplified for classification purposes, excluding the need for separate water signal acquisition, baseline correction or phasing.

  1. Misdiagnosis of Child Abuse Related to Delay in Diagnosing a Paediatric Brain Tumour

    Directory of Open Access Journals (Sweden)

    Lynne Wrennall Ph.D.

    2008-01-01

    Full Text Available Conflicting opinion regarding the relative weight that should be allocated to the investigation of organic causes of child illness, compared to the pursuit of suspicions of child abuse, has generated considerable public debate. The discourse of Munchausen Syndrome by Proxy/Fabricated and Induced Illness is at the centre of contention. In particular, concern has arisen that children's medical needs are being neglected when their conditions are misdiagnosed as child abuse. This paper documents a case study in which the use of Child Protection procedures was linked to the belief that the child's illness had “no organic cause.” The case study is contextualised in a review of literature relevant to the diagnostic process. The deployment of the Child Protection perspective resulted in significant delay in the diagnosis of the child's brain tumour. The child was ultimately found to be suffering from an optic chasm mass lesion involving the hypothalamus and the medial temporal regions, resulting in Diencephalic Syndrome. The evidence in this case is that erring on the side of suspecting Munchausen Syndrome by Proxy/Fabricated and Induced Illness, was not “erring on the side of the child.” Several lessons need to be learned from the case. The importance of ensuring that the Child Protection perspective does not displace adequate assessment of alternative explanations for the child's condition is emphasised, as is the need for good communication in medical relationships. Strategies involving empathy, mediation, negotiation and conflict resolution may provide a more appropriate and therapeutic alternative to the use of Child Protection procedures in cases where the diagnosis is contentious. The need to re-write relevant policy, protocols and guidance is imperative.

  2. Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results

    International Nuclear Information System (INIS)

    Fellner, C.; Friedrich-Alexander-Univ., Erlangen-Nuernberg; Schlaier, J.; Schwerdtner, J.; Brawanski, A.; Fellner, F.; Oberoesterreichische Landesnervenklinik, Linz; Held, P.; Blank, M.; Kalender, W.A.

    1999-01-01

    The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. (orig.) [de

  3. A case series discussing the anaesthetic management of pregnant patients with brain tumours [v1; ref status: indexed, http://f1000r.es/y7

    Directory of Open Access Journals (Sweden)

    Alaa A Abd-Elsayed

    2013-03-01

    Full Text Available Pregnancy may aggravate the natural history of an intracranial tumour, and may even unmask a previously unknown diagnosis. Here we present a series of seven patients who had brain tumours during pregnancy. The aim of this case series is to characterize the current perioperative management and to suggest evidence based guidelines for the anaesthetic management of pregnant females with brain tumours. This is a retrospective study. Information on pregnant patients diagnosed with brain tumours that underwent caesarean section (CS and/or brain tumour resection from May 2003 through June 2008 was obtained from the Department of General Anaesthesia and the Rose Ella Burkhardt Brain Tumour & Neuro-Oncology Centre (BBTC at the Cleveland Clinic, OH, USA. The mean age was 34.5 years (range 29-40 years old. Six patients had glioma, two of whom had concomitant craniotomy and CS. Six cases had the tumour in the frontal lobe. Four cases were operated on under general anaesthesia and three underwent awake craniotomy. The neonatal outcomes of the six patients with elective or emergent delivery were six viable infants with normal Apgar scores. Pregnancy was terminated in the 7th patient. In conclusion, management of brain tumours in pregnant women is mainly reliant on case reports and the doctor’s personal experience. Therefore, close communication between the neurosurgeon, neuroanaesthetist, obstetrician and the patient is crucial. General anaesthesia, propofol, dexmedetomidine and remifentanil were used in our study and were safe. Although this may not agree with previous studies, desflurane and isoflurane were used in our patients with no detectable complications.

  4. Dosimetry comparison of irradiation with conformal radiotherapy, intensity modulated radiotherapy, conformal radiotherapy in stereotactic conditions and robotic stereotactic radiotherapy for benign brain tumours

    International Nuclear Information System (INIS)

    Spasic, E.; Noel, A.; Buchheit, I.; Bernier, V.

    2011-01-01

    Purpose. - To compare several techniques in order to determine the best treatment for benign brain tumours. Methods and patients. - A retrospective study was performed for five patients who received 3D-conformal radiotherapy, intensity modulated radiotherapy or CyberKnife R . These patients had a meningioma, a pituitary tumour, a cranio-pharyngioma or a neurinoma. In each case, these treatment plans were optimised and compared with the three other dosimetries. Radiobiological or positioning parameters were evaluated, as well as dosimetric parameters, in order to compare treatments with different characteristics. Results. - The dosimetric parameters showed that the choice of treatment seemed to be determined mostly by tumour size, shape and proximity with organs at risk (not tumour localisation). Whereas the results showed no significant deviations with regards to the radiobiological parameters. Therefore, with these parameters, it was difficult to give priority to a treatment. Conclusions. - With regards to benign brain tumours of medium or large size, intensity modulated radiotherapy seemed the recommended treatment. It enabled to obtain a good ratio between efficacy and toxicity for tumours that are really close to organs at risk. Concerning small benign brain tumours, the CyberKnife R was probably the best treatment. (authors)

  5. Hyperthermia improves the antitumour effect of metronomic cyclophosphamide in a rat transplantable brain tumour

    International Nuclear Information System (INIS)

    Dahl Borkamo, Erling; Fluge, Oystein; Mella, Olav; Akslen, Lars A.; Bruland, Ove; Dahl, Olav

    2008-01-01

    Background and purpose: As low-dose metronomic cyclophosphamide (CTX) and hyperthermia (HT) both exert antitumour effects in part through antiangiogenic mechanisms, interactive effects of the two modalities were explored. Materials and methods: Subcutaneously implanted rat tumours (BT4An) were treated with CTX 35 mg/kg i.p. three doses a week for two weeks, local water-bath HT yielding mean tumour temperature of 43 o C for one hour at day 0, both modalities combined (CTX-HT 0 ), or saline. TUNEL assays, immunohistochemical staining of thrombospondin 1 (TSP-1) and real time RT-PCR of TSP-1 mRNA were analysed the first three hours after completed treatment day 0. Results: Metronomic dosed CTX (p = 0.006) and HT (p 0 (41%) treated rats. TSP-1 protein was specifically upregulated in the vascular matrix of tumours receiving CTX (weak), HT (moderate) and CTX-HT 0 (strong). In contrast, reduced expression of TSP-1 protein was observed in tumour cells after HT alone and CTX-HT 0 . TUNEL assays indicated induction of apoptosis by HT and CTX-HT 0 90 minutes after end of the first treatment. Conclusion: A single session of local HT enhances the effects of low-dose metronomic CTX, possibly in part mediated through a differential effect on TSP-1 protein levels in tumour cells and tumour vasculature

  6. In vivo bio-distribution and homing of endothelial outgrowth cells in a tumour model

    International Nuclear Information System (INIS)

    Bertelsen, Lotte B.; Hagensen, Mette; Busk, Morten; Zhang, Rui; Knudsen, Anne S.; Nielsen, Nathalie; Falborg, Lise; Møller, Bjarne K.; Horsman, Michael R.; Stødkilde-Jørgensen, Hans

    2014-01-01

    Introduction: Endothelial progenitor cells (EPCs) has been reported to have the potential for advancing revascularization of ischemic tissue. However, the heterogeneous nature of these cells calls for specification of the angiogenic potential of each subtype. The purpose of this study was to gain additional insight on the homing capacity of the EPC subtype, endothelial outgrowth cells (EOCs) in tumours using a well-established tumour model. Methods: 111 Indium ( 111 In) – and 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) labelled EOCs derived from human umbilical cord blood were injected into mice with a C3H mammary carcinoma foot tumour. The subsequent capture of the EOCs was traced by estimation of activity in individual organs, autoradiography and fluorescence microscopy. Results: 111 In activity was found in tumour and other organs. However, varying parts of the activity originated from free 111 In lost from EOCs. Autoradiography demonstrated accumulation of 111 In activity in the tumour rim. Microscopy proved that a least part of this radioactivity originated from the presence of human derived EOCs and that those EOCs were not located in the endothelial lining of vessels, in the tumour. Conclusion: The results demonstrated the presence of xenotransplanted EOCs in the rim of a C3H mammary carcinoma. They were, however, not located in the endothelial lining of the vessels, thus indicating that their effect in vasculogenesis might be mediated via paracrine mechanisms rather than differentiating into endothelial cells (ECs) in tumour vessels

  7. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    LENUS (Irish Health Repository)

    Zagozdzon, Agnieszka M

    2012-05-30

    AbstractBackgroundNumerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.ResultsA new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.ConclusionsWe have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and\\/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  8. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    Directory of Open Access Journals (Sweden)

    Zagozdzon Agnieszka M

    2012-05-01

    Full Text Available Abstract Background Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. Results A new mouse strain (MMTV-Luc2 mice expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. Conclusions We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  9. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  10. Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen.

    Science.gov (United States)

    Benedykcinska, Anna; Ferreira, Andreia; Lau, Joanne; Broni, Jessica; Richard-Loendt, Angela; Henriquez, Nico V; Brandner, Sebastian

    2016-02-01

    Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS) can be limited, when the promoter (such as GFAP) is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER) allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours. © 2016. Published by The Company of Biologists Ltd.

  11. Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen

    Directory of Open Access Journals (Sweden)

    Anna Benedykcinska

    2016-02-01

    Full Text Available Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS can be limited, when the promoter (such as GFAP is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours.

  12. Separation of type and grade in cervical tumours using non-mono-exponential models of diffusion-weighted MRI

    International Nuclear Information System (INIS)

    Winfield, Jessica M.; Collins, David J.; Morgan, Veronica A.; DeSouza, Nandita M.; Orton, Matthew R.; Ind, Thomas E.J.; Attygalle, Ayoma; Hazell, Steve

    2017-01-01

    Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours. Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm -2 ). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively. Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis), f and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models. Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours. (orig.)

  13. Separation of type and grade in cervical tumours using non-mono-exponential models of diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, Jessica M.; Collins, David J.; Morgan, Veronica A.; DeSouza, Nandita M. [The Royal Marsden NHS Foundation Trust, MRI Unit, Sutton, Surrey (United Kingdom); The Institute of Cancer Research, Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, London (United Kingdom); Orton, Matthew R. [The Institute of Cancer Research, Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, London (United Kingdom); Ind, Thomas E.J. [The Royal Marsden NHS Foundation Trust, Gynaecology Unit, London (United Kingdom); Attygalle, Ayoma; Hazell, Steve [The Royal Marsden NHS Foundation Trust, Department of Histopathology, London (United Kingdom)

    2017-02-15

    Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours. Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm{sup -2}). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively. Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis), f and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models. Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours. (orig.)

  14. Failure of the PTEN/aPKC/Lgl Axis Primes Formation of Adult Brain Tumours in Drosophila

    Directory of Open Access Journals (Sweden)

    Simona Paglia

    2017-01-01

    Full Text Available Different regions in the mammalian adult brain contain immature precursors, reinforcing the concept that brain cancers, such as glioblastoma multiforme (GBM, may originate from cells endowed with stem-like properties. Alterations of the tumour suppressor gene PTEN are very common in primary GBMs. Very recently, PTEN loss was shown to undermine a specific molecular axis, whose failure is associated with the maintenance of the GBM stem cells in mammals. This axis is composed of PTEN, aPKC, and the polarity determinant Lethal giant larvae (Lgl: PTEN loss promotes aPKC activation through the PI3K pathway, which in turn leads to Lgl inhibition, ultimately preventing stem cell differentiation. To find the neural precursors responding to perturbations of this molecular axis, we targeted different neurogenic regions of the Drosophila brain. Here we show that PTEN mutation impacts aPKC and Lgl protein levels also in Drosophila. Moreover, we demonstrate that PI3K activation is not sufficient to trigger tumourigenesis, while aPKC promotes hyperplastic growth of the neuroepithelium and a noticeable expansion of the type II neuroblasts. Finally, we show that these neuroblasts form invasive tumours that persist and keep growing in the adult, leading the affected animals to untimely death, thus displaying frankly malignant behaviours.

  15. Dynamic CT perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CNS lymphomas

    International Nuclear Information System (INIS)

    Schramm, Peter; Xyda, Argyro; Knauth, Michael; Klotz, Ernst; Tronnier, Volker; Hartmann, Marius

    2010-01-01

    Perfusion computed tomography (PCT) allows to quantitatively assess haemodynamic characteristics of brain tissue. We investigated if different brain tumor types can be distinguished from each other using Patlak analysis of PCT data. PCT data from 43 patients with brain tumours were analysed with a commercial implementation of the Patlak method. Four patients had low-grade glioma (WHO II), 31 patients had glioblastoma (WHO IV) and eight patients had intracerebral lymphoma. Tumour regions of interest (ROIs) were drawn in a morphological image and automatically transferred to maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability (K Trans ). Mean values were calculated, group differences were tested using Wilcoxon and Mann Whitney U-tests. In comparison with normal parenchyma, low-grade gliomas showed no significant difference of perfusion parameters (p > 0.05), whereas high-grade gliomas demonstrated significantly higher values (p Trans , p Trans values compared with unaffected cerebral parenchyma (p = 0.0078) but no elevation of CBV. High-grade gliomas show significant higher CBV values than lymphomas (p = 0.0078). PCT allows to reliably classify gliomas and lymphomas based on quantitative measurements of CBV and K Trans . (orig.)

  16. Improving fMRI reliability in presurgical mapping for brain tumours.

    Science.gov (United States)

    Stevens, M Tynan R; Clarke, David B; Stroink, Gerhard; Beyea, Steven D; D'Arcy, Ryan Cn

    2016-03-01

    Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps. Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test-retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel. The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively). We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

  17. Advance care planning in patients with primary malignant brain tumours: a systematic review

    Directory of Open Access Journals (Sweden)

    Krystal Song

    2016-10-01

    Full Text Available Advance care planning (ACP is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumours (pmBT. A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus and Web of Science up to July 2016. Manual search of bibliographies of articles and grey literature search were also conducted. Two independent reviewers selected studies, extracted data and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included (1 RCT, 17 cohort studies, 1 qualitative study with 4686 participants. All studies scored low to moderate on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision–making. However, the effect of the intervention on quality of life and care at the end-of-life were unclear. There was a low rate of use of ACP discussions at the end-of-life. Advance Directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  18. 2D VS 3D imaging of brain tumours with 18F-Fluoromisonidazole (FMISO) and positron emission tomography (PET)

    International Nuclear Information System (INIS)

    Pathmaraj, K.; Scott, A.M.; Egan, G.F.; Hannah, A.; Tauro, A.; Tochon-Danguy, A.; Sachinidis, J.; Berlangieri, S.U.; Fabinyi, G.; McKay, W.J.; Cher, L.

    1998-01-01

    Full text: 18 F-FMISO accumulates in hypoxic cells and can be used in the PET imaging of brain tumours containing viable but hypoxic cells. The limited activity (typically 130 MBq) of injected 18 F-FMISO yield poor statistics, requiring prolonged imaging in the conventional 2D mode of PET scanning. 3D (septa retracted) imaging allows for more counts to be collected over a shorter time period making it a more practical alternative. This study investigates the contrast resolution that can be obtained from 3D PET scans compared to the corresponding 2D scan. A patient recently diagnosed with brain tumour was injected with 18 -FMISO 2 hours prior to scanning and imaged supine on a 951/31R PET scanner with the head secured firmly in a head holder. The imaging protocol consisted of a 3 min emission rectilinear scan to position the brain in the FOV, a 10 min post-emission transmission scan, a 20 min 2D emission scan and a 5X10 min frames 3D emission scan. Both the 2D and 3D scans were reconstructed with filtered backprojection algorithm. The first 10 min frame of the 3D acquisition was reconstructed. The total true counts were 3 million and 6.06 million in the 2D image and 3D images respectively. The random events were 0.24 million and 0.96 million in the 2D and 3D images respectively. The Noise Equivalent Counts (NEC) were 2.2 million and 2.02 million for the 2D and 3D images respectively indicating that the 2D and 3D scans (in spite of the nominal true events being vastly different in the 2 scans) had similar Signal to Noise Ratio (SNR). Circular ROI's were defined in the tumour and the contralateral cortex in comparable transaxial slices of the 2D and 3D images. Contrast resolution of the tumour to the background was calculated as 1.4 and 1.38 in the 2D and 3D images respectively. Thus comparable contrast resolution is obtained in the brain with both 3D and 2D images, making 3D imaging a viable alternative to 2D imaging and greatly reducing imaging time. Optimum time

  19. Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

    International Nuclear Information System (INIS)

    Neuner, Irene; Kaffanke, Joachim B.; Langen, Karl-Josef; Kops, Elena Rota; Tellmann, Lutz; Stoffels, Gabriele; Weirich, Christoph; Filss, Christian; Scheins, Juergen; Herzog, Hans; Shah, N. Jon

    2012-01-01

    The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as 18 F-fluoroethyl-l-tyrosine (FET) or 11 C-l-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. (orig.)

  20. Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

    Energy Technology Data Exchange (ETDEWEB)

    Neuner, Irene [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Psychiatry, Psychotherapy and Psychosomatics, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany); Kaffanke, Joachim B. [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); MR-Transfer e.K., Wuppertal (Germany); Langen, Karl-Josef; Kops, Elena Rota; Tellmann, Lutz; Stoffels, Gabriele; Weirich, Christoph; Filss, Christian; Scheins, Juergen; Herzog, Hans [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Neurology, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany)

    2012-12-15

    The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as {sup 18}F-fluoroethyl-l-tyrosine (FET) or {sup 11}C-l-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. (orig.)

  1. Modeling Structural Brain Connectivity

    DEFF Research Database (Denmark)

    Ambrosen, Karen Marie Sandø

    The human brain consists of a gigantic complex network of interconnected neurons. Together all these connections determine who we are, how we react and how we interpret the world. Knowledge about how the brain is connected can further our understanding of the brain’s structural organization, help...... improve diagnosis, and potentially allow better treatment of a wide range of neurological disorders. Tractography based on diffusion magnetic resonance imaging is a unique tool to estimate this “structural connectivity” of the brain non-invasively and in vivo. During the last decade, brain connectivity...... has increasingly been analyzed using graph theoretic measures adopted from network science and this characterization of the brain’s structural connectivity has been shown to be useful for the classification of populations, such as healthy and diseased subjects. The structural connectivity of the brain...

  2. Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: model for the hyperparathyroidism-jaw tumour syndrome.

    Science.gov (United States)

    Walls, G V; Stevenson, M; Lines, K E; Newey, P J; Reed, A A C; Bowl, M R; Jeyabalan, J; Harding, B; Bradley, K J; Manek, S; Chen, J; Wang, P; Williams, B O; Teh, B T; Thakker, R V

    2017-07-13

    The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73 +/- ) and conditional parathyroid-specific (Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73 +/+ and Cdc73 +/+ /PTH-Cre) littermates. Survival of Cdc73 +/- mice, when compared to Cdc73 +/+ mice was reduced (Cdc73 +/- =80%; Cdc73 +/+ =90% at 18 months of age, Pfourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73 +/- , Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73 +/- mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73 +/- mice did not develop bone or renal tumours but female Cdc73 +/- mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73 +/- mice had increased proliferation rates that were 2-fold higher than in Cdc73 +/+ mice (P<0.05). Thus, our studies, which have established mouse models for parathyroid tumours and uterine neoplasms that develop in the HPT-JT syndrome, provide in vivo models for future studies of these tumours.

  3. Pinhole SPECT: high resolution imaging of brain tumours in small laboratory animals

    International Nuclear Information System (INIS)

    Franceschim, M.; Bokulic, T.; Kusic, Z.; Strand, S.E.; Erlandsson, K.

    1994-01-01

    The performance properties of pinhole SPECT and the application of this technology to evaluate radionuclide uptake in brain in small laboratory animals were investigated. System sensitivity and spatial resolution measurements of a rotating scintillation camera system were made for a low energy pinhole collimator equipped with 2.0 mm aperture pinhole insert. Projection data were acquired at 4 degree increments over 360 degrees in the step and shoot mode using a 4.5 cm radius of rotation. Pinhole planar and SPECT imaging were obtained to evaluate regional uptake of Tl-201, Tc-99m-MIBI, Tc-99m-HMPAO and Tc-99m-DTPA in tumor and control regions of the brain in a primary brain tumor model in Fisher 344 rats. Pinhole SPECT images were reconstructed using a modified cone- beam algorithm developed from a two dimensional fan-beam filtered backprojection algorithm. The reconstructed transaxial resolution of 2.8 FWHM and system sensitivity of 0.086 c/s/kBq with the 2.0 mm pinhole collimator aperture were measured. Tumor to non-tumor uptake ratios at 19-28 days post tumor cell inoculation varied by a factor > 20:1 on SPECT images. Pinhole SPECT provides an important new approach for performing high resolution imaging: the resolution properties of pinhole SPECT are superior to those which have been achieved with conventional SPECT or PET imaging technologies. (author)

  4. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  5. Primary brain tumours, meningiomas and brain metastases in pregnancy: report on 27 cases and review of literature

    NARCIS (Netherlands)

    Verheecke, M.; Halaska, M.J.; Lok, C.A.; Ottevanger, P.B.; Fruscio, R.; Dahl-Steffensen, K.; Kolawa, W.; Gziri, M.M.; Han, S.N.; Calsteren, K. van; Heuvel, F. van den; Vleeschouwer, S. De; Clement, P.M.; Menten, J.; Amant, F.; et al.,

    2014-01-01

    BACKGROUND: The concurrence of intracranial tumours with pregnancy is rare. The purpose of this study was to describe all reported patients registered in the international Cancer in Pregnancy registration study (CIP study; http://www.cancerinpregnancy.org), and to review the literature in order to

  6. Diagnostic benefits of presurgical fMRI in patients with brain tumours in the primary sensorimotor cortex

    Energy Technology Data Exchange (ETDEWEB)

    Wengenroth, Martina; Blatow, M.; Guenther, J. [University of Heidelberg Medical School, Department of Neuroradiology, Heidelberg (Germany); Akbar, M. [University of Heidelberg Medical School, Department of Orthopaedics, Heidelberg (Germany); Tronnier, V.M. [University of Schleswig-Holstein, Department of Neurosurgery, Luebeck (Germany); Stippich, C. [University Hospital Basle, Department of Diagnostic and Interventional Neuroradiology, Basle (Switzerland)

    2011-07-15

    Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data. Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks. fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome. Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time. (orig.)

  7. A viscoelastic model of the correlation between respiratory lung tumour motion and an external abdominal signal

    International Nuclear Information System (INIS)

    Cavan, A.E.; Wilson, P.L.; Meyer, J.; Berbeco, R.I.

    2010-01-01

    Full text: Accuracy of radiotherapy treatment of lung cancer is limited by respiratory induced tumour motion. Compensation for this motion is required to increase treatment efficacy. The lung tumour motion is related to motion of an external abdominal marker, but a reliable model of this correlation is essential. Three viscoelastic systems were developed, in order to determine the best model and analyse its effectiveness on clinical data. Three 1D viscoelastic systems (a spring and dash pot in parallel, series and a combination) were developed and compared using a simulated breathing pattern. The most effective model was applied to 60 clinical data sets (consisting of co-ordinates of tumour and abdominal motion) from multiple treatment fractions of ten patients. The model was optimised for each data set, and efficacy determined by calculating the root mean square (RMS) error between the mo elled position and the actual tumour motion. Upon application to clinical data the parallel configuration achieved an average RMS error of 0.95 mm (superior-inferior direction). The model had patient specific parameters, and displayed good consistency over extended treatment periods. The model ha dled amplitude, frequency and baseline variations of the input signal, and phase shifts between tumour and abdominal motions. This study has shown that a viscoelastic model can be used to cor relate internal lung tumour motion with an external abdominal signal. The ability to handle breathing pattern in'egularities is comparable or better than previous models. Extending the model to a full 3D, pr dictive system could allow clinical implementation for radiotherapy.

  8. A study of tumour growth based on stoichiometric principles: a continuous model and its discrete analogue.

    Science.gov (United States)

    Saleem, M; Agrawal, Tanuja; Anees, Afzal

    2014-01-01

    In this paper, we consider a continuous mathematically tractable model and its discrete analogue for the tumour growth. The model formulation is based on stoichiometric principles considering tumour-immune cell interactions in potassium (K (+))-limited environment. Our both continuous and discrete models illustrate 'cancer immunoediting' as a dynamic process having all three phases namely elimination, equilibrium and escape. The stoichiometric principles introduced into the model allow us to study its dynamics with the variation in the total potassium in the surrounding of the tumour region. It is found that an increase in the total potassium may help the patient fight the disease for a longer period of time. This result seems to be in line with the protective role of the potassium against the risk of pancreatic cancer as has been reported by Bravi et al. [Dietary intake of selected micronutrients and risk of pancreatic cancer: An Italian case-control study, Ann. Oncol. 22 (2011), pp. 202-206].

  9. Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.

    Science.gov (United States)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika; Wang, Zhaoming; Henriksson, Roger; Hallmans, Göran; Bondy, Melissa L; Johansen, Christoffer; Feychting, Maria; Ahlbom, Anders; Kitahara, Cari M; Wang, Sophia S; Ruder, Avima M; Carreón, Tania; Butler, Mary Ann; Inskip, Peter D; Purdue, Mark; Hsing, Ann W; Mechanic, Leah; Gillanders, Elizabeth; Yeager, Meredith; Linet, Martha; Chanock, Stephen J; Hartge, Patricia; Rajaraman, Preetha

    2013-05-15

    Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours. Copyright © 2012 UICC.

  10. Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

    International Nuclear Information System (INIS)

    Christian, Nicolas; Bol, Anne; Bast, Marc de; Labar, Daniel; Lee, John; Mahy, Pierre; Gregoire, Vincent

    2007-01-01

    The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [ 18 F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [ 18 F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). C3H mice were injected i.v. with an average of 12.95 MBq of [ 18 F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Ornidazole decreased the urinary excretion and increased the liver uptake of [ 18 F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation. (orig.)

  11. Determination of tumour hypoxia with the PET tracer [{sup 18}F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Christian, Nicolas; Bol, Anne; Bast, Marc de; Labar, Daniel; Lee, John; Mahy, Pierre; Gregoire, Vincent [Universite Catholique de Louvain, Center for Molecular Imaging and Experimental Radiotherapy, Brussels (Belgium)

    2007-09-15

    The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [{sup 18}F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [{sup 18}F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). C3H mice were injected i.v. with an average of 12.95 MBq of [{sup 18}F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Ornidazole decreased the urinary excretion and increased the liver uptake of [{sup 18}F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation. (orig.)

  12. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  13. A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.

    Science.gov (United States)

    Frascoli, Federico; Flood, Emelie; Kim, Peter S

    2017-06-01

    We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  14. An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy

    DEFF Research Database (Denmark)

    Bach, L.A.; Bentzen, S.M.; Alsner, Jan

    2001-01-01

    Evolutionary games have been applied as simple mathematical models of populations where interactions between individuals control the dynamics. Recently, it has been proposed to use this type of model to describe the evolution of tumour cell populations with interactions between cells. We extent...

  15. A Right Brain/Left Brain Model of Acting.

    Science.gov (United States)

    Bowlen, Clark

    Using current right brain/left brain research, this paper develops a model that explains acting's underlying quality--the actor is both himself and the character. Part 1 presents (1) the background of the right brain/left brain theory, (2) studies showing that propositional communication is a left hemisphere function while affective communication…

  16. Hyaluronan and hyaluronectin in the extracellular matrix of human brain tumour stroma.

    Science.gov (United States)

    Delpech, B; Maingonnat, C; Girard, N; Chauzy, C; Maunoury, R; Olivier, A; Tayot, J; Creissard, P

    1993-01-01

    Hyaluronan (HA) and the hyaluronan-binding glycoprotein hyaluronectin (HN) were measured in 23 gliomas and 8 meningiomas and their location was revisited in 35 tumours. A clear-cut difference was found in the HN/HA ratio values of glioblastomas (below 0.5) and that of astrocytomas (above 0.5 P edification of the extracellular matrix. In meningiomas only the stroma would be responsible for HA and HN production.

  17. Cerebellar mutism syndrome in children with brain tumours of the posterior fossa

    DEFF Research Database (Denmark)

    Wibroe, Morten; Cappelen, Johan; Castor, Charlotte

    2017-01-01

    , the clinical course and strategies for prevention and treatment are yet to be determined.Methods: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres...... for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition....

  18. Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bortolussi, S., E-mail: silva.bortolussi@pv.infn.i [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Ballarini, F. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Gadan, M.A. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Protti, N.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Clerici, A.; Ferrari, C.; Cansolino, L.; Zonta, C.; Zonta, A. [Department of Surgery, University of Pavia, via Ferrata 27100 Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, via Ferrata 27100 Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy)

    2011-02-15

    Lung carcinoma is the leading cause of cancer mortality in the Western countries. Despite the introduction over the last few years of new therapeutic agents, survival from lung cancer has shown no discernible improvement in the last 20 years. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely. The selective boron uptake in the tumour with respect to healthy tissues makes Boron Neutron Capture Therapy a potentially advantageous option in the treatment of tumours that affect whole vital organs, and that are surgically inoperable. To study the possibility of applying BNCT to the treatment of diffuse pulmonary tumours, an animal model for boron uptake measurements in lung metastases was developed. Both healthy and tumour-bearing rats were infused with Boronophenylalanine (BPA) and sacrificed at different time intervals after drug administration. The lungs were extracted, and prepared for boron analysis by neutron autoradiography and {alpha}-spectroscopy. The boron concentrations in tumour and normal lung were plotted as a function of the time elapsed after BPA administration. The concentration in tumour is almost constant within the error bars for all the time intervals of the experiment (1-8 h), while the curve in normal lung decreases after 4 h from BPA infusion. At 4 h, the ratio of boron concentration in tumour to boron concentration in healthy lung is higher than 3, and it stays above this level up to 8 h. Also the images of boron distribution in the samples, obtained by neutron autoradiography, show a selective absorption in the metastases.

  19. Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents

    DEFF Research Database (Denmark)

    Andersen, T V; Schmidt, L S; Poulsen, A H

    2013-01-01

    of childhours at daycare, attending baby groups, birth order or living with other children. Cases of glioma and embryonal tumours had more frequent sick days with infections in the first 6 years of life compared with controls. In 7-19 year olds with 4+ monthly sick day, the respective odds ratios were 2.93 (95......BACKGROUND: Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence. METHODS: CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7......-19 years with primary intracranial brain tumours diagnosed between 2004 and 2008 and matched population controls. RESULTS: The study included 352 cases (participation rate: 83%) and 646 controls (71%). There was no association with various measures of social contacts: daycare attendance, number...

  20. A parameter study to determine the optimal source neutron energy in boron neutron capture therapy of brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Nievaart, V A [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Moss, R L [Joint Research Centre of the European Commission, Postbus 2, 1755ZG Petten (Netherlands); Kloosterman, J L [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Hagen, T H J J van der [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Dam, H van [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands)

    2004-09-21

    The values of the parameters used in boron neutron capture therapy (BNCT) to calculate a given dose to human tissue vary with patients due to different physical, biological and/or medical circumstances. Parameters include the tissue dimensions, the {sup 10}B concentration and the relative biological effectiveness (RBE) factors for the different dose components associated with BNCT. Because there is still no worldwide agreement on RBE values, more often than not, average values for these parameters are used. It turns out that the RBE-problem can be circumvented by taking into account all imaginable parameter values. Approaching this quest from another angle: the outcome will also provide the parameters (and values) which influence the optimal source neutron energy. For brain tumours it turns out that the {sup 10}B concentration, the RBE factors for {sup 10}B as well as fast neutrons, together with the dose limit set for healthy tissue, affect the optimal BNCT source neutron energy. By using source neutrons of a few keV together with neutrons of a few eV, it ensures that, under all imaginable circumstances, a maximum of alpha (and lithium) particles can be delivered in the tumour.

  1. Bayesian Calibration, Validation and Uncertainty Quantification for Predictive Modelling of Tumour Growth: A Tutorial.

    Science.gov (United States)

    Collis, Joe; Connor, Anthony J; Paczkowski, Marcin; Kannan, Pavitra; Pitt-Francis, Joe; Byrne, Helen M; Hubbard, Matthew E

    2017-04-01

    In this work, we present a pedagogical tumour growth example, in which we apply calibration and validation techniques to an uncertain, Gompertzian model of tumour spheroid growth. The key contribution of this article is the discussion and application of these methods (that are not commonly employed in the field of cancer modelling) in the context of a simple model, whose deterministic analogue is widely known within the community. In the course of the example, we calibrate the model against experimental data that are subject to measurement errors, and then validate the resulting uncertain model predictions. We then analyse the sensitivity of the model predictions to the underlying measurement model. Finally, we propose an elementary learning approach for tuning a threshold parameter in the validation procedure in order to maximize predictive accuracy of our validated model.

  2. Brain tumours at 7T MRI compared to 3T - contrast effect after half and full standard contrast agent dose: initial results

    International Nuclear Information System (INIS)

    Noebauer-Huhmann, Iris-Melanie; Weber, M.; Szomolanyi, P.; Juras, V.; Kronnerwetter, C.; Widhalm, G.; Nemec, S.; Prayer, D.; Ladd, M.E.; Trattnig, S.

    2015-01-01

    To compare the contrast agent effect of a full dose and half the dose of gadobenate dimeglumine in brain tumours at 7 Tesla (7T) MR versus 3 Tesla (3T). Ten patients with primary brain tumours or metastases were examined. Signal intensities were assessed in the lesion and normal brain. Tumour-to-brain contrast and lesion enhancement were calculated. Additionally, two independent readers subjectively graded the image quality and artefacts. The enhanced mean tumour-to-brain contrast and lesion enhancement were significantly higher at 7T than at 3T for both half the dose (91.8 ± 45.8 vs. 43.9 ± 25.3 [p = 0.010], 128.1 ± 53.7 vs. 75.5 ± 32.4 [p = 0.004]) and the full dose (129.2 ± 50.9 vs. 66.6 ± 33.1 [p = 0.002], 165.4 ± 54.2 vs. 102.6 ± 45.4 [p = 0.004]). Differences between dosages at each field strength were also significant. Lesion enhancement was higher with half the dose at 7T than with the full dose at 3T (p =.037), while the tumour-to-brain contrast was not significantly different. Subjectively, contrast enhancement, visibility, and lesion delineation were better at 7T and with the full dose. All parameters were rated as good, at the least. Half the routine contrast agent dose at 7T provided higher lesion enhancement than the full dose at 3T which indicates the possibility of dose reduction at 7T. (orig.)

  3. Brain tumours at 7T MRI compared to 3T - contrast effect after half and full standard contrast agent dose: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Noebauer-Huhmann, Iris-Melanie; Weber, M. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Szomolanyi, P.; Juras, V. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Kronnerwetter, C. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Nemec, S.; Prayer, D. [Medical University of Vienna, Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ladd, M.E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); German Cancer Research Center (DKFZ), Division of Medical Physics in Radiology, Heidelberg (Germany); Trattnig, S. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Vienna (Austria)

    2015-01-15

    To compare the contrast agent effect of a full dose and half the dose of gadobenate dimeglumine in brain tumours at 7 Tesla (7T) MR versus 3 Tesla (3T). Ten patients with primary brain tumours or metastases were examined. Signal intensities were assessed in the lesion and normal brain. Tumour-to-brain contrast and lesion enhancement were calculated. Additionally, two independent readers subjectively graded the image quality and artefacts. The enhanced mean tumour-to-brain contrast and lesion enhancement were significantly higher at 7T than at 3T for both half the dose (91.8 ± 45.8 vs. 43.9 ± 25.3 [p = 0.010], 128.1 ± 53.7 vs. 75.5 ± 32.4 [p = 0.004]) and the full dose (129.2 ± 50.9 vs. 66.6 ± 33.1 [p = 0.002], 165.4 ± 54.2 vs. 102.6 ± 45.4 [p = 0.004]). Differences between dosages at each field strength were also significant. Lesion enhancement was higher with half the dose at 7T than with the full dose at 3T (p =.037), while the tumour-to-brain contrast was not significantly different. Subjectively, contrast enhancement, visibility, and lesion delineation were better at 7T and with the full dose. All parameters were rated as good, at the least. Half the routine contrast agent dose at 7T provided higher lesion enhancement than the full dose at 3T which indicates the possibility of dose reduction at 7T. (orig.)

  4. Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer.

    Science.gov (United States)

    Yu, Huixin; Hendrikx, Jeroen J M A; Rottenberg, Sven; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R

    2016-03-01

    In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir.

  5. Multiple model predictive control for optimal drug administration of mixed immunotherapy and chemotherapy of tumours.

    Science.gov (United States)

    Sharifi, N; Ozgoli, S; Ramezani, A

    2017-06-01

    Mixed immunotherapy and chemotherapy of tumours is one of the most efficient ways to improve cancer treatment strategies. However, it is important to 'design' an effective treatment programme which can optimize the ways of combining immunotherapy and chemotherapy to diminish their imminent side effects. Control engineering techniques could be used for this. The method of multiple model predictive controller (MMPC) is applied to the modified Stepanova model to induce the best combination of drugs scheduling under a better health criteria profile. The proposed MMPC is a feedback scheme that can perform global optimization for both tumour volume and immune competent cell density by performing multiple constraints. Although current studies usually assume that immunotherapy has no side effect, this paper presents a new method of mixed drug administration by employing MMPC, which implements several constraints for chemotherapy and immunotherapy by considering both drug toxicity and autoimmune. With designed controller we need maximum 57% and 28% of full dosage of drugs for chemotherapy and immunotherapy in some instances, respectively. Therefore, through the proposed controller less dosage of drugs are needed, which contribute to suitable results with a perceptible reduction in medicine side effects. It is observed that in the presence of MMPC, the amount of required drugs is minimized, while the tumour volume is reduced. The efficiency of the presented method has been illustrated through simulations, as the system from an initial condition in the malignant region of the state space (macroscopic tumour volume) transfers into the benign region (microscopic tumour volume) in which the immune system can control tumour growth. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. A combined MRI and MRSI based multiclass system for brain tumour recognition using LS-SVMs with class probabilities and feature selection.

    NARCIS (Netherlands)

    Luts, J.; Heerschap, A.; Suykens, J.A.; Huffel, S. van

    2007-01-01

    OBJECTIVE: This study investigates the use of automated pattern recognition methods on magnetic resonance data with the ultimate goal to assist clinicians in the diagnosis of brain tumours. Recently, the combined use of magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging

  7. Glioblastoma and ABO blood groups: further evidence of an association between the distribution of blood group antigens and brain tumours.

    Science.gov (United States)

    Allouh, Mohammed Z; Al Barbarawi, Mohammed M; Hiasat, Mohammad Y; Al-Qaralleh, Mohammed A; Ababneh, Emad I

    2017-10-01

    Glioblastoma is a highly malignant brain tumour that usually leads to death. Several studies have reported a link between the distribution of ABO blood group antigens and a risk of developing specific types of cancer, although no consensus has been reached. This study aims to investigate the relationship between the distribution of ABO blood group antigens and the incidence of glioblastoma. The study cohort consisted of 115 glioblastoma patients who were diagnosed at King Abdullah University Hospital, Jordan, between 2004 and 2015. Three different patient populations made up three control groups and these were selected from among patients at the same institution between 2014 and 2015 as follows: 3,847 healthy blood donors, 654 accidental trauma patients admitted to the Departments of Neurosurgery and Orthopaedics, and 230 age- and sex-matched control subjects recruited blindly from the Departments of Paediatrics and Internal Medicine. There was a significant association between the distribution of ABO blood group antigens and the incidence of glioblastoma. Post hoc residual analysis revealed that individuals with group A had a higher than expected chance of developing glioblastoma, while individuals with group O had a lower than expected chance. Furthermore, individuals with group A were found to be at a 1.62- to 2.28-fold increased risk of developing glioblastoma compared to individuals with group O. In the present study, we demonstrate that, in Jordan, individuals with group A have an increased risk of developing glioblastoma, while individuals with group O have a reduced risk. These findings suggest that the distribution of ABO blood group antigens is associated with a risk of brain tumours and may play an important role in their development. However, further clinical and experimental investigations are required to confirm this association.

  8. Treatment fractionation for stereotactic radiotherapy of lung tumours: a modelling study of the influence of chronic and acute hypoxia on tumour control probability

    International Nuclear Information System (INIS)

    Lindblom, Emely; Antonovic, Laura; Dasu, Alexandru; Lax, Ingmar; Wersäll, Peter; Toma-Dasu, Iuliana

    2014-01-01

    Stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) has led to promising local control and overall survival for fractionation schemes with increasingly high fractional doses. A point has however been reached where the number of fractions used might be too low to allow efficient local inter-fraction reoxygenation of the hypoxic cells residing in the tumour. It was therefore the purpose of this study to investigate the impact of hypoxia and extreme hypofractionation on the tumour control probability (TCP) from SBRT. A three-dimensional model of tumour oxygenation able to simulate oxygenation changes on the microscale was used. The TCP was determined for clinically relevant SBRT fractionation schedules of 1, 3 and 5 fractions assuming either static tumour oxygenation or that the oxygenation changes locally between fractions due to fast reoxygenation of acute hypoxia without an overall reduction in chronic hypoxia. For the schedules applying three or five fractions the doses required to achieve satisfying levels of TCP were considerably lower when local oxygenation changes were assumed compared to the case of static oxygenation; a decrease in D 50 of 17.7 Gy was observed for a five-fractions schedule applied to a 20% hypoxic tumour when fast reoxygenation was modelled. Assuming local oxygenation changes, the total doses required for a tumor control probability of 50% were of similar size for one, three and five fractions. Although attractive from a practical point of view, extreme hypofractionation using just one single fraction may result in impaired local control of hypoxic tumours, as it eliminates the possibility for any kind of reoxygenation

  9. Relative clinical effectiveness of carbon ion radiotherapy. Theoretical modelling for H and N tumours

    International Nuclear Information System (INIS)

    Antonovic, Laura; Toma-Dasu, Iuliana; Dasu, Alexandru; Furusawa, Yoshiya

    2015-01-01

    Comparison of the efficiency of photon and carbon ion radiotherapy (RT) administered with the same number of fractions might be of limited clinical interest, since a wide range of fractionation patterns are used clinically today. Due to advanced photon treatment techniques, hypofractionation is becoming increasingly accepted for prostate and lung tumours, whereas patients with head and neck tumours still benefit from hyperfractionated treatments. In general, the number of fractions is considerably lower in carbon ion RT. A clinically relevant comparison would be between fractionation schedules that are optimal within each treatment modality category. In this in silico study, the relative clinical effectiveness (RCE) of carbon ions was investigated for human salivary gland tumours, assuming various radiation sensitivities related to their oxygenation. The results indicate that, for hypoxic tumours in the absence of reoxygenation, the RCE (defined as the ratio of D 50 for photons to carbon ions) ranges from 3.5 to 5.7, corresponding to carbon ion treatments given in 36 and 3 fractions, respectively, and 30 fractions for photons. Assuming that interfraction local oxygenation changes take place, results for RCE are lower than that for an oxic tumour if only a few fractions of carbon ions are used. If the carbon ion treatment is given in more than 12 fractions, the RCE is larger for the hypoxic than for the well-oxygenated tumour. In conclusion, this study showed that in silico modelling enables the study of a wide range of factors in the clinical considerations and could be an important step towards individualisation of RT treatments. (author)

  10. Modelling the interplay between hypoxia and proliferation in radiotherapy tumour response

    International Nuclear Information System (INIS)

    Jeong, J; Deasy, J O; Shoghi, K I

    2013-01-01

    A tumour control probability computational model for fractionated radiotherapy was developed, with the goal of incorporating the fundamental interplay between hypoxia and proliferation, including reoxygenation over a course of radiotherapy. The fundamental idea is that the local delivery of oxygen and glucose limits the amount of proliferation and metabolically-supported cell survival a tumour sub-volume can support. The model has three compartments: a proliferating compartment of cells receiving oxygen and glucose; an intermediate, metabolically-active compartment receiving glucose; and a highly hypoxic compartment of starving cells. Following the post-mitotic cell death of proliferating cells, intermediate cells move into the proliferative compartment and hypoxic cells move into the intermediate compartment. A key advantage of the proposed model is that the initial compartmental cell distribution is uniquely determined from the assumed local growth fraction (GF) and volume doubling time (T D ) values. Varying initial cell state distributions, based on the local (voxel) GF and T D , were simulated. Tumour response was simulated for head and neck squamous cell carcinoma using relevant parameter values based on published sources. The tumour dose required to achieve a 50% local control rate (TCD 50 ) was found for various GFs and T D ’s, and the effect of fraction size on TCD 50 was also evaluated. Due to the advantage of reoxygenation over a course of radiotherapy, conventional fraction sizes (2–2.4 Gy fx −1 ) were predicted to result in smaller TCD 50 's than larger fraction sizes (4–5 Gy fx –1 ) for a 10 cc tumour with GFs of around 0.15. The time to eliminate hypoxic cells (the reoxygenation time) was estimated for a given GF and decreased as GF increased. The extra dose required to overcome accelerated stem cell accumulation in longer treatment schedules was estimated to be 0.68 Gy/day (in EQD2 6.6 ), similar to published values derived from clinical

  11. Non-invasive grading of brain tumours using dynamic amino acid PET imaging: does it work for 11C-Methionine?

    International Nuclear Information System (INIS)

    Moulin-Romsee, Gerard; D'Hondt, Eduard; Mortelmans, Luc; Laere, Koen van; Groot, Tjibbe de; Goffin, Jan; Sciot, Raf; Menten, Johan; Bormans, Guy

    2007-01-01

    Static imaging of amino acids does not allow differentiation of low versus high grade brain tumours. It has been shown that dynamic imaging of the amino acid analogue 18 F-fluoroethyltyrosine (FET) can achieve this goal. In many centres, 11 C-methionine (MET) is used for tumour imaging, but no clinical studies on the use of dynamic scanning for grading have been performed. Thirty-four patients with primary brain glioma and histopathological confirmation were retrospectively studied using 40 min dynamic MET-PET with 220 MBq 11C-methionine. In relation to histopathological grading, various metabolic indices and temporal parameters as documented by Poepperl et al. (JNM 2006;47:393-403) were analyzed. None of the evaluated static or temporal parameters allowed discrimination between high and low grade tumours. On average, low grade tumours showed washout after the initial uptake maximum, while both increases and decreases were seen for high grade tumours. Only the relative early versus late uptake ratio showed a trend towards significance (-0.16 ± 0.17 for low grade versus 0.01 ± 0.25 for high grade; p = 0.07). Unlike FET-PET, the uptake characteristics of MET-PET do not allow classification of low and high grade tumours on an individual patient basis. Since literature data indicate that both tracers have a similar performance regarding biopsy location, tumour delineation, and detection of recurrence, FET-PET should be advocated over MET-PET as its uptake mechanism also allows noninvasive grading in glioma. (orig.)

  12. Intra-operative cerebrospinal fluid sampling versus post-operative lumbar puncture for detection of leptomeningeal disease in malignant paediatric brain tumours.

    Directory of Open Access Journals (Sweden)

    Sharon Y Y Low

    Full Text Available Leptomeningeal disease is a feared sequelae of malignant paediatric brain tumours. Current methods for its detection is the combined use of cranio-spinal MRI, and CSF cytology from a post-operative lumbar puncture. In this study, the authors hypothesize that CSF taken at the start of surgery, either from an external ventricular drain or neuroendoscope will have equal sensitivity for positive tumour cells, in comparison to lumbar puncture. Secondary hypotheses include positive correlation between CSF cytology and MRI findings of LMD. From a clinical perspective, the key aim of the study was for affected paediatric patients to avoid an additional procedure of a lumbar puncture, often performed under anaesthesia after neurosurgical intervention.This is single-institution, retrospective study of paediatric patients diagnosed with malignant brain tumours. Its main aim was to compare cytological data from CSF collected at the time of surgery versus data from an interval lumbar puncture. In addition, MRI imaging of the same cohort of patients was examined for leptomeningeal disease and corroborated against CSF tumour cytology findings.Thirty patients are recruited for this study. Data analysis demonstrates a statistically significant association between our intra-operative CSF and LP sampling. Furthermore, our results also show for significant correlation between evidence of leptomeningeal disease on MRI findings versus intra-operative CSF positivity for tumour cells.Although this is a retrospective study with a limited population, our data concurs with potential to avoid an additional procedure for the paediatric patient diagnosed with a malignant brain tumour.

  13. Down-regulation of DNA mismatch repair enhances initiation and growth of neuroblastoma and brain tumour multicellular spheroids.

    Directory of Open Access Journals (Sweden)

    Samuel L Collins

    Full Text Available Multicellular tumour spheroid (MCTS cultures are excellent model systems for simulating the development and microenvironmental conditions of in vivo tumour growth. Many documented cell lines can generate differentiated MCTS when cultured in suspension or in a non-adhesive environment. While physiological and biochemical properties of MCTS have been extensively characterized, insight into the events and conditions responsible for initiation of these structures is lacking. MCTS are formed by only a small subpopulation of cells during surface-associated growth but the processes responsible for this differentiation are poorly understood and have not been previously studied experimentally. Analysis of gene expression within spheroids has provided clues but to date it is not known if the observed differences are a cause or consequence of MCTS growth. One mechanism linked to tumourigenesis in a number of cancers is genetic instability arising from impaired DNA mismatch repair (MMR. This study aimed to determine the role of MMR in MCTS initiation and development. Using surface-associated N2a and CHLA-02-ATRT culture systems we have investigated the impact of impaired MMR on MCTS growth. Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be significantly down-regulated at the mRNA level compared with non-spheroid-forming cells. By using small interfering RNA (siRNA against these genes we show that silencing of MLH1 and PMS2 enhances both MCTS initiation and subsequent expansion. This effect was prolonged over several passages following siRNA transfection. Down-regulation of DNA MMR can contribute to tumour initiation and progression in N2a and CHLA-02-ATRT MCTS models. Studies of surface-associated MCTS differentiation may have broader applications in studying events in the initiation of cancer foci.

  14. Flow cytometric techniques for detection of candidate cancer stem cell subpopulations in canine tumour models.

    Science.gov (United States)

    Blacking, T M; Waterfall, M; Samuel, K; Argyle, D J

    2012-12-01

    The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of 'CSC'. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell-associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker-defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context-dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria. © 2011 Blackwell Publishing Ltd.

  15. The food processing contaminant glyoxal promotes tumour growth in the multiple intestinal neoplasia (Min) mouse model.

    Science.gov (United States)

    Svendsen, Camilla; Høie, Anja Hortemo; Alexander, Jan; Murkovic, Michael; Husøy, Trine

    2016-08-01

    Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens. C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21. There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice. Copyright © 2016 Norwegian Institute of Public Health. Published by Elsevier Ltd.. All rights reserved.

  16. Development and characterization of a microfluidic model of the tumour microenvironment.

    Science.gov (United States)

    Ayuso, Jose M; Virumbrales-Muñoz, María; Lacueva, Alodia; Lanuza, Pilar M; Checa-Chavarria, Elisa; Botella, Pablo; Fernández, Eduardo; Doblare, Manuel; Allison, Simon J; Phillips, Roger M; Pardo, Julián; Fernandez, Luis J; Ochoa, Ignacio

    2016-10-31

    The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live 'window' into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device's potential to enable more physiological in vitro drug screening.

  17. A role for the malignant brain tumour (MBT domain protein LIN-61 in DNA double-strand break repair by homologous recombination.

    Directory of Open Access Journals (Sweden)

    Nicholas M Johnson

    Full Text Available Malignant brain tumour (MBT domain proteins are transcriptional repressors that function within Polycomb complexes. Some MBT genes are tumour suppressors, but how they prevent tumourigenesis is unknown. The Caenorhabditis elegans MBT protein LIN-61 is a member of the synMuvB chromatin-remodelling proteins that control vulval development. Here we report a new role for LIN-61: it protects the genome by promoting homologous recombination (HR for the repair of DNA double-strand breaks (DSBs. lin-61 mutants manifest numerous problems associated with defective HR in germ and somatic cells but remain proficient in meiotic recombination. They are hypersensitive to ionizing radiation and interstrand crosslinks but not UV light. Using a novel reporter system that monitors repair of a defined DSB in C. elegans somatic cells, we show that LIN-61 contributes to HR. The involvement of this MBT protein in HR raises the possibility that MBT-deficient tumours may also have defective DSB repair.

  18. Towards personalized computational oncology: from spatial models of tumour spheroids, to organoids, to tissues.

    Science.gov (United States)

    Karolak, Aleksandra; Markov, Dmitry A; McCawley, Lisa J; Rejniak, Katarzyna A

    2018-01-01

    A main goal of mathematical and computational oncology is to develop quantitative tools to determine the most effective therapies for each individual patient. This involves predicting the right drug to be administered at the right time and at the right dose. Such an approach is known as precision medicine. Mathematical modelling can play an invaluable role in the development of such therapeutic strategies, since it allows for relatively fast, efficient and inexpensive simulations of a large number of treatment schedules in order to find the most effective. This review is a survey of mathematical models that explicitly take into account the spatial architecture of three-dimensional tumours and address tumour development, progression and response to treatments. In particular, we discuss models of epithelial acini, multicellular spheroids, normal and tumour spheroids and organoids, and multi-component tissues. Our intent is to showcase how these in silico models can be applied to patient-specific data to assess which therapeutic strategies will be the most efficient. We also present the concept of virtual clinical trials that integrate standard-of-care patient data, medical imaging, organ-on-chip experiments and computational models to determine personalized medical treatment strategies. © 2018 The Author(s).

  19. A joint frailty-copula model between tumour progression and death for meta-analysis.

    Science.gov (United States)

    Emura, Takeshi; Nakatochi, Masahiro; Murotani, Kenta; Rondeau, Virginie

    2017-12-01

    Dependent censoring often arises in biomedical studies when time to tumour progression (e.g., relapse of cancer) is censored by an informative terminal event (e.g., death). For meta-analysis combining existing studies, a joint survival model between tumour progression and death has been considered under semicompeting risks, which induces dependence through the study-specific frailty. Our paper here utilizes copulas to generalize the joint frailty model by introducing additional source of dependence arising from intra-subject association between tumour progression and death. The practical value of the new model is particularly evident for meta-analyses in which only a few covariates are consistently measured across studies and hence there exist residual dependence. The covariate effects are formulated through the Cox proportional hazards model, and the baseline hazards are nonparametrically modeled on a basis of splines. The estimator is then obtained by maximizing a penalized log-likelihood function. We also show that the present methodologies are easily modified for the competing risks or recurrent event data, and are generalized to accommodate left-truncation. Simulations are performed to examine the performance of the proposed estimator. The method is applied to a meta-analysis for assessing a recently suggested biomarker CXCL12 for survival in ovarian cancer patients. We implement our proposed methods in R joint.Cox package.

  20. Application of independent component analysis to H-1 MR spectroscopic imaging exams of brain tumours

    NARCIS (Netherlands)

    Szabo de Edelenyi, F.; Simonetti, A.W.; Postma, G.; Huo, R.; Buydens, L.M.C.

    2005-01-01

    The low spatial resolution of clinical H-1 MRSI leads to partial volume effects. To overcome this problem, we applied independent component analysis (ICA) on a set of H-1 MRSI exams of brain turnours. With this method, tissue types that yield statistically independent spectra can be separated. Up to

  1. Diagnosis and treatment of cognitive deficits caused by radiation in patients with brain tumours

    International Nuclear Information System (INIS)

    Ishiuchi, Shogo

    2011-01-01

    This paper discusses about the diagnosis and evaluation of brain higher functions, feature of their impairment induced by radiotherapy for brain tumor, and association of the impairment and neurogenesis in hippocampus (H). Radiation is one of important causes of cognitive impairment in patients with brain tumor: exempli gratia (e.g.) single irradiation of 2 Gy increases its risk. The impairment is usually diagnosed and evaluated with neuropsychological tests like mini-mental state examination (MMSE), authors' Ryudai version of the brief neuropsychological test battery, etc. The neurotoxicity of radiation is classified in acute effect caused by destruction of the blood brain barrier (BBB) appearing within 2 weeks after irradiation, early-late one of demyelination as a result of BBB rupture within 1-6 months after radiotherapy and late-late effect accompanying serious symptoms like necrosis of irradiated region at later than a few months to several years. Lowered neurogenic function in H and invasion of microglia cells are observed in autopsy specimen of the irradiated brain, and single X-irradiation at 5 or 10 Gy is known to result in the arrest of neurogenesis in the mouse H dentate gyrus. Lowered cognition by irradiation of H in clinical cases is particularly reported in children. Inflammatory biomarkers like cytokines are detected in the serum of irradiated patients as well as of animals. Although fMRI alone is not satisfactory to diagnose and evaluate the radiation-induced impairment, the imaging reveals the association of anatomically different regions in cognition through neural network. It has been recently shown that the impairment can be partially protected by planning the irradiation field so as to avoid H, by medication with donepezil, memantine, erythropoietin and indomethacin, and by hyperbaric oxygen therapy. (T.T.)

  2. Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

    International Nuclear Information System (INIS)

    Imai, Misa; Muraki, Miho; Takamatsu, Kiyoshi; Saito, Hidekazu; Seiki, Motoharu; Takahashi, Yuji

    2008-01-01

    Granulosa cell tumours (GCTs) are frequently seen in menopausal women and are relatively indolent. Although the physiological properties of normal granulosa cells have been studied extensively, little is known about the molecular mechanism of GCT progression. Here, we characterise the unique behavioural properties of a granulosa tumour cell line, KGN cells, for the molecular analysis of GCT progression. Population doubling was carried out to examine the proliferation capacity of KGN cells. Moreover, the invasive capacity of these cells was determined using the in vitro invasion assay. The expression level of tumour markers in KGN cells at different passages was then determined by Western blot analysis. Finally, the growth and metastasis of KGN cells injected subcutaneously (s.c.) into nude mice was observed 3 months after injection. During in vitro culture, the advanced passage KGN cells grew 2-fold faster than the early passage cells, as determined by the population doubling assay. Moreover, we found that the advanced passage cells were 2-fold more invasive than the early passage cells. The expression pattern of tumour markers, such as p53, osteopontin, BAX and BAG-1, supported the notion that with passage, KGN cells became more aggressive. Strikingly, KGN cells at both early and advanced passages metastasized to the bowel when injected s.c. into nude mice. In addition, more tumour nodules were formed when the advanced passage cells were implanted. KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo

  3. Germline PMS2 and somatic POLE exonuclease mutations cause hypermutability of the leading DNA strand in biallelic mismatch repair deficiency syndrome brain tumours.

    Science.gov (United States)

    Andrianova, Maria A; Chetan, Ghati Kasturirangan; Sibin, Madathan Kandi; Mckee, Thomas; Merkler, Doron; Narasinga, Rao Kvl; Ribaux, Pascale; Blouin, Jean-Louis; Makrythanasis, Periklis; Seplyarskiy, Vladimir B; Antonarakis, Stylianos E; Nikolaev, Sergey I

    2017-11-01

    Biallelic mismatch repair deficiency (bMMRD) in tumours is frequently associated with somatic mutations in the exonuclease domains of DNA polymerases POLE or POLD1, and results in a characteristic mutational profile. In this article, we describe the genetic basis of ultramutated high-grade brain tumours in the context of bMMRD. We performed exome sequencing of two second-cousin patients from a large consanguineous family of Indian origin with early onset of high-grade glioblastoma and astrocytoma. We identified a germline homozygous nonsense variant, p.R802*, in the PMS2 gene. Additionally, by genome sequencing of these tumours, we found extremely high somatic mutation rates (237/Mb and 123/Mb), as well as somatic mutations in the proofreading domain of POLE polymerase (p.P436H and p.L424V), which replicates the leading DNA strand. Most interestingly, we found, in both cancers, that the vast majority of mutations were consistent with the signature of POLE exo - , i.e. an abundance of C>A and C>T mutations, particularly in special contexts, on the leading strand. We showed that the fraction of mutations under positive selection among mutations in tumour suppressor genes is more than two-fold lower in ultramutated tumours than in other glioblastomas. Genetic analyses enabled the diagnosis of the two consanguineous childhood brain tumours as being due to a combination of PMS2 germline and POLE somatic variants, and confirmed them as bMMRD/POLE exo - disorders. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  4. Sensitivity and specificity of thallium-201 single-photon emission tomography in the functional detection and differential diagnosis of brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, R.A. (Dept. of Nuclear Medicine, Middelheim Hospital, Antwerp (Belgium)); Martin, J.J. (Dept. of Neurology, University Hospital, Antwerp (Belgium) Lab. of Neuropathology, Born-Bunge Foundation, Univ. of Antwerp (Belgium)); Dobbeleir, A. (Dept. of Nuclear Medicine, Middelheim Hospital, Antwerp (Belgium)); Crols, R. (Dept. of Neurology, Middelheim Hospital, Antwerp (Belgium)); Neetens, I. (Dept. of Pathology, Middelheim Hospital, Antwerp (Belgium)); Deyn, P.P. de (Lab. of Neuropathology, Born-Bunge Foundation, Univ. of Antwerp (Belgium) Lab. of Neurochemistry and Behaviour, Born-Bunge Foundation, Univ. of Antwerp (Belgium))

    1994-07-01

    Histologically tumours consisted of astrocytoma stage I or II, astrocytoma stage III, glioblastoma multiforme and oligodendroglioma, brain metastasis, lymphoma, meningioma, pituitary adenoma, pineal tumour, colloid cyst and craniopharyngioma. False-negative studies included pineal tumour, colloid cyst, craniopharyngioma, astrocytomas stage I or II and stage III, oligodendroglioma and metastasis in the brain stem. Additional metastases approximately < 1.5 cm were not detected in two patients and [sup 201]Tl SPET underestimated tumoral extent in one patient suffering from glioblastoma multiforme. A false-positive study was obtained in a patient with skull metastasis. All 15 patients who were finally shown to suffer from ischaemic infarction had a normal SPET study 9-28 days after the onset of symptomatology. Of five patients with haemorrhagic infarction, studied within 2 weeks, four were false-positive. Of six patients with intracranial haemorrhage, studied 9-39 days later, one showed focal [sup 201]Tl accumulation. Two further false-positive studies consisted of angioma and epidural haematoma. Finally, SPET studies were normal in six patients with definite diagnosis of (reactive) gliosis, Binswanger's encephalopathy, postinfectious encephalopathy and multiple sclerosis. In the patient population presented, sensitivity of [sup 201]Tl SPET for supratentorial brain tumours was 71.7% and specificity was 80.9%. Clinical information and control SPET studies in combination with early, 30-min and 3- to 4-h delayed imaging may be expected to improve on these figures. On the other hand it seems that, in addition to tumoral histology, the presence of tumours in the fossa posterior and small volumes contribute to the occurrence of false-negative [sup 201]Tl SPET studies. (orig.)

  5. Seizure characteristics and the use of anti-epileptic drugs in children and young people with brain tumours and epileptic seizures: Analysis of regional paediatric cancer service population.

    Science.gov (United States)

    Pilotto, Chiara; Liu, Jo-Fen; Walker, David A; Whitehouse, William P

    2018-03-21

    Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED). we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service. data was available on 117/120 (98%) children seizures. A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9-17.3). At a median follow up of 24 months (IQR 25°-75° : 15-48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR 25°-75° 5-14 months), and the median follow up after withdrawal was 15 months (IQR 25°-75° 5-34 months). Seizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex. The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control. Copyright © 2018. Published by Elsevier Ltd.

  6. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression.

    Science.gov (United States)

    Estrada, Marta F; Rebelo, Sofia P; Davies, Emma J; Pinto, Marta T; Pereira, Hugo; Santo, Vítor E; Smalley, Matthew J; Barry, Simon T; Gualda, Emilio J; Alves, Paula M; Anderson, Elizabeth; Brito, Catarina

    2016-02-01

    3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results

    Energy Technology Data Exchange (ETDEWEB)

    Fellner, C. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Inst. of Medical Physics]|[Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Dept. of Diagnostic Radiology; Schlaier, J.; Schwerdtner, J.; Brawanski, A. [Regensburg Univ. (Germany). Dept. of Radiology; Fellner, F. [Regensburg Univ. (Germany). Dept. of Neurosurgery]|[Oberoesterreichische Landesnervenklinik, Linz (Austria). Dept. of Neuroradiology; Held, P. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Dept. of Diagnostic Radiology; Blank, M.; Kalender, W.A. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Inst. of Medical Physics

    1999-06-01

    The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. (orig.) [Deutsch] Das Ziel der vorliegenden Studie war ein Vergleich der funktionellen MR-Bildgebung (fMRI: Functional magnetic resonance imaging) des Motorkortex bei gesunden Probanden und Patienten mit Hirntumor. Die funktionelle MR-Bildgebung wurde bei 14 gesunden Probanden und bei 14 Patienten mit einem Tumor im oder nahe des primaeren Motorkortex durchgefuehrt, wobei beide Kollektive

  8. Mid-ventilation position planning: Optimal model for dose distribution in lung tumour

    International Nuclear Information System (INIS)

    Benchalal, M.; Leseur, J.; Chajon, E.; Cazoulat, G.; Haigron, P.; Simon, A.; Bellec, J.; Lena, H.; Crevoisier, R. de

    2012-01-01

    Purpose. - The dose distribution for lung tumour is estimated using a 3D-CT scan, and since a person breathes while the images are captured, the dose distribution doesn't reflect the reality. A 4D-CT scan integrates the motion of the tumour during breathing and, therefore, provides us with important information regarding tumour's motion in all directions, the motion volume (ITV) and the time-weighted average position (MVP). Patient and methods. - Based on these two concepts, we have estimated, for a lung carcinoma case a 3D dose distribution from a 3D-CT scan, and a 4D dose distribution from a 4-D CT scan. To this, we have applied a non-rigid registration to estimate the cumulative dose. Results. - Our study shows that the 4D dose estimation of the GTV is almost the same when made using MVP and ITV concepts, but sparring of the healthy lung is better done using the MPV model (MVP), as compared to the ITV model. This improvement of the therapeutic index allows, from a projection on the theoretical maximal dose to PTV (strictly restricted to doses for the lungs and the spinal cord), for an increase of about 11% on the total dose (maximal dose of 86 Gy for the ITV and 96 Gy for the MVP). Conclusion. - Further studies with more patients are needed to confirm our data. (authors)

  9. Assessing occupational and domestic ELF magnetic field exposure in the UK Adult Brain Tumour Study: Results of a feasibility study

    International Nuclear Information System (INIS)

    Van Tongeren, M.; Mee, T.; Whatmough, P.; Broad, L.; Mashlanyj, M.; Allen, S.; Muir, K.; McKinney, P.

    2004-01-01

    The feasibility of measuring exposure to extremely low frequency magnetic fields (ELF MF) in the UK Adult Brain Tumour Study (UKABTS) was examined. During the study, 81 individuals and 30 companies were approached with 79 individuals and 25 companies agreeing to participate. Exposure data were collected using EMDEX II dosemeters worn by the participants for 3-4 consecutive days. Data were collected over a total of 321 d, including non-occupational periods. The results showed occupational exposure to be the main determinant of overall exposure. Moderate to strong correlations were found between arithmetic mean exposure and all other metrics with the possible exception of maximum exposure. Significant differences in exposure were found between job categories with large variability in certain categories. Highest average exposures were found for security officers (arithmetic mean, AM: 0.78 μT), secretaries (AM: 0.48 μT) and dentists (AM: 0.42 μT). Welding and working near high-voltage power lines were associated with elevated exposure. In summary, acceptably precise measures of ELF MF exposure are feasible at relatively moderate cost. The results were used to develop a protocol for data collection from subjects in the UKABTS. (authors)

  10. The frequency and cause of anxiety and depression amongst patients with malignant brain tumours between surgery and radiotherapy.

    Science.gov (United States)

    Kilbride, Lynn; Smith, Graeme; Grant, Robin

    2007-09-01

    Between surgery and radiotherapy patients with a malignant glioma may encounter a number of psychosocial issues that could invoke an anxious or depressive response. This study explored the frequency, severity and cause of anxiety and depression in patients with presumed malignant brain tumours in the period between their surgery and radiotherapy. A prospective study of 51 patients used mixed methods to measure anxiety and depression at three time points; post surgery, three weeks post surgery and pre radiotherapy. Analysis was undertaken using statistical and content analysis of the Hospital Anxiety and Depression (HAD) scores and unstructured interviews respectively. Analysis of HAD scores indicated a heightened level of anxiety in patients pre radiotherapy. This anxiety is more prevalent in younger patients and is not related to the patients change in functional state. Five patients had a significant depression at one or more time points between surgery and radiotherapy. Four of the five patients who reported scores consistent with depression had past histories of depression. Content analysis of unstructured interviews indicated that the HAD scores underestimated the presence of anxiety and depression amongst this group of patients. Anxiety was more common in younger patients. Anxiety was slightly more frequent pre-radiotherapy. A past medical history of depression is a predictor of significant depression in the post-operative period. The HAD scale although useful is not an adequate measurement tool for detecting anxiety and depression amongst all patients and health care professionals should adopt other means to monitor for these signs and symptoms.

  11. Modelling radiation-induced cell death and tumour re-oxygenation: local versus global and instant versus delayed cell death

    International Nuclear Information System (INIS)

    Gago-Arias, Araceli; Espinoza, Ignacio; Sánchez-Nieto, Beatriz; Aguiar, Pablo; Pardo-Montero, Juan

    2016-01-01

    The resistance of hypoxic cells to radiation, due to the oxygen dependence of radiosensitivity, is well known and must be taken into account to accurately calculate the radiation induced cell death. A proper modelling of the response of tumours to radiation requires deriving the distribution of oxygen at a microscopic scale. This usually involves solving the reaction-diffusion equation in tumour voxels using a vascularization distribution model. Moreover, re-oxygenation arises during the course of radiotherapy, one reason being the increase of available oxygen caused by cell killing, which can turn hypoxic tumours into oxic. In this work we study the effect of cell death kinetics in tumour oxygenation modelling, analysing how it affects the timing of re-oxygenation, surviving fraction and tumour control. Two models of cell death are compared, an instantaneous cell killing, mimicking early apoptosis, and a delayed cell death scenario in which cells can die shortly after being damaged, as well as long after irradiation. For each of these scenarios, the decrease in oxygen consumption due to cell death can be computed globally (macroscopic voxel average) or locally (microscopic). A re-oxygenation model already used in the literature, the so called full re-oxygenation, is also considered. The impact of cell death kinetics and re-oxygenation on tumour responses is illustrated for two radiotherapy fractionation schemes: a conventional schedule, and a hypofractionated treatment. The results show large differences in the doses needed to achieve 50% tumour control for the investigated cell death models. Moreover, the models affect the tumour responses differently depending on the treatment schedule. This corroborates the complex nature of re-oxygenation, showing the need to take into account the kinetics of cell death in radiation response models. (paper)

  12. Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

    Science.gov (United States)

    Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

    2004-01-01

    In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

  13. Cancerous Tumour Model Analysis and Constructing schemes of Anti-angiogenesis Therapy at an Early Stage

    Directory of Open Access Journals (Sweden)

    O. Yu. Mukhomorova

    2015-01-01

    Full Text Available Anti-angiogenesis therapy is an alternative and successfully employed method for treatment of cancerous tumour. However, this therapy isn't widely used in medicine because of expensive drugs. It leads naturally to elaboration of such treatment regimens which use minimum amount of drugs.The aim of the paper is to investigate the model of development of illness and elaborate appropriate treatment regimens in the case of early diagnosis of the disease. The given model reflects the therapy at an intermediate stage of the disease treatment. Further treatment is aimed to destroy cancer cells and may be continued by other means, which are not reflected in the model.Analysis of the main properties of the model was carried out with consideration of two types of auxiliary systems. In the first case, the system is considered without control, as a model of tumour development in the absence of medical treatment. The study of the equilibrium point and determination of its type allowed us to describe disease dynamics and to determine tumour size resulting in death. In the second case a model with a constant control was investigated. The study of its equilibrium point showed that continuous control is not sufficient to support satisfactory patient's condition, and it is necessary to elaborate more complex treatment regimens. For this purpose, we used the method of terminal problems consisting in the search for such program control which forces system to a given final state. Selecting the initial and final states is due to medical grounds.As a result, we found two treatment regimens | one-stage treatment regimen and multi-stage one. The properties of each treatment regimen are analyzed and compared. The total amount of used drugs was a criterion for comparing these two treatment regimens. The theoretical conclusions obtained in this work are supported by computer modeling in MATLAB environment.

  14. Hierarchical models in the brain.

    Directory of Open Access Journals (Sweden)

    Karl Friston

    2008-11-01

    Full Text Available This paper describes a general model that subsumes many parametric models for continuous data. The model comprises hidden layers of state-space or dynamic causal models, arranged so that the output of one provides input to another. The ensuing hierarchy furnishes a model for many types of data, of arbitrary complexity. Special cases range from the general linear model for static data to generalised convolution models, with system noise, for nonlinear time-series analysis. Crucially, all of these models can be inverted using exactly the same scheme, namely, dynamic expectation maximization. This means that a single model and optimisation scheme can be used to invert a wide range of models. We present the model and a brief review of its inversion to disclose the relationships among, apparently, diverse generative models of empirical data. We then show that this inversion can be formulated as a simple neural network and may provide a useful metaphor for inference and learning in the brain.

  15. Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [{sup 18}F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, Otto M.; Hansen, Adam E.; Law, Ian [Copenhagen University Hospital Rigshospitalet Blegdamsvej, Department of Clinical Physiology Nuclear Medicine and PET, Copenhagen (Denmark); Larsen, Vibeke A. [Copenhagen University Hospital Rigshospitalet Blegdamsvej, Department of Radiology, Copenhagen (Denmark); Muhic, Aida; Poulsen, Hans S. [Copenhagen University Hospital Rigshospitalet Blegdamsvej, Department of Oncology, Copenhagen (Denmark); Larsson, Henrik B.W. [Copenhagen University Hospital Rigshospitalet Glostrup, Functional Imaging Unit, Department of Clinical Physiology Nuclear Medicine and PET, Glostrup (Denmark)

    2016-01-15

    imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials. (orig.)

  16. The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses

    Directory of Open Access Journals (Sweden)

    Mercadal Guillem

    2010-11-01

    Full Text Available Abstract Background Proton Magnetic Resonance (MR Spectroscopy (MRS is a widely available technique for those clinical centres equipped with MR scanners. Unlike the rest of MR-based techniques, MRS yields not images but spectra of metabolites in the tissues. In pathological situations, the MRS profile changes and this has been particularly described for brain tumours. However, radiologists are frequently not familiar to the interpretation of MRS data and for this reason, the usefulness of decision-support systems (DSS in MRS data analysis has been explored. Results This work presents the INTERPRET DSS version 3.0, analysing the improvements made from its first release in 2002. Version 3.0 is aimed to be a program that 1st, can be easily used with any new case from any MR scanner manufacturer and 2nd, improves the initial analysis capabilities of the first version. The main improvements are an embedded database, user accounts, more diagnostic discrimination capabilities and the possibility to analyse data acquired under additional data acquisition conditions. Other improvements include a customisable graphical user interface (GUI. Most diagnostic problems included have been addressed through a pattern-recognition based approach, in which classifiers based on linear discriminant analysis (LDA were trained and tested. Conclusions The INTERPRET DSS 3.0 allows radiologists, medical physicists, biochemists or, generally speaking, any person with a minimum knowledge of what an MR spectrum is, to enter their own SV raw data, acquired at 1.5 T, and to analyse them. The system is expected to help in the categorisation of MR Spectra from abnormal brain masses.

  17. Optimum parameters in a model for tumour control probability, including interpatient heterogeneity: evaluation of the log-normal distribution

    International Nuclear Information System (INIS)

    Keall, P J; Webb, S

    2007-01-01

    The heterogeneity of human tumour radiation response is well known. Researchers have used the normal distribution to describe interpatient tumour radiosensitivity. However, many natural phenomena show a log-normal distribution. Log-normal distributions are common when mean values are low, variances are large and values cannot be negative. These conditions apply to radiosensitivity. The aim of this work was to evaluate the log-normal distribution to predict clinical tumour control probability (TCP) data and to compare the results with the homogeneous (δ-function with single α-value) and normal distributions. The clinically derived TCP data for four tumour types-melanoma, breast, squamous cell carcinoma and nodes-were used to fit the TCP models. Three forms of interpatient tumour radiosensitivity were considered: the log-normal, normal and δ-function. The free parameters in the models were the radiosensitivity mean, standard deviation and clonogenic cell density. The evaluation metric was the deviance of the maximum likelihood estimation of the fit of the TCP calculated using the predicted parameters to the clinical data. We conclude that (1) the log-normal and normal distributions of interpatient tumour radiosensitivity heterogeneity more closely describe clinical TCP data than a single radiosensitivity value and (2) the log-normal distribution has some theoretical and practical advantages over the normal distribution. Further work is needed to test these models on higher quality clinical outcome datasets

  18. A novel murine model for evaluating bovine papillomavirus prophylactics/therapeutics for equine sarcoid-like tumours.

    Science.gov (United States)

    Bogaert, Lies; Woodham, Andrew W; Da Silva, Diane M; Martens, Ann; Meyer, Evelyne; Kast, W Martin

    2015-09-01

    Equine sarcoids are highly recurrent bovine papillomavirus (BPV)-induced fibroblastic neoplasms that are the most common skin tumours in horses. In order to facilitate the study of potential equine sarcoid prophylactics or therapeutics, which can be a slow and costly process in equines, a murine model for BPV-1 protein-expressing equine sarcoid-like tumours was developed in mice through stable transfection of BPV-1 E5 and E6 in a murine fibroblast tumour cell line (K-BALB). Like equine sarcoids, these murine tumour cells (BPV-KB) were of fibroblast origin, were tumorigenic and expressed BPV-1 proteins. As an initial investigation of the preclinical potential of this tumour model for equine sarcoids prophylactics, mice were immunized with BPV-1 E5E6 Venezuelan equine encephalitis virus replicon particles, prior to BPV-KB challenge, which resulted in an increased tumour-free period compared with controls, indicating that the BPV-KB murine model may be a valuable preclinical alternative to equine clinical trials.

  19. A margin model to account for respiration-induced tumour motion and its variability

    International Nuclear Information System (INIS)

    Coolens, Catherine; Webb, Steve; Evans, Phil M; Shirato, H; Nishioka, K

    2008-01-01

    In order to reduce the sensitivity of radiotherapy treatments to organ motion, compensation methods are being investigated such as gating of treatment delivery, tracking of tumour position, 4D scanning and planning of the treatment, etc. An outstanding problem that would occur with all these methods is the assumption that breathing motion is reproducible throughout the planning and delivery process of treatment. This is obviously not a realistic assumption and is one that will introduce errors. A dynamic internal margin model (DIM) is presented that is designed to follow the tumour trajectory and account for the variability in respiratory motion. The model statistically describes the variation of the breathing cycle over time, i.e. the uncertainty in motion amplitude and phase reproducibility, in a polar coordinate system from which margins can be derived. This allows accounting for an additional gating window parameter for gated treatment delivery as well as minimizing the area of normal tissue irradiated. The model was illustrated with abdominal motion for a patient with liver cancer and tested with internal 3D lung tumour trajectories. The results confirm that the respiratory phases around exhale are most reproducible and have the smallest variation in motion amplitude and phase (approximately 2 mm). More importantly, the margin area covering normal tissue is significantly reduced by using trajectory-specific margins (as opposed to conventional margins) as the angular component is by far the largest contributor to the margin area. The statistical approach to margin calculation, in addition, offers the possibility for advanced online verification and updating of breathing variation as more data become available

  20. Investigation of various growth mechanisms of solid tumour growth within the linear-quadratic model for radiotherapy

    International Nuclear Information System (INIS)

    McAneney, H; O'Rourke, S F C

    2007-01-01

    The standard linear-quadratic survival model for radiotherapy is used to investigate different schedules of radiation treatment planning to study how these may be affected by different tumour repopulation kinetics between treatments. The laws for tumour cell repopulation include the logistic and Gompertz models and this extends the work of Wheldon et al (1977 Br. J. Radiol. 50 681), which was concerned with the case of exponential re-growth between treatments. Here we also consider the restricted exponential model. This has been successfully used by Panetta and Adam (1995 Math. Comput. Modelling 22 67) in the case of chemotherapy treatment planning.Treatment schedules investigated include standard fractionation of daily treatments, weekday treatments, accelerated fractionation, optimized uniform schedules and variation of the dosage and α/β ratio, where α and β are radiobiological parameters for the tumour tissue concerned. Parameters for these treatment strategies are extracted from the literature on advanced head and neck cancer, prostate cancer, as well as radiosensitive parameters. Standardized treatment protocols are also considered. Calculations based on the present analysis indicate that even with growth laws scaled to mimic initial growth, such that growth mechanisms are comparable, variation in survival fraction to orders of magnitude emerged. Calculations show that the logistic and exponential models yield similar results in tumour eradication. By comparison the Gompertz model calculations indicate that tumours described by this law result in a significantly poorer prognosis for tumour eradication than either the exponential or logistic models. The present study also shows that the faster the tumour growth rate and the higher the repair capacity of the cell line, the greater the variation in outcome of the survival fraction. Gaps in treatment, planned or unplanned, also accentuate the differences of the survival fraction given alternative growth

  1. Detection of human cancer in an animal model using radio-labelled tumour-associated monoclonal antibodies

    International Nuclear Information System (INIS)

    Epenetos, A.A.; Arklie, J.; Knowles, R.W.; Bodmer, W.F.

    1982-01-01

    Monoclonal antibodies to epithelial-cell antigenic determinants, labelled with 123 I and 125 I, were administered parenterally to immunodeficient mice bearing human tumours derived from a human cancer cell line. Anterior, posterior and lateral radioscans of the body were taken with a gamma scintillation camera at various times from immediately to 65 days after injection. Visual displays of the images were processed by standard computer techniques. The model used a human colon-cancer cell line, HT29, and the monoclonal antibody, AUAl, which is specific to an epithelial proliferating antigen. Tumour detection was achieved in all the mice. The smallest tumour detectable appeared to be about 1 mm in diameter. The degree of antibody uptake in a tumour depended on its size and the blood supply of its surrounding tissues. (author)

  2. Intra-individual, randomised comparison of the MRI contrast agents gadobutrol versus gadoteridol in patients with primary and secondary brain tumours, evaluated in a blinded read

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, M. [Klinikum Luenen St. Marien-Hospital, Department of Diagnostic and Interventional Radiology and Neuroradiology, Luenen (Germany); Schulte-Altedorneburg, G. [Staedtisches Klinikum Muenchen Harlaching, Department of Diagnostic and Interventional Radiology, Neuroradiology and Nuclear Medicine, Muenchen (Germany); Piontek, M.; Heuser, L. [Universitaetsklinikum Knappschaftskrankenhaus GmbH, Department of Diagnostic and Interventional Radiology, Neuroradiology and Nuclear Medicine, Bochum (Germany); Hentsch, A. [Radiologisches Institut Hohenzollernstrasse, Koblenz (Germany); Spangenberg, P. [Universitaetsklinikum Knappschaftskrankenhaus GmbH, Department of Neurosurgery, Bochum (Germany); Schwenke, C. [SCO:SSiS, Berlin (Germany); Harders, A. [Universitaetsklinikum Knappschaftskrankenhaus GmbH, Department of Neurosurgery Knappschaftskrankenhaus, Bochum (Germany)

    2013-12-15

    To prove that 1.0 M gadobutrol provides superior contrast enhancement and MRI image characteristics of primary and secondary brain tumours compared with 0.5 M gadoteridol, thereby providing superior diagnostic information. Brain MRI was performed in two separate examinations in patients scheduled for neurosurgery. Independent injections of 1.0 M gadobutrol and 0.5 M gadoteridol at doses of 0.1 mmol Gd/kg body weight were administered per patient in randomised order. Evaluation was performed in an off-site blinded read. Fifty-one patients in the full analysis set (FAS) were eligible for efficacy analysis and 44 for the per-protocol analysis. For the primary efficacy variable ''preference in contrast enhancement for one contrast agent or the other'', the rate of ''gadobutrol preferred'' was estimated at 0.73 (95 % confidence interval 0.61; 0.83), showing significant superiority of gadobutrol over gadoteridol. Calculated lesion-to-brain contrast and the results of all qualitative secondary efficacy variables were also in favour of gadobutrol. Keeping a sufficient time delay after contrast application proved to be essential to get optimal image quality. Compared with 0.5 M gadoteridol, 1.0 M gadobutrol was proven to have significantly superior contrast enhancement characteristics in a routine MRI protocol of primary and secondary brain tumours. (orig.)

  3. Intra-individual, randomised comparison of the MRI contrast agents gadobutrol versus gadoteridol in patients with primary and secondary brain tumours, evaluated in a blinded read

    International Nuclear Information System (INIS)

    Koenig, M.; Schulte-Altedorneburg, G.; Piontek, M.; Heuser, L.; Hentsch, A.; Spangenberg, P.; Schwenke, C.; Harders, A.

    2013-01-01

    To prove that 1.0 M gadobutrol provides superior contrast enhancement and MRI image characteristics of primary and secondary brain tumours compared with 0.5 M gadoteridol, thereby providing superior diagnostic information. Brain MRI was performed in two separate examinations in patients scheduled for neurosurgery. Independent injections of 1.0 M gadobutrol and 0.5 M gadoteridol at doses of 0.1 mmol Gd/kg body weight were administered per patient in randomised order. Evaluation was performed in an off-site blinded read. Fifty-one patients in the full analysis set (FAS) were eligible for efficacy analysis and 44 for the per-protocol analysis. For the primary efficacy variable ''preference in contrast enhancement for one contrast agent or the other'', the rate of ''gadobutrol preferred'' was estimated at 0.73 (95 % confidence interval 0.61; 0.83), showing significant superiority of gadobutrol over gadoteridol. Calculated lesion-to-brain contrast and the results of all qualitative secondary efficacy variables were also in favour of gadobutrol. Keeping a sufficient time delay after contrast application proved to be essential to get optimal image quality. Compared with 0.5 M gadoteridol, 1.0 M gadobutrol was proven to have significantly superior contrast enhancement characteristics in a routine MRI protocol of primary and secondary brain tumours. (orig.)

  4. A systems-based mathematical modelling framework for investigating the effect of drugs on solid tumours

    Directory of Open Access Journals (Sweden)

    Liu Cong

    2011-12-01

    Full Text Available Abstract Background Elucidating the effects of drugs on solid tumours is a highly challenging multi-level problem, since this involves many complexities associated with transport and cellular response, which in turn is characterized by highly non-linear chemical signal transduction. Appropriate systems frameworks are needed to seriously address the sources of these complexities, especially from the cellular side. Results We develop a skeletal modelling framework incorporating interstitial drug transport, intracellular signal processing and cell population descriptions. The descriptions aim to appropriately capture the nature of information flow. The model is deliberately formulated to start with simple intracellular descriptions so that additional features can be incorporated in a modular fashion. Two kinds of intracellular signalling modules which describe the drug effect were considered, one a monostable switch and the other a bistable switch. Analysis of our model revealed how different drug stimuli can lead to cell killing in the tumour. Interestingly both modules considered exhibited similar trends. The effects of important parameters were also studied. Conclusions We have created a predictive systems platform integrating drug transport and cellular response which can be systematically augmented to include additional layers of cellular complexity. Our results indicate that intracellular signalling models which are qualitatively different can give rise to similar behaviour to simple (and typical stimuli, and that validating intracellular descriptions must be performed with care by considering a variety of drug stimuli.

  5. Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation

    Science.gov (United States)

    Eng, Jason W.-L.; Reed, Chelsey B.; Kokolus, Kathleen M.; Pitoniak, Rosemarie; Utley, Adam; Bucsek, Mark J.; Ma, Wen Wee; Repasky, Elizabeth A.; Hylander, Bonnie L.

    2015-03-01

    Cancer research relies heavily on murine models for evaluating the anti-tumour efficacy of therapies. Here we show that the sensitivity of several pancreatic tumour models to cytotoxic therapies is significantly increased when mice are housed at a thermoneutral ambient temperature of 30 °C compared with the standard temperature of 22 °C. Further, we find that baseline levels of norepinephrine as well as the levels of several anti-apoptotic molecules are elevated in tumours from mice housed at 22 °C. The sensitivity of tumours to cytotoxic therapies is also enhanced by administering a β-adrenergic receptor antagonist to mice housed at 22 °C. These data demonstrate that standard housing causes a degree of cold stress sufficient to impact the signalling pathways related to tumour-cell survival and affect the outcome of pre-clinical experiments. Furthermore, these data highlight the significant role of host physiological factors in regulating the sensitivity of tumours to therapy.

  6. Tumour control in ion beam radiotherapy with different ions in the presence of hypoxia: an oxygen enhancement ratio model based on the microdosimetric kinetic model

    Science.gov (United States)

    Strigari, L.; Torriani, F.; Manganaro, L.; Inaniwa, T.; Dalmasso, F.; Cirio, R.; Attili, A.

    2018-03-01

    Few attempts have been made to include the oxygen enhancement ratio (OER) in treatment planning for ion beam therapy, and systematic studies to evaluate the impact of hypoxia in treatment with the beam of different ion species are sorely needed. The radiobiological models used to quantify the OER in such studies are mainly based on the dose-averaged LET estimates, and do not explicitly distinguish between the ion species and fractionation schemes. In this study, a new type of OER modelling, based on the microdosimetric kinetic model, taking into account the specificity of the different ions, LET spectra, tissues and fractionation schemes, has been developed. The model has been benchmarked with published in vitro data, HSG, V79 and CHO cells in aerobic and hypoxic conditions, for different ion irradiation. The model has been included in the simulation of treatments for a clinical case (brain tumour) using proton, lithium, helium, carbon and oxygen ion beams. A study of the tumour control probability (TCP) as a function of oxygen partial pressure, dose per fraction and primary ion type has been performed. The modelled OER depends on both the LET and ion type, also showing a decrease for an increased dose per fraction with a slope that depends on the LET and ion type, in good agreement with the experimental data. In the investigated clinical case, a significant increase in TCP has been found upon increasing the ion charge. Higher OER variations as a function of dose per fraction have also been found for low-LET ions (up to 15% varying from 2 to 8 Gy(RBE) for protons). This model could be exploited in the identification of treatment condition optimality in the presence of hypoxia, including fractionation and primary particle selection.

  7. Tracer kinetic modelling of tumour angiogenesis based on dynamic contrast-enhanced CT and MRI measurements

    Energy Technology Data Exchange (ETDEWEB)

    Brix, Gunnar [Federal Office for Radiation Protection, Department of Medical and Occupational Radiation Protection, Oberschleissheim (Germany); Bundesamt fuer Strahlenschutz (BfS), Abteilung fuer medizinischen und beruflichen Strahlenschutz, Oberschleissheim (Germany); Griebel, Juergen [Federal Office for Radiation Protection, Department of Medical and Occupational Radiation Protection, Oberschleissheim (Germany); Kiessling, Fabian [RWTH-Aachen University, Department of Experimental Molecular Imaging, Aachen (Germany); Wenz, Frederik [University Medical Center Mannheim, University of Heidelberg, Department of Radiation Oncology, Mannheim (Germany)

    2010-08-15

    Technical developments in both magnetic resonance imaging (MRI) and computed tomography (CT) have helped to reduce scan times and expedited the development of dynamic contrast-enhanced (DCE) imaging techniques. Since the temporal change of the image signal following the administration of a diffusible, extracellular contrast agent (CA) is related to the local blood supply and the extravasation of the CA into the interstitial space, DCE imaging can be used to assess tissue microvasculature and microcirculation. It is the aim of this review to summarize the biophysical and tracer kinetic principles underlying this emerging imaging technique offering great potential for non-invasive characterization of tumour angiogenesis. In the first part, the relevant contrast mechanisms are presented that form the basis to relate signal variations measured by serial CT and MRI to local tissue concentrations of the administered CA. In the second part, the concepts most widely used for tracer kinetic modelling of concentration-time courses derived from measured DCE image data sets are described in a consistent and unified manner to highlight their particular structure and assumptions as well as the relationships among them. Finally, the concepts presented are exemplified by the analysis of representative DCE data as well as discussed with respect to present and future applications in cancer diagnosis and therapy. Depending on the specific protocol used for the acquisition of DCE image data and the particular model applied for tracer kinetic analysis of the derived concentration-time courses, different aspects of tumour angiogenesis can be quantified in terms of well-defined physiological tissue parameters. DCE imaging offers promising prospects for improved tumour diagnosis, individualization of cancer treatment as well as the evaluation of novel therapeutic concepts in preclinical and early-stage clinical trials. (orig.)

  8. Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

    Science.gov (United States)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

    This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

  9. Neurocomputational models of brain disorders

    NARCIS (Netherlands)

    Cutsuridis, Vassilis; Heida, Tjitske; Duch, Wlodek; Doya, Kenji

    2011-01-01

    Recent decades have witnessed dramatic accumulation of knowledge about the genetic, molecular, pharmacological, neurophysiological, anatomical, imaging and psychological characteristics of brain disorders. Despite these advances, however, experimental brain science has offered very little insight

  10. Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models

    International Nuclear Information System (INIS)

    Phelan, J. P.; Reen, F. J.; Dunphy, N.; O'Connor, R.; O'Gara, F.

    2016-01-01

    The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1α subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor. HIF-1 overexpression is an early biomarker of tumour metastasis and is associated with tumour resistance to conventional therapies, and poor prognosis in a range of different cancers. Here we investigated the effects of bile acids on the cancer growth and migratory potential of cell lines where HIF-1α is known to be active under hypoxic conditions. HIF-1α status was investigated in A-549 lung, DU-145 prostate and MCF-7 breast cancer cell lines exposed to bile acids (CDCA and DCA). Cell adhesion, invasion, migration was assessed in DU-145 cells while clonogenic growth was assessed in all cell lines. Intracellular HIF-1α was destabilised in the presence of bile acids in all cell lines tested. Bile acids were not cytotoxic but exhibited greatly reduced clonogenic potential in two out of three cell lines. In the migratory prostate cancer cell line DU-145, bile acids impaired cell adhesion, migration and invasion. CDCA and DCA destabilised HIF-1α in all cells and significantly suppressed key cancer progression associated phenotypes; clonogenic growth, invasion and migration in DU-145 cells. These findings suggest previously unobserved roles for bile acids as physiologically relevant molecules targeting hypoxic tumour progression

  11. Proliferation index: a continuous model to predict prognosis in patients with tumours of the Ewing's sarcoma family.

    Directory of Open Access Journals (Sweden)

    Samantha Brownhill

    Full Text Available The prognostic value of proliferation index (PI and apoptotic index (AI, caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT. Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100 of tumours with a median PI of 14 (range 0-87. Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79 of ESFT; the median AI was 3 (range 0-33. Caspase-8 protein expression was negative (0 in 14% (11/79, low (1 in 33% (26/79, medium (2 in 38% (30/79 and high (3 in 15% (12/79 of tumours, caspase-9 expression was low (1 in 66% (39/59 and high (3 in 34% (20/59, and caspase-10 protein was low (1 in 37% (23/62 and negative (0 in 63% (39/62 of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; p = 0.011 and overall survival (OS; p = <0.001 in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (p = 0.054, log rank test, although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (p = 0.003. Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (p = 0.028; patients with a pelvic tumour and a PI≥20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT.

  12. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  13. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  14. Outcome of secondary high-grade glioma in children previously treated for a malignant condition: A study of the Canadian Pediatric Brain Tumour Consortium

    International Nuclear Information System (INIS)

    Carret, Anne-Sophie; Tabori, Uri; Crooks, Bruce; Hukin, Juliette; Odame, Isaac; Johnston, Donna L.; Keene, Daniel L.; Freeman, Carolyn; Bouffet, Eric

    2006-01-01

    Background and purpose: Reports of secondary high-grade glioma (HGG) in survivors of childhood cancer are scarce. The aim of this study was to review the pattern of diagnosis, the treatment, and outcome of secondary pediatric HGG. Patients and methods: We performed a multi-center retrospective study among the 17 paediatric institutions participating in the Canadian Pediatric Brain Tumour Consortium (CPBTC). Results: We report on 18 patients (14 males, 4 females) treated in childhood for a primary cancer, who subsequently developed a HGG as a second malignancy. All patients had previously received radiation therapy +/- chemotherapy for either acute lymphoblastic leukaemia (n = 9) or solid tumour (n = 9). All HGG occurred within the previous radiation fields. At the last follow-up, 17 patients have died and the median survival time is 9.75 months. Conclusion: Although aggressive treatment seems to provide sustained remissions in some patients, the optimal management is still to be defined. Further documentation of such cases is necessary in order to better understand the pathogenesis, the natural history and the prevention of these tumours

  15. Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model.

    Directory of Open Access Journals (Sweden)

    Araceli Tobío

    Full Text Available Yessotoxins (YTXs are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant. In addition, YTX exhibited strong cytotoxicity against the human B-chronic lymphocytic leukaemia cell line MEC1 and the murine melanoma cell line B16F10. To analyse the potential role of YTX as an anti-cancer drug in vivo we used the well-established B16F10 melanoma preclinical mouse model. Our results demonstrate that a few local application of YTX around established tumours dramatically diminished tumour growth in the absence of any significant toxicity as determined by the absence of weight loss and haematological alterations. Our data support that YTX may have a minor role as an anti-allergic drug, but reveals an important potential for its use as an anti-cancer drug.

  16. Modeling High-Dimensional Multichannel Brain Signals

    KAUST Repository

    Hu, Lechuan; Fortin, Norbert J.; Ombao, Hernando

    2017-01-01

    aspects: first, there are major statistical and computational challenges for modeling and analyzing high-dimensional multichannel brain signals; second, there is no set of universally agreed measures for characterizing connectivity. To model multichannel

  17. A mathematical model of brain glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  18. Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model

    DEFF Research Database (Denmark)

    Julien, S; Picco, G; Sewell, R

    2009-01-01

    challenge. We show that synthetic STn coupled to keyhole limpet haemocyanin (Theratope), induced antibodies to STn that recognised the glycan carried on a number of glycoproteins and in these mice a significant delay in tumour growth was observed. The protection was dependent on STn being expressed...... by the tumour and was antibody mediated. Affinity chromatography of the STn-expressing tumour cell line, followed by mass spectrometry, identified osteopontin as a novel STn-carrying glycoprotein which was highly expressed by the tumours. These results suggest that if antibodies can be induced to a number...

  19. In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

    Directory of Open Access Journals (Sweden)

    Hadlich Stefan

    2011-01-01

    Full Text Available Abstract Background Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability. Methods 6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA. Results MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p 3+/-243 mm3 with MRI (mean 918 mm3+/-193 mm3 with MRI being more precise. Histology (n = 5 confirmed MRI tumour measurements (mean size MRI 38.5 mm2+/-22.8 mm2 versus 32.6 mm2+/-22.6 mm2 (histology, p 3+/-56.7 mm3 after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p Conclusions This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.

  20. 4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT.

    Science.gov (United States)

    Selvaraj, J; Uzan, J; Baker, C; Nahum, A

    2015-01-01

    To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability ([Formula: see text]) using an in-house developed dose model. Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and [Formula: see text] was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain [Formula: see text] for each plan. The average variation observed in mean dose to the target volumes were -0.76% ± 0.36% for the 20-fraction treatment and -0.26% ± 0.68% and -1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in [Formula: see text] was -1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was -2.80% ± 1.68% and -4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min(-1) for the single-fraction treatments, the drop in [Formula: see text] was reduced by approximately 1.5%. The effect of interplay on [Formula: see text] is negligible for conventionally fractionated treatments, whereas considerable drop in [Formula: see text] is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect. A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on [Formula: see text].

  1. Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

    Science.gov (United States)

    Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

    2016-01-01

    The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

  2. Beyond anaemia management: evolving role of erythropoietin therapy in neurological disorders, multiple myeloma and tumour hypoxia models.

    Science.gov (United States)

    Boogaerts, Marc; Mittelman, Moshe; Vaupel, Peter

    2005-01-01

    Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results. Copyright 2005 S. Karger AG, Basel.

  3. Decrease of deleted in malignant brain tumour-1 (DMBT-1) expression is a crucial late event in intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Sasaki, M; Huang, S-F; Chen, M-F

    2003-01-01

    AIMS: To investigate the participation of DMBT-1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN-L) arising in hepatolithiasis. DMBT-1 plays a role in mucosal immune defence. METHODS AND RESULTS: The e...

  4. Hyperthermic treatment at 56 °C induces tumour-specific immune protection in a mouse model of prostate cancer in both prophylactic and therapeutic immunization regimens.

    Science.gov (United States)

    De Sanctis, Francesco; Sandri, Sara; Martini, Matteo; Mazzocco, Marta; Fiore, Alessandra; Trovato, Rosalinda; Garetto, Stefano; Brusa, Davide; Ugel, Stefano; Sartoris, Silvia

    2018-06-14

    Most active cancer immunotherapies able to induce a long-lasting protection against tumours are based on the activation of tumour-specific cytotoxic T lymphocytes (CTLs). Cell death by hyperthermia induces apoptosis followed by secondary necrosis, with the production of factors named "danger associated molecular pattern" (DAMP) molecules (DAMPs), that activate dendritic cells (DCs) to perform antigen uptake, processing and presentation, followed by CTLs cross priming. In many published studies, hyperthermia treatment of tumour cells is performed at 42-45 °C; these temperatures mainly promote cell surface expression of DAMPs. Treatment at 56 °C of tumour cells was shown to induce DAMPs secretion rather than their cell surface expression, improving DC activation and CTL cross priming in vitro. Thus we tested the relevance of this finding in vivo on the generation of a tumour-specific memory immune response, in the TRAMP-C2 mouse prostate carcinoma transplantable model. TRAMP-C2 tumour cells treated at 56 °C were able not only to activate DCs in vitro but also to trigger a tumour-specific CTL-dependent immune response in vivo. Prophylactic vaccination with 56 °C-treated TRAMP-C2 tumour cells alone provided protection against TRAMP-C2 tumour growth in vivo, whilst in the therapeutic regimen, control of tumour growth was achieved combining immunization with adjuvant chemotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Three-Dimensional Printing Model as a Tool to Assist in Surgery for Large Mandibular Tumour: a Case Report

    Directory of Open Access Journals (Sweden)

    Kazuyuki Yusa

    2017-06-01

    Full Text Available Objectives: Recently, three-dimensional printing models based on preoperative computed tomography and magnetic resonance imaging images have been widely used in medical fields. This study presents an effective use of the three-dimensional printing model in exploring complex spatial relationship between the tumour and surrounding tissue and in simulation surgery based planning of the operative procedure. Material and Methods: The patient was a 7-year-old boy with ameloblastic fibro-odontoma. Prior to surgery, a hybrid three-dimensional printing model consisting of the jaw bone, the tumour and the inferior alveolar nerve was fabricated. After the simulation surgery based on this model, enucleation of the tumour, leaving tooth 46 intact (Universal Numbering System by ADA safe, was planned. Results: Enucleation of the tumour was successfully carried out. One year later, healing was found to be satisfactory both clinically and radiographically. Conclusions: The study presented an effective application of a novel hybrid three-dimensional printing model composed of hard and soft tissues. Such innovations can bring significant benefits, especially to the field of oncological surgery.

  6. The effects of X-irradiation, N-ethyl-N-nitrosourea or combined treatment on O6-alkylguanine-DNA alkyltransferase activity in fetal rat brain and liver and the induction of CNS tumours

    International Nuclear Information System (INIS)

    Stammberger, I.; Nice, L.; Schmahl, W.

    1990-01-01

    Wistar rats were treated in utero on day 16 of gestation either by X-irradiation, N-ethyl-N-nitrosourea (ENU), or both in combination. The O 6 -alkylguanine-DNA alkyltransferase (AT) activity of the fetal brain and liver was analyzed and long-term observations were made to reveal any relationship between the O 6 -ethylguanine repair capability and tumour incidence in the organs of the offspring. The AT activity in the brain was affected to the same extent in the fetuses as in the dams. There was a 60.9% decrease in AT activity in fetuses 24 h after ENU treatment. This correlates with a significant increase in the incidence of brain tumours in the treated offspring (44.1%) compared to control animals. The inductive effect of X-irradiation on AT activity corresponded in turn with a reduction of the incidence of tumours after the combined treatment. In the liver of the rat fetuses, there was generally no effect of treatment on AT activity in contrast to the results obtained for the dams, where an increased AT activity was observed. There were no tumours of the liver observed in the offspring after either treatment alone or after combined treatment. It is suggested that the combined treatment of rat fetuses could significantly reduce the incidence of brain tumours in adult life. (author)

  7. The effects of X-irradiation, N-ethyl-N-nitrosourea or combined treatment on O sup 6 -alkylguanine-DNA alkyltransferase activity in fetal rat brain and liver and the induction of CNS tumours

    Energy Technology Data Exchange (ETDEWEB)

    Stammberger, I.; Nice, L. (Muenchen Univ. (Germany, F.R.). Walter-Straub-Institut fuer Pharmakologie und Toxikologie); Schmahl, W. (Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg (Germany, F.R.). Inst. fuer Pathologie)

    1990-02-01

    Wistar rats were treated in utero on day 16 of gestation either by X-irradiation, N-ethyl-N-nitrosourea (ENU), or both in combination. The O{sup 6}-alkylguanine-DNA alkyltransferase (AT) activity of the fetal brain and liver was analyzed and long-term observations were made to reveal any relationship between the O{sup 6}-ethylguanine repair capability and tumour incidence in the organs of the offspring. The AT activity in the brain was affected to the same extent in the fetuses as in the dams. There was a 60.9% decrease in AT activity in fetuses 24 h after ENU treatment. This correlates with a significant increase in the incidence of brain tumours in the treated offspring (44.1%) compared to control animals. The inductive effect of X-irradiation on AT activity corresponded in turn with a reduction of the incidence of tumours after the combined treatment. In the liver of the rat fetuses, there was generally no effect of treatment on AT activity in contrast to the results obtained for the dams, where an increased AT activity was observed. There were no tumours of the liver observed in the offspring after either treatment alone or after combined treatment. It is suggested that the combined treatment of rat fetuses could significantly reduce the incidence of brain tumours in adult life. (author).

  8. Clinical thermometry, using the 27 MHz multi-electrode current-source interstitial hyperthermia system in brain tumours

    International Nuclear Information System (INIS)

    Kaatee, Robert S.J.P.; Nowak, Peter C.J.M.; Zee, Jacoba van der; Bree, Jacob de; Kanis, Bart P.; Crezee, Hans; Levendag, Peter C.; Visser, Andries G.

    2001-01-01

    Background and purpose: In interstitial hyperthermia, temperature measurements are mainly performed inside heating applicators, and therefore, give the maximum temperatures of a rather heterogeneous temperature distribution. The problem of how to estimate lesion temperatures using the multi-electrode current-source interstitial hyperthermia (MECS-IHT) system in the brain was studied. Materials and methods: Temperatures were measured within the electrodes and in an extra catheter at the edge of a 4x4x4.5 cm 3 glioblastoma multiforme resection cavity. From the temperature decays during a power-off period, information was obtained about local maximum and minimum tissue temperatures. The significance of these data was examined through model calculations. Results: Maximum tissue temperatures could be estimated roughly by switching off all electrodes for about 5 s. Model calculations showed that the minimum tissue temperatures near a certain afterloading catheter correspond well with the temperature of the applicator inside, about 1 min after this applicator was switched off. Conclusions: Although the electrode temperatures read during heating are not suitable to assess the temperature distribution, it is feasible to heat the brain adequately using the MECS-IHT system with extra sensors outside the electrodes and/or application of decay methods

  9. Case-control study of the association between malignant brain tumours diagnosed between 2007 and 2009 and mobile and cordless phone use.

    Science.gov (United States)

    Hardell, Lennart; Carlberg, Michael; Söderqvist, Fredrik; Mild, Kjell Hansson

    2013-12-01

    Previous studies have shown a consistent association between long-term use of mobile and cordless phones and glioma and acoustic neuroma, but not for meningioma. When used these phones emit radiofrequency electromagnetic fields (RF-EMFs) and the brain is the main target organ for the handheld phone. The International Agency for Research on Cancer (IARC) classified in May, 2011 RF-EMF as a group 2B, i.e. a 'possible' human carcinogen. The aim of this study was to further explore the relationship between especially long-term (>10 years) use of wireless phones and the development of malignant brain tumours. We conducted a new case-control study of brain tumour cases of both genders aged 18-75 years and diagnosed during 2007-2009. One population-based control matched on gender and age (within 5 years) was used to each case. Here, we report on malignant cases including all available controls. Exposures on e.g. use of mobile phones and cordless phones were assessed by a self-administered questionnaire. Unconditional logistic regression analysis was performed, adjusting for age, gender, year of diagnosis and socio-economic index using the whole control sample. Of the cases with a malignant brain tumour, 87% (n=593) participated, and 85% (n=1,368) of controls in the whole study answered the questionnaire. The odds ratio (OR) for mobile phone use of the analogue type was 1.8, 95% confidence interval (CI)=1.04‑3.3, increasing with >25 years of latency (time since first exposure) to an OR=3.3, 95% CI=1.6-6.9. Digital 2G mobile phone use rendered an OR=1.6, 95% CI=0.996-2.7, increasing with latency >15-20 years to an OR=2.1, 95% CI=1.2-3.6. The results for cordless phone use were OR=1.7, 95% CI=1.1-2.9, and, for latency of 15-20 years, the OR=2.1, 95% CI=1.2-3.8. Few participants had used a cordless phone for >20-25 years. Digital type of wireless phones (2G and 3G mobile phones, cordless phones) gave increased risk with latency >1-5 years, then a lower risk in the following

  10. Correlation of Ultrasound Shear Wave Elastography with Pathological Analysis in a Xenografic Tumour Model

    DEFF Research Database (Denmark)

    Elyas, Eli; Papaevangelou, Efthymia; Alles, Erwin J

    2017-01-01

    whether non-invasive evaluation of tissue stiffness is indicative of pathological tumour changes and can be used to monitor therapeutic efficacy. US-SWE was performed in tumour xenografts in 15 NCr nude immunodeficient mice, which were treated with either the cytotoxic drug, Irinotecan, or saline...

  11. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  12. Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study

    Science.gov (United States)

    Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

    2012-01-01

    Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2. Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most

  13. Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study.

    Science.gov (United States)

    Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

    2012-03-27

    Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1-7.2. Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1-7.2 is most promising.

  14. Role of magnetic resonance tractography in the preoperative planning and intraoperative assessment of patients with intra-axial brain tumours.

    Science.gov (United States)

    Romano, A; Ferrante, M; Cipriani, V; Fasoli, F; Ferrante, L; D'Andrea, G; Fantozzi, L M; Bozzao, A

    2007-09-01

    This study was conducted to assess the possibility of identifying precise white matter tracts situated in proximity to intracranial tumours, to define the anatomical and topographical relations between the same white matter tracts and the tumour, to verify the possibility of integrating tractographic images in the context of a package of three-dimensional anatomical images to send to the neuronavigation system, to assess the impact of this information on surgical planning, and to analyse, both pre-and postoperatively, the patient's clinical conditions as an index of the functional integrity of the fibres themselves. Twenty-five patients underwent diffusion tensor study prior to neurosurgery. With the use of dedicated software, relative colour maps were obtained and the trajectories of the white matter tracts adjacent to the tumour were reconstructed in three dimensions. These were then processed for preoperative planning. Planning, which was performed with the neuronavigator, was based on analysis of the location of the course of the main white matter tracts adjacent to the lesion (pyramidal tract, optic radiation and arcuate fasciculus). Two neurosurgeons were asked whether the tractography images had modified the access and/or intraoperative approach to the tumour. All patients were clinically assessed both pre-and postoperatively 1 month after the procedure to define the presence of symptoms related to the involvement of the white matter tracts studied and therefore to assess the integrity of the fibres after the operation. In one patient, the tumour was situated away from all the tracts studied and did not compress them in any way. Overall, 40/75 tracts studied had no anatomical relation with the tumour, were not displaced by the tumour or could not be visualised in their entire course. Analysis of the remaining 35 white matter tracts led to an a priori change in the surgical approach for corticotomy in four patients (16%), with no disagreement between the two

  15. Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [18F]-fluoroethyltyrosine (FET) PET/MRI

    DEFF Research Database (Denmark)

    Henriksen, Otto M.; Larsen, Vibeke A; Muhic, Aida

    2016-01-01

    PURPOSE: Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility...... of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. METHODS: A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens m......MR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial...

  16. Development of immune memory to glial brain tumours after tumour regression induced by immunotherapeutic Toll-like receptor 7/8 activation

    NARCIS (Netherlands)

    Stathopoulos, A.; Pretto, C.; Devilliers, L.; Hofman, F.M.; Kruse, C.A.; Jadus, M.; Chen, T.C.; Schijns, V.E.J.C.

    2012-01-01

    The efficacy of immunotherapeutic TLR7/8 activation by resiquimod (R848) was evaluated in vivo, in the CNS-1 rat glioma model syngeneic to Lewis rats. The immune treatment was compared with cytotoxic cyclophosphamide chemotherapy, and as well, was compared with the combination cytotoxic and

  17. Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster

    Science.gov (United States)

    Jeibmann, Astrid; Eikmeier, Kristin; Linge, Anna; Kool, Marcel; Koos, Björn; Schulz, Jacqueline; Albrecht, Stefanie; Bartelheim, Kerstin; Frühwald, Michael C.; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin

    2014-06-01

    Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.

  18. Through tissue imaging of a live breast cancer tumour model using handheld surface enhanced spatially offset resonance Raman spectroscopy (SESORRS).

    Science.gov (United States)

    Nicolson, Fay; Jamieson, Lauren E; Mabbott, Samuel; Plakas, Konstantinos; Shand, Neil C; Detty, Michael R; Graham, Duncan; Faulds, Karen

    2018-04-21

    In order to improve patient survival and reduce the amount of unnecessary and traumatic biopsies, non-invasive detection of cancerous tumours is of imperative and urgent need. Multicellular tumour spheroids (MTS) can be used as an ex vivo cancer tumour model, to model in vivo nanoparticle (NP) uptake by the enhanced permeability and retention (EPR) effect. Surface enhanced spatially offset Raman spectroscopy (SESORS) combines both surface enhanced Raman spectroscopy (SERS) and spatially offset Raman spectroscopy (SORS) to yield enhanced Raman signals at much greater sub-surface levels. By utilizing a reporter that has an electronic transition in resonance with the laser frequency, surface enhanced resonance Raman scattering (SERRS) yields even greater enhancement in Raman signal. Using a handheld SORS spectrometer with back scattering optics, we demonstrate the detection of live breast cancer 3D MTS containing SERRS active NPs through 15 mm of porcine tissue. False color 2D heat intensity maps were used to determine tumour model location. In addition, we demonstrate the tracking of SERRS-active NPs through porcine tissue to depths of up to 25 mm. This unprecedented performance is due to the use of red-shifted chalcogenpyrylium-based Raman reporters to demonstrate the novel technique of surface enhanced spatially offset resonance Raman spectroscopy (SESORRS) for the first time. Our results demonstrate a significant step forward in the ability to detect vibrational fingerprints from a tumour model at depth through tissue. Such an approach offers significant promise for the translation of NPs into clinical applications for non-invasive disease diagnostics based on this new chemical principle of measurement.

  19. Impact of brain tumour location on emotion and personality: a voxel-based lesion-symptom mapping study on mentalization processes.

    Science.gov (United States)

    Campanella, Fabio; Shallice, Tim; Ius, Tamara; Fabbro, Franco; Skrap, Miran

    2014-09-01

    Patients affected by brain tumours may show behavioural and emotional regulation deficits, sometimes showing flattened affect and sometimes experiencing a true 'change' in personality. However, little evidence is available to the surgeon as to what changes are likely to occur with damage at specific sites, as previous studies have either relied on single cases or provided only limited anatomical specificity, mostly reporting associations rather than dissociations of symptoms. We investigated these aspects in patients undergoing surgery for the removal of cerebral tumours. We argued that many of the problems described can be ascribed to the onset of difficulties in one or more of the different levels of the process of mentalizing (i.e. abstracting and reflecting upon) emotion and intentions, which impacts on everyday behaviour. These were investigated in terms of (i) emotion recognition; (ii) Theory of Mind; (iii) alexithymia; and (iv) self-maturity (personality disorder). We hypothesized that temporo/limbic areas would be critical for processing emotion and intentions at a more perceptual level, while frontal lobe structures would be more critical when higher levels of mentalization/abstraction are required. We administered four different tasks, Task 1: emotion recognition of Ekman faces; Task 2: the Eyes Test (Theory of Mind); Task 3: Toronto Alexithymia Scale; and Task 4: Temperament and Character Inventory (a personality inventory), both immediately before and few days after the operation for the removal of brain tumours in a series of 71 patients (age range: 18-75 years; 33 female) with lesions located in the left or right frontal, temporal and parietal lobes. Lobe-based and voxel-based analysis confirmed that tasks requiring interpretation of emotions and intentions at more basic (less mentalized) levels (Tasks 1 and 2) were more affected by temporo/insular lesions, with emotion recognition (Task 1) being maximally impaired by anterior temporal and amygdala

  20. Bayesian Modelling of Functional Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Røge, Rasmus

    the prevalent strategy of standardizing of fMRI time series and model data using directional statistics or we model the variability in the signal across the brain and across multiple subjects. In either case, we use Bayesian nonparametric modeling to automatically learn from the fMRI data the number......This thesis deals with parcellation of whole-brain functional magnetic resonance imaging (fMRI) using Bayesian inference with mixture models tailored to the fMRI data. In the three included papers and manuscripts, we analyze two different approaches to modeling fMRI signal; either we accept...... of funcional units, i.e. parcels. We benchmark the proposed mixture models against state of the art methods of brain parcellation, both probabilistic and non-probabilistic. The time series of each voxel are most often standardized using z-scoring which projects the time series data onto a hypersphere...

  1. Electrochemotherapy of tumours

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Rudolf, Z.; Miklavcic, D.

    2006-01-01

    Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumour to increase drug delivery into cells. Drug uptake can be increased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold increase of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either of the drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease and accessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients. (author)

  2. Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

    Science.gov (United States)

    Ong, S M; Saeki, K; Kok, M K; Tanaka, Y; Choisunirachon, N; Yoshitake, R; Nishimura, R; Nakagawa, T

    2017-08-01

    Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. A spatio-temporal simulation model of the response of solid tumours to radiotherapy in vivo: parametric validation concerning oxygen enhancement ratio and cell cycle duration

    International Nuclear Information System (INIS)

    Antipas, Vassilis P; Stamatakos, Georgios S; Uzunoglu, Nikolaos K; Dionysiou, Dimitra D; Dale, Roger G

    2004-01-01

    Advanced bio-simulation methods are expected to substantially improve radiotherapy treatment planning. To this end a novel spatio-temporal patient-specific simulation model of the in vivo response of malignant tumours to radiotherapy schemes has been recently developed by our group. This paper discusses recent improvements to the model: an optimized algorithm leading to conformal shrinkage of the tumour as a response to radiotherapy, the introduction of the oxygen enhancement ratio (OER), a realistic initial cell phase distribution and finally an advanced imaging-based algorithm simulating the neovascularization field. A parametric study of the influence of the cell cycle duration T c , OER, OER β for the beta LQ parameter on tumour growth, shrinkage and response to irradiation under two different fractionation schemes has been made. The model has been applied to two glioblastoma multiforme (GBM) cases, one with wild type (wt) and another one with mutated (mt) p53 gene. Furthermore, the model has been applied to a hypothetical GBM tumour with α and β values corresponding to those of generic radiosensitive tumours. According to the model predictions, a whole tumour with shorter T c tends to repopulate faster, as is to be expected. Furthermore, a higher OER value for the dormant cells leads to a more radioresistant whole tumour. A small variation of the OER β value does not seem to play a major role in the tumour response. Accelerated fractionation proved to be superior to the standard scheme for the whole range of the OER values considered. Finally, the tumour with mt p53 was shown to be more radioresistant compared to the tumour with wt p53. Although all simulation predictions agree at least qualitatively with the clinical experience and literature, a long-term clinical adaptation and quantitative validation procedure is in progress

  4. Deleted in malignant brain tumour 1 (DMBT1) is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

    DEFF Research Database (Denmark)

    Ambruosi, Barbara; Accogli, Gianluca; Douet, Cecile

    2013-01-01

    fertilization rate, and that this effect is cancelled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase of the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization...... allowed us to identify the DMBT1 protein as well as a DMBT1-like protein in several mammals. Our results strongly suggest an important role of DMBT1 in the process of fertilization.......Oviductal environment affects preparation of gametes for fertilization, fertilization itself, and the subsequent embryo development. The aim of this study is to evaluate the effect of oviductal fluid and the possible involvement of Deleted in Malignant Brain Tumours 1 (DMBT1) on in vitro...

  5. Effects of an alveolar recruitment maneuver on subdural pressure, brain swelling, and mean arterial pressure in patients undergoing supratentorial tumour resection: a randomized crossover study.

    Science.gov (United States)

    Flexman, Alana M; Gooderham, Peter A; Griesdale, Donald E; Argue, Ruth; Toyota, Brian

    2017-06-01

    Although recruitment maneuvers have been advocated as part of a lung protective ventilation strategy, their effects on cerebral physiology during elective neurosurgery are unknown. Our objectives were to determine the effects of an alveolar recruitment maneuver on subdural pressure (SDP), brain relaxation score (BRS), and cerebral perfusion pressure among patients undergoing supratentorial tumour resection. In this prospective crossover study, patients scheduled for resection of a supratentorial brain tumour were randomized to undergo either a recruitment maneuver (30 cm of water for 30 sec) or a "sham" maneuver (5 cm of water for 30 sec), followed by the alternative intervention after a 90-sec equilibration period. Subdural pressure was measured through a dural perforation following opening of the cranium. Subdural pressure and mean arterial pressure (MAP) were recorded continuously. The blinded neurosurgeon provided a BRS at baseline and at the end of each intervention. During each treatment, the changes in SDP, BRS, and MAP were compared. Twenty-one patients underwent the study procedure. The increase in SDP was higher during the recruitment maneuver than during the sham maneuver (difference, 3.9 mmHg; 95% confidence interval [CI], 2.2 to 5.6; P < 0.001). Mean arterial pressure decreased further in the recruitment maneuver than in the sham maneuver (difference, -9.0 mmHg; 95% CI, -12.5 to -5.6; P < 0.001). Cerebral perfusion pressure decreased 14 mmHg (95% CI, 4 to 24) during the recruitment maneuver. The BRS did not change with either maneuver. Our results suggest that recruitment maneuvers increase subdural pressure and reduce cerebral perfusion pressure, although the clinical importance of these findings is thus far unknown. This trial was registered with ClinicalTrials.gov, NCT02093117.

  6. New Zealand adolescents’ cellphone and cordless phone user-habits: are they at increased risk of brain tumours already? A cross-sectional study

    Science.gov (United States)

    2013-01-01

    Background Cellphone and cordless phone use is very prevalent among early adolescents, but the extent and types of use is not well documented. This paper explores how, and to what extent, New Zealand adolescents are typically using and exposed to active cellphones and cordless phones, and considers implications of this in relation to brain tumour risk, with reference to current research findings. Methods This cross-sectional study recruited 373 Year 7 and 8 school students with a mean age of 12.3 years (range 10.3-13.7 years) from the Wellington region of New Zealand. Participants completed a questionnaire and measured their normal body-to-phone texting distances. Main exposure-metrics included self-reported time spent with an active cellphone close to the body, estimated time and number of calls on both phone types, estimated and actual extent of SMS text-messaging, cellphone functions used and people texted. Statistical analyses used Pearson Chi2 tests and Pearson’s correlation coefficient (r). Analyses were undertaken using SPSS version 19.0. Results Both cellphones and cordless phones were used by approximately 90% of students. A third of participants had already used a cordless phone for ≥ 7 years. In 4 years from the survey to mid-2013, the cordless phone use of 6% of participants would equal that of the highest Interphone decile (≥ 1640 hours), at the surveyed rate of use. High cellphone use was related to cellphone location at night, being woken regularly, and being tired at school. More than a third of parents thought cellphones carried a moderate-to-high health risk for their child. Conclusions While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies. PMID:23302218

  7. New Zealand adolescents' cellphone and cordless phone user-habits: are they at increased risk of brain tumours already? A cross-sectional study.

    Science.gov (United States)

    Redmayne, Mary

    2013-01-10

    Cellphone and cordless phone use is very prevalent among early adolescents, but the extent and types of use is not well documented. This paper explores how, and to what extent, New Zealand adolescents are typically using and exposed to active cellphones and cordless phones, and considers implications of this in relation to brain tumour risk, with reference to current research findings. This cross-sectional study recruited 373 Year 7 and 8 school students with a mean age of 12.3 years (range 10.3-13.7 years) from the Wellington region of New Zealand. Participants completed a questionnaire and measured their normal body-to-phone texting distances. Main exposure-metrics included self-reported time spent with an active cellphone close to the body, estimated time and number of calls on both phone types, estimated and actual extent of SMS text-messaging, cellphone functions used and people texted. Statistical analyses used Pearson Chi2 tests and Pearson's correlation coefficient (r). Analyses were undertaken using SPSS version 19.0. Both cellphones and cordless phones were used by approximately 90% of students. A third of participants had already used a cordless phone for ≥ 7 years. In 4 years from the survey to mid-2013, the cordless phone use of 6% of participants would equal that of the highest Interphone decile (≥ 1640 hours), at the surveyed rate of use. High cellphone use was related to cellphone location at night, being woken regularly, and being tired at school. More than a third of parents thought cellphones carried a moderate-to-high health risk for their child. While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies.

  8. D-galactose-induced brain ageing model

    DEFF Research Database (Denmark)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

    2017-01-01

    Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

  9. Multivariate Heteroscedasticity Models for Functional Brain Connectivity

    Directory of Open Access Journals (Sweden)

    Christof Seiler

    2017-12-01

    Full Text Available Functional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI. We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.

  10. A three-dimensional point process model for the spatial distribution of disease occurrence in relation to an exposure source

    DEFF Research Database (Denmark)

    Grell, Kathrine; Diggle, Peter J; Frederiksen, Kirsten

    2015-01-01

    We study methods for how to include the spatial distribution of tumours when investigating the relation between brain tumours and the exposure from radio frequency electromagnetic fields caused by mobile phone use. Our suggested point process model is adapted from studies investigating spatial...... the Interphone Study, a large multinational case-control study on the association between brain tumours and mobile phone use....

  11. Modeling high dimensional multichannel brain signals

    KAUST Repository

    Hu, Lechuan

    2017-03-27

    In this paper, our goal is to model functional and effective (directional) connectivity in network of multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The primary challenges here are twofold: first, there are major statistical and computational difficulties for modeling and analyzing high dimensional multichannel brain signals; second, there is no set of universally-agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with sufficiently high order so that complex lead-lag temporal dynamics between the channels can be accurately characterized. However, such a model contains a large number of parameters. Thus, we will estimate the high dimensional VAR parameter space by our proposed hybrid LASSLE method (LASSO+LSE) which is imposes regularization on the first step (to control for sparsity) and constrained least squares estimation on the second step (to improve bias and mean-squared error of the estimator). Then to characterize connectivity between channels in a brain network, we will use various measures but put an emphasis on partial directed coherence (PDC) in order to capture directional connectivity between channels. PDC is a directed frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative all possible receivers in the network. Using the proposed modeling approach, we have achieved some insights on learning in a rat engaged in a non-spatial memory task.

  12. Modeling high dimensional multichannel brain signals

    KAUST Repository

    Hu, Lechuan; Fortin, Norbert; Ombao, Hernando

    2017-01-01

    In this paper, our goal is to model functional and effective (directional) connectivity in network of multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The primary challenges here are twofold: first, there are major statistical and computational difficulties for modeling and analyzing high dimensional multichannel brain signals; second, there is no set of universally-agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with sufficiently high order so that complex lead-lag temporal dynamics between the channels can be accurately characterized. However, such a model contains a large number of parameters. Thus, we will estimate the high dimensional VAR parameter space by our proposed hybrid LASSLE method (LASSO+LSE) which is imposes regularization on the first step (to control for sparsity) and constrained least squares estimation on the second step (to improve bias and mean-squared error of the estimator). Then to characterize connectivity between channels in a brain network, we will use various measures but put an emphasis on partial directed coherence (PDC) in order to capture directional connectivity between channels. PDC is a directed frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative all possible receivers in the network. Using the proposed modeling approach, we have achieved some insights on learning in a rat engaged in a non-spatial memory task.

  13. Influence of Coloured Correlated Noises on Probability Distribution and Mean of Tumour Cell Number in the Logistic Growth Model

    Institute of Scientific and Technical Information of China (English)

    HAN Li-Bo; GONG Xiao-Long; CAO Li; WU Da-Jin

    2007-01-01

    An approximate Fokker-P1anck equation for the logistic growth model which is driven by coloured correlated noises is derived by applying the Novikov theorem and the Fox approximation. The steady-state probability distribution (SPD) and the mean of the tumour cell number are analysed. It is found that the SPD is the single extremum configuration when the degree of correlation between the multiplicative and additive noises, λ, is in -1<λ ≤ 0 and can be the double extrema in 0<λ<1. A configuration transition occurs because of the variation of noise parameters. A minimum appears in the curve of the mean of the steady-state tumour cell number, 〈x〉, versus λ. The position and the value of the minimum are controlled by the noise-correlated times.

  14. Analysis of a time-delayed mathematical model for tumour growth with an almost periodic supply of external nutrients.

    Science.gov (United States)

    Xu, Shihe; Bai, Meng; Zhang, Fangwei

    2017-12-01

    In this paper, the existence, uniqueness and exponential stability of almost periodic solutions for a mathematical model of tumour growth are studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a delay in the cell proliferation process. Using a fixed-point theorem in cones, the existence and uniqueness of almost periodic solutions for different parameter values of the model is proved. Moreover, by the Gronwall inequality, sufficient conditions are established for the exponential stability of the unique almost periodic solution. Results are illustrated by computer simulations.

  15. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  16. Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

    NARCIS (Netherlands)

    van Bree, Chris; Barten-van Rijbroek, Angeliqué D.; Leen, René; Rodermond, Hans M.; van Kuilenburg, André B. P.; Kal, Henk B.

    2009-01-01

    Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether OPEC enhances

  17. Interstitial diffusion and the relationship between compartment modelling and multi-scale spatial-temporal modelling of (18)F-FLT tumour uptake dynamics.

    Science.gov (United States)

    Liu, Dan; Chalkidou, Anastasia; Landau, David B; Marsden, Paul K; Fenwick, John D

    2014-09-07

    Tumour cell proliferation can be imaged via positron emission tomography of the radiotracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT). Conceptually, the number of proliferating cells might be expected to correlate more closely with the kinetics of 18F-FLT uptake than with uptake at a fixed time. Radiotracer uptake kinetics are standardly visualized using parametric maps of compartment model fits to time-activity-curves (TACs) of individual voxels. However the relationship between the underlying spatiotemporal accumulation of FLT and the kinetics described by compartment models has not yet been explored. In this work tumour tracer uptake is simulated using a mechanistic spatial-temporal model based on a convection-diffusion-reaction equation solved via the finite difference method. The model describes a chain of processes: the flow of FLT between the spatially heterogeneous tumour vasculature and interstitium; diffusion and convection of FLT within the interstitium; transport of FLT into cells; and intracellular phosphorylation. Using values of model parameters estimated from the biological literature, simulated FLT TACs are generated with shapes and magnitudes similar to those seen clinically. Results show that the kinetics of the spatial-temporal model can be recovered accurately by fitting a 3-tissue compartment model to FLT TACs simulated for those tumours or tumour sub-volumes that can be viewed as approximately closed, for which tracer diffusion throughout the interstitium makes only a small fractional change to the quantity of FLT they contain. For a single PET voxel of width 2.5-5 mm we show that this condition is roughly equivalent to requiring that the relative difference in tracer uptake between the voxel and its neighbours is much less than one.

  18. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours

    International Nuclear Information System (INIS)

    Hornblower, V D M; Yu, E; Fenster, A; Battista, J J; Malthaner, R A

    2007-01-01

    The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial 'tumours' were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the 'tumours' were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure 'tumour' volumes both in vivo and ex vivo

  19. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours

    Energy Technology Data Exchange (ETDEWEB)

    Hornblower, V D M [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Yu, E [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Fenster, A [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Battista, J J [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada); Malthaner, R A [Canadian Surgical Technologies and Advanced Robotics, London, Ontario (Canada)

    2007-01-07

    The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial 'tumours' were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the 'tumours' were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure 'tumour' volumes both in vivo and ex vivo.

  20. Modeling High-Dimensional Multichannel Brain Signals

    KAUST Repository

    Hu, Lechuan

    2017-12-12

    Our goal is to model and measure functional and effective (directional) connectivity in multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The difficulties from analyzing these data mainly come from two aspects: first, there are major statistical and computational challenges for modeling and analyzing high-dimensional multichannel brain signals; second, there is no set of universally agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with potentially high lag order so that complex lead-lag temporal dynamics between the channels can be captured. Estimates of the VAR model will be obtained by our proposed hybrid LASSLE (LASSO + LSE) method which combines regularization (to control for sparsity) and least squares estimation (to improve bias and mean-squared error). Then we employ some measures of connectivity but put an emphasis on partial directed coherence (PDC) which can capture the directional connectivity between channels. PDC is a frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative to all possible receivers in the network. The proposed modeling approach provided key insights into potential functional relationships among simultaneously recorded sites during performance of a complex memory task. Specifically, this novel method was successful in quantifying patterns of effective connectivity across electrode locations, and in capturing how these patterns varied across trial epochs and trial types.

  1. New Zealand adolescents’ cellphone and cordless phone user-habits: are they at increased risk of brain tumours already? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Redmayne Mary

    2013-01-01

    Full Text Available Abstract Background Cellphone and cordless phone use is very prevalent among early adolescents, but the extent and types of use is not well documented. This paper explores how, and to what extent, New Zealand adolescents are typically using and exposed to active cellphones and cordless phones, and considers implications of this in relation to brain tumour risk, with reference to current research findings. Methods This cross-sectional study recruited 373 Year 7 and 8 school students with a mean age of 12.3 years (range 10.3-13.7 years from the Wellington region of New Zealand. Participants completed a questionnaire and measured their normal body-to-phone texting distances. Main exposure-metrics included self-reported time spent with an active cellphone close to the body, estimated time and number of calls on both phone types, estimated and actual extent of SMS text-messaging, cellphone functions used and people texted. Statistical analyses used Pearson Chi2 tests and Pearson’s correlation coefficient (r. Analyses were undertaken using SPSS version 19.0. Results Both cellphones and cordless phones were used by approximately 90% of students. A third of participants had already used a cordless phone for ≥ 7 years. In 4 years from the survey to mid-2013, the cordless phone use of 6% of participants would equal that of the highest Interphone decile (≥ 1640 hours, at the surveyed rate of use. High cellphone use was related to cellphone location at night, being woken regularly, and being tired at school. More than a third of parents thought cellphones carried a moderate-to-high health risk for their child. Conclusions While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies.

  2. Experimental tumour treatment

    International Nuclear Information System (INIS)

    1985-08-01

    This report of 1984 is the seventh in a series and presents that year's results of continuous studies in the domain of experimental tumour radiotherapy. In the year under review, more personnel has been available for the studies, and the scientific programmes for the assessment of acute and chronic side effects of radiotherapies have been extended. New models have been developed, among them a first system based on animal experiments, for quantifying the mucositis of the oral and pharyngeal mucosa, a limiting condition in the radiotherapy of head and throat tumours. Another significant advancement is a model for quantification of chronical damage to the ureter, which still is a serious problem in the radiotherapy of gynaecological tumours. The 1984 experimental tumour studies have been mainly devoted to the repopulation and split-dose recovery in various tumours, concentrating on dose fractionation as one of the major problems studies. Particular interest has been attached to the processes involved in treatments over several weeks with a daily effective dose of 2 Gy. (orig./MG) [de

  3. Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

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    Lunt Sarah

    2008-05-01

    Full Text Available Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG lesions in the transgenic polyomavirus middle T (PyMT breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs, demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

  4. Brain-inspired Stochastic Models and Implementations

    KAUST Repository

    Al-Shedivat, Maruan

    2015-05-12

    One of the approaches to building artificial intelligence (AI) is to decipher the princi- ples of the brain function and to employ similar mechanisms for solving cognitive tasks, such as visual perception or natural language understanding, using machines. The recent breakthrough, named deep learning, demonstrated that large multi-layer networks of arti- ficial neural-like computing units attain remarkable performance on some of these tasks. Nevertheless, such artificial networks remain to be very loosely inspired by the brain, which rich structures and mechanisms may further suggest new algorithms or even new paradigms of computation. In this thesis, we explore brain-inspired probabilistic mechanisms, such as neural and synaptic stochasticity, in the context of generative models. The two questions we ask here are: (i) what kind of models can describe a neural learning system built of stochastic components? and (ii) how can we implement such systems e ̆ciently? To give specific answers, we consider two well known models and the corresponding neural architectures: the Naive Bayes model implemented with a winner-take-all spiking neural network and the Boltzmann machine implemented in a spiking or non-spiking fashion. We propose and analyze an e ̆cient neuromorphic implementation of the stochastic neu- ral firing mechanism and study the e ̄ects of synaptic unreliability on learning generative energy-based models implemented with neural networks.

  5. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  6. MRI of primary meningeal tumours in children

    International Nuclear Information System (INIS)

    Yoon, H.K.; Na, D.G.; Byun, H.S.; Han, B.K.; Kim, S.S.; Kim, I.O.; Shin, H.J.

    1999-01-01

    Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours. (orig.)

  7. Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dominietto, Marco [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); University of Basel, Biomaterials Science Center, Allschwil (Switzerland); Dobosz, Michael; Renner, Anja; Scheuer, Werner [Roche Innovation Center Penzberg, Discovery Oncology, Pharmaceutical Research and Early Development (pRED), Penzberg (Germany); Buergi, Sandra; Rudin, Markus [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); Zahlmann, Gudrun [pRED, Oncology DTA, Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel (Switzerland)

    2017-07-15

    This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity. Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results. Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups. Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time. (orig.)

  8. Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model.

    Directory of Open Access Journals (Sweden)

    Tzong-Tyng Hung

    Full Text Available BACKGROUND: The bisphosphonate, zoledronic acid (ZOL, can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM, to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. METHODS: The model involves intracardiac injection for arterial dissemination of the RM1(BM cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. FINDINGS: Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. CONCLUSIONS: ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a

  9. Inverse relationship between tumour proliferation markers and connexin expression in a malignant cardiac tumour originating from mesenchymal stem cell engineered tissue in a rat in-vivo model.

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    Cathleen eSpath

    2013-04-01

    Full Text Available Background: Recently, we demonstrated the beneficial effects of engineered heart tissues for the treatment of dilated cardiomyopathy in rats. For further development of this technique we started to produce engineered tissue (ET from mesenchymal stem cells. Interestingly, we observed a malignant tumour invading the heart with an inverse relationship between proliferation markers and connexin-expression.Methods: Commercial CD54+/CD90+/CD34-/CD45- bone marrow derived mesenchymal rat stem cells (cBM-MSC, characterized were used for production of mesenchymal stem-cell-ET (MSC-ET by suspending them in a collagen-I, matrigel-mixture and cultivating for 14 days with electrical stimulation. 3 MSC-ET were implanted around the beating heart of adult rats for days. Another 3 MSC-ET were produced from freshly isolated rat bone marrow derived stem cells (sBM-MSC.Results: 3 weeks after implantation of the MSC-ETs the hearts were surgically excised. While in 5/6 cases the ET was clearly distinguishable and was found as a ring containing mostly connective tissue around the heart, in 1/6 the heart was completely surrounded by a huge, undifferentiated, pleomorphic tumour originating from the cMSC-ET (cBM-MSC, classified as a high grade malignant sarcoma. Quantitatively we found a clear inverse relationship between cardiac connexin-expression (Cx43, Cx40 or Cx45 and increased Ki-67 expression (Cx43: p<0.0001, Cx45: p<0.03, Cx40: p<0.014. At the tumour-heart border there were significantly more Ki-67 positive cells (p=0.001, and only 2% Cx45 and Ki-67-expressing cells, while the other connexins were nearly completely absent (p<0.0001.Conclusions and hypothesis: These observations strongly suggest the hypothesis, that invasive tumour growth is accompanied by reduction in connexins. This implicates that gap junction communication between tumour and normal tissue is reduced or absent, which could mean that growth and differentiation signals can not be exchanged.

  10. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  11. Translation and pilot validation of Hindi translation of assessing quality of life in patients with primary brain tumours using EORTC brain module (BN-20

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    Budrukkar Ashwini

    2006-01-01

    Full Text Available Aim: To translate and validate the European Organisation for Research and Treatment for Cancer (EORTC brain cancer module (BN-20 into Hindi to make it available for patients and scientific community. Methods and Results: The EORTC BN-20 was translated into Hindi using standard guidelines by EORTC. The process included forward translation by two translators, discussion with the translators in case of discrepancies and formation of first intermediate questionnaire. This questionnaire was then given to two more translators who translated this questionnaire back into English. These 2 questionnaires were then compared with the original EORTC questionnaire and the second intermediate questionnaire was formed. The second intermediate questionnaire was subsequently administered in 10 patients with brain tumors who had never seen the questionnaire before, for pilot-testing. Each of these 10 patients after filling up the questionnaire themselves was then interviewed for any difficulty encountered during the filling up of the questionnaire. These were in the form of specific modules including difficulty in answering, confusion while answering and difficulty to understand, whether the questions were upsetting and if patients would have asked the question in any different way. There were major suggestions in three questions, which were incorporated into the second intermediate questionnaire to form the final Hindi BN-20 questionnaire. Conclusion: The final Hindi BN-20 has been approved by EORTC and can be used in clinical practice and studies for patients with brain tumors.

  12. Relationship of clonogenic cells and 'tumour-rescuing cells', modelled in irradiated spheroids in vitro

    International Nuclear Information System (INIS)

    Moore, J.V.; Hendry, J.H.

    1984-01-01

    Using the method of double negative logs (Gilbert, 1974), in which the probability of death (Pm) of a structure (e.g. spheroid, tumour or organism) after a given dose D, is related to the survival characteristics after irradiation of target cells (TRC) within the structure, the authors have reexamined the data of Durand (1975) for spheroids of V79-171 Chinese hamster cells grown in spinner culture, and of Pourreau-Schneider and Malaise (1981) for Na II human melanoma grown on agar. (U.K.)

  13. Occurrence studies of intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Larjavaara, S.

    2011-07-01

    approximately two-thirds (64%; 95% CI, 50 - 78). The underreporting was more pronounced among the elderly and in those with no histological confirmation of the meningioma diagnosis. An increasing trend of VS incidence was observed, but with considerable differences between countries. The overall annual increase of VS incidence was 2.8% per year (95% CI, 2.3 - 3.2) in 1987 - 2007, when all the four countries and both sexes were combined. However, no statistically significant increase was seen in the rates of VS incidence in Finnish men or Swedish women, and the incidence even showed some decrease in Finnish women (-0.4%, 95% CI, -1.8 to +1.1) during the study period. The overall increase in rates stabilized in the late 1990s, with relatively constant incidence rates and even some decline after 2000. Gliomas were distributed unevenly in the brain, with substantial variation between the cerebral lobes showing an excess of gliomas in the frontal and temporal lobes (over four-fold relative to occipital lobe, even after accounting for tissue volume). In the detailed spatial 3D-analysis, statistically significant heterogeneity was found with most gliomas in the anterior subcortical part of the brain. There was no excess of gliomas in the parts of the brain nearest to the typical location where mobile phones are held. Gliomas among never-regular mobile phone users and contralateral users (phone held on the opposite side of the head than the side of tumour) were closer to the source of electromagnetic field (EMF) than among regular and ipsilateral (exposure at the same side as the tumour location) users. In the case-specular analysis, the distance from the glioma cases to the mobile phone was shorter than for the speculars (hypothetical controls assigned for each glioma case). However, no such association was found in analyses by amount of phone use. In both models, glioma cases were closer to the source of exposure in long-term users (over ten years of use), but the differences

  14. Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model.

    Science.gov (United States)

    Mestas, Jean-Louis; Fowler, R Andrew; Evjen, Tove J; Somaglino, Lucie; Moussatov, Alexei; Ngo, Jacqueline; Chesnais, Sabrina; Røgnvaldsson, Sibylla; Fossheim, Sigrid L; Nilssen, Esben A; Lafon, Cyril

    2014-09-01

    The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomes as a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24-48 h post intravenous administration. Animals injected 6 mg kg(-1) liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg(-1), however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.

  15. Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.

    Directory of Open Access Journals (Sweden)

    Mohamed A Alfaleh

    Full Text Available Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN. Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

  16. Tumours of the pineal region in childhood

    International Nuclear Information System (INIS)

    Herrmann, H.D.; Schulte, F.J.; Winkler, D.; Mueller, D.

    1988-01-01

    36 patients with tumours in the pineal region were treated between 1980 and 1986, 19 of whom were under 20 years of age. Diagnosis was based on cranial CT, supplemented to by MRI as from 1986. Preoperative angiography was peformed on all patients to demonstrate tumour vascularization and type of vascular supply. Stereotactic biopsies were complemented by intraoperative ventriculography. Stereotactic biopsy only was performed in 13 patients out of the total group to verify tumour histology. 23 patients were directly operated on primarily. 3 of these died postoperative. In cases of germ-cell tumours and pineal blastomas the total brain and the vertebral canal were irradiated. (orig./MG) [de

  17. Endothelial progenitor cells physiology and metabolic plasticity in brain angiogenesis and blood-brain barrier modeling

    Directory of Open Access Journals (Sweden)

    Natalia Malinovskaya

    2016-12-01

    Full Text Available Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons. Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies.

  18. Oxygen Distributions-Evaluation of Computational Methods, Using a Stochastic Model for Large Tumour Vasculature, to Elucidate the Importance of Considering a Complete Vascular Network.

    Directory of Open Access Journals (Sweden)

    Jakob H Lagerlöf

    Full Text Available To develop a general model that utilises a stochastic method to generate a vessel tree based on experimental data, and an associated irregular, macroscopic tumour. These will be used to evaluate two different methods for computing oxygen distribution.A vessel tree structure, and an associated tumour of 127 cm3, were generated, using a stochastic method and Bresenham's line algorithm to develop trees on two different scales and fusing them together. The vessel dimensions were adjusted through convolution and thresholding and each vessel voxel was assigned an oxygen value. Diffusion and consumption were modelled using a Green's function approach together with Michaelis-Menten kinetics. The computations were performed using a combined tree method (CTM and an individual tree method (ITM. Five tumour sub-sections were compared, to evaluate the methods.The oxygen distributions of the same tissue samples, using different methods of computation, were considerably less similar (root mean square deviation, RMSD≈0.02 than the distributions of different samples using CTM (0.001< RMSD<0.01. The deviations of ITM from CTM increase with lower oxygen values, resulting in ITM severely underestimating the level of hypoxia in the tumour. Kolmogorov Smirnov (KS tests showed that millimetre-scale samples may not represent the whole.The stochastic model managed to capture the heterogeneous nature of hypoxic fractions and, even though the simplified computation did not considerably alter the oxygen distribution, it leads to an evident underestimation of tumour hypoxia, and thereby radioresistance. For a trustworthy computation of tumour oxygenation, the interaction between adjacent microvessel trees must not be neglected, why evaluation should be made using high resolution and the CTM, applied to the entire tumour.

  19. O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

    International Nuclear Information System (INIS)

    Brell, Marta; Ibáñez, Javier; Tortosa, Avelina

    2011-01-01

    The DNA repair protein O 6 -Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably

  20. O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Ibáñez Javier

    2011-01-01

    Full Text Available Abstract Background The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP the most commonly used for promoter methylation study, while immunohistochemistry (IHC has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009, EBSCO (1966-October 2009 and EMBASE (1974-October 2009 was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5% met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

  1. Gastric Calcifying Fibrous Tumour

    Directory of Open Access Journals (Sweden)

    Tan Attila

    2006-01-01

    Full Text Available Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours; however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

  2. Targeted radionuclide therapy with RAFT-RGD radiolabelled with {sup 90}Y or {sup 177}Lu in a mouse model of αvβ3-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bozon-Petitprin, A.; Bacot, S.; Ahmadi, M.; Marti-Batlle, D.; Perret, P.; Broisat, A.; Riou, L.M. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); Gauchez, A.S.; Bourre, J.C.; Fagret, D.; Vuillez, J.P. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); CHRU Grenoble, Hopital Michallon, Service de Medecine Nucleaire, Grenoble (France); Claron, M.; Boturyn, D. [CNRS, UMR 5250, Departement de Chimie Moleculaire, Grenoble (France); Ghezzi, Catherine [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); INSERM U1039, Radiopharmaceutiques biocliniques, Batiment Jean Roget, Domaine de la Merci, Faculte de Medecine, La Tronche (France)

    2014-08-28

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK]){sub 4} (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β{sup -} emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD and {sup 90}Y-RAFT-RAD or {sup 177}Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of {sup 90}Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of {sup 177}Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of {sup 90}Y-RAFT-RAD or 37 MBq of {sup 177}Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of {sup 90}Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. {sup 90}Y-RAFT-RGD and {sup 177}Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy. (orig.)

  3. Targeted radionuclide therapy with RAFT-RGD radiolabelled with (90)Y or (177)Lu in a mouse model of αvβ3-expressing tumours.

    Science.gov (United States)

    Bozon-Petitprin, A; Bacot, S; Gauchez, A S; Ahmadi, M; Bourre, J C; Marti-Batlle, D; Perret, P; Broisat, A; Riou, L M; Claron, M; Boturyn, D; Fagret, D; Ghezzi, Catherine; Vuillez, J P

    2015-02-01

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β(-) emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD and (90)Y-RAFT-RAD or (177)Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of (90)Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of (177)Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of (90)Y-RAFT-RAD or 37 MBq of (177)Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of (90)Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. (90)Y-RAFT-RGD and (177)Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy.

  4. Supratentorial tumours. Part II: tumors of neurolglial cells

    International Nuclear Information System (INIS)

    Sage, M.R.

    1991-01-01

    Tumors arising from neuroglial cells are the most common primary brain tumours, representing approximately 45% of all tumours. A simplified classification of these tumours is given, based on the degree of anaplasia. Both computed tomography and magnetic resonance imaging appearance of such lesions is presented and the relevance of these techniques in the detection and differential diagnosis of neuroglial cells tumours is discussed. 39 refs., 1 tab., 11 figs

  5. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

    Science.gov (United States)

    Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna; Seyfried, Thomas N

    2010-07-23

    GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  6. Calorie Restriction as an Anti-Invasive Therapy for Malignant Brain Cancer in the VM Mouse

    Directory of Open Access Journals (Sweden)

    Laura M Shelton

    2010-07-01

    Full Text Available GBM (glioblastoma multiforme is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  7. Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model

    International Nuclear Information System (INIS)

    Lo Dico, A.; Martelli, C.; Valtorta, S.; Belloli, S.; Raccagni, I.; Moresco, R.M.; Diceglie, C.; Gianelli, U.; Bosari, S.; Vaira, V.; Politi, L.S.; Lucignani, G.; Ottobrini, L.

    2015-01-01

    Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model. U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging. This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action. The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures. (orig.)

  8. Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model

    Energy Technology Data Exchange (ETDEWEB)

    Lo Dico, A.; Martelli, C. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); Valtorta, S.; Belloli, S. [National Researches Council (CNR), Institute of Molecular Bioimaging and Physiology (IBFM), Segrate, MI (Italy); IRCCS San Raffaele Scientific Institute, Experimental Imaging Center, Milan (Italy); Raccagni, I.; Moresco, R.M. [IRCCS San Raffaele Scientific Institute, Experimental Imaging Center, Milan (Italy); University of Milano-Bicocca, Department of Health Sciences, Monza (Italy); Diceglie, C. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Doctorate School of Molecular Medicine, Milan (Italy); Gianelli, U.; Bosari, S. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Division of Pathology, Milan (Italy); Vaira, V. [Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Division of Pathology, Milan (Italy); Istituto Nazionale Genetica Molecolare ' ' Romeo ed Enrica Invernizzi' ' (INGM), Milan (Italy); Politi, L.S. [IRCCS San Raffaele Scientific Institute, Neuroradiology Department and Neuroradiology Research Group, Milan (Italy); Lucignani, G. [University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); University of Milan, Department of Health Sciences, Milan (Italy); San Paolo Hospital, Department of Diagnostic Services, Unit of Nuclear Medicine, Milan (Italy); Ottobrini, L. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); National Researches Council (CNR), Institute of Molecular Bioimaging and Physiology (IBFM), Segrate, MI (Italy)

    2015-03-27

    Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model. U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging. This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action. The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures. (orig.)

  9. Coarse-graining and hybrid methods for efficient simulation of stochastic multi-scale models of tumour growth

    International Nuclear Information System (INIS)

    Cruz, Roberto de la; Guerrero, Pilar; Calvo, Juan; Alarcón, Tomás

    2017-01-01

    The development of hybrid methodologies is of current interest in both multi-scale modelling and stochastic reaction–diffusion systems regarding their applications to biology. We formulate a hybrid method for stochastic multi-scale models of cells populations that extends the remit of existing hybrid methods for reaction–diffusion systems. Such method is developed for a stochastic multi-scale model of tumour growth, i.e. population-dynamical models which account for the effects of intrinsic noise affecting both the number of cells and the intracellular dynamics. In order to formulate this method, we develop a coarse-grained approximation for both the full stochastic model and its mean-field limit. Such approximation involves averaging out the age-structure (which accounts for the multi-scale nature of the model) by assuming that the age distribution of the population settles onto equilibrium very fast. We then couple the coarse-grained mean-field model to the full stochastic multi-scale model. By doing so, within the mean-field region, we are neglecting noise in both cell numbers (population) and their birth rates (structure). This implies that, in addition to the issues that arise in stochastic-reaction diffusion systems, we need to account for the age-structure of the population when attempting to couple both descriptions. We exploit our coarse-graining model so that, within the mean-field region, the age-distribution is in equilibrium and we know its explicit form. This allows us to couple both domains consistently, as upon transference of cells from the mean-field to the stochastic region, we sample the equilibrium age distribution. Furthermore, our method allows us to investigate the effects of intracellular noise, i.e. fluctuations of the birth rate, on collective properties such as travelling wave velocity. We show that the combination of population and birth-rate noise gives rise to large fluctuations of the birth rate in the region at the leading edge

  10. An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

    Science.gov (United States)

    Klein, B; Schuppe, H-C; Bergmann, M; Hedger, M P; Loveland, B E; Loveland, K L

    2017-07-01

    Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6

  11. Coarse-graining and hybrid methods for efficient simulation of stochastic multi-scale models of tumour growth

    Science.gov (United States)

    de la Cruz, Roberto; Guerrero, Pilar; Calvo, Juan; Alarcón, Tomás

    2017-12-01

    The development of hybrid methodologies is of current interest in both multi-scale modelling and stochastic reaction-diffusion systems regarding their applications to biology. We formulate a hybrid method for stochastic multi-scale models of cells populations that extends the remit of existing hybrid methods for reaction-diffusion systems. Such method is developed for a stochastic multi-scale model of tumour growth, i.e. population-dynamical models which account for the effects of intrinsic noise affecting both the number of cells and the intracellular dynamics. In order to formulate this method, we develop a coarse-grained approximation for both the full stochastic model and its mean-field limit. Such approximation involves averaging out the age-structure (which accounts for the multi-scale nature of the model) by assuming that the age distribution of the population settles onto equilibrium very fast. We then couple the coarse-grained mean-field model to the full stochastic multi-scale model. By doing so, within the mean-field region, we are neglecting noise in both cell numbers (population) and their birth rates (structure). This implies that, in addition to the issues that arise in stochastic-reaction diffusion systems, we need to account for the age-structure of the population when attempting to couple both descriptions. We exploit our coarse-graining model so that, within the mean-field region, the age-distribution is in equilibrium and we know its explicit form. This allows us to couple both domains consistently, as upon transference of cells from the mean-field to the stochastic region, we sample the equilibrium age distribution. Furthermore, our method allows us to investigate the effects of intracellular noise, i.e. fluctuations of the birth rate, on collective properties such as travelling wave velocity. We show that the combination of population and birth-rate noise gives rise to large fluctuations of the birth rate in the region at the leading edge of

  12. Approximate Analytical Solutions for Mathematical Model of Tumour Invasion and Metastasis Using Modified Adomian Decomposition and Homotopy Perturbation Methods

    Directory of Open Access Journals (Sweden)

    Norhasimah Mahiddin

    2014-01-01

    Full Text Available The modified decomposition method (MDM and homotopy perturbation method (HPM are applied to obtain the approximate solution of the nonlinear model of tumour invasion and metastasis. The study highlights the significant features of the employed methods and their ability to handle nonlinear partial differential equations. The methods do not need linearization and weak nonlinearity assumptions. Although the main difference between MDM and Adomian decomposition method (ADM is a slight variation in the definition of the initial condition, modification eliminates massive computation work. The approximate analytical solution obtained by MDM logically contains the solution obtained by HPM. It shows that HPM does not involve the Adomian polynomials when dealing with nonlinear problems.

  13. Surface anatomy scanning (SAS) in intracranial tumours: comparison with surgical findings

    International Nuclear Information System (INIS)

    Sumida, M.; Uozumi, T.; Kiya, K.; Arita, K.; Kurisu, K.; Onda, J.; Satoh, H.; Ikawa, F.; Yukawa, O.; Migita, K.; Hada, H.; Katada, K.

    1995-01-01

    We evaluated the usefulness of surface anatomy scanning (SAS) in intracranial tumours, comparing it with surgical findings. We examined 31 patients with brain tumours preoperatively. The tumours included 16 meningiomas, 8 gliomas, 4 metastases and 3 others. SAS clearly demonstrated the tumours, allowing them to be distinguished from the structures of the brain surface, including oedema, except in cases of metastasis. SAS clearly demonstrated large cortical veins. SAS is useful for three-dimensional delineation of the brain surface before surgery. (orig.)

  14. A Culture-Behavior-Brain Loop Model of Human Development.

    Science.gov (United States)

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The enhanced radiation response of an in vitro tumour model by cyanide released from hydrolysed amygdalin

    International Nuclear Information System (INIS)

    Biaglow, J.E.; Durand, R.E.

    1978-01-01

    Any inhibition of oxygen consumption by respiring cells should result in indirect radiosensitization of the more centrally located hypoxic cells of a tumour. Amygdalin (D-mandelonitrile-β-D-glucosido-6-β-D-glucoside) when hydrolysed by the enzyme β-D-glucoside glycohydrolase (β-glucosidase) releases the respiratory inhibitor cyanide. A study has been made of the conditions for enhancing the gamma radiation response of multi-cell spheroids of V79 cells by cyanide or by cyanide released by enzymatic hydrolysis of amygdalin. Amygdalin hydrolysis was monitored by the increase in absorbancy at 250nm (production of benzaldehyde). Oxygen utilization was recorded by an oxygen electrode. The respiratory effects produced by the additon of amygdalin to cell suspensions containing β-glucosidase were immediate and essentially the same as those obtained by adding the equivalent amounts of KCN to the cell suspensions. The radio-resistant 'tail' of the survival curve of multi-cell spheroids was reduced in the presence of cyanide (added directly or secondarily released). The radiation response of the spheroids in the presence of cyanide was slightly greater than that for reoxygenation alone. (U.K.)

  16. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...... models then use the directions of greatest diffusion as estimates of white matter fibre orientation. Several fibre tracking algorithms have emerged in the last few years that provide reproducible visualizations of three-dimensional fibre bundles. One class of these algorithms is probabilistic...... the possibility of using high-field experimental MR scanners and long scanning times, thereby significantly improving the signal-to-noise ratio (SNR) and anatomical resolution. Moreover, many of the degrading effects observed in vivo, such as physiological noise, are no longer present. However, the post mortem...

  17. Depletion of intracellular polyamine content does not alter the survival of 9L rat brain tumour cells after X-irradiation

    International Nuclear Information System (INIS)

    Seidenfeld, J.; Deen, D.F.; Marton, L.J.

    1980-01-01

    A 24-hour preincubation of 9L rat brain tumour cells with 10 mM DL-α methylornithine (αMO) reduced 9L putrescine content by more than 97%, spermidine content by 67% and total polyamine content by 50%. This did not increase the sensitivity of 9L cells to killing by X-rays. Polyamine content of treated and untreated cells did not vary with X-ray dose. A similar experiment was performed with 9L cells incubated for 48 hours in the presence and absence of 25 mM DL-α-difluoromethylornithine (DFMO). X-ray dose again did not affect polyamine contents of either DFMO treated or untreated cells. The reduction of total polyamine content by 75% produced by this treatment did not affect the X-ray dose-response curve of 9L cells. Incubation of 9L cells with 40 μM methylglyoxal bis (guanylhydrazone) (MGBG) for 48 hours also did not increase the sensitivity of the treated cells to killing by X-rays. Measurement of intracellular polyamine contents for MGBG-treated and untreated cell showed that Sd was reduced by 70% and Sp by 66%. The increase in Pu content resulted in equal total polyamine contents on a molar basis for both groups of cells. Cultures of 9L cells were incubated for 48 hours in the presence or absence of 40 μM MGBG + 25 mM DFMO, producing an 87% reduction in total polyamine content of treated cells. The Sd content of cells treated with DFMO alone was lower than that of cells treated with DFMO + MGBG, and the combination of the two inhibitors had no effect on the X-ray dose-response. 0.1 mM DFMO did not affect the CFE of untreated unirradiated 9L cells. Addition of 1 mM DFMO caused a greater reduction in the CFE of 9L cells when added at the same time as seeding the cells than when added 24 hours later. There was no difference between the effects of 10 and 25 mM DFMO on the CFE of 9L cells. (U.K.)

  18. The role of rehabilitation measures in reintegration of children with brain tumours or leukaemia and their families after completion of cancer treatment: a study protocol.

    Science.gov (United States)

    Peikert, Mona Leandra; Inhestern, Laura; Bergelt, Corinna

    2017-08-11

    For ill children as well as for their parents and siblings, childhood cancer poses a major challenge. Little is known about the reintegration into daily life of childhood cancer survivors and their families. The aim of this prospective observational study is to further the understanding of the role of rehabilitation measures in the reintegration process of childhood leukaemia or brain tumour survivors and their family members after the end of cancer treatment. This prospective observational study consists of three study arms: a quantitative study in cooperation with three German paediatric oncological study registries (study arm 1), a quantitative study in cooperation with a rehabilitation clinic that offers a family-oriented paediatric oncological rehabilitation programme (study arm 2) and a qualitative study at 12-month follow-up including families from the study arms 1 and 2 (study arm 3). In study arm 1, children, parents and siblings are surveyed after treatment (baseline), 4-6 months after baseline measurement and at 12-month follow-up. In study arm 2, data are collected at the beginning and at the end of the rehabilitation measure and at 12-month follow-up. Families are assessed with standardised questionnaires on quality of life, emotional and behavioural symptoms, depression, anxiety, fear of progression, coping and family functioning. Furthermore, self-developed items on rehabilitation aims and reintegration into daily life are used. Where applicable, users and non-users of rehabilitation measures will be compared regarding the outcome parameters. Longitudinal data will be analysed by means of multivariate analysis strategies. Reference values will be used for comparisons if applicable. Qualitative data will be analysed using thematic analysis. This study has been approved by the medical ethics committee of the Medical Chamber of Hamburg. Data will be published in peer-reviewed journals and presented at conferences. © Article author(s) (or their

  19. Tumour sleuths

    International Nuclear Information System (INIS)

    Beyers, M.; Springolo, E.; Conradie, J.D.

    1986-01-01

    Hepatocellular carcinoma is a common disease in South Africa and its identification difficult. Methods for the diagnosis of this disease includes the production of hybridoma cell lines by inoculating laboratory mice with a purified human tumour-associated antigen or the antigen-containing surface membranes or the intact cells. In the diagnosis of hepatocellular carcinoma, high concentrations of serum alpha fetoprotein (AFP) can be measured by means of radioimmunoassay techniques. The need for specific methods of diagnosis and treatment of hepatocellular carcinoma led to the investigation by the Isotope Production Centre at Pelindaba into the possibility of using radiolabelled monoclonal anti-AFP for diagnosis, and later, therapy of hepatocellular carcinoma. The monoclonal antibodies can also be labelled with 131 I. Recently the Department of Nuclear Medicine of the University of the Witwatersrand is conducting diagnostic trials on patients who have given their informed consent, to assess the specificity of 131 I radiolabelled anti-AFP monoclonal antibodies to hepatocellular carcinoma cells in humans. Although the investigation is still in its infancy, monoclonal antibodies may prove to be successful non-invasive agents for detecting tumors in early stages

  20. Adnexal Tumours Of Skin

    Directory of Open Access Journals (Sweden)

    Parate Sanjay N

    1998-01-01

    Full Text Available A total 120 cases of epidermal appendage tumours of skin were analysed and classified according to the classification provided by WHO’. Epidermal appendage tumours accounted for 12.87% of all skin tumours, of which 29.17% were benign and 70.83% were malignant. Most of the tumours (75.83% were in the head and face region. The most common tumour was basal cell epithelioma (55%.

  1. Comparing Structural Brain Connectivity by the Infinite Relational Model

    DEFF Research Database (Denmark)

    Ambrosen, Karen Marie Sandø; Herlau, Tue; Dyrby, Tim

    2013-01-01

    The growing focus in neuroimaging on analyzing brain connectivity calls for powerful and reliable statistical modeling tools. We examine the Infinite Relational Model (IRM) as a tool to identify and compare structure in brain connectivity graphs by contrasting its performance on graphs from...

  2. On a Mathematical Model of Brain Activities

    International Nuclear Information System (INIS)

    Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.

    2007-01-01

    The procedure of recognition can be described as follows: There is a set of complex signals stored in the memory. Choosing one of these signals may be interpreted as generating a hypothesis concerning an 'expexted view of the world'. Then the brain compares a signal arising from our senses with the signal chosen from the memory leading to a change of the state of both signals. Furthermore, measurements of that procedure like EEG or MEG are based on the fact that recognition of signals causes a certain loss of excited neurons, i.e. the neurons change their state from 'excited' to 'nonexcited'. For that reason a statistical model of the recognition process should reflect both--the change of the signals and the loss of excited neurons. A first attempt to explain the process of recognition in terms of quantum statistics was given. In the present note it is not possible to present this approach in detail. In lieu we will sketch roughly a few of the basic ideas and structures of the proposed model of the recognition process (Section). Further, we introduce the basic spaces and justify the choice of spaces used in this approach. A more elaborate presentation including all proofs will be given in a series of some forthcoming papers. In this series also the procedures of creation of signals from the memory, amplification, accumulation and transformation of input signals, and measurements like EEG and MEG will be treated in detail

  3. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  4. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    Science.gov (United States)

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  5. Mathematical modelling of blood-brain barrier failure and edema

    Science.gov (United States)

    Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

    2015-11-01

    Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

  6. A revised dosimetric model of the adult head and brain

    International Nuclear Information System (INIS)

    Bouchet, L.G.; Bolch, W.E.; Weber, D.A.

    1996-01-01

    During the last decade, new radiopharmaceutical have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head. Brain and head models developed in the past have been only simplistic representations of this anatomic region. For example, the brain within the phantom of MIRD Pamphlet No. 5 Revised is modeled simply as a single ellipsoid of tissue With no differentiation of its internal structures. To address this need, the MIRD Committee established a Task Group in 1992 to construct a more detailed brain model to include the cerebral cortex, the white matter, the cerebellum, the thalamus, the caudate nucleus, the lentiform nucleus, the cerebral spinal fluid, the lateral ventricles, and the third ventricle. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. This model has been incorporated into the radiation transport code EGS4 so as to calculate photon and electron absorbed fractions in the energy range 10 keV to 4 MeV for each of thirteen sources in the brain. Furthermore, explicit positron transport have been considered, separating the contribution by the positron itself and its associated annihilations photons. No differences are found between the electron and positron absorbed fractions; however, for initial energies of positrons greater than ∼0.5 MeV, significant differences are found between absorbed fractions from explicit transport of annihilation photons and those from an assumed uniform distribution of 0.511-MeV photons. Subsequently, S values were calculated for a variety of beta-particle and positron emitters brain imaging agents. Moreover, pediatric head and brain dosimetric models are currently being developed based on this adult head model

  7. Radiation damage, repopulation and cell recovery analysis of in vitro tumour cell megacolony culture data using a non-Poissonian cell repopulation TCP model

    International Nuclear Information System (INIS)

    Stavrev, P; Weldon, M; Warkentin, B; Stavreva, N; Fallone, B G

    2005-01-01

    The effects of radiation damage, tumour repopulation and cell sublethal damage repair and the possibility of extracting information about the model parameters describing them are investigated in this work. Previously published data on two different cultured cell lines were analysed with the help of a tumour control probability (TCP) model that describes tumour cell dynamics properly. Different versions of a TCP model representing the cases of full or partial cell recovery between fractions of radiation, accompanied by repopulation or no repopulation were used to fit the data and were ranked according to statistical criteria. The data analysis shows the importance of the linear-quadratic mechanism of cell damage for the description of the in vitro cell dynamics. In a previous work where in vivo data were analysed, the employment of the single hit model of cell kill and cell repopulation produced the best fit, while ignoring the quadratic term of cell damage in the current analysis leads to poor fits. It is also concluded that more experiments using different fractionation regimes producing diverse data are needed to help model analysis and better ranking of the models

  8. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia

    2017-11-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  9. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia; Pluta, Dustin; Shen, Tong; Chen, Chuansheng; Xue, Gui; Ombao, Hernando

    2017-01-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible

  10. Brain-inspired Stochastic Models and Implementations

    KAUST Repository

    Al-Shedivat, Maruan

    2015-01-01

    One of the approaches to building artificial intelligence (AI) is to decipher the princi- ples of the brain function and to employ similar mechanisms for solving cognitive tasks, such as visual perception or natural language understanding, using

  11. Modelling DW-MRI data from primary and metastatic ovarian tumours

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, Jessica M. [Institute of Cancer Research, CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Surrey (United Kingdom); Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Surrey (United Kingdom); DeSouza, Nandita M.; Collins, David J. [Institute of Cancer Research, CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Surrey (United Kingdom); Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Priest, Andrew N.; Hodgkin, Charlotte; Freeman, Susan [University of Cambridge, Department of Radiology, Addenbrooke' s Hospital, Cambridge (United Kingdom); Wakefield, Jennifer C.; Orton, Matthew R. [Institute of Cancer Research, CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Surrey (United Kingdom)

    2015-07-15

    To assess goodness-of-fit and repeatability of mono-exponential, stretched exponential and bi-exponential models of diffusion-weighted MRI (DW-MRI) data in primary and metastatic ovarian cancer. Thirty-nine primary and metastatic lesions from thirty-one patients with stage III or IV ovarian cancer were examined before and after chemotherapy using DW-MRI with ten diffusion-weightings. The data were fitted with (a) a mono-exponential model to give the apparent diffusion coefficient (ADC), (b) a stretched exponential model to give the distributed diffusion coefficient (DDC) and stretching parameter (α), and (c) a bi-exponential model to give the diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*). Coefficients of variation, established from repeated baseline measurements, were: ADC 3.1 %, DDC 4.3 %, α 7.0 %, D 13.2 %, f 44.0 %, D* 165.1 %. The bi-exponential model was unsuitable in these data owing to poor repeatability. After excluding the bi-exponential model, analysis using Akaike Information Criteria showed that the stretched exponential model provided the better fit to the majority of pixels in 64 % of lesions. The stretched exponential model provides the optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph nodes in pre-treatment and post-treatment measurements with good repeatability. (orig.)

  12. SU-E-T-144: Bayesian Inference of Local Relapse Data Using a Poisson-Based Tumour Control Probability Model

    Energy Technology Data Exchange (ETDEWEB)

    La Russa, D [The Ottawa Hospital Cancer Centre, Ottawa, ON (Canada)

    2015-06-15

    Purpose: The purpose of this project is to develop a robust method of parameter estimation for a Poisson-based TCP model using Bayesian inference. Methods: Bayesian inference was performed using the PyMC3 probabilistic programming framework written in Python. A Poisson-based TCP regression model that accounts for clonogen proliferation was fit to observed rates of local relapse as a function of equivalent dose in 2 Gy fractions for a population of 623 stage-I non-small-cell lung cancer patients. The Slice Markov Chain Monte Carlo sampling algorithm was used to sample the posterior distributions, and was initiated using the maximum of the posterior distributions found by optimization. The calculation of TCP with each sample step required integration over the free parameter α, which was performed using an adaptive 24-point Gauss-Legendre quadrature. Convergence was verified via inspection of the trace plot and posterior distribution for each of the fit parameters, as well as with comparisons of the most probable parameter values with their respective maximum likelihood estimates. Results: Posterior distributions for α, the standard deviation of α (σ), the average tumour cell-doubling time (Td), and the repopulation delay time (Tk), were generated assuming α/β = 10 Gy, and a fixed clonogen density of 10{sup 7} cm−{sup 3}. Posterior predictive plots generated from samples from these posterior distributions are in excellent agreement with the observed rates of local relapse used in the Bayesian inference. The most probable values of the model parameters also agree well with maximum likelihood estimates. Conclusion: A robust method of performing Bayesian inference of TCP data using a complex TCP model has been established.

  13. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. ...

  14. Reptiles: a new model for brain evo-devo research.

    Science.gov (United States)

    Nomura, Tadashi; Kawaguchi, Masahumi; Ono, Katsuhiko; Murakami, Yasunori

    2013-03-01

    Vertebrate brains exhibit vast amounts of anatomical diversity. In particular, the elaborate and complex nervous system of amniotes is correlated with the size of their behavioral repertoire. However, the evolutionary mechanisms underlying species-specific brain morphogenesis remain elusive. In this review we introduce reptiles as a new model organism for understanding brain evolution. These animal groups inherited ancestral traits of brain architectures. We will describe several unique aspects of the reptilian nervous system with a special focus on the telencephalon, and discuss the genetic mechanisms underlying reptile-specific brain morphology. The establishment of experimental evo-devo approaches to studying reptiles will help to shed light on the origin of the amniote brains. Copyright © 2013 Wiley Periodicals, Inc.

  15. The Virtual Brain Integrates Computational Modeling and Multimodal Neuroimaging

    Science.gov (United States)

    Schirner, Michael; McIntosh, Anthony R.; Jirsa, Viktor K.

    2013-01-01

    Abstract Brain function is thought to emerge from the interactions among neuronal populations. Apart from traditional efforts to reproduce brain dynamics from the micro- to macroscopic scales, complementary approaches develop phenomenological models of lower complexity. Such macroscopic models typically generate only a few selected—ideally functionally relevant—aspects of the brain dynamics. Importantly, they often allow an understanding of the underlying mechanisms beyond computational reproduction. Adding detail to these models will widen their ability to reproduce a broader range of dynamic features of the brain. For instance, such models allow for the exploration of consequences of focal and distributed pathological changes in the system, enabling us to identify and develop approaches to counteract those unfavorable processes. Toward this end, The Virtual Brain (TVB) (www.thevirtualbrain.org), a neuroinformatics platform with a brain simulator that incorporates a range of neuronal models and dynamics at its core, has been developed. This integrated framework allows the model-based simulation, analysis, and inference of neurophysiological mechanisms over several brain scales that underlie the generation of macroscopic neuroimaging signals. In this article, we describe how TVB works, and we present the first proof of concept. PMID:23442172

  16. Fresh Frozen Plasma Modulates Brain Gene Expression in a Swine Model of Traumatic Brain Injury and Shock

    DEFF Research Database (Denmark)

    Sillesen, Martin; Bambakidis, Ted; Dekker, Simone E

    2017-01-01

    BACKGROUND: Resuscitation with fresh frozen plasma (FFP) decreases brain lesion size and swelling in a swine model of traumatic brain injury and hemorrhagic shock. We hypothesized that brain gene expression profiles after traumatic brain injury and hemorrhagic shock would be modulated by FFP resu...

  17. Modeling the brain morphology distribution in the general aging population

    Science.gov (United States)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  18. A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

    Science.gov (United States)

    Goebel, Katie; Merner, Nancy D

    2017-05-01

    Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

  19. Immunity to tumour antigens.

    Science.gov (United States)

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  20. Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma.

    Science.gov (United States)

    Mario Gonzalez-Meljem, Jose; Haston, Scott; Carreno, Gabriela; Apps, John R; Pozzi, Sara; Stache, Christina; Kaushal, Grace; Virasami, Alex; Panousopoulos, Leonidas; Neda Mousavy-Gharavy, Seyedeh; Guerrero, Ana; Rashid, Mamunur; Jani, Nital; Goding, Colin R; Jacques, Thomas S; Adams, David J; Gil, Jesus; Andoniadou, Cynthia L; Martinez-Barbera, Juan Pedro

    2017-11-28

    Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2- cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis. We show that expression of oncogenic β-catenin in Hesx1+ embryonic precursors also results in stem cell clusters and paracrine tumours. We reveal that human and mouse clusters are analogous and share a common signature of senescence and SASP. Finally, we show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potential. Together, we provide evidence that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in vivo in an age-dependent fashion.

  1. Perinatal tumours: the contribution of radiology to management

    Energy Technology Data Exchange (ETDEWEB)

    Donoghue, Veronica; Ryan, Stephanie; Twomey, Eilish [Children' s University Hospital, Radiology Department, Dublin (Ireland)

    2008-06-15

    A formal classification does not exist and they are probably best classified by their location. Overall the most common neoplasms are - Extracranial teratoma - Neuroblastoma - Soft-tissue tumours - Brain tumours - Leukaemia - Renal tumours - Liver tumours - Retinoblastoma. The prognosis is generally poor, although there are some exceptions such as congenital neuroblastoma and hepatoblastoma. These tumours have a tendency to regress and have a benign clinical course despite a clear malignant histological picture. Other tumours, though histologically benign, may be fatal because of their size and location. Large benign masses may cause airway or cardiovascular compromise and death. Others may cause significant mass effect preventing normal organ development. As normal embryonic cells have a high mitotic rate it is not surprising that perinatal tumours may have a rapid growth rate and become enormous in size. (orig.)

  2. Development of a model for whole brain learning of physiology.

    Science.gov (United States)

    Eagleton, Saramarie; Muller, Anton

    2011-12-01

    In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed elaborates on these layers by relating the personality traits central to learning to the different quadrants of brain preference, as described by Neethling's brain profile, as the inner layer of the onion. This layer is encircled by the learning styles that describe different information-processing preferences for each brain quadrant. For the middle layer, the different stages of Kolb's learning cycle are classified into the four brain quadrants associated with the different brain processing strategies within the information processing circle. Each of the stages of Kolb's learning cycle is also associated with a specific cognitive learning strategy. These two inner circles are enclosed by the circle representing the role of the environment and instruction on learning. It relates environmental factors that affect learning and distinguishes between face-to-face and technology-assisted learning. This model informs on the design of instructional interventions for physiology to encourage whole brain learning.

  3. A Dirichlet process mixture model for brain MRI tissue classification.

    Science.gov (United States)

    Ferreira da Silva, Adelino R

    2007-04-01

    Accurate classification of magnetic resonance images according to tissue type or region of interest has become a critical requirement in diagnosis, treatment planning, and cognitive neuroscience. Several authors have shown that finite mixture models give excellent results in the automated segmentation of MR images of the human normal brain. However, performance and robustness of finite mixture models deteriorate when the models have to deal with a variety of anatomical structures. In this paper, we propose a nonparametric Bayesian model for tissue classification of MR images of the brain. The model, known as Dirichlet process mixture model, uses Dirichlet process priors to overcome the limitations of current parametric finite mixture models. To validate the accuracy and robustness of our method we present the results of experiments carried out on simulated MR brain scans, as well as on real MR image data. The results are compared with similar results from other well-known MRI segmentation methods.

  4. An inverse model for locating skin tumours in 3D using the genetic algorithm with the Dual Reciprocity Boundary Element Method

    Directory of Open Access Journals (Sweden)

    Fabrício Ribeiro Bueno

    Full Text Available Here, the Dual Reciprocity Boundary Element Method is used to solve the 3D Pennes Bioheat Equation, which together with a Genetic Algorithm, produces an inverse model capable of obtaining the location and the size of a tumour, having as data input the temperature distribution measured on the skin surface. Given that the objective function, which is solved inversely, involves the DRBEM (Dual Reciprocity Boundary Element Method the Genetic Algorithm in its usual form becomes slower, in such a way that it was necessary to develop functions based the solution history in order that the process becomes quicker and more accurate. Results for 8 examples are presented including cases with convection and radiation boundary conditions. Cases involving noise in the readings of the equipment are also considered. This technique is intended to assist health workers in the diagnosis of tumours.

  5. A Bayesian Model of Category-Specific Emotional Brain Responses

    Science.gov (United States)

    Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

    2015-01-01

    Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

  6. Fuzzy object models for newborn brain MR image segmentation

    Science.gov (United States)

    Kobashi, Syoji; Udupa, Jayaram K.

    2013-03-01

    Newborn brain MR image segmentation is a challenging problem because of variety of size, shape and MR signal although it is the fundamental study for quantitative radiology in brain MR images. Because of the large difference between the adult brain and the newborn brain, it is difficult to directly apply the conventional methods for the newborn brain. Inspired by the original fuzzy object model introduced by Udupa et al. at SPIE Medical Imaging 2011, called fuzzy shape object model (FSOM) here, this paper introduces fuzzy intensity object model (FIOM), and proposes a new image segmentation method which combines the FSOM and FIOM into fuzzy connected (FC) image segmentation. The fuzzy object models are built from training datasets in which the cerebral parenchyma is delineated by experts. After registering FSOM with the evaluating image, the proposed method roughly recognizes the cerebral parenchyma region based on a prior knowledge of location, shape, and the MR signal given by the registered FSOM and FIOM. Then, FC image segmentation delineates the cerebral parenchyma using the fuzzy object models. The proposed method has been evaluated using 9 newborn brain MR images using the leave-one-out strategy. The revised age was between -1 and 2 months. Quantitative evaluation using false positive volume fraction (FPVF) and false negative volume fraction (FNVF) has been conducted. Using the evaluation data, a FPVF of 0.75% and FNVF of 3.75% were achieved. More data collection and testing are underway.

  7. Development of a Model for Whole Brain Learning of Physiology

    Science.gov (United States)

    Eagleton, Saramarie; Muller, Anton

    2011-01-01

    In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed…

  8. Bio-Mechanical Model of the Brain for a Per-Operative Image-Guided Neuronavigator Compensating for "Brain-Shift" Deformations

    OpenAIRE

    Bucki, Marek; Lobos, Claudio; Payan, Yohan

    2007-01-01

    International audience; In this paper we present a methodology to address the problem of brain tissue deformation referred to as 'brain-shift'. This deformation occurs throughout a neurosurgery intervention and strongly alters the accuracy of the neuronavigation systems used to date in clinical routine which rely solely on pre-operative patient imaging to locate the surgical target, such as a tumour or a functional area. After a general description of the framework of our intra-operative imag...

  9. Magnetic resonance-imaging of the effect of targeted antiangiogenic gene delivery in a melanoma tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Hundt, Walter [Stanford School of Medicine, Department of Radiology, Lucas MRS Research Center, Stanford, CA (United States); Philipps University Marburg, Department of Radiology, Marburg (Germany); Steinbach, Silke [Philipps University Marburg, Department of Otolaryngology Head and Neck Surgery, Marburg (Germany); Mayer, Dirk; Guccione, Samira [Stanford School of Medicine, Department of Radiology, Lucas MRS Research Center, Stanford, CA (United States); Burbelko, Mykhaylo; Kiessling, Andreas; Figiel, Jens [Philipps University Marburg, Department of Radiology, Marburg (Germany)

    2015-04-01

    We investigated the effect of targeted gene therapy to melanoma tumours (M21) by MR-imaging. M21 and M21-L tumours were grown to a size of 850 mm{sup 3}. M21 and M21-L tumours were intravenously treated with an αvβ3-integrin-ligand-coupled nanoparticle (RGDNP)/RAF(-) complex five times every 72 hours. MRI was performed at set time intervals 24h and 72h after the i.v. injection of the complex. The MRI protocol was T1-wt-SE±CM, T2-wt-FSE, DCE-MRI, Diffusion-wt-STEAM-sequence, T2-time obtained on a 1.5-T-GE-MRI device. The size of the treated M21 tumours kept nearly constant during the treatment phase (847.8±31.4 mm{sup 3} versus 904.8±44.4 mm{sup 3}). The SNR value (T2-weighted images) of the tumours was 36.7±0.6 and dropped down to 30.6±1.9 (p=0.004). At the beginning the SNR value (T1-weighted images) of the tumours after contrast medium application was 42.3±1.9 and dropped down to 28.5±3.0 (p<0.001). In the treatment group the diffusion coefficient increased significantly under therapy (0.54±0.01x10{sup -3} mm{sup 2}/s versus 0.67±0.04x10{sup -3} mm{sup 2}/s). The DCE-MRI showed a reduction of the slope and of the Akep of 67.8±4.3 % respectively 64.8±3.3 % compared to baseline. Targeted gene delivery therapy induces significant changes in MR-imaging. MRI showed a significant reduction of contrast medium uptake parameters and increase of the diffusion coefficient of the tumours. (orig.)

  10. Preparation of 125IUdR and its evaluation in animal tumour model as a potential therapeutic agent

    International Nuclear Information System (INIS)

    Korde, A.; Venkatesh, M.; Banerjee, S.; Pillai, M.R.A.; Sarma, H.D.

    1998-01-01

    5-Iodo-2'-deoxyuridine or iodoxyuridine (IUdR), an analogue of thymidine, is taken up by the proliferating cells during DNA synthesis. Radioiodinated IUdR is a potential therapeutic agent since radiohalogenated thymidine analogues are used for in-vivo tumour targeting and Auger electrons from radionuclides such as 123 I and 125 I are very effective in cell destruction when internalised. 125 IUdR was prepared and studied for its suitability as an in-vivo tumour therapy agent. 125 IUdR was prepared both by direct iodination of 2'-deoxyuridine and iododemercuration of 5-chloromercury-2'-deoxyuridine. Radioiodination yields were between 60-80% at pH 7. Iododemercuration was preferred since with direct iodination poor yields were observed when high specific activity product was desired and also the purification procedure was lengthier. The identity of 125 IUdR was established by comparison of TLC and HPLC patterns with those of authentic IUdR. The purified 125 IUdR had radiochemical purity >95% and was stable for 20 days at 4 deg. C and for a week at 23 deg. C and 37 deg. C. Bio-uptake of 125 IUdR was studied by injecting the tracer in tumour bearing mice (Sarcoma S-180). The uptake in tumour cells was 4.28 +- 2.7% per gram at 3 h and 1.48 +- 0.19% at 24 h post injection. In-vivo deiodination of the product was observed as seen by the uptake of the activity in the thyroid. About 40% the activity from all other organs was excreted in 70 h. The optimum time for injection of the tracer for therapy was studied by observing the delay in tumour growth and survival rate in mice injected at 0,3,9 and 12 days after tumour induction. Injection of the tracer on the third day was found to be the most beneficial for retardation of tumour growth, while injection of the activity on the zeroth and ninth day had no effect. (author)

  11. Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants - a bio-mathematical model

    International Nuclear Information System (INIS)

    Yue Ning; Chen Zhe; Nath, Ravinder

    2002-01-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125 I and 103 Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T)=V p (1+M exp(-0.693T/T e )) where V p is the prostate volume before implantation, M is the edema magnitude and T e is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. D radical S k Δg(r) φ-bar an /r 2 , where r is the distance between a seed and a given point. The distance r is now a function of time because of edema. The g(r) was approximated as 1/r 0.4 and 1/r 0.8 for 125 I and 103 Pd, respectively. By expanding the mathematical expression of the resultant dose rate in a Taylor series of exponential functions of time, the dose rate was made equivalent to that produced from multiple fictitious radionuclides of different decay constants and strengths. The biologically effective dose (BED) for an edematous prostate implant was then calculated using a generalized Dale equation. The cell surviving fraction was computed as exp(-αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125 I and 103 Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days

  12. In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use

    OpenAIRE

    Helms, Hans C; Abbott, N Joan; Burek, Malgorzata; Cecchelli, Romeo; Couraud, Pierre-Olivier; Deli, Maria A; Förster, Carola; Galla, Hans J; Romero, Ignacio A; Shusta, Eric V; Stebbins, Matthew J; Vandenhaute, Elodie; Weksler, Babette; Brodin, Birger

    2016-01-01

    The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This “blood-brain barrier” function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized br...

  13. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  14. A porcine model of haematogenous brain infectionwith staphylococcus aureus

    DEFF Research Database (Denmark)

    Astrup, Lærke Boye; Agerholm, Jørgen Steen; Nielsen, Ole Lerberg

    2012-01-01

    A PORCINE MODEL OF HAEMATOGENOUS BRAIN INFECTION WITH STAPHYLOCOCCUS AUREUS Astrup Lærke1, Agerholm Jørgen1, Nielsen Ole1, Jensen Henrik1, Leifsson Páll1, Iburg Tine2. 1: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark boye@life.ku.dk 2: National Veterinary Institute......, Uppsala, Sweden Introduction Staphylococcus aureus (S.aureus) is a common cause of sepsis and brain abscesses in man and a frequent cause of porcine pyaemia. Here we present a porcine model of haematogenous S. aureus-induced brain infection. Materials and Methods Four pigs had two intravenous catheters...... thromboemboli (two pigs). The venous catheter was used for blood sampling before, during and after inoculation. The pigs were euthanized either 24 or 48 hours after inoculation. The brains were collected and examined histologically. Results We describe unifocal suppurative encephalitis 48 hours after...

  15. Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

    Science.gov (United States)

    2015-09-01

    craniotomy was cut with a trephine by hand over the right motor cortex . An injury cannula was fashioned from the hub of a female leur-lock 20g needle...ABSTRACT This project evaluated the effect of a moderate-level brain injury on risk for opioid abuse using preclinical models in rats . We assessed the...effect of brain injury on the rewarding effects of oxycodone in three rat self-administration procedures and found significant differences in the

  16. Model brain based learning (BBL and whole brain teaching (WBT in learning

    Directory of Open Access Journals (Sweden)

    Baiq Sri Handayani

    2017-08-01

    Full Text Available The learning process is a process of change in behavior as a form of the result of learning. The learning model is a crucial component of the success of the learning process. The learning model is growing fastly, and each model has different characteristics. Teachers are required to be able to understand each model to teach the students optimally by matching the materials and the learning model. The best of the learning model is the model that based on the brain system in learning that are the model of Brain Based Learning (BBL and the model of Whole Brain Teaching (WBT. The purposes of this article are to obtain information related to (1 the brain’s natural learning system, (2 analyze the characteristics of the model BBL and WBT based on theory, brain sections that play a role associated with syntax, similarities, and differences, (3 explain the distinctive characteristics of both models in comparison to other models. The results of this study are: (1 the brain’s natural learning system are: (a the nerves in each hemisphere do not work independently, (b doing more activities can connect more brain nerves, (c the right hemisphere controls the left side motoric sensor of the body, and vice versa; (2 the characteristics of BBL and WBT are: (a BBL is based on the brain’s structure and function, while the model WBT is based on the instructional approach, neurolinguistic, and body language, (b the parts of the brain that work in BBL are: cerebellum, cerebral cortex, frontal lobe, limbic system, and prefrontal cortex; whereas the parts that work WBT are: prefrontal cortex, visual cortex, motor cortex, limbic system, and amygdala, (c the similarities between them are that they both rely on the brain’s system and they both promote gesture in learning, whereas the differences are on the view of the purposes of gestures and the learning theory that they rely on. BBL relies on cognitive theory while WBT relies on social theory; (3 the typical

  17. Epidemiology of childhood cancer and the SACCSG tumour regis try

    African Journals Online (AJOL)

    (biochemistry, cell biology, immunology and genetics); (ii) the tissular or organ level ... geographical distribution, sex and ethnicity. It provides .... developed countries, in South Africa brain tumours ... substantial underreporting, the difference.

  18. Imaging of sacral tumours

    International Nuclear Information System (INIS)

    Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S.; Leclere, J.; Vanel, D.; Missenard, G.; Pinieux, G. de

    2008-01-01

    All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

  19. Imaging of sacral tumours

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S. [Institut Curie, Department of Radiology, Paris (France); Leclere, J. [Institut Gustave Roussy, Department of Radiology, Villejuif (France); Vanel, D. [The Rizzoli Institute, Department of Radiology, Bologna (Italy); Missenard, G. [Institut Gustave Roussy, Comite de pathologie tumorale de l' appareil locomoteur, Villejuif (France); Pinieux, G. de [CHRU de Tours, Department of Pathology, Hopital Trousseau, Tours (France)

    2008-04-15

    All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

  20. Cognitive Models as Bridge between Brain and Behavior.

    Science.gov (United States)

    Love, Bradley C

    2016-04-01

    How can disparate neural and behavioral measures be integrated? Turner and colleagues propose joint modeling as a solution. Joint modeling mutually constrains the interpretation of brain and behavioral measures by exploiting their covariation structure. Simultaneous estimation allows for more accurate prediction than would be possible by considering these measures in isolation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Creating physical 3D stereolithograph models of brain and skull.

    Directory of Open Access Journals (Sweden)

    Daniel J Kelley

    2007-10-01

    Full Text Available The human brain and skull are three dimensional (3D anatomical structures with complex surfaces. However, medical images are often two dimensional (2D and provide incomplete visualization of structural morphology. To overcome this loss in dimension, we developed and validated a freely available, semi-automated pathway to build 3D virtual reality (VR and hand-held, stereolithograph models. To evaluate whether surface visualization in 3D was more informative than in 2D, undergraduate students (n = 50 used the Gillespie scale to rate 3D VR and physical models of both a living patient-volunteer's brain and the skull of Phineas Gage, a historically famous railroad worker whose misfortune with a projectile tamping iron provided the first evidence of a structure-function relationship in brain. Using our processing pathway, we successfully fabricated human brain and skull replicas and validated that the stereolithograph model preserved the scale of the VR model. Based on the Gillespie ratings, students indicated that the biological utility and quality of visual information at the surface of VR and stereolithograph models were greater than the 2D images from which they were derived. The method we developed is useful to create VR and stereolithograph 3D models from medical images and can be used to model hard or soft tissue in living or preserved specimens. Compared to 2D images, VR and stereolithograph models provide an extra dimension that enhances both the quality of visual information and utility of surface visualization in neuroscience and medicine.

  2. MHC class II molecules and tumour immunotherapy

    International Nuclear Information System (INIS)

    Oven, I.

    2005-01-01

    Background. Tumour immunotherapy attempts to use the specificity and capability of the immune system to kill malignant cells with a minimum damage to normal tissue. Increasing knowledge of the identity of tumour antigens should help us design more effective therapeutic vaccines. Increasing evidence has demonstrated that MHC class II molecules and CD4+ T cells play important roles in generating and maintaining antitumour immune responses in animal models. These data suggest that it may be necessary to involve both CD4+ and CD8+ T cells for more effective antitumour therapy. Novel strategies have been developed for enhancing T cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells, by the inclusion of MHC class II-restricted tumour antigens and by genetically modifying tumour cells to present antigen to T lymphocytes directly. Conclusions. Vaccines against cancers aim to induce tumour-specific effector T cells that can reduce tumour mass and induce development of tumour-specific T cell memory, that can control tumour relapse. (author)

  3. Fused cerebral organoids model interactions between brain regions.

    Science.gov (United States)

    Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

    2017-07-01

    Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

  4. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. J.; Lee, D. S.; Kim, J. H.; Hwang, D. W.; Jung, J. G.; Lee, M. C [College of Medicine, Seoul National University, Seoul (Korea, Republic of); Lim, S. M [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advance of microPET scanner, it is possible to image small animals. However, the image quality was not so much satisfactory as human image. As cats have relatively large sized brain, cat brain imaging was superior to mice or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 ul was injected using 30G needle for 5 minutes to establish the infarction model. F-18 FDG microPET (Concorde Microsystems Inc., Knoxville. TN) scans were performed 1. 11 and 32 days after the infarction. In addition. 18F-FDG PET scans were performed using Gemini PET scanner (Philips medical systems. CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infraction lesion improved with time. An infarction lesion was also distinguishable in the Gemini PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using F-18 FDG microPET scanner.

  5. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Jin; Lee, Dong Soo; Kim, Yun Hui; Hwang, Do Won; Kim, Jin Su; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lim, Sang Moo [Korea Institite of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-12-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advent of microPET scanner, it is possible to image small animals. However, the image quality was not good enough as human image. Due to larger brain, cat brain imaging was superior to mouse or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCI. A burr hole was made at 1 cm right lateral to the bregma. Collagenase type IV 10 {mu}l was injected using 30 G needle for 5 minutes to establish the infarction model. {sup 18}F-FDG microPET (Concorde Microsystems Inc., Knoxville, TN) scans were performed 1, 11 and 32 days after the infarction. In addition, {sup 18}F-FDG PET scans were performed using human PET scanner (Gemini, Philips medical systems, CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infarction lesion improved with time. An infarction lesion was also distinguishable in the human PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using {sup 18}F-FDG microPET scanner.

  6. Evaluation of cat brain infarction model using microPET

    International Nuclear Information System (INIS)

    Lee, Jong Jin; Lee, Dong Soo; Kim, Yun Hui; Hwang, Do Won; Kim, Jin Su; Chung, June Key; Lee, Myung Chul; Lim, Sang Moo

    2004-01-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advent of microPET scanner, it is possible to image small animals. However, the image quality was not good enough as human image. Due to larger brain, cat brain imaging was superior to mouse or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCI. A burr hole was made at 1 cm right lateral to the bregma. Collagenase type IV 10 μl was injected using 30 G needle for 5 minutes to establish the infarction model. 18 F-FDG microPET (Concorde Microsystems Inc., Knoxville, TN) scans were performed 1, 11 and 32 days after the infarction. In addition, 18 F-FDG PET scans were performed using human PET scanner (Gemini, Philips medical systems, CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infarction lesion improved with time. An infarction lesion was also distinguishable in the human PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using 18 F-FDG microPET scanner

  7. Evaluation of cat brain infarction model using microPET

    International Nuclear Information System (INIS)

    Lee, J. J.; Lee, D. S.; Kim, J. H.; Hwang, D. W.; Jung, J. G.; Lee, M. C; Lim, S. M

    2004-01-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advance of microPET scanner, it is possible to image small animals. However, the image quality was not so much satisfactory as human image. As cats have relatively large sized brain, cat brain imaging was superior to mice or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 ul was injected using 30G needle for 5 minutes to establish the infarction model. F-18 FDG microPET (Concorde Microsystems Inc., Knoxville. TN) scans were performed 1. 11 and 32 days after the infarction. In addition. 18F-FDG PET scans were performed using Gemini PET scanner (Philips medical systems. CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infraction lesion improved with time. An infarction lesion was also distinguishable in the Gemini PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using F-18 FDG microPET scanner

  8. Predictive modeling of neuroanatomic structures for brain atrophy detection

    Science.gov (United States)

    Hu, Xintao; Guo, Lei; Nie, Jingxin; Li, Kaiming; Liu, Tianming

    2010-03-01

    In this paper, we present an approach of predictive modeling of neuroanatomic structures for the detection of brain atrophy based on cross-sectional MRI image. The underlying premise of applying predictive modeling for atrophy detection is that brain atrophy is defined as significant deviation of part of the anatomy from what the remaining normal anatomy predicts for that part. The steps of predictive modeling are as follows. The central cortical surface under consideration is reconstructed from brain tissue map and Regions of Interests (ROI) on it are predicted from other reliable anatomies. The vertex pair-wise distance between the predicted vertex and the true one within the abnormal region is expected to be larger than that of the vertex in normal brain region. Change of white matter/gray matter ratio within a spherical region is used to identify the direction of vertex displacement. In this way, the severity of brain atrophy can be defined quantitatively by the displacements of those vertices. The proposed predictive modeling method has been evaluated by using both simulated atrophies and MRI images of Alzheimer's disease.

  9. Data-driven forward model inference for EEG brain imaging

    DEFF Research Database (Denmark)

    Hansen, Sofie Therese; Hauberg, Søren; Hansen, Lars Kai

    2016-01-01

    Electroencephalography (EEG) is a flexible and accessible tool with excellent temporal resolution but with a spatial resolution hampered by volume conduction. Reconstruction of the cortical sources of measured EEG activity partly alleviates this problem and effectively turns EEG into a brain......-of-concept study, we show that, even when anatomical knowledge is unavailable, a suitable forward model can be estimated directly from the EEG. We propose a data-driven approach that provides a low-dimensional parametrization of head geometry and compartment conductivities, built using a corpus of forward models....... Combined with only a recorded EEG signal, we are able to estimate both the brain sources and a person-specific forward model by optimizing this parametrization. We thus not only solve an inverse problem, but also optimize over its specification. Our work demonstrates that personalized EEG brain imaging...

  10. Large Scale Computing for the Modelling of Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Albers, Kristoffer Jon

    organization of the brain in continuously increasing resolution. From these images, networks of structural and functional connectivity can be constructed. Bayesian stochastic block modelling provides a prominent data-driven approach for uncovering the latent organization, by clustering the networks into groups...... of neurons. Relying on Markov Chain Monte Carlo (MCMC) simulations as the workhorse in Bayesian inference however poses significant computational challenges, especially when modelling networks at the scale and complexity supported by high-resolution whole-brain MRI. In this thesis, we present how to overcome...... these computational limitations and apply Bayesian stochastic block models for un-supervised data-driven clustering of whole-brain connectivity in full image resolution. We implement high-performance software that allows us to efficiently apply stochastic blockmodelling with MCMC sampling on large complex networks...

  11. Resolving structural variability in network models and the brain.

    Directory of Open Access Journals (Sweden)

    Florian Klimm

    2014-03-01

    Full Text Available Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar graph metrics, but presented here in a more complete statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus specifically on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling--in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity do not in general simultaneously display a second (e.g., hierarchy. This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful

  12. Effects of sensitizers on cell respiration. 3. The effects of hypoxic cell radiosensitizers on oxidative metabolism and the radiation response of an in vitro tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Durand, R E [Wisconsin Clinical Cancer Center, Madison (USA). Dept. of Human Oncology; Biaglow, J E; Greenstock, C L

    1978-06-01

    Physiological factors are important when considering the effects of radiosensitizers on the radiation response of complex systems such as multi-cellular spheroids. In this system, under conditions of unlimited nutrient supply, cells are rendered hypoxic by metabolism. Thus, using the spheroid system as an in vitro model of the tumour-cell microenvironment, we have determined the relative contribution of radiosensitization and respiratory effects of a number of electron-affinic sensitizers having potential clinical use. These studies are indicative of physiological responses at the cellular level, and suggest optimal drug administration schemes for obtaining maximal radiation response in vivo with hypoxic cell sensitizers.

  13. Wilms' tumour (nephroblastoma)

    African Journals Online (AJOL)

    Wilms' tumour or nephroblastoma is a cancer of the kidney that ... It may be noticed by parents or it may be an incidental finding ... patients. It may lead to iron deficiency anaemia. Rarely Wilms' tumour may present with acquired von Willebrand's ... the best treatment approach. ... with multimodality therapy in paediatric.

  14. An Evolutionary Game Theory Model of Spontaneous Brain Functioning.

    Science.gov (United States)

    Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro; Mocenni, Chiara; Santarnecchi, Emiliano

    2017-11-22

    Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.

  15. Multilayer modeling and analysis of human brain networks

    Science.gov (United States)

    2017-01-01

    Abstract Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer’s or Parkinson’s, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. PMID:28327916

  16. Nano-Modeling and Computation in Bio and Brain Dynamics

    Directory of Open Access Journals (Sweden)

    Paolo Di Sia

    2016-04-01

    Full Text Available The study of brain dynamics currently utilizes the new features of nanobiotechnology and bioengineering. New geometric and analytical approaches appear very promising in all scientific areas, particularly in the study of brain processes. Efforts to engage in deep comprehension lead to a change in the inner brain parameters, in order to mimic the external transformation by the proper use of sensors and effectors. This paper highlights some crossing research areas of natural computing, nanotechnology, and brain modeling and considers two interesting theoretical approaches related to brain dynamics: (a the memory in neural network, not as a passive element for storing information, but integrated in the neural parameters as synaptic conductances; and (b a new transport model based on analytical expressions of the most important transport parameters, which works from sub-pico-level to macro-level, able both to understand existing data and to give new predictions. Complex biological systems are highly dependent on the context, which suggests a “more nature-oriented” computational philosophy.

  17. Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn–177Lu is superior to 90Y–177Lu in peptide receptor radiotherapy

    International Nuclear Information System (INIS)

    Walrand, Stephan; Hanin, François-Xavier; Pauwels, Stanislas; Jamar, François

    2012-01-01

    Clinical trials on 177 Lu– 90 Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace 90 Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1–25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for 93 Y, 90 Y and 125 Sn in combination with 177 Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75–25% combination of 177 Lu and 90 Y activity. However, 125 Sn– 177 Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. 125 Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics 125 Sn is the best RN for combination with 177 Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of 125 Sn-labelled somatostatin analogues. (paper)

  18. Fast, Sequence Adaptive Parcellation of Brain MR Using Parametric Models

    DEFF Research Database (Denmark)

    Puonti, Oula; Iglesias, Juan Eugenio; Van Leemput, Koen

    2013-01-01

    In this paper we propose a method for whole brain parcellation using the type of generative parametric models typically used in tissue classification. Compared to the non-parametric, multi-atlas segmentation techniques that have become popular in recent years, our method obtains state-of-the-art ...

  19. Mechanical properties of brain tissue: characterisation and constitutive modelling

    NARCIS (Netherlands)

    Dommelen, van J.A.W.; Hrapko, M.; Peters, G.W.M.; Kamkin, A.; Kiseleva, I.

    2009-01-01

    The head is often considered as the most critical region of the human body for life-threatening injuries sustained in accidents. In order to develop effective protective measures, a better understanding of the process of injury development in the brain is required. Finite Element (FE) models are

  20. Brain metastases of solid tumour. Treatment distribution and analysis of survival in the period 1/01/2004 to 31/12/2008

    International Nuclear Information System (INIS)

    Xavier, F.; Rodriguez, R.; Lima, R.; Rios, A.; Mara, C.

    2010-01-01

    Objective: To retrospectively analyze the characteristics, treatments and survival analysis in patients with solid tumors with brain metastases (E IV) assisted in Unit Neuro-Oncology over a period of five years. Patients and methods: The records of patients (pts) with diagnosis of brain metastases from solid tumors assisted in Neuro-Oncology Unit, from 1/01/2004 and 31/12/2008. Results: 51 new patients carriers of brain metastases were treated with solid tumors. The median age at diagnosis was 57 years, ranging from 30 to 75. They corresponded to the male 37 and female 14 ratio 2.5 / 1. The majority was presented as metastases 31/51. The location was in the supratentorial region in 27 cases, posterior fossa in 11 and 13 were supra and infratentorial. In only 5 patients cranial MRI was performed in only one case and it changed the therapeutical strategy. In 35 patients he corresponded to the lung primary tumor (CBP), following cancer renal (5/51). Within the CBP, the most common histologic subtypes were to large cells and adenocarcinomas, 11 and 10, respectively. In 32 patients were not found dissemination elsewhere. Surgery + RT was performed in 30 cases, in 11 exclusive RT, exclusive surgery in 4 and 3 patients symptomatic treatment. In 39 cases did not Systemic treatment diagnosis. When a progression was only diagnosed It could make systemic treatment 5 pts. The median survival was 15.4 weeks (1-301 weeks). Conclusions: Lung cancer is the most common source of metastases brain, with a poor survival. The results of other characteristics patients, systemic treatments performed and survival according to the treatments performed will be presented during the congresss

  1. Riemannian multi-manifold modeling and clustering in brain networks

    Science.gov (United States)

    Slavakis, Konstantinos; Salsabilian, Shiva; Wack, David S.; Muldoon, Sarah F.; Baidoo-Williams, Henry E.; Vettel, Jean M.; Cieslak, Matthew; Grafton, Scott T.

    2017-08-01

    This paper introduces Riemannian multi-manifold modeling in the context of brain-network analytics: Brainnetwork time-series yield features which are modeled as points lying in or close to a union of a finite number of submanifolds within a known Riemannian manifold. Distinguishing disparate time series amounts thus to clustering multiple Riemannian submanifolds. To this end, two feature-generation schemes for brain-network time series are put forth. The first one is motivated by Granger-causality arguments and uses an auto-regressive moving average model to map low-rank linear vector subspaces, spanned by column vectors of appropriately defined observability matrices, to points into the Grassmann manifold. The second one utilizes (non-linear) dependencies among network nodes by introducing kernel-based partial correlations to generate points in the manifold of positivedefinite matrices. Based on recently developed research on clustering Riemannian submanifolds, an algorithm is provided for distinguishing time series based on their Riemannian-geometry properties. Numerical tests on time series, synthetically generated from real brain-network structural connectivity matrices, reveal that the proposed scheme outperforms classical and state-of-the-art techniques in clustering brain-network states/structures.

  2. Comparison of tumour age response to radiation for cells derived from tissue culture or solid tumours

    International Nuclear Information System (INIS)

    Keng, P.C.; Siemann, D.W.; Rochester Univ., NY; Rochester Univ., NY; Wheeler, K.T.

    1984-01-01

    Direct comparison of the cell age response of 9L and KHT tumour cells derived either from tissue culture or solid tumours was achieved. Cells from dissociated KHT and 9L tumours (the latter implanted either subcutaneously or intracerebrally) and cells from tissue culture were separated into homogenous sized populations by centrifugal elutriation. In both tumour models these homogeneous sized populations correspond to populations enriched at different stages of the cell cycle. The survival of these elutriated cell populations was measured after a single dose of Cs-137 gamma rays. For cells isolated from 9L solid tumours, there was little variation in radiosensitivity throughout the cell cycle; however, a very small but significant increase in resistance was found in late G 1 cells. This lack of a large variation in radiosensitivity through the cell cycle for 9L cells from solid tumours also was seen in 9L cells growing in monolayer tissue culture. When similar experiments were performed using the KHT sarcoma tumour model, the results showed that KHT cells in vitro exhibited a fairly conventional increase in radioresistance in both mid G 1 and late S. However, the cell age response of KHT cells from solid tumours was different; particularly in the late S and G 2 + M phases. (author)

  3. Fetal brain extracellular matrix boosts neuronal network formation in 3D bioengineered model of cortical brain tissue.

    Science.gov (United States)

    Sood, Disha; Chwalek, Karolina; Stuntz, Emily; Pouli, Dimitra; Du, Chuang; Tang-Schomer, Min; Georgakoudi, Irene; Black, Lauren D; Kaplan, David L

    2016-01-01

    The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using in vitro 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.

  4. Magnetic resonance spectroscopy of traumatic brain in SD rats model

    International Nuclear Information System (INIS)

    Li Ke; Li Yangbin; Li Zhiming; Huang Yong; Li Bin; Lu Guangming

    2009-01-01

    Objective: To assess the value and prospect of magnetic resonance spectroscopy (MRS) in early diagnosis of traumatic brain with traumatic brain model in SD rats. Methods: Traumatic brain modal was established in 40 male SD rats utilizing a weigh-drop device, and MRS was performed before trauma and 4,8,24 and 48 hours after trauma. The ratio of N-acetylaspartate/creatine (NAA/Ct) and choline/creatine (Cho/Cr) were calculated and compared with pathological findings respectively. Results: Axonal changes were confirmed in microscopic study 4 hours after injury. The ratio of NAA/Ct decreased distinctly at 4 hours after trauma, followed by a steadily recover at 8 hours, and no significant change from 24h to 48h. There was no significant change in the ratio of Cho/Cr before and after trauma. Conclusion: MRS can be used to monitor the metabolic changes of brain non-invasively. MRS could play a positive role in early diagnosis, prognosis and follow-up of traumatic brain. (authors)

  5. Dosha brain-types: A neural model of individual differences.

    Science.gov (United States)

    Travis, Frederick T; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations.

  6. Dosha brain-types: A neural model of individual differences

    Directory of Open Access Journals (Sweden)

    Frederick T Travis

    2015-01-01

    Full Text Available This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations.

  7. Corticonic models of brain mechanisms underlying cognition and intelligence

    Science.gov (United States)

    Farhat, Nabil H.

    The concern of this review is brain theory or more specifically, in its first part, a model of the cerebral cortex and the way it: (a) interacts with subcortical regions like the thalamus and the hippocampus to provide higher-level-brain functions that underlie cognition and intelligence, (b) handles and represents dynamical sensory patterns imposed by a constantly changing environment, (c) copes with the enormous number of such patterns encountered in a lifetime by means of dynamic memory that offers an immense number of stimulus-specific attractors for input patterns (stimuli) to select from, (d) selects an attractor through a process of “conjugation” of the input pattern with the dynamics of the thalamo-cortical loop, (e) distinguishes between redundant (structured) and non-redundant (random) inputs that are void of information, (f) can do categorical perception when there is access to vast associative memory laid out in the association cortex with the help of the hippocampus, and (g) makes use of “computation” at the edge of chaos and information driven annealing to achieve all this. Other features and implications of the concepts presented for the design of computational algorithms and machines with brain-like intelligence are also discussed. The material and results presented suggest, that a Parametrically Coupled Logistic Map network (PCLMN) is a minimal model of the thalamo-cortical complex and that marrying such a network to a suitable associative memory with re-entry or feedback forms a useful, albeit, abstract model of a cortical module of the brain that could facilitate building a simple artificial brain. In the second part of the review, the results of numerical simulations and drawn conclusions in the first part are linked to the most directly relevant works and views of other workers. What emerges is a picture of brain dynamics on the mesoscopic and macroscopic scales that gives a glimpse of the nature of the long sought after brain code

  8. Tumour-induced osteomalacia.

    Science.gov (United States)

    Minisola, Salvatore; Peacock, Munro; Fukumoto, Seijii; Cipriani, Cristiana; Pepe, Jessica; Tella, Sri Harsha; Collins, Michael T

    2017-07-13

    Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 (FGF23). Owing to the role of FGF23 in renal phosphate handling and vitamin D synthesis, TIO is characterized by decreased renal tubular reabsorption of phosphate, by hypophosphataemia and by low levels of active vitamin D. Chronic hypophosphataemia ultimately results in osteomalacia (that is, inadequate bone mineralization). The diagnosis of TIO is usually suspected when serum phosphate levels are chronically low in the setting of bone pain, fragility fractures and muscle weakness. Locating the offending tumour can be very difficult, as the tumour is often very small and can be anywhere in the body. Surgical removal of the tumour is the only definitive treatment. When the tumour cannot be located or when complete resection is not possible, medical treatment with phosphate salts or active vitamin D is necessary. One of the most promising emerging treatments for unresectable tumours that cause TIO is the anti-FGF23 monoclonal antibody KRN23. The recent identification of a fusion of fibronectin and fibroblast growth factor receptor 1 (FGFR1) as a molecular driver in some tumours not only sheds light on the pathophysiology of TIO but also opens the door to a better understanding of the transcription, translocation, post-translational modification and secretion of FGF23, as well as suggesting approaches to targeted therapy. Further study will reveal if the FGFR1 pathway is also involved in tumours that do not harbour the translocation.

  9. Introduction of Hypermatrix and Operator Notation into a Discrete Mathematics Simulation Model of Malignant Tumour Response to Therapeutic Schemes In Vivo. Some Operator Properties

    Directory of Open Access Journals (Sweden)

    Georgios S. Stamatakos

    2009-10-01

    Full Text Available The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code. However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators’ commutativity and outline the “summarize and jump” strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83–02, thus strengthening the reliability of the model developed.

  10. Introduction of hypermatrix and operator notation into a discrete mathematics simulation model of malignant tumour response to therapeutic schemes in vivo. Some operator properties.

    Science.gov (United States)

    Stamatakos, Georgios S; Dionysiou, Dimitra D

    2009-10-21

    The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code). However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators' commutativity and outline the "summarize and jump" strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83-02, thus strengthening the reliability of the model developed.

  11. Tumours associated with medical X-ray therapy exposure in childhood

    International Nuclear Information System (INIS)

    Colman, M.; Kirsch, M.; Creditor, M.

    1978-01-01

    A total of 5166 persons who were exposed to limited field (80-100 cm 2 ) X-ray irradiation to the head, neck and upper chest region during childhood and adolescence have provided an outstanding opportunity for the study of tumour incidence following medical X-ray therapy. More than 3254 subjects have been traced, 3108 have completed questionnaires eliciting information on tumour incidence, and 1539 of these were subjected to a thorough clinical screening procedure that included a thyroid scintigram. The prevalence of thyroid tumours in the 1539 clinically screened subjects and the prevalence of all other tumours in the 3254 subjects traced can therefore be assumed to reflect the risks in the group of irradiated subjects as a whole. Median age at irradiation was 3.5 years, and median radiation dose 790 rads (7.9 Gy). Thyroid tumour was diagnosed in 413 subjects. Of those undergoing surgery (273) 30.3% were found to have thyroid cancer. A total of 366 surgical pathology specimens of the thyroid, including 93 from subjects who were diagnosed at other hospitals, were examined revealing 73 papillary carcinomas, 12 follicular carcinomas and 26 microscopic papillary carcinomas. One hundred and eighty-seven other (non-thyroid) neoplasmas identified included 27 benign and 10 malignant salivary gland tumours, 16 benign and seven malignant tumours of neural origin (brain, spinal cord, cranial and peripheral nerves), 37 skin tumours, 9 lymphomas, 8 gonadal tumours, 45 breast tumours and 28 tumours of miscellaneous sites. The incidence of thyroid tumours, salivary gland tumours and primary brain tumours was considerably in excess of the expected incidence (p values<0.0001), and a radiation dose-effect correlation was observed for thyroid and brain tumours. Gonadal tumours and lymphomas did not occur in excess of the expected incidence

  12. Malignant thyroid tumours

    International Nuclear Information System (INIS)

    Boerner, W.; Reiners, C.

    1987-01-01

    The subjects dealt with at the symposium cover all topical aspects of pathology, epidemiology, diagnosis, therapy, and aftercare of the malignant thyroid tumours. A survey of the histological classification of the thyroid tumours and a review of the latest findings concerning the radiocarcinogenesis are followed by a detailed discussion of the most significant tumours. There are also papers dealing with controversial aspects of the histological classification, the value of diagnostic methods, radicality of the therapy, or after care. For five conference papers, separate records are available in the database. (orig./ECB) With 59 figs.; 57 tabs [de

  13. Acetyltransferases and tumour suppression

    International Nuclear Information System (INIS)

    Phillips, A C; Vousden, Karen H

    2000-01-01

    The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers

  14. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

    Science.gov (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

    2015-12-01

    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

  15. Closed Loop Brain Model of Neocortical Information Based Exchange

    Directory of Open Access Journals (Sweden)

    James eKozloski

    2016-01-01

    Full Text Available Here we describe an information based exchange' model of brain function that ascribes to neocortex, basal ganglia, and thalamus distinct network functions. The model allows us to analyze whole brain system set point measures, such as the rate and heterogeneity of transitions in striatum and neocortex, in the context of neuromodulation and other perturbations. Our closed-loop model is grounded in neuroanatomical observations, proposing a novel Grand Loop through neocortex, and invokes different forms of plasticity at specific tissue interfaces and their principle cell synapses to achieve these transitions. By implementing a system for maximum information based exchange of action potentials between modeled neocortical areas, we observe changes to these measures in simulation. We hypothesize that similar dynamic set points and modulations exist in the brain's resting state activity, and that different modifications to information based exchange may shift the risk profile of different component tissues, resulting in different neurodegenerative diseases. This model is targeted for further development using IBM's Neural Tissue Simulator, which allows scalable elaboration of networks, tissues, and their neural and synaptic components towards ever greater complexity and biological realism.

  16. Computational brain models: Advances from system biology and future challenges

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-02-01

    Full Text Available Computational brain models focused on the interactions between neurons and astrocytes, modeled via metabolic reconstructions, are reviewed. The large source of experimental data provided by the -omics techniques and the advance/application of computational and data-management tools are being fundamental. For instance, in the understanding of the crosstalk between these cells, the key neuroprotective mechanisms mediated by astrocytes in specific metabolic scenarios (1 and the identification of biomarkers for neurodegenerative diseases (2,3. However, the modeling of these interactions demands a clear view of the metabolic and signaling pathways implicated, but most of them are controversial and are still under evaluation (4. Hence, to gain insight into the complexity of these interactions a current view of the main pathways implicated in the neuron-astrocyte communication processes have been made from recent experimental reports and reviews. Furthermore, target problems, limitations and main conclusions have been identified from metabolic models of the brain reported from 2010. Finally, key aspects to take into account into the development of a computational model of the brain and topics that could be approached from a systems biology perspective in future research are highlighted.

  17. Oxidative stress specifically downregulates survivin to promote breast tumour formation.

    Science.gov (United States)

    Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

    2013-03-05

    Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

  18. Dose-volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours

    International Nuclear Information System (INIS)

    Iori, Mauro; Cattaneo, Giovanni Mauro; Cagni, Elisabetta; Fiorino, Claudio; Borasi, Gianni; Riccardo, Calandrino; Iotti, Cinzia; Fazio, Ferruccio; Nahum, Alan E.

    2008-01-01

    Background and purpose: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. Materials and methods: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. Results: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP = 5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. Conclusions: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT

  19. Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model.

    Science.gov (United States)

    Sugumaran, Abimanyu; Ponnusamy, Chandrasekar; Kandasamy, Palanivel; Krishnaswami, Venkateshwaran; Palanichamy, Rajaguru; Kandasamy, Ruckmani; Lakshmanan, Manikandan; Natesan, Subramanian

    2018-04-30

    Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59±6.12% at 24h), acceptable hemolytic potential, significant cytotoxicity (IC 50 =176±4.3ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84±568.46ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Targeting radiation to tumours

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Greater Glasgow Health Board, Glasgow

    1994-01-01

    Biologically targeted radiotherapy entails the preferential delivery of radiation to solid tumours or individual tumour cells by means of tumour-seeking delivery vehicles to which radionuclides can be conjugated. Monoclonal antibodies have attracted attention for some years as potentially selective targeting agents, but advances in tumour and molecular biology are now providing a much wider choice of molecular species. General radiobiological principles may be derived which are applicable to most forms of targeted radiotherapy. These principles provide guidelines for the appropriate choice of radionuclide in specific treatment situations and its optimal combination with other treatment modalities. In future, the availability of gene targeting agents will focus attention on the use of Auger electron emitters whose high potency and short range selectivity makes them attractive choices for specific killing of cancer cells whose genetic peculiarities are known. (author)

  1. [Gastric mesenchymal tumours (GIST)].

    Science.gov (United States)

    Spivach, Arrigo; Fezzi, Margherita; Sartori, Alberto; Belgrano, Manuel; Rimondini, Alessandra; Cuttin-Zernich, Roberto; Covab, Maria Assunta; Bonifacio, Daniela; Buri, Luigi; Pagani, Carlo; Zanconati, Fabrizio

    2008-01-01

    The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.

  2. Combination radiotherapy in an orthotopic mouse brain tumor model.

    Science.gov (United States)

    Kramp, Tamalee R; Camphausen, Kevin

    2012-03-06

    Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 μl every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without

  3. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Using computational models to relate structural and functional brain connectivity

    Czech Academy of Sciences Publication Activity Database

    Hlinka, Jaroslav; Coombes, S.

    2012-01-01

    Roč. 36, č. 2 (2012), s. 2137-2145 ISSN 0953-816X R&D Projects: GA MŠk 7E08027 EU Projects: European Commission(XE) 200728 - BRAINSYNC Institutional research plan: CEZ:AV0Z10300504 Keywords : brain disease * computational modelling * functional connectivity * graph theory * structural connectivity Subject RIV: FH - Neurology Impact factor: 3.753, year: 2012

  5. Globalization and migration: A "unified brain drain" model

    OpenAIRE

    Brezis, Elise S.; Soueri, Ariel

    2012-01-01

    Globalization has led to a vast flow of migration of workers but also of students. The purpose of this paper is to analyze the migration of individuals encompassing decisions already at the level of education. We develop a unified brain drain model that incorporates the decisions of an individual vis - à - vis both education and migration. In the empirical part, this paper addresses international flows of migration within the EU and presents strong evidence of concentration of students in cou...

  6. A STUDY OF TUMOURS OF THE CRANIAL NERVE AND PARASPINAL NERVE

    Directory of Open Access Journals (Sweden)

    Sudesh Shetty

    2016-03-01

    Full Text Available INTRODUCTION One of the frequent sites of tumour formation is the cranial nerves and paraspinal nerves. The cranial nerves perform a plethora of functions and so the signs and symptoms caused may be different. They are mainly classified into four different types. The aim of the study is: 1. To study the tumours arising from the cranial nerves in an epidemiological point of view. 2. To study the tumours histopathologically. 3. To classify the tumours according to WHO classification. Thirty-eight brain tumor cases were studied in the Department of Medicine, A. J. Shetty Institute of Medical Sciences, Mangalore. Cranial nerve tumours accounts for 4(10% among the intracranial tumours. Schwannomas makes up 3(7.39% among the Intracranial tumours. and constituted 3(75% among cranial nerve tumours. All the 3 schwannomas were located in CP angle. The geographic distribution of cases was found to be 28 cases from Mangalore and 10 cases from Kerala.

  7. Brain SPECT in children

    International Nuclear Information System (INIS)

    Guyot, M.; Baulieu, J.L.

    1996-01-01

    Brain SPECT in child involves specific trends regarding the patient cooperation, irradiation, resolution and especially interpretation because of the rapid scintigraphic modifications related to the brain maturation. In a general nuclear medicine department, child brain SPECT represents about 2 % of the activity. The choice indications are the perfusion children: thallium and MIB