Comparison of IMRT Treatment Plans Between Linac and Helical Tomotherapy Based on Integral Dose and Inhomogeneity Index

International Nuclear Information System (INIS)

Shi Chengyu; Penagaricano, Jose; Papanikolaou, Niko

2008-01-01

Intensity modulated radiotherapy (IMRT) is an advanced treatment technology for radiation therapy. There are several treatment planning systems (TPS) that can generate IMRT plans. These plans may show different inhomogeneity indices to the planning target volume (PTV) and integral dose to organs at risk (OAR). In this study, we compared clinical cases covering different anatomical treatment sites, including head and neck, brain, lung, prostate, pelvis, and cranio-spinal axis. Two treatment plans were developed for each case using Pinnacle 3 and helical tomotherapy (HT) TPS. The inhomogeneity index of the PTV and the non-tumor integral dose (NTID) were calculated and compared for each case. Despite the difference in the number of effective beams, in several cases, NTID did not increase from HT as compared to the step-and-shoot delivery method. Six helical tomotherapy treatment plans for different treatment sites have been analyzed and compared against corresponding step-and-shoot plans generated with the Pinnacle 3 planning system. Results show that HT may produce plans with smaller integral doses to healthy organs, and fairly homogeneous doses to the target as compared to linac-based step-and-shoot IMRT planning in special treatment site such as cranio-spinal

MR image-guided portal verification for brain treatment field

International Nuclear Information System (INIS)

Yin, F.-F.; Gao, Q.H.; Xie, H.; Nelson, D.F.; Yu, Y.; Kwok, W.E.; Totterman, S.; Schell, M.C.; Rubin, P.

1996-01-01

Purpose/Objective: Although MR images have been extensively used for the treatment planning of radiation therapy of cancers, especially for brain cancers, they are not effectively used for the portal verification due to lack of bone/air information in MR images and geometric distortions. Typically, MR images are utilized through correlation with CT images, and this procedure is usually very labor and time consuming. For many brain cancer patients to be treated using conventional external beam radiation, MR images with proper distortion correction provide sufficient information for treatment planning and dose calculation, and a projection images may be generated for each specific treatment port and to be used as a reference image for treatment verification. The question is how to transfer anatomical features in MR images to the projection image as landmarks which could be correlated automatically to those in the portal image. The goal of this study is to generate digitally reconstructed projection images from MR brain images with some important anatomical features (brain contour, skull and gross tumor) as well as their relative locations to be used as references for the development of computerized portal verification scheme. Materials/Methods: Compared to conventional digital reconstructed radiograph from CT images, generation of digitally reconstructed projection images from MR images is heavily involved with pixel manipulation of MR images to correlate information from two types of images (MR, portal x-ray images) which are produced based on totally different imaging principles. Initially a wavelet based multi-resolution adaptive thresholding method is used to segment the skull slice-by-slice in MR brain axial images, and identified skull pixels are re-assigned to relatively higher intensities so that projection images will have comparable grey-level information as that in typical brain portal images. Both T1- and T2-weighted images are utilized to eliminate fat

Activation of glucocorticoid receptors increases 5-HT2A receptor levels

DEFF Research Database (Denmark)

Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

2009-01-01

an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

The 5-HT(1F) receptor agonist lasmiditan as a potential treatment of migraine attacks

DEFF Research Database (Denmark)

Tfelt-Hansen, Peer C; Olesen, Jes

2012-01-01

Lasmiditan is a novel selective 5-HT(1F) receptor agonist. It is both scientifically and clinically relevant to review whether a 5-HT(1F) receptor agonist is effective in the acute treatment of migraine. Two RCTs in the phase II development of lasmiditan was reviewed. In the intravenous placebo...

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission.

Science.gov (United States)

Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

2017-02-15

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT 2A and 5-HT 1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT 1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders

First MR images obtained during megavoltage photon irradiation from a prototype integrated linac-MR system

International Nuclear Information System (INIS)

Fallone, B. G.; Murray, B.; Rathee, S.; Stanescu, T.; Steciw, S.; Vidakovic, S.; Blosser, E.; Tymofichuk, D.

2009-01-01

The authors report the first magnetic resonance (MR) images produced by their prototype MR system integrated with a radiation therapy source. The prototype consists of a 6 MV linac mounted onto the open end of a biplanar 0.2 T permanent MR system which has 27.9 cm pole-to-pole opening with flat gradients (40 mT/m) running under a TMX NRC console. The distance from the magnet isocenter to the linac target is 80 cm. The authors' design has resolved the mutual interferences between the two devices such that the MR magnetic field does not interfere with the trajectory of the electron in the linac waveguide, and the radiofrequency (RF) signals from each system do not interfere with the operation of the other system. Magnetic and RF shielding calculations were performed and confirmed with appropriate measurements. The prototype is currently on a fixed gantry; however, in the very near future, the linac and MR magnet will rotate in unison such that the linac is always aimed through the opening in the biplanar magnet. MR imaging was found to be fully operational during linac irradiation and proven by imaging a phantom with conventional gradient echo sequences. Except for small changes in SNR, MR images produced during irradiation were visually and quantitatively very similar to those taken with the linac turned off. This prototype system provides proof of concept that the design has decreased the mutual interferences sufficiently to allow the development of real-time MR-guided radiotherapy. Low field-strength systems (0.2-0.5 T) have been used clinically as diagnostic tools. The task of the linac-MR system is, however, to provide MR guidance to the radiotherapy beam. Therefore, the 0.2 T field strength would provide adequate image quality for this purpose and, with the addition of fast imaging techniques, has the potential to provide 4D soft-tissue visualization not presently available in image-guided radiotherapy systems. The authors' initial design incorporates a

PET/MR in oncology: an introduction with focus on MR and future perspectives for hybrid imaging

Science.gov (United States)

Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin; Zamogilnaya, Yanna; Højgaard, Liselotte; Fischer, Barbara M

2012-01-01

After more than 20 years of research, a fully integrated PET/MR scanner was launched in 2010 enabling simultaneous acquisition of PET and MR imaging. Currently, no clinical indication for combined PET/MR has been established, however the expectations are high. In this paper we will discuss some of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number of different MRI techniques, such as DWI-MR (diffusion weighted imaging MR), DCE-MR (dynamic contrast enhanced MR), MRS (MR spectroscopy) and MR for attenuation correction of PET. All MR techniques presented in this paper have shown promising results in the treatment of patients with solid tumors and could be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new tracers and drugs will be discussed. PMID:23145362

Single- and double- lumen silicone breast implant integrity: prospective evaluation of MR and US criteria.

Science.gov (United States)

Berg, W A; Caskey, C I; Hamper, U M; Kuhlman, J E; Anderson, N D; Chang, B W; Sheth, S; Zerhouni, E A

1995-10-01

To evaluate the accuracy of magnetic resonance (MR) and ultrasound (US) criteria for breast implant integrity. One hundred twenty-two single-lumen silicone breast implants and 22 bilumen implants were evaluated with surface coil MR imaging and US and surgically removed. MR criteria for implant failure were a collapsed implant shell ("linguine sign"), foci of silicone outside the shell ("noose sign"), and extracapsular gel, US criteria were collapsed shell, low-level echoes within the gel, and "snowstorm" echoes of extracapsular silicone. Among single-lumen implants, MR imaging depicted 39 of 40 ruptures, 14 of 28 with minimal leakage; 49 of 54 intact implants were correctly interpreted. US depicted 26 of 40 ruptured implants, four of 28 with minimal leakage, and 30 of 54 intact implants. Among bilumen implants, MR imaging depicted four of five implants with rupture of both lumina and nine of 10 as intact; US depicted one rupture and helped identify two of 10 as intact. Mammography accurately depicted the status of 29 of 30 bilumen implants with MR imaging correlation. MR imaging depicts implant integrity more accurately than US; neither method reliably depicts minimal leakage with shell collapse. Mammography is useful in screening bilumen implant integrity.

Psychopharmacology of 5-HT1A receptors

International Nuclear Information System (INIS)

Cowen, Philip J.

2000-01-01

Serotonin 1A (5-HT 1A ) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT 1A receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT 1A receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT 1A receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT 1A receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT 1A receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT 1A autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT 1A receptor antagonists

Quantitative myocardial blood flow imaging with integrated time-of-flight PET-MR.

Science.gov (United States)

Kero, Tanja; Nordström, Jonny; Harms, Hendrik J; Sörensen, Jens; Ahlström, Håkan; Lubberink, Mark

2017-12-01

The use of integrated PET-MR offers new opportunities for comprehensive assessment of cardiac morphology and function. However, little is known on the quantitative accuracy of cardiac PET imaging with integrated time-of-flight PET-MR. The aim of the present work was to validate the GE Signa PET-MR scanner for quantitative cardiac PET perfusion imaging. Eleven patients (nine male; mean age 59 years; range 46-74 years) with known or suspected coronary artery disease underwent 15 O-water PET scans at rest and during adenosine-induced hyperaemia on a GE Discovery ST PET-CT and a GE Signa PET-MR scanner. PET-MR images were reconstructed using settings recommended by the manufacturer, including time-of-flight (TOF). Data were analysed semi-automatically using Cardiac VUer software, resulting in both parametric myocardial blood flow (MBF) images and segment-based MBF values. Correlation and agreement between PET-CT-based and PET-MR-based MBF values for all three coronary artery territories were assessed using regression analysis and intra-class correlation coefficients (ICC). In addition to the cardiac PET-MR reconstruction protocol as recommended by the manufacturer, comparisons were made using a PET-CT resolution-matched reconstruction protocol both without and with TOF to assess the effect of time-of-flight and reconstruction parameters on quantitative MBF values. Stress MBF data from one patient was excluded due to movement during the PET-CT scanning. Mean MBF values at rest and stress were (0.92 ± 0.12) and (2.74 ± 1.37) mL/g/min for PET-CT and (0.90 ± 0.23) and (2.65 ± 1.15) mL/g/min for PET-MR (p = 0.33 and p = 0.74). ICC between PET-CT-based and PET-MR-based regional MBF was 0.98. Image quality was improved with PET-MR as compared to PET-CT. ICC between PET-MR-based regional MBF with and without TOF and using different filter and reconstruction settings was 1.00. PET-MR-based MBF values correlated well with PET-CT-based MBF values and

Revealing vilazodone's binding mechanism underlying its partial agonism to the 5-HT1A receptor in the treatment of major depressive disorder.

Science.gov (United States)

Zheng, Guoxun; Xue, Weiwei; Yang, Fengyuan; Zhang, Yang; Chen, Yuzong; Yao, Xiaojun; Zhu, Feng

2017-11-01

It has been estimated that major depressive disorder (MDD) will become the second largest global burden among all diseases by 2030. Various types of drugs, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and serotonin receptor partial agonist/reuptake inhibitors (SPARIs), have been approved and become the primary or first-line medications prescribed for MDD. SPARI was expected to demonstrate more enhanced drug efficacy and a rapid onset of action as compared to SSRI and SNRI. As one of the most famous SPARIs, vilazodone was approved by the FDA for the treatment of MDD. Because of the great clinical importance of vilazodone, its binding mechanism underlying its partial agonism to the 5-HT 1A receptor (5-HT 1A R) could provide valuable information to SPARIs' drug-like properties. However, this mechanism has not been reported to date; consequently, the rational design of new efficacious SPARI-based MDD drugs is severely hampered. To explore the molecular mechanism of vilazodone, an integrated computational strategy was adopted in this study to reveal its binding mechanism and prospective structural feature at the agonist binding site of 5-HT 1A R. As a result, 22 residues of this receptor were identified as hotspots, consistently favoring the binding of vilazodone and its analogues, and a common binding mechanism underlying their partial agonism to 5-HT 1A R was, therefore, discovered. Moreover, three main interaction features between vilazodone and 5-HT 1A R have been revealed and schematically summarized. In summary, this newly identified binding mechanism will provide valuable information for medicinal chemists working in the field of rational design of novel SPARIs for MDD treatment.

Transmission imaging for integrated PET-MR systems.

Science.gov (United States)

Bowen, Spencer L; Fuin, Niccolò; Levine, Michael A; Catana, Ciprian

2016-08-07

Attenuation correction for PET-MR systems continues to be a challenging problem, particularly for body regions outside the head. The simultaneous acquisition of transmission scan based μ-maps and MR images on integrated PET-MR systems may significantly increase the performance of and offer validation for new MR-based μ-map algorithms. For the Biograph mMR (Siemens Healthcare), however, use of conventional transmission schemes is not practical as the patient table and relatively small diameter scanner bore significantly restrict radioactive source motion and limit source placement. We propose a method for emission-free coincidence transmission imaging on the Biograph mMR. The intended application is not for routine subject imaging, but rather to improve and validate MR-based μ-map algorithms; particularly for patient implant and scanner hardware attenuation correction. In this study we optimized source geometry and assessed the method's performance with Monte Carlo simulations and phantom scans. We utilized a Bayesian reconstruction algorithm, which directly generates μ-map estimates from multiple bed positions, combined with a robust scatter correction method. For simulations with a pelvis phantom a single torus produced peak noise equivalent count rates (34.8 kcps) dramatically larger than a full axial length ring (11.32 kcps) and conventional rotating source configurations. Bias in reconstructed μ-maps for head and pelvis simulations was  ⩽4% for soft tissue and  ⩽11% for bone ROIs. An implementation of the single torus source was filled with (18)F-fluorodeoxyglucose and the proposed method quantified for several test cases alone or in comparison with CT-derived μ-maps. A volume average of 0.095 cm(-1) was recorded for an experimental uniform cylinder phantom scan, while a bias of  <2% was measured for the cortical bone equivalent insert of the multi-compartment phantom. Single torus μ-maps of a hip implant phantom showed significantly

Psychopharmacology of 5-HT{sub 1A} receptors

Energy Technology Data Exchange (ETDEWEB)

Cowen, Philip J

2000-07-01

Serotonin{sub 1A} (5-HT{sub 1A}) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT{sub 1A} receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT{sub 1A} receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT{sub 1A} receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT{sub 1A} receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT{sub 1A} receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT{sub 1A} autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT{sub 1A} receptor antagonists.

What would 5-HT do? Regional diversity of 5-HT1 receptor modulation of primary afferent neurotransmission

OpenAIRE

Connor, Mark

2012-01-01

5-HT (serotonin) is a significant modulator of sensory input to the CNS, but the only analgesics that selectively target G-protein-coupled 5-HT receptors are highly specific for treatment of headache. Two recent papers in BJP shed light on this puzzling situation by showing that primary afferent neurotransmission to the superficial layers of the spinal and trigeminal dorsal is inhibited by different subtypes of the 5-HT1 receptor – 5-HT1B(and 1D) in the trigeminal dorsal horn and 5-HT1A in th...

3D stereotaxis for epileptic foci through integrating MR imaging with neurological electrophysiology data

International Nuclear Information System (INIS)

Luo Min; Peng Chenglin; Wang Kang; Lei Wenyong; Luo Song; Wang Xiaolin; Wang Xuejian; Wu Ruoqiu; Wu Guofeng

2005-01-01

Objective: To improve the accuracy of the epilepsy diagnoses by integrating MR image from PACS with data from neurological electrophysiology. The integration is also very important for transmiting diagnostic information to 3D TPS of radiotherapy. Methods: The electroencephalogram was redisplayed by EEG workstation, while MR image was reconstructed by Brainvoyager software. 3D model of patient brain was built up by combining reconstructed images with electroencephalogram data in Base 2000. 30 epileptic patients (18 males and 12 females) with their age ranged from 12 to 54 years were confirmed by using the integrated MR images and the data from neurological electrophysiology and their 3D stereolocating. Results: The corresponding data in 3D model could show the real situation of patients' brain and visually locate the precise position of the focus. The suddessful rate of 3D guided operation was greatly improved, and the number of epileptic onset was markedly decreased. The epilepsy was stopped for 6 months in 8 of the 30 patients. Conclusion: The integration of MR image and information of neurological electrophysiology can improve the diagnostic level for epilepsy, and it is crucial for imp roving the successful rate of manipulations and the epilepsy analysis. (authors)

Serotonin 5-HT3 and 5-HT4 ligands: an update of medicinal chemistry research in the last few years.

Science.gov (United States)

Modica, M N; Pittalà, V; Romeo, G; Salerno, L; Siracusa, M A

2010-01-01

The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is one of the most studied neurotransmitters in the central nervous system. It acts through the activation of at least fourteen 5-HT receptor subtypes. Over the last two decades, high attention was devoted to the 5-HT(3) and 5-HT(4) receptors due to their colocalization in the gastrointestinal tract and because their ligands are useful in the treatment of intestinal serotonergic system dysfunctions. The focus of this review is to discuss the literature concerning recent advances on 5-HT(3)R and 5-HT(4)R ligands and their structure-activity relationships from a medicinal chemistry perspective. During the last few years, new and significant progresses have been made in the field of novel potent and selective ligands, mixed ligands, agonists, partial agonists, and antagonists, and a number of patents have been filed. Furthermore several ligands targeting the 5-HT(3)R and 5-HT(4)R have been proposed for novel therapeutic indications such as the treatment of various psychiatric disorders.

Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

Directory of Open Access Journals (Sweden)

Nilgun Gurbuz

Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

Directory of Open Access Journals (Sweden)

Nilgun Gurbuz

Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D- mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

MR Imaging in Monitoring and Predicting Treatment Response in Multiple Sclerosis.

Science.gov (United States)

Río, Jordi; Auger, Cristina; Rovira, Àlex

2017-05-01

MR imaging is the most sensitive tool for identifying lesions in patients with multiple sclerosis (MS). MR imaging has also acquired an essential role in the detection of complications arising from these treatments and in the assessment and prediction of efficacy. In the future, other radiological measures that have shown prognostic value may be incorporated within the models for predicting treatment response. This article examines the role of MR imaging as a prognostic tool in patients with MS and the recommendations that have been proposed in recent years to monitor patients who are treated with disease-modifying drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

WE-EF-BRD-00: New Developments in Hybrid MR-Treatment: Applications

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

MRI-guided treatment is a growing area of medicine, particularly in radiotherapy and surgery. The exquisite soft tissue anatomic contrast offered by MRI, along with functional imaging, makes the use of MRI during therapeutic procedures very attractive. Challenging the utility of MRI in the therapy room are many issues including the physics of MRI and the impact on the environment and therapeutic instruments, the impact of the room and instruments on the MRI; safety, space, design and cost. In this session, the applications and challenges of MRI-guided treatment will be described. The session format is: Past, present and future: MRI-guided radiotherapy from 2005 to 2025: Jan Lagendijk Battling Maxwell’s equations: Physics challenges and solutions for hybrid MRI systems: Paul Keall I want it now!: Advances in MRI acquisition, reconstruction and the use of priors to enable fast anatomic and physiologic imaging to inform guidance and adaptation decisions: Yanle Hu MR in the OR: The growth and applications of MRI for interventional radiology and surgery: Rebecca Fahrig Learning Objectives: To understand the history and trajectory of MRI-guided radiotherapy To understand the challenges of integrating MR imaging systems with linear accelerators To understand the latest in fast MRI methods to enable the visualisation of anatomy and physiology on radiotherapy treatment timescales To understand the growing role and challenges of MRI for image-guided surgical procedures My disclosures are publicly available and updated at: http://sydney.edu.au/medicine/radiation-physics/about-us/disclosures.php.

WE-EF-BRD-00: New Developments in Hybrid MR-Treatment: Applications

International Nuclear Information System (INIS)

2015-01-01

MRI-guided treatment is a growing area of medicine, particularly in radiotherapy and surgery. The exquisite soft tissue anatomic contrast offered by MRI, along with functional imaging, makes the use of MRI during therapeutic procedures very attractive. Challenging the utility of MRI in the therapy room are many issues including the physics of MRI and the impact on the environment and therapeutic instruments, the impact of the room and instruments on the MRI; safety, space, design and cost. In this session, the applications and challenges of MRI-guided treatment will be described. The session format is: Past, present and future: MRI-guided radiotherapy from 2005 to 2025: Jan Lagendijk Battling Maxwell’s equations: Physics challenges and solutions for hybrid MRI systems: Paul Keall I want it now!: Advances in MRI acquisition, reconstruction and the use of priors to enable fast anatomic and physiologic imaging to inform guidance and adaptation decisions: Yanle Hu MR in the OR: The growth and applications of MRI for interventional radiology and surgery: Rebecca Fahrig Learning Objectives: To understand the history and trajectory of MRI-guided radiotherapy To understand the challenges of integrating MR imaging systems with linear accelerators To understand the latest in fast MRI methods to enable the visualisation of anatomy and physiology on radiotherapy treatment timescales To understand the growing role and challenges of MRI for image-guided surgical procedures My disclosures are publicly available and updated at: http://sydney.edu.au/medicine/radiation-physics/about-us/disclosures.php

MR image-guided portal verification for brain treatment field

International Nuclear Information System (INIS)

Yin Fangfang; Gao Qinghuai; Xie Huchen; Nelson, Diana F.; Yu Yan; Kwok, W. Edmund; Totterman, Saara; Schell, Michael C.; Rubin, Philip

1998-01-01

Purpose: To investigate a method for the generation of digitally reconstructed radiographs directly from MR images (DRR-MRI) to guide a computerized portal verification procedure. Methods and Materials: Several major steps were developed to perform an MR image-guided portal verification procedure. Initially, a wavelet-based multiresolution adaptive thresholding method was used to segment the skin slice-by-slice in MR brain axial images. Some selected anatomical structures, such as target volume and critical organs, were then manually identified and were reassigned to relatively higher intensities. Interslice information was interpolated with a directional method to achieve comparable display resolution in three dimensions. Next, a ray-tracing method was used to generate a DRR-MRI image at the planned treatment position, and the ray tracing was simply performed on summation of voxels along the ray. The skin and its relative positions were also projected to the DRR-MRI and were used to guide the search of similar features in the portal image. A Canny edge detector was used to enhance the brain contour in both portal and simulation images. The skin in the brain portal image was then extracted using a knowledge-based searching technique. Finally, a Chamfer matching technique was used to correlate features between DRR-MRI and portal image. Results: The MR image-guided portal verification method was evaluated using a brain phantom case and a clinical patient case. Both DRR-CT and DRR-MRI were generated using CT and MR phantom images with the same beam orientation and then compared. The matching result indicated that the maximum deviation of internal structures was less than 1 mm. The segmented results for brain MR slice images indicated that a wavelet-based image segmentation technique provided a reasonable estimation for the brain skin. For the clinical patient case with a given portal field, the MR image-guided verification method provided an excellent match between

Study of the effects of austenitizing and tempering heat treatments on the alloy HT-9

International Nuclear Information System (INIS)

Redmon, J.W.

1982-01-01

This paper investigates the potential use of the ferritic alloy Sandvik HT-9 (12 Cr - 1 Mo) as an alternative to stainless steels used in high-neutron-fluence environments. The neutron radiation influences embrittlement where the impact-energy versus test-temperature curve is seen displaced to the right. As a result, commercially effective solutioning and tempering processes are needed to suppress this effect in the pre-irradiated condition. The effects of austenitizing treatments on the impact energy of HT-9 were identified. 18 figures, 6 tables

Modeling and simulation of a 100 kWe HT-PEMFC subsystem integrated with an absorption chiller subsystem

DEFF Research Database (Denmark)

Arsalis, Alexandros

2012-01-01

A 100 kWe liquid-cooled HT-PEMFC subsystem is integrated with an absorption chiller subsystem to provide electricity and cooling. The system is designed, modeled and simulated to investigate the potential of this technology for future novel energy system applications. Liquid-cooling can provide...

5-HT causes splanchnic venodilation.

Science.gov (United States)

Seitz, Bridget M; Orer, Hakan S; Krieger-Burke, Teresa; Darios, Emma S; Thompson, Janice M; Fink, Gregory D; Watts, Stephanie W

2017-09-01

Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT 7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT 7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT 1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT 7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT 7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT 7 receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg -1 ·min -1 ) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT 7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT 7 receptor, an in vitro observation (venorelaxation) with in vivo events

Successful treatment with risperidone increases 5-HT 3A receptor gene expression in patients with paranoid schizophrenia - data from a prospective study.

Science.gov (United States)

Chen, Hongying; Fan, Yong; Zhao, Lei; Hao, Yong; Zhou, Xiajun; Guan, Yangtai; Li, Zezhi

2017-09-01

The relationship between peripheral 5-HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown. A total 52 first-episode and drug-naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week. There was no difference in 5-HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline ( p  = .24). Among 47 patients who completed 8-week naturalistic follow-up, 37 were responders to risperidone treatment. 5-HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8-week treatment with risperidone ( p  = .29). However, 5-HT3A receptor mRNA level in responders increased significantly ( p  = .04), but not in nonresponders ( p  = .81). Successful treatment with risperidone increases 5-HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5-HT3A receptor may be involved in the mechanism of risperidone effect.

Repeated 7-Day Treatment with the 5-HT2C Agonist Lorcaserin or the 5-HT2A Antagonist Pimavanserin Alone or in Combination Fails to Reduce Cocaine vs Food Choice in Male Rhesus Monkeys.

Science.gov (United States)

Banks, Matthew L; Negus, S Stevens

2017-04-01

Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT 2C agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT 2A inverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT 2C receptor activation nor 5-HT 2A receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT 2C agonists and 5-HT 2A inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.

Effect of multiple austenitizing treatments on HT-9 steels

International Nuclear Information System (INIS)

Emigh, R.A.

1985-12-01

The effect of multiple austenitizing treatments on the toughness of an Fe-12Cr-1.0Mo-0.5W-0.3V (HT-9) steel was studied. The resulting microstructures were characterized by their mechanical properties, precipitated carbide distribution, and fracture surface appearance. It was proposed that multiple transformations would refine the martensite structure and improve toughness. Optical and scanning electron microscopic observations revealed that the martensite packet structure was somewhat refined by a second austenite transformation. Transmission electron microscopy studies of carbon extraction replicas showed that this multiple step treatment had eliminated grain boundary carbide films seen in single treated specimens on prior austenite grain boundaries. The 0.2% yield strength, tensile strength, and elongation were relatively unchanged, but the toughness measured by fatigue pre-cracked Charpy impact tests increased for the multiple step specimens

Mediastinal lymphoma: quantitative changes in gadolinium enhancement at MR imaging after treatment.

Science.gov (United States)

Rahmouni, A; Divine, M; Lepage, E; Jazaerli, N; Belhadj, K; Gaulard, P; Golli, M; Reyes, F; Vasile, N

2001-06-01

To compare changes in gadolinium enhancement at magnetic resonance (MR) imaging with outcome in mediastinal lymphoma after treatment. Thirty-one patients with bulky mediastinal lymphoma (17 with Hodgkin disease, 14 with non-Hodgkin lymphoma) underwent serial MR imaging before and up to 50 months after treatment, with routine follow-up (including computed tomography). Signal intensity ratios between masses and muscle were calculated on T1-weighted, T2-weighted, and contrast material-enhanced T1-weighted spin-echo MR images. The percentage enhancement and signal intensity ratios of mediastinal masses on T2-weighted MR images were calculated at diagnosis and during and after treatment. Twenty-one patients with persistent complete remission had a mean percentage enhancement of residual masses (4%; range, -26% to 40%) that was significantly lower than that of initial masses (78%; range, 41%-124%). Although the mean signal intensity ratio of residual masses on T2-weighted images was significantly lower than that of initial masses, an increase in this ratio was observed in four patients after treatment. In seven patients with relapse, the percentage enhancement value of the residual mass was as high as that of the initial mass. Gadolinium enhancement of lymphomatous masses of the mediastinum decreased markedly after treatment in patients in continuous complete remission but not in patients with relapse.

Clinical utility of nitisinone for the treatment of hereditary tyrosinemia type-1 (HT-1

Directory of Open Access Journals (Sweden)

Das AM

2017-07-01

Full Text Available Anibh Martin Das Department of Pediatrics, Hannover Medical School, Hannover, Germany Abstract: Medical therapy for hereditary hepatorenal tyrosinemia (hereditary tyrosinemia type 1, HT-1 with nitisinone was discovered incidentally, and is a by-product of agrochemistry. It blocks the catabolic pathway of tyrosine, thereby leading to a reduction in the accumulation of toxic metabolites in HT-1. It has to be combined with a low-protein diet supplemented with amino acid mixtures devoid of tyrosine and phenylalanine. This treatment option has completely changed the clinical course of patients suffering from HT-1 who used to die in the first few months to years of life from liver failure, renal dysfunction, and/or hepatocellular carcinoma (HCC. It is essential to start nitisinone therapy early in life to avoid sequelae; beginning treatment in the newborn period is ideal. As initial clinical symptoms of HT-1 are often atypical and because there is a clinically latent phase during the first few months of life in many patients, newborn screening is required to secure early diagnosis. Succinylacetone in blood is a reliable screening parameter whereas tyrosine is neither specific nor sensitive. Especially HCC, but also liver and kidney dysfunction, rickets, and neurological crises can be prevented in most patients if nitisinone therapy is started in the newborn period. It is essential to adhere to a low-protein diet to avoid tyrosine toxicity. Reversible eye symptoms may occur as a side-effect of nitisinone, but other side effects are rare. Neurocognitive development is impaired in some patients, and the reason for this is unclear. Metabolic monitoring includes measurement of tyrosine, succinylacetone, and nitisinone concentrations in blood. Keywords: diet, hepatocellular carcinoma, hepatorenal tyrosinemia, nitisinone, newborn screening, succinylacetone

Integration Of An MR Image Network Into A Clinical PACS

Science.gov (United States)

Ratib, Osman M.; Mankovich, Nicholas J.; Taira, Ricky K.; Cho, Paul S.; Huang, H. K.

1988-06-01

A direct link between a clinical pediatric PACS module and a FONAR MRI image network was implemented. The original MR network combines together the MR scanner, a remote viewing station and a central archiving station. The pediatric PACS directly connects to the archiving unit through an Ethernet TCP-IP network adhering to FONAR's protocol. The PACS communication software developed supports the transfer of patient studies and the patient information directly from the MR archive database to the pediatric PACS. In the first phase of our project we developed a package to transfer data between a VAX-111750 and the IBM PC I AT-based MR archive database through the Ethernet network. This system served as a model for PACS-to-modality network communication. Once testing was complete on this research network, the software and network hardware was moved to the clinical pediatric VAX for full PACS integration. In parallel to the direct transmission of digital images to the Pediatric PACS, a broadband communication system in video format was developed for real-time broadcasting of images originating from the MR console to 8 remote viewing stations distributed in the radiology department. These analog viewing stations allow the radiologists to directly monitor patient positioning and to select the scan levels during a patient examination from remote locations in the radiology department. This paper reports (1) the technical details of this implementation, (2) the merits of this network development scheme, and (3) the performance statistics of the network-to-PACS interface.

Integrated PET/MR breast cancer imaging: Attenuation correction and implementation of a 16-channel RF coil

Energy Technology Data Exchange (ETDEWEB)

Oehmigen, Mark, E-mail: mark.oehmigen@uni-due.de; Lindemann, Maike E. [High Field and Hybrid MR Imaging, University Hospital Essen, Essen 45147 (Germany); Lanz, Titus [Rapid Biomedical GmbH, Rimpar 97222 (Germany); Kinner, Sonja [Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen 45147 (Germany); Quick, Harald H. [High Field and Hybrid MR Imaging, University Hospital Essen, Essen 45147, Germany and Erwin L. Hahn Institute for MR Imaging, University Duisburg-Essen, Essen 45141 (Germany)

2016-08-15

Purpose: This study aims to develop, implement, and evaluate a 16-channel radiofrequency (RF) coil for integrated positron emission tomography/magnetic resonance (PET/MR) imaging of breast cancer. The RF coil is designed for optimized MR imaging performance and PET transparency and attenuation correction (AC) is applied for accurate PET quantification. Methods: A 16-channel breast array RF coil was designed for integrated PET/MR hybrid imaging of breast cancer lesions. The RF coil features a lightweight rigid design and is positioned with a spacer at a defined position on the patient table of an integrated PET/MR system. Attenuation correction is performed by generating and applying a dedicated 3D CT-based template attenuation map. Reposition accuracy of the RF coil on the system patient table while using the positioning frame was tested in repeated measurements using MR-visible markers. The MR, PET, and PET/MR imaging performances were systematically evaluated using modular breast phantoms. Attenuation correction of the RF coil was evaluated with difference measurements of the active breast phantoms filled with radiotracer in the PET detector with and without the RF coil in place, serving as a standard of reference measurement. The overall PET/MR imaging performance and PET quantification accuracy of the new 16-channel RF coil and its AC were then evaluated in first clinical examinations on ten patients with local breast cancer. Results: The RF breast array coil provides excellent signal-to-noise ratio and signal homogeneity across the volume of the breast phantoms in MR imaging and visualizes small structures in the phantoms down to 0.4 mm in plane. Difference measurements with PET revealed a global loss and thus attenuation of counts by 13% (mean value across the whole phantom volume) when the RF coil is placed in the PET detector. Local attenuation ranging from 0% in the middle of the phantoms up to 24% was detected in the peripheral regions of the phantoms at

Enhancement of cortical extracellular 5-HT by 5-HT1A and 5-HT2C receptor blockade restores the antidepressant-like effect of citalopram in non-responder mice.

Science.gov (United States)

Calcagno, Eleonora; Guzzetti, Sara; Canetta, Alessandro; Fracasso, Claudia; Caccia, Silvio; Cervo, Luigi; Invernizzi, Roberto W

2009-07-01

We recently found that the response of DBA/2 mice to SSRIs in the forced swim test (FST) was impaired and they also had a smaller basal and citalopram-stimulated increase in brain extracellular serotonin (5-HT) than 'responder' strains. We employed intracerebral microdialysis, FST and selective antagonists of 5-HT1A and 5-HT2C receptors to investigate whether enhancing the increase in extracellular 5-HT reinstated the anti-immobility effect of citalopram in the FST. WAY 100635 (0.3 mg/kg s.c.) or SB 242084 (1 mg/kg s.c.), respectively a selective 5-HT1A and 5-HT2C receptor antagonist, raised the effect of citalopram (5 mg/kg) on extracellular 5-HT in the medial prefrontal cortex of DBA/2N mice (citalopram alone 5.2+/-0.3 fmol/20 microl, WAY 100635+citalopram 9.9+/-2.1 fmol/20 microl, SB 242084+ citalopram 7.6+/-1.0 fmol/20 microl) to the level reached in 'responder' mice given citalopram alone. The 5-HT receptor antagonists had no effect on the citalopram-induced increase in extracellular 5-HT in the dorsal hippocampus. The combination of citalopram with WAY 100635 or SB 242084 significantly reduced immobility time in DBA/2N mice that otherwise did not respond to either drug singly. Brain levels of citalopram in mice given citalopram alone or with 5-HT antagonists did not significantly differ. The results confirm that impaired 5-HT transmission accounts for the lack of effect of citalopram in the FST and suggest that enhancing the effect of SSRIs on extracellular 5-HT, through selective blockade of 5-HT1A and 5-HT2C receptors, could be a useful strategy to restore the response in treatment-resistant depression.

Systematisation of spatial uncertainties for comparison between a MR and a CT-based radiotherapy workflow for prostate treatments

International Nuclear Information System (INIS)

Nyholm, Tufve; Nyberg, Morgan; Karlsson, Magnus G; Karlsson, Mikael

2009-01-01

In the present work we compared the spatial uncertainties associated with a MR-based workflow for external radiotherapy of prostate cancer to a standard CT-based workflow. The MR-based workflow relies on target definition and patient positioning based on MR imaging. A solution for patient transport between the MR scanner and the treatment units has been developed. For the CT-based workflow, the target is defined on a MR series but then transferred to a CT study through image registration before treatment planning, and a patient positioning using portal imaging and fiducial markers. An 'open bore' 1.5T MRI scanner, Siemens Espree, has been installed in the radiotherapy department in near proximity to a treatment unit to enable patient transport between the two installations, and hence use the MRI for patient positioning. The spatial uncertainty caused by the transport was added to the uncertainty originating from the target definition process, estimated through a review of the scientific literature. The uncertainty in the CT-based workflow was estimated through a literature review. The systematic uncertainties, affecting all treatment fractions, are reduced from 3-4 mm (1Sd) with a CT based workflow to 2-3 mm with a MR based workflow. The main contributing factor to this improvement is the exclusion of registration between MR and CT in the planning phase of the treatment. Treatment planning directly on MR images reduce the spatial uncertainty for prostate treatments

PHP-HT (VitaResc Biotech).

Science.gov (United States)

Baldwin, A; Wiley, E

2001-04-01

VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680].

HT-PEM Fuel Cell System with Integrated Thermoelectric Exhaust Heat Recovery

DEFF Research Database (Denmark)

Gao, Xin

This thesis presents two case studies on improving the efficiency and the loadfollowing capability of a high temperature polymer electrolyte membrane (HTPEM) fuel cell system by the application of thermoelectric (TE) devices. TE generators (TEGs) are harnessed to recover the system exhaust gas...... developed three-dimensional numerical model in ANSYS Fluent®. This thesis introduces the progress of this project in a cognitive order. The first chapter initially prepares the theory and characteristics of the fuel cell system and TE devices. Project motivations are conceived. Then similar studies existing...... power output on the subsystem design and performance were also systematically analyzed. The TEG subsystem configuration is optimized. The usefulness and convenience of the model are proved. TE coolers (TECs) are integrated into the methanol evaporator of the HT-PEM system for improving the whole system...

Targeting to 5-HT1F Receptor Subtype for Migraine Treatment

DEFF Research Database (Denmark)

Mitsikostas, Dimos D; Tfelt-Hansen, Peer

2012-01-01

attacks with efficacy in the same range as oral sumatriptan 100mg, the gold standard for triptans. The LY334370 project withdrew because of toxicity in animals, while lasmiditan is still testing. In this review we present all the available preclinical and clinical data on the 5-HT1F agonists...... inhibited markers associated with electrical stimulation of the TG. Thus 5-HT1F receptor represents an ideal target for anti-migraine drugs. So far two selective 5-HT1F agonists have been tested in human trials for migraine: LY334370 and lasmiditan. Both molecules were efficient in attenuating migraine...

Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity

Directory of Open Access Journals (Sweden)

Darya V. Bazovkina

2015-01-01

Full Text Available In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors.

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

Directory of Open Access Journals (Sweden)

Malgorzata S. Martin-Gronert

2016-04-01

Full Text Available Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC peptides within the arcuate nucleus of the hypothalamus (ARC. We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus of in utero growth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist.

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

Science.gov (United States)

Martin-Gronert, Malgorzata S; Stocker, Claire J; Wargent, Edward T; Cripps, Roselle L; Garfield, Alastair S; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S H; Cawthorne, Michael A; Arch, Jonathan R S; Heisler, Lora K; Ozanne, Susan E

2016-04-01

Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. © 2016. Published by The Company of Biologists Ltd.

The renewed HT-7 plasma control system based on real-time Linux cluster

Energy Technology Data Exchange (ETDEWEB)

Yuan, Q.P., E-mail: qpyuan@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Xiao, B.J.; Zhang, R.R. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Walker, M.L.; Penaflor, B.G.; Piglowski, D.A.; Johnson, R.D. [General Atomics, DIII-D National Fusion Facility, San Diego, CA (United States)

2012-12-15

Highlights: Black-Right-Pointing-Pointer The hardware and software structure of the new HT-7 plasma control system (HT-7 PCS) is reported. Black-Right-Pointing-Pointer All original systems were integrated in the new HT-7 PCS. And the implementation details of the control algorithms are given in the paper. Black-Right-Pointing-Pointer Different from EAST PCS, the AC operation mode is realized in HT-7 PCS. Black-Right-Pointing-Pointer The experiment results are discussed. Good control performance has been obtained. - Abstract: In order to improve the synchronization, flexibility and expansibility of the plasma control on HT-7, a new plasma control system (HT-7 PCS) was constructed. The HT-7 PCS was based on a real-time Linux cluster with a well-defined, robust and flexible software infrastructure which was adapted from DIII-D PCS. In this paper, the hardware structure and system customization details for HT-7 PCS are reported. The plasma position and current control, plasma density control and off-normal event detection, which were realized in separated systems originally, have been integrated and implemented in such HT-7 PCS. All these control algorithms have been successfully validated in the last several HT-7 experiment campaigns. Good control performance has been achieved and the experiment results are discussed in the paper.

Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function.

Science.gov (United States)

Holbrook, Joanna D; Gill, Catherine H; Zebda, Noureddine; Spencer, Jon P; Leyland, Rebecca; Rance, Kim H; Trinh, Han; Balmer, Gemma; Kelly, Fiona M; Yusaf, Shahnaz P; Courtenay, Nicola; Luck, Jane; Rhodes, Andrew; Modha, Sundip; Moore, Stephen E; Sanger, Gareth J; Gunthorpe, Martin J

2009-01-01

The 5-HT(3) receptor is a member of the 'Cys-loop' family of ligand-gated ion channels that mediate fast excitatory and inhibitory transmission in the nervous system. Current evidence points towards native 5-HT(3) receptors originating from homomeric assemblies of 5-HT(3A) or heteromeric assembly of 5-HT(3A) and 5-HT(3B). Novel genes encoding 5-HT(3C), 5-HT(3D), and 5-HT(3E) have recently been described but the functional importance of these proteins is unknown. In the present study, in silico analysis (confirmed by partial cloning) indicated that 5-HT(3C), 5-HT(3D), and 5-HT(3E) are not human-specific as previously reported: they are conserved in multiple mammalian species but are absent in rodents. Expression profiles of the novel human genes indicated high levels in the gastrointestinal tract but also in the brain, Dorsal Root Ganglion (DRG) and other tissues. Following the demonstration that these subunits are expressed at the cell membrane, the functional properties of the recombinant human subunits were investigated using patch clamp electrophysiology. 5-HT(3C), 5-HT(3D), and 5-HT(3E) were all non-functional when expressed alone. Co-transfection studies to determine potential novel heteromeric receptor interactions with 5-HT(3A) demonstrated that the expression or function of the receptor was modified by 5-HT(3C) and 5-HT(3E), but not 5-HT(3D). The lack of distinct effects on current rectification, kinetics or pharmacology of 5-HT(3A) receptors does not however provide unequivocal evidence to support a direct contribution of 5-HT(3C) or 5-HT(3E) to the lining of the ion channel pore of novel heteromeric receptors. The functional and pharmacological contributions of these novel subunits to human biology and diseases such as irritable bowel syndrome for which 5-HT(3) receptor antagonists have major clinical usage, therefore remains to be fully determined.

MR-based source localization for MR-guided HDR brachytherapy

Science.gov (United States)

Beld, E.; Moerland, M. A.; Zijlstra, F.; Viergever, M. A.; Lagendijk, J. J. W.; Seevinck, P. R.

2018-04-01

For the purpose of MR-guided high-dose-rate (HDR) brachytherapy, a method for real-time localization of an HDR brachytherapy source was developed, which requires high spatial and temporal resolutions. MR-based localization of an HDR source serves two main aims. First, it enables real-time treatment verification by determination of the HDR source positions during treatment. Second, when using a dummy source, MR-based source localization provides an automatic detection of the source dwell positions after catheter insertion, allowing elimination of the catheter reconstruction procedure. Localization of the HDR source was conducted by simulation of the MR artifacts, followed by a phase correlation localization algorithm applied to the MR images and the simulated images, to determine the position of the HDR source in the MR images. To increase the temporal resolution of the MR acquisition, the spatial resolution was decreased, and a subpixel localization operation was introduced. Furthermore, parallel imaging (sensitivity encoding) was applied to further decrease the MR scan time. The localization method was validated by a comparison with CT, and the accuracy and precision were investigated. The results demonstrated that the described method could be used to determine the HDR source position with a high accuracy (0.4–0.6 mm) and a high precision (⩽0.1 mm), at high temporal resolutions (0.15–1.2 s per slice). This would enable real-time treatment verification as well as an automatic detection of the source dwell positions.

Treatment plan quality of tri-Co-60 MR-IGRT system in comparison with that of VMAT

Energy Technology Data Exchange (ETDEWEB)

Park, Jong Min; Park, So Yeon; Kim, Jung In [Dept. of Nuclear Engineering, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Hak Jae; Wu, Hong Gyun [Dept. of Nuclear Engineering, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2016-04-15

The ViewRay{sup TM} system combines a 0.35-T MR imaging system and a radiation therapy system using a total of three Co-60 sources. It can perform static intensity-modulated radiation therapy (IMRT) with multi-leaf collimators (MLCs) with leaf widths of 1.05 cm at the plane of isocenter, at source to axis distance (SAD) of 105 cm. Since the tri-Co-60 MR-IGRT system can acquire near-real-time cine sagittal MR images during treatment, automated respiratory gating can be performed based on these cine images, thus, the target margins for lung stereotactic ablative radiotherapy (SABR) could be reduced considerably by comparison with the internal tarvet volume (ITV) approach. we compared lung SABR treatment plans of the tri-Co-60 MR-IGRT system with gross tumor volume (GTV) to those of volumetric modulated arc therapy (VMAT) using TrueBeam STx™ (Varian Medical Systems, Palo Alto, CA) with ITV in this study. The plan quality of the target volume of the VMAT with ITV was better than that of the GTV-based tri-Co-60 MR-IGRT for lung SABR. No significant differences for OARs were observed between the tri-Co-60 MR-IGRT and VMAT. However, the plan quality of the tri-Co-60 MR-IGRT system was clinically acceptable. Despite the relatively poor plan quality of the tri-Co-60 MR-IGRT system, it still has the advantage of real-time monitoring of tumor motion during treatment.

SU-F-J-150: Development of An End-To-End Chain Test for the First-In-Man MR-Guided Treatments with the MRI Linear Accelerator by Using the Alderson Phantom

Energy Technology Data Exchange (ETDEWEB)

Hoogcarspel, S; Kerkmeijer, L; Lagendijk, J; Van Vulpen, M; Raaymakers, B [University Medical Center Utrecht, Utrecht, Utrecht (Netherlands)

2016-06-15

The Alderson phantom is a human shaped quality assurance tool that has been used for over 30 years in radiotherapy. The phantom can provide integrated tests of the entire chain of treatment planning and delivery. The purpose of this research was to investigate if this phantom can be used to chain test a treatment on the MRI linear accelerator (MRL) which is currently being developed at the UMC Utrecht, in collaboration with Elekta and Philips. The latter was demonstrated by chain testing the future First-in-Man treatments with this system.An Alderson phantom was used to chain test an entire treatment with the MRL. First, a CT was acquired of the phantom with additional markers that are both visible on MR and CT. A treatment plan for treating bone metastases in the sacrum was made. The phantom was consecutively placed in the MRL. For MRI imaging, an 3D volume was acquired. The initially developed treatment plan was then simulated on the new MRI dataset. For simulation, both the MR and CT data was used by registering them together. Before treatment delivery a MV image was acquired and compared with a DRR that was calculated form the MR/CT registration data. Finally, the treatment was delivered. Figure 1 shows both the T1 weighted MR-image of the phantom and the CT that was registered to the MR image. Figure 2 shows both the calculated and measured MV image that was acquired by the MV panel. Figure 3 shows the dose distribution that was simulated. The total elapsed time for the entire procedure excluding irradiation was 13:35 minutes.The Alderson Phantom yields sufficient MR contrast and can be used for full MR guided radiotherapy treatment chain testing. As a result, we are able to perform an end-to-end chain test of the future First-in-Man treatments.

TU-F-BRF-02: MR-US Prostate Registration Using Patient-Specific Tissue Elasticity Property Prior for MR-Targeted, TRUS-Guided HDR Brachytherapy

International Nuclear Information System (INIS)

Yang, X; Rossi, P; Ogunleye, T; Jani, A; Curran, W; Liu, T

2014-01-01

Purpose: High-dose-rate (HDR) brachytherapy has become a popular treatment modality for prostate cancer. Conventional transrectal ultrasound (TRUS)-guided prostate HDR brachytherapy could benefit significantly from MR-targeted, TRUS-guided procedure where the tumor locations, acquired from the multiparametric MRI, are incorporated into the treatment planning. In order to enable this integration, we have developed a MR-TRUS registration with a patient-specific biomechanical elasticity prior. Methods: The proposed method used a biomechanical elasticity prior to guide the prostate volumetric B-spline deformation in the MRI and TRUS registration. The patient-specific biomechanical elasticity prior was generated using ultrasound elastography, where two 3D TRUS prostate images were acquired under different probe-induced pressures during the HDR procedure, which takes 2-4 minutes. These two 3D TRUS images were used to calculate the local displacement (elasticity map) of two prostate volumes. The B-spline transformation was calculated by minimizing the Euclidean distance between the normalized attribute vectors of the prostate surface landmarks on the MR and TRUS. This technique was evaluated through two studies: a prostate-phantom study and a pilot study with 5 patients undergoing prostate HDR treatment. The accuracy of our approach was assessed through the locations of several landmarks in the post-registration and TRUS images; our registration results were compared with the surface-based method. Results: For the phantom study, the mean landmark displacement of the proposed method was 1.29±0.11 mm. For the 5 patients, the mean landmark displacement of the surface-based method was 3.25±0.51 mm; our method, 1.71±0.25 mm. Therefore, our proposed method of prostate registration outperformed the surfaced-based registration significantly. Conclusion: We have developed a novel MR-TRUS prostate registration approach based on patient-specific biomechanical elasticity prior

Integrated three-dimensional display of MR, CT, and PET images of the brain

International Nuclear Information System (INIS)

Levin, D.N.; Herrmann, A.; Chen, G.T.Y.

1988-01-01

MR, CT, and PET studies depict complementary aspects of brain anatomy and function. The authors' own image-processing software and a Pixar image computer were used to create three-dimensional models of brain soft tissues from MR images, of the skull and calcifications from CT scans, and of brain metabolism from PET images. An image correlation program, based on surface fitting, was used for retrospective registration and merging of these three-dimensional models. The results are demonstrated in a video clip showing how the operator may rotate and perform electronic surgery on the integrated, multimodality three-dimensional model of each patient's brain

SU-F-J-144: Scatter and Leakage Survey of An Integrated MR-Linac System

Energy Technology Data Exchange (ETDEWEB)

Wang, J; Bosco, G; Darenbourg, B; Ibbott, G [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: To assess the scatter and leakage radiation of an integrated 1.5T MRI-Linac system. Methods: A 150cc chamber (model 96020C, Inovision) was used in all the scatter and leakage measurements, after being recalibrated for MV energy by the Accredited Dosimetry Calibration Laboratory at MD Anderson. The scatter radiation was measured by placing a 25 cm stack of solid-water materials at iso-center on the patient couch to simulate patient scatter. Gantry angles were positioned at 0 degree (beam pointing downward) and 270 (beam pointing laterally). Scatter radiation was measured at selective locations inside the RF room. Beam stopper leakage was measured at the exterior panel of the gantry. The head leakage was measured at 1 meter away from the Linac head in the direction which was determined to be the area of maximum leakage by wrapped films test. All measurements were repeated with the 1.5T magnetic field turned off to study the effect of magnetic field. Results: When the magnet was on (B=1.5T), the maximum head leakage at 1 meter was 191.6mR/1000MU. The scatter radiation at 1 meter from the iso-center was 1.091R/1000MU when the radiation beam was pointing downward, 1.296R/1000MU when the beam pointed laterally. The beam stopper leakage was measured as 299.4 mR/1000MU at the exterior panel of the gantry. When magnet was off (B=0), the head leakage was measured as 198.6mR/1000MU. The scatter radiation at 1 meter was 1.153R/1000MU when beam pointed downward, 1.287R/1000MU when beam pointed laterally. The beam stopper leakage was measured as 309.4 mR/1000MU at the exterior panel of the gantry. Conclusion: The measurements indicate that the scatter and leakage radiation from the integrated MR-Linac system are in-line with the expected values. The beam stopper leakage is approximately 300 mR/1000MU. The leakage and scatter difference with the magnetic field ON and OFF was within 5%. The authors received a corporate sponsored grant from Elekta which is the vendor of

The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory

Directory of Open Access Journals (Sweden)

Oliver eStiedl

2015-08-01

Full Text Available Serotonin (5-hydroxytryptamine, 5-HT is a multifunctional neurotransmitter innervating cortical and limbic areas involved in cognition and emotional regulation. Dysregulation of serotonergic transmission is associated with emotional and cognitive deficits in psychiatric patients and animal models. Drugs targeting the 5-HT system are widely used to treat mood disorders and anxiety-like behaviors. Among the fourteen 5-HT receptor (5-HTR subtypes, the 5-HT1AR and 5-HT7R are associated with the development of anxiety, depression and cognitive function linked to mechanisms of emotional learning and memory. In rodents fear conditioning and passive avoidance (PA are associative learning paradigms to study emotional memory. This review assesses the role of 5-HT1AR and 5-HT7R as well as their interplay at the molecular, neurochemical and behavioral level. Activation of postsynaptic 5-HT1ARs impairs emotional memory through attenuation of neuronal activity, whereas presynaptic 5-HT1AR activation reduces 5-HT release and exerts pro-cognitive effects on PA retention. Antagonism of the 5-HT1AR facilitates memory retention possibly via 5-HT7R activation and evidence is provided that 5HT7R can facilitate emotional memory upon reduced 5-HT1AR transmission. These findings highlight the differential role of these 5-HTRs in cognitive/emotional domains of behavior. Moreover, the results indicate that tonic and phasic 5-HT release can exert different and potentially opposing effects on emotional memory, depending on the states of 5-HT1ARs and 5-HT7Rs and their interaction. Consequently, individual differences due to genetic and/or epigenetic mechanisms play an essential role for the responsiveness to drug treatment, e.g., by SSRIs which increase intrasynaptic 5-HT levels thereby activating multiple pre- and postsynaptic 5-HTR subtypes.

MO-F-CAMPUS-J-04: Tissue Segmentation-Based MR Electron Density Mapping Method for MR-Only Radiation Treatment Planning of Brain

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Yu, H [Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Lee, Y [Sunnybrook Odette Cancer Centre, Toronto, Ontario (Canada); Ruschin, M [Odette Cancer Centre, Toronto, ON (Canada); Karam, I [Sunnybrook Odette Cancer Center, Toronto, Ontario (Canada); Sahgal, A [University of Toronto, Toronto, ON (Canada)

2015-06-15

Purpose: Automatically derive electron density of tissues using MR images and generate a pseudo-CT for MR-only treatment planning of brain tumours. Methods: 20 stereotactic radiosurgery (SRS) patients’ T1-weighted MR images and CT images were retrospectively acquired. First, a semi-automated tissue segmentation algorithm was developed to differentiate tissues with similar MR intensities and large differences in electron densities. The method started with approximately 12 slices of manually contoured spatial regions containing sinuses and airways, then air, bone, brain, cerebrospinal fluid (CSF) and eyes were automatically segmented using edge detection and anatomical information including location, shape, tissue uniformity and relative intensity distribution. Next, soft tissues - muscle and fat were segmented based on their relative intensity histogram. Finally, intensities of voxels in each segmented tissue were mapped into their electron density range to generate pseudo-CT by linearly fitting their relative intensity histograms. Co-registered CT was used as a ground truth. The bone segmentations of pseudo-CT were compared with those of co-registered CT obtained by using a 300HU threshold. The average distances between voxels on external edges of the skull of pseudo-CT and CT in three axial, coronal and sagittal slices with the largest width of skull were calculated. The mean absolute electron density (in Hounsfield unit) difference of voxels in each segmented tissues was calculated. Results: The average of distances between voxels on external skull from pseudo-CT and CT were 0.6±1.1mm (mean±1SD). The mean absolute electron density differences for bone, brain, CSF, muscle and fat are 78±114 HU, and 21±8 HU, 14±29 HU, 57±37 HU, and 31±63 HU, respectively. Conclusion: The semi-automated MR electron density mapping technique was developed using T1-weighted MR images. The generated pseudo-CT is comparable to that of CT in terms of anatomical position of

Vibration control of a cable-stayed bridge using electromagnetic induction based sensor integrated MR dampers

International Nuclear Information System (INIS)

Cho, Sang Won; Koo, Jeong Hoi; Jo, Ji Seong

2007-01-01

This paper presents a novel electromagnetic induction (EMI) system integrated in magneto rheological (MR) dampers: The added EMI system converts reciprocal motions of MR damper into electiral energy (electromotive force or emf) according to the Faraday's law of electromagnetic induction. Maximum energy dissipation algorithm (MEDA) is employed to regulate the MR dampers because it strives to simplify a complex design process by employing the Lyapunov's direct approach. The emf signal, produced from the EMI, provides the necessary measurement information (i.e., realtive velocity across the damper) for the MEDA controller. Thus, the EMI acts as a sensor in the proposed MR-EMI system. In order to evaluate the performance and robustness of the MR-EMI sensor system with the MEDA control, this study performed an extensive simulation study using the first generation benchmark cable-stayed bridge. Moreover, it compared the performance and the robustness of proposed system with those of Clipped-Optimal Control (COC) and Sliding Mode Control (SMC), which were previously studied for the benchmark cable-stayed bridge. The results show that the MR-EMI system reduced the vibrations of the bridge structure more than those of COC and SMC and show more robust performance than that of SMC. These results suggest that EMIs can be used cost-effective sensing devices for MR damper control systems without compromising the performance of them

Chronic 5-HT4 receptor agonist treatment restores learning and memory deficits in a neuroendocrine mouse model of anxiety/depression.

Science.gov (United States)

Darcet, Flavie; Gardier, Alain M; David, Denis J; Guilloux, Jean-Philippe

2016-03-11

Cognitive disturbances are often reported as serious invalidating symptoms in patients suffering from major depression disorders (MDD) and are not fully corrected by classical monoaminergic antidepressant drugs. If the role of 5-HT4 receptor agonists as cognitive enhancers is well established in naïve animals or in animal models of cognitive impairment, their cognitive effects in the context of stress need to be examined. Using a mouse model of anxiety/depression (CORT model), we reported that a chronic 5-HT4 agonist treatment (RS67333, 1.5mg/kg/day) restored chronic corticosterone-induced cognitive deficits, including episodic-like, associative and spatial learning and memory impairments. On the contrary, a chronic monoaminergic antidepressant drug treatment with fluoxetine (18mg/kg/day) only partially restored spatial learning and memory deficits and had no effect in the associative/contextual task. These results suggest differential mechanisms underlying cognitive effects of these drugs. Finally, the present study highlights 5-HT4 receptor stimulation as a promising therapeutic mechanism to alleviate cognitive symptoms related to MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

Science.gov (United States)

Moreno, José L.; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C.; González-Maeso, Javier

2013-01-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [3H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. PMID:23333599

Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

Science.gov (United States)

Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

2013-03-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

Science.gov (United States)

Banks, Matthew L

2016-08-01

Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

Osteochondrosis dissecans of the knee: Evaluation of the evolution of MR morphology during treatment

International Nuclear Information System (INIS)

Palczewski, P.; Golebiowski, M.; Strzelczyk, P.

2008-01-01

To assess the evolution of MR morphology of OCD lesions in response to treatment and feasibility of MRI as a control study in patients with treated OCD. 11 patients (6 women and 5 men, aged 11-24 years, average age 17 years) with lesions affecting 12 knee joints were followed for approximately 24.2 months with repeated clinical examination and MR imaging. All MR studies were performed on a 1.5 Tesla unit. MR arthrography was performed in 3 patients. The evolution of MR morphology of the lesions was assessed with a 5-point scale and correlated with the results of clinical assessment with a modified Lysholm scale. In 10 patients, a good clinical result was achieved. In 7 knee joints of patients from this group, the features of the healing of the OCD lesion were observed in MRI and in 4 knees the morphology of the OCD lesion was stable. In 5 MR examinations, a transient deterioration was observed, which in 4 cases preceded healing and in 1 case stabilization in MR morphology. Transient deterioration may be observed in MR studies prior to the healing of OCD lesions irrespective of the improvement in clinical examination. The follow up of patients with OCD should be based mainly on clinical examination, with MR studies reserved for late control or patients with clinical signs of deterioration. (author)

Haliotis tuberculata hemocyanin (HtH): analysis of oligomeric stability of HtH1 and HtH2, and comparison with keyhole limpet hemocyanin KLH1 and KLH2.

Science.gov (United States)

Harris, J R; Scheffler, D; Gebauer, W; Lehnert, R; Markl, J

2000-12-01

an almost 100% conversion into didecamers, whereas the HtH2 subunit produced a mixture containing large numbers of short multidecamers and relatively few didecamers, together with a considerable number of smaller diameter helical/tubular polymers. The association properties of the HtH1 and HtH2 decamers, and the subunit reassociation, firmly indicate the integrity and structural competency of the protein under the experimental conditions used. Data on the association of KLH2 decamers is also presented, which together with previously published data on the association KLH1 decamers and the reassociation of KLH1 and KLH2 subunits, enables a detailed comparison of the two hemocyanin isoforms from both molluscan species to be made. Biochemical manipulation of the oligomer states and the subunit reassociation of molluscan hemocyanins can usefully be assessed by the study of negatively stained TEM specimens.

Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT neurons in mice with altered 5-HT homeostasis

Directory of Open Access Journals (Sweden)

Naozumi eAraragi

2013-08-01

Full Text Available Firing activity of serotonin (5-HT neurons in the dorsal raphe nucleus (DRN is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert -/- and tryptophan hydroxylase-2 knockout (Tph2 -/- mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+-8-hydroxy-2-(di-n-propylaminotetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2 -/- mice and Sert -/- mice, respectively. While 5-HT neurons from Tph2 -/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert -/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP, neurons from both Tph2 -/- and Sert -/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling.

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

Science.gov (United States)

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Multipurpose simulator ''MR TRIOS'' for reprocessing plant

International Nuclear Information System (INIS)

Mitsui, Takeshi; Uehara, Shigeru; Takata, Hideo; Kamishima, Naoyuki

1993-01-01

MHI (Mitsubishi Heavy Industries) has developed MR TRIOS (Mitsubishi Reprocessing plant TRansient simulation code for Integrated process for Operation Support), the realtime dynamic simulator, for multipurpose use to support the Reprocessing Plant operation in various aspects. MR TRIOS integrates the Simulation Models of the unit process in a Reprocessing Plant, including Shearing, Dissolution, NOx absorption, Accountability and Adjustment and Co-decontamination process, where each Simulation Model has two kinds of models: Process and Control System. MR TRIOS can simulate the process behavior of the unit process in an integrated manner as well as independently. It is supported by MR CONTROL, the simulator control program developed by MHI. From MR TRIOS one can obtain real-time process values, such as temperature, pressure, density, flow rate, and concentration of nuclides, enabling the evaluation of the process dynamic characteristics under various operating conditions. MR TRIOS has proved to be an effective tool for the comprehensive study of the process and system dynamics, for operation technique improvements and for training

Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy

Directory of Open Access Journals (Sweden)

Paul R Albert

2010-06-01

Full Text Available Major depression is the most common form of mental illness, and is treated with antidepressant compounds that increase serotonin (5-HT neurotransmission. Increased 5-HT1A autoreceptor levels in the raphe nuclei act as a “brake” to inhibit the 5-HT system, leading to depression and resistance to antidepressants. Several 5-HT1A receptor agonists (buspirone, flesinoxan, ipsapirone that preferentially desensitize 5-HT1A autoreceptors have been tested for augmentation of antidepressant drugs with mixed results. One explanation could be the presence of the C(-1019G 5-HT1A promoter polymorphism that prevents gene repression of the 5-HT1A autoreceptor. Furthermore, down-regulation of 5-HT1A autoreceptor expression, not simply desensitization of receptor signaling, appears to be required to enhance and accelerate antidepressant action. The current review focuses on the transcriptional regulators of 5-HT1A autoreceptor expression, their roles in permitting response to 5-HT1A-targeted treatments and their potential as targets for new antidepressant compounds for treatment-resistant depression.

Converging evidence for central 5-HT effects in acute tryptophan depletion

DEFF Research Database (Denmark)

Crockett, Molly; Clark, Luke; Roiser, Jonathan

2012-01-01

the validity of ATD.2 Although we agree that ATD's effects on 5-HT activity at the molecular level need further clarification, van Donkelaar et al.2 goes too far in challenging whether ATD exerts its effects through serotonergic mechanisms. There is strong evidence that ATD reduces brain 5-HT and disrupts......Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned...

Anterior Cruciate Ligament Tear: Reliability of MR Imaging to Predict Stability after Conservative Treatment

Energy Technology Data Exchange (ETDEWEB)

Chung, Hye Won; Ahn, Jin Hwan; Ahn, Joong Mo; Yoon, Young Cheol; Hong, Hyun Pyo; Yoo, So Young; Kim, Seon Woo [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2007-06-15

The aim of this study is to evaluate the reliability of MR imaging to predict the stability of the torn anterior cruciate ligament (ACL) after complete recovery of the ligament's continuity. Twenty patients with 20 knee injuries (13 males and 7 females; age range, 20 54) were enrolled in the study. The inclusion criteria were a positive history of acute trauma, diagnosis of the ACL tear by both the physical examination and the MR imaging at the initial presentation, conservative treatment, complete recovery of the continuity of the ligament on the follow up (FU) MR images and availability of the KT-2000 measurements. Two radiologists, who worked in consensus, graded the MR findings with using a 3-point system for the signal intensity, sharpness, straightness and the thickness of the healed ligament. The insufficiency of ACL was categorized into three groups according to the KT-2000 measurements. The statistic correlations between the grades of the MR findings and the degrees of ACL insufficiency were analyzed using the Cochran-Mantel-Haenszel test (p < 0.05). The p-values for each category of the MR findings according to the different groups of the KT-2000 measurements were 0.9180 for the MR signal intensity, 1.0000 for sharpness, 0.5038 for straightness and 0.2950 for thickness of the ACL. The MR findings were not significantly different between the different KT-2000 groups. MR imaging itself is not a reliable examination to predict stability of the ACL rupture outcome, even when the MR images show an intact appearance of the ACL.

SU-F-J-143: Initial Assessment of Image Quality of An Integrated MR-Linac System with ACR Phantom

Energy Technology Data Exchange (ETDEWEB)

Wang, J; Fuller, C [MD Anderson Cancer Center, Houston, TX (United States); Yung, J; Kadbi, M; Ding, Y; Ibbott, G [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose/Objective(s): To assess the image quality of an integrated MR-Linac system and compare with other MRI systems that are primarily used for diagnostic purposes. Materials/Methods: An ACR MRI quality control (QC) phantom was used to evaluate the image quality of a fully integrated 1.5T MRI-Linac system recently installed at our institution. This system has a new split magnet design which gives the magnetic field strength of 1.5T. All images were acquired with a set of phased-array surface coils which are designed to have minimal attention of radiation beam. The anterior coil rests on a coil holder which keeps the anterior coil’s position consistent for QA purposes. The posterior coil is imbedded in the patient couch. Multiple sets of T1, T2/PD images were acquired using the protocols as prescribed by the ACR on three different dates, ranging 3 months apart. Results: The geometric distortion are within 0.5 mm in the axial scans and within 1mm in the saggital (z-direction) scans. Slice thickness accuracy, image uniformity, ghosting ratio, high contrast detectability are comparable to other 1.5T diagnostic MRI scanners. The low-contrast object detectability are lower comparatively, which is a result of using the body array coil. Additionally, the beam’s-eye-view images (oblique coronal and saggital images) have minimal geometric distortion at all linac gantry angles tested. No observable changes or drift in image quality is found from images acquired 3 month apart. Conclusion: Despite the use of a body array surface coil, the image quality is comparable to that of an 1.5T MRI scanner and is of sufficient quality to pass the ACR MRI accreditation program. The geometric distortion of the MRI system of the integrated MR-Linac is within 1mm for an object size similar to the ACR phantom, sufficient for radiation therapy treatment purpose. The authors received corporate sponsored research grants from Elekta which is the vendor for the MR-Linac evaluated in this

MR imaging of the skin and nipple of the breast: differentiation between tumour recurrence and post-treatment change

International Nuclear Information System (INIS)

Ralleigh, G.; Walker, A.E.; Hall-Craggs, M.A.; Lakhani, S.R.; Saunders, C.

2001-01-01

Contrast-enhanced MR imaging of the breast has been found to be valuable in the assessment of local recurrence of previously treated breast cancer. We looked specifically at the appearances of the skin and nipple of the treated breast in order to describe the appearances of post-treatment change and recurrence in this region. Thirty-nine women treated for breast cancer had MR imaging of one or both breasts reviewed retrospectively with particular attention to the nipple and skin. The skin and chest wall were assessed for patients with mastectomies. All available histology of the skin and/or nipple, obtained following MR imaging, was reviewed. In patients who did not undergo surgery following MR imaging, clinical follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR imaging, which correlated with histology demonstrating tumour recurrence within the skin and/or nipple. Of the remaining 33 patients, changes of linear or diffuse enhancement were seen in the skin and/or nipple of 15 patients. These changes were shown to be benign post-treatment changes at surgery/biopsy in 4 cases or by clinical follow-up in the remainder. In this article we demonstrate differing patterns of contrast enhancement within the skin and nipple in recurrent breast carcinoma vs post-treatment changes. This suggests that contrast-enhanced MR imaging of the breast may be a useful tool in differentiating tumour recurrence from post-treatment changes within the skin and nipple. (orig.)

5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

Science.gov (United States)

Solati, Jalal; Salari, Ali-Akbar; Bakhtiari, Amir

2011-10-31

Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 μg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 μg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 μg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 μg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Evaluation of PET and MR datasets in integrated 18F-FDG PET/MRI: A comparison of different MR sequences for whole-body restaging of breast cancer patients

International Nuclear Information System (INIS)

Grueneisen, Johannes; Sawicki, Lino Morris; Wetter, Axel; Kirchner, Julian; Kinner, Sonja; Aktas, Bahriye; Forsting, Michael; Ruhlmann, Verena; Umutlu, Lale

2017-01-01

Objectives: To investigate the diagnostic value of different MR sequences and 18F-FDG PET data for whole-body restaging of breast cancer patients utilizing PET/MRI. Methods: A total of 36 patients with suspected tumor recurrence of breast cancer based on clinical follow-up or abnormal findings in follow-up examinations (e.g. CT, MRI) were prospectively enrolled in this study. All patients underwent a PET/CT and subsequently an additional PET/MR scan. Two readers were instructed to identify the occurrence of a tumor relapse in subsequent MR and PET/MR readings, utilizing different MR sequence constellations for each session. The diagnostic confidence for the determination of a malignant or benign lesion was qualitatively rated (3-point ordinal scale) for each lesion in the different reading sessions and the lesion conspicuity (4-point ordinal scale) for the three different MR sequences was additionally evaluated. Results: Tumor recurrence was present in 25/36 (69%) patients. All three PET/MRI readings showed a significantly higher accuracy as well as higher confidence levels for the detection of recurrent breast cancer lesions when compared to MRI alone (p < 0.05). Furthermore, all three PET/MR sequence constellations showed comparable diagnostic accuracy for the identification of a breast cancer recurrence (p > 0.05), yet the highest confidence levels were obtained, when all three MR sequences were used for image interpretation. Moreover, contrast-enhanced T1-weighted VIBE imaging showed significantly higher values for the delineation of malignant and benign lesions when compared to T2 w HASTE and diffusion-weighted imaging. Conclusion: Integrated PET/MRI provides superior restaging of breast cancer patients over MRI alone. Facing the need for appropriate and efficient whole-body PET/MR protocols, our results show the feasibility of fast and morphologically adequate PET/MR protocols. However, considering an equivalent accuracy for the detection of breast cancer

Evaluation of PET and MR datasets in integrated 18F-FDG PET/MRI: A comparison of different MR sequences for whole-body restaging of breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Grueneisen, Johannes, E-mail: Johannes.grueneisen@uk-essen.de [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen (Germany); Sawicki, Lino Morris [Department of Diagnostic and Interventional Radiology, University Hospital, Dusseldorf, University of Dusseldorf, D-40225 Dusseldorf (Germany); Wetter, Axel [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen (Germany); Kirchner, Julian [Department of Diagnostic and Interventional Radiology, University Hospital, Dusseldorf, University of Dusseldorf, D-40225 Dusseldorf (Germany); Kinner, Sonja [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen (Germany); Aktas, Bahriye [Department of Obstetrics and Gynecology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen (Germany); Forsting, Michael [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen (Germany); Ruhlmann, Verena [Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen (Germany); Umutlu, Lale [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen (Germany)

2017-04-15

Objectives: To investigate the diagnostic value of different MR sequences and 18F-FDG PET data for whole-body restaging of breast cancer patients utilizing PET/MRI. Methods: A total of 36 patients with suspected tumor recurrence of breast cancer based on clinical follow-up or abnormal findings in follow-up examinations (e.g. CT, MRI) were prospectively enrolled in this study. All patients underwent a PET/CT and subsequently an additional PET/MR scan. Two readers were instructed to identify the occurrence of a tumor relapse in subsequent MR and PET/MR readings, utilizing different MR sequence constellations for each session. The diagnostic confidence for the determination of a malignant or benign lesion was qualitatively rated (3-point ordinal scale) for each lesion in the different reading sessions and the lesion conspicuity (4-point ordinal scale) for the three different MR sequences was additionally evaluated. Results: Tumor recurrence was present in 25/36 (69%) patients. All three PET/MRI readings showed a significantly higher accuracy as well as higher confidence levels for the detection of recurrent breast cancer lesions when compared to MRI alone (p < 0.05). Furthermore, all three PET/MR sequence constellations showed comparable diagnostic accuracy for the identification of a breast cancer recurrence (p > 0.05), yet the highest confidence levels were obtained, when all three MR sequences were used for image interpretation. Moreover, contrast-enhanced T1-weighted VIBE imaging showed significantly higher values for the delineation of malignant and benign lesions when compared to T2 w HASTE and diffusion-weighted imaging. Conclusion: Integrated PET/MRI provides superior restaging of breast cancer patients over MRI alone. Facing the need for appropriate and efficient whole-body PET/MR protocols, our results show the feasibility of fast and morphologically adequate PET/MR protocols. However, considering an equivalent accuracy for the detection of breast cancer

Midterm Results after Uterine Artery Embolization Versus MR-Guided High-Intensity Focused Ultrasound Treatment for Symptomatic Uterine Fibroids

Energy Technology Data Exchange (ETDEWEB)

Froeling, V., E-mail: vera.froeling@charite.de; Meckelburg, K., E-mail: katrin.meckelburg@charite.de; Scheurig-Muenkler, C., E-mail: christian.scheurig-muenkler@charite.de; Schreiter, N. F., E-mail: nils.schreiter@charite.de; Kamp, J., E-mail: julia.kamp@charite.de; Maurer, M. H., E-mail: martin.maurer@charite.de; Beck, A., E-mail: alexander.beck@charite.de; Hamm, B., E-mail: bernd.hamm@charite.de; Kroencke, T. J., E-mail: Thomas.kroencke@charite.de [Charite-Universitaetsmedizin Berlin, Department of Radiology (Germany)

2013-12-15

Purpose: To compare the rate of reintervention and midterm changes in symptom severity (SS) and Total health-related quality of life (HRQoL) scores after uterine artery embolization (UAE) and magnetic resonance-guided high-intensity focused ultrasound (MR-g HIFU) for symptomatic uterine fibroids. Methods: Eighty women (median age 38.3 years), equally eligible for MR-g HIFU and UAE who underwent one of both treatments between 2002 and 2009 at our institution, were included. The primary end point of the study was defined as the rate of reintervention after both therapies. The secondary outcome was defined as changes in SS and Total HRQoL scores after treatment. SS and Total HRQoL scores before treatment and at midterm follow-up (median 13.3 months) were assessed by the uterine fibroid symptom and quality-of-life questionnaire (UFS-QoL) and compared. Results: The rate of reintervention was significantly lower after UAE than after MR-g HIFU (p = 0.002). After both treatments, SS and Total HRQoL scores improved significantly from baseline to follow-up (UAE: p < 0.001, p < 0.001; MR-g HIFU: p = 0.002, p < 0.001). Total HRQoL scores were significantly higher after UAE than after MR-g HIFU (p = 0.032). Changes in the SS scores did not differ significantly for both treatments (p = 0.061). Conclusion: UAE and MR-g HIFU significantly improved the health-related quality of life of women with symptomatic uterine fibroids. After UAE, the change in Total HRQoL score improvement was significantly better, and a significantly lower rate of reintervention was observed.

Midterm Results after Uterine Artery Embolization Versus MR-Guided High-Intensity Focused Ultrasound Treatment for Symptomatic Uterine Fibroids

International Nuclear Information System (INIS)

Froeling, V.; Meckelburg, K.; Scheurig-Muenkler, C.; Schreiter, N. F.; Kamp, J.; Maurer, M. H.; Beck, A.; Hamm, B.; Kroencke, T. J.

2013-01-01

Purpose: To compare the rate of reintervention and midterm changes in symptom severity (SS) and Total health-related quality of life (HRQoL) scores after uterine artery embolization (UAE) and magnetic resonance–guided high-intensity focused ultrasound (MR-g HIFU) for symptomatic uterine fibroids. Methods: Eighty women (median age 38.3 years), equally eligible for MR-g HIFU and UAE who underwent one of both treatments between 2002 and 2009 at our institution, were included. The primary end point of the study was defined as the rate of reintervention after both therapies. The secondary outcome was defined as changes in SS and Total HRQoL scores after treatment. SS and Total HRQoL scores before treatment and at midterm follow-up (median 13.3 months) were assessed by the uterine fibroid symptom and quality-of-life questionnaire (UFS-QoL) and compared. Results: The rate of reintervention was significantly lower after UAE than after MR-g HIFU (p = 0.002). After both treatments, SS and Total HRQoL scores improved significantly from baseline to follow-up (UAE: p < 0.001, p < 0.001; MR-g HIFU: p = 0.002, p < 0.001). Total HRQoL scores were significantly higher after UAE than after MR-g HIFU (p = 0.032). Changes in the SS scores did not differ significantly for both treatments (p = 0.061). Conclusion: UAE and MR-g HIFU significantly improved the health-related quality of life of women with symptomatic uterine fibroids. After UAE, the change in Total HRQoL score improvement was significantly better, and a significantly lower rate of reintervention was observed

5-HT in the enteric nervous system: gut function and neuropharmacology.

Science.gov (United States)

McLean, Peter G; Borman, Richard A; Lee, Kevin

2007-01-01

In recent times, the perception of functional gastrointestinal disorders such as irritable bowel syndrome (IBS) has shifted fundamentally. Such disorders are now thought of as serious diseases characterized by perturbations in the neuronal regulation of gastrointestinal function. The concept of visceral hypersensitivity, the characterization of neuronal networks in the 'brain-gut axis' and the identification of several novel 5-HT-mediated mechanisms have contributed to this shift. Here, we review how some of the more promising of these new mechanisms (e.g. those involving 5-HT transporters and the 5-HT(2B), 5-HT(7) and putative 5-HT(1p) receptors) might lead to a range of second-generation therapies that could revolutionize the treatment of functional gastrointestinal disorders, particularly IBS.

Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors

Science.gov (United States)

García-Iglesias, Brenda B.; Mendoza-Garrido, María E.; Gutiérrez-Ospina, Gabriel; Rangel-Barajas, Claudia; Noyola-Díaz, Martha; Terrón, José A.

2013-01-01

Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex

5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT

Directory of Open Access Journals (Sweden)

Tiong Cheng Sia

2013-08-01

Full Text Available Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit ? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT. In control animals, peristaltic contractions were blocked temporarily by ondansetron (1-10µM and SDZ-205-557 (1-10µM in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis.

Evaluation of PET and MR datasets in integrated 18F-FDG PET/MRI: A comparison of different MR sequences for whole-body restaging of breast cancer patients.

Science.gov (United States)

Grueneisen, Johannes; Sawicki, Lino Morris; Wetter, Axel; Kirchner, Julian; Kinner, Sonja; Aktas, Bahriye; Forsting, Michael; Ruhlmann, Verena; Umutlu, Lale

2017-04-01

To investigate the diagnostic value of different MR sequences and 18F-FDG PET data for whole-body restaging of breast cancer patients utilizing PET/MRI. A total of 36 patients with suspected tumor recurrence of breast cancer based on clinical follow-up or abnormal findings in follow-up examinations (e.g. CT, MRI) were prospectively enrolled in this study. All patients underwent a PET/CT and subsequently an additional PET/MR scan. Two readers were instructed to identify the occurrence of a tumor relapse in subsequent MR and PET/MR readings, utilizing different MR sequence constellations for each session. The diagnostic confidence for the determination of a malignant or benign lesion was qualitatively rated (3-point ordinal scale) for each lesion in the different reading sessions and the lesion conspicuity (4-point ordinal scale) for the three different MR sequences was additionally evaluated. Tumor recurrence was present in 25/36 (69%) patients. All three PET/MRI readings showed a significantly higher accuracy as well as higher confidence levels for the detection of recurrent breast cancer lesions when compared to MRI alone (psequence constellations showed comparable diagnostic accuracy for the identification of a breast cancer recurrence (p>0.05), yet the highest confidence levels were obtained, when all three MR sequences were used for image interpretation. Moreover, contrast-enhanced T1-weighted VIBE imaging showed significantly higher values for the delineation of malignant and benign lesions when compared to T2w HASTE and diffusion-weighted imaging. Integrated PET/MRI provides superior restaging of breast cancer patients over MRI alone. Facing the need for appropriate and efficient whole-body PET/MR protocols, our results show the feasibility of fast and morphologically adequate PET/MR protocols. However, considering an equivalent accuracy for the detection of breast cancer recurrences in the three PET/MR readings, the application of contrast-agent and the

5-HT(1A) receptor antagonism reverses and prevents fluoxetine-induced sexual dysfunction in rats.

Science.gov (United States)

Sukoff Rizzo, Stacey J; Pulicicchio, Claudine; Malberg, Jessica E; Andree, Terrance H; Stack, Gary P; Hughes, Zoë A; Schechter, Lee E; Rosenzweig-Lipson, Sharon

2009-09-01

Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapies. 5-HT(1A) antagonists have been suggested as beneficial adjunctive treatment in respect of antidepressant efficacy; however, the effects of 5-HT(1A) antagonism on antidepressant-induced side-effects has not been fully examined. The present study was conducted to evaluate the ability of acute or chronic treatment with 5-HT(1A) antagonists to alter chronic fluoxetine-induced impairments in sexual function. Chronic 14-d treatment with fluoxetine resulted in a marked reduction in the number of non-contact penile erections in sexually experienced male rats, relative to vehicle-treated controls. Acute administration of the 5-HT(1A) antagonist WAY-101405 resulted in a complete reversal of chronic fluoxetine-induced deficits on non-contact penile erections at doses that did not significantly alter baselines. Chronic co-administration of the 5-HT(1A) antagonists WAY-100635 or WAY-101405 with fluoxetine prevented fluoxetine-induced deficits in non-contact penile erections in sexually experienced male rats. Moreover, withdrawal of WAY-100635 from co-treatment with chonic fluoxetine, resulted in a time-dependent reinstatement of chronic fluoxetine-induced deficits in non-contact penile erections. Additionally, chronic administration of SSA-426, a molecule with dual activity as both a SSRI and 5-HT(1A) antagonist, did not produce deficits in non-contact penile erections at doses demonstrated to have antidepressant-like activity in the olfactory bulbectomy model. Taken together, these data suggest that 5-HT(1A) antagonist treatment may have utility for the management of SSRI-induced sexual dysfunction.

Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

Energy Technology Data Exchange (ETDEWEB)

Matsuno, Y.; Yamashita, Y.; Takahashi, M. [Dept. of Radiology, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Katabuchi, H.; Okamura, H. [Dept. of Gynecology and Obstetrics, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Kitano, Y.; Shimamura, T. [Dept. of Gynecology and Obstetrics, Amakusa Chuou General Hospital, Hondo (Japan)

1999-11-01

Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29{+-}0.11). The size ratio for the hypointense tumors was 0.82{+-}0.14, and 0.82{+-}0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

International Nuclear Information System (INIS)

Matsuno, Y.; Yamashita, Y.; Takahashi, M.; Katabuchi, H.; Okamura, H.; Kitano, Y.; Shimamura, T.

1999-01-01

Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29±0.11). The size ratio for the hypointense tumors was 0.82±0.14, and 0.82±0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

PET/MR Imaging in Gynecologic Oncology.

Science.gov (United States)

Ohliger, Michael A; Hope, Thomas A; Chapman, Jocelyn S; Chen, Lee-May; Behr, Spencer C; Poder, Liina

2017-08-01

MR imaging and PET using 2-Deoxy-2-[ 18 F]fluoroglucose (FDG) are both useful in the evaluation of gynecologic malignancies. MR imaging is superior for local staging of disease whereas fludeoxyglucose FDG PET is superior for detecting distant metastases. Integrated PET/MR imaging scanners have great promise for gynecologic malignancies by combining the advantages of each modality into a single scan. This article reviews the technology behind PET/MR imaging acquisitions and technical challenges relevant to imaging the pelvis. A dedicated PET/MR imaging protocol; the roles of PET and MR imaging in cervical, endometrial, and ovarian cancers; and future directions for PET/MR imaging are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Significance of MR imaging determining the suitability of patients with metastatic changes in the liver for treatment procedures

International Nuclear Information System (INIS)

Jaruszewska-Orlicka, K.; Czyszkowski, P.; Lasek, W.; Szylberg, T.

2004-01-01

Liver resection is the preferred method of treatment of hepatic metastases. Unfortunately, only 10-20% of patients can be qualified for surgery. One of the alternative palliative methods of treatment is percutaneous alcoholisation of metastatic foci (PEIT). The treatment procedure is determined primarily by the progression of the process in the liver, assessed with non-invasive imaging techniques. Assessment of diagnostic value of MR for patients with focal changes in the liver, an attempt to establish the algorithm of diagnostic and therapeutic procedure, and determination of the criteria qualifying for PEIT. The patients (after USG and BAC) due for liver resection because of liver metastases were subjected to MRI performed with a GYROSCAN NT apparatus with 1T field using a 'body' type solenoid in T2-weighted sequences and STIR/LONG and T1-weighted ones, before and after intravenous administration of a contrast medium in arterial and venous phase, in transversal and frontal planes. MR examination changed the procedure of treatment as a result of larger number and size of metastatic foci found by MRI than by USG. The results of MR examination caused a decrease in the number of patients qualified for liver resection, with a rise in the number of patients referred for PEIT. The application of another diagnostic method (e.g. MR) after USG examination is necessary for patients due for liver resection. MR examination of the liver allows a precise assessment of the operability criteria of hepatic metastases and significantly influences the treatment procedure in patients with metastatic changes in the liver. (author)

Low 5-HT1B receptor binding in the migraine brain

DEFF Research Database (Denmark)

Deen, Marie; Hansen, Hanne D; Hougaard, Anders

2018-01-01

Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding....... Patients who reported migraine brain regions involved in pain modulation as regions of interest and applied a latent variable model (LVM) to assess the group effect on binding across these regions. Results Our data...... support a model wherein group status predicts the latent variable ( p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor...

The role of the 5-HT2C receptor in emotional processing in healthy adults

OpenAIRE

2010-01-01

Serotonin (5-HT) has long been implicated in the pathophysiology of depression and anxiety, and the therapeutic effect of treatments. Several drugs useful in treatment produce either acute or neuroadaptive changes in 5-HT2C receptor activity, and there has been growing interest in how alterations in the 5-HT2C receptor might be important in mediating antidepressant and anxiolytic activity. The neuropsychological hypothesis of drug action implies that the clinical effects of medications a...

Fabrication of P3HT/gold nanoparticle LB films by P3HT templating Langmuir monolayer

International Nuclear Information System (INIS)

Chen, Liang-Huei; Hsu, Wen-Ping; Chan, Han-Wen; Lee, Yuh-Lang

2014-01-01

Highlights: • Addition of ODA into the P3HT monolayer can significantly improve the dispersion ability of P3HT molecules. • The adsorption ability of the P3HT monolayer to the dispersed AuNPs can also be enhanced by the presence of ODA. - Abstract: Regioregular poly(3-hexyl thiophene) (rr-P3HT) and mixed P3HT/octadecyl amine (ODA) were used as template monolayers to adsorb the gold nanoparticles (AuNPs) dispersed in subphase. The behaviors of P3HT and P3HT/ODA monolayers were investigated by surface pressure area per molecule (π–A) isotherms, transmission electron microscopy (TEM) and atomic force microscopy (AFM). The experimental results show that P3HT does not form a homogeneous film and tends to aggregate at the air/water interface. Meanwhile, the amount of AuNPs adsorbed by the P3HT monolayers is low, attributable to the weak interaction between AuNPs and P3HT. By introduction of ODA molecules into the P3HT monolayer, the spreading of P3HT molecules at the air/water interface is improved and the aggregation of P3HT is significantly inhibited. A nearly uniform and homogeneously mixed P3HT/ODA monolayer can be obtained when 50% of ODA is introduced. It is also found that the introduction of ODA can significantly increase the adsorption of AuNPs. For the mixed monolayer with low ratio of ODA (P3HT/ODA = 1/0.2), a higher concentration of adsorbed AuNPs was observed on the corresponding monolayer. However, when the ODA/P3HT ratio increases to 1/1, the AuNPs tend to form three-dimensional (3D) aggregates and the AuNPs cannot distribute well as a homogeneous monolayer. This result is ascribed to the increasing hydrophobicity of the adsorbed AuNPs because of capping of more ODA molecules

MR imaging of the shoulder

International Nuclear Information System (INIS)

Fritts, H.M.; Craig, E.; Kyle, R.; Strefling, M.; Miller, D.; Heithoff, K.; Schellhas, K.

1988-01-01

Magnetic resonance (MR) imaging (1.5-T unit) was performed in over 600 shoulders to evaluate shoulder pain. Ultrasound (US) and arthrography were performed in over 100 patients. Surgery was performed in over 75 patients. MR imaging offers information not well evaluated with other modalities, including bony impingement, tendinitis, bursitis, and osseous abnormalities, such as primary arthritis, avascular necrosis, occult fractures, and tumors. US and MR findings correlate well with surgical findings for medium to large rotator cuff tears. MR imaging with T2 weighting is superior for differentiating small tears from associated tendinitis. An algorithm for cost-effective shoulder imaging integrating US, MR imaging, arthrography, and computed tomographic arthrography are presented

Fundamentals of functional imaging II: emerging MR techniques and new methods of analysis.

Science.gov (United States)

Luna, A; Martín Noguerol, T; Mata, L Alcalá

2018-05-01

Current multiparameter MRI protocols integrate structural, physiological, and metabolic information about cancer. Emerging techniques such as arterial spin-labeling (ASL), blood oxygen level dependent (BOLD), MR elastography, chemical exchange saturation transfer (CEST), and hyperpolarization provide new information and will likely be integrated into daily clinical practice in the near future. Furthermore, there is great interest in the study of tumor heterogeneity as a prognostic factor and in relation to resistance to treatment, and this interest is leading to the application of new methods of analysis of multiparametric protocols. In parallel, new oncologic biomarkers that integrate the information from MR with clinical, laboratory, genetic, and histologic findings are being developed, thanks to the application of big data and artificial intelligence. This review analyzes different emerging MR techniques that are able to evaluate the physiological, metabolic, and mechanical characteristics of cancer, as well as the main clinical applications of these techniques. In addition, it summarizes the most novel methods of analysis of functional radiologic information in oncology. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

HTO/HT discriminating samplers constructed for the french experiment on the environmental behaviour of HT

International Nuclear Information System (INIS)

Ogram, G.L.

1988-12-01

The French Experiment on Environmental Tritium Behaviour was a field experiment carried out to determine the rate of formation of atmospheric HTO from a release of HT to the natural environment. The Canadian Fusion Fuels Technology Project and Ontario Hydro contributed to the project by supplying HTO/HT-discriminating, atmospheric tritium samplers. Each sampler consisted of a molecular-sieve trap to capture HTO followed by a Pd-impregnated molecular-sieve trap to oxidise and collect HT from the same air stream. This method was selected as it provided high sensitivity over short sampling periods and was convenient for field use. Laboratory tests indicated that this system measured HT concentrations reliably, but only achieved limited discrimination between HT and HTO at HTO/HT concentration ratios below 10 -2 to 10 -3 . Small cold traps were therefore operated during the French experiment in addition to the molecular-sieve samplers exhibited much improved discrimination in the field (approaching 10 4 ), possibly due to higher sampling flow rates than used in the laboratory. These results demonstrate that care should be taken in using desiccant-based, HTO/HT-discriminating samplers when the HT concentration is much higher than HTO concentration, and suggest the need to systematically characterize and perhaps improve the performance of discriminating samplers at low HTO/HT ratios

MR/PET quantification tools: Registration, segmentation, classification, and MR-based attenuation correction

Science.gov (United States)

Fei, Baowei; Yang, Xiaofeng; Nye, Jonathon A.; Aarsvold, John N.; Raghunath, Nivedita; Cervo, Morgan; Stark, Rebecca; Meltzer, Carolyn C.; Votaw, John R.

2012-01-01

Purpose: Combined MR/PET is a relatively new, hybrid imaging modality. A human MR/PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR/PET for brain imaging. Methods: The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR/PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with [11C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. Results: For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. Conclusions: MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR

MR/PET quantification tools: Registration, segmentation, classification, and MR-based attenuation correction

Energy Technology Data Exchange (ETDEWEB)

Fei, Baowei, E-mail: bfei@emory.edu [Department of Radiology and Imaging Sciences, Emory University School of Medicine, 1841 Clifton Road Northeast, Atlanta, Georgia 30329 (United States); Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322 (United States); Department of Mathematics and Computer Sciences, Emory University, Atlanta, Georgia 30322 (United States); Yang, Xiaofeng; Nye, Jonathon A.; Raghunath, Nivedita; Votaw, John R. [Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia 30329 (United States); Aarsvold, John N. [Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia 30329 (United States); Nuclear Medicine Service, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia 30033 (United States); Cervo, Morgan; Stark, Rebecca [The Medical Physics Graduate Program in the George W. Woodruff School, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); Meltzer, Carolyn C. [Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia 30329 (United States); Department of Neurology and Department of Psychiatry and Behavior Sciences, Emory University School of Medicine, Atlanta, Georgia 30322 (United States)

2012-10-15

Purpose: Combined MR/PET is a relatively new, hybrid imaging modality. A human MR/PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR/PET for brain imaging. Methods: The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR/PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with [{sup 11}C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. Results: For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. Conclusions: MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR/PET.

MR/PET quantification tools: Registration, segmentation, classification, and MR-based attenuation correction

International Nuclear Information System (INIS)

Fei, Baowei; Yang, Xiaofeng; Nye, Jonathon A.; Raghunath, Nivedita; Votaw, John R.; Aarsvold, John N.; Cervo, Morgan; Stark, Rebecca; Meltzer, Carolyn C.

2012-01-01

Purpose: Combined MR/PET is a relatively new, hybrid imaging modality. A human MR/PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR/PET for brain imaging. Methods: The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR/PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with ["1"1C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. Results: For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. Conclusions: MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR/PET.

Novel selective and potent 5-HT reuptake inhibitors with 5-HT1D antagonist activity: chemistry and pharmacological evaluation of a series of thienopyran derivatives.

Science.gov (United States)

Torrado, Alicia; Lamas, Carlos; Agejas, Javier; Jiménez, Alma; Diaz, Nuria; Gilmore, Jeremy; Boot, John; Findlay, Jeremy; Hayhurst, Lorna; Wallace, Louise; Broadmore, Richard; Tomlinson, Rosemarie

2004-10-15

A series of compounds combining the naphthylpiperazine and thienopyran scaffolds has been prepared and evaluated for 5-HT reuptake inhibition with 5-HT1D antagonist activity. The design of these compounds has been based on the 'overlapping type' strategy where two pharmacophores are linked in a single molecule. The resultant dual pharmacological profile has the potential to deliver a more efficient treatment for depression.

J/sub 1c/ fracture toughness transition behavior of HT-9

International Nuclear Information System (INIS)

Huang, F.H.

1984-01-01

Small compact tension specimens of two heats of HT-9 were tested at temperatures ranging from room temperature to -192 0 C. The ductile-brittle transition toughness of HT-9 was evaluated using the J-integral approach. There were two loading rates of 2.1 x 10 -5 m/s and 3.2 x 10 -2 m/s. The ductile-brittle transition temperatures of HT-9 (number 1 heat) tested at 2.1 x 10 -5 m/s and HT-9 (number 2 heat) tested at 3.2 x 10 -2 m/s were found to be -60 and -10 0 C, respectively. Results showed the fracture toughness of the former was not sensitive to loading rate and the lower shelf toughness decreased with temperature to a J/sub 1c/ value of 5 kJ/m 2 at -190 0 C. Furthermore, the values of J/sub 1c/ were valid since the thickness of the test specimens was well above the thickness criterion

Paroxetine-induced reduction of sexual incentive motivation in female rats is not modified by 5-HT1B or 5-HT2C antagonists.

Science.gov (United States)

Kaspersen, Helge; Agmo, Anders

2012-03-01

Clinical data show that paroxetine causes sexual dysfunction in a substantial proportion of women taking this compound. This work was conducted to determine whether chronic paroxetine reduces sexual incentive motivation in female rats and whether this compound can modify any aspect of paced mating. The role of the 5-HT(1B) and 5-HT(2C) receptors in any potential effects was also evaluated. Ovariectomized female rats were implanted with osmotic minipumps releasing 10 mg/kg per day of paroxetine or vehicle for 28 days. Tests for sexual incentive motivation and paced mating were performed just before implantation and at regular intervals thereafter. The females were primed with estradiol benzoate (25 μg/rat) and progesterone (1 mg/rat) before each of these tests. On days 25-27 of treatment, the females were injected with the 5-HT(1B) antagonist GR125,743 (5 mg/kg), the 5-HT(2C) antagonist SB206,553 (5 mg/kg) and vehicle in counterbalanced order. Preinjection time was 30 min. Paroxetine reduced sexual incentive motivation on day 20 of treatment without affecting any aspect of paced mating. None of the antagonists modified the inhibitory effect of paroxetine on sexual incentive motivation. In the group chronically treated with vehicle, SB206,553 reduced proceptive behaviors in the paced mating test. No other effect was obtained. The effects of paroxetine seen in female rats are similar to those observed in women, suggesting that disturbances of sexual incentive motivation in rats are predictive of sexual dysfunction in women. The 5-HT(1B) and 5-HT(2C) receptors do not seem to be of any importance for paroxetine's inhibitory effect.

MR-based automatic delineation of volumes of interest in human brain PET images using probability maps

DEFF Research Database (Denmark)

Svarer, Claus; Madsen, Karina; Hasselbalch, Steen G.

2005-01-01

subjects' MR-images, where VOI sets have been defined manually. High-resolution structural MR-images and 5-HT(2A) receptor binding PET-images (in terms of (18)F-altanserin binding) from 10 healthy volunteers and 10 patients with mild cognitive impairment were included for the analysis. A template including...... 35 VOIs was manually delineated on the subjects' MR images. Through a warping algorithm template VOI sets defined from each individual were transferred to the other subjects MR-images and the voxel overlap was compared to the VOI set specifically drawn for that particular individual. Comparisons were...... delineation of the VOI set. The approach was also shown to work equally well in individuals with pronounced cerebral atrophy. Probability-map-based automatic delineation of VOIs is a fast, objective, reproducible, and safe way to assess regional brain values from PET or SPECT scans. In addition, the method...

Pancreatic adenocarcinoma: combination of MR imaging, MR angiography and MR cholangiopancreatography for the diagnosis and assessment of resectability

International Nuclear Information System (INIS)

Catalano, C.; Pavone, P.; Laghi, A.; Panebianco, V.; Scipioni, A.; Fanelli, F.; Brillo, R.; Passariello, R.

1998-01-01

The purpose of this study was to determine the possibility of integrating MR cholangiopancreatography (MRCP) and MR angiography (MRA) to conventional MR images in the diagnosis and assessment of resectability of pancreatic adenocarcinoma. Twenty-three patients with pancreatic adenocarcinoma were prospectively examined with MR. Conventional MR images were acquired in all patients. Three-dimensional MRCP and MRA images were acquired in all patients with suspected biliary and vascular involvement. Acquisition time was less than 45 min in all cases. Images were independently evaluated by two radiologists, with final reading decided by consensus among readers. Diagnosis was confirmed with surgery in 16 patients and with percutaneous biopsy in 7. Concordance among readers was high with a kappa value of 0.83. Pancreatic adenocarcinoma was observed in all patients. Correct assessment of unresectability due to vascular involvement was found in 22 of 23 patients. Biliary obstruction was evident in 13 patients, involving the biliary and pancreatic ducts in 9 and the biliary ducts only in 4. Technical advances permit extensive use of MRI in the evaluation of abdominal pathologies. The combination of MR imaging, MRCP, and MRA can provide sufficient information for the diagnosis and assessment of resectability of pancreatic adenocarcinoma, which otherwise would require three different exams. (orig.)

Multi-purpose simulator 'MR TRIOS' for reprocessing plant

International Nuclear Information System (INIS)

Mitsui, Takeshi; Ariyoshi, Masahiro

1993-01-01

MHI(Mitsubishi Heavy Industries, Ltd.) has developed MR TRIOS(Mitsubishi Reprocessing plant TRansient simulator of Integrated process for Operation Support), the realtime dynamic simulator, for multipurpose use to support the Reprocessing Plant operation in various aspects. MR TRIOS integrates the simulation models of the unit process in reprocessing plant, including shearing, dissolution, NO x absorption, accountability and adjustment and co-decontamination process, where each simulation model has two kinds of models, one is Process and the other is Control System. MR TRIOS can simulate the process behavior of the above listed unit process in an integrated manner as well as independently. It is realized by MR CONTROL, the simulator control program developed by MHI. We can get from MR TRIOS the real-time process values, such as temperature, pressure, density, flow rate and concentration of eminent nuclides etc. enabling the evaluation of the process dynamic characteristics under various operating conditions. MR TRIOS has been proved to be an effective tool for the comprehensive study of the process and system dynamics, for operation technique improvements and for training. In this report we will show the introductory outline of multi-purpose simulator 'MR TRIOS' for reprocessing plant and also show the possibility to clarify the fundamental technical requirement to realize the effective material accountancy measure for Head-end Area. (author)

Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness

Directory of Open Access Journals (Sweden)

Albert Paul R

2011-05-01

Full Text Available Abstract The serotonin-1A (5-HT1A receptor is among the most abundant and widely distributed 5-HT receptors in the brain, but is also expressed on serotonin neurons as an autoreceptor where it plays a critical role in regulating the activity of the entire serotonin system. Over-expression of the 5-HT1A autoreceptor has been implicated in reducing serotonergic neurotransmission, and is associated with major depression and suicide. Extensive characterization of the transcriptional regulation of the 5-HT1A gene (HTR1A using cell culture systems has revealed a GC-rich "housekeeping" promoter that non-selectively drives its expression; this is flanked by a series of upstream repressor elements for REST, Freud-1/CC2D1A and Freud-2/CC2D1B factors that not only restrict its expression to neurons, but may also regulate the level of expression of 5-HT1A receptors in various subsets of neurons, including serotonergic neurons. A separate set of allele-specific factors, including Deaf1, Hes1 and Hes5 repress at the HTR1A C(-1019G (rs6295 polymorphism in serotonergic neurons in culture, as well as in vivo. Pet1, an obligatory enhancer for serotonergic differentiation, has been identified as a potent activator of 5-HT1A autoreceptor expression. Taken together, these results highlight an integrated regulation of 5-HT1A autoreceptors that differs in several aspects from regulation of post-synaptic 5-HT1A receptors, and could be selectively targeted to enhance serotonergic neurotransmission.

Clinical-pathologic correlation in early cervical carcinoma: CT-MR imaging comparison for effect on staging and treatment choices

International Nuclear Information System (INIS)

Rubens, D.; Thornbury, J.R.; Weiss, S.L.; Lerner, R.M.; Angel, C.; Beecham, J.; Stoler, M.H.

1986-01-01

A group of patients with clinical stage I or II squamous cell cervical carcinoma have been examined using a 1.5-T magnet. Of these, six have had radical hysterectomy (by April 1986), providing specimens for pathologic correlation. In this preliminary group of patients, MR imaging gave a more accurate assessment of primary tumor extent than did clinical staging. In three of six patients, the disease was underestimated clinically at examination under anesthesia. These patients would have been managed with preoperative radiation rather than surgery alone if the investigative MR imaging information had been used in treatment planning. CT examinations of these patients did not contribute useful information for patient management. Preoperative MR imaging has the potential to alter patient treatment in early cervical carcinoma

Novel hyperthermia applicator system allows adaptive treatment planning: Preliminary clinical results in tumour-bearing animals.

Science.gov (United States)

Dressel, S; Gosselin, M-C; Capstick, M H; Carrasco, E; Weyland, M S; Scheidegger, S; Neufeld, E; Kuster, N; Bodis, S; Rohrer Bley, C

2017-09-11

Hyperthermia (HT) as an adjuvant to radiation therapy (RT) is a multimodality treatment method to enhance therapeutic efficacy in different tumours. High demands are placed on the hardware and treatment planning software to guarantee adequately planned and applied HT treatments. The aim of this prospective study was to determine the effectiveness and safety of the novel HT system in tumour-bearing dogs and cats in terms of local response and toxicity as well as to compare planned with actual achieved data during heating. A novel applicator with a flexible number of elements and integrated closed-loop temperature feedback control system, and a tool for patient-specific treatment planning were used in a combined thermoradiotherapy protocol. Good agreement between predictions from planning and clinical outcome was found in 7 of 8 cases. Effective HT treatments were planned and verified with the novel system and provided improved quality of life in all but 1 patient. This individualized treatment planning and controlled heat exposure allows adaptive, flexible and safe HT treatments in palliatively treated animal patients. © 2017 John Wiley & Sons Ltd.

The Effect of Paroxetine on Depressive Symptom with Somatic Disease and Change of Platelet 5-HT Concentration

Institute of Scientific and Technical Information of China (English)

郑凯; 史庭慧; 刘晓晴

2003-01-01

To study the effect of paroxetine on depressive symptom accompanying somatic disease and the value of platelet 5-HT concentration in the diagnosis of depression, 30 patients with depressive symptom were treated with paroxetine. All patients were evaluated on Zung and HAMD scale and assayed of platelet 5-HT concentration before and after treatment. It was found that patients had a lower level of platelet 5-HT concentration than healthy people (P＜0. 01). After six weeks of treatment, depressive and somatic symptoms were both improved (P＜0. 01) and platelet 5-HT concentration was even lower (P＞0. 05). It was suggested that paroxetine was a good antidepressant and platelet 5-HT concentration was useful in the screening of depression.

Antidepressant activity: contribution of brain microdialysis in knock-out mice to the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions

Directory of Open Access Journals (Sweden)

Alain M Gardier

2013-08-01

Full Text Available Why antidepressants vary in terms of efficacy is currently unclear. Despite the leadership of Selective serotonin reuptake inhibitors (SSRIs in the treatment of depression, the precise neurobiological mechanisms involved in their therapeutic action are poorly understood. A better knowledge of molecular interactions between monoaminergic system, pre- and post-synaptic partners, brain neuronal circuits and regions involved may help to overcome limitations of current treatments and to identify new therapeutic targets. Intracerebral in vivo microdialysis (ICM already provided important information about the brain mechanism of action of antidepressants first in anesthetized rats in the early 90s, and since then in conscious wild-type or knockout mice. The principle of ICM is based on the balance between release of neurotransmitters (e.g., monoamines, and re-uptake by selective transporters (e.g., SERT for serotonin 5-HT. Complementary to electrophysiology, this technique reflects presynaptic monoamines release and intrasynaptic events corresponding to ≈ 80% of whole brain tissue content. The inhibitory role of serotonergic autoreceptors infers that they limit somatodendritic and nerve terminal 5-HT release. It has been proposed that activation of 5-HT1A and 5-HT1B receptor sub-types limit the antidepressant-like activity of Selective Serotonin Reuptake Inhibitors (SSRI. This hypothesis is based partially on results obtained in ICM experiments performed in naïve, non-stressed Rodents. The present review will first remind the principle and methodology of ICM performed in mice. The crucial need of developing animal models that display anxiety and depression-like behaviors, neurochemical and brain morphological phenotypes reminiscent of these mood disorders in Human, will be underlined. Recently developed genetic mouse models have been generated to independently manipulate 5-HT1A auto and hetero-receptors and ICM helped to clarify the role of the

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

Science.gov (United States)

Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

2016-04-01

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (ppsilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Implications for dosimetric changes when introducing MR-guided brachytherapy for small volume cervix cancer: a comparison of CT and MR-based treatments in a single centre

International Nuclear Information System (INIS)

Dempsey, Claire; Govindarajulu, Geetha; Sridharan, Swetha; Capp, Anne; O'Brien, Peter

2014-01-01

To evaluate cervix brachytherapy dosimetry with the introduction of magnetic resonance (MR) based treatment planning and volumetric prescriptions and propose a method for plan evaluation in the transition period. The treatment records of 69 patients were reviewed retrospectively. Forty one patients were treated using computed tomography (CT)-based, Point A-based prescriptions and 28 patients were treated using magnetic resonance (MR)-based, volumetric prescriptions. Plans were assessed for dose to Point A and organs at risk (OAR) with additional high-risk clinical target volume (HR-CTV) dose assessment for MR-based brachytherapy plans. ICRU-38 point doses and GEC-ESTRO recommended volumetric doses (D2 cc for OAR and D 100 , D 98 and D 90 for HR-CTV) were also considered. For patients with small HR-CTV sizes, introduction of MR-based volumetric brachytherapy produced a change in dose delivered to Point A and OAR. Point A doses fell by 4.8 Gy (p = 0.0002) and ICRU and D 2cc doses for OAR also reduced (p < 0.01). Mean Point A doses for MR-based brachytherapy treatment plans were closer to those of HR-CTV D 100 for volumes less than 20 cm 3 and HR-CTV D 98 for volumes between 20 and 35 cm 3 , with a significant difference (p < 0.0001) between Point A and HR-CTV D 90 doses in these ranges. In order to maintain brachytherapy dose consistency across varying HR-CTV sizes there must be a relationship between the volume of the HR-CTV and the prescription dose. Rather than adopting a ‘one size fits all’ approach during the transition to volume-based prescriptions, this audit has shown that separating prescription volumes into HR-CTV size categories of less than 20 cm 3 , between 20 and 35 cm 3 , and more than 35 cm 3 the HR-CTV can provide dose uniformity across all volumes and can be directly linked to traditional Point A prescriptions.

Combined PET/MR imaging in neurology

DEFF Research Database (Denmark)

Andersen, Flemming Littrup; Ladefoged, Claes Nøhr; Beyer, Thomas

2014-01-01

AIM: Combined PET/MR systems have now become available for clinical use. Given the lack of integrated standard transmission (TX) sources in these systems, attenuation and scatter correction (AC) must be performed using the available MR-images. Since bone tissue cannot easily be accounted for duri...

Volumetric MR-Guided High-Intensity Focused Ultrasound with Direct Skin Cooling for the Treatment of Symptomatic Uterine Fibroids: Proof-of-Concept Study

Directory of Open Access Journals (Sweden)

Marlijne E. Ikink

2015-01-01

Full Text Available Objective. To prospectively assess the safety and technical feasibility of volumetric magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU ablation with direct skin cooling (DISC during treatment of uterine fibroids. Methods. In this proof-of-concept study, eight patients were consecutively selected for clinical MR-HIFU ablation of uterine fibroids with the use of an additional DISC device to maintain a constant temperature (T≈20°C at the interface between the HIFU table top and the skin. Technical feasibility was verified by successful completion of MR-HIFU ablation. Contrast-enhanced T1-weighted MRI was used to measure the treatment effect (nonperfused volume (NPV ratio. Safety was evaluated by recording of adverse events (AEs within 30 days’ follow-up. Results. All MR-HIFU treatments were successfully completed in an outpatient setting. The median NPV ratio was 0.56 (IQR [0.27–0.72]. Immediately after treatment, two patients experienced coldness related discomfort which resolved at the same day. No serious (device-related AEs were reported. Specifically, no skin burns, cold injuries, or subcutaneous edema were observed. Conclusion. This study showed that it is safe and technically feasible to complete a volumetric MR-HIFU ablation with DISC. This technique may reduce the risk of thermal injury to the abdominal wall during MR-HIFU ablation of uterine fibroids. This trial is registered with NTR4189.

Combustion of gadolinium and dysprosium chelates as a cellular integrity marker in MR imaging

International Nuclear Information System (INIS)

Ericsson, A.; Bach-Gansmo, T.; Niklasson, F.; Hemmingsson, A.

1995-01-01

A combination of gadolinium (Gd) and dysprosium (Dy) chelates was investigated as a potential marker of cell-membrane integrity by means of a double-contrast effect in MR imaging. Blood samples with varying hematocrit (Hct) levels containing intact or lysed cells were used as model systems. With intact cells, the agents were assumed to be distributed solely extracellularly and the highest Hct studied (69%) was assumed to mimic the ratio of extracellular to intracellular water in tissue. The combined effect on image intensity of Gd (in a concentration corresponding to 0.2 mmol/kg b.w. in humans) and Dy (0.6 mmol/kg b.w.) applied simultaneously was a marked difference in signal intensity between samples with intact and lysed cells in both the T1- and T2-weighted spin-echo images with a corresponding increase in the contrast-to-noise ratio. This was the result of a T1 reduction caused by Gd with a negligible Dy susceptibility effect in areas with lysed cells. On the other hand, the Dy susceptibility effect (i.e. reduced apparent T2) dominated in areas with intact cells. Thus, the combination of Gd and Dy may serve as a marker of cell-membrane integrity in MR examinations. (orig.)

Effects of AET, MEA, or 5-HT treatment before X-irradiation of pregnant C57B mice

International Nuclear Information System (INIS)

Mazur, L.

1985-01-01

C57B mice were either whole body X-irradiated with a dose of 200 R or, 15 minutes before X-radiation injected with AET, MEA, or 5-HT, in a dose of 40 mg/kg of body weight, on the first day of gestation. Uterine contents were examined on the nineteenth day of pregnancy. The number of corpora lutea was assumed as 100% and the percentage values of live and dead foetuses, resorptions, and non-implanted embryos were calculated. The percentage ratio of females with live foetuses in the uterus, in relation to the total number of those with a vaginal plug was also determined. X-irradiation of pregnant mice influenced the embryonic survival. As compared with controls, in only X-irradiated mice a lower percentage value of live foetuses and higher percentage values of non-implanted embryos and resorptions were found. One dead foetus was only observed in X-irradiated females. Percentage value of X-irradiated females with live foetuses was lower than that of control ones. High mortality of embryos occurred more often before than after the implantation of blastocysts. The percentage value of non-implanted embryos was higher than that of resorptions. AET, MEA, and 5-HT when injected to mice before their X-irradiation acted as radioprotectors. The strongest radioprotective effect was obtained following AET administration, intermediate after 5-HT treatment and the weakest one when MEA was injected. (orig.) [de

Experimental investigations of an endoluminal ultrasound applicator for MR-guided thermal therapy of pancreatic cancer

Science.gov (United States)

Adams, Matthew; Salgaonkar, Vasant; Jones, Peter; Plata, Juan; Chen, Henry; Pauly, Kim Butts; Sommer, Graham; Diederich, Chris

2017-03-01

An MR-guided endoluminal ultrasound applicator has been proposed for palliative and potential curative thermal therapy of pancreatic tumors. Minimally invasive ablation or hyperthermia treatment of pancreatic tumor tissue would be performed with the applicator positioned in the gastrointestinal (GI) lumen, and sparing of the luminal tissue would be achieved with a water-cooled balloon surrounding the ultrasound transducers. This approach offers the capability of conformal volumetric therapy for fast treatment times, with control over the 3D spatial deposition of energy. Prototype endoluminal ultrasound applicators have been fabricated using 3D printed fixtures that seat two 3.2 or 5.6 MHz planar or curvilinear transducers and contain channels for wiring and water flow. Spiral surface coils have been integrated onto the applicator body to allow for device localization and tracking for therapies performed under MR guidance. Heating experiments with a tissue-mimicking phantom in a 3T MR scanner were performed and demonstrated capability of the prototype to perform volumetric heating through duodenal luminal tissue under real-time PRF-based MR temperature imaging (MRTI). Additional experiments were performed in ex vivo pig carcasses with the applicator inserted into the esophagus and aimed towards liver or soft tissue surrounding the spine under MR guidance. These experiments verified the capacity of heating targets up to 20-25 mm from the GI tract. Active device tracking and automated prescription of imaging and temperature monitoring planes through the applicator were made possible by using Hadamard encoded tracking sequences to obtain the coordinates of the applicator tracking coils. The prototype applicators have been integrated with an MR software suite that performs real-time device tracking and temperature monitoring.

Current status of MR colonography.

LENUS (Irish Health Repository)

Thornton, Eavan

2010-01-01

The search for an acceptable colorectal cancer screening examination has led to the development of virtual colonoscopy, which includes both computed tomographic (CT) colonography and magnetic resonance (MR) colonography. As indicated by the much larger number of published studies on CT colonography than on MR colonography, multidetector CT appears to be more suitable for colorectal screening than does MR colonography, in part reflecting the ease and speed of performing CT, as well as the increased spatial resolution, decreased cost, and wider availability of CT colonography. The main advantage of MR colonography over CT colonography is that it does not use ionizing radiation, which has important implications for colorectal cancer screening. The use of dark-lumen MR colonography to screen patients for colorectal cancer as well as other abdominopelvic disease could make it more attractive than CT. With the integration of 3.0-T MR colonography, fecal tagging, and parallel imaging into research and clinical settings, new MR colonography protocols must be optimized. Future MR colonography research should address issues such as image characteristics, presence of artifacts, management of specific absorption rate, and hardware-related modifications.

SU-E-J-162: Quality Assurance Procedures for MR Guided Focused Ultrasound Treatment of Bone Metastasis

Energy Technology Data Exchange (ETDEWEB)

Chen, L; Chen, X; Wang, B; Gupta, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

2014-06-01

Purpose: The purpose of this work is to develop and verify our quality assurance (QA) procedures to ensure the safety and efficacy of MR-guided focused ultrasound (MRgFUS) treatment of bone metastases. Methods: A practical QA program was developed. Monthly and daily QA (DQA) procedures were performed. The major QA items included the checks of the machine hardware, software and patient safety features. Briefly, these checks/tests include: 1) the cooling system reservoir and treatment table; 2) power to the treatment table; 3) the MR coil; 4) the transducer position with MRI; 5) image display on the treatment work station; 6) the effective focal spot in 3 directions using MR thermometry; and 7) all the safety devices including a sonication lamp, and the emergency stop-sonication switches. In order to avoid patient skin burn, it is important to remove gas bubbles in the interfaces between the treatment table and the gel pad, and the gel pad and patients skin during the patient setup. Our QA procedures have been verified and evaluated through patient treatments. Seven patients with scapula, humeral head, sacrum, ilium, pubic ramus and acetabular bone metastases were treated using MRgFUS. Results: Our study showed that all seven patients tolerated the MRgFUS treatment well. No skin toxicity or other complications were observed. The pain score (0–10) using the visual analog scale (VAS) was significantly reduced from 8.0 ± 1.1 before treatment to 4.7 ± 3.0, 3.0 ± 1.5, 3.2 ± 2.8 and 3.4 ± 1.5 at one day, one month, two months and three months after the MRgFUS treatment, respectively. Conclusion: We demonstrated that with the appropriate QA procedures, MRgFUS is a safe, effective and noninvasive treatment modality for palliation of bone metastases.

SU-E-J-162: Quality Assurance Procedures for MR Guided Focused Ultrasound Treatment of Bone Metastasis

International Nuclear Information System (INIS)

Chen, L; Chen, X; Wang, B; Gupta, R; Ma, C

2014-01-01

Purpose: The purpose of this work is to develop and verify our quality assurance (QA) procedures to ensure the safety and efficacy of MR-guided focused ultrasound (MRgFUS) treatment of bone metastases. Methods: A practical QA program was developed. Monthly and daily QA (DQA) procedures were performed. The major QA items included the checks of the machine hardware, software and patient safety features. Briefly, these checks/tests include: 1) the cooling system reservoir and treatment table; 2) power to the treatment table; 3) the MR coil; 4) the transducer position with MRI; 5) image display on the treatment work station; 6) the effective focal spot in 3 directions using MR thermometry; and 7) all the safety devices including a sonication lamp, and the emergency stop-sonication switches. In order to avoid patient skin burn, it is important to remove gas bubbles in the interfaces between the treatment table and the gel pad, and the gel pad and patients skin during the patient setup. Our QA procedures have been verified and evaluated through patient treatments. Seven patients with scapula, humeral head, sacrum, ilium, pubic ramus and acetabular bone metastases were treated using MRgFUS. Results: Our study showed that all seven patients tolerated the MRgFUS treatment well. No skin toxicity or other complications were observed. The pain score (0–10) using the visual analog scale (VAS) was significantly reduced from 8.0 ± 1.1 before treatment to 4.7 ± 3.0, 3.0 ± 1.5, 3.2 ± 2.8 and 3.4 ± 1.5 at one day, one month, two months and three months after the MRgFUS treatment, respectively. Conclusion: We demonstrated that with the appropriate QA procedures, MRgFUS is a safe, effective and noninvasive treatment modality for palliation of bone metastases

Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task.

Science.gov (United States)

Meneses, Alfredo

2002-05-01

Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the

The inhibition of cholera toxin-induced 5-HT release by the 5-HT3 receptor antagonist, granisetron, in the rat

Science.gov (United States)

Turvill, J L; Connor, P; Farthing, M J G

2000-01-01

The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT2 dependent) and neuronally (5-HT3 dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release. These include basolateral 5-HT3 receptors, the activation of which is known to enhance 5-HT release. Until now, 5-HT3 receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT3 receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 μg kg−1, lidoocaine 6 mg kg−1 or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT3 receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion. PMID:10882387

Optimization of a novel large field of view distortion phantom for MR-only treatment planning.

Science.gov (United States)

Price, Ryan G; Knight, Robert A; Hwang, Ken-Pin; Bayram, Ersin; Nejad-Davarani, Siamak P; Glide-Hurst, Carri K

2017-07-01

MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution. To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously published 1.0 T results, and integrated into the 3D Slicer application platform. All foam samples provided sufficient MR image contrast with paintball landmarks. Urethane foam (compressive strength ∼1000 psi, density ~20 lb/ft 3 ) was selected for its accurate machinability and weight characteristics. For smaller bores, a phantom version with the following parameters was used: 15 foam plates, 55 × 55 × 37.5 cm 3 (L×W×H), 5,082 landmarks, and weight ~30 kg. To accommodate > 70 cm wide bores, an extended build used 20 plates spanning 55 × 55 × 50 cm 3 with 7,497 landmarks and weight ~44 kg. Distortion characterization software was implemented as an external module into 3D Slicer's plugin framework and results agreed with the literature. The design and implementation of a modular, extendable distortion phantom was optimized for several bore

WE-H-207B-02: MR-Driven RT Planning

Energy Technology Data Exchange (ETDEWEB)

Cao, M. [UCLA School of Medicine (United States)

2016-06-15

In recent years, steady progress has been made towards the implementation of MRI in external beam radiation therapy for processes ranging from treatment simulation to in-room guidance. Novel procedures relying mostly on MR data are currently implemented in the clinic. This session will cover topics such as (a) commissioning and quality control of the MR in-room imagers and simulators specific to RT, (b) treatment planning requirements, constraints and challenges when dealing with various MR data, (c) quantification of organ motion with an emphasis on treatment delivery guidance, and (d) MR-driven strategies for adaptive RT workflows. The content of the session was chosen to address both educational and practical key aspects of MR guidance. Learning Objectives: Good understanding of MR testing recommended for in-room MR imaging as well as image data validation for RT chain (e.g. image transfer, filtering for consistency, spatial accuracy, manipulation for task specific); Familiarity with MR-based planning procedures: motivation, core workflow requirements, current status, challenges; Overview of the current methods for the quantification of organ motion; Discussion on approaches for adaptive treatment planning and delivery. T. Stanescu - License agreement with Modus Medical Devices to develop a phantom for the quantification of MR image system-related distortions.; T. Stanescu, N/A.

WE-H-207B-02: MR-Driven RT Planning

International Nuclear Information System (INIS)

Cao, M.

2016-01-01

In recent years, steady progress has been made towards the implementation of MRI in external beam radiation therapy for processes ranging from treatment simulation to in-room guidance. Novel procedures relying mostly on MR data are currently implemented in the clinic. This session will cover topics such as (a) commissioning and quality control of the MR in-room imagers and simulators specific to RT, (b) treatment planning requirements, constraints and challenges when dealing with various MR data, (c) quantification of organ motion with an emphasis on treatment delivery guidance, and (d) MR-driven strategies for adaptive RT workflows. The content of the session was chosen to address both educational and practical key aspects of MR guidance. Learning Objectives: Good understanding of MR testing recommended for in-room MR imaging as well as image data validation for RT chain (e.g. image transfer, filtering for consistency, spatial accuracy, manipulation for task specific); Familiarity with MR-based planning procedures: motivation, core workflow requirements, current status, challenges; Overview of the current methods for the quantification of organ motion; Discussion on approaches for adaptive treatment planning and delivery. T. Stanescu - License agreement with Modus Medical Devices to develop a phantom for the quantification of MR image system-related distortions.; T. Stanescu, N/A

Both exogenous 5-HT and endogenous 5-HT, released by fluoxetine, enhance distension evoked propulsion in guinea-pig ileum in vitro

Directory of Open Access Journals (Sweden)

Rachel M Gwynne

2014-09-01

Full Text Available The roles of 5-HT3 and 5-HT4 receptors in the modulation of intestinal propulsion by luminal application of 5-HT and augmentation of endogenous 5-HT effects were studied in segments of guinea-pig ileum in vitro. Persistent propulsive contractions evoked by saline distension were examined using a modified Trendelenburg method. When 5-HT (30 nM, fluoxetine (selective serotonin reuptake inhibitor; 1 nM, 2-methyl-5-HT (5-HT3 receptor agonist; 1 mM or RS 67506 (5-HT4 receptor agonist, 1 µM was infused into the lumen, the pressure needed to initiate persistent propulsive activity fell significantly. A specific 5-HT4 receptor antagonist, SB 207266 (10 nM in lumen, abolished the effects of 5-HT, fluoxetine, and RS 67506, but not those of 2-methyl-5-HT. Granisetron (5-HT3 receptor antagonist; 1 µM in lumen abolished the effect of 5-HT, fluoxetine, RS 67506 and 2-methyl-5-HT. The NK3 receptor antagonist SR 142801 (100 nM in lumen blocked the effects of 5-HT, fluoxetine and 2-methyl-5-HT. SB 207266, granisetron and SR 142801 had no effect by themselves. Higher concentrations of fluoxetine (100 nM and 300 nM and RS 67506 (3 µM and 10 µM had no effect on the distension threshold for propulsive contractions. These results indicate that luminal application of exogenous 5-HT, or increased release of endogenous mucosal 5-HT above basal levels, acts to lower the threshold for propulsive contractions in the guinea-pig ileum via activation of 5-HT3 and 5-HT4 receptors and the release of tachykinins. The results further indicate that basal release of 5-HT is insufficient to alter the threshold for propulsive motor activity.

SHEDS-HT: an integrated probabilistic exposure model for prioritizing exposures to chemicals with near-field and dietary sources.

Science.gov (United States)

Isaacs, Kristin K; Glen, W Graham; Egeghy, Peter; Goldsmith, Michael-Rock; Smith, Luther; Vallero, Daniel; Brooks, Raina; Grulke, Christopher M; Özkaynak, Halûk

2014-11-04

United States Environmental Protection Agency (USEPA) researchers are developing a strategy for high-throughput (HT) exposure-based prioritization of chemicals under the ExpoCast program. These novel modeling approaches for evaluating chemicals based on their potential for biologically relevant human exposures will inform toxicity testing and prioritization for chemical risk assessment. Based on probabilistic methods and algorithms developed for The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals (SHEDS-MM), a new mechanistic modeling approach has been developed to accommodate high-throughput (HT) assessment of exposure potential. In this SHEDS-HT model, the residential and dietary modules of SHEDS-MM have been operationally modified to reduce the user burden, input data demands, and run times of the higher-tier model, while maintaining critical features and inputs that influence exposure. The model has been implemented in R; the modeling framework links chemicals to consumer product categories or food groups (and thus exposure scenarios) to predict HT exposures and intake doses. Initially, SHEDS-HT has been applied to 2507 organic chemicals associated with consumer products and agricultural pesticides. These evaluations employ data from recent USEPA efforts to characterize usage (prevalence, frequency, and magnitude), chemical composition, and exposure scenarios for a wide range of consumer products. In modeling indirect exposures from near-field sources, SHEDS-HT employs a fugacity-based module to estimate concentrations in indoor environmental media. The concentration estimates, along with relevant exposure factors and human activity data, are then used by the model to rapidly generate probabilistic population distributions of near-field indirect exposures via dermal, nondietary ingestion, and inhalation pathways. Pathway-specific estimates of near-field direct exposures from consumer products are also modeled

Deep MR to CT synthesis using unpaired data

NARCIS (Netherlands)

Wolterink, Jelmer M.; Dinkla, Anna M.; Savenije, Mark H.F.; Seevinck, Peter R.; van den Berg, Cornelis A.T.; Išgum, Ivana

2017-01-01

MR-only radiotherapy treatment planning requires accurate MR-to-CT synthesis. Current deep learning methods for MR-to-CT synthesis depend on pairwise aligned MR and CT training images of the same patient. However, misalignment between paired images could lead to errors in synthesized CT images. To

Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

Science.gov (United States)

Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

2010-01-01

the 5-HT(1B) receptor, the 5-HT(1A) receptor signal plays the dominant role in improving the anti-immobility effect of fluoxetine in the IFN-alpha-induced depression; (2) combination of the 5-HT(1A) antagonist with subactive fluoxetine can be helpful in IFN-alpha-induced depression treatment.

Mr imaging and mr spectroscopy of brain metastases by mr perfusion

International Nuclear Information System (INIS)

Weber, Marc-Andre; Lichy, M.P.; Thilmann, C.; Guenther, M.; Bachert, P.; Delorme, S.; Schad, L.R.; Debus, J.; Schlemmer, H.P.; Maudsley, A.A.

2003-01-01

In follow-up examinations of irradiated brain metastases conventional contrast-enhanced morphological MR imaging is often unable to distinguish between transient radiation effects, radionecrosis, and tumor recurrence. To evaluate changes of relative cerebral blood flow (rCBF) in irradiated brain metastases arterial spin-labeling techniques (ASL) were applied and compared to the outcome of 1 H MR spectroscopy and spectroscopic imaging ( 1 H MRS, SI). Patients and methods In 2 patients follow-up examinations of irradiated brain metastases were performed on a 1.5-T tomograph (average single dose: 20 Gy/80% isodose). Relative CBF values of gray matter (GM), white matter (WM), and metastases (Met) were measured by means of the ASL techniques ITS-FAIR and Q2TIPS. 1 H MRS was performed with PRESS 1500/135. In both patients with initially hyperperfused metastases (Met/GM >1) the reduction of rCBF after stereotactic radiosurgery indicated response to treatment - even if the contrast-enhancing region increased - while increasing rCBF values indicated tumor progression. The findings were confirmed by 1 H MRS, SI and subsequent follow-up. The ASL techniques ITS-FAIR and Q2TIPS are able to monitor changes of rCBF in irradiated brain metastases. The two cases imply a possible role for ASL-MR perfusion imaging and 1 H MR spectroscopy in differentiating radiation effects from tumor progression. (orig.) [de

Characterization and evaluation of a flexible MRI receive coil array for radiation therapy MR treatment planning using highly decoupled RF circuits

Science.gov (United States)

McGee, Kiaran P.; Stormont, Robert S.; Lindsay, Scott A.; Taracila, Victor; Savitskij, Dennis; Robb, Fraser; Witte, Robert J.; Kaufmann, Timothy J.; Huston, John, III; Riederer, Stephen J.; Borisch, Eric A.; Rossman, Phillip J.

2018-04-01

The growth in the use of magnetic resonance imaging (MRI) data for radiation therapy (RT) treatment planning has been facilitated by scanner hardware and software advances that have enabled RT patients to be imaged in treatment position while providing morphologic and functional assessment of tumor volumes and surrounding normal tissues. Despite these advances, manufacturers have been slow to develop radiofrequency (RF) coils that closely follow the contour of a RT patient undergoing MR imaging. Instead, relatively large form surface coil arrays have been adapted from diagnostic imaging. These arrays can be challenging to place on, and in general do not conform to the patient’s body habitus, resulting in sub optimal image quality. The purpose of this study is to report on the characterization of a new flexible and highly decoupled RF coil for use in MR imaging of RT patients. Coil performance was evaluated by performing signal-to-noise ratio (SNR) and noise correlation measurements using two coil (SNR) and four coil (noise correlation) element combinations as a function of coil overlap distance and comparing these values to those obtained using conventional coil elements. In vivo testing was performed in both normal volunteers and patients using a four and 16 element RF coil. Phantom experiments demonstrate the highly decoupled nature of the new coil elements when compared to conventional RF coils, while in vivo testing demonstrate that these coils can be integrated into extremely flexible and form fitting substrates that follow the exact contour of the patient. The new coil design addresses limitations imposed by traditional surface coil arrays and have the potential to significantly impact MR imaging for both diagnostic and RT applications.

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

Science.gov (United States)

Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte

2016-01-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [11C]SB207145 for quantification of brain 5-HT4R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. PMID:26772668

5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

Directory of Open Access Journals (Sweden)

Urszula eSlawinska

2014-08-01

Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

A fully automatic approach for multimodal PET and MR image segmentation in gamma knife treatment planning.

Science.gov (United States)

Rundo, Leonardo; Stefano, Alessandro; Militello, Carmelo; Russo, Giorgio; Sabini, Maria Gabriella; D'Arrigo, Corrado; Marletta, Francesco; Ippolito, Massimo; Mauri, Giancarlo; Vitabile, Salvatore; Gilardi, Maria Carla

2017-06-01

Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [ 11 C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation. A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife ® treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTV MRI . A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without treatment response assessment

5-HT6 receptor antagonist attenuates the memory deficits associated with neuropathic pain and improves the efficacy of gabapentinoids.

Science.gov (United States)

Jayarajan, Pradeep; Nirogi, Ramakrishna; Shinde, Anil; Goura, Venkatesh; Babu, Vuyyuru Arun; Yathavakilla, Sumanth; Bhyrapuneni, Gopinadh

2015-10-01

Memory deficit is a co-morbid disorder in patients suffering from neuropathic pain. Gabapentin and pregabalin (gabapentinoids) are among the widely prescribed medications for the treatment of neuropathic pain. Memory loss and sedation are the commonly reported side effects with gabapentinoids. Improving the cognitive functions and attenuating drug-induced side effects may play a crucial role in the management of pain. We evaluated the effects of 5-HT6 receptor antagonists on the memory deficits associated with neuropathy. We also studied the effects of 5-HT6 receptor antagonists on the side effects, and the analgesic effects of gabapentinoids. 5-HT6 receptor antagonists attenuated the cognitive deficits in neuropathic rats. Neuropathic rats co-treated with 5-HT6 receptor antagonist and gabapentinoids showed improvement in memory. 5-HT6 receptor antagonists enhanced the analgesic effects of gabapentinoids but had no effect on the motor side effects. The observed effects may not be due to pharmacokinetic interactions. 5-HT6 receptor antagonist attenuate the cognitive deficits associated with neuropathy, and this effect is also seen when co-treated with gabapentinoids. Since, 5-HT6 antagonists improved the effectiveness of gabapentinoids, reduction in the dosage and frequency of gabapentinoids treatment may reduce the side effects. Combining 5-HT6 receptor antagonist with gabapentinoids may offer a novel treatment strategy for neuropathic pain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Partial fourier and parallel MR image reconstruction with integrated gradient nonlinearity correction.

Science.gov (United States)

Tao, Shengzhen; Trzasko, Joshua D; Shu, Yunhong; Weavers, Paul T; Huston, John; Gray, Erin M; Bernstein, Matt A

2016-06-01

To describe how integrated gradient nonlinearity (GNL) correction can be used within noniterative partial Fourier (homodyne) and parallel (SENSE and GRAPPA) MR image reconstruction strategies, and demonstrate that performing GNL correction during, rather than after, these routines mitigates the image blurring and resolution loss caused by postreconstruction image domain based GNL correction. Starting from partial Fourier and parallel magnetic resonance imaging signal models that explicitly account for GNL, noniterative image reconstruction strategies for each accelerated acquisition technique are derived under the same core mathematical assumptions as their standard counterparts. A series of phantom and in vivo experiments on retrospectively undersampled data were performed to investigate the spatial resolution benefit of integrated GNL correction over conventional postreconstruction correction. Phantom and in vivo results demonstrate that the integrated GNL correction reduces the image blurring introduced by the conventional GNL correction, while still correcting GNL-induced coarse-scale geometrical distortion. Images generated from undersampled data using the proposed integrated GNL strategies offer superior depiction of fine image detail, for example, phantom resolution inserts and anatomical tissue boundaries. Noniterative partial Fourier and parallel imaging reconstruction methods with integrated GNL correction reduce the resolution loss that occurs during conventional postreconstruction GNL correction while preserving the computational efficiency of standard reconstruction techniques. Magn Reson Med 75:2534-2544, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

DEFF Research Database (Denmark)

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald

2016-01-01

of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145......Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels...... for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well...

Postnatal development of progeny after 5-HT and/or 32P treatment of mice on the first day of gestation

International Nuclear Information System (INIS)

Manowska, Jadwiga; Mazur, Lidia

1986-01-01

C57B mice were injected intraperitoneally with 5-HT (serotonin-creatinine sulphate) in a dose of 40 mg/kg body weight and/or radioactive P in the form of Na 2 H 32 PO 4 in a dose of 1 μCi/g body weight, on the first day of gestation. Litter size of newborns, and growth and mortality of progeny during the postnatal thirty days were determined. As compared with controls, the litter size of newborns was smaller in mice treated with 32 P or 5-HT; the smallest one was found among those injected with 5-HT and 32 P. The sex ratio of newborns was disturbed only in animals treated with 5-HT. The mortality of progeny occurred only in mice treated with 32 P. Body weight in relation to controls was lower in mice injected with both 5-HT and 32 P, and also in those receiving 32 P only but it was greater during lactation in those treated with 5-HT. Under these experimental conditions, 5-HT did not show a radioprotective role. (author)

Advanced MR diagnostic imaging in pediatric glial cell tumors: from morphological to pathophysiological evaluation

International Nuclear Information System (INIS)

Balev, B.; Georgiev, R.; Novakova, M.

2013-01-01

Full text: Introduction: The conventional MR imaging is important, and in most cases necessary imaging tool for studying the macroscopic structure, for localization and distribution of a glial brain tumor. It is an integral part of the optimal MR protocol, which further comprises a diffusion, perfusion techniques, techniques for the permeability and oxygenation assessment, as well as MR spectroscopy to the metabolism assessment. What you will learn: Glial brain tumors in children - incidence, histology, classification, diagnosis; Nature and principles of MR diffusion, perfusion, techniques for permeability and oxygenation assessment, MR spectroscopy; Contemporary techniques allowing to obtain not only MR morphological information but also to evaluate the tumor the pathophysiology: the cellular atypia, cellularity, tumor neovascularization, oxygen consumption, metabolism, status of the blood-brain barrier. This assessment determines the biological potential of the tumor, treatment options and prognosis. Discussion: The findings from conventional MR examinations, incl. administration of gadolinium contrast agents are associated with the degree of glioma and can be useful for their classification. Taking into account that from 20% to 45 % of the unenhanced supratentorial gliomas are malignant, some low-grade gliomas enhance (ganglioglioma, pilocytic astrocytoma, oligodendroglioma), 9% of malignant gliomas have no contrast enhancement, and in general, the contrast enhancement is not seen as a reliable indicator for the infiltration extent. The contemporary MR techniques improve the assessment of the pathophysiology of the tumor which is relevant to its histology and biological potential. Conclusion: Modern MR techniques besides purely diagnostic advantages (determine the extent and distribution of glioma), enable: differentiation of tumor recurrence from radiation necrosis; identification of optimal locations for biopsy or operative resection; prognosis, planning and

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding.

Science.gov (United States)

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos

2016-04-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Intracranial tuberculoma: MR imaging

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Salgado, P; Zenteno, M A; Rodriguez-Carbajal, J; Brutto, O.H. del; Talamas, O

1989-09-01

MR studies of 6 patients with intracranial tuberculoma are reviewed. All patients also underwent CT scans which showed hypo- or isodense lesions with abnormal enhancement following contrast administration. MR showed lesions with prolongation of the T1 relaxation time in every case. On the T2-weighted sequences, the signal properties of the tuberculoma varied according to the stage of evolution of the lesion. Incipient tuberculomas appeared as scattered areas of hypointensity surrounded by edema. Mature tuberculomas were composed of a dark necrotic center surrounded by an isointense capsule which was, in turn, surrounded by edema. In one patient, the center of the lesion was hyperintense probably because of liquefaction and pus formation (tuberculous abscess). While both, CT and MR, were equally sensitive in visualizing the intracranial tuberculoma in every patient, MR was slightly superior in demonstrating the extent of the lesion, especially for brainstem tuberculomas. Nevertheless, the potential role for MR diagnosis of intracranial tuberculoma is limited by the fact that other infectious or neoplasic diseases may present similar findings. The diagnosis of intracranial tuberculoma should rest on a proper integration of data from clinical manifestations, cerebrospinal fluid analysis, and neuroimaging studies. (orig.).

Intracranial tuberculoma: MR imaging

International Nuclear Information System (INIS)

Salgado, P.; Zenteno, M.A.; Rodriguez-Carbajal, J.; Brutto, O.H. del; Talamas, O.

1989-01-01

MR studies of 6 patients with intracranial tuberculoma are reviewed. All patients also underwent CT scans which showed hypo- or isodense lesions with abnormal enhancement following contrast administration. MR showed lesions with prolongation of the T1 relaxation time in every case. On the T2-weighted sequences, the signal properties of the tuberculoma varied according to the stage of evolution of the lesion. Incipient tuberculomas appeared as scattered areas of hypointensity surrounded by edema. Mature tuberculomas were composed of a dark necrotic center surrounded by an isointense capsule which was, in turn, surrounded by edema. In one patient, the center of the lesion was hyperintense probably because of liquefaction and pus formation (tuberculous abscess). While both, CT and MR, were equally sensitive in visualizing the intracranial tuberculoma in every patient, MR was slightly superior in demonstrating the extent of the lesion, especially for brainstem tuberculomas. Nevertheless, the potential role for MR diagnosis of intracranial tuberculoma is limited by the fact that other infectious or neoplasic diseases may present similar findings. The diagnosis of intracranial tuberculoma should rest on a proper integration of data from clinical manifestations, cerebrospinal fluid analysis, and neuroimaging studies. (orig.)

MR imaging for staging of cervical carcinoma: Update

Energy Technology Data Exchange (ETDEWEB)

Yoon, Seong Kuk; Kim, Dong Won [Dong A University Hospital, Busan(Korea, Republic of)

2017-08-15

Uterine cervical cancer is globally the third most common cancer among women, and shows high mortality with invasive cervical carcinoma. Early detection of the disease, its correct staging, and treatment are therefore of great importance. The staging system updated in 2009 by the International Federation of Gynecology and Obstetrics (FIGO), is commonly used for planning the treatment. However, there are significant inaccuracies in the FIGO staging system. Accurate tumor staging is very important to decide the treatment strategy. Although not included in the staging system, magnetic resonance (MR) imaging is a valuable tool for local staging of the disease, and is useful in assessing the spread of the tumor and metastatic lymph nodes, thereby becoming a more accurate substitute for clinical staging of cervical carcinoma. In addition, it is capable of assessing the disease response to surgery or chemoradiation. This review briefly describes the role of MR imaging and the basic MR scanning protocol in evaluating cervical carcinoma. The MR findings with staging, and MR evaluation of treatment response, are further addressed.

Treatment of osteoid osteoma using CT-guided radiofrequency ablation versus MR-guided laser ablation: A cost comparison

International Nuclear Information System (INIS)

Maurer, M.H.; Gebauer, B.; Wieners, G.; De Bucourt, M.; Renz, D.M.; Hamm, B.; Streitparth, F.

2012-01-01

Objective: To compare the costs of CT-guided radiofrequency ablation (RFA) and MR-guided laser ablation (LA) for minimally invasive percutaneous treatment of osteoid osteoma. Materials and methods: Between November 2005 and October 2011, 20 patients (14 males, 6 females, mean age 20.3 ± 9.1 years) underwent CT-guided RFA and 24 patients (18 males, 6 females; mean age, 23.8 ± 13.8 years) MR-guided LA (open 1.0 Tesla, Panorama HFO, Philips, Best, Netherlands) for osteoid osteoma diagnosed on the basis of clinical presentation and imaging findings. Prorated costs of equipment use (purchase, depreciation, and maintenance), staff costs, and expenditure for disposables were identified for CT-guided RFA and MR-guided LA procedures. Results: The average total costs per patient were EUR 1762 for CT-guided RFA and EUR 1417 for MR-guided LA. These were (RFA/LA) EUR 92/260 for equipment use, EUR 149/208 for staff, and EUR 870/300 for disposables. Conclusion: MR-guided LA is less expensive than CT-guided RFA for minimally invasive percutaneous ablation of osteoid osteoma. The higher costs of RFA are primarily due to the higher price of the disposable RFA probes.

An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

Science.gov (United States)

Steegmann, Juan Luis; Colomer, Dolors; Gómez-Casares, Maria-Teresa; García-Gutiérrez, Valentín; Ortí, Guillermo; Ramírez-Payer, Angel; Olavarria, Eduardo; Vall-Llovera, Ferrán; Giraldo, Pilar; Conde, Eulogio; Vallansot, Rolando; López-Lorenzo, Jose Luis; Palomera, Luis; Álvarez-Larrán, Alberto; Conesa, Venancio; Bautista, Guiomar; Casas, Laura; Giles, Frank; Hochhaus, Andreas; Casado-Montero, Luis Felipe

2017-10-01

This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation

DEFF Research Database (Denmark)

Cremer, Signe Emilie; Zois, Nora Elisabeth; Moesgaard, S. G.

2015-01-01

surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary......-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent...... muscle (AP) and left ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV (P SERT and TPH-1 were up-regulated in AP and LV compared...

PET/MR in oncology

DEFF Research Database (Denmark)

Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin

2012-01-01

of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number...... be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new...

Down-regulation of dopamine D-2, 5-HT2 receptors and β-adrenoceptors in rat brain after prolonged treatment with a new potential antidepressant, Lu 19-005

International Nuclear Information System (INIS)

Nowak, G.; Arnt, J.; Hyttel, J.; Svendsen, O.

1985-01-01

Lu 19-005 is a new phenylindan derivative with strong and equipotent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake. The adaptive effects of 2 weeks treatment with Lu 19-005, on receptor binding in vitro and on d-amphetamine responsiveness in vivo have been investigated in rats. One or 3 days after the final dose the number of β-adrenoceptors and of 5-HT 2 and DA D-2 receptors was decreased by 20-30%, whereas αsub1-adrenoceptor number was slightly decreased only 1 day after withdrawal. The DA D-2 receptor number remained decreased at 7 days withdrawal, but returned to normal after another 3 days. The brain levels of DA, NA and 5-HT were not changed by 2 weeks' Lu 19-005 treatment. The down-regulation of DA D-2 receptors was accompanied by tolerance to d-amphetamine-induced hypermotility (after low doses) and stereotyped licking or biting (after a high dose). The tolerance to d-amphetamine-induced hypermotility was maximal 3-5 days withdrawal time, and remained significant also 15 days after the last dose. The results are discussed in relation to the effect of prolonged treatment with other antidepressant drugs. (Author)

[Other Possible Clinical Applications of Drugs with 5HT2A effect in Liaison Psychiatry: Cases Report].

Science.gov (United States)

Corredor, Catalina Ayala; Castillo, Carolina Solís

2012-03-01

In liaison psychiatry it is possible to get an integral view of patient's treatment and needs, paying special attention to pharmacological interactions and contraindications. Some particular cases motivated the description, report and review about other possible applications of 5HT2A and 5HT3 antagonist, particularly Mirtazapine and Olanzapine, in hyperalgesia syndrome, tinnitus and Progressive Multifocal Leukoencephalopathy by JC virus. Cases report. We describe 3 cases of patients in which Mirtazapine and Olanzapine were necessary not only to control psychiatric symptoms (affective / behavioral symptoms and insomnia) but to act as adjuvant therapy in axis III diseases. The use of any drug in psychiatry must take in to account the context of the patient, the presence of comorbidity, contraindications and pharmacological interactions so as to grant a positive outcome also promoting the multidisciplinary work between specialists. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Part-body hyperthermia with a radiofrequency multiantenna applicator under online control in 1,5 T MR-tomograph

International Nuclear Information System (INIS)

Wust, P.; Gellermann, J.; Faehling, H.; Wlodarczyk, W.; Felix, R.; Seebass, M.; Turner, P.; Nadobny, J.; Rau, B.; Hildebrandt, B.; Schlag, P.M.; Oppelt, A.

2004-01-01

Objective of this study is the integration of a multiantenna applicator for part-body hyperthermia (BSD 2000/3D) in a 1.5 T MR-tomograph (Siemens Magnetom Symphony) in order to perform noninvasive MR monitoring in real time to increase safety and effectiveness of heat treatments. The positioning unit is mechanically coupled to the MR gantry from the back side and the body coil is utilised for imaging. For that purpose, the hyperthermia antenna system (100 MHz, 1.500 W) and the MR receiver(63.9 MHs) have to be decoupled in terms of high frequency (filter) and electromagnetically (emc). The processing of MR data sets is performed in a hyperthermia planning system. A simultaneous operation of radiofrequency hyperthermia and MR system is possible at clinically relevant power levels. MR imaging is used for tumor diagnostics (standard spin echo sequences), for hyperthermia planning (T1-weighted gradient echo sequences in equal- and opposed-phase techniques), and for temperature measurements according to the proton resonance frequency method (PRF method, phase evaluation registration using a gradient echo sequence with long echo time). In 33 patients with advanced pelvic and abdominal tumors we performed 150 heat sessions under MR monitoring. For 70% of these patients a visualisation of temperature sensitive data during treatment was possible. The evaluated difference images represent a superposition of real temperature increase and a (temperature-induced) perfusion elevation. The hybrid approach renders development of part body hyperthermia possible as an MR-controlled intervention in radiology. (orig.) [de

MR myelography of sacral meningeal cysts

International Nuclear Information System (INIS)

Tsuchiya, K.; Katase, S.; Hachiya, J.

1999-01-01

Purpose: To describe the findings of sacral meningeal cysts (SMCs) on MR myelography and assess its value for the diagnosis of SMCs. Material and Methods: We evaluated the MR images and MR myelograms obtained from 10 patients with SMC. MR myelograms were obtained using a 2D or 3D single-shot fast spin-echo sequence. In 5 patients, X-ray myelograms and postmyelographic CT images were compared with the MR myelograms. Results: A total of 33 SMCs were diagnosed within the spinal canal and/or sacral foramen. MR myelograms clearly revealed each cyst as a well-defined mass showing hyperintensity (10 cysts) or isointensity (23 cysts) compared to cerebrospinal fluid. MR myelograms demonstrated SMCs better than X-ray myelograms and postmyelographic CT images in 3 of the 5 patients. Conclusion: MR myelography can be an adjunct to conventional imaging techniques when surgical treatment is indicated, because it can precisely delineate the extent of SMCs. (orig.)

The Use of Healing Touch in Integrative Oncology

Science.gov (United States)

Hart, Laura K.; Freel, Mildred I.; Haylock, Pam J.; Lutgendorf, Susan K.

2013-01-01

The use of complementary therapies by cancer patients has become so prevalent that nurses working in oncology are finding it necessary to understand these therapies and the evidence-based support for their use. The integrative use of the biofield therapy Healing Touch (HT) in conjunction with the chemoradiation received by patients with cervical cancer (stages 1B1 to IVA) during a recent research study is described. Findings indicated effects of HT on the immune response and on depression, in contrast to patients receiving relaxation or standard care. Specifically, HT patients demonstrated a minimal decrease in natural killer cell cytotoxicity (NKCC) over the course of treatment whereas NKCC of patients receiving relaxation therapy (RT) and standard care (SC) declined sharply during radiation (p = 0.018). HT patients also showed significant decreases in depressed mood compared to RT and SC (p < 0.05). These findings, as well as the energetic effects of chemoradiation that were observed, and the proposed mechanisms and potential contributions of biofield therapy are addressed. It is suggested that the appropriate integration of complementary modalities into oncology care has the potential to enhance the impact of conventional care by putting the patient in the best condition to use their innate healing resources. PMID:21951738

Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality.

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Jacobus J Dudok

Full Text Available The serotonin (5-HT system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival.

PET motion correction in context of integrated PET/MR: Current techniques, limitations, and future projections.

Science.gov (United States)

Gillman, Ashley; Smith, Jye; Thomas, Paul; Rose, Stephen; Dowson, Nicholas

2017-12-01

Patient motion is an important consideration in modern PET image reconstruction. Advances in PET technology mean motion has an increasingly important influence on resulting image quality. Motion-induced artifacts can have adverse effects on clinical outcomes, including missed diagnoses and oversized radiotherapy treatment volumes. This review aims to summarize the wide variety of motion correction techniques available in PET and combined PET/CT and PET/MR, with a focus on the latter. A general framework for the motion correction of PET images is presented, consisting of acquisition, modeling, and correction stages. Methods for measuring, modeling, and correcting motion and associated artifacts, both in literature and commercially available, are presented, and their relative merits are contrasted. Identified limitations of current methods include modeling of aperiodic and/or unpredictable motion, attaining adequate temporal resolution for motion correction in dynamic kinetic modeling acquisitions, and maintaining availability of the MR in PET/MR scans for diagnostic acquisitions. Finally, avenues for future investigation are discussed, with a focus on improvements that could improve PET image quality, and that are practical in the clinical environment. © 2017 American Association of Physicists in Medicine.

Morphological modulation of human fibrosarcoma HT-1080 cells by hydroxybenzoate compounds during apoptosis

Directory of Open Access Journals (Sweden)

Jassem G Mahdi

2015-10-01

Full Text Available Hydroxybenzoate (HB compounds have shown to modulate the morphology in human fibrosarcoma HT-1080 cells. The changes in HT-1080 cells showed marker signs of apoptosis, which included the condensation of nucleus, cell round, blebbing and the formation of apoptotic bodies. The different stages of apoptosis were assessed microscopically using different staining and immunohistochemical techniques, as well as scanning electron microscopy. In addition, HB compounds increased the expression of caspase-3, which is closely associated with the development of the modulation in HT-1080 cells that are undergoing the programmed cell death. Both acetyl salicylic acid (ASA and HBZn compounds were dose and treatment duration dependent.

Role of 5-HT3 Receptor on Food Intake in Fed and Fasted Mice

Science.gov (United States)

Li, Bingjin; Shao, Dongyuan; Luo, Yungang; Wang, Pu; Liu, Changhong; Zhang, Xingyi; Cui, Ranji

2015-01-01

Background Many studies have shown that 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the regulation of feeding behavior. However, the relative contribution of 5-HT3 receptor remains unclear. The present study was aimed to investigate the role of 5-HT3 receptor in control of feeding behavior in fed and fasted mice. Methodology/Principal Findings Food intake and expression of c-Fos, tyrosine hydroxylase (TH), proopiomelanocortin (POMC) and 5-HT in the brain were examined after acute treatment with 5-HT3 receptor agonist SR-57227 alone or in combination with 5-HT3 receptor antagonist ondansetron. Food intake was significantly inhibited within 3 h after acute treatment with SR 57227 in fasted mice but not fed mice, and this inhibition was blocked by ondansetron. Immunohistochemical study revealed that fasting-induced c-Fos expression was further enhanced by SR 57227 in the brainstem and the hypothalamus, and this enhancement was also blocked by ondansetron. Furthermore, the fasting-induced downregulation of POMC expression in the hypothalamus and the TH expression in the brain stem was blocked by SR 57227 in the fasted mice, and this effect of SR 57227 was also antagonized by ondansetron. Conclusion/Significance Taken together, our findings suggest that the effect of SR 57227 on the control of feeding behavior in fasted mice may be, at least partially, related to the c-Fos expression in hypothalamus and brain stem, as well as POMC system in the hypothalamus and the TH system in the brain stem. PMID:25789930

Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action

DEFF Research Database (Denmark)

Lucas, Guillaume; Rymar, Vladimir V; Du, Jenny

2007-01-01

parameters considered to be key markers of antidepressant action, but that are observed only after 2-3 week treatments with classical molecules: desensitization of 5-HT(1A) autoreceptors, increased tonus on hippocampal postsynaptic 5-HT(1A) receptors, and enhanced phosphorylation of the CREB protein...... intake consecutive to a chronic mild stress. These findings point out 5-HT(4) receptor agonists as a putative class of antidepressants with a rapid onset of action. Udgivelsesdato: 2007-Sep-6...

Integration of functional and morphological MR data for preoperative 3D visualisation of tumours. Cervical carcinoma

International Nuclear Information System (INIS)

Evers, H.; Meinzer, H.P.; Hawighorst, H.; Kaick, G. van; Knapstein, P.G.

1998-01-01

Purpose: The goal of this exemplary study was to integrate morphological and functional MRI to establish computer-based, preoperative therapy planning for tumors, instancing cervical carcinoma. Results: Segmentation of organs and vessels as well as tissue differentiation yielded a morphological visualisation of anatomical structures that were overlaid with pharmacokinetic parameters derived from dynamic MRI, subsequently. Thereby, three-dimensional, arbitrary views on the functional data were displayed. Conclusions: Image analysis and visualisation of the acquired MR data establishes both a morphologic and functional evaluation of suspect lesions and adjacent organs. By integrating morphologic and functional MRI additional information can be gathered that possibly impinge on preoperative planning. (orig./AJ) [de

Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior.

Science.gov (United States)

Vahid-Ansari, Faranak; Daigle, Mireille; Manzini, M Chiara; Tanaka, Kenji F; Hen, René; Geddes, Sean D; Béïque, Jean-Claude; James, Jonathan; Merali, Zul; Albert, Paul R

2017-12-06

Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo , we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons ( cF1ko ). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knock-out ( cF1/1A dko ) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behavior was seen upon knock-out of Freud-1 on the 5-HT1A autoreceptor-negative background; rather, a reduction in depression-like behavior emerged. These studies implicate transcriptional dysregulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors, such as Freud-1, to restore transcriptional balance may augment response to antidepressant treatment. SIGNIFICANCE STATEMENT Altered regulation of the 5-HT1A autoreceptor has been implicated in human anxiety, major depression, suicide, and resistance to antidepressants. This study uniquely identifies a single transcription factor, Freud-1, as crucial for 5-HT1A autoreceptor expression in vivo Disruption of Freud-1 in serotonin neurons in mice links upregulation of 5-HT1A autoreceptors to anxiety/depression-like behavior and provides a new model of antidepressant resistance. Treatment strategies to reestablish transcriptional regulation of 5-HT1A autoreceptors could provide a more robust and sustained antidepressant response. Copyright © 2017 the authors 0270-6474/17/3711967-12$15.00/0.

Effects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task.

Science.gov (United States)

Perez-García, Georgina S; Meneses, A

2005-08-30

This work aimed to evaluate further the role of 5-HT7 receptors during memory formation in an autoshaping Pavlovian/instrumental learning task. Post-training administration of the potential 5-HT7 receptor agonist AS 19 or antagonist SB-269970 enhanced memory formation or had no effect, respectively. The AS 19 facilitatory effect was reversed by SB-269970, but not by the selective 5-HT1A antagonist WAY100635. Amnesia induced by scopolamine (cholinergic antagonist) or dizocilpine (NMDA antagonist) was also reversed by AS 19. Certainly, reservations regarding the selectivity of AS 19 for 5-HT7 and other 5-HT receptors in vivo are noteworthy and, therefore, its validity for use in animal models as a pharmacological tool. Having mentioned that, it should be noticed that together these data are providing further support to the notion of the 5-HT7 receptors role in memory formation. Importantly, this 5-HT7 receptor agonist AS 19 appears to represent a step forward respect to the notion that potent and selective 5-HT7 receptor agonists can be useful in the treatment of dysfunctional memory in aged-related decline and Alzheimer's disease.

G-LiHT: Goddard's LiDAR, Hyperspectral and Thermal Airborne Imager

Science.gov (United States)

Cook, Bruce; Corp, Lawrence; Nelson, Ross; Morton, Douglas; Ranson, Kenneth J.; Masek, Jeffrey; Middleton, Elizabeth

2012-01-01

Scientists at NASA's Goddard Space Flight Center have developed an ultra-portable, low-cost, multi-sensor remote sensing system for studying the form and function of terrestrial ecosystems. G-LiHT integrates two LIDARs, a 905 nanometer single beam profiler and 1550 nm scanner, with a narrowband (1.5 nanometers) VNIR imaging spectrometer and a broadband (8-14 micrometers) thermal imager. The small footprint (approximately 12 centimeters) LIDAR data and approximately 1 meter ground resolution imagery are advantageous for high resolution applications such as the delineation of canopy crowns, characterization of canopy gaps, and the identification of sparse, low-stature vegetation, which is difficult to detect from space-based instruments and large-footprint LiDAR. The hyperspectral and thermal imagery can be used to characterize species composition, variations in biophysical variables (e.g., photosynthetic pigments), surface temperature, and responses to environmental stressors (e.g., heat, moisture loss). Additionally, the combination of LIDAR optical, and thermal data from G-LiHT is being used to assess forest health by sensing differences in foliage density, photosynthetic pigments, and transpiration. Low operating costs (approximately $1 ha) have allowed us to evaluate seasonal differences in LiDAR, passive optical and thermal data, which provides insight into year-round observations from space. Canopy characteristics and tree allometry (e.g., crown height:width, canopy:ground reflectance) derived from G-LiHT data are being used to generate realistic scenes for radiative transfer models, which in turn are being used to improve instrument design and ensure continuity between LiDAR instruments. G-LiHT has been installed and tested in aircraft with fuselage viewports and in a custom wing-mounted pod that allows G-LiHT to be flown on any Cessna 206, a common aircraft in use throughout the world. G-LiHT is currently being used for forest biomass and growth estimation

The Role of MR Enterography in Assessing Crohn’s Disease Activity and Treatment Response

Directory of Open Access Journals (Sweden)

Matthew P. Moy

2016-01-01

Full Text Available MR enterography (MRE has become the primary imaging modality in the assessment of Crohn’s disease (CD in both children and adults at many institutions in the United States and worldwide, primarily due to its noninvasiveness, superior soft tissue contrast, and lack of ionizing radiation. MRE technique includes distention of the small bowel with oral contrast media with the acquisition of T2-weighted, balanced steady-state free precession, and multiphase T1-weighted fat suppressed gadolinium contrast-enhanced sequences. With the introduction of molecule-targeted biologic agents into the clinical setting for CD and their potential to reverse the inflammatory process, MRE is increasingly utilized to evaluate disease activity and response to therapy as an imaging complement to clinical indices or optical endoscopy. New and emerging MRE techniques, such as diffusion-weighted imaging (DWI, magnetization transfer, ultrasmall superparamagnetic iron oxide- (USPIO- enhanced MRI, and PET-MR, offer the potential for an expanded role of MRI in detecting occult disease activity, evaluating early treatment response/resistance, and differentiating inflammatory from fibrotic strictures. Familiarity with MR enterography is essential for radiologists and gastroenterologists as the technique evolves and is further incorporated into the clinical management of CD.

Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.

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Gianotti, Massimo; Botta, Maurizio; Brough, Stephen; Carletti, Renzo; Castiglioni, Emiliano; Corti, Corrado; Dal-Cin, Michele; Delle Fratte, Sonia; Korajac, Denana; Lovric, Marija; Merlo, Giancarlo; Mesic, Milan; Pavone, Francesca; Piccoli, Laura; Rast, Slavko; Roscic, Maja; Sava, Anna; Smehil, Mario; Stasi, Luigi; Togninelli, Andrea; Wigglesworth, Mark J

2010-11-11

Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

Pharmacological Characterization of H05, a Novel Serotonin and Noradrenaline Reuptake Inhibitor with Moderate 5-HT2A Antagonist Activity for the Treatment of Depression.

Science.gov (United States)

Xu, Xiangqing; Wei, Yaqin; Guo, Qiang; Zhao, Song; Liu, Zhiqiang; Xiao, Ting; Liu, Yani; Qiu, Yinli; Hou, Yuanyuan; Zhang, Guisen; Wang, KeWei

2018-06-01

Multitarget antidepressants selectively inhibiting monoaminergic transporters and 5-hydroxytryptamine (5-HT) 2A receptor have demonstrated higher efficacy and fewer side effects than selective serotonin reuptake inhibitors. In the present study, we synthesized a series of novel 3-(benzo[d][1,3]dioxol-4-yloxy)-3-arylpropyl amine derivatives, among which compound H05 was identified as a lead, exhibiting potent inhibitory effects on both serotonin ( K i = 4.81 nM) and norepinephrine (NE) ( K i = 6.72 nM) transporters and moderate 5-HT 2A antagonist activity (IC 50 = 60.37 nM). H05 was able to dose-dependently reduce the immobility duration in mouse forced swimming test and tail suspension test, with the minimal effective doses lower than those of duloxetine, and showed no stimulatory effect on locomotor activity. The administration of H05 (5, 10, and 20 mg/kg, by mouth) significantly shortened the immobility time of adrenocorticotropin-treated rats that serve as a model of treatment-resistant depression, whereas imipramine (30 mg/kg, by mouth) and duloxetine (30 mg/kg, by mouth) showed no obvious effects. Chronic treatment with H05 reversed the depressive-like behaviors in a rat model of chronic unpredictable mild stress and a mouse model of corticosterone-induced depression. Microdialysis analysis revealed that the administration of H05 at either 10 or 20 mg/kg increased the release of 5-HT and NE from the frontal cortex. The pharmacokinetic (PK) and brain penetration analyses suggest that H05 has favorable PK properties with good blood-brain penetration ability. Therefore, it can be concluded that H05, a novel serotonin and NE reuptake inhibitor with 5-HT 2A antagonist activity, possesses efficacious activity in the preclinical models of depression and treatment-resistant depression, and it may warrant further evaluation for clinical development. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review.

Science.gov (United States)

van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Hofman, Paul A M; Vlooswijk, Marielle C G; Rouhl, Rob P W; de Louw, Anton J; Backes, Walter H; Jansen, Jacobus F A

2015-12-01

As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

MR imaging of the juvenile temporomandibular joint before orthodontic treatment

International Nuclear Information System (INIS)

Lieberman, J.M.; Hans, M.G.; Rozencweig, G.; Goldberg, J.S.; Bellon, E.M.

1990-01-01

This paper determines the prevalence of internal derangement (ID) of the temporomandibular joint (TM) in a population of children prior to orthodontic therapy. Thirty-two children, aged 7-15 years, with a variety of orthodontic disorders underwent both MR imaging and physical examination to assess ID of the TMJ. With MR imaging, the disks were graded as normal, borderline anterior displaced, or anterior displaced. Fifty-nine TMJs in 32 patients were successfully imaged. Five TMJ MR examinations could not be interpreted because of patient motion. Fifty seven of the 59 joints (97%) were normal. One disk (1.7%) was anterior displaced, and one (1.7%) was considered borderline

Preparation and characterization of Sr-Ti-hardystonite (Sr-Ti-HT nanocomposite for bone repair application

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Hossein Mohammadi

2015-07-01

Full Text Available Objective(s: Hardystonite (HT is Zn-modified silicate bioceramics with promising results for bone tissue regeneration. However, HT possesses no obvious apatite formation. Thus, in this study we incorporated Sr and Ti into HT to prepare Sr-Ti-hardystonite (Sr-Ti-HT nanocomposite and evaluated its in vitro bioactivity with the purpose of developing a more bioactive bone substitute material. Materials and methods:The HT and Sr-Ti-HT were prepared by mechanical milling and subsequent heat treatment. Calcium oxide (CaO, zinc oxide (ZnO and silicon dioxide (SiO2 (all from Merck were mixed with molar ratio of 2:1:2. The mixture of powders mixture was then milled in a planetary ball mill for 20 h. In the milling run, the ball-to-powder weight ratio was 10:1 and the rotational speed was 200 rpm. After synthesis of HT, 3% nanotitanium dioxide (TiO2, Degussa and 3% strontium carbonate (SrCO3, Merck were added to HT and then the mixture was ball milled and calcined at 1150°C for 6 h. Simultaneous thermal analysis (STA, X-ray diffraction (XRD, Transmission electron microscopy (TEM and Fourier transform infra-red spectroscopy (FT-IR performed to characterize the powders. Results:XRD and FT-IR confirmed the crystal phase and silicate structure of HT and TEM images demonstrated the nanostructure of powders. Further, Sr-Ti-HT induced apatite formation and showed a higher human mesenchymal stem cell (hMSCs adhesion and proliferation compared to HT. Conclusion:Our study revealed that Sr-Ti-HT with a nanostructured crystal structure of 50 nm, can be prepared by mechanical activation to use as biomaterials for orthopedic applications.

Changes of Serotonin (5-HT), 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression,Myocardial Infarction and Myocardial Infarction Co-exist with Depression

Institute of Scientific and Technical Information of China (English)

Mei-Yan Liu; Yah-Ping Ren; Wan-Lin Wei; Guo-Xiang Tian; Guo Li

2015-01-01

Background:To evaluate whether serotonin (5-HT),5-HT2A receptor (5-HT2AR),and 5-HT transporter (serotonin transporter [SERT]) are associated with different disease states of depression,myocardial infarction (MI) and MI co-exist with depression in Sprague-Dawley rats.Methods:After established the animal model of four groups include control,depression,MI and MI with depression,we measured 5-HT,5-HT2AR and SERT from serum and platelet lysate.Results:The serum concentration of 5-HT in depression rats decreased significantly compared with the control group (303.25 ± 9.99 vs.352.98 ± 13.73;P =0.000),while that in MI group increased (381.78 ± 14.17 vs.352.98 ± 13.73;P =0.000).However,the depression + MI group had no change compared with control group (360.62 ± 11.40 vs.352.98 ± 13.73;P =0.036).The changes of the platelet concentration of 5-HT in the depression,MI,and depression + MI group were different from that of serum.The levels of 5-HT in above three groups were lower than that in the control group (380.40 ± 17.90,387.75 ± 22.28,246.40 ± 18.99 vs.500.29 ± 20.91;P =0.000).The platelet lysate concentration of 5-HT2AR increased in depression group,MI group,and depression + MI group compared with the control group (370.75 ± 14.75,393.47 ± 15.73,446.66 ± 18.86 vs.273.66 ± 16.90;P =0.000).The serum and platelet concentration of SERT in the depression group,MI group and depression + MI group were all increased compared with the control group (527.51 ± 28.32,602.02 ± 23.32,734.76 ± 29.59 vs.490.56 ± 16.90;P =0.047,P =0.000,P =0.000 in each and 906.38 ± 51.84,897.33 ± 60.34,1030.17 ± 58.73 vs.708.62 ± 51.15;P =0.000 in each).Conclusions:The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression.Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors.

Science.gov (United States)

Eriksson, Therese M; Holst, Sarah; Stan, Tiberiu L; Hager, Torben; Sjögren, Benita; Ogren, Sven Öve; Svenningsson, Per; Stiedl, Oliver

2012-11-01

This study utilized pharmacological manipulations to analyze the role of direct and indirect activation of 5-HT(7) receptors (5-HT(7)Rs) in passive avoidance learning by assessing emotional memory in male C57BL/6J mice. Additionally, 5-HT(7)R binding affinity and 5-HT(7)R-mediated protein phosphorylation of downstream signaling targets were determined. Elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated emotional memory performance when combined with the 5-HT(1A)R antagonist NAD-299. This facilitation was blocked by the selective 5-HT(7)R antagonist SB269970, revealing excitatory effects of the SSRI via 5-HT(7)Rs. The enhanced memory retention by NAD-299 was blocked by SB269970, indicating that reduced activation of 5-HT(1A)Rs results in enhanced 5-HT stimulation of 5-HT(7)Rs. The putative 5-HT(7)R agonists LP-44 when administered systemically and AS19 when administered both systemically and into the dorsal hippocampus failed to facilitate memory. This finding is consistent with the low efficacy of LP-44 and AS19 to stimulate protein phosphorylation of 5-HT(7)R-activated signaling cascades. In contrast, increasing doses of the dual 5-HT(1A)R/5-HT(7)R agonist 8-OH-DPAT impaired memory, while co-administration with NAD-299 facilitated of emotional memory in a dose-dependent manner. This facilitation was blocked by SB269970 indicating 5-HT(7)R activation by 8-OH-DPAT. Dorsohippocampal infusion of 8-OH-DPAT impaired passive avoidance retention through hippocampal 5-HT(1A)R activation, while 5-HT(7)Rs appear to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone. Copyright © 2012 Elsevier Ltd. All rights reserved.

Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

Science.gov (United States)

Röser, Claudia; Jordan, Nadine; Balfanz, Sabine; Baumann, Arnd; Walz, Bernd; Baumann, Otto; Blenau, Wolfgang

2012-01-01

Secretion in blowfly (Calliphora vicina) salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT), which activates both inositol 1,4,5-trisphosphate (InsP(3))/Ca(2+) and cyclic adenosine 3',5'-monophosphate (cAMP) signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7) that share high similarity with mammalian 5-HT(2) and 5-HT(7) receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+)] in a dose-dependent manner (EC(50) = 24 nM). In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i) (EC(50) = 4 nM). We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α) or Cv5-HT(7) in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM) activates only the Cv5-HT(2α) receptor, 5-carboxamidotryptamine (300 nM) activates only the Cv5-HT(7) receptor, and clozapine (1 µM) antagonizes the effects of 5-HT via Cv5-HT(7) in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+)- and cAMP-signalling cascades.

Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

Directory of Open Access Journals (Sweden)

Claudia Röser

Full Text Available Secretion in blowfly (Calliphora vicina salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT, which activates both inositol 1,4,5-trisphosphate (InsP(3/Ca(2+ and cyclic adenosine 3',5'-monophosphate (cAMP signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7 that share high similarity with mammalian 5-HT(2 and 5-HT(7 receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+] in a dose-dependent manner (EC(50 = 24 nM. In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i (EC(50 = 4 nM. We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α or Cv5-HT(7 in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM activates only the Cv5-HT(2α receptor, 5-carboxamidotryptamine (300 nM activates only the Cv5-HT(7 receptor, and clozapine (1 µM antagonizes the effects of 5-HT via Cv5-HT(7 in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+- and cAMP-signalling cascades.

MR-guided HIFU treatment of symptomatic uterine fibroids using novel feedback-regulated volumetric ablation: effectiveness and clinical practice.

Science.gov (United States)

Ruhnke, H; Eckey, T; Bohlmann, M K; Beldoch, M P; Neumann, A; Agic, A; Hägele, J; Diedrich, K; Barkhausen, J; Hunold, P

2013-09-01

To evaluate a novel feedback-regulated volumetric sonication method in MR-guided HIFU treatment of symptomatic uterine fibroids. 27 fibroids with an average volume of 124.9 ± 139.8 cc in 18 women with symptomatic uterine fibroids were ablated using the new HIFU system Sonalleve (1.5 T MR system Achieva, Philips). 21 myomas in 13 women were reevaluated 6 months later. Standard (treatment) cells (TC) and feedback-regulated (feedback) cells (FC) with a diameter of 4, 8, 12, and 16 mm were used and compared concerning sonication success, diameter of induced necrosis, and maximum achieved temperature. The non-perfused volume ratio (NPV related to myoma volume) was quantified. The fibroid volume was measured before, 1 month, and 6 months after therapy. Symptoms were quantified using a specific questionnaire (UFS-QoL). In total, 205 TC and 227 FC were applied. The NPV ratio was 23 ± 15 % (2 - 55). The TC were slightly smaller than intended (-3.9 ± 52 %; range, -100 - 81), while the FC were 20.1 ± 25.3 % bigger (p = 0.02). Feedback mechanism is less diversifying in diameter (p feedback cells leads to more contiguous necrosis in diameter and a less diversifying temperature. ▶ MR-guided HIFU ablation of symptomatic uterine fibroids is a valuable treatment option. ▶ By non-invasive HIFU fibroid volumes can be reduced and symptoms improved. ▶ The novel feedback-regulated treatment cells offer advantages over standard treatment cells. © Georg Thieme Verlag KG Stuttgart · New York.

Dosimetric Study of Current Treatment Options for Radiotherapy in Retinoblastoma

Energy Technology Data Exchange (ETDEWEB)

Eldebawy, Eman [Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Department of Radiation Oncology, Children' s Cancer Hospital, Cairo (Egypt); Parker, William, E-mail: william.parker@mcgill.ca [Department of Medical Physics, McGill University Health Centre, Montreal, Quebec (Canada); Abdel Rahman, Wamied [Department of Medical Physics, McGill University Health Centre, Montreal, Quebec (Canada); Freeman, Carolyn R. [Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada)

2012-03-01

Purpose: To determine the best treatment technique for patients with retinoblastoma requiring radiotherapy to the whole eye. Methods and Materials: Treatment plans for 3 patients with retinoblastoma were developed using 10 radiotherapy techniques including electron beams, photon beam wedge pair (WP), photon beam three-dimensional conformal radiotherapy (3D-CRT), fixed gantry intensity-modulated radiotherapy (IMRT), photon volumetric arc therapy (VMAT), fractionated stereotactic radiotherapy, and helical tomotherapy (HT). Dose-volume analyses were carried out for each technique. Results: All techniques provided similar target coverage; conformity was highest for VMAT, nine-field (9F) IMRT, and HT (conformity index [CI] = 1.3) and lowest for the WP and two electron techniques (CI = 1.8). The electron techniques had the highest planning target volume dose gradient (131% of maximum dose received [D{sub max}]), and the CRT techniques had the lowest (103% D{sub max}) gradient. The volume receiving at least 20 Gy (V{sub 20Gy}) for the ipsilateral bony orbit was lowest for the VMAT and HT techniques (56%) and highest for the CRT techniques (90%). Generally, the electron beam techniques were superior in terms of brain sparing and delivered approximately one-third of the integral dose of the photon techniques. Conclusions: Inverse planned image-guided radiotherapy delivered using HT or VMAT gives better conformity index, improved orbital bone and brain sparing, and a lower integral dose than other techniques.

MR imaging of the kidneys: new diagnostic strategies; MR-Bildgebung der Nieren. Neue Ansaetze in der Diagnostik

Energy Technology Data Exchange (ETDEWEB)

Schoenberg, S.O.; Knopp, M.V.; Bock, M.; Floemer, F.; Essig, M.; Hawighorst, H.; Kaick, G. van [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Forschungsschwerpunkt Radiologische Diagnostik; Kallinowski, F. [Heidelberg Univ. (Germany). Chirurgische Universitaetsklinik; Just, A. [Heidelberg Univ. (Germany). 1. Physiologisches Inst.; Laub, G. [Siemens AG, Erlangen (Germany). Unternehmensbereich Medizinische Technik; Prince, M.R [Michigan Univ., Ann Arbor, MI (United States). Dept. of Radiology

1999-05-01

Aim: New diagnostic strategies for evaluation of the kidney by fast MR imaging of renal morphology, multiphase 3D gadolinium MR angiography, MR urography and MR flow measurements. A signal MR examination is designed to grade renovascular disease and assess the hemodynamic and functional significance, detect and characterize renal lesions and evaluate the urinary tract. Results: The combined analysis of morphologic and functional data allows reliable assessment of renal artery stenosis, benign and malignant renal masses and diseases of the renal collecting system and ureters, as well as congenital abnormalities in good agreement to the results of conventional imaging modalities. The improved tissue contrast and additional functional information compensates for the disadvantage of a lower spatial resolution. Conclusion: Combined morphologic and functional MR examination represents a reliable, non-invasive and cost-effective alternative imaging modality for comprehensive diagnostic evaluation of renal disease. (orig.) [Deutsch] Fragestellung: Darstellung neuer diagnostischer Moeglichkeiten im Bereich der Niere mittels schneller Magnetresonanz (MR)-Bildgebung. Methodik: Vorgestellt wird ein kombiniertes morphologisches und funktionelles Untersuchungskonzept bestehend aus schneller morphologischer Bildgebung, multiphasischer 3D-Gadolinium-MR-Angiographie, MR-Urographie und MR-Flussmessung. In einer einzigen MR-Untersuchung sollen vaskulaere Erkrankungen erfasst, eingestuft und auf ihre haemodynamische und funktionelle Signifikanz ueberprueft werden, renale Laesionen detektiert und differenziert sowie die Harnabflusswege beurteilt werden. Ergebnisse: Durch Integration der gewonnenen morphologischen und funktionellen Daten lassen sich Nierenarterienstenosen, benigne und maligne renale Tumoren, Harnabflussstoerungen und kongenitale Fehlbildungen mit aehnlicher Genauigkeit wie in den konventionellen radiologischen Verfahren erfassen. Der Nachteil der geringeren raeumlichen

Liquid metal reactor core material HT9

International Nuclear Information System (INIS)

Kim, S. H.; Kuk, I. H.; Ryu, W. S. and others

1998-03-01

A state-of-the art is surveyed on the liquid metal reactor core materials HT9. The purpose of this report is to give an insight for choosing and developing the materials to be applied to the KAERI prototype liquid metal reactor which is planned for the year of 2010. In-core stability of cladding materials is important to the extension of fuel burnup. Austenitic stainless steel (AISI 316) has been used as core material in the early LMR due to the good mechanical properties at high temperatures, but it has been found to show a poor swelling resistance. So many efforts have been made to solve this problem that HT9 have been developed. HT9 is 12Cr-1MoVW steel. The microstructure of HT9 consisted of tempered martensite with dispersed carbide. HT9 has superior irradiation swelling resistance as other BCC metals, and good sodium compatibility. HT9 has also a good irradiation creep properties below 500 dg C, but irradiation creep properties are degraded above 500 dg C. Researches are currently in progress to modify the HT9 in order to improve the irradiation creep properties above 500 dg C. New design studies for decreasing the core temperature below 500 dg C are needed to use HT9 as a core material. On the contrary, decrease of the thermal efficiency may occur due to lower-down of the operation temperature. (author). 51 refs., 6 tabs., 19 figs

Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice

DEFF Research Database (Denmark)

Klein, A B; Santini, M A; Aznar, S

2010-01-01

Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF(2L/2LCk-cre)). A severe impairment...... specific for the serotonin 2A receptor (5-HT(2A)R) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT(2A)Rs have been linked to neuropsychiatric disorders and anxiety-related behavior. Here we further characterized the serotonin receptor alterations triggered...... was decreased in hippocampus of BDNF mutants, but unchanged in frontal cortex. Molecular analysis indicated corresponding changes in 5-HT(2A) and 5-HT(1A) mRNA expression but normal 5-HT(2C) content in these brain regions in BDNF(2L/2LCk-cre) mice. We investigated whether the reduction in frontal 5-HT(2A...

5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

Science.gov (United States)

Amodeo, D A; Rivera, E; Cook, E H; Sweeney, J A; Ragozzino, M E

2017-03-01

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT 2A receptor activity is altered in autism, while recent work indicates that systemic 5HT 2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT 2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT 2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT 2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT 2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT 2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

LOCUS MR: Localization of unaffected spins in MR tomography and MR spectroscopy

International Nuclear Information System (INIS)

Matthael, D.; Haase, A.

1986-01-01

Different pulse sequences have been proposed for localized in vivo MR spectroscopy. For localized MR tomography and MR spectroscopy, a method is proposed, dubbed LOCUS (LOCalization of Unaffected Spins) MR. The method uses the initial saturation of regions surrounding the region of interest (ROI) in the presence of gradients. This is followed by a conventional MR study of the unaffected ROI. In animals, human extremities, and phantoms, proton MR studies demonstrated that the method provides an optimal signal-to-noise ratio, an easily variable ROI, and ROI shim. The method can be combined with two- and three-dimensional imaging, and it allows localized measurement of MR parameters. The multinuclear capability is discussed

Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling.

Science.gov (United States)

Buchborn, Tobias; Schröder, Helmut; Höllt, Volker; Grecksch, Gisela

2014-06-01

A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [(35)S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling. © The Author(s) 2014.

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

International Nuclear Information System (INIS)

Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan

2012-01-01

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT 4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT 4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT 4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg −1 ·day −1 , days 36-42), tegaserod (1 mg·kg −1 ·day −1 , day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT 4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT 4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Directory of Open Access Journals (Sweden)

Chi Yan

2012-10-01

Full Text Available Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05 and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05. Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42, tegaserod (1 mg·kg-1·day-1, day 43, or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01 but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654. These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

Dynamic MR imaging of hepatoma treated by transcatheter arterial embolization therapy

International Nuclear Information System (INIS)

Yamashita, Y.; Yoshimatsu, S.; Sumi, M.; Harada, M.; Takahashi, M.

1993-01-01

The effect of transcatheter arterial chemo-embolization theory (TACE) for hepatoma was evaluated with dynamic MR imaging with Gd-DTPA in 37 patients (44 tumors). TACE was performed using Lipiodol/cis-platinum and gelatin sponge (or microspheres) as an embolic material. All patients were examined with dynamic CT and MR imaging before and after treatment. On conventional spin echo images, changes of signal intensity after treatment varied regardless of presence of Lipiodol. Dynamic MR imaging revealed changes of tumor vascularity before and after treatment. On histologic correlation, areas of persistent tumor enhancement on dynamic MR imaging corresponded to areas of viable tumor cells while areas of nonenhancement corresponded to areas of necrosis. Dynamic MR imaging was superior in contrast resolution and was not influenced by the presence of Lipiodol compared with dynamic CT, and therefore residual viable tumors were better defined by dynamic MR imaging. (orig.)

Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

Science.gov (United States)

Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

2014-01-01

The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation

DEFF Research Database (Denmark)

Jensen, Jesper Bornø; du Jardin, Kristian Gaarn; Song, Dekun

2014-01-01

Depressed patients suffer from cognitive dysfunction, including memory deficits. Acute serotonin (5-HT) depletion impairs memory and mood in vulnerable patients. The investigational multimodal acting antidepressant vortioxetine is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor...... depletion impaired memory performance in rats through one or more of its receptor activities....... partial agonist, 5-HT1A receptor agonist and 5-HT transporter (SERT) inhibitor that enhances memory in normal rats in novel object recognition (NOR) and conditioned fear (Mørk et al., 2013). We hypothesized that vortioxetine's 5-HT receptor mechanisms are involved in its memory effects, and therefore...

Pavement subgrade MR design values for Michigan's seasonal changes : appendices.

Science.gov (United States)

2009-07-22

The resilient modulus (MR) of roadbed soil plays an integral role in the design of pavement systems. Currently, the various regions of the Michigan Department of Transportation (MDOT) use different procedures to determine the MR values. Most of these...

Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy

Science.gov (United States)

Maspero, Matteo; van den Berg, Cornelis A. T.; Zijlstra, Frank; Sikkes, Gonda G.; de Boer, Hans C. J.; Meijer, Gert J.; Kerkmeijer, Linda G. W.; Viergever, Max A.; Lagendijk, Jan J. W.; Seevinck, Peter R.

2017-10-01

An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of 1.1 × 1.1 × 1.2 mm3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a

Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy.

Science.gov (United States)

Maspero, Matteo; van den Berg, Cornelis A T; Zijlstra, Frank; Sikkes, Gonda G; de Boer, Hans C J; Meijer, Gert J; Kerkmeijer, Linda G W; Viergever, Max A; Lagendijk, Jan J W; Seevinck, Peter R

2017-10-03

An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of [Formula: see text] mm 3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a

MR-guided pulsed high intensity focused ultrasound enhancement of docetaxel combined with radiotherapy for prostate cancer treatment

International Nuclear Information System (INIS)

Mu Zhaomei; Ma, C-M; Chen Xiaoming; Cvetkovic, Dusica; Chen Lili; Pollack, Alan

2012-01-01

The purpose of this study is to evaluate the efficacy of the enhancement of docetaxel by pulsed focused ultrasound (pFUS) in combination with radiotherapy (RT) for treatment of prostate cancer in vivo. LNCaP cells were grown in the prostates of male nude mice. When the tumors reached a designated volume by MRI, tumor bearing mice were randomly divided into seven groups (n = 5): (1) pFUS alone; (2) RT alone; (3) docetaxel alone; (4) docetaxel + pFUS; (5) docetaxel + RT; (6) docetaxel + pFUS + RT, and (7) control. MR-guided pFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner. Animals were treated once with pFUS, docetaxel, RT or their combinations. Docetaxel was given by i.v. injection at 5 mg kg −1 before pFUS. RT was given 2 Gy after pFUS. Animals were euthanized 4 weeks after treatment. Tumor volumes were measured on MRI at 1 and 4 weeks post-treatment. Results showed that triple combination therapies of docetaxel, pFUS and RT provided the most significant tumor growth inhibition among all groups, which may have potential for the treatment of prostate cancer due to an improved therapeutic ratio. (paper)

MR-guided pulsed high intensity focused ultrasound enhancement of docetaxel combined with radiotherapy for prostate cancer treatment

Science.gov (United States)

Mu, Zhaomei; Ma, C.-M.; Chen, Xiaoming; Cvetkovic, Dusica; Pollack, Alan; Chen, Lili

2012-01-01

The purpose of this study is to evaluate the efficacy of the enhancement of docetaxel by pulsed focused ultrasound (pFUS) in combination with radiotherapy (RT) for treatment of prostate cancer in vivo. LNCaP cells were grown in the prostates of male nude mice. When the tumors reached a designated volume by MRI, tumor bearing mice were randomly divided into seven groups (n = 5): (1) pFUS alone; (2) RT alone; (3) docetaxel alone; (4) docetaxel + pFUS (5) docetaxel + RT (6) docetaxel + pFUS + RT, and (7) control. MR-guided pFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner. Animals were treated once with pFUS, docetaxel, RT or their combinations. Docetaxel was given by i.v. injection at 5 mg kg-1 before pFUS. RT was given 2 Gy after pFUS. Animals were euthanized 4 weeks after treatment. Tumor volumes were measured on MRI at 1 and 4 weeks post-treatment. Results showed that triple combination therapies of docetaxel, pFUS and RT provided the most significant tumor growth inhibition among all groups, which may have potential for the treatment of prostate cancer due to an improved therapeutic ratio.

MR-guided pain therapy: principles and clinical applications; MR-gesteuerte Schmerztherapie: Prinzipien und klinische Applikationen

Energy Technology Data Exchange (ETDEWEB)

Fritz, J.; Pereira, P.L. [Diagnostische Radiologie, Eberhard-Karls-Universitaet, Tuebingen (Germany)

2007-09-15

X-ray fluoroscopy and computed tomography are frequently used to perform percutaneous interventions in pain therapy. The development of MR-compatible therapy needles now allows these interventions to be performed under MR imaging guidance. MR-guided interventions may be performed using most clinical MR scanners; however, systems with an open configuration are advantageous. Multiplanar pre- and intra-procedural MR imaging provides the interventionalist with essential information, such as evaluation of anatomy and pathology, as well as the planning of the procedure and monitoring of fluid distribution without the use of contrast agents. With the use of non-ionizing radiation, interventional MR imaging is especially suited for the treatment of children and young adults as well as for serial injection therapy. For spinal MR interventions, passive needle visualization is an easily achievable and reliable method. The resulting needle artifact is influenced by several factors such as the alloy of the needle, the strength of the static magnetic field, the sequence type, the spatial orientation of the therapy needle as well as the echo time and may further be optimized during the intervention by alteration of the last three factors. Fast acquisition techniques and image processing allow for continuous, near real-time MR imaging (so-called MR fluoroscopy) and interactive needle navigations, comparable to X-ray fluoroscopy and CT fluoroscopy. The purpose of this review is to illustrate and discuss general concepts of interventional MR imaging. A spectrum of interventional MR imaging procedures in spinal pain therapy is described and illustrated, including procedures such as lumbar facet joint injections, sacroiliac joint injections, lumbar spinal nerve root infiltrations and drug delivery to the lumbar sympathetic chain. (orig.)

Experimental validation of hyperthermia SAR treatment planning using MR B1+ imaging

International Nuclear Information System (INIS)

Berg, Cornelis A T van den; Bartels, Lambertus W; Leeuw, Astrid A C De; Lagendijk, Jan J W; Kamer, Jeroen B Van de

2004-01-01

In this paper the concept of using B 1+ imaging as a means to validate SAR models for radiofrequency hyperthermia is presented. As in radiofrequency hyperthermia, in common clinical MR imaging which applies RF frequencies between 64 and 128 MHz, the RF field distribution inside a patient is largely determined by the dielectric distribution of the anatomy. Modern MR imaging techniques allow measurement of the RF magnetic field component B 1+ making it possible to measure at high resolution the dielectric interaction of the RF field with the patient. Given these considerations, we propose to use MR imaging to verify the validity of our dielectric patient model used for SAR models of radiofrequency hyperthermia. The aim of this study was to investigate the feasibility of this concept by performing B 1+ measurements and simulations on cylindrical split phantoms consisting of materials with dielectric properties similar to human tissue types. Important topics of investigation were the accuracy and sensitivity of B 1+ measurements and the validity of the electric model of the MR body coil. The measurements were performed on a clinical 1.5 T MR scanner with its quadrature body coil operating at 64 MHz. It was shown that even small B 1+ variations of 2 to 5% could be measured reliably in the phantom experiments. An electrical model of the transmit coil was implemented on our FDTD-based hyperthermia treatment planning platform and the RF field distributions were calculated assuming an idealized quadrature current distribution in the coil. A quantitatively good correlation between measurements and simulations was found for phantoms consisting of water and oil, while highly conductive phantoms show considerable deviations. However, assuming linear excitation for these conductive phantoms resulted in good correspondence. As an explanation it is suggested that the coil is being detuned due to the inductive nature of the conductive phantoms, breaking up the phase difference of �

Functional expression of 5-HT{sub 2A} receptor in osteoblastic MC3T3-E1 cells

Energy Technology Data Exchange (ETDEWEB)

Hirai, Takao; Kaneshige, Kota; Kurosaki, Teruko [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan); Nishio, Hiroaki, E-mail: nishio@fupharm.fukuyama-u.ac.jp [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan)

2010-05-28

In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT{sub 2} receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT{sub 2A} and 5-HT{sub 2C} receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT{sub 2A} receptor specific antagonist. Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT{sub 2A} receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells.

Fracture behavior of unirradiated HT-9 and modified 9Cr-1Mo welds

International Nuclear Information System (INIS)

Huang, F.H.; Gelles, D.S.

1983-05-01

Fracture toughness tests on HT-9 weld and HAZ samples and modified 9Cr-1Mo weld samples were performed at 93, 205, 427 and 538 0 C. Specimens were of circular compact tension type fabricated from welded material with the notch orientation parallel to the fusion line. The test results were analyzed using the J-integral approach. The results demonstrated that the toughness of HT-9 and 9Cr-1Mo was not significantly reduced due to welding. However, the tearing modulus of the welded material was lower than that of base metal, indicating that the alloys become less resistant to crack propagation as a result of welding

NASA Goddards LiDAR, Hyperspectral and Thermal (G-LiHT) Airborne Imager

Science.gov (United States)

Cook, Bruce D.; Corp, Lawrence A.; Nelson, Ross F.; Middleton, Elizabeth M.; Morton, Douglas C.; McCorkel, Joel T.; Masek, Jeffrey G.; Ranson, Kenneth J.; Ly, Vuong; Montesano, Paul M.

2013-01-01

The combination of LiDAR and optical remotely sensed data provides unique information about ecosystem structure and function. Here, we describe the development, validation and application of a new airborne system that integrates commercial off the shelf LiDAR hyperspectral and thermal components in a compact, lightweight and portable system. Goddard's LiDAR, Hyperspectral and Thermal (G-LiHT) airborne imager is a unique system that permits simultaneous measurements of vegetation structure, foliar spectra and surface temperatures at very high spatial resolution (approximately 1 m) on a wide range of airborne platforms. The complementary nature of LiDAR, optical and thermal data provide an analytical framework for the development of new algorithms to map plant species composition, plant functional types, biodiversity, biomass and carbon stocks, and plant growth. In addition, G-LiHT data enhance our ability to validate data from existing satellite missions and support NASA Earth Science research. G-LiHT's data processing and distribution system is designed to give scientists open access to both low- and high-level data products (http://gliht.gsfc.nasa.gov), which will stimulate the community development of synergistic data fusion algorithms. G-LiHT has been used to collect more than 6,500 km2 of data for NASA-sponsored studies across a broad range of ecoregions in the USA and Mexico. In this paper, we document G-LiHT design considerations, physical specifications, instrument performance and calibration and acquisition parameters. In addition, we describe the data processing system and higher-level data products that are freely distributed under NASA's Data and Information policy.

MR imaging of sacral and perisacral lesions

International Nuclear Information System (INIS)

Wetzel, L.H.; Levine, E.; Murphey, M.D.

1987-01-01

This exhibit demonstrates the utility of MR imaging in evaluating sacral and perisacral lesions. Thirty-two lesions were studied using a superconducting 1.0-T MR imager. Eleven primary and 13 metastatic tumors, four congenital lesions, and four arachnoid cysts were evaluated. MR did not usually enable a more specific histologic diagnosis than other imaging techniques. However, extraosseous and proximal spinal extent of tumors was well defined without use of oral or intravenous contrast material. MR imaging is an excellent noninvasive technique for evaluating most sacral and perisacral lesions and is particularly helpful when precise tumor extent must be determined for treatment planning

Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach

DEFF Research Database (Denmark)

Haugbøl, Steven; Pinborg, Lars H; Arfan, Haroon M

2006-01-01

PURPOSE: To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach. Further, to estimate the sample size needed to detect regional differences between two groups and, finally, to evaluate how partial volume correction affects...... reproducibility and the required sample size. METHODS: For assessment of the variability, six subjects were investigated with [18F]altanserin PET twice, at an interval of less than 2 weeks. The sample size required to detect a 20% difference was estimated from [18F]altanserin PET studies in 84 healthy subjects....... Regions of interest were automatically delineated on co-registered MR and PET images. RESULTS: In cortical brain regions with a high density of 5-HT2A receptors, the outcome parameter (binding potential, BP1) showed high reproducibility, with a median difference between the two group measurements of 6...

Integrative analysis of cardiac function and metabolism in patients with idiopathic hypertrophic cardiomyopathy with H-1 cine MR imaging and P-31 MR spectroscopy

International Nuclear Information System (INIS)

Wagner, S.; Chew, W.M.; Semelka, R.; Tomei, E.; Caputo, G.; O'Sullivan, M.; Chatterjee, K.; Parmley, W.W.; Wolfe, C.L.; Higgins, C.B.

1989-01-01

The purpose of the study was to use MR imaging and P-31 spectroscopy for the functional and metabolic characterization of patients with hypertrophic cardiomyopathy (HCM). Nine patients with HCM underwent combined P-31 spectroscopy (one-dimensional chemical shift imaging) and MR imaging at 1.5 T. MR imaging localized the distribution of ventricular hypertrophy and cine MR imaging quantitated cardiac volumes, contractility, and left ventricular mass. The phosphodiester/phosphocreatine ratio (PDE/PCr) in six HCM patients was not different from normal, but in three patients it was significantly (P <.01) higher. This finding could not be attributed to contractible abnormalities, the distribution of hypertrophy, or the left ventricular mass. The abnormal PDE/PCr ratio was found only in patients with echocardiographic findings of resting left ventricular outflow obstruction but was not associated with severity or distribution of hypertrophy. The study shows the use of combined MR imaging and MR spectroscopy to characterize HCM and possibly to identify abnormal myocardial tissue

AVN-211, Novel and Highly Selective 5-HT6 Receptor Small Molecule Antagonist, for the Treatment of Alzheimer's Disease.

Science.gov (United States)

Ivachtchenko, Alexandre V; Lavrovsky, Yan; Ivanenkov, Yan A

2016-03-07

Within the past decade several novel targets have been indicated as key players in Alzheimer-type dementia and associated conditions, including a "frightening" memory loss as well as severe cognitive impairments. These proteins are deeply implicated in crucial cell processes, e.g., autophagy, growth and progression, apoptosis, and metabolic equilibrium. Since recently, 5-HT6R has been considered as one of the most prominent biological targets in AD drug therapy. Therefore, we investigated the potential procognitive and neuroprotective effects of our novel selective 5-HT6R antagonist, AVN-211. During an extensive preclinical evaluation the lead compound demonstrated a relatively high therapeutic potential and improved selectivity toward 5-HT6R as compared to reference drug candidates. It was thoroughly examined in different in vivo behavioral models directly related to AD and showed evident improvements in cognition and learning. In many cases, the observed effect was considerably greater than that determined for the reported drugs and drug candidates, including memantine, SB-742457, and Lu AE58054, evaluated under the same conditions. In addition, AVN-211 showed a similar or better anxiolytic efficacy than fenobam, rufinamide, lorazepam, and buspirone in an elevated plus-maze model, elevated platform, and open field tests. The compound demonstrated low toxicity and no side effects in vivo, an appropriate pharmacokinetic profile, and stability. In conclusion, AVN-211 significantly delayed or partially halted the progressive decline in memory function associated with AD, which makes it an interesting drug candidate for the treatment of neurodegenerative and psychiatric disorders. Advanced clinical trials are currently under active discussion and in high priority.

Implication of 5-HT(2B) receptors in the serotonin syndrome.

Science.gov (United States)

Diaz, Silvina Laura; Maroteaux, Luc

2011-09-01

The serotonin (5-HT) syndrome occurs in humans after antidepressant overdose or combination of drugs inducing a massive increase in extracellular 5-HT. Several 5-HT receptors are known to participate in this syndrome in humans and animal models. The 5-HT(2B) receptor has been proposed as a positive modulator of serotonergic activity, but whether it is involved in 5-HT syndrome has not yet been studied. We analyzed here, a putative role of 5-HT(2B) receptors in this disorder by forced swimming test (FST) and behavioral assessment in the open field. In FST, genetic (5-HT(2B)(-/-) mice) or pharmacological (antagonist RS127445 at 0.5 mg/kg) ablation of 5-HT(2B) receptors facilitated selective 5-HT reuptake inhibitors (SSRI)-induced increase of immobility time as well as expression of other symptoms related to 5-HT syndrome like hind limb abduction and Straub tail. Increase in immobility was also developed in FST by both wild type (WT) and 5-HT(2B)(-/-) mice after the administration of 5-HT(1A), 5-HT(2A) or 5-HT(2C) receptor agonists, 8-OH-DPAT (5 mg/kg), DOI (1 mg/kg), or WAY161503 (5 mg/kg), respectively. In contrast, the 5-HT(2B) receptor agonist BW723C86 (3 mg/kg) or 5-HT(1B) receptor agonist CGS12066A (2 mg/kg) decreased immobility time in both genotypes. The 5-HT syndrome induced by fluoxetine at high doses was blocked in WT and 5-HT(2B)(-/-) mice by administration of 5-HT(1A) and 5-HT(2C) receptor antagonists (WAY100635 0.5 mg/kg and SB242084 0.5 mg/kg) but not by the 5-HT(2A) receptor antagonist MDL100907 (1 mg/kg). By behavioral assessment, we confirmed that 5-HT(2B)(-/-) mice were more prone to develop 5-HT syndrome symptoms after administration of high dose of SSRIs or the 5-HT precursor 5-Hydroxytryptophan, 5-HTP, even if increases in 5-HT plasma levels were similar in both genotypes. This evidence suggests that the presence of 5-HT(2B) receptors hinders acute 5-HT toxicity once high levels of 5-HT are attained. Therefore, differential agonism

Multidisciplinary Functional MR Imaging for Prostate Cancer

International Nuclear Information System (INIS)

Kim, Jeong Kon; Jang, Yun Jin; Cho, Gyung Goo

2009-01-01

Various functional magnetic resonance (MR) imaging techniques are used for evaluating prostate cancer including diffusion-weighted imaging, dynamic contrast- enhanced MR imaging, and MR spectroscopy. These techniques provide unique information that is helpful to differentiate prostate cancer from non-cancerous tissue and have been proven to improve the diagnostic performance of MRI not only for cancer detection, but also for staging, post-treatment monitoring, and guiding prostate biopsies. However, each functional MR imaging technique also has inherent challenges. Therefore, in order to make accurate diagnoses, it is important to comprehensively understand their advantages and limitations, histologic background related with image findings, and their clinical relevance for evaluating prostate cancer. This article will review the basic principles and clinical significance of functional MR imaging for evaluating prostate cancer

MR guided percutaneous laser lumbar disk hernia ablation

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Takuo; Terao, Tohru; Ishibashi, Toshihiro; Yuhki, Ichiro; Harada, Junta; Tashima, Michiko [Jikei Univ., Chiba (Japan). Kashiwa Hospital; Abe, Toshiaki

1998-03-01

An MRI unit for interventional procedure is very useful for minimally invasive surgery of the brain and spine. Percutaneous laser disc decompression (PLDD) utilizing X-ray fluoroscopy is a relatively new less invasive procedure for treatment of lumbar disc herniation. MR guided laser surgery is applied to patients with disc herniation at our department. Approaching the target of the disc protrusion was easily conducted and vaporizing the disc hernia directly using a laser was possible under MR fluoroscopy. The purpose of the present study is to evaluate the usefulness of MR guided percutaneous laser disc hernia ablation (MR-guided PLDHA). As subjects, 36 patients with lumbar disc herniation, including 23 cases with L4/5 involvement and 13 cases with L5/S1 involvement were studied. Among these, 26 were males and 10 were females, age ranging from 24 to 62. We used an open type MR system (Hitachi, Airis 0.3T), a permanent, open configuration MR system. A YAG laser (LaserScope, USA) was used for PLDHA. An MR compatible 18G titanium needle 15 cm in length was used to puncture the herniated discs. The MR compatible needle was clearly visualized, and used to safely and accurately puncture the target herniated disc in each case with multidimensional guidance. Application of the laser was performed with MR guidance. The energy dose from the laser ranged from 800 to 2100 joules. In most cases, signs and symptoms improved in the patients immediately after disc vaporization. The overall success rate was 88.9%. The complication rate was 2.8%, including one case of discitis after PLDHA. MR fluoroscopy sequence permits near real time imaging and provides an easy approach to the therapeutic target of disc herniation. MR guided PLDHA is a minimally invasive procedure and is very useful for the treatment of lumbar disc protrusion. (author)

MR guided percutaneous laser lumbar disk hernia ablation

International Nuclear Information System (INIS)

Hashimoto, Takuo; Terao, Tohru; Ishibashi, Toshihiro; Yuhki, Ichiro; Harada, Junta; Tashima, Michiko; Abe, Toshiaki.

1998-01-01

An MRI unit for interventional procedure is very useful for minimally invasive surgery of the brain and spine. Percutaneous laser disc decompression (PLDD) utilizing X-ray fluoroscopy is a relatively new less invasive procedure for treatment of lumbar disc herniation. MR guided laser surgery is applied to patients with disc herniation at our department. Approaching the target of the disc protrusion was easily conducted and vaporizing the disc hernia directly using a laser was possible under MR fluoroscopy. The purpose of the present study is to evaluate the usefulness of MR guided percutaneous laser disc hernia ablation (MR-guided PLDHA). As subjects, 36 patients with lumbar disc herniation, including 23 cases with L4/5 involvement and 13 cases with L5/S1 involvement were studied. Among these, 26 were males and 10 were females, age ranging from 24 to 62. We used an open type MR system (Hitachi, Airis 0.3T), a permanent, open configuration MR system. A YAG laser (LaserScope, USA) was used for PLDHA. An MR compatible 18G titanium needle 15 cm in length was used to puncture the herniated discs. The MR compatible needle was clearly visualized, and used to safely and accurately puncture the target herniated disc in each case with multidimensional guidance. Application of the laser was performed with MR guidance. The energy dose from the laser ranged from 800 to 2100 joules. In most cases, signs and symptoms improved in the patients immediately after disc vaporization. The overall success rate was 88.9%. The complication rate was 2.8%, including one case of discitis after PLDHA. MR fluoroscopy sequence permits near real time imaging and provides an easy approach to the therapeutic target of disc herniation. MR guided PLDHA is a minimally invasive procedure and is very useful for the treatment of lumbar disc protrusion. (author)

Time-course of 5-HT(6) receptor mRNA expression during memory consolidation and amnesia.

Science.gov (United States)

Huerta-Rivas, A; Pérez-García, G; González-Espinosa, C; Meneses, A

2010-01-01

Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptor(6) (5-HT(6)) improve memory and reverse amnesia although the mechanisms involved are poorly understood. Hence, in this paper RT-PCR was used to evaluate changes in mRNA expression of 5-HT(6) receptor in trained and untrained rats treated with the 5-HT(6) receptor antagonist SB-399885 and amnesic drugs scopolamine or dizocilpine. Changes in mRNA expression of 5-HT(6) receptor were investigated at different times in prefrontal cortex, hippocampus and striatum. Data indicated that memory in the Pavlovian/instrumental autoshaping task was a progressive process associated to reduced mRNA expression of 5-HT(6) receptor in the three structures examined. SB-399885 improved long-term memory at 48h, while the muscarinic receptor antagonist scopolamine or the non-competitive NMDA receptor antagonist dizocilpine impaired it at 24h. Autoshaping training and treatment with SB-399885 increased 5-HT(6) receptor mRNA expression in (maximum increase) prefrontal cortex and striatum, 24 or 48h. The scopolamine-induced amnesia suppressed 5-HT(6) receptor mRNA expression while the dizocilpine-induced amnesia did not modify 5-HT(6) receptor mRNA expression. SB-399885 and scopolamine or dizocilpine were able to reestablish memory and 5-HT(6) receptor mRNA expression. These data confirmed previous memory evidence and of more interest is the observation that training, SB-399885 and amnesic drugs modulated 5-HT(6) receptor mRNA expression in prefrontal cortex, hippocampus and striatum. Further investigation in different memory tasks, times and amnesia models together with more complex control groups might provide further clues. Copyright 2009 Elsevier Inc. All rights reserved.

Irradiation experience with HT9-clad metallic fuel

International Nuclear Information System (INIS)

Pahl, R.G.; Lahm, C.E.; Tsai, H.; Billone, M.C.

1991-01-01

The safe and reliable performance of metallic fuel is currently under study and demonstration in the Integral Fast Reactor program. In-reactor tests of HT9-clad metallic fuel have now reached maturity and have all shown good performance characteristics to burnups exceeding 17.5 at. % in the lead assembly. Because this low-swelling tempered martensitic alloy is the cladding of choice for high fluence applications, the experimental observations and performance modelling efforts reported in this paper play an important role in demonstrating reliability

Magnetic sensorless control experiment without drift problem on HT-7

International Nuclear Information System (INIS)

Nakamura, K.; Luo, J.R.; Wang, H.Z.; Ji, Z.S.; Wang, H.; Wang, F.; Qi, N.; Sato, K.N.; Hanada, K.; Sakamoto, M.; Idei, H.; Hasegawa, M.; Iyomasa, A.; Kawasaki, S.; Nakashima, H.; Higashijima, A.

2006-01-01

Magnetic sensorless control experiments of the plasma horizontal position have been carried out in the superconducting tokamak HT-7. Previously the horizontal position was calculated from the vertical field coil current and voltage without using signals of magnetic sensors like magnetic coils and flux loops placed near the plasma. The calculations are made focusing on the ripple frequency component of the power supply with thyristor and directly from them without time integration. There is no drift problem of integrator of magnetic sensors. Two kinds of experiments were carried out, to keep the position constant and swing the position in a triangular waveform

Value of MR-guided localization and biopsy in breast lesions; Stellenwert der MR-gestuetzten Lokalisation und Biopsie von Brustlaesionen

Energy Technology Data Exchange (ETDEWEB)

Obenauer, S.; Grabbe, E.; Knollmann, F. [Abt. Diagnostische Radiologie, Georg-August-Univ. Goettingen (Germany)

2006-05-15

Contrast-enhanced dynamic MR mammography can provide important additional diagnostic information when performed for certain indications. When suspicious lesions are identified on MR mammography and cannot be reproduced using other imaging modalities, a decision must be made as to its management, i.e. further diagnostic work-up. One possibility is the short-term follow-up of such findings, resulting in higher costs and a possible delay in the start of treatment of a malignant lesion. An alternative to a follow-up is an MR-guide intervention. MR-compatible equipment has been developed for this purpose. This includes equipment specialized for percutaneous biopsy and preoperative localization. The following is an overview of the diagnostic value of MR-guided biopsy and preoperative localization including the relevant literature. (orig.)

MR findings of wernicke encephalopathy

International Nuclear Information System (INIS)

Yoon, Hyun Ki; Chang, Kee Hyun; Lee, Goo; Han, Moon Hee; Park, Sung Ho; Na, Duk Yull; Song, Chi Sung

1991-01-01

Seven patients (33 to 58 years old) with clinical diagnoses of Wernicke encephalopathy were examined with MR on either a 2.0T (5 cases) or a 0.5T scanner (2 cases) using spin-echo pulse sequences. In 2 patients, follow-up MR studies were performed 1 and 5 weeks after thiamine (vitamine B1) treatment. Five patients (4 chronic alcoholics and 1 with hyperemesis gravidarum) showed atrophy of both mamillary bodies, along with patchy lesions around the third ventricle, medial thalami, tectum of the midbrain, and periaqueductal gray matter. Another patient with hyperemesis of gravidrum demonstrated only slightly atrophic mamillary bodies, and the last patient with severe vomiting after gastrojejunostomy showed only diencephaic/mesencephalic lesions with apparently normal mamillary bodies. A follow-up MR showed a decrease in previously-noted diencephalic/-/mesencephalic lesions but no change in the size of the mamillary bodies. Diencephalic/mesencephalic lesions were well seen as a high-signal intensity on proton-and T2-weighted axial images, while atrophy of the mamillary bodies was seen best on T1-weighted sagittal images. MR imaging is very useful in demonstrating the characteristic lesions of Wernicke encephalopathy and in evaluating the result of treatment on follow-up study

Diffusion and Perfusion MR Imaging in Acute Stroke: Clinical Utility and Potential Limitations for Treatment Selection

DEFF Research Database (Denmark)

Bateman, Mathew; Slater, Lee-Anne; Leslie-Mazwi, Thabele M

2017-01-01

Magnetic resonance (MR) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) offer unique insight into acute ischemic stroke pathophysiology. These techniques may offer the ability to apply pathophysiology to accurately individualize acute stroke reperfusion treatment, including ...... to be investigated in ongoing randomized controlled trials, and continued research into these techniques will help achieve the goal of tissue-based decision making and individualized acute stroke treatment....... extending the opportunity of reperfusion treatment to well beyond the current time-based treatment windows. This review examines the use of DWI and PWI in the major stroke trials, their current clinical utility, and potential limitations for reperfusion treatment selection. DWI and PWI continue...

TU-F-BRB-03: Clinical Implementation of MR-Based Motion Management

International Nuclear Information System (INIS)

Glide-Hurst, C.

2015-01-01

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has high temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant

TU-F-BRB-03: Clinical Implementation of MR-Based Motion Management

Energy Technology Data Exchange (ETDEWEB)

Glide-Hurst, C. [Henry Ford Health System (United States)

2015-06-15

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has high temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.

MR-guided MR arthrography of the shoulder

International Nuclear Information System (INIS)

Tratting, S.; Breitenseher, M.; Pretterklieber, M.; Kontaxis, G.; Rand, T.; Imhof, H.

1996-01-01

Purpose: To develop an MR-guided technique for joint puncture in MR arthrography of the shoulder and to confirm the intracapsular position of the needle tip by visualization of the flow of contrast media into the joint. Materials and methods: Three unfixed human shoulder joint specimens were examined on a 1.0 T unit. The optimal point of entrance and depth for joint puncture were estimated by means of MR-compatible markers on the skin. Needle orientation and localization of the needle tip (MR-compatible 22-gauge needle) in the shoulder joint were monitored by rapid localizer gradient-echo sequences in two orthogonal planes. To confirm the intracapsular position of the needle tip, diluted gadolinium-DTPA was administered via a long connecting tube and the flow of contrast media into the joint was viewed directly on an LCD screen using real-time MR imaging (local look technique). Results: The MR-compatible markers on the skin allowed determination of the optimal point of entrance and estimation of the depth for joint puncture. Passive visualization of the MR-compatible needle due to spin dephasing and signal loss provided adequate localization of the intra-articular needle tip position in all specimens, although significant artefacts were present on rapid localizer gradient-echo sequences with an increase in width of the apparent needle shaft. Real-time MR imaging of the flow of contrast media was possible using the local look technique and the LCD screen of the MR unit and allowed confirmation of the intracapsular position. Conclusion: MR-guided joint puncture and real-time MR-assisted contrast media application results in improved MR arthrography and may replace conventional fluoroscopic guidance. (orig.) [de

AVN-492, A Novel Highly Selective 5-HT6R Antagonist: Preclinical Evaluation.

Science.gov (United States)

Ivachtchenko, Alexandre V; Okun, Ilya; Aladinskiy, Vladimir; Ivanenkov, Yan; Koryakova, Angela; Karapetyan, Ruben; Mitkin, Oleg; Salimov, Ramiz; Ivashchenko, Andrey

2017-01-01

Discovery of 5-HT6 receptor subtype and its exclusive localization within the central nervous system led to extensive investigations of its role in Alzheimer's disease, schizophrenia, and obesity. In the present study, we present preclinical evaluation of a novel highly-potent and highly-selective 5-HT6R antagonist, AVN-492. The affinity of AVN-492 to bind to 5-HT6R (Ki = 91 pM) was more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (Ki = 170 nM). Thus, the compound displayed great 5-HT6R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc. AVN-492 demonstrates good in vitro and in vivo ADME profile with high oral bioavailability and good brain permeability in rodents. In behavioral tests, AVN-492 shows anxiolytic effect in elevated plus-maze model, prevents an apomorphine-induced disruption of startle pre-pulse inhibition (the PPI model) and reverses a scopolamine- and MK-801-induced memory deficit in passive avoidance model. No anti-obesity effect of AVN-492 was found in a murine model. The data presented here strongly indicate that due to its high oral bioavailability, extremely high selectivity, and potency to block the 5-HT6 receptor, AVN-492 is a very promising tool for evaluating the role the 5-HT6 receptor might play in cognitive and neurodegenerative impairments. AVN-492 is an excellent drug candidate to be tested for treatment of such diseases, and is currently being tested in Phase I trials.

Evaluation of portal hypertension by MR portography

International Nuclear Information System (INIS)

Nagaoka, Shirou; Hagiwara, Masaru; Imanisi, Yosimasa

1997-01-01

Seventy-eight examinations of MR portography were totally performed in 24 controls and 33 patients with esophageal varices. Portal vein, SMV, hepatic vein, and IVC were entirely depicted in 21, 24, 22, and 24, respectively, of the 24 controls. As to intrahepatic upward branches of portal vein in the right lobe of the liver, the 4th branch was at least depicted in all of the 24. Although the portal vein trunk and SMV were entirely depicted in all of the 8 patients without treatment and liver dysfunction of Child A, there was no depiction of them in 1 of the 8 patients with liver dysfunction of Child B, and 1 of 5 patients with liver dysfunction of Child C. The 4th upward branch of portal vein in the right lobe of the liver was depicted in none of the 33 patients. Besides, none of the intrahepatic portal branches were depicted in 1 of 8 patients without treatment and liver dysfunction of Child B, and 1 of the 5 patients without treatment and liver dysfunction of Child C. There was a significant difference of depicted terminal upward branch of portal vein between the controls and patients without any treatment. In the patients without any significant difference of depicted terminal upward branch of portal vein was also present between Child's classification A and Child's classification B and C. Gastric coronary vein varices were detected by MR portography is 18 of 19 patients without treatment on the esophageal varices, and paraesophageal/esophageal varices were also depicted by MR portography in 13 of the 19. The collaterals were depicted by MR portography in all of the 6 patients with recurrent collaterals after Hassab's operation or splenectomy. MR portography was able to depict flow in trunk branches and collaterals of the portal vein system in a physiological state. (K.H.)

Evaluation of portal hypertension by MR portography

Energy Technology Data Exchange (ETDEWEB)

Nagaoka, Shirou; Hagiwara, Masaru; Imanisi, Yosimasa [St. Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine

1997-02-01

Seventy-eight examinations of MR portography were totally performed in 24 controls and 33 patients with esophageal varices. Portal vein, SMV, hepatic vein, and IVC were entirely depicted in 21, 24, 22, and 24, respectively, of the 24 controls. As to intrahepatic upward branches of portal vein in the right lobe of the liver, the 4th branch was at least depicted in all of the 24. Although the portal vein trunk and SMV were entirely depicted in all of the 8 patients without treatment and liver dysfunction of Child A, there was no depiction of them in 1 of the 8 patients with liver dysfunction of Child B, and 1 of 5 patients with liver dysfunction of Child C. The 4th upward branch of portal vein in the right lobe of the liver was depicted in none of the 33 patients. Besides, none of the intrahepatic portal branches were depicted in 1 of 8 patients without treatment and liver dysfunction of Child B, and 1 of the 5 patients without treatment and liver dysfunction of Child C. There was a significant difference of depicted terminal upward branch of portal vein between the controls and patients without any treatment. In the patients without any significant difference of depicted terminal upward branch of portal vein was also present between Child`s classification A and Child`s classification B and C. Gastric coronary vein varices were detected by MR portography is 18 of 19 patients without treatment on the esophageal varices, and paraesophageal/esophageal varices were also depicted by MR portography in 13 of the 19. The collaterals were depicted by MR portography in all of the 6 patients with recurrent collaterals after Hassab`s operation or splenectomy. MR portography was able to depict flow in trunk branches and collaterals of the portal vein system in a physiological state. (K.H.)

Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.

Science.gov (United States)

Meneses, Alfredo

2004-12-06

There is an important debate regarding the functional role of the 5-HT(1A) and 5-HT(7) receptor in memory systems. Hence, the objective of this paper is to investigate the function of serotonin (5-hydroxytryptamine, 5-HT) in memory consolidation, utilising an autoshaping Pavlovian/instrumental learning test. Specific antagonists at 5-HT(1A) (WAY 100635) and 5-HT(7) (SB-269970 or DR 4004) receptors administered i.p. or s.c.) after training, significantly decreased the improvement of performance produced by the 5-HT(1A/7) agonist 8-OH-DPAT to levels lower than controls'. These same antagonists attenuated the decreased level of performance produced by mCPP, although they decrease the performance levels after p-chloroamphetamine (PCA) lesion of the 5-HT system, which has no effect on its own on the conditioned response. Moreover, SB-269970 or DR 4004 reversed amnesia induced by scopolamine and dizocilpine. These data confirm a role for 5-HT(1A) and 5-HT(7) receptors in memory formation and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals. These findings support a potential role for both 5-HT(1A) and 5-HT(7) receptors in the pathophysiology and/or treatment of schizophrenia, cognitive deficits and the mechanism of action of atypical antipsychotic drugs.

Pavement subgrade MR design values for Michigan's seasonal changes : final report.

Science.gov (United States)

2009-07-22

The resilient modulus (MR) of roadbed soil plays an integral role in the design of pavement systems. Currently, the : various regions of the Michigan Department of Transportation (MDOT) use different procedures to determine the : MR values. Most of t...

Computer modelling of HT gas metabolism in humans

International Nuclear Information System (INIS)

Peterman, B.F.

1982-01-01

A mathematical model was developed to simulate the metabolism of HT gas in humans. The rate constants of the model were estimated by fitting the calculated curves to the experimental data by Pinson and Langham in 1957. The calculations suggest that the oxidation of HT gas (which probably occurs as a result of the enzymatic action of hydrogenase present in bacteria of human gut) occurs at a relatively low rate with a half-time of 10-12 hours. The inclusion of the dose due to the production of the HT oxidation product (HTO) in the soft tissues lowers the value of derived air concentration by about 50%. Furthermore the relationship between the concentration of HTO in urine and the dose to the lung from HT in the air in lungs is linear after short HT exposures, and hence HTO concentrations in urine can be used to estimate the upper limits on the lung dose from HT exposures. (author)

Image Fusion of CT and MR with Sparse Representation in NSST Domain

Directory of Open Access Journals (Sweden)

Chenhui Qiu

2017-01-01

Full Text Available Multimodal image fusion techniques can integrate the information from different medical images to get an informative image that is more suitable for joint diagnosis, preoperative planning, intraoperative guidance, and interventional treatment. Fusing images of CT and different MR modalities are studied in this paper. Firstly, the CT and MR images are both transformed to nonsubsampled shearlet transform (NSST domain. So the low-frequency components and high-frequency components are obtained. Then the high-frequency components are merged using the absolute-maximum rule, while the low-frequency components are merged by a sparse representation- (SR- based approach. And the dynamic group sparsity recovery (DGSR algorithm is proposed to improve the performance of the SR-based approach. Finally, the fused image is obtained by performing the inverse NSST on the merged components. The proposed fusion method is tested on a number of clinical CT and MR images and compared with several popular image fusion methods. The experimental results demonstrate that the proposed fusion method can provide better fusion results in terms of subjective quality and objective evaluation.

5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.

Science.gov (United States)

Ferguson, Marcus C; Nayyar, Tultul; Deutch, Ariel Y; Ansah, Twum A

2010-01-01

Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease. Published by Elsevier Ltd.

Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese Ay mice

International Nuclear Information System (INIS)

Nonogaki, Katsunori; Nozue, Kana; Oka, Yoshitomo

2006-01-01

Serotonin (5-hydroxytryptamine; 5-HT) 2A receptors contribute to the effects of 5-HT on platelet aggregation and vascular smooth muscle cell proliferation, and are reportedly involved in decreases in plasma levels of adiponectin, an adipokine, in diabetic subjects. Here, we report that systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, 5-HT2C, and 5-HT1B receptor gene expression. A y mice, which have ectopic expression of the agouti protein, significantly increased hypothalamic 5-HT2A receptor gene expression in association with obesity compared with wild-type mice matched for age. Systemic administration of sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese A y mice, whereas it did not increase plasma adiponectin levels. These results suggest that obesity increases hypothalamic 5-HT2A receptor gene expression, and pharmacologic inactivation of 5-HT2A receptors inhibits overfeeding and obesity in A y mice, but did not increase plasma adiponectin levels

MDMA self-administration fails to alter the behavioral response to 5-HT(1A) and 5-HT(1B) agonists.

Science.gov (United States)

Aronsen, Dane; Schenk, Susan

2016-04-01

Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT(1A) and 5-HT(1B) receptor subtypes since they have been implicated in several of the behaviors that have been shown to be impacted in ecstasy users and in animals exposed to MDMA. This study aimed to determine the effect of extensive MDMA self-administration on behavioral responses to the 5-HT(1A) agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), and the 5-HT(1B/1A) agonist, RU 24969. Male Sprague-Dawley rats self-administered a total of 350 mg/kg MDMA, or vehicle, over 20-58 daily self-administration sessions. Two days after the last self-administration session, the hyperactive response to 8-OH-DPAT (0.03-1.0 mg/kg) or the adipsic response to RU 24969 (0.3-3.0 mg/kg) were assessed. 8-OH-DPAT dose dependently increased horizontal activity, but this response was not altered by MDMA self-administration. The dose-response curve for RU 24969-produced adipsia was also not altered by MDMA self-administration. Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT(1A) or 5-HT(1B) receptor mechanisms.

Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice.

Science.gov (United States)

Lee, Min Jung; Cho, Kang Hun; Park, Hyun Min; Sung, Hyun Jung; Choi, Sunghak; Im, Weonbin

2014-07-15

DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation. Copyright © 2014 Elsevier B.V. All rights reserved.

Design and validation of an MR-conditional robot for transcranial focused ultrasound surgery in infants

Energy Technology Data Exchange (ETDEWEB)

Price, Karl D., E-mail: karl.price@sickkids.ca [Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, Ontario M5G 1X8 (Canada); The Department of Mechanical Engineering, The University of Toronto, Toronto, Ontario M5S 3G8 (Canada); Sin, Vivian W. [Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, Ontario M5G 1X8 (Canada); Mougenot, Charles [Philips Healthcare Canada, Markham, Ontario L6C 2S3 (Canada); Pichardo, Samuel [Electrical Engineering, Lakehead University, Thunder Bay, Ontario P7B 5E1 (Canada); Looi, Thomas [Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, Ontario M5G 1X8 (Canada); The Institute of Biomaterials and Biomedical Engineering, The University of Toronto, Toronto, Ontario M5G 3G9 (Canada); Waspe, Adam C. [Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, Ontario M5G 1X8 (Canada); Department of Medical Imaging, The University of Toronto, Toronto, Ontario M5T 1W7 (Canada); Drake, James M. [Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, Ontario M5G 1X8 (Canada); Department of Neurosurgery, The University of Toronto, Toronto, Ontario M5S 1A1 (Canada); The Institute of Biomaterials and Biomedical Engineering, The University of Toronto, Toronto, Ontario M5G 3G9 (Canada)

2016-09-15

Purpose: Current treatment of intraventricular hemorrhage (IVH) involves cerebral shunt placement or an invasive brain surgery. Magnetic resonance-guided focused ultrasound (MRgFUS) applied to the brains of pediatric patients presents an opportunity to treat IVH in a noninvasive manner, termed “incision-less surgery.” Current clinical and research focused ultrasound systems lack the capability to perform neonatal transcranial surgeries due to either range of motion or dexterity requirements. A novel robotic system is proposed to position a focused ultrasound transducer accurately above the head of a neonatal patient inside an MRI machine to deliver the therapy. Methods: A clinical Philips Sonalleve MRgFUS system was expanded to perform transcranial treatment. A five degree-of-freedom MR-conditional robot was designed and manufactured using MR compatible materials. The robot electronics and control were integrated into existing Philips electronics and software interfaces. The user commands the position of the robot with a graphical user interface, and is presented with real-time MR imaging of the patient throughout the surgery. The robot is validated through a series of experiments that characterize accuracy, signal-to-noise ratio degeneration of an MR image as a result of the robot, MR imaging artifacts generated by the robot, and the robot’s ability to operate in a representative surgical environment inside an MR machine. Results: Experimental results show the robot responds reliably within an MR environment, has achieved 0.59 ± 0.25 mm accuracy, does not produce severe MR-imaging artifacts, has a workspace providing sufficient coverage of a neonatal brain, and can manipulate a 5 kg payload. A full system demonstration shows these characteristics apply in an application environment. Conclusions: This paper presents a comprehensive look at the process of designing and validating a new robot from concept to implementation for use in an MR environment. An MR

Design and validation of an MR-conditional robot for transcranial focused ultrasound surgery in infants

International Nuclear Information System (INIS)

Price, Karl D.; Sin, Vivian W.; Mougenot, Charles; Pichardo, Samuel; Looi, Thomas; Waspe, Adam C.; Drake, James M.

2016-01-01

Purpose: Current treatment of intraventricular hemorrhage (IVH) involves cerebral shunt placement or an invasive brain surgery. Magnetic resonance-guided focused ultrasound (MRgFUS) applied to the brains of pediatric patients presents an opportunity to treat IVH in a noninvasive manner, termed “incision-less surgery.” Current clinical and research focused ultrasound systems lack the capability to perform neonatal transcranial surgeries due to either range of motion or dexterity requirements. A novel robotic system is proposed to position a focused ultrasound transducer accurately above the head of a neonatal patient inside an MRI machine to deliver the therapy. Methods: A clinical Philips Sonalleve MRgFUS system was expanded to perform transcranial treatment. A five degree-of-freedom MR-conditional robot was designed and manufactured using MR compatible materials. The robot electronics and control were integrated into existing Philips electronics and software interfaces. The user commands the position of the robot with a graphical user interface, and is presented with real-time MR imaging of the patient throughout the surgery. The robot is validated through a series of experiments that characterize accuracy, signal-to-noise ratio degeneration of an MR image as a result of the robot, MR imaging artifacts generated by the robot, and the robot’s ability to operate in a representative surgical environment inside an MR machine. Results: Experimental results show the robot responds reliably within an MR environment, has achieved 0.59 ± 0.25 mm accuracy, does not produce severe MR-imaging artifacts, has a workspace providing sufficient coverage of a neonatal brain, and can manipulate a 5 kg payload. A full system demonstration shows these characteristics apply in an application environment. Conclusions: This paper presents a comprehensive look at the process of designing and validating a new robot from concept to implementation for use in an MR environment. An MR

MR imaging of appendicular musculoskeletal trauma

International Nuclear Information System (INIS)

Kathol, M.H.; Montgomery, W.J.; Yuh, W.T.C.; El-Khoury, G.Y.

1987-01-01

Thirty cases of musculoskeletal trauma to the extremities examined by MR imaging have been reviewed retrospectively. Examples of various injuries will be shown, including disruption of ligament and tendon, muscular tear and edema, hemorrhage (local or diffuse), vascular injury, bone marrow contusion, osteocartilaginous fracture, meniscal tear, and joint fluid. Many of these patients were collegiate athletes, and MR was valuable in establishing a rapid, accurate diagnosis influencing not only treatment but also return to competition. Negative examinations allowed resumption of competition with a high degree of confidence. The advantages and disadvantages of MR in musculo-skeletal trauma are discussed

Do dorsal raphe 5-HT neurons encode "beneficialness"?

Science.gov (United States)

Luo, Minmin; Li, Yi; Zhong, Weixin

2016-11-01

The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) affects numerous behavioral and physiological processes. Drugs that alter 5-HT signaling treat several major psychiatric disorders and may lead to widespread abuse. The dorsal raphe nucleus (DRN) in the midbrain provides a majority of 5-HT for the forebrain. The importance of 5-HT signaling propels the search for a general theoretical framework under which the diverse functions of the DRN 5-HT neurons can be interpreted and additional therapeutic solutions may be developed. However, experimental data so far support several seeming irreconcilable theories, suggesting that 5-HT neurons mediate behavioral inhibition, aversive processing, or reward signaling. Here, we review recent progresses and propose that DRN 5-HT neurons encode "beneficialness" - how beneficial the current environmental context represents for an individual. Specifically, we speculate that the activity of these neurons reflects the possible net benefit of the current context as determined by p·R-C, in which p indicates reward probability, R the reward value, and C the cost. Through the widespread projections of these neurons to the forebrain, the beneficialness signal may reconfigure neural circuits to bias perception, boost positive emotions, and switch behavioral choices. The "beneficialness" hypothesis can explain many conflicting observations, and at the same time raises new questions. We suggest additional experiments that will help elucidate the exact computational functions of the DRN 5-HT neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus.

Science.gov (United States)

McAllister, C E; Creech, R D; Kimball, P A; Muma, N A; Li, Q

2012-08-01

Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT(1A)) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT(1A) receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT(1A) receptor desensitization. We previously showed that estrogen receptor β is not necessary for 5-HT(1A) receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT(1A) receptor as measured by hormonal responses to the selective 5-HT(1A) receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT(1A) receptor signaling components including 5-HT(1A) receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT(1A) receptor protein but increased 5-HT(1A) mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT(1A) receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT(1A) receptor signaling pathway and desensitization of 5-HT(1A) receptor signaling. Copyright © 2012 Elsevier Ltd. All rights reserved.

Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

Science.gov (United States)

Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

2002-11-01

Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their

Changes of renal blood flow after ESWL: Assessment by ASL MR imaging, contrast enhanced MR imaging, and renal resistive index

Energy Technology Data Exchange (ETDEWEB)

Abd Ellah, Mohamed, E-mail: dr_m_hamdy2006@hotmail.co [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Kremser, Christian, E-mail: christian.kremser@i-med.ac.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Pallwein, Leo, E-mail: leo.pallwein-prettner@uki.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Aigner, Friedrich, E-mail: friedrich.Aigner@uki.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Schocke, Michael, E-mail: michael.schocke@i-med.ac.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Peschel, Reinhard, E-mail: reinhard.peschel@uki.a [Innsbruck Medical University, Urology Dept., Anich St. 35, 6020 Innsbruck (Austria); Pedross, Florian, E-mail: florian.pedross@i-med.ac.a [Innsbruck Medical University, Medical Statistics Dept., Anich St. 35, 6020 Innsbruck (Austria); Pinggera, Germar-Michael, E-mail: germar.pinggera@uki.a [Innsbruck Medical University, Urology Dept., Anich St. 35, 6020 Innsbruck (Austria); Wolf, Christian, E-mail: christian.wolf@bkh-reutte.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Alsharkawy, Mostafa A.M., E-mail: drmostafamri@yahoo.co [Assiut University, Radiology Dept., Assiut (Egypt); Jaschke, Werner, E-mail: werner.jaschke@i-med.ac.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Frauscher, Ferdinand, E-mail: ferdinand.frauscher@uki.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria)

2010-10-15

The annual incidence of stone formation is increased in the industrialised world. Extracorporeal shockwave lithotripsy is a non-invasive effective treatment of upper urinary tract stones. This study is aimed to evaluate changes of renal blood flow in patients undergoing extracorporeal shock wave lithotripsy (ESWL) by arterial spin labeling (ASL) MR imaging, contrast enhanced dynamic MR imaging, and renal resistive index (RI). Thirteen patients with nephrolithiasis were examined using MR imaging and Doppler ultrasound 12 h before and 12 h after ESWL. ASL sequence was done for both kidneys and followed by contrast enhanced MR imaging. In addition RI Doppler ultrasound measurements were performed. A significant increase in RI (p < 0.001) was found in both treated and untreated kidneys. ASL MR imaging also showed significant changes in both kidneys (p < 0.001). Contrast enhanced dynamic MR imaging did not show significant changes in the kidneys. ESWL causes changes in RI and ASL MR imaging, which seem to reflect changes in renal blood flow.

The binding characteristics and orientation of a novel radioligand with distinct properties at 5-HT3A and 5-HT3AB receptors

NARCIS (Netherlands)

Thompson, Andrew J; Verheij, Mark H P; Verbeek, Joost; Windhorst, Albert D; de Esch, Iwan J P; Lummis, Sarah C R

2014-01-01

VUF10166 (2-chloro-3-(4-methyl piperazin-1-yl)quinoxaline) is a ligand that binds with high affinity to 5-HT3 receptors. Here we synthesise [(3)H]VUF10166 and characterise its binding properties at 5-HT3A and 5-HT3AB receptors. At 5-HT3A receptors [(3)H]VUF10166 displayed saturable binding with a Kd

Effects of Constant Flickering Light on Refractive Status, 5-HT and 5-HT2A Receptor in Guinea Pigs.

Science.gov (United States)

Li, Bing; Luo, Xiumei; Li, Tao; Zheng, Changyue; Ji, Shunmei; Ma, Yuanyuan; Zhang, Shuangshuang; Zhou, Xiaodong

2016-01-01

To investigate the effects of constant flickering light on refractive development, the role of serotonin (i.e.5-hydroxytryptamine, 5-HT)and 5-HT2A receptor in myopia induced by flickering light in guinea pigs. Forty-five guinea pigs were randomly divided into three groups: control, form deprivation myopia (FDM) and flickering light induced myopia (FLM) groups(n = 15 for each group). The right eyes of the FDM group were covered with semitransparent hemispherical plastic shells serving as eye diffusers. Guinea pigs in FLM group were raised with illumination of a duty cycle of 50% at a flash frequency of 0.5Hz. The refractive status, axial length (AL), corneal radius of curvature(CRC) were measured by streak retinoscope, A-scan ultrasonography and keratometer, respectively. Ultramicroscopy images were taken by electron microscopy. The concentrations of 5-HTin the retina, vitreous body and retinal pigment epithelium (RPE) were assessed by high performance liquid chromatography, the retinal 5-HT2A receptor expression was evaluated by immunohistofluorescence and western blot. The refraction of FDM and FLM eyes became myopic from some time point (the 4th week and the 6th week, respectively) in the course of the experiment, which was indicated by significantly decreased refraction and longer AL when compared with the controls (plight could cause progressive myopia in guinea pigs. 5-HT and 5-HT2A receptor increased both in form deprivation myopia and flickering light induced myopia, indicating that 5-HT possibly involved in myopic development via binding to5-HT2A receptor.

Conduction-band valley spin splitting in single-layer H-T l2O

Science.gov (United States)

Ma, Yandong; Kou, Liangzhi; Du, Aijun; Huang, Baibiao; Dai, Ying; Heine, Thomas

2018-02-01

Despite numerous studies, coupled spin and valley physics is currently limited to two-dimensional (2D) transition-metal dichalcogenides (TMDCs). Here, we predict an exceptional 2D valleytronic material associated with the spin-valley coupling phenomena beyond 2D TMDCs—single-layer (SL) H-T l2O . It displays large valley spin splitting (VSS), significantly larger than that of 2D TMDCs, and a finite band gap, which are both critically attractive for the integration of valleytronics and spintronics. More importantly, in sharp contrast to all the experimentally confirmed 2D valleytronic materials, where the strong valence-band VSS (0.15-0.46 eV) supports the spin-valley coupling, the VSS in SL H-T l2O is pronounced in its conduction band (0.61 eV), but negligibly small in its valence band (21 meV), thus opening a way for manipulating the coupled spin and valley physics. Moreover, SL H-T l2O possesses extremely high carrier mobility, as large as 9.8 ×103c m2V-1s-1 .

Polymeric nanomedicine for cancer MR imaging and drug delivery.

Science.gov (United States)

Khemtong, Chalermchai; Kessinger, Chase W; Gao, Jinming

2009-06-28

Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (nanoscopic therapeutic and diagnostic systems have been translated into clinical practice. In this feature article, we will provide an up-to-date review on the development and biomedical applications of nanocomposite materials for cancer diagnosis and therapy. An overview of each functional component, i.e. polymer carriers, MR imaging agents, and therapeutic drugs, will be presented. Integration of different functional components will be illustrated in several highlighted examples to demonstrate the synergy of the multifunctional nanomedicine design.

The 5-HT2A receptor antagonist M100907 produces antiparkinsonian effects and decreases striatal glutamate

Directory of Open Access Journals (Sweden)

Twum eAnsah

2011-06-01

Full Text Available 5-HT plays a regulatory role in voluntary movements of the basal ganglia and have a major impact on disorders of the basal ganglia such as Parkinson’s disease (PD. Clinical studies have suggested that 5-HT2 receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT2A receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT2A receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT2A receptors may represent a novel therapeutic target for the motor symptoms of Parkinson’s disease.

The Fabrication of Bulk Heterojunction P3HT: PCBM Organic Photovoltaics

Science.gov (United States)

Darwis, D.; Sesa, E.; Farhamza, D.; Iqbal

2018-05-01

Bulk heterojunction Organic photovoltaic (OPV) devices are gaining a lot of interest due to their potential for ease of processing and lower manufacturing cost sustainable energy generation. In consequence, the number of studies into the properties and characteristics of organic solar cell devices has been increased to improving their power conversion. A further advancement over past decade has shown that improved efficiency could be obtained by mixed of poly(3 - hexylthiophene) (P3HT) and [1] – phenyl - C61-butyric acid methyl ester (PCBM) as an active layer. A series of optimizations of this P3HT: PCBM blends, such as the mixture ratio variation, the annealing treatments, and solvent treatment, have been emerged to improve the efficiency of the OPV. As a result, significant improvements were achieved. Here, we report the fabrication heterojunction devices of 2.9 % efficiency. This result has been achieved using the configuration of a typical heterojunction solar cell modules consists of layered glass/ITO/PEDOT: PSS/active layer/cathode interlayer

MR of experimental cerebral ischemia

International Nuclear Information System (INIS)

DeLaPaz, R.; Steinberg, G.; Rocklage, S.; Glover, G.H.

1990-01-01

This paper reports on MR imaging of cerebral ischemia and treatment with N-methyl-D-aspartate (NMDA) antagonists in an animal model. Forty-four New Zealand white rabbits underwent 1-hour transorbital ICA-MCA-ACA occlusion and pretreatment or immediate posttreatment with systemic dextromethorphan (DM, n = 14), dextrorphan (DX, n = 14), or normal saline (NS, n = 16). Serial MR studies (1.5 T) were performed 1--6 hours after occlusion with T1- and T2-weighted spinecho, IVIM (b = 1,352), gradient recalled acquisition in a steady-state, and chemical shift sequences (for magnetic susceptibility, T2* and T2') and DyDTPA-BMA intravenous contrast material (Salutar). Spatial correlation between MR findings, histologic findings (ischemic neuronal damage), and regional cerebral blood flow (microspheres) was done

MR imaging of septic sacroiliitis

Energy Technology Data Exchange (ETDEWEB)

Stuerzenbecher, A.; Hamm, B.; Bollow, M. [Humboldt-Universitaet, Berlin (DD). Bereich Medizin (Charite); Braun, J. [Freie Univ. Berlin (Germany). Universitaetsklinikum Benjamin Franklin; Paris, S. [Unfallkrankenhaus Berlin (Germany). Dept. of Radiology; Biedermann, T. [Krankenhaus Berlin-Buch (Germany). II. Kinderklinik

2000-08-01

Objective. To investigate the diagnostic value of magnetic resonance (MR) imaging in detecting septic sacroiliitis and to determine whether the MR characteristics allow this entity to be differentiated from sacroiliitis in spondylarthropathy (SpA).Patients and design. The imaging findings of 11 patients with septic sacroiliitis were retrospectively analyzed by two experienced radiologists. Radiographic surveys of the pelvis as well as computed tomography (CT) and MR images of the sacroiliac joints were available in all cases. Seven of the patients additionally underwent a follow-up MR examination. The MR imaging protocol comprised combinations of coronal and transverse T1-weighted spin-echo (SE) or fast SE sequences, T2-weighted gradient-echo (GE) sequences and short tau inversion recovery sequence (STIR) sequences as well as dynamic contrast- enhanced T1-weighted acquisitions.Results. Three patients with a short disease history showed anterior and/or posterior subperiosteal infiltrations (''lava cleft phenomenon''), transcapsular infiltrations of juxta-articular muscle layers, which obscured the fasciae, and periarticular bone marrow edema. The eight patients with more advanced stages of sacroiliitis additionally showed abscess formation, sequestration, and erosion. At follow-up MR examination (n=7) under systemic antibiotic treatment, the morphologic characteristics showed progression (n=1), regression (n=4), unchanged findings (n=1), or a mixed response (n=1). Clinical improvement precedes resolution of the MR findings.Conclusions. Anterior and/or posterior subperiosteal infiltrations and transcapsular infiltrations of juxta-articular muscle layers were depicted in all patients. These MR imaging findings are characteristic of septic sacroiliitis and may be used to differentiate this entity from sacroiliitis in SpA. (orig.)

Pavement subgrade MR design values for Michigan's seasonal changes : table E4.

Science.gov (United States)

2009-07-22

The resilient modulus (MR) of roadbed soil plays an integral role in the design of pavement systems. Currently, the various regions of the Michigan Department of Transportation (MDOT) use different procedures to determine the MR values. Most of these...

Pavement subgrade MR design values for Michigan's seasonal changes : table E5.

Science.gov (United States)

2010-06-22

The resilient modulus (MR) of roadbed soil plays an integral role in the design of pavement systems. Currently, the various regions of the Michigan Department of Transportation (MDOT) use different procedures to determine the MR values. Most of these...

Serotonin Signaling through Prefrontal Cortex 5-HT1A Receptors during Adolescence Can Determine Baseline Mood-Related Behaviors

Directory of Open Access Journals (Sweden)

Alvaro L. Garcia-Garcia

2017-01-01

Full Text Available Lifelong homeostatic setpoints for mood-related behaviors emerge during adolescence. Serotonin (5-HT plays an important role in refining the formation of brain circuits during sensitive developmental periods. In rodents, the role of 5-HT1A receptors in general and autoreceptors in particular has been characterized in anxiety. However, less is known about the role of 5-HT1A receptors in depression-related behavior. Here, we show that whole-life suppression of heteroreceptor expression results in a broad depression-like behavioral phenotype accompanied by physiological and cellular changes within medial prefrontal cortex-dorsal raphe proper (mPFC-DRN circuitry. These changes include increased basal 5-HT in a mPFC that is hyporesponsive to stress and decreased basal 5-HT levels and firing rates in a DRN hyperactivated by the same stressor. Remarkably, loss of heteroreceptors in the PFC at adolescence is sufficient to recapitulate this depression-like behavioral syndrome. Our results suggest that targeting mPFC 5-HT1A heteroreceptors during adolescence in humans may have lifelong ramifications for depression and its treatment.

Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality

NARCIS (Netherlands)

Dudok, J.J.; Groffen, A.J.A.; Toonen, R.F.G.; Verhage, M.

2011-01-01

The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT)

Dynamic MR imaging of mandibular osteoradionecrosis

International Nuclear Information System (INIS)

Store, G.; Smith, H.J.; Larheim, T.A.

2000-01-01

Osteoradionecrotic bone has been characterised as hypovascular and metabolically inactive tissue with impaired perfusion. The present study was conducted to determine if dynamic contrast-enhanced MR imaging could provide additional information about the vascularity of radionecrotic mandibular bone. Dynamic contrast-enhanced MR imaging was performed on 10 patients with mandibular osteoradionecrosis (ORN), and on 6 patients, irradiated for oropharyngeal tumours, without symptoms or signs of ORN. Nine patients in the ORN group received a series of 20 hyperbaric oxygen (HBO) treatments, after which the dynamic MR investigation was repeated. Radiation per se did not lead to increased contrast enhancement, whereas all patients with ORN showed marked contrast enhancement of the osteoradionecrotic bone marrow. After HBO treatment, pathological contrast enhancement of the abnormal bone marrow could still be seen, but the rate of enhancement was less than before in 7 of 9 patients. Two patients had an increase in the enhancement rate. The findings suggest the existence of an increased and patent microvasculature

Effect of the 5-HT{sub 4} receptor and serotonin transporter on visceral hypersensitivity in rats

Energy Technology Data Exchange (ETDEWEB)

Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan [Department of Gastroenterology, Peking University First Hospital, Beijing (China)

2012-07-27

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT{sub 4} receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT{sub 4} receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT{sub 4} receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg{sup −1}·day{sup −1}, days 36-42), tegaserod (1 mg·kg{sup −1}·day{sup −1}, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT{sub 4} receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT{sub 4} receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT

5-HT radioligands for human brain imaging with PET and SPECT

DEFF Research Database (Denmark)

Paterson, Louise M; Kornum, Birgitte R; Nutt, David J

2013-01-01

The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used...

MR-guided high intensity focused ultrasound thermoablation under temperature mapping monitoring for the treatment of uterine fibroids

International Nuclear Information System (INIS)

Xu Yonghua; Fu Zhongxiang; Yang Lixia; Chen Wenzhi; Liu Yingjiang; Ye Fangwei; Wang Zhibiao

2010-01-01

Objective: To assess the feasibility and effectiveness of MR-guided high intensity focused ultrasound (MRgHIFU) thermoablation under temperature mapping monitoring for the treatment of uterine fibroids. Methods: MRgHIFU was carried out in 52 patients with a total of 61 uterine fibroids. The mean age was (39.6 ± 7.3) years (ranged between 23-56 years), and the average diameter of the fibroids was(6.1 ± 2.1) cm (ranged between 1.2-10.7 cm). This procedure was accomplished by a JM-HIFU system (Mode JM15100, Chongqing Haifu Technology Co., Ltd., China), in combination with a 1.5-Tesla MRI system (Avanto TIM, Siemens, Germany), which provided real-time guidance and temperature mapping. Contrast-enhanced MR imaging was performed both immediately and three months after MRgHIFU treatment in order to evaluate the efficacy of thermal ablation. The treatment time and adverse events were recorded. The percentage of ablation volume was calculated after the procedure. The changes in the size of the uterine fibroid and in the clinical symptoms three months after the procedure were evaluated. Results: The mean fibroid volume for each case before and three months after MRgHIFU treatment was (113.3 ± 87.7) cm 3 and (58.1 ± 45.0) cm 3 respectively(P 3 (ranged between 7.7-282.9 cm 3 ) of fibroid volume was (19.8 ± 8.8) minutes. The mean energy of focused ultrasound delivered into the ablated fibroid tissue was (7.1 ± 6.7) J/mm 3 (ranged between 0.9-32.1 J/mm 3 ). The symptoms were relieved, the mean overall points decreased from (24.7 ± 4.8) to (16.7 ± 3.2) after therapy (P < 0.05). One patient experienced mild skin burn (small blisters), which subsided within two days. No other adverse events and complications were observed. Two patients got pregnant at three months after the treatment. Conclusion: MR-guided high intensity focused ultrasound treatment is a safe, effective and non-invasive technique for ablating uterine fibroids. A single thermoablation procedure is enough to

A Pharmacological Analysis of an Associative Learning Task: 5-HT1 to 5-HT7 Receptor Subtypes Function on a Pavlovian/Instrumental Autoshaped Memory

Science.gov (United States)

Meneses, Alfredo

2003-01-01

Recent studies using both invertebrates and mammals have revealed that endogenous serotonin (5-hydroxytryptamine [5-HT]) modulates plasticity processes, including learning and memory. However, little is currently known about the mechanisms, loci, or time window of the actions of 5-HT. The aim of this review is to discuss some recent results on the effects of systemic administration of selective agonists and antagonists of 5-HT on associative learning in a Pavlovian/instrumental autoshaping (P/I-A) task in rats. The results indicate that pharmacological manipulation of 5-HT1-7 receptors or 5-HT reuptake sites might modulate memory consolidation, which is consistent with the emerging notion that 5-HT plays a key role in memory formation. PMID:14557609

The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

DEFF Research Database (Denmark)

Licht, Cecilie Löe; Marcussen, Anders Bue; Wegener, Gregers

2009-01-01

The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography....... In the Flinders Sensitive Line, the 5-HT(4) receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16-47% down-regulation of 5-HT(4......) receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT(4) receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT(2A) receptor binding was decreased in the frontal and cingulate...

Control of 4-DOF MR haptic master for medical application

Science.gov (United States)

Oh, Jong-Seok; Choi, Seung-Hyun; Choi, Seung-Bok

2014-03-01

In this work, magnetorheological (MR) based haptic master for robot-assisted minimally invasive surgery (RMIS) is proposed and analyzed. Using a controllable MR fluid, the masters can generate a reflection force with the 4-DOF motion. The proposed master consists of two actuators: MR clutch featuring gimbal mechanism for 2-DOF rotational motion (X and Y axes) and MR clutch attached at gripper of gimbal structures for 1-DOF rotational motion (Z axis) and 1-DOF translational motion. After analyzing the dynamic motion by integrating mechanical and physical properties of the actuators, torque model of the proposed haptic master is derived. For realization of master-slave system, an encoder which can measure position information is integrated with the MR haptic master. In the RMIS system, the measured position is converted as a command signal and sent to the slave robot. In this work, slave and organ of patient are modeled in virtual space. In order to embody a human organ into virtual space, a volumetric deformable object is mathematically formulated by a shape retaining chain linked (S-chain) model. Accordingly, the haptic architecture is established by incorporating the virtual slave with the master device in which the reflection force and desired position originated from the object of the virtual slave and operator of the master, respectively, are transferred to each other. In order to achieve the desired force trajectories, a proportional-integral-derivative (PID) controller is designed and implemented. It has been demonstrated that the effective tracking control performance for the desired motion of reflection force is well presented in time domain.

Technical Note: Development and performance of a software tool for quality assurance of online replanning with a conventional Linac or MR-Linac

Energy Technology Data Exchange (ETDEWEB)

Chen, Guang-Pei, E-mail: gpchen@mcw.edu; Ahunbay, Ergun; Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 (United States)

2016-04-15

Purpose: To develop an integrated quality assurance (QA) software tool for online replanning capable of efficiently and automatically checking radiation treatment (RT) planning parameters and gross plan quality, verifying treatment plan data transfer from treatment planning system (TPS) to record and verify (R&V) system, performing a secondary monitor unit (MU) calculation with or without a presence of a magnetic field from MR-Linac, and validating the delivery record consistency with the plan. Methods: The software tool, named ArtQA, was developed to obtain and compare plan and treatment parameters from both the TPS and the R&V system database. The TPS data are accessed via direct file reading and the R&V data are retrieved via open database connectivity and structured query language. Plan quality is evaluated with both the logical consistency of planning parameters and the achieved dose–volume histograms. Beams in between the TPS and R&V system are matched based on geometry configurations. To consider the effect of a 1.5 T transverse magnetic field from MR-Linac in the secondary MU calculation, a method based on modified Clarkson integration algorithm was developed and tested for a series of clinical situations. Results: ArtQA has been used in their clinic and can quickly detect inconsistencies and deviations in the entire RT planning process. With the use of the ArtQA tool, the efficiency for plan check including plan quality, data transfer, and delivery check can be improved by at least 60%. The newly developed independent MU calculation tool for MR-Linac reduces the difference between the plan and calculated MUs by 10%. Conclusions: The software tool ArtQA can be used to perform a comprehensive QA check from planning to delivery with conventional Linac or MR-Linac and is an essential tool for online replanning where the QA check needs to be performed rapidly.

Technical Note: Development and performance of a software tool for quality assurance of online replanning with a conventional Linac or MR-Linac.

Science.gov (United States)

Chen, Guang-Pei; Ahunbay, Ergun; Li, X Allen

2016-04-01

To develop an integrated quality assurance (QA) software tool for online replanning capable of efficiently and automatically checking radiation treatment (RT) planning parameters and gross plan quality, verifying treatment plan data transfer from treatment planning system (TPS) to record and verify (R&V) system, performing a secondary monitor unit (MU) calculation with or without a presence of a magnetic field from MR-Linac, and validating the delivery record consistency with the plan. The software tool, named ArtQA, was developed to obtain and compare plan and treatment parameters from both the TPS and the R&V system database. The TPS data are accessed via direct file reading and the R&V data are retrieved via open database connectivity and structured query language. Plan quality is evaluated with both the logical consistency of planning parameters and the achieved dose-volume histograms. Beams in between the TPS and R&V system are matched based on geometry configurations. To consider the effect of a 1.5 T transverse magnetic field from MR-Linac in the secondary MU calculation, a method based on modified Clarkson integration algorithm was developed and tested for a series of clinical situations. ArtQA has been used in their clinic and can quickly detect inconsistencies and deviations in the entire RT planning process. With the use of the ArtQA tool, the efficiency for plan check including plan quality, data transfer, and delivery check can be improved by at least 60%. The newly developed independent MU calculation tool for MR-Linac reduces the difference between the plan and calculated MUs by 10%. The software tool ArtQA can be used to perform a comprehensive QA check from planning to delivery with conventional Linac or MR-Linac and is an essential tool for online replanning where the QA check needs to be performed rapidly.

MR angiography in diagnosing and following up the treatment result: arteria lusoria

International Nuclear Information System (INIS)

Vogl, T.J.; Juergens, M.; Harms, J.; Pegios, W.; Zimmermann, A.; Hetzer, R.; Felix, R.

1994-01-01

Diagnostic and therapeutic procedures are presented in a 29-year-old female patient who suffered from severe dysphagia and rapid loss in weight. In the conventional X-ray examination and barium swallow an aberrant right subclavian artery was suspected. MR imaging (MRI) and MR angiography (MRA) were done to plan the surgical correction. Post-operative MRA documented exactly the complex topography after surgical correction and the flow pattern in the implanted Gore-Tex stretch graft prosthesis. Non-invasive MR angiography renders possible the concrete planning of complex corrections of thoracic vessels replacing invasive catheter angiography. (orig.) [de

Initial experience on protocol optimization for integrated PET/MR%PET/MR一体机操作优化的初步经验

Institute of Scientific and Technical Information of China (English)

刘家金; 陈英茂; 张雄伟; 富丽萍; 田嘉禾; 尹大一; 徐白萱

2014-01-01

目的 通过比较PET/CT和PET/MR,初步探索PET/MR一体机的操作流程和成像优化方案.方法 228例患者同日内接受PET/CT和PET/MR检查,通过6种不同MR序列与PET采集组合方案,比较图像质量的优劣,以在保证诊断信息基础上缩短患者扫描时间的原则分析判断,并初步确定最优PET/MR一体机采集方案.结果 PET/MR结果与PET/CT相近,但其操作流程和注意事项有独特之处;在6种方案中,以躯干和头部各有独立序列组合、兼顾各向同性结构显示与突出病灶特点的方案6效果最优;PET/MR比PET/CT更易产生伪影.结论 在优化方案基础上,PET/MR可获得与PET/CT一致的诊断级图像,但PET/MR采集时间长、伪影多,有待进一步完善.%Objective To investigate the optimal workflow and protocol for integrated PET/MR by comparison with PET/CT.Methods A total of 228 patients were enrolled in this study for PET/CT and PET/MR evaluation on the same day.Six PET/MR protocols with different MR sequences but the same PET acquisition protocol were investigated and the optimal protocol was identified based on image quality,acquisition time and diagnostic performance.Results PET/MR workflow was similar to PET/CT,however,some special issues needed to be considered for PET/MR.Among the 6 protocols,protocol No.6 outperformed others for body and head regions.Types of artifacts were found more often in PET/MR than in PET/CT.Conclusions By optimizing the protocol,PET/MR could achieve almost the same diagnostic performance as PET/CT.However,the issues of long acquisition time and artifacts on PET/MR need to be further improved.

Positron emission tomography study of pindolol occupancy of 5-HT1A receptors in humans: preliminary analyses

International Nuclear Information System (INIS)

Martinez, Diana; Mawlawi, Osama; Hwang, Dah-Ren; Kent, Justine; Simpson, Norman; Parsey, Ramin V.; Hashimoto, Tomoki; Slifstein, Mark; Huang Yiyun; Heertum, Ronald van; Abi-Dargham, Anissa; Caltabiano, Stephen; Malizia, Andrea; Cowley, Hugh; Mann, J. John; Laruelle, Marc

2000-01-01

Preclinical studies in rodents suggest that augmentation of serotonin reuptake inhibitors (SSRIs) therapy by the 5-hydroxytryptamine 1A (5-HT 1A ) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response. This hypothesis is based on the ability of pindolol to potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an effect achieved by blockade of the 5-HT 1A autoreceptors in the dorsal raphe nuclei (DRN). However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT 1A receptors following treatment with controlled release pindolol in nine healthy volunteers with positron-emission tomography (PET). Each subject was studied four times: at baseline (scan 1), following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and following one dose of pindolol CR (30 mg) (at peak level, 4 h) (scan 4). Pindolol occupancy of 5-HT 1A receptors was evaluated in the DRN and cortical regions as the decrease in binding potential (BP) of the radiolabelled selective 5-HT 1A antagonist [carbonyl- 11 C]WAY-100635 or [carbonyl- 11 C] N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide abbreviated as [ 11 C]WAY-100635. Pindolol dose-dependently decreased [ 11 C]WAY-100635 BP. Combining all the regions, occupancy was 20 ± 8% at scan 2, 14 ± 8% at scan 3, and 44 ± 8% at scan 4. The results of this study suggest that at doses used in clinical studies of augmentation of the SSRI effect by pindolol (2.5 mg t.i.d.), the occupancy of 5-HT 1A receptors is moderate and highly variable between subjects. This factor might explain the variable results obtained in clinical studies. On the other hand, at each dose tested, pindolol occupancy of 5-HT 1A receptors was higher in the DRN compared to

Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats.

Science.gov (United States)

Wu, Zhong-Min; Yang, Li-Hua; Cui, Rong; Ni, Gui-Lian; Wu, Feng-Tian; Liang, Yong

2017-05-01

One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT 3 receptor in the development of PTSD, even though 5-HT 3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT 3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT 3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT 3A subunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT 3A expression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT 3 receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.

Principles of Simultaneous PET/MR Imaging.

Science.gov (United States)

Catana, Ciprian

2017-05-01

Combined PET/MR imaging scanners capable of acquiring simultaneously the complementary information provided by the 2 imaging modalities are now available for human use. After addressing the hardware challenges for integrating the 2 imaging modalities, most of the efforts in the field have focused on developing MR-based attenuation correction methods for neurologic and whole-body applications, implementing approaches for improving one modality by using the data provided by the other and exploring research and clinical applications that could benefit from the synergistic use of the multimodal data. Copyright © 2017 Elsevier Inc. All rights reserved.

MR-Guided PTA in Experimental Bilateral Rabbit Renal Artery Stenosis and MR Angiography Follow-Up Versus Histomorphometry

International Nuclear Information System (INIS)

Le Blanche, Alain-Ferdinand; Rossert, Jerome; Wassef, Michel; Levy, Bernard; Bigot, Jean-Michel; Boudghene, Frank

2000-01-01

Purpose: To assess in vivo 1) MR-guided percutaneous transluminal renal angioplasty (PTRA) in experimental bilateral rabbit renal artery stenosis (RAS); 2) postprocedural follow-up by gadolinium-enhanced MR angiography versus histomorphometry.Methods: Fifteen male NZW rabbits of mean weight 4.0 kg (range 3.5-4.2 kg) underwent bilateral RAS induction by combined overdilation-deendothelialization with a gadolinium-filled balloon, passively MR-guided by the artifact of a 0.014-inch guidewire. After 4 weeks the rabbits were randomized into two groups: group A (n = 8) underwent right-sided PTRA for treatment of RAS, group B (n = 7) underwent left-sided PTRA. After another 4 weeks the rabbits were killed to assess by histomorphometry recurrent stenosis and contralateral induction injury stenosis lesions. Each step was preceded by gadolinium-enhanced three-dimensional MR angiography, and the cortex-to-aorta (C/A) signal intensity ratio was calculated.Results: RAS induction was successful in all cases. Fourteen arteries developed restenosis and 13 only initial stenosis. MR-guided PTRAs were feasible in 22 arteries (73%). For a successful catheterization of the ostium (20 arteries, 66% success rate), 10-25 steps were required. Five to eight steps were required for balloon localization and inflation for each PTRA. The restenosis effect was reflected by a 16% (12%-27%) decrease in C/A values on MR angiograms (p < 0.05).Conclusion: MR guidance and MR angiography represent a feasible, less invasive alternative for performing and assessing experimental PTRA in RAS

Effect of juvenile hormone and serotonin (5-HT) on mixis induction of the rotifer Brachionus plicatilis Muller.

Science.gov (United States)

Gallardo; Hagiwara; Snell

2000-09-05

Juvenile hormone (JH) and serotonin (5-HT) were previously shown to enhance mictic (sexual) female production of the rotifer Brachionus plicatilis in batch cultures. To explore the basis of these effects, experiments were conducted on isolated individuals. JH treatment of maternal rotifers with 5 and 50 µgml(-1) (18.8 and 187.7 µM) resulted in significantly higher (P<0.05) mictic female production in the second (F(2)) and third (F(3)) generations. JH treatment was effective even at a lower food concentration of 7x10(5) cellsml(-1), but it was not effective when free ammonia was added at 2.4 and 3.1 µgml(-1). Mictic female production was not increased with exposure to 5-HT up to 50 µgml(-1) (129.1 µM) concentrations. When food level was reduced to 7x10(5) cellsml(-1), however, 5-HT-treated rotifers produced significantly (P<0.05) more mictic females than the control, particularly in F(3) generation. Mictic female production of 5-HT-treated rotifers did not differ from that of the control with or without free ammonia, but the intrinsic rate of natural increase (r) of 5-HT-treated rotifers at 3.1 µgml(-1) free ammonia was significantly higher than the control. These results show that juvenile hormone increases mictic female production under optimum and sub-optimum food levels, whereas 5-HT increases both mictic female production at low food level and population growth rate at high free ammonia concentrations. These compounds could be used to manage rotifer cultures and probe the mechanisms controlling the rotifer life cycle as it switches to mictic reproduction.

Rapid phase segregation of P3HT:PCBM composites by thermal annealing for high-performance bulk-heterojunction solar cells

Energy Technology Data Exchange (ETDEWEB)

Fan, X.; Fang, G.J.; Qin, P.L.; Cheng, F.; Zhao, X.Z. [Wuhan University, Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, Department of Electronic Science and Technology, School of Physics and Technology, Wuhan (China)

2011-12-15

The performances of bulk-heterojunction (BHJ) solar cells are investigated for time-dependent thermal annealing with different morphology evolution scales, having special consideration for the diffusion and aggregation of fullerene derivative molecules based on blends of poly(3-hexylthiophene):[6,6]-phenyl-C{sub 61}-butyric acid methyl ester (P3HT:PCBM). Meaningfully, rapid formation of dot-like and needle-like crystalline PCBM structures of a few micrometers up to 60 {mu}m in size is obtained with thermal annealing treatment from 2 to 15 min, which dynamically reflects a fast process of PCBM molecule and cluster aggregation. Upon ultrasonic-assisted processing and annealing treatment, the scale of P3HT crystals is drastically increased in view of X-ray diffraction (XRD) patterns, leading to a high hole mobility. And, the P3HT domains can be gradually converted into larger P3HT crystals approved by the decreased full width at half-maximum in the XRD patterns. Corresponding current-voltage curves are measured in quantity and we propose a model to explain the effect of the crystalline degree of P3HT domains and aggregation of PCBM molecules and clusters on the phase segregation, expressing a viewpoint towards high performance of BHJ solar cells. (orig.)

Peripheral and spinal 5-HT receptors participate in the pronociceptive and antinociceptive effects of fluoxetine in rats.

Science.gov (United States)

Cervantes-Durán, C; Rocha-González, H I; Granados-Soto, V

2013-11-12

The role of 5-HT receptors in fluoxetine-induced nociception and antinociception in rats was assessed. Formalin produced a typical pattern of flinching and licking/lifting behaviors. Local peripheral ipsilateral, but not contralateral, pre-treatment with fluoxetine (0.3-3 nmol/paw) increased in a dose-dependent fashion 0.5% formalin-induced nociception. In contrast, intrathecal pretreatment with fluoxetine (0.3-3 nmol/rat) prevented nociception induced by formalin. The peripheral pronociceptive effect of fluoxetine was prevented by the 5-HT2A (ketanserin, 3-10 pmol/paw), 5-HT2B (3-(2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl)-2,4(1H,3H)-quinazolinedione(+) tartrate, RS-127445, 3-10 pmol/paw), 5-HT2C (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido) phenyl-5-oxopentyl]1,3,8-triazaspiro[4.5] decane-2,4-dione hydrochloride, RS-102221, 3-10 pmol/paw), 5-HT3 (ondansetron, 3-10 nmol/paw), 5-HT4 ([1-[2-methylsulphonylamino ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate, GR-113808, 3-100 fmol/paw), 5-HT6 (4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfonamide hydrochloride, SB-258585, 3-10 pmol/paw) and 5-HT7 ((R)-3-(2-(2-(4-methylpiperidin-1-yl) ethyl) pyrrolidine-1-sulfonyl) phenol hydrochloride, SB-269970, 0.3-1 nmol/paw), but not by the 5-HT1A (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate, WAY-100635, 0.3-1 nmol/paw), 5-HT1B/1D (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-carboxamide hydrochloride hydrate, GR-127935, 0.3-1 nmol/paw), 5-HT1B (1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine hydrochloride, SB-224289, 0.3-1 nmol/paw), 5-HT1D (4-(3-chlorophenyl)-α-(diphenylmethyl)-1-piperazineethanol hydrochloride, BRL-15572, 0.3-1nmol/paw) nor 5-HT5A ((N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl][1,1'-biphenyl]-4

Helium-induced weld degradation of HT-9 steel

International Nuclear Information System (INIS)

Wang, Chin-An; Chin, B.A.; Lin, Hua T.; Grossbeck, M.L.

1992-01-01

Helium-bearing Sandvik HT-9 ferritic steel was tested for weldability to simulate the welding of structural components of a fusion reactor after irradiation. Helium was introduced into HT-9 steel to 0.3 and 1 atomic parts per million (appm) by tritium doping and decay. Autogenous single pass full penetration welds were produced using the gas tungsten arc (GTA) welding process under laterally constrained conditions. Macroscopic examination showed no sign of any weld defect in HT-9 steel containing 0.3 appm helium. However, intergranular micro cracks were observed in the HAZ of HT-9 steel containing 1 appm helium. The microcracking was attributed to helium bubble growth at grain boundaries under the influence of high stresses and temperatures that were present during welding. Mechanical test results showed that both yield strength (YS) and ultimate tensile strength (UTS) decreased with increasing temperature, while the total elongation increased with increasing temperature for all control and helium-bearing HT-9 steels

Towards Implementing an MR-based PET Attenuation Correction Method for Neurological Studies on the MR-PET Brain Prototype

Science.gov (United States)

Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J.; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A. Gregory

2013-01-01

A number of factors have to be considered for implementing an accurate attenuation correction (AC) in a combined MR-PET scanner. In this work, some of these challenges were investigated and an AC method based entirely on the MR data obtained with a single dedicated sequence was developed and used for neurological studies performed with the MR-PET human brain scanner prototype. Methods The focus was on the bone/air segmentation problem, the bone linear attenuation coefficient selection and the RF coil positioning. The impact of these factors on the PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultra-short echo time (DUTE) MR sequence was proposed for head imaging. Simultaneous MR-PET data were acquired and the PET images reconstructed using the proposed MR-DUTE-based AC method were compared with the PET images reconstructed using a CT-based AC. Results Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm−1 to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. Based on these results, the segmented CT AC method was established as the “silver standard” for the segmented MR-based AC method. Particular to an integrated MR-PET scanner, ignoring the RF coil attenuation can cause large underestimations (i.e. up to 50%) in the reconstructed images. Furthermore, the coil location in the PET field of view has to be accurately known. Good quality bone/air segmentation can be performed using the DUTE data. The PET images obtained using the MR-DUTE- and CT-based AC methods compare favorably in most of the brain structures. Conclusion An MR-DUTE-based AC

The spectrum of MR imaging in athletic pubalgia.

Science.gov (United States)

Zoga, Adam C; Mullens, Frank E; Meyers, William C

2010-11-01

Many athletes struggle with groin pain for years without ever receiving a clear diagnosis or being offered an effective treatment plan. Confusion among treatment providers can also frequently lead to suboptimal surgeries for presumed hernias or nerve entrapment syndromes. Imaging, and in particular magnetic resonance (MR) imaging, should play a primary role in the workup, diagnosis, and treatment of athletic pubalgia. This review outlines standard of care, cutting-edge MR imaging techniques for athletic pubalgia, and reviews the spectrum of imaging findings that are encountered in this patient group. Copyright © 2010 Elsevier Inc. All rights reserved.

Integrated nonthermal treatment system study

International Nuclear Information System (INIS)

Biagi, C.; Bahar, D.; Teheranian, B.; Vetromile, J.; Quapp, W.J.; Bechtold, T.; Brown, B.; Schwinkendorf, W.; Swartz, G.

1997-01-01

This report presents the results of a study of nonthermal treatment technologies. The study consisted of a systematic assessment of five nonthermal treatment alternatives. The treatment alternatives consist of widely varying technologies for safely destroying the hazardous organic components, reducing the volume, and preparing for final disposal of the contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. The alternatives considered were innovative nonthermal treatments for organic liquids and sludges, process residue, soil and debris. Vacuum desorption or various washing approaches are considered for treatment of soil, residue and debris. Organic destruction methods include mediated electrochemical oxidation, catalytic wet oxidation, and acid digestion. Other methods studied included stabilization technologies and mercury separation of treatment residues. This study is a companion to the integrated thermal treatment study which examined 19 alternatives for thermal treatment of MLLW waste. The quantities and physical and chemical compositions of the input waste are based on the inventory database developed by the US Department of Energy. The Integrated Nonthermal Treatment Systems (INTS) systems were evaluated using the same waste input (2,927 pounds per hour) as the Integrated Thermal Treatment Systems (ITTS). 48 refs., 68 figs., 37 tabs

Integrated nonthermal treatment system study

Energy Technology Data Exchange (ETDEWEB)

Biagi, C.; Bahar, D.; Teheranian, B.; Vetromile, J. [Morrison Knudsen Corp. (United States); Quapp, W.J. [Nuclear Metals (United States); Bechtold, T.; Brown, B.; Schwinkendorf, W. [Lockheed Martin Idaho Technologies Co., Idaho Falls, ID (United States); Swartz, G. [Swartz and Associates (United States)

1997-01-01

This report presents the results of a study of nonthermal treatment technologies. The study consisted of a systematic assessment of five nonthermal treatment alternatives. The treatment alternatives consist of widely varying technologies for safely destroying the hazardous organic components, reducing the volume, and preparing for final disposal of the contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. The alternatives considered were innovative nonthermal treatments for organic liquids and sludges, process residue, soil and debris. Vacuum desorption or various washing approaches are considered for treatment of soil, residue and debris. Organic destruction methods include mediated electrochemical oxidation, catalytic wet oxidation, and acid digestion. Other methods studied included stabilization technologies and mercury separation of treatment residues. This study is a companion to the integrated thermal treatment study which examined 19 alternatives for thermal treatment of MLLW waste. The quantities and physical and chemical compositions of the input waste are based on the inventory database developed by the US Department of Energy. The Integrated Nonthermal Treatment Systems (INTS) systems were evaluated using the same waste input (2,927 pounds per hour) as the Integrated Thermal Treatment Systems (ITTS). 48 refs., 68 figs., 37 tabs.

Changes of renal blood flow after ESWL: assessment by ASL MR imaging, contrast enhanced MR imaging, and renal resistive index.

Science.gov (United States)

Abd Ellah, Mohamed; Kremser, Christian; Pallwein, Leo; Aigner, Friedrich; Schocke, Michael; Peschel, Reinhard; Pedross, Florian; Pinggera, Germar-Michael; Wolf, Christian; Alsharkawy, Mostafa A M; Jaschke, Werner; Frauscher, Ferdinand

2010-10-01

The annual incidence of stone formation is increased in the industrialised world. Extracorporeal shockwave lithotripsy is a non-invasive effective treatment of upper urinary tract stones. This study is aimed to evaluate changes of renal blood flow in patients undergoing extracorporeal shock wave lithotripsy (ESWL) by arterial spin labeling (ASL) MR imaging, contrast enhanced dynamic MR imaging, and renal resistive index (RI). Thirteen patients with nephrolithiasis were examined using MR imaging and Doppler ultrasound 12h before and 12h after ESWL. ASL sequence was done for both kidneys and followed by contrast enhanced MR imaging. In addition RI Doppler ultrasound measurements were performed. A significant increase in RI (pESWL causes changes in RI and ASL MR imaging, which seem to reflect changes in renal blood flow. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

HT-COMET: a novel automated approach for high throughput assessment of human sperm chromatin quality

Science.gov (United States)

Albert, Océane; Reintsch, Wolfgang E.; Chan, Peter; Robaire, Bernard

2016-01-01

STUDY QUESTION Can we make the comet assay (single-cell gel electrophoresis) for human sperm a more accurate and informative high throughput assay? SUMMARY ANSWER We developed a standardized automated high throughput comet (HT-COMET) assay for human sperm that improves its accuracy and efficiency, and could be of prognostic value to patients in the fertility clinic. WHAT IS KNOWN ALREADY The comet assay involves the collection of data on sperm DNA damage at the level of the single cell, allowing the use of samples from severe oligozoospermic patients. However, this makes comet scoring a low throughput procedure that renders large cohort analyses tedious. Furthermore, the comet assay comes with an inherent vulnerability to variability. Our objective is to develop an automated high throughput comet assay for human sperm that will increase both its accuracy and efficiency. STUDY DESIGN, SIZE, DURATION The study comprised two distinct components: a HT-COMET technical optimization section based on control versus DNAse treatment analyses (n = 3–5), and a cross-sectional study on 123 men presenting to a reproductive center with sperm concentrations categorized as severe oligozoospermia, oligozoospermia or normozoospermia. PARTICIPANTS/MATERIALS, SETTING, METHODS Sperm chromatin quality was measured using the comet assay: on classic 2-well slides for software comparison; on 96-well slides for HT-COMET optimization; after exposure to various concentrations of a damage-inducing agent, DNAse, using HT-COMET; on 123 subjects with different sperm concentrations using HT-COMET. Data from the 123 subjects were correlated to classic semen quality parameters and plotted as single-cell data in individual DNA damage profiles. MAIN RESULTS AND THE ROLE OF CHANCE We have developed a standard automated HT-COMET procedure for human sperm. It includes automated scoring of comets by a fully integrated high content screening setup that compares well with the most commonly used semi

The love of a lifetime: 5-HT in the cardiovascular system.

Science.gov (United States)

Watts, Stephanie W

2009-02-01

Serotonin [5-hydroxytryptamine (5-HT)] is an amine made from the essential amino acid tryptophan. 5-HT serves numerous functions in the body, including mood, satiety, and gastrointestinal function. Less understood is the role 5-HT plays in the cardiovascular system, although 5-HT receptors have been localized to every important cardiovascular organ and 5-HT-induced changes in physiological function attributed to activation of these receptors. This manuscript relates a few scientific stories that test the idea that 5-HT is important to the control of normal vascular tone, more so in the hypertensive condition. Currently, our laboratory is faced with two different lines of experimentation from which one could draw vastly different conclusions as to the ability of 5-HT to modify endogenous vascular tone and blood pressure. Studies point to 5-HT being important in maintaining high blood pressure, but other studies solidly support the ability of 5-HT to reduce elevated blood pressure. This work underscores that our knowledge of the functions of 5-HT in the cardiovascular system is significantly incomplete. As such, this field is an exciting one in which to be, because there are superb questions to be asked.

Environmental HTO/HT sampler development

International Nuclear Information System (INIS)

Workman, W.J.G.; Brown, R.M.; Wood, M.J.

1992-12-01

Tests of retention by several drying agents of HTO from an air stream containing HT have been performed. Two batches of Molecular Sieve (MS) 4A retained up to 1.3% of HT passed through them in contrast to material tested in 1986, when retention was -4 . Retention of 10 -5 to 10 -6 was observed for DRIERITE (anhydrous calcium sulphate) and Silica Gel. DRIERITE is preferred over Silica Gel as a desiccant in an air sampler for environmental HTO/HT, because it is much easier to decontaminate for reuse. An improved air sampler has been designed, 2 units constructed and components procured for 3 more. The air sampler may be line or battery operated, accommodates up to four 120 g drier or oxidizer traps, and will pump up to 4 L/min for up to 24 hours on battery power. It is build into a rugged aluminum case and weighs approximately 11 kg overall, facilitating deployment in the field

Environmental HTO/HT sampler development

International Nuclear Information System (INIS)

Workman, W.J.G.; Brown, R.M.; Wood, M.J.

1994-01-01

Tests of retention by several drying agents of HTO from an air stream containing HT have been performed. Two batches of Molecular Sieve (MS) 4A retained up to 1.3% of HT passed through them, in contrast to material tested in 1986, when retention was -4 . Retention of 10 -5 to 10 -6 was observed for DRIERITE (anhydrous calcium sulphate) and Silica Gel. DRIERITE is preferred over Silica Gel as a desiccant in an air sampler for environmental HTO/HT, because it is much easier to decontaminate for reuse. An improved air sampler has been designed, 2 units constructed and components procured for 3 more. The air sampler may be line or battery operated, accommodates up to four 120 g drier or oxidizer traps, and will pump up to 4 L/min for up to 24 hours on battery power. It is built into a rugged aluminum case and weighs approximately 11 kg overall, facilitating deployment in the field. (author). 5 refs., 2 tabs., 4 figs

The reconstruction of HT-7 superconducting tokamak and the present status of HT-7U project

International Nuclear Information System (INIS)

Weng, P.D.

2000-01-01

The first Chinese superconducting tokamak HT-7 was reconstructed from T-7. The main purposes of reconstruction are to improve the accessibility of the device and to provide a possibility of long pulse operation with high performance. The reconstruction has been done successfully. The HT-7U project has been approved and funded as a National Project, the engineering design and R and D are on the way. (author)

Optimizing MR imaging-guided navigation for focused ultrasound interventions in the brain

Science.gov (United States)

Werner, B.; Martin, E.; Bauer, R.; O'Gorman, R.

2017-03-01

MR imaging during transcranial MR imaging-guided Focused Ultrasound surgery (tcMRIgFUS) is challenging due to the complex ultrasound transducer setup and the water bolus used for acoustic coupling. Achievable image quality in the tcMRIgFUS setup using the standard body coil is significantly inferior to current neuroradiologic standards. As a consequence, MR image guidance for precise navigation in functional neurosurgical interventions using tcMRIgFUS is basically limited to the acquisition of MR coordinates of salient landmarks such as the anterior and posterior commissure for aligning a stereotactic atlas. Here, we show how improved MR image quality provided by a custom built MR coil and optimized MR imaging sequences can support imaging-guided navigation for functional tcMRIgFUS neurosurgery by visualizing anatomical landmarks that can be integrated into the navigation process to accommodate for patient specific anatomy.

On-line MR imaging for dose validation of abdominal radiotherapy

International Nuclear Information System (INIS)

Glitzner, M; Crijns, S P M; De Senneville, B Denis; Kontaxis, C; Prins, F M; Lagendijk, J J W; Raaymakers, B W

2015-01-01

For quality assurance and adaptive radiotherapy, validation of the actual delivered dose is crucial.Intrafractional anatomy changes cannot be captured satisfactorily during treatment with hitherto available imaging modalitites. Consequently, dose calculations are based on the assumption of static anatomy throughout the treatment. However, intra- and interfraction anatomy is dynamic and changes can be significant.In this paper, we investigate the use of an MR-linac as a dose tracking modality for the validation of treatments in abdominal targets where both respiratory and long-term peristaltic and drift motion occur.The on-line MR imaging capability of the modality provides the means to perform respiratory gating of both delivery and acquisition yielding a model-free respiratory motion management under free breathing conditions.In parallel to the treatment, the volumetric patient anatomy was captured and used to calculate the applied dose. Subsequently, the individual doses were warped back to the planning grid to obtain the actual dose accumulated over the entire treatment duration. Ultimately, the planned dose was validated by comparison with the accumulated dose.Representative for a site subject to breathing modulation, two kidney cases (25 Gy target dose) demonstrated the working principle on volunteer data and simulated delivery. The proposed workflow successfully showed its ability to track local dosimetric changes. Integration of the on-line anatomy information could reveal local dose variations  −2.3–1.5 Gy in the target volume of a volunteer dataset. In the adjacent organs at risk, high local dose errors ranging from  −2.5 to 1.9 Gy could be traced back. (paper)

On-line MR imaging for dose validation of abdominal radiotherapy

Science.gov (United States)

Glitzner, M.; Crijns, S. P. M.; de Senneville, B. Denis; Kontaxis, C.; Prins, F. M.; Lagendijk, J. J. W.; Raaymakers, B. W.

2015-11-01

For quality assurance and adaptive radiotherapy, validation of the actual delivered dose is crucial. Intrafractional anatomy changes cannot be captured satisfactorily during treatment with hitherto available imaging modalitites. Consequently, dose calculations are based on the assumption of static anatomy throughout the treatment. However, intra- and interfraction anatomy is dynamic and changes can be significant. In this paper, we investigate the use of an MR-linac as a dose tracking modality for the validation of treatments in abdominal targets where both respiratory and long-term peristaltic and drift motion occur. The on-line MR imaging capability of the modality provides the means to perform respiratory gating of both delivery and acquisition yielding a model-free respiratory motion management under free breathing conditions. In parallel to the treatment, the volumetric patient anatomy was captured and used to calculate the applied dose. Subsequently, the individual doses were warped back to the planning grid to obtain the actual dose accumulated over the entire treatment duration. Ultimately, the planned dose was validated by comparison with the accumulated dose. Representative for a site subject to breathing modulation, two kidney cases (25 Gy target dose) demonstrated the working principle on volunteer data and simulated delivery. The proposed workflow successfully showed its ability to track local dosimetric changes. Integration of the on-line anatomy information could reveal local dose variations  -2.3-1.5 Gy in the target volume of a volunteer dataset. In the adjacent organs at risk, high local dose errors ranging from  -2.5 to 1.9 Gy could be traced back.

MR plaque imaging of the carotid artery

International Nuclear Information System (INIS)

Watanabe, Yuji; Nagayama, Masako

2010-01-01

Atherosclerotic carotid plaque represents a major cause of cerebral ischemia. The detection of vulnerable plaque is important for preventing future cardiovascular events. The key factors in advanced plaque that are most likely to lead to patient complications are the condition of the fibrous cap, the size of the necrotic core and hemorrhage, and the extent of inflammatory activity within the plaque. Magnetic resonance (MR) imaging has excellent soft tissue contrast and can allow for a more accurate and objective estimation of carotid wall morphology and plaque composition. Recent advances in MR imaging techniques have permitted serial monitoring of atherosclerotic disease evolution and the identification of intraplaque risk factors for accelerated progression. The purpose of this review article is to review the current state of techniques of carotid wall MR imaging and the characterization of plaque components and surface morphology with MR imaging, and to describe the clinical practice of carotid wall MR imaging for the determination of treatment plan. (orig.)

MR appearance of skeletal neoplasms following cryotherapy

Energy Technology Data Exchange (ETDEWEB)

Richardson, M.L. [Dept. of Radiology SB-05, Washington Univ., Seattle, WA (United States); Lough, L.R. [Pitts Radiological Associates, Columbia, SC (United States); Shuman, W.P. [Dept. of Radiology, Medical Center Hospital of Vermont, Burlington, VT (United States); Lazerte, G.D. [Dept. of Pathology RC-72, Washington Univ., Medical Center Hospital of Vermont, Burlington, VT (United States); Conrad, E.U. [Dept. of Orthopedic Surgery RK-10, Washington Univ., Medical Center of Vermont, Burlington, VT (United States)

1994-02-01

Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

MR appearance of skeletal neoplasms following cryotherapy

International Nuclear Information System (INIS)

Richardson, M.L.; Lough, L.R.; Shuman, W.P.; Lazerte, G.D.; Conrad, E.U.

1994-01-01

Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

Methanolic extracts of Uncaria rhynchophylla induce cytotoxicity and apoptosis in HT-29 human colon carcinoma cells.

Science.gov (United States)

Jo, Kyung-Jin; Cha, Mi-Ran; Lee, Mi-Ra; Yoon, Mi-Young; Park, Hae-Ryong

2008-06-01

In this paper, we report the anticancer activities of Uncaria rhynchophylla extracts, a Rubiaceae plant native to China. Traditionally, Uncaria rhynchophylla has been used in the prevention and treatment of neurotoxicity. However, the cytotoxic activity of Uncaria rhynchophylla against human colon carcinoma cells has not, until now, been elucidated. We found that the methanolic extract of Uncaria rhynchophylla (URE) have cytotoxic effects on HT-29 cells. The URE showed highly cytotoxic effects via the MTT reduction assay, LDH release assay, and colony formation assay. As expected, URE inhibited the growth of HT-29 cells in a dose-dependent manner. In particular, the methanolic URE of the 500 microg/ml showed 15.8% inhibition against growth of HT-29 cells. It induced characteristic apoptotic effects in HT-29 cells, including chromatin condensation and sharking occurring 24 h when the cells were treated at a concentration of the 500 microg/ml. The activation of caspase-3 and the specific proteolytic cleavage of poly (ADP-ribose) polymerase were detected over the course of apoptosis induction. These results indicate that URE contains bioactive materials with strong activity, and is a potential chemotherapeutic agent candidate against HT-29 human colon carcinoma cells.

CT and MR imaging characteristics of infantile hepatic hemangioendothelioma

International Nuclear Information System (INIS)

Feng Shiting; Chan Tao; Ching, A.S.C.; Sun Canhui; Guo Huanyi; Fan Miao; Meng Quanfei; Li Ziping

2010-01-01

Aim: This study aims to analyze computed tomography (CT) and magnetic resonance (MR) imaging features of infantile hepatic hemangioendotheliomas before and after treatment. Materials and methods: CT and MR examinations of seven infants with biopsy proven hepatic hemangioendotheliomas were retrospectively analyzed. The distribution, number, size, imaging appearance, enhancement pattern and post-treatment changes of the tumors were evaluated. Results: A total of 153 hepatic hemangioendotheliomas were detected on CT (111) and MR (42) imaging. In six infants, 109/111 (98.2%) tumors were hypodense and 2/111 (1.8%) lesions contained calcification on unenhanced CT. On MR imaging, all 42 lesions in one infant were heterogeneously T1-hypointense and T2-hyperintense compared to the normal liver parenchyma. Contrast-enhanced CT and MRI showed peripheral rim (51.6%), uniform (48.4%), fibrillary (33.3%), and nodular (28.8%) contrast enhancement in the hepatic arterial phase. Homogeneous (100%), rim (98.2%) and mixed enhancement patterns were noted in tumors 2.0 cm and 1.0-2.0 cm in diameter respectively in the hepatic arterial phase. In three patients who underwent steroid therapy, follow-up CT examination demonstrated tumor size reduction and increased intra-tumoral calcification in two patients. Conclusion: Infantile hepatic hemangioendotheliomas show some typical imaging features and size-dependent pattern of contrast enhancement on CT and MR imaging, which allow accurate imaging diagnosis and post-treatment evaluation.

Changes of Serotonin (5-HT, 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression, Myocardial Infarction and Myocardial Infarction Co-exist with Depression

Directory of Open Access Journals (Sweden)

Mei-Yan Liu

2015-01-01

Conclusions: The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression. Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

Serotonin Signaling through Prefrontal Cortex 5-HT1A Receptors during Adolescence Can Determine Baseline Mood-Related Behaviors.

Science.gov (United States)

Garcia-Garcia, Alvaro L; Meng, Qingyuan; Canetta, Sarah; Gardier, Alain M; Guiard, Bruno P; Kellendonk, Christoph; Dranovsky, Alex; Leonardo, E David

2017-01-31

Lifelong homeostatic setpoints for mood-related behaviors emerge during adolescence. Serotonin (5-HT) plays an important role in refining the formation of brain circuits during sensitive developmental periods. In rodents, the role of 5-HT 1A receptors in general and autoreceptors in particular has been characterized in anxiety. However, less is known about the role of 5-HT 1A receptors in depression-related behavior. Here, we show that whole-life suppression of heteroreceptor expression results in a broad depression-like behavioral phenotype accompanied by physiological and cellular changes within medial prefrontal cortex-dorsal raphe proper (mPFC-DRN) circuitry. These changes include increased basal 5-HT in a mPFC that is hyporesponsive to stress and decreased basal 5-HT levels and firing rates in a DRN hyperactivated by the same stressor. Remarkably, loss of heteroreceptors in the PFC at adolescence is sufficient to recapitulate this depression-like behavioral syndrome. Our results suggest that targeting mPFC 5-HT 1A heteroreceptors during adolescence in humans may have lifelong ramifications for depression and its treatment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The role of MR imaging in scaphoid disorders

International Nuclear Information System (INIS)

Karantanas, Apostolos; Dailiana, Zoe; Malizos, Konstantinos

2007-01-01

The scaphoid bone of the wrist is one of the most commonly fractured bones in the body. Due to its importance in the biomechanics and functionality of the wrist, it is important to depict and characterize the type of injury. Plain radiographs and scintigraphy may fail to disclose the type and severity of the injury. In patients with normal initial plain radiographs, MR imaging can discriminate occult fractures from bone bruises and may also demonstrate ligamentous disruption. MR imaging can also discriminate the proximal pole viability versus avascular necrosis secondary to previous fracture, which is important for treatment planning. Treatment of non-united fractures with vascularized grafts can be evaluated with contrast-enhanced MR imaging. Idiopathic osteonecrosis or Preiser's disease was originally described after trauma. The non-traumatic disorders of the scaphoid include post-traumatic osteoarthritis, inflammatory bone marrow edema in patients with rheumatoid arthritis, and osteomyelitis. MR imaging is helpful in all the above disorders to demonstrate early bone marrow edema, cartilage degeneration and associated subchondral marrow changes. The most commonly found tumors in the scaphoid are usually benign and include enchondroma, osteoblastoma and osteoid osteoma. MR imaging is not mandatory for the initial diagnosis, which should be based on plain X-ray findings. (orig.)

The role of MR imaging in scaphoid disorders

Energy Technology Data Exchange (ETDEWEB)

Karantanas, Apostolos [University of Crete, Department of Radiology, Medical School, Heraklion (Greece); University Hospital, Department of Radiology, Stavrakia, Heraklion (Greece); Dailiana, Zoe; Malizos, Konstantinos [University of Thessaly, Department of Orthopedic Surgery, School of Health Sciences, Larissa (Greece)

2007-11-15

The scaphoid bone of the wrist is one of the most commonly fractured bones in the body. Due to its importance in the biomechanics and functionality of the wrist, it is important to depict and characterize the type of injury. Plain radiographs and scintigraphy may fail to disclose the type and severity of the injury. In patients with normal initial plain radiographs, MR imaging can discriminate occult fractures from bone bruises and may also demonstrate ligamentous disruption. MR imaging can also discriminate the proximal pole viability versus avascular necrosis secondary to previous fracture, which is important for treatment planning. Treatment of non-united fractures with vascularized grafts can be evaluated with contrast-enhanced MR imaging. Idiopathic osteonecrosis or Preiser's disease was originally described after trauma. The non-traumatic disorders of the scaphoid include post-traumatic osteoarthritis, inflammatory bone marrow edema in patients with rheumatoid arthritis, and osteomyelitis. MR imaging is helpful in all the above disorders to demonstrate early bone marrow edema, cartilage degeneration and associated subchondral marrow changes. The most commonly found tumors in the scaphoid are usually benign and include enchondroma, osteoblastoma and osteoid osteoma. MR imaging is not mandatory for the initial diagnosis, which should be based on plain X-ray findings. (orig.)

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

Directory of Open Access Journals (Sweden)

Drew J. Puxty

2017-07-01

Full Text Available Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol, which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg, combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg. Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations. Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.

MR-Guided High-Intensity Focused Ultrasound Ablation of Breast Cancer with a Dedicated Breast Platform

International Nuclear Information System (INIS)

Merckel, Laura G.; Bartels, Lambertus W.; Köhler, Max O.; Bongard, H. J. G. Desirée van den; Deckers, Roel; Mali, Willem P. Th. M.; Binkert, Christoph A.; Moonen, Chrit T.; Gilhuijs, Kenneth G. A.; Bosch, Maurice A. A. J. van den

2013-01-01

Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta.

Science.gov (United States)

Rossi, Dania V; Dai, Ying; Thomas, Peter; Carrasco, Gonzalo A; DonCarlos, Lydia L; Muma, Nancy A; Li, Qian

2010-08-01

Estradiol regulates serotonin 1A (5-HT(1A)) receptor signaling. Since desensitization of 5-HT(1A) receptors may be an underlying mechanism by which selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is important to determine which estrogen receptors are capable of desensitizating 5-HT(1A) receptor function. We previously demonstrated that selective activation of the estrogen receptor, GPR30, desensitizes 5-HT(1A) receptor signaling in rat hypothalamic paraventricular nucleus (PVN). However, since estrogen receptor-beta (ERbeta), is highly expressed in the PVN, we investigated the role of ERbeta in estradiol-induced desensitization of 5-HT(1A) receptor signaling. We first showed that a selective ERbeta agonist, diarylpropionitrile (DPN) has a 100-fold lower binding affinity than estradiol for GPR30. Administration of DPN did not desensitize 5-HT(1A) receptor signaling in rat PVN as demonstrated by agonist-stimulated hormone release. Second, we used a recombinant adenovirus containing ERbeta siRNAs to decrease ERbeta expression in the PVN. Reductions in ERbeta did not alter the estradiol-induced desensitization of 5-HT(1A) receptor signaling in oxytocin cells. In contrast, in animals with reduced ERbeta, estradiol administration, instead of producing desensitization, augmented the ACTH response to a 5-HT(1A) agonist. Combined with the results from the DPN treatment experiments, desensitization of 5-HT(1A) receptor signaling does not appear to be mediated by ERbeta in oxytocin cells, but that ERbeta, together with GPR30, may play a complex role in central regulation of 5-HT(1A)-mediated ACTH release. Determining the mechanisms by which estrogens induce desensitization may aid in the development of better treatments for mood disorders. Copyright 2010 Elsevier Ltd. All rights reserved.

Facilitation of acetylcholine release in rat frontal cortex by indeloxazine hydrochloride: involvement of endogenous serotonin and 5-HT4 receptors.

Science.gov (United States)

Yamaguchi, T; Suzuki, M; Yamamoto, M

1997-12-01

Effects of indeloxazine hydrochloride, an inhibitor of serotonin (5-HT) and norepinephrine (NE) reuptake with a facilitatory effect on 5-HT release, on acetylcholine (ACh) output in frontal cortex of conscious rats were characterized using an in vivo microdialysis technique. Systemic administration of indeloxazine (3 and 10 mg/kg, i.p.) increased ACh and 5-HT output in a dose-dependent manner. Depletion of endogenous monoamines by reserpine and of 5-HT by p-chlorophenylalanine, but not that of catecholamines by alpha-methyl-p-tyrosine, significantly attenuated the facilitatory effect of indeloxazine on ACh release. When applied locally by reverse dialysis, indeloxazine (10 and 30 microM) and the selective 5-HT reuptake inhibitor citalopram (10 microM), but not the NE reuptake inhibitor maprotiline (30 microM), increased cortical ACh output. Indeloxazine (10 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT4 receptor antagonists RS23597 (50 microM) and GR113803 (1 microM), while the 5-HT1A antagonist WAY-100135 (100 microM), 5-HT1A/1B/beta-adrenoceptor antagonist (-)propranolol (150 microM), 5-HT2A/2C antagonist ritanserin (10 microM) and 5-HT3 antagonist ondansetron (10 microM) failed to significantly modify this effect. Neither depletion of monoamines nor treatment with serotonergic antagonists significantly changed the basal ACh level, indicating that endogenous monoamines do not tonically activate ACh release. These results suggest that indeloxazine-induced facilitation of ACh release in rat frontal cortex is mediated by endogenous 5-HT and involves at least in part cortical 5-HT4 receptors.

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis.

Science.gov (United States)

Morrow, Gary R; Schwartzberg, Lee; Barbour, Sally Y; Ballinari, Gianluca; Thorn, Michael D; Cox, David

2014-07-01

No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, 7particularly delayed nausea. To compare the effcacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea. Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively. Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs. This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be infuenced by interindividual variability. Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable tolerability. Dr Schwartzberg is a consultant to and Dr Cox an

Positron emission tomography study of pindolol occupancy of 5-HT{sub 1A} receptors in humans: preliminary analyses

Energy Technology Data Exchange (ETDEWEB)

Martinez, Diana; Mawlawi, Osama; Hwang, Dah-Ren; Kent, Justine; Simpson, Norman; Parsey, Ramin V.; Hashimoto, Tomoki; Slifstein, Mark; Huang Yiyun; Heertum, Ronald van; Abi-Dargham, Anissa; Caltabiano, Stephen; Malizia, Andrea; Cowley, Hugh; Mann, J. John; Laruelle, Marc

2000-07-01

Preclinical studies in rodents suggest that augmentation of serotonin reuptake inhibitors (SSRIs) therapy by the 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response. This hypothesis is based on the ability of pindolol to potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an effect achieved by blockade of the 5-HT{sub 1A} autoreceptors in the dorsal raphe nuclei (DRN). However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT{sub 1A} receptors following treatment with controlled release pindolol in nine healthy volunteers with positron-emission tomography (PET). Each subject was studied four times: at baseline (scan 1), following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and following one dose of pindolol CR (30 mg) (at peak level, 4 h) (scan 4). Pindolol occupancy of 5-HT{sub 1A} receptors was evaluated in the DRN and cortical regions as the decrease in binding potential (BP) of the radiolabelled selective 5-HT{sub 1A} antagonist [carbonyl-{sup 11}C]WAY-100635 or [carbonyl-{sup 11}C] N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide abbreviated as [{sup 11}C]WAY-100635. Pindolol dose-dependently decreased [{sup 11}C]WAY-100635 BP. Combining all the regions, occupancy was 20 {+-} 8% at scan 2, 14 {+-} 8% at scan 3, and 44 {+-} 8% at scan 4. The results of this study suggest that at doses used in clinical studies of augmentation of the SSRI effect by pindolol (2.5 mg t.i.d.), the occupancy of 5-HT{sub 1A} receptors is moderate and highly variable between subjects. This factor might explain the variable results obtained in clinical studies. On the other hand, at each dose tested, pindolol occupancy of 5

Usefulness of perfusion MR imaging in hyperacute ischemic stroke

International Nuclear Information System (INIS)

Park, Ji Hoon; Kim, Jae Hyoung; Shin, Tae Min; Lee, Eun Ja; Chung, Sung Hoon; Choi, Nack Cheon; Lim, Byeong Hoon; Kim, In One

1998-01-01

Perfusion MR imaging is a new technique for the assessment of acute ischemic stroke. The aim of this study was to evaluate the usefulness of this imaging in hyperacute ischemic stroke in comparison with conventional CT and MR imaging. Eight patients presenting the symptoms of acute ischemic stroke due to middle cerebral artery occlusion were included in this study. Within 2 hours of initial CT scan and 6 hours after the onset of stroke, perfusion MR imaging was performed in all patients using a single-section dynamic contrast-enhanced T2*-weighted imager in conjunction with conventional routine MR imaging and MR angiography. Cerebral blood volume (CBV) maps were then obtained from dynamic MR imaging data by using numerical integration techniques. The findings of CBV maps were compared with those of initial and follow-up CT or MR images. The findings of CBV maps were obviously abnormal in all patients, as compared with normal or focal subtle abnormal findings seen on initial CT and MR images. CBV in the occluded arterial territory was lower in all eight patients;two had focal regions of increased CBV within the affected territory, indicating reperfusion hyperemia. In all patients, regions of abnormal CBV were eventually converted to infarctions on follow-up images. Perfusion MR imaging was useful for the evaluation of hemodynamic change occurring during cerebral perfusion in hyperacute ischemic stroke, and prediction of the final extent of infarction. These results suggest that pertusion MR imaging can play an important role in the diagnosis and management of hyperacute ischemic stroke.=20

Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets.

Science.gov (United States)

Penatti, E M; Berniker, A V; Kereshi, B; Cafaro, C; Kelly, M L; Niblock, M M; Gao, H G; Kinney, H C; Li, A; Nattie, E E

2006-10-01

Acute inhibition of serotonergic (5-HT) neurons in the medullary raphé (MR) using a 5-HT(1A) receptor agonist had an age-dependent impact on the "CO(2) response" of piglets (33). Our present study explored the effect of chronic 5-HT neuron lesions in the MR and extra-raphé on the ventilatory response to hypercapnia and hypoxia in piglets, with possible implications on the role of 5-HT in the sudden infant death syndrome. We established four experimental groups. Group 1 (n = 11) did not undergo any treatment. Groups 2, 3, and 4 were injected with either vehicle or the neurotoxin 5,7-dihydroxytryptamine in the cisterna magna during the first week of life (group 2, n = 9; group 4, n = 11) or second week of life (group 3, n = 10). Ventilation was recorded in response to 5% CO(2) (all groups) and 12% O(2) (group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO(2) sensitivity during early postnatal development. Overall, considerable lesions of 5-HT neurons (up to 65% decrease) in the MR and extra-raphé had no impact on the CO(2) response, regardless of injection time. Postlesion raphé plasticity could explain why we observed no effect. 5,7-Dihydroxytryptamine-treated males, however, did present a lower CO(2) response during sleep. Hypoxia significantly altered the frequency during sleep in lesioned piglets. Further studies are necessary to elucidate the role of plasticity, sex, and 5-HT abnormalities in sudden infant death syndrome.

Role of MR imaging in chronic wrist pain

Energy Technology Data Exchange (ETDEWEB)

Zanetti, Marco; Saupe, Nadja [University Hospital Balgrist, Department of Radiology, Zurich (Switzerland); Nagy, Ladislav [University Hospital Balgrist, Department of Orthopedic Surgery, Zurich (Switzerland)

2007-04-15

Magnetic resonance (MR) imaging for chronic wrist pain is challenging. Correct assessment of the triangular fibrocartilage, hyaline cartilage, ligaments, and tendons has become mandatory for comprehensive decision making in wrist surgery. The MR technique, potential and limits of MR imaging in patients with chronic wrist pain will be discussed. MR arthrography with injection of gadolinium-containing contrast material into the distal radioulnar joint is suggested for evaluation of the triangular fibrocartilage. The clinically meaningful ulnar-sided peripheral tears are otherwise hard to diagnose. The diagnostic performance of MR imaging for interosseous ligament tears varies considerably. The sensitivity for scapholunate ligament tears is consistently better than for lunotriquetral ligament tears. Gadolinium-enhanced MR imaging is considered to be the best technique for detecting established avascularity of bone, but the assessment of the MR results remains challenging. Most cases of ulnar impaction syndrome have characteristic focal signal intensity changes in the ulnar aspect of the lunate. Avascular necrosis of the lunate (Kienboeck's disease) is characterized by signal changes starting in the proximal radial aspect of the lunate. MR imaging is extremely sensitive for occult fractures. Questions arise if occult posttraumatic bone lesions seen on MR images only necessarily require the same treatment as fractures evident on plain films or computed tomography (CT) images. MR imaging and ultrasound are equally effective for detecting occult carpal ganglia. Carpe bossu (carpal boss) is a bony protuberance of a carpometacarpal joint II and III which may be associated with pain. (orig.)

Role of MR imaging in chronic wrist pain

International Nuclear Information System (INIS)

Zanetti, Marco; Saupe, Nadja; Nagy, Ladislav

2007-01-01

Magnetic resonance (MR) imaging for chronic wrist pain is challenging. Correct assessment of the triangular fibrocartilage, hyaline cartilage, ligaments, and tendons has become mandatory for comprehensive decision making in wrist surgery. The MR technique, potential and limits of MR imaging in patients with chronic wrist pain will be discussed. MR arthrography with injection of gadolinium-containing contrast material into the distal radioulnar joint is suggested for evaluation of the triangular fibrocartilage. The clinically meaningful ulnar-sided peripheral tears are otherwise hard to diagnose. The diagnostic performance of MR imaging for interosseous ligament tears varies considerably. The sensitivity for scapholunate ligament tears is consistently better than for lunotriquetral ligament tears. Gadolinium-enhanced MR imaging is considered to be the best technique for detecting established avascularity of bone, but the assessment of the MR results remains challenging. Most cases of ulnar impaction syndrome have characteristic focal signal intensity changes in the ulnar aspect of the lunate. Avascular necrosis of the lunate (Kienboeck's disease) is characterized by signal changes starting in the proximal radial aspect of the lunate. MR imaging is extremely sensitive for occult fractures. Questions arise if occult posttraumatic bone lesions seen on MR images only necessarily require the same treatment as fractures evident on plain films or computed tomography (CT) images. MR imaging and ultrasound are equally effective for detecting occult carpal ganglia. Carpe bossu (carpal boss) is a bony protuberance of a carpometacarpal joint II and III which may be associated with pain. (orig.)

5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol.

Science.gov (United States)

Belmer, Arnauld; Patkar, Omkar L; Lanoue, Vanessa; Bartlett, Selena E

2018-02-01

Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT 1A ) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT 1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT 1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT 1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT 1A partial agonists represent a promising treatment strategy for alcohol abuse.

Indirect MR venography: contrast medium protocols, postprocessing and combination in diagnosing pulmonary emboli with MRI; Indirekte MR-Phlebografie: Kontrastmittelprotokolle, Nachverarbeitung und Kombination mit Lungenemboliediagnostik in der MRT

Energy Technology Data Exchange (ETDEWEB)

Kluge, A.; Bachmann, G. [Diagnostische Radiologie, Kerckhoff-Klinik, Bad Nauheim (Germany); Rominger, M. [Diagnostische Radiologie, Phillips-Univ. Marburg (Germany); Schoenburg, M. [Herzchirurgie, Kerckhoff-Klinik, Bad Nauheim (Germany)

2004-07-01

Purpose: Integration of MR venography in a comprehensive MR imaging protocol in patients with suspected pulmonary embolism (PE) and evaluation of contrast media dosage, timing and postprocessing for diagnostic accuracy. Materials and Methods: Fortyeight consecutive inpatients with suspected PE or deep vein thrombosis were examined by MR venography according to one of the following protocols: protocol I: MR venography only, 0.25 mmol/kg bodyweight (BW) Gadopentate dimeglumine(Gd-DTPA) as single dose, bolus timing; protocol II: MR angiography of pulmonary arteries with a cumulative dosage of 0.25 mmol/kg contrast media, modification of coil setting for MR venography without further contrast media application; protocol III: as protocol II but with 0.125 mmol/kg BW, followed by MR venography. Signal-to-noise ratio, contrast-to-noise ratio, number of definable vascular segments and image quality were evaluated. The results were compared to conventional bilateral venography. Results: All MR venography examinations were of diagnostic quality and the examination time was below 10 min. MR venography could be performed in all 48 patients comparted to 43 of 48 patients for conventional venography. Significantly more superficial and deep veins of the leg could be visualized by MR venography (94% compared to 83% for conventional venography). Sensitivity and specificity were 100% and 92%, respectively. Quality differed significantly between 0.125 mmol/kg (protocol III) and 0.25 mmol/kg Gd-DTPA (protocols I and II) while timing did not influence quality (protocol I vs. II). (orig.) [German] Ziel: Integration der MR-Phlebografie in ein umfassendes Konzept der MRT-Diagnostik bei Verdacht auf Lungenembolie (LE). Untersuchung des Einflusses von Kontrastmittelmenge, -bolusform und Verzoegerungszeit sowie der Nachverarbeitung auf die diagnostische Qualitaet von MR-Phlebografien. Material und Methode: Bei 48 konsekutiven stationaeren Patienten mit Verdacht auf Beinvenenthrombose (TVT

Recombinant HT{sub m4} gene, protein and assays

Science.gov (United States)

Lim, B.; Adra, C.N.; Lelias, J.M.

1996-09-03

The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

DEFF Research Database (Denmark)

Paterson, Louise M; Tyacke, Robin J; Nutt, David J

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron......, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors and the serotonin reuptake transporter...... have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made...

Liraglutide, a GLP-1 Receptor Agonist, Which Decreases Hypothalamic 5-HT2A Receptor Expression, Reduces Appetite and Body Weight Independently of Serotonin Synthesis in Mice

Directory of Open Access Journals (Sweden)

Katsunori Nonogaki

2018-01-01

Full Text Available A recent report suggested that brain-derived serotonin (5-HT is critical for maintaining weight loss induced by glucagon-like peptide-1 (GLP-1 receptor activation in rats and that 5-HT2A receptors mediate the feeding suppression and weight loss induced by GLP-1 receptor activation. Here, we show that changes in daily food intake and body weight induced by intraperitoneal administration of liraglutide, a GLP-1 receptor agonist, over 4 days did not differ between mice treated with the tryptophan hydroxylase (Tph inhibitor p-chlorophenylalanine (PCPA for 3 days and mice without PCPA treatment. Treatment with PCPA did not affect hypothalamic 5-HT2A receptor expression. Despite the anorexic effect of liraglutide disappearing after the first day of treatment, the body weight loss induced by liraglutide persisted for 4 days in mice treated with or without PCPA. Intraperitoneal administration of liraglutide significantly decreased the gene expression of hypothalamic 5-HT2A receptors 1 h after injection. Moreover, the acute anorexic effects of liraglutide were blunted in mice treated with the high-affinity 5-HT2A agonist (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl methylamine hydrobromide 14 h or 24 h before liraglutide injection. These findings suggest that liraglutide reduces appetite and body weight independently of 5-HT synthesis in mice, whereas GLP-1 receptor activation downregulates the gene expression of hypothalamic 5-HT2A receptors.

Data products of NASA Goddard's LiDAR, hyperspectral, and thermal airborne imager (G-LiHT)

Science.gov (United States)

Corp, Lawrence A.; Cook, Bruce D.; McCorkel, Joel; Middleton, Elizabeth M.

2015-06-01

Scientists in the Biospheric Sciences Laboratory at NASA's Goddard Space Flight Center have undertaken a unique instrument fusion effort for an airborne package that integrates commercial off the shelf LiDAR, Hyperspectral, and Thermal components. G-LiHT is a compact, lightweight and portable system that can be used on a wide range of airborne platforms to support a number of NASA Earth Science research projects and space-based missions. G-LiHT permits simultaneous and complementary measurements of surface reflectance, vegetation structure, and temperature, which provide an analytical framework for the development of new algorithms for mapping plant species composition, plant functional types, biodiversity, biomass, carbon stocks, and plant growth. G-LiHT and its supporting database are designed to give scientists open access to the data that are needed to understand the relationship between ecosystem form and function and to stimulate the advancement of synergistic algorithms. This system will enhance our ability to design new missions and produce data products related to biodiversity and climate change. G-LiHT has been operational since 2011 and has been used to collect data for a number of NASA and USFS sponsored studies, including NASA's Carbon Monitoring System (CMS) and the American ICESat/GLAS Assessment of Carbon (AMIGA-Carb). These acquisitions target a broad diversity of forest communities and ecoregions across the United States and Mexico. Here, we will discuss the components of G-LiHT, their calibration and performance characteristics, operational implementation, and data processing workflows. We will also provide examples of higher level data products that are currently available.

Barriers to Implementing Treatment Integrity Procedures: Survey of Treatment Outcome Researchers

Science.gov (United States)

Perepletchikova, Francheska; Hilt, Lori M.; Chereji, Elizabeth; Kazdin, Alan E.

2009-01-01

Treatment integrity refers to implementing interventions as intended. Treatment integrity is critically important for experimental validity and for drawing valid inferences regarding the relationship between treatment and outcome. Yet, it is rarely adequately addressed in psychotherapy research. The authors examined barriers to treatment integrity…

Transient failure behavior of HT9

International Nuclear Information System (INIS)

Huang, F.H.

1994-07-01

Alloy HT9 has-been chosen as candidate materials for fast and fusion reactor applications because the.material exhibits excellent resistance to void swelling. However, ferritic alloys are known to undergo a ductile-brittle transition as the test temperature is decreased. This inherent problem has limited their applications to reactor component materials subjected to low neutron exposures. Despite the ductile-brittle transition problem, results show that the materials exhibit superior resistance to fracture under very high neutron fluences at irradiation temperatures above 380C. Results also show that the transient behavior for HT9 cladding specimens taken from the fuel column region and cladding taken from outside the fuel column or unirradiated cladding are the same. HT9 cladding maintained its transient strength with irradiation to a fluence of 9 x 10 22 n/cm 2 (E > 0.1 MeV)

Effects of acetone-soaking treatment on the performance of polymer solar cells based on P3HT/PCBM bulk heterojunction

International Nuclear Information System (INIS)

Liu Yu-Xuan; Lü Long-Feng; Ning Yu; Lu Yun-Zhang; Lu Qi-Peng; Zhang Chun-Mei; Fang Yi; Hu Yu-Feng; Lou Zhi-Dong; Teng Feng; Hou Yan-Bing; Tang Ai-Wei

2014-01-01

The improvement of the acetone-soaking treatment to the performance of polymer solar cells based on the P3HT/PCBM bulk heterojunction is reported. Undergoing acetone-soaking, the PCBM does not distribute uniformly in the vertical direction, a PCBM enrichment layer forms on the top of the active layer, which is beneficial to the collection of the carriers and blocking the inverting diffusion carriers. X-ray photoelectron spectroscopy (XPS) analysis reveals that the PCBM weight ratio on the top of the active layer increases by 20% after the acetone-soaking treatment. Due to the nonuniform distribution of PCBM, the short-circuit current density, the open-circuit voltage, and the fill factor are enhanced significantly. Finally, the power conversion efficiency of the acetone-soaking device increases by 31% compared with the control device. (interdisciplinary physics and related areas of science and technology)

P3HT-graphene bilayer electrode for Schottky junction photodetectors

Science.gov (United States)

Aydın, H.; Kalkan, S. B.; Varlikli, C.; Çelebi, C.

2018-04-01

We have investigated the effect of a poly (3-hexylthiophene-2.5-diyl)(P3HT)-graphene bilayer electrode on the photoresponsivity characteristics of Si-based Schottky photodetectors. P3HT, which is known to be an electron donor and absorb light in the visible spectrum, was placed on CVD grown graphene by dip-coating method. The results of the UV-vis and Raman spectroscopy measurements have been evaluated to confirm the optical and electronic modification of graphene by the P3HT thin film. Current-voltage measurements of graphene/Si and P3HT-graphene/Si revealed rectification behavior confirming a Schottky junction formation at the graphene/Si interface. Time-resolved photocurrent spectroscopy measurements showed the devices had excellent durability and a fast response speed. We found that the maximum spectral photoresponsivity of the P3HT-graphene/Si photodetector increased more than three orders of magnitude compared to that of the bare graphene/Si photodetector. The observed increment in the photoresponsivity of the P3HT-graphene/Si samples was attributed to the charge transfer doping from P3HT to graphene within the spectral range between near-ultraviolet and near-infrared. Furthermore, the P3HT-graphene electrode was found to improve the specific detectivity and noise equivalent power of graphene/Si photodetectors. The obtained results showed that the P3HT-graphene bilayer electrodes significantly improved the photoresponsivity characteristics of our samples and thus can be used as a functional component in Si-based optoelectronic device applications.

Image artifacts from MR-based attenuation correction in clinical, whole-body PET/MRI

DEFF Research Database (Denmark)

Keller, Sune H; Holm, Søren; Hansen, Adam E

2013-01-01

Integrated whole-body PET/MRI tomographs have become available. PET/MR imaging has the potential to supplement, or even replace combined PET/CT imaging in selected clinical indications. However, this is true only if methodological pitfalls and image artifacts arising from novel MR-based attenuation...

The role of 5-HT(1A) receptors in learning and memory.

Science.gov (United States)

Ogren, Sven Ove; Eriksson, Therese M; Elvander-Tottie, Elin; D'Addario, Claudio; Ekström, Joanna C; Svenningsson, Per; Meister, Björn; Kehr, Jan; Stiedl, Oliver

2008-12-16

The ascending serotonin (5-HT) neurons innervate the cerebral cortex, hippocampus, septum and amygdala, all representing brain regions associated with various domains of cognition. The 5-HT innervation is diffuse and extensively arborized with few synaptic contacts, which indicates that 5-HT can affect a large number of neurons in a paracrine mode. Serotonin signaling is mediated by 14 receptor subtypes with different functional and transductional properties. The 5-HT(1A) subtype is of particular interest, since it is one of the main mediators of the action of 5-HT. Moreover, the 5-HT(1A) receptor regulates the activity of 5-HT neurons via autoreceptors, and it regulates the function of several neurotransmitter systems via postsynaptic receptors (heteroreceptors). This review assesses the pharmacological and genetic evidence that implicates the 5-HT(1A) receptor in learning and memory. The 5-HT(1A) receptors are in the position to influence the activity of glutamatergic, cholinergic and possibly GABAergic neurons in the cerebral cortex, hippocampus and in the septohippocampal projection, thereby affecting declarative and non-declarative memory functions. Moreover, the 5-HT(1A) receptor regulates several transduction mechanisms such as kinases and immediate early genes implicated in memory formation. Based on studies in rodents the stimulation of 5-HT(1A) receptors generally produces learning impairments by interfering with memory-encoding mechanisms. In contrast, antagonists of 5-HT(1A) receptors facilitate certain types of memory by enhancing hippocampal/cortical cholinergic and/or glutamatergic neurotransmission. Some data also support a potential role for the 5-HT(1A) receptor in memory consolidation. Available results also implicate the 5-HT(1A) receptor in the retrieval of aversive or emotional memories, supporting an involvement in reconsolidation. The contribution of 5-HT(1A) receptors in cognitive impairments in various psychiatric disorders is still

MR-imaging of anterior tibiotalar impingement syndrome: Agreement, sensitivity and specificity of MR-imaging and indirect MR-arthrography

Energy Technology Data Exchange (ETDEWEB)

Haller, Joerg [Department of Radiology, Hanusch Hospital, Heinrich Collin-Strasse 30, A-1140 Vienna (Austria); Ludwig Boltzmann Institute for Osteology, Hanusch Hospital, Heinrich Collin-Strasse 30, A-1140 Vienna (Austria); Bernt, Reinhard [Department of Radiology, Hanusch Hospital, Heinrich Collin-Strasse 30, A-1140 Vienna (Austria)]. E-mail: reinhard.bernt@wgkk.sozvers.at; Seeger, Thomas [Department of Trauma Surgery, Hanusch Hospital, Heinrich Collin-Strasse 30, A-1140 Vienna (Austria); Weissenbaeck, Alexander [Department of Trauma Surgery, Hanusch Hospital, Heinrich Collin-Strasse 30, A-1140 Vienna (Austria); Tuechler, Heinrich [Ludwig Boltzmann Institute for Hematology, Hanusch Hospital, Heinrich Collin-Strasse 30, A-1140 Vienna (Austria); Resnick, Donald [Department of Radiology, VA Medical Center, UCSD, 3350 La Jolla Village Dr, San Diego, CA 92161 (United States)

2006-06-15

Objective: To clarify the role of MR-imaging in the diagnosis of anterior ankle impingement syndromes. Materials and methods: We prospectively examined 51 consecutive patients with chronic ankle pain by MR-imaging. Arthroscopy was performed in 29 patients who previously underwent non-enhanced MR-imaging; in 11 patients, indirect MR-arthrography additionally was performed. MR-examinations were correlated with clinical findings; MR and arthroscopy scores were statistically compared, agreement was measured. Results: Arthroscopy demonstrated granulation tissue in the lateral gutter (38%) and anterior recess (31%), lesions of the anterior tibiofibular (31%) and the anterior talofibular ligament (21%) as well as intraarticular bodies (10%). Stenosing tenosynovitis and a ganglionic cyst were revealed as extraarticular causes for chronic ankle pain by MR-examination (17%). Agreement of MR-imaging and arthroscopy was fair for the anterior talofibular ligament and the anterior joint cavity (kappa 0.40). Major discrepancy was found for non-enhanced MR scans (kappa 0.49) when compared with indirect MR-arthrography (kappa 0.03) in the anterior cavity. The sensitivity for lesions of the anterior talofibular and calcaneofibular ligament and the anterior cavity (0.91-0.87) detected by MR-imaging was superior in comparison to lesions of the anterior tibiofibular ligament and anteromedial cavity (0.50-0.24). Conclusion: MR-imaging provides additional information about the mechanics of chronic ankle impingement rather than an accurate diagnosis of this clinical entity. The method is helpful in differentiating extra- from intra-articular causes of ankle impingement. Indirect MR-arthrography has little or no additional value in patients with ankle impingement syndrome.

MR-imaging of anterior tibiotalar impingement syndrome: Agreement, sensitivity and specificity of MR-imaging and indirect MR-arthrography

International Nuclear Information System (INIS)

Haller, Joerg; Bernt, Reinhard; Seeger, Thomas; Weissenbaeck, Alexander; Tuechler, Heinrich; Resnick, Donald

2006-01-01

Objective: To clarify the role of MR-imaging in the diagnosis of anterior ankle impingement syndromes. Materials and methods: We prospectively examined 51 consecutive patients with chronic ankle pain by MR-imaging. Arthroscopy was performed in 29 patients who previously underwent non-enhanced MR-imaging; in 11 patients, indirect MR-arthrography additionally was performed. MR-examinations were correlated with clinical findings; MR and arthroscopy scores were statistically compared, agreement was measured. Results: Arthroscopy demonstrated granulation tissue in the lateral gutter (38%) and anterior recess (31%), lesions of the anterior tibiofibular (31%) and the anterior talofibular ligament (21%) as well as intraarticular bodies (10%). Stenosing tenosynovitis and a ganglionic cyst were revealed as extraarticular causes for chronic ankle pain by MR-examination (17%). Agreement of MR-imaging and arthroscopy was fair for the anterior talofibular ligament and the anterior joint cavity (kappa 0.40). Major discrepancy was found for non-enhanced MR scans (kappa 0.49) when compared with indirect MR-arthrography (kappa 0.03) in the anterior cavity. The sensitivity for lesions of the anterior talofibular and calcaneofibular ligament and the anterior cavity (0.91-0.87) detected by MR-imaging was superior in comparison to lesions of the anterior tibiofibular ligament and anteromedial cavity (0.50-0.24). Conclusion: MR-imaging provides additional information about the mechanics of chronic ankle impingement rather than an accurate diagnosis of this clinical entity. The method is helpful in differentiating extra- from intra-articular causes of ankle impingement. Indirect MR-arthrography has little or no additional value in patients with ankle impingement syndrome

MR-fluid yield surface determination in disc-type MR rotary brakes

International Nuclear Information System (INIS)

Farjoud, Alireza; Vahdati, Nader; Fah, Yap Fook

2008-01-01

Magneto-rheological (MR) fluids are currently attracting a great deal of attention because of their unique rheological behavior. Many devices have been designed using MR fluids, and of potential interest here are disc-type MR rotary brakes. The plug flow region in MR devices is defined as the region where the fluid is not flowing. The plug flow region plays an important role in design and analysis of MR devices. In MR dampers, the damping coefficient is a function of the plug thickness. In MR valves, the plug thickness is used to control the flow rate through, and the pressure drop across, the MR valve. A MR clutch is performing at the highest efficiency when the entire MR gap is the plug region. For an MR rotary brake, the highest restraining torque is obtained when the entire gap is the plug region as far as there are no wall slip effects. In this paper, using the Bercovier and Engelman constitutive model, the MR fluid flow in disc-type MR brakes is modeled to determine the plug flow region. The resulting system of equations is solved numerically. It is shown that the existence of a plug flow region in the brake will affect the control torque ratio. Better estimation of the plug flow region results in better estimation of the viscous torque

MrSkn7 controls sporulation, cell wall integrity, autolysis, and virulence in Metarhizium robertsii.

Science.gov (United States)

Shang, Yanfang; Chen, Peilin; Chen, Yixiong; Lu, Yuzhen; Wang, Chengshu

2015-04-01

Two-component signaling pathways generally include sensor histidine kinases and response regulators. We identified an ortholog of the response regulator protein Skn7 in the insect-pathogenic fungus Metarhizium robertsii, which we named MrSkn7. Gene deletion assays and functional characterizations indicated that MrSkn7 functions as a transcription factor. The MrSkn7 null mutant of M. robertsii lost the ability to sporulate and had defects in cell wall biosynthesis but was not sensitive to oxidative and osmotic stresses compared to the wild type. However, the mutant was able to produce spores under salt stress. Insect bioassays using these spores showed that the virulence of the mutant was significantly impaired compared to that of the wild type due to the failures to form the infection structure appressorium and evade host immunity. In particular, deletion of MrSkn7 triggered cell autolysis with typical features such as cell vacuolization, downregulation of repressor genes, and upregulation of autolysis-related genes such as extracellular chitinases and proteases. Promoter binding assays confirmed that MrSkn7 could directly or indirectly control different putative target genes. Taken together, the results of this study help us understand the functional divergence of Skn7 orthologs as well as the mechanisms underlying the development and control of virulence in insect-pathogenic fungi. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

CT- and MR-guided interventions in radiology. 2. ed.

International Nuclear Information System (INIS)

Mahnken, Andreas H.; Wilhelm, Kai E.; Ricke, Jens

2013-01-01

Revised and extended second edition that covers a broad range of non-vascular interventions guided by CT or MR imaging. Discusses in detail indications, materials, techniques, and results. Includes a comprehensive section on interventional oncology. Richly illustrated source of information and guidance for all radiologists who deal with non-vascular procedures. Interventional radiology is an indispensable and still expanding area of modern medicine that encompasses numerous diagnostic and therapeutic procedures. Cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance (MR) have emerged as important techniques for non-vascular interventions, including percutaneous biopsy, drainage, ablation, and neurolysis. Various organs, diseases, and lesions can be approached in this way, permitting the treatment and management of tumors, fluid collections, and pain, the embolization of endoleaks, the provision of access to hollow organs, etc. Accordingly, interventional radiology is now an integral component of the interdisciplinary management of numerous disorders. The revised and significantly extended second edition of this volume covers a broad range of non-vascular interventions guided by CT or MR imaging. Indications, materials, techniques, and results are all carefully discussed. A particularly comprehensive section is devoted to interventional oncology as the most rapidly growing branch of interventional radiology. In addition, detailed information is provided that will assist in establishing and developing an interventional service. This richly illustrated book will be a most valuable source of information and guidance for all radiologists who deal with non-vascular procedures.

On the accuracy and reproducibility of a novel probabilistic atlas-based generation for calculation of head attenuation maps on integrated PET/MR scanners.

Science.gov (United States)

Chen, Kevin T; Izquierdo-Garcia, David; Poynton, Clare B; Chonde, Daniel B; Catana, Ciprian

2017-03-01

To propose an MR-based method for generating continuous-valued head attenuation maps and to assess its accuracy and reproducibility. Demonstrating that novel MR-based photon attenuation correction methods are both accurate and reproducible is essential prior to using them routinely in research and clinical studies on integrated PET/MR scanners. Continuous-valued linear attenuation coefficient maps ("μ-maps") were generated by combining atlases that provided the prior probability of voxel positions belonging to a certain tissue class (air, soft tissue, or bone) and an MR intensity-based likelihood classifier to produce posterior probability maps of tissue classes. These probabilities were used as weights to generate the μ-maps. The accuracy of this probabilistic atlas-based continuous-valued μ-map ("PAC-map") generation method was assessed by calculating the voxel-wise absolute relative change (RC) between the MR-based and scaled CT-based attenuation-corrected PET images. To assess reproducibility, we performed pair-wise comparisons of the RC values obtained from the PET images reconstructed using the μ-maps generated from the data acquired at three time points. The proposed method produced continuous-valued μ-maps that qualitatively reflected the variable anatomy in patients with brain tumor and agreed well with the scaled CT-based μ-maps. The absolute RC comparing the resulting PET volumes was 1.76 ± 2.33 %, quantitatively demonstrating that the method is accurate. Additionally, we also showed that the method is highly reproducible, the mean RC value for the PET images reconstructed using the μ-maps obtained at the three visits being 0.65 ± 0.95 %. Accurate and highly reproducible continuous-valued head μ-maps can be generated from MR data using a probabilistic atlas-based approach.

On the accuracy and reproducibility of a novel probabilistic atlas-based generation for calculation of head attenuation maps on integrated PET/MR scanners

Energy Technology Data Exchange (ETDEWEB)

Chen, Kevin T. [Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown, MA (United States); Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, MA (United States); Izquierdo-Garcia, David; Catana, Ciprian [Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown, MA (United States); Poynton, Clare B. [Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown, MA (United States); Massachusetts General Hospital, Department of Psychiatry, Boston, MA (United States); University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Chonde, Daniel B. [Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown, MA (United States); Harvard University, Program in Biophysics, Cambridge, MA (United States)

2017-03-15

To propose an MR-based method for generating continuous-valued head attenuation maps and to assess its accuracy and reproducibility. Demonstrating that novel MR-based photon attenuation correction methods are both accurate and reproducible is essential prior to using them routinely in research and clinical studies on integrated PET/MR scanners. Continuous-valued linear attenuation coefficient maps (''μ-maps'') were generated by combining atlases that provided the prior probability of voxel positions belonging to a certain tissue class (air, soft tissue, or bone) and an MR intensity-based likelihood classifier to produce posterior probability maps of tissue classes. These probabilities were used as weights to generate the μ-maps. The accuracy of this probabilistic atlas-based continuous-valued μ-map (''PAC-map'') generation method was assessed by calculating the voxel-wise absolute relative change (RC) between the MR-based and scaled CT-based attenuation-corrected PET images. To assess reproducibility, we performed pair-wise comparisons of the RC values obtained from the PET images reconstructed using the μ-maps generated from the data acquired at three time points. The proposed method produced continuous-valued μ-maps that qualitatively reflected the variable anatomy in patients with brain tumor and agreed well with the scaled CT-based μ-maps. The absolute RC comparing the resulting PET volumes was 1.76 ± 2.33 %, quantitatively demonstrating that the method is accurate. Additionally, we also showed that the method is highly reproducible, the mean RC value for the PET images reconstructed using the μ-maps obtained at the three visits being 0.65 ± 0.95 %. Accurate and highly reproducible continuous-valued head μ-maps can be generated from MR data using a probabilistic atlas-based approach. (orig.)

Whole body MR in patients with multiple myeloma

International Nuclear Information System (INIS)

Piekarek, A.; Sosnowski, P.; Nowicki, A.; Komarnicki, M.

2009-01-01

Background: Multiple myeloma is a cancer of plasma cells which leads to bone marrow infiltration. Aim: Whole-body MR is the most sensitive imaging method available to detect multiple myeloma lesions. Ma terial and methods: MR scans were performed in 100 patients with multiple myeloma who were receiving treatment in the Haematology Clinic in Poznan in the years 2005 - 2006. Whole-body MR scans were performed with general coil 1.0 T in STIR sequences and T1 sequences, in coronal and sagittal planes with scanning area covering the head, neck, trunk and the limbs (FOV for specific regions was 36 -48 cm). The bone lesions were classified as focal (monofocal/multifocal lesions), infiltrative, mixed and 'salt and pepper' type. Depending on the size of the lesions the patients were included in one of three groups according to Salmon-Durie Plus classification. Results: Four main types of multiple myeloma were distinguished based on MR scans: focal (48 patients; monofocal in 10 patients), infiltrative (17 patients), mixed type (19 patients) and 'salt and pepper' type (4 patients). The remaining 12 patients had no multiple myeloma lesions in the bone marrow. Additionally, in 18% of patients a soft tissue mass could be observed. According to Salmon-Durie Plus categorisation 27 subjects were classified as having stage I, 16 patients stage and 57 patients stage III disease. In 12% of patients MR data changed the disease staging. Conclusions: WB MR is a sensitive and effective diagnostic method with an important impact on staging and further treatment of multiple myeloma. (authors)

MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors.

Directory of Open Access Journals (Sweden)

Tsuicheng D Chiu

Full Text Available Multi-modality image-guided radiotherapy is the standard of care in contemporary cancer management; however, it is not common in preclinical settings due to both hardware and software limitations. Soft tissue lesions, such as orthotopic prostate tumors, are difficult to identify using cone beam computed tomography (CBCT imaging alone. In this study, we characterized a research magnetic resonance (MR scanner for preclinical studies and created a protocol for combined MR-CBCT image-guided small animal radiotherapy. Two in-house dual-modality, MR and CBCT compatible, phantoms were designed and manufactured using 3D printing technology. The phantoms were used for quality assurance tests and to facilitate end-to-end testing for combined preclinical MR and CBCT based treatment planning. MR and CBCT images of the phantoms were acquired utilizing a Varian 4.7 T scanner and XRad-225Cx irradiator, respectively. The geometry distortion was assessed by comparing MR images to phantom blueprints and CBCT. The corrected MR scans were co-registered with CBCT and subsequently used for treatment planning. The fidelity of 3D printed phantoms compared to the blueprint design yielded favorable agreement as verified with the CBCT measurements. The geometric distortion, which varied between -5% and 11% throughout the scanning volume, was substantially reduced to within 0.4% after correction. The distortion free MR images were co-registered with the corresponding CBCT images and imported into a commercial treatment planning software SmART Plan. The planning target volume (PTV was on average 19% smaller when contoured on the corrected MR-CBCT images relative to raw images without distortion correction. An MR-CBCT based preclinical workflow was successfully designed and implemented for small animal radiotherapy. Combined MR-CBCT image-guided radiotherapy for preclinical research potentially delivers enhanced relevance to human radiotherapy for various disease sites. This

MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors.

Science.gov (United States)

Chiu, Tsuicheng D; Arai, Tatsuya J; Campbell Iii, James; Jiang, Steve B; Mason, Ralph P; Stojadinovic, Strahinja

2018-01-01

Multi-modality image-guided radiotherapy is the standard of care in contemporary cancer management; however, it is not common in preclinical settings due to both hardware and software limitations. Soft tissue lesions, such as orthotopic prostate tumors, are difficult to identify using cone beam computed tomography (CBCT) imaging alone. In this study, we characterized a research magnetic resonance (MR) scanner for preclinical studies and created a protocol for combined MR-CBCT image-guided small animal radiotherapy. Two in-house dual-modality, MR and CBCT compatible, phantoms were designed and manufactured using 3D printing technology. The phantoms were used for quality assurance tests and to facilitate end-to-end testing for combined preclinical MR and CBCT based treatment planning. MR and CBCT images of the phantoms were acquired utilizing a Varian 4.7 T scanner and XRad-225Cx irradiator, respectively. The geometry distortion was assessed by comparing MR images to phantom blueprints and CBCT. The corrected MR scans were co-registered with CBCT and subsequently used for treatment planning. The fidelity of 3D printed phantoms compared to the blueprint design yielded favorable agreement as verified with the CBCT measurements. The geometric distortion, which varied between -5% and 11% throughout the scanning volume, was substantially reduced to within 0.4% after correction. The distortion free MR images were co-registered with the corresponding CBCT images and imported into a commercial treatment planning software SmART Plan. The planning target volume (PTV) was on average 19% smaller when contoured on the corrected MR-CBCT images relative to raw images without distortion correction. An MR-CBCT based preclinical workflow was successfully designed and implemented for small animal radiotherapy. Combined MR-CBCT image-guided radiotherapy for preclinical research potentially delivers enhanced relevance to human radiotherapy for various disease sites. This novel protocol

Structure-activity relationships of constrained phenylethylamine ligands for the serotonin 5-ht2 receptors

DEFF Research Database (Denmark)

Isberg, Vignir; Paine, James; Leth-Petersen, Sebastian

2013-01-01

Serotonergic ligands have proven effective drugs in the treatment of migraine, pain, obesity, and a wide range of psychiatric and neurological disorders. There is a clinical need for more highly 5-HT2 receptor subtype-selective ligands and the most attention has been given to the phenethylamine...... about the bioactive conformation of the amine functionality. However, combined 1,2-constriction by cyclization has only been tested with one compound. Here, we present three new 1,2-cyclized phenylethylamines, 9-11, and describe their synthetic routes. Ligand docking in the 5-HT2B crystal structure...... but shift the placement of the core scaffold. The constraints in 9-11 resulted in docking poses with the 4-bromine in closer vicinity to 5.46, which is polar only in the human 5-HT2A subtype, for which 9-11 have the lowest affinity. The new ligands, conformational analysis and docking expand the structure...

Synthesis and characterization of magneto-rheological (MR fluids for MR brake application

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Bhau K. Kumbhar

2015-09-01

Full Text Available Magneto rheological (MR fluid technology has been proven for many industrial applications like shock absorbers, actuators, etc. MR fluid is a smart material whose rheological characteristics change rapidly and can be controlled easily in presence of an applied magnetic field. MR brake is a device to transmit torque by the shear stress of MR fluid. However, MR fluids exhibit yield stress of 50–90 kPa. In this research, an effort has been made to synthesize MR fluid sample/s which will typically meet the requirements of MR brake applications. In this study, various electrolytic and carbonyl iron powder based MR fluids have been synthesized by mixing grease as a stabilizer, oleic acid as an antifriction additive and gaur gum powder as a surface coating to reduce agglomeration of the MR fluid. MR fluid samples based on sunflower oil, which is bio-degradable, environmentally friendly and abundantly available have also been synthesized. These MR fluid samples are characterized for determination of magnetic, morphological and rheological properties. This study helps identify most suitable localized MR fluid meant for MR brake application.

Ultra-low power transmitter for encoding non-MR signals in Magnetic Resonance (MR) recordings

DEFF Research Database (Denmark)

Petersen, Jan Raagaard; Pedersen, Jan Ole; Zhurbenko, Vitaliy

collection of data from non-MRI sensors. The transmitter consumes only 1.3mW while transmitting 2.7µW at 120MHz with high frequency stability. The presented design is useful in low power applications requiring high frequency stability and is intended for wireless transmission of non-MR signal recordings......Advancing Magnetic Resonance Imaging (MRI) technology requires integration of the MRI scanners with sensors and systems for monitoring various non-MRI signals. In this paper, we present design and integration of a low power AM radio transmitter into a 3T MRI scanner, which can be used for efficient...

Distribution of serotonin 5-HT1A-binding sites in the brainstem and the hypothalamus, and their roles in 5-HT-induced sleep and ingestive behaviors in rock pigeons (Columba livia).

Science.gov (United States)

Dos Santos, Tiago Souza; Krüger, Jéssica; Melleu, Fernando Falkenburger; Herold, Christina; Zilles, Karl; Poli, Anicleto; Güntürkün, Onur; Marino-Neto, José

2015-12-15

Serotonin 1A receptors (5-HT1ARs), which are widely distributed in the mammalian brain, participate in cognitive and emotional functions. In birds, 5-HT1ARs are expressed in prosencephalic areas involved in visual and cognitive functions. Diverse evidence supports 5-HT1AR-mediated 5-HT-induced ingestive and sleep behaviors in birds. Here, we describe the distribution of 5-HT1ARs in the hypothalamus and brainstem of birds, analyze their potential roles in sleep and ingestive behaviors, and attempt to determine the involvement of auto-/hetero-5-HT1ARs in these behaviors. In 6 pigeons, the anatomical distribution of [(3)H]8-OH-DPAT binding in the rostral brainstem and hypothalamus was examined. Ingestive/sleep behaviors were recorded (1h) in 16 pigeons pretreated with MM77 (a heterosynaptic 5-HT1AR antagonist; 23 or 69 nmol) for 20 min, followed by intracerebroventricular ICV injection of 5-HT (N:8; 150 nmol), 8-OH-DPAT (DPAT, a 5-HT1A,7R agonist, 30 nmol N:8) or vehicle. 5-HT- and DPAT-induced sleep and ingestive behaviors, brainstem 5-HT neuronal density and brain 5-HT content were examined in 12 pigeons, pretreated by ICV with the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (N:6/group). The distribution of brainstem and diencephalic c-Fos immunoreactivity after ICV injection of 5-HT, DPAT or vehicle (N:5/group) into birds provided with or denied access to water is also described. 5-HT1ARs are concentrated in the brainstem 5-HTergic areas and throughout the periventricular hypothalamus, preoptic nuclei and circumventricular organs. 5-HT and DPAT produced a complex c-Fos expression pattern in the 5-HT1AR-enriched preoptic hypothalamus and the circumventricular organs, which are related to drinking and sleep regulation, but modestly affected c-Fos expression in 5-HTergic neurons. The 5-HT-induced ingestivebehaviors and the 5-HT- and DPAT-induced sleep behaviors were reduced by MM77 pretreatment. 5,7-DHT increased sleep per se, decreased tryptophan

Analysis of pairwise correlations in multi-parametric PET/MR data for biological tumor characterization and treatment individualization strategies

Energy Technology Data Exchange (ETDEWEB)

Leibfarth, Sara; Moennich, David; Thorwarth, Daniela [University Hospital Tuebingen, Section for Biomedical Physics, Department of Radiation Oncology, Tuebingen (Germany); Simoncic, Urban [University Hospital Tuebingen, Section for Biomedical Physics, Department of Radiation Oncology, Tuebingen (Germany); University of Ljubljana, Faculty of Mathematics and Physics, Ljubljana (Slovenia); Jozef Stefan Institute, Ljubljana (Slovenia); Welz, Stefan; Zips, Daniel [University Hospital Tuebingen, Department of Radiation Oncology, Tuebingen (Germany); Schmidt, Holger; Schwenzer, Nina [University Hospital Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany)

2016-07-15

The aim of this pilot study was to explore simultaneous functional PET/MR for biological characterization of tumors and potential future treatment adaptations. To investigate the extent of complementarity between different PET/MR-based functional datasets, a pairwise correlation analysis was performed. Functional datasets of N=15 head and neck (HN) cancer patients were evaluated. For patients of group A (N=7), combined PET/MR datasets including FDG-PET and ADC maps were available. Patients of group B (N=8) had FMISO-PET, DCE-MRI and ADC maps from combined PET/MRI, an additional dynamic FMISO-PET/CT acquired directly after FMISO tracer injection as well as an FDG-PET/CT acquired a few days earlier. From DCE-MR, parameter maps K{sup trans}, v{sub e} and v{sub p} were obtained with the extended Tofts model. Moreover, parameter maps of mean DCE enhancement, ΔS{sub DCE}, and mean FMISO signal 0-4 min p.i., anti A{sub FMISO}, were derived. Pairwise correlations were quantified using the Spearman correlation coefficient (r) on both a voxel and a regional level within the gross tumor volume. Between some pairs of functional imaging modalities moderate correlations were observed with respect to the median over all patient datasets, whereas distinct correlations were only present on an individual basis. Highest inter-modality median correlations on the voxel level were obtained for FDG/FMISO (r = 0.56), FDG/ anti A{sub FMISO} (r = 0.55), anti A{sub FMISO}/ΔS{sub DCE} (r = 0.46), and FDG/ADC (r = -0.39). Correlations on the regional level showed comparable results. The results of this study suggest that the examined functional datasets provide complementary information. However, only pairwise correlations were examined, and correlations could still exist between combinations of three or more datasets. These results might contribute to the future design of individually adapted treatment approaches based on multiparametric functional imaging.

PET and MR imaging: the odd couple or a match made in heaven?

Science.gov (United States)

Catana, Ciprian; Guimaraes, Alexander R; Rosen, Bruce R

2013-05-01

PET and MR imaging are modalities routinely used for clinical and research applications. Integrated scanners capable of acquiring PET and MR imaging data in the same session, sequentially or simultaneously, have recently become available for human use. In this article, we describe some of the technical advances that allowed the development of human PET/MR scanners; briefly discuss methodologic challenges and opportunities provided by this novel technology; and present potential oncologic, cardiac, and neuropsychiatric applications. These examples range from studies that might immediately benefit from PET/MR to more advanced applications on which future development might have an even broader impact.

Luteolin inhibits the colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition: an experimental study

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Xin Meng

2017-11-01

Full Text Available Objective: To study the regulating effect of luteolin on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition. Methods: Colon cancer HT-29 cells were cultured and randomly divided into two groups, control group were treated with serum-free medium without drugs and LUT group were treated with serum-free medium containing luteolin. After 24 h of treatment, cells were collected to extract RNA, and then fluorescent quantitative PCR method was used to determine the mRNA expression of proliferation genes, migration genes and epithelial-mesenchymal transition genes. Results: After 24 h of luteolin treatment, Lrig1, TSPYL5, Bim, SOX15 and DLC1 mRNA expression in LUT group were significantly higher than those in control group while RPS15a, Bad, TRPV5, TRPV6, PLD2, IBP, SphK1, FAK, Vimentin and N-cadherin mRNA expression were significantly lower than those in control group. Conclusion: Luteolin has inhibiting effect on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition.

Phthalate SHEDS-HT runs

Data.gov (United States)

U.S. Environmental Protection Agency — Inputs and outputs for SHEDS-HT runs of DiNP, DEHP, DBP. This dataset is associated with the following publication: Moreau, M., J. Leonard, K. Phillips, J. Campbell,...

MR arthrography: how I do it

International Nuclear Information System (INIS)

Bankaoglu, M.

2012-01-01

Full text: Magnetic resonance imaging has to rely on improving new various sequences and techniques and to get the best imaging quality so magnetic resonance (MR) arthrography is one of the most important technique in the assessment of selected musculoskeletal disorders. It is now widely utilized and considered by most musculoskeletal radiologists and some orthopedists to be an integral part of their clinical practice. The technique include: desired degree of joint distension with contrast medium; markedly improved imaging quality of intra-articular structures with the direct delineation so improved detection of pathology with MRI. As appliance and technique of MR arthrography is completely based on traditional arthrography of X ray. In MR arthrography additional very little amount of Gadolinium based contrast agent is added to the desired mixture of contrast material injected to the joint. As in conventional radiography MR arthrography is used to get extra information for conventional MRI . Practically any joint that can be accessed by a needle can be imaged using MR arthrography but it has been applied to limited number of joints to compare with the traditional arthrography so shoulder, knee, wrist, elbow, ankle, and hip are mostly subjects to do in MR arthrography. The procedure is also less invasive and expensive rather than diagnostic arthroscopy and should carefully indicated because it is not completely noninvasive technique so previous imaging modalities and MRI of the patients should be completed and evaluated well. During or after the procedure there has been no major complication reported by so far but more than two third of patients are known to complain some degree of pain right after or several times later than the procedure. As it is more than twenty years now it has been widely accepted helpful for diagnosis and adds some extra sensitivity to conventional MRI . Up to this time MR arthrography has proven to increase sensitivity of conventional MRI in

Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

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Hector Guillen-Ahlers

Full Text Available Matrix metalloproteinase 7 (MMP7, a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+ colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

BDNF downregulates 5-HT(2A) receptor protein levels in hippocampal cultures

DEFF Research Database (Denmark)

Trajkovska, V; Santini, M A; Marcussen, Anders Bue

2009-01-01

Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT(2A)) have been related to depression pathology. Specific 5-HT(2A) receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT(2A) receptor level. Here we show a direct effect of BDNF...... on 5-HT(2A) receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT(2A) receptor levels were further corroborated in (BDNF +/-) mice...... with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50ng/mL BDNF resulted in downregulation of 5-HT(2A), but not of 5-HT(1A), receptor protein levels. The BDNF-associated downregulation of 5-HT(2A) receptor levels was also observed in mature hippocampal organotypic cultures...

Perfusion of surgical cavity wall enhancement in early post-treatment MR imaging may stratify the time-to-progression in glioblastoma.

Directory of Open Access Journals (Sweden)

Ji Eun Park

Full Text Available To determine if perfusion in surgical cavity wall enhancement (SCWE obtained in early post-treatment MR imaging can stratify time-to-progression (TTP in glioblastoma.This study enrolled 60 glioblastoma patients with more than 5-mm-thick SCWEs as detected on contrast-enhanced MR imaging after concurrent chemoradiation therapy. Two independent readers categorized the shape and perfusion state of SCWEs as nodular or non-nodular and as having positive or negative perfusion compared with the contralateral grey matter on arterial spin labeling (ASL. The perfusion fraction on ASL within the contrast-enhancing lesion was calculated. The independent predictability of TTP was analyzed using the Kaplan-Meier method and Cox proportional hazards modelling.The perfusion fraction was higher in the non-progression group, significantly for reader 2 (P = 0.03 and borderline significantly for reader 1 (P = 0.08. A positive perfusion state and (P = 0.02 a higher perfusion fraction of the SCWE were found to become an independent predictor of longer TTP (P = 0.001 for reader 1 and P < 0.001 for reader 2. The contrast enhancement pattern did not become a TTP predictor.Assessment of perfusion in early post-treatment MR imaging can stratify TTP in patients with glioblastoma for adjuvant temozolomide therapy. Positive perfusion in SCWEs can become a predictor of a longer TTP.

Curcumin induces apoptosis and cell cycle arrest via the activation of reactive oxygen species-independent mitochondrial apoptotic pathway in Smad4 and p53 mutated colon adenocarcinoma HT29 cells.

Science.gov (United States)

Agarwal, Ayushi; Kasinathan, Akiladdevi; Ganesan, Ramamoorthi; Balasubramanian, Akhila; Bhaskaran, Jahnavi; Suresh, Samyuktha; Srinivasan, Revanth; Aravind, K B; Sivalingam, Nageswaran

2018-03-01

Curcumin is a natural dietary polyphenol compound that has various pharmacological activities such as antiproliferative and cancer-preventive activities on tumor cells. Indeed, the role reactive oxygen species (ROS) generated by curcumin on cell death and cell proliferation inhibition in colon cancer is poorly understood. In the present study, we hypothesized that curcumin-induced ROS may promote apoptosis and cell cycle arrest in colon cancer. To test this hypothesis, the apoptosis-inducing potential and cell cycle inhibition effect of ROS induced by curcumin was investigated in Smd4 and p53 mutated HT-29 colon adenocarcinoma cells. We found that curcumin treatment significantly increased the level of ROS in HT-29 cells in a dose- and time-dependent manner. Furthermore, curcumin treatment markedly decreased the cell viability and proliferation potential of HT-29 cells in a dose- and time-dependent manner. Conversely, generation of ROS and inhibitory effect of curcumin on HT-29 cells were abrogated by N-acetylcysteine treatment. In addition, curcumin treatment did not show any cytotoxic effects on HT-29 cells. Furthermore, curcumin-induced ROS generation caused the DNA fragmentation, chromatin condensation, and cell nuclear shrinkage and significantly increased apoptotic cells in a dose- and time-dependent manner in HT-29 cells. However, pretreatment of N-acetylcysteine inhibited the apoptosis-triggering effect of curcumin-induced ROS in HT-29 cells. In addition, curcumin-induced ROS effectively mediated cell cycle inhibition in HT-29 cells. In conclusion, our data provide the first evidence that curcumin induces ROS independent apoptosis and cell cycle arrest in colon cancer cells that carry mutation on Smad4 and p53. Copyright © 2018. Published by Elsevier Inc.

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

Science.gov (United States)

Paterson, Louise M; Tyacke, Robin J; Nutt, David J; Knudsen, Gitte M

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system. The principles behind visualising fluctuations in neurotransmitters are introduced, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT1A, 5-HT2A, and 5-HT4 receptors and the serotonin reuptake transporter have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made as to how the selection of targets, radiotracers, challenge paradigms, and experimental design might be optimised to improve our chances of successfully imaging endogenous neurotransmitters in the future. PMID:20664611

Luffa echinata Roxb. Induces Human Colon Cancer Cell (HT-29 Death by Triggering the Mitochondrial Apoptosis Pathway

Directory of Open Access Journals (Sweden)

Yan Yu

2012-05-01

Full Text Available The antiproliferative properties and cell death mechanism induced by the extract of the fruits of Luffa echinata Roxb. (LER were investigated. The methanolic extract of LER inhibited the proliferation of human colon cancer cells (HT-29 in both dose-dependent and time-dependent manners and caused a significant increase in the population of apoptotic cells. In addition, obvious shrinkage and destruction of the monolayer were observed in LER-treated cells, but not in untreated cells. Analysis of the cell cycle after treatment of HT-29 cells with various concentrations indicated that LER extracts inhibited the cellular proliferation of HT-29 cells via G2/M phase arrest of the cell cycle. The Reactive oxygen species (ROS level determination revealed that LER extracts induced apoptotic cell death via ROS generation. In addition, LER treatment led to a rapid drop in mitochondrial membrane potential (MMP as a decrease in fluorescence. The transcripts of several apoptosis-related genes were investigated by RT-PCR analysis. The caspase-3 transcripts of HT-29 cells significantly accumulated and the level of Bcl-XL mRNA was decreased after treatment with LER extract. Furthermore, the ratio of mitochondria-dependent apoptosis genes (Bax and Bcl-2 was sharply increased from 1.6 to 54.1. These experiments suggest that LER has anticancer properties via inducing the apoptosis in colon cancer cells, which provided the impetus for further studies on the therapeutic potential of LER against human colon carcinoma.

A Passive Diffusion Sampler for HT- and HTO-in-Air

International Nuclear Information System (INIS)

Surette, R.A.; Nunes, J.C.

2005-01-01

Fusion research and tritium removal facilities potentially handle large inventories of tritium gas (HT). If any HT is released into the workplace, a fraction may be converted to tritiated water vapour (HTO). A convenient method to determine the activity concentration of each species is necessary to assess the potential hazard since the radiological hazard of HTO is more than 10 4 that due to HT. Passive samplers for measuring tritiated water vapour (HTO) have been shown to be suitable for use indoors and outdoors. These simple samplers consist of a standard 20-mL liquid scintillation vial with a diffusion orifice that determines the sampling rate.The total tritium samplers described herein are passive or diffusion samplers that contain a small amount of AECL-proprietary wet-proofed catalyst fixed to the underside of the sampling heads to allow conversion of the HT to HTO that is subsequently collected in the sink, (HTO), in the bottom of the sampler. After an appropriate sampling time, liquid scintillation cocktail is added to the vial and the activity collected determined by liquid scintillation analysis. When used in conjunction with the conventional HTO passive sampler the difference between the total and HTO samplers can be used to determine the HT fraction ((HT+HTO) - HTO HT). The sampling rates for the modified diffusion sampler were measured to be 4.6 and 8.1 L/d for HTO and HT, respectively. For a fifteen-minute sampling period, passive samplers can be used to measure tritium activity concentrations from 37 kBq/m 3 to 115 MBq/m 3

Necrosis - the dominant form of cell death after phototoxicity impact of hypericin in colon adenocarcinoma cells HT29

International Nuclear Information System (INIS)

Mikes, J.; Kleban, J.; Sackova, V.; Solar, P.; Fedorocko, P.

2006-01-01

Photodynamic therapy (PDT) is a therapeutical approach for the treatment of malignant as well as non-malignant disorders based on administration of nontoxic/weakly toxic photosensitive compound and its activation with light. Hypericin, one of the promising photosensitizers, is known to induce apoptosis with high efficiency in various cell line models. However, here we report the prevalence of necrosis in colon adenocarcinoma HT-29 cells exposed to an extensive range of PDT doses evoked by variations in two variables - hypericin concentration and light dose. Necrosis was the principal mode of cell death despite different PDT doses and the absence of anti-apoptotic Bcl-2 expression. It is likely that the mutation in p53 plays a crucial role in cell death signaling in HT-29. Data indicating proliferation shifting in HT29 cells, incidence of cell death (apoptosis, necrosis and secondary necrosis) and comparison of cytotoxicity and caspase-3 activity of HT29 with HeLa cells are presented. (authors)

A Herbal Formula HT048, Citrus unshiu and Crataegus pinnatifida, Prevents Obesity by Inhibiting Adipogenesis and Lipogenesis in 3T3-L1 Preadipocytes and HFD-Induced Obese Rats

Directory of Open Access Journals (Sweden)

Yoon Hee Lee

2015-05-01

Full Text Available HT048 is a combination composed of Crataegus pinnatifida leaf and Citrus unshiu peel extracts. This study aimed to investigate potential anti-obesity effect of the combination. The 3T3-L1 adipocytes were treated with different doses of HT048 and triglyceride accumulation, glycerol release and adipogenesis-related genes were analyzed. For in vivo study, male Sprague Dawley rats were divided according to experimental diets: the chow diet group, the high-fat diet (HFD group, the HFD supplemented with orlistat group, the HFD supplemented with HT048 group (0.2% or 0.4% for 12 weeks. We measured the body weight, serum lipid levels and the expression of genes involved lipid metabolism. HT048 treatment dose-dependently suppressed adipocyte differentiation and stimulated glycerol release. The expressions of PPARγ and C/EBPα mRNA were decreased by HT048 treatment in adipocytes. HT048 supplementation significantly reduced the body and fat weights in vivo. Serum lipid levels were significantly lower in the HT048 supplemented groups than those of the HFD group. Expression of the hepatic lipogenesis-related genes were decreased and expression of the β-oxidation-related genes were increased in rats fed HT048 compared to that of animals fed HFD. These results suggest that HT048 has a potential benefit in preventing obesity through the inhibition of lipogenesis and adipogenesis.

A novel self-powered MR damper: theoretical and experimental analysis

International Nuclear Information System (INIS)

Xinchun, Guan; Hui, Li; Jinping, Ou; Yonghu, Huang; Yi, Ru

2015-01-01

This paper presents a novel magnetorheological (MR) damper with a self-powered capability, which is proposed to have energy harvesting and MR damping technologies integrated into a single device. Vibration energy harvesting mechanisms were adopted, based on ball-screw mechanisms and a rotary permanent magnet dc generator, to convert the external vibration energy into electrical energy to power the MR damping unit. The configuration and operating principles of the proposed self-powered MR damper were presented. Considering the core loss effect on the magnetic field, a theoretical analysis of the proposed MR damper was carried out and a mechanical model was developed. Finally, a prototype with a capacity of 10 kN was fabricated and experimentally investigated in both the direct-supply mode and the supply-with-rectifier mode. The results indicated that the proposed configuration is feasible and that both modes can realize good self-adaptability of the MR damping force. However, the direct-supply mode has a sag effect in the force–displacement curve and provides a lower energy-dissipating capacity than the direct-supply mode does under the same conditions. (paper)

Value of new MR techniques in MR-PET; Stellenwert neuer MR-Techniken in der MR-PET

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Attenberger, U.I.; Schoenberg, S.O. [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim der Universitaet Heidelberg, Institut fuer klinische Radiologie und Nuklearmedizin, Mannheim (Germany); Quick, H.H. [Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Institut fuer Medizinische Physik, Erlangen (Germany); Guimaraes, A. [Massachusetts General Hospital, Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown (United States); Catalano, O. [University of Naples Federico II, Naples (Italy); Morelli, J.N. [The Johns Hopkins Hospital, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore (United States)

2013-12-15

The unparalleled soft tissue contrast of magnetic resonance imaging (MRI) and the functional information obtainable with 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) render MR-PET well-suited for oncological and psychiatric imaging. The lack of ionizing radiation with MRI also makes MR-PET a promising modality for oncology patients requiring frequent follow-up and pediatric patients. Lessons learned with PET computed tomography (CT) over the last few years do not directly translate to MR-PET. For example, in PET-CT the Hounsfield units derived from CT are used for attenuation correction (AC). As 511 keV photons emitted in PET examinations are attenuated by the patient's body CT data are converted directly to linear attenuation coefficients (LAC); however, proton density measured by MRI is not directly related to the radiodensity or LACs of biological tissue. Thus, direct conversion to LAC data is not possible making AC more challenging in simultaneous MRI-PET scanning. In addition to these constraints simultaneous MRI-PET acquisitions also improve on some solutions to well-known challenges of hybrid imaging techniques, such as limitations in motion correction. This article reports on initial clinical experiences with simultaneously acquired MRI-PET data, focusing on the potential benefits and limitations of MRI with respect to motion correction as well as metal and attenuation correction artefacts. (orig.) [German] Die klinische Implementierung der neuen Hybridtechnologie MR-Positronenemissionstomographie (MR-PET) bietet durch die Kombination aus hochaufloesender Morphologie, Funktion und Metabolismus bisher ungeahnte diagnostische Moeglichkeiten, die nicht nur fuer die Diagnose und die Verlaufskontrolle onkologischer und psychiatrischer Erkrankungen von hoher Bedeutung sind. Verglichen mit der PET-CT wird dies mit reduzierter Strahlenbelastung fuer den Patienten moeglich, was wiederum insbesondere fuer Patienten in der Tumornachsorge, die

Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7 receptors.

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Hołuj, Małgorzata; Popik, Piotr; Nikiforuk, Agnieszka

2015-12-01

Social withdrawal, one of the core negative symptoms of schizophrenia, can be modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate receptor glutamate receptor antagonists. We have recently shown that amisulpride, an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed ketamine-induced SI deficits in rats. The aim of the present study was to further elucidate the potential involvement of 5-HT7 receptors in the prosocial action of amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1 mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal, whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective. The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2 mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg) and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine-induced SI deficits. The present study suggests that the antagonism of 5-HT7 receptors may contribute towards the mechanisms underlying the prosocial action of amisulpride. These results may have therapeutic implications for the treatment of negative symptoms in schizophrenia and other disorders characterized by social withdrawal.

SU-F-J-225: Histology Study of MR Guided Pulsed Focused Ultrasound On Treatment of Prostate Cancer in Vivo

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Chen, L; Cvetkovic, D; Chen, X; Wang, B; Gupta, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

2016-06-15

Purpose: Our previous study demonstrated significant tumor growth delay in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. The temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized at pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level using the DAB analysis software. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality may synergize with PARP inhibitors to achieve better therapeutic result.

SU-F-J-225: Histology Study of MR Guided Pulsed Focused Ultrasound On Treatment of Prostate Cancer in Vivo

International Nuclear Information System (INIS)

Chen, L; Cvetkovic, D; Chen, X; Wang, B; Gupta, R; Ma, C

2016-01-01

Purpose: Our previous study demonstrated significant tumor growth delay in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. The temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized at pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level using the DAB analysis software. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality may synergize with PARP inhibitors to achieve better therapeutic result.

Synergistic inhibitory effects of curcumin and 5-fluorouracil on the growth of the human colon cancer cell line HT-29.

Science.gov (United States)

Du, Boyu; Jiang, Liping; Xia, Quan; Zhong, Laifu

2006-01-01

The synergistic effect of combination treatment with COX-2 inhibitors and chemotherapy may be another promising therapy regimen in the future treatment of colorectal cancer. Curcumin, a major yellow pigment in turmeric which is used widely all over the world, inhibits the growth of human colon cancer cell line HT-29 significantly and specifically inhibits the expression of COX-2 protein. However, the worldwide exposure of populations to curcumin raised the question of whether this agent would enhance or inhibit the effects of chemotherapy. In this report, we evaluated the growth-inhibitory effect of curcumin and a traditional chemotherapy agent, 5-FU, against the proliferation of a human colon cancer cell line (HT-29). The combination effect was quantitatively determined using the method of median-effect principle and the combination index. The inhibition of COX-2 expression after treatment with the curcumin-5-FU combination was also evaluated by Western blot analysis. The IC(50) value in the HT-29 cells for curcumin was 15.9 +/- 1.96 microM and for 5-FU it was 17.3 +/- 1.85 microM. When curcumin and 5-FU were used concurrently, synergistic inhibition of growth was quantitatively demonstrated. The level of COX-2 protein expression was reduced almost 6-fold after the combination treatment. Our results demonstrate synergism between curcumin and 5-FU at higher doses against the human colon cancer cell line HT-29. This synergism was associated with the decreased expression of COX-2 protein. Copyright 2006 S. Karger AG, Basel.

SHEDS-HT: An Integrated Probabilistic Exposure Model for Prioritizing Exposures to Chemicals with Near-Field and Dietary Sources

Science.gov (United States)

United States Environmental Protection Agency (USEPA) researchers are developing a strategy for highthroughput (HT) exposure-based prioritization of chemicals under the ExpoCast program. These novel modeling approaches for evaluating chemicals based on their potential for biologi...

Autroadiographic characterization of 125I-labeled 2,5-dimethoxy-4-iodophenylisopropylamine (DOI): A phenylisopropylamine derivative labeling both 5HT2 and 5HT1c receptors

International Nuclear Information System (INIS)

Appel, N.M.; Mitchell, W.M.; Garlick, R.K.; Glennon, R.A.; Titeler, M.; De Souza, E.B.

1990-01-01

The best-characterized 5HT 2 radioligands, such as [ 3 H]ketanserin and [ 3 H]spiperone, are antagonists that label both high- and low-affinity states of this receptor. Recently, the radiolabeled phenylisopropylamine hallucinogens DOB and DOI, which are agonists at 5HT 2 receptors, have been demonstrated to label selectively the high-affinity state of brain 5HT 2 receptors. In the present study, the authors determined optimum conditions for autoradiographic visualization of [ 125 I]DOI binding and characterized its pharmacology and guanine nucleotide sensitivity under those conditions. In slide-mounted tissue sections (rat forebrain; two 10 μm sections/slide), (±)[ 125 I]DOI binding was saturable, of high affinity (K D ∼4nM) and displayed a pharmacological profile [R(-)DOI > spiperone > DOB > (±)DOI > ketanserin > S(+)DOI > 5HT > DOM] comparable to that seen in homogenate assays. Consistent with coupling of 5HT 2 receptors to a guanine nucleotide regulatory protein, [ 125 I]DOI binding was inhibited by guanine nucleotides but not by ATP. In autoradiograms, high densities of [ 125 I]DOI binding sites were present in frontal cortex, olfactory tubercle, claustrum, caudate/putamen and mamillary nuclei with lower densities in trigeminal and solitary nuclei. The highest density of [ 125 l]DOI binding was observed in choroid plexus; these binding sites displayed a pharmacological profile characteristic of 5HT 1C receptors. These data suggest that [ 125 I]DOI labels both 5HT 2 and 5HT 1C receptors

Performance of a high sensitivity time-of-flight PET ring operating simultaneously within a 3T MR system

International Nuclear Information System (INIS)

Levin, Craig S; Jansen, Floris; Deller, Tim; Maramraju, Sri Harsha; Grant, Alex; Iagaru, Andrei

2014-01-01

A time-of-flight (TOF)-PET/MR research system installed at Stanford will be used to test the hypotheses that (a) it is possible to acquire simultaneous TOF-PET and 3T MR data while achieving uncompromised performance in both modalities and (b) simultaneous TOF-PET/MR is a tool for multi-parameter characterization of disease. In this paper we will describe the design as well as performance measurements both for the standalone PET ring, and with the two systems integrated. We will also show a selection of clinical images to compare the performance of the integrated TOF-PET/MR system with that of a state-of-the-art PET/CT system.

Vibration control of an MR vehicle suspension system considering both hysteretic behavior and parameter variation

International Nuclear Information System (INIS)

Choi, Seung-Bok; Seong, Min-Sang; Ha, Sung-Hoon

2009-01-01

This paper presents vibration control responses of a controllable magnetorheological (MR) suspension system considering the two most important characteristics of the system; the field-dependent hysteretic behavior of the MR damper and the parameter variation of the suspension. In order to achieve this goal, a cylindrical MR damper which is applicable to a middle-sized passenger car is designed and manufactured. After verifying the damping force controllability, the field-dependent hysteretic behavior of the MR damper is identified using the Preisach hysteresis model. The full-vehicle suspension model is then derived by considering vertical, pitch and roll motions. An H ∞ controller is designed by treating the sprung mass of the vehicle as a parameter variation and integrating it with the hysteretic compensator which produces additional control input. In order to demonstrate the effectiveness and robustness of the proposed control system, the hardware-in-the-loop simulation (HILS) methodology is adopted by integrating the suspension model with the proposed MR damper. Vibration control responses of the vehicle suspension system such as vertical acceleration are evaluated under both bump and random road conditions

Intensity-Modulated Radiotherapy (IMRT) vs Helical Tomotherapy (HT) in Concurrent Chemoradiotherapy (CRT) for Patients with Anal Canal Carcinoma (ACC): an analysis of dose distribution and toxicities

International Nuclear Information System (INIS)

Yeung, Rosanna; McConnell, Yarrow; Warkentin, Heather; Graham, Darren; Warkentin, Brad; Joseph, Kurian; Doll, Corinne M

2015-01-01

Intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) have been adopted for radiotherapy treatment of anal canal carcinoma (ACC) due to better conformality, dose homogeneity and normal-tissue sparing compared to 3D-CRT. To date, only one published study compares dosimetric parameters of IMRT vs HT in ACC, but there are no published data comparing toxicities. Our objectives were to compare dosimetry and toxicities between these modalities. This is a retrospective study of 35 ACC patients treated with radical chemoradiotherapy at two tertiary cancer institutions from 2008–2010. The use of IMRT vs HT was primarily based on center availability. The majority of patients received fluorouracil (5-FU) and 1–2 cycles of mitomycin C (MMC); 2 received 5-FU and cisplatin. Primary tumor and elective nodes were prescribed to ≥54Gy and ≥45Gy, respectively. Patients were grouped into two cohorts: IMRT vs HT. The primary endpoint was a dosimetric comparison between the cohorts; the secondary endpoint was comparison of toxicities. 18 patients were treated with IMRT and 17 with HT. Most IMRT patients received 5-FU and 1 MMC cycle, while most HT patients received 2 MMC cycles (p < 0.01), based on center policy. HT achieved more homogenous coverage of the primary tumor (HT homogeneity and uniformity index 0.14 and 1.02 vs 0.29 and 1.06 for IMRT, p = 0.01 and p < 0.01). Elective nodal coverage did not differ. IMRT achieved better bladder, femoral head and peritoneal space sparing (V30 and V40, p ≤ 0.01), and lower mean skin dose (p < 0.01). HT delivered lower bone marrow (V10, p < 0.01) and external genitalia dose (V20 and V30, p < 0.01). Grade 2+ hematological and non-hematological toxicities were similar. Febrile neutropenia and unscheduled treatment breaks did not differ (both p = 0.13), nor did 3-year overall and disease-free survival (p = 0.13, p = 0.68). Chemoradiotherapy treatment of ACC using IMRT vs HT results in differences in dose homogenity and

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

Science.gov (United States)

Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

2014-01-03

Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

Generation of structural MR images from amyloid PET: Application to MR-less quantification.

Science.gov (United States)

Choi, Hongyoon; Lee, Dong Soo

2017-12-07

Structural magnetic resonance (MR) images concomitantly acquired with PET images can provide crucial anatomical information for precise quantitative analysis. However, in the clinical setting, not all the subjects have corresponding MR. Here, we developed a model to generate structural MR images from amyloid PET using deep generative networks. We applied our model to quantification of cortical amyloid load without structural MR. Methods: We used florbetapir PET and structural MR data of Alzheimer's Disease Neuroimaging Initiative database. The generative network was trained to generate realistic structural MR images from florbetapir PET images. After the training, the model was applied to the quantification of cortical amyloid load. PET images were spatially normalized to the template space using the generated MR and then standardized uptake value ratio (SUVR) of the target regions was measured by predefined regions-of-interests. A real MR-based quantification was used as the gold standard to measure the accuracy of our approach. Other MR-less methods, a normal PET template-based, multi-atlas PET template-based and PET segmentation-based normalization/quantification methods, were also tested. We compared performance of quantification methods using generated MR with that of MR-based and MR-less quantification methods. Results: Generated MR images from florbetapir PET showed visually similar signal patterns to the real MR. The structural similarity index between real and generated MR was 0.91 ± 0.04. Mean absolute error of SUVR of cortical composite regions estimated by the generated MR-based method was 0.04±0.03, which was significantly smaller than other MR-less methods (0.29±0.12 for the normal PET-template, 0.12±0.07 for multiatlas PET-template and 0.08±0.06 for PET segmentation-based methods). Bland-Altman plots revealed that the generated MR-based SUVR quantification was the closest to the SUVR values estimated by the real MR-based method. Conclusion

COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine.

Science.gov (United States)

Bosia, Marta; Lorenzi, Cristina; Pirovano, Adele; Guglielmino, Carmelo; Cocchi, Federica; Spangaro, Marco; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

2015-01-01

Clozapine is still considered the gold standard for treatment-resistant schizophrenia patients; however, up to 40% of patients do not respond adequately. Identifying potential predictors of clinical response to this last-line antipsychotic could represent an important goal for treatment. Among these, functional polymorphisms involved in dopamine system modulation, known to be disrupted in schizophrenia, may play a role. We examined the COMT Val158Met polymorphism, which plays a key role in dopamine regulation at the prefrontal level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity involved in the interaction between the serotonin and dopamine systems. 107 neuroleptic-refractory, biologically unrelated Italian patients (70 males and 37 females) with a DSM-IV diagnosis of schizophrenia who were being treated with clozapine were recruited. Psychopathology was assessed by the Positive and Negative Symptoms Scale (PANSS) at the beginning of treatment, and at weeks 8 and 12. Genomic DNA was extracted from venous blood samples. COMT rs4680 (Val158Met) and 5-HT1A-R rs6295 (-1019 C/G) polymorphisms were analyzed by PCR-based restriction fragment length and direct sequencing, respectively. We found a significant effect of COMT and 5-HT1A-R on the PANSS Negative Subscale variation, with greater improvement among COMT Val/Val and 5-HT1A-R G/G subjects. The findings support the hypothesis that COMT rs4680 and 5-HT1A-R rs6295 polymorphisms could influence the negative symptom response to clozapine, probably through modulation of the dopaminergic system.

On-line Measurement of Boiler Tube Corrosion Rates using Dedicated EMAT (HT-EMAT) Phase 1

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Borggreen, Kjeld (SydTek AB, Malmoe (Sweden))

2009-06-15

The project includes development of prototype HT-EMAT (High Temperature Electro Magnetic Acoustic Transducer) probes and testing of these in laboratory environment at high temperatures. The following results were obtained: Standard Alnico (Al-Ni-Co-Fe) magnets are sufficiently strong to drive a HT-EMAT probe in the magnetostrictive mode at temperatures up to 550 deg C. With a standard (diam)20 x 40 mm Alnico magnet, the number of turns in the coil using a 0.25 mm wire should be 25 - 30 to give optimum response and highest accuracy. The velocity of shear type sound waves in metals varies linearly with temperature in the interval considered. The prototype HT-EMAT only needs to be calibrated at room temperature, which is a simple procedure. If the temperature dependence of the velocity of the sound waves in steels is taking into account, the prototype probe gives excellent results at temperatures up to 550 deg C. The coil and the connection wire should preferably have a high electric conductivity to minimize damping, skin effects, and impedance mismatch, and also a high oxidation resistance. Pure copper and fine silver are the candidate materials for the HT-EMAT. Deposition of magnetostrictive layers on steel surfaces has been resolved. Magnetite seems as the only useful material until further. Thin layers of natural grown magnetite can be made by long term heat treatments. Thicker layers of artificial magnetite can be made by thermal spraying. Most of the reduction in efficiency of the HT-EMAT probe at high temperatures may be explained by the thermal dependence of the magnetostrictive constant for magnetite. Because the magnetostriction of magnetite disappears at its Curie temperature, the theoretical temperature limit for the HT-EMAT probe is foreseen to be 575 deg C. The prototype HT-EMAT performed well up to 550 deg C both during long time testing and at dynamic testing. The electronic and mechanical stabilities were excellent

Attachment of personal computer to CALVET HT-1000 microcalorimeter (Preprint No. NI.01)

International Nuclear Information System (INIS)

Venkiteswaran, S.; Samuel, J.K.

1989-01-01

CALVET HT-1000 is a double cell differential microcalorimeter used for determining heat capacity and other thermodynamical values of compounds formed due to the interaction of nuclear fuel with clad and coolant. A set of thermopiles at the two cells detects the heat flow and the output is connected to a recorder through a differential amplifier. The attachment of a PC to the microcalorimeter permits recording of output at predetermined time intervals and direct integration of area from the recorded data. This not only eliminates the cumbersome and time consuming integration procedures but also increases the precision. In addition further processing of data can also be integrated into the system. The incorporation of PC has been achieved by minimum modification/alteration to the existing microcalorimeter system. (author)

Field studies of HT oxidation and dispersion in the environment

International Nuclear Information System (INIS)

Brown, R.M.; Ogram, G.L.; Spencer, F.S.; Ontario Hydro, Toronto, ON

1988-10-01

A tracer quantity of 3.54 TBq tritiated hydrogen (HT) was released into the atmosphere at a Chalk River, Ontario field site to determine the behaviour of HT in the environment. The primary objective was to establish the oxidation rate of HT to tritiated water (HTO) in air, soil and vegetation compartments. HTO/HT atmospheric concentration ratios observed during the release ranged from 0.14 x 10 -4 at 5 m to 7.0 x 10 -4 at 400 m distance from the release point indicating an effective oxidation rate of about 1.5% h -1 . Gas phase oxidation in the atmosphere would be less than this effective rate. Results confirm that surface soils play the dominant role in converting HT to HTO. Soil HT deposition velocities were between 2.7 x 10 -4 and 11 x 10 -4 m s -1 for an open field of varied composition, and between 3.3 x 10 -4 and 12 x 10 -4 m s -1 for a conifer forest. Soil HTO loss rates were initially 1 to 3 % h -1 averaged over the first 24 h after release. Vegetation tissue-free water tritium (TFWT) resulted from uptake of soil HTO and exchange with atmospheric HTO vapour. Upper limit HT deposition velocities to vegetation measured as TFWT in 5 species were 0.23 x 10 -7 to 6 x 10 -7 m s -1 expressed on a leaf area basis. TFWT loss rates were 5.2 to 8.1 % h -1 from about 12 to 48 h after release with low activity rain and 0.42 to 0.56 % h -1 from about 48 to 335 h. Vegetation organically-bound tritium/TFWT specific activity ratios (Bq g -1 H) were about 0.1 initially, increasing to 16 after 113 days as TFWT specific activity declined more rapidly than that of OBT. The effective HT oxidation rate, deposition velocities and HTO loss rates were in good agreement with a 1986 HT field release and previous laboratory experiments

Novel aza-analogous ergoline derived scaffolds as potent serotonin 5-HT6 and dopamine D2 receptor ligands

DEFF Research Database (Denmark)

Krogsgaard-Larsen, Niels; Jensen, Anders A.; Schrøder, T.J.

2014-01-01

By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D2 and serotonin 5-HT6 receptor subtype, respectively. While the 5-HT6 ligands were antagonists......, the D2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson’s disease, and cognitive deficits....

Gadolinium-enhanced MR imaging in evaluation of Bell palsy

International Nuclear Information System (INIS)

Wang, A.M.; Wesolowski, D.P.; Bojrab, D.I.; Ernstoff, R.M.; Farah, J.

1989-01-01

Eight patients with Bell palsy were evaluated with Gd-DTPA (Magnevist)-enhanced MR imaging in a 1.0-T Siemen's Magnetom unit. Axial pre-and postcontrast and coronal postcontrast T1-weighted MR images of facial nerves were studied. Significant unilateral enhancement of the facial nerve within the internal auditory canal, with or without involvement of the geniculate ganglia, was found in six patients. Three of these patients without satisfactory response to medical treatment underwent surgical decompression, with excellent recovery of facial nerve function. The authors believe that gadolinium-enhanced MR imaging is valuable in the evaluation and management of Bell palsy

Mechanical Stimulation of the HT7 Acupuncture Point to Reduce Ethanol Self-Administration in Rats

Directory of Open Access Journals (Sweden)

Suk-Yun Kang

2017-01-01

Full Text Available Background. Alcoholism, which is a disabling addiction disorder, is a major public health problem worldwide. The present study was designed to determine whether the application of acupuncture at the Shenmen (HT7 point suppresses voluntary alcohol consumption in addicted rats and whether this suppressive effect is potentiated by the administration of naltrexone. Methods. Rats were initially trained to self-administer a sucrose solution by operating a lever. A mechanical acupuncture instrument (MAI for objective mechanical stimulation was used on rats whose baseline response had been determined. In addition, the effect of HT7 acupuncture on beta-endorphin concentration and ethanol intake via naltrexone were investigated in different groups. Results. We found that ethanol intake and beta-endorphin level in rats being treated with the MAI at the HT7 point reduced significantly. The treatment of naltrexone at high doses reduced the ethanol intake and low-dose injection of naltrexone in conjunction with the MAI also suppressed ethanol intake. Conclusions. The results of the current study indicate that using the MAI at the HT7 point effectively reduces ethanol consumption in rats. Furthermore, the coadministration of the MAI and a low dose of naltrexone can produce some more potent reducing effect of ethanol intake than can acupuncture alone.

Lateral epicondylitis. Associations of MR imaging and clinical assessments with treatment options in patients receiving conservative and arthroscopic managements

Energy Technology Data Exchange (ETDEWEB)

Jeon, Ji Young [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Gachon University, Department of Radiology, Incheon (Korea, Republic of); Lee, Min Hee; Chung, Hye Won; Lee, Sang Hoon; Shin, Myung Jin [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Jeon, In-Ho [University of Ulsan College of Medicine, Department of Orthopedic Surgery, Seoul (Korea, Republic of)

2018-03-15

We assessed the implications of MR imaging with clinical history in lateral epicondylitis management by evaluating imaging and clinical features in patients with lateral epicondylitis treated conservatively or operatively. Sixty patients with lateral epicondylitis treated conservatively (n = 38) or operatively (n = 22) from 2011-2015 were included. MR imaging findings of common extensor tendon (CET), lateral collateral ligament (LCL) complex, muscle oedema, ulnar nerve and elbow joint were reviewed. Clinical data recorded were frequency, duration and intensity of pain, history of trauma and injection therapy, range of motion. MRI-assessed CET and LCL complex abnormalities, muscle oedema, radiocapitellar joint widening, joint effusion/synovitis, pain frequency and intensity differed significantly between the two groups (p <.05) with increased severity in operative group. Persistent pain (OR 12.2, p <.01), CET abnormality on longitudinal plane (OR 7.5, p =.03 for grade 2; OR 22.4, p <.01 for grade 3) and muscle oedema (OR 6.7, p =.03) were major factors associated with operative treatment. Area under the ROC curve of predicted probabilities for combination of these factors was 0.83. MR imaging, combined with clinical assessment, could facilitate appropriate management planning for patients with lateral epicondylitis. (orig.)

Lateral epicondylitis. Associations of MR imaging and clinical assessments with treatment options in patients receiving conservative and arthroscopic managements

International Nuclear Information System (INIS)

Jeon, Ji Young; Lee, Min Hee; Chung, Hye Won; Lee, Sang Hoon; Shin, Myung Jin; Jeon, In-Ho

2018-01-01

We assessed the implications of MR imaging with clinical history in lateral epicondylitis management by evaluating imaging and clinical features in patients with lateral epicondylitis treated conservatively or operatively. Sixty patients with lateral epicondylitis treated conservatively (n = 38) or operatively (n = 22) from 2011-2015 were included. MR imaging findings of common extensor tendon (CET), lateral collateral ligament (LCL) complex, muscle oedema, ulnar nerve and elbow joint were reviewed. Clinical data recorded were frequency, duration and intensity of pain, history of trauma and injection therapy, range of motion. MRI-assessed CET and LCL complex abnormalities, muscle oedema, radiocapitellar joint widening, joint effusion/synovitis, pain frequency and intensity differed significantly between the two groups (p <.05) with increased severity in operative group. Persistent pain (OR 12.2, p <.01), CET abnormality on longitudinal plane (OR 7.5, p =.03 for grade 2; OR 22.4, p <.01 for grade 3) and muscle oedema (OR 6.7, p =.03) were major factors associated with operative treatment. Area under the ROC curve of predicted probabilities for combination of these factors was 0.83. MR imaging, combined with clinical assessment, could facilitate appropriate management planning for patients with lateral epicondylitis. (orig.)

Analysis of Current HT9 Creep Correlations and Modification

International Nuclear Information System (INIS)

Lee, Cheol Min; Sohn, Dongseong; Cheon, Jin Sik

2014-01-01

It has high thermal conductivity, high mechanical strength and low irradiation induced swelling. However high temperature creep of HT9 has always been a life limiting factor. Above 600 .deg. C, the dislocation density in HT9 is decreased and the M 23 C 6 precipitates coarsen, these processes are accelerated if there is irradiation. Finally microstructural changes at high temperature lead to lower creep strength and large creep strain. For HT9 to be used as a future cladding, creep behavior of the HT9 should be predicted accurately based on the physical understanding of the creep phenomenon. Most of the creep correlations are composed of irradiation creep and thermal creep terms. However, it is certain that in-pile thermal creep and out-of-pile thermal creep are different because of the microstructure changes induced from neutron irradiation. To explain creep behavior more accurately, thermal creep contributions other than neutron irradiation should be discriminated in a creep correlation. To perform this work, existing HT9 creep correlations are analyzed, and the results are used to develop more accurate thermal creep correlation. Then, the differences between in-pile thermal creep and out-of-pile thermal creep are examined

Strength and rupture-life transitions caused by secondary carbide precipitation in HT-9 during high-temperature low-rate mechanical testing

International Nuclear Information System (INIS)

DiMelfi, R.J.; Gruber, E.E.; Kramer, J.M.; Hughes, T.H.

1992-01-01

The martensitic-ferritic alloy HT-9 is slated for long-term use as a fuel-cladding material in the Integral Fast Reactor. Analysis of published high-temperature mechanical property data suggests that secondary carbide precipitation would occur during service life causing substantial strengthening of the as-heat-treated material. Aspects of the kinetics of this precipitation process are extracted from calculations of the back stress necessary to produce the observed strengthening effect under various creep loading conditions. The resulting Arrhenius factor is shown to agree quantitatively with shifts to higher strength of crept material in reference to the intrinsic strength of HT-9. The results of very low constant strain-rate high-temperature tensile tests on as-heat-treated HT-9 that focus on the transition in strength with precipitation will be presented and related to rupture-life

MR imaging findings and MR criteria for instability in osteochondritis dissecans of the elbow in children

International Nuclear Information System (INIS)

Jans, Lennart B.O.; Ditchfield, Michael; Anna, Gomez; Jaremko, Jacob L.; Verstraete, Koenraad L.

2012-01-01

Purpose: Osteochondritis dissecans (OCD) of the elbow is an uncommon cause of elbow pain in adolescents and occurs at different locations in the elbow joint. Early diagnosis and treatment may prevent surgery. The aim of the study is to describe the MR imaging features of OCD at initial imaging, and to correlate these findings with surgical findings of stability and instability with arthroscopic findings as the reference standard. Methods: Patients were identified through a keyword search of the radiology information system from 2000 to 2009. Twenty-five patients (26 elbows) with OCD of the elbow were identified (age 10.4–18 years, mean age 14 years). MR studies were retrospectively reviewed by two radiologists in consensus to define MR imaging findings and to determine the presence of previously described MR imaging criteria for OCD instability (i.e., high T2 signal rim, surrounding cysts, high T2 signal fracture line, fluid-filled osteochondral defect). Sensitivity of the individual and combined criteria was calculated. Results: OCD occurred in the capitellum in 24 patients (92%), in the trochlea in 2 patients (8%) and radial head in 1 patient (4%). Loose bodies were identified in 11 (42%) patients. Eighteen patients demonstrated MRI findings in keeping with unstable lesions. In all 11 patients who had surgery the surgical findings of instability correlated with the MRI findings. When combined, the MR criteria were 100% sensitive for instability of OCD lesions of the elbow. Conclusion: The vast majority of OCD of the elbow occurs in the capitellum. When used together, the MR criteria for instability were 100% sensitive for evaluation OCD lesions of the elbow.

Preliminary evaluation of the MLAA algorithm with the Philips Ingenuity PET/MR

International Nuclear Information System (INIS)

Lougovski, Alexandr; Schramm, Georg; Maus, Jens; Hofheinz, Frank; Ho, Jörg van den

2014-01-01

Combined PET/MR is a promising tool for simultaneous investigation of soft tissue morphology and function. However, contrary to CT, MR images do not provide information on photon attenuation in tissue. In the currently available systems issue is solved by synthesizing attenuation maps from MR images using segmentation algorithms. This approach has been shown to provide reason-able results in most cases. However, sporadically occurring segmentation errors can cause serious problems. Recently, algorithms for simultaneous estimation of attenuation and tracer distribution (MLAA) have been introduced. So far, validity of MLAA has mainly been demonstrated in simulated data. We have integrated the MLAA algorithm [2] into the THOR reconstruction []. An evaluation of MLAA was performed using both phantom and patient data acquired with the Ingenuity PET/MR.

Recurrent postoperative sciatica: Evaluation with MR imaging and enhanced CT

International Nuclear Information System (INIS)

Duvauferrier, R.; Frocain, L.; Husson, J.L.

1987-01-01

The authors prospectively compared MR imaging performed with a surface coil and CT performed with iodinated contrast agent enhancement in 50 patients with recurrent postoperative sciatica. Surgical decision was an objective measure of accuracy. Surgical treatment was selected for 27 patients. All 27 underwent MR imaging. The 15 patients who underwent CT/surgical treatment were included in the 27 indications of SCMR. All predictions based on MR imaging findings were confirmed at surgery. There were 25 recurrent disk herniations, including five with scar tissue, and two disk herniations above or below the level of the diskectomy. In the 12 patients with scar tissue detected on CT there were seven recurrent disk hernitions, four recurrent disk herniations with scar tissue, and one disk herniation below the level of the diskectomy

MR imaging in the neonatal period

International Nuclear Information System (INIS)

Aida, Noriko; Inuzuka, Michiko; Odagiri, Kunio

1994-01-01

We reviewed 118 MR examinations in the neonatal period to define its indication, problem, and usefulness. The patients were 58 term infants under 28 days of age and 46 preterm infants under 46 week of their post conceptional age. Almost all patients were examined under sedation. We used pulse wave monitoring and respiration was monitored only by observing the chest motion. Hot water bags were used in some cases to keep the patient warm. No serious accidents or sequelae occurred, although a very few patients had a brief apnea attacks during sedation and some developed hypothermia after the examination. The MR provided many useful information such as basal ganglial lesions after perinatal asphyxia and multiplaner demonstration of the CN5 anomalies which no other modality could. The detection rate of abnormality in the study was about 65%. Although MR studies in the neonatal period have many difficulties to be overcome including sedation, maintenance of body temperature and monitoring, they can demonstrate useful information that are helpful for their early treatment and care. Thus we believe that the MR study should be performed in a more positive manner in a variety of clinical setting in the neonatal period. (author)

MR imaging in the neonatal period

Energy Technology Data Exchange (ETDEWEB)

Aida, Noriko; Inuzuka, Michiko; Odagiri, Kunio (Kanagawa Children' s Medical Center (Japan))

1994-01-01

We reviewed 118 MR examinations in the neonatal period to define its indication, problem, and usefulness. The patients were 58 term infants under 28 days of age and 46 preterm infants under 46 week of their post conceptional age. Almost all patients were examined under sedation. We used pulse wave monitoring and respiration was monitored only by observing the chest motion. Hot water bags were used in some cases to keep the patient warm. No serious accidents or sequelae occurred, although a very few patients had a brief apnea attacks during sedation and some developed hypothermia after the examination. The MR provided many useful information such as basal ganglial lesions after perinatal asphyxia and multiplaner demonstration of the CN5 anomalies which no other modality could. The detection rate of abnormality in the study was about 65%. Although MR studies in the neonatal period have many difficulties to be overcome including sedation, maintenance of body temperature and monitoring, they can demonstrate useful information that are helpful for their early treatment and care. Thus we believe that the MR study should be performed in a more positive manner in a variety of clinical setting in the neonatal period. (author).

Hyperthermia system working in combination with an MR imaging unit

International Nuclear Information System (INIS)

LeBihan, D.J.; Delannoy, J.; Levin, R.L.; Hoult, D.I.

1988-01-01

The authors propose a hyperthermia device to be used for temperature monitoring. It consists of a modified miniannular phased array (MAPA) radio-frequency applicator designed for limb tumor treatment that works in combination with a whole-body MR imaging unit operating at 21 MHz. Highly accurate (0.5 0 c/0.8 cm 2 ) temperature images are obtained noninvasively throughout the heated volume from MR images of molecular diffusion, the relation of which with temperature is well known. The MAPA, electrically modified to be compatible with MR imagers, can be centered inside the MR head coil. The combined system was tested on a phantom in which the temperature distribution was confirmed by miniature thermocouples

5-HT7 Receptor Antagonists with an Unprecedented Selectivity Profile.

Science.gov (United States)

Ates, Ali; Burssens, Pierre; Lorthioir, Olivier; Lo Brutto, Patrick; Dehon, Gwenael; Keyaerts, Jean; Coloretti, Francis; Lallemand, Bénédicte; Verbois, Valérie; Gillard, Michel; Vermeiren, Céline

2018-04-23

Selective leads: In this study, we generated a new series of serotonin 5-HT 7 receptor antagonists. Their synthesis, structure-activity relationships, and selectivity profiles are reported. This series includes 5-HT 7 antagonists with unprecedented high selectivity for the 5-HT 7 receptor, setting the stage for lead optimization of drugs acting on a range of neurological targets. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Standardized uptake value and apparent diffusion coefficient of endometrial cancer evaluated with integrated whole-body PET/MR: Correlation with pathological prognostic factors.

Science.gov (United States)

Shih, I-Lun; Yen, Ruoh-Fang; Chen, Chi-An; Chen, Bang-Bin; Wei, Shwu-Yuan; Chang, Wen-Chun; Sheu, Bor-Ching; Cheng, Wen-Fang; Tseng, Yao-Hui; Chen, Xin-Jia; Chen, Chi-Hau; Wei, Lin-Hung; Chiang, Ying-Cheng; Torng, Pao-Ling; Yen, Men-Luh; Shih, Tiffany Ting-Fang

2015-12-01

To evaluate the correlation between maximum standardized uptake value (SUVmax ) and minimum apparent diffusion coefficient (ADCmin ) of endometrial cancer derived from an integrated positron emission tomography / magnetic resonance (PET/MR) system and to determine their correlation with pathological prognostic factors. This prospective study was approved by the Institutional Review Board of the hospital, and informed consent was obtained. Between April and December 2014, 47 consecutive patients with endometrial cancer were enrolled and underwent simultaneous PET/MR examinations before surgery. Thirty-six patients with measurable tumors on PET/MR were included for image analysis. Pearson's correlation coefficient was used to evaluate the correlation between SUVmax and ADCmin of the tumors. The Mann-Whitney U-test was utilized to evaluate relationships between these two imaging biomarkers and pathological prognostic factors. The mean SUVmax and ADCmin were 14.7 ± 7.1 and 0.48 ± 0.13 × 10(-3) mm(2) /s, respectively. A significant inverse correlation was found between SUVmax and ADCmin (r = -0.53; P = 0.001). SUVmax was significantly higher in tumors with advanced stage, deep myometrial invasion, cervical invasion, lymphovascular space involvement, and lymph node metastasis (P correlated and are associated with pathological prognostic factors. © 2015 Wiley Periodicals, Inc.

Volumetric MR-Guided High-Intensity Focused Ultrasound with Direct Skin Cooling for the Treatment of Symptomatic Uterine Fibroids : Proof-of-Concept Study

NARCIS (Netherlands)

Ikink, Marlijne E; van Breugel, Johanna M M; Schubert, Gerald; Nijenhuis, Robbert J; Bartels, LW; Moonen, Chrit T W; van den Bosch, Maurice A A J

2015-01-01

Objective. To prospectively assess the safety and technical feasibility of volumetric magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation with direct skin cooling (DISC) during treatment of uterine fibroids. Methods. In this proof-of-concept study, eight patients were

MR tractography

International Nuclear Information System (INIS)

Kinosada, Yasutomi; Okuda, Yasuyuki; Ono, Mototsugu

1993-01-01

We developed a new noninvasive technique to visualize the anatomical structure of the nerve fiber system in vivo, and named this technique magnetic resonance (MR) tractography and the acquired image an MR tractogram. MR tractography has two steps. One is to obtain diffusion-weighted images sensitized along axes appropriate for depicting the intended nerve fibers with anisotropic water diffusion MR imaging. The other is to extract the anatomical structure of the nerve fiber system from a series of diffusion-weighted images by the maximum intensity projection method. To examine the clinical usefulness of the proposed technique, many contiguous, thin (3 mm) coronal two-dimensional sections of the brain were acquired sequentially in normal volunteers and selected patients with paralyses, on a 1.5 Tesla MR system (Signa, GE) with an ECG-gated Stejskal-Tanner pulse sequence. The structure of the nerve fiber system of normal volunteers was almost the same as the anatomy. The tractograms of patients with paralyses clearly showed the degeneration of nerve fibers and were correlated with clinical symptoms. MR tractography showed great promise for the study of neuroanatomy and neuroradiology. (author)

Adult tibial intercondylar eminence fracture: evaluation with MR imaging

International Nuclear Information System (INIS)

Toye, Leon R.; Cummings, Dean P.; Armendariz, Gus

2002-01-01

Tibial intercondylar eminence (TIE) fractures are well described in the pediatric orthopedic literature. Adult TIEs are much less common, and limited literature exists on the subject. Adult knee hyperextension injuries commonly result in anterior cruciate ligament (ACL) injury; however, with significant trauma, a TIE enters the differential diagnosis. Identification and classification of TIE fractures typically has been provided by radiography. The incidence of concomitant injuries with magnetic resonance (MR) imaging in patients with adult TIE fractures has not been determined. We present a case of an adult type III TIE fracture seen on radiography that only with further MR imaging revealed a concomitant lateral tibial plateau fracture. Utilization of MR imaging altered the surgeon's course of treatment and postoperative care. Radiographic and MR images and a review of the literature are provided. (orig.)

Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice

DEFF Research Database (Denmark)

Licht, Cecilie L; Kirkegaard, Lisbeth; Zueger, Maha

2010-01-01

. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen......]citalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control....... Among post hoc analyzed regions, there was a 14% decrease in 5-HT(4) receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus...

Investigating the Role of Serotonin in Methamphetamine Psychosis: Unaltered Behavioral Effects of Chronic Methamphetamine in 5-HT1A Knockout Mice

Directory of Open Access Journals (Sweden)

Maarten van den Buuse

2017-04-01

Full Text Available Methamphetamine (Meth is a widely abused stimulant drug, but this abuse is associated with an increased risk of developing psychosis. In addition to its well-known action on brain dopamine, Meth also affects serotonergic (5-HT neurons. The aim of this study was to investigate this role in mice, which lack one of the main serotonin receptors, the 5-HT1A receptor, which has been implicated in both schizophrenia and Meth-induced psychosis. Male and female wild-type or 5-HT1A knockout (KO mice received daily treatment with increasing doses of methamphetamine from 6 to 9 weeks of age (1–4 mg/kg/day twice a day. At least 2 weeks after the last injection, the mice underwent a battery of behavioral tests focusing on psychosis-related behaviors, including Meth-induced hyperactivity, prepulse inhibition (PPI, social interaction, elevated plus maze (EPM, and Y-maze. Meth pretreatment resulted in significantly increased hyperlocomotion in response to an acute Meth challenge, but this effect was independent of genotype. Chronic Meth treatment resulted in decreased levels of anxiety in the EPM in both sexes, as well as increased startle responses in female mice only, again independent of genotype. 5-HT1A KO mice showed an increased locomotor response to acute Meth in both sexes, as well as increased PPI and decreased startle responses in female mice only, independent of Meth pretreatment. In conclusion, the effects of chronic Meth appear unaffected by the absence of the 5-HT1A receptor. These results do not support a role of the 5-HT1A receptor in Meth-induced psychosis.