Targeted Gene Transfer to the Brain via the Delivery of Brain-Penetrating DNA Nanoparticles with Focused Ultrasound

Science.gov (United States)

Mead, Brian P.; Mastorakos, Panagiotis; Suk, Jung Soo; Klibanov, Alexander L.; Hanes, Justin; Price, Richard J.

2016-01-01

Gene therapy holds promise for the treatment of many pathologies of the central nervous system (CNS), including brain tumors and neurodegenerative diseases. However, the delivery of systemically administered gene carriers to the CNS is hindered by both the blood-brain barrier (BBB) and the nanoporous and electrostatically charged brain extracelluar matrix (ECM), which acts as a steric and adhesive barrier. We have previously shown that these physiological barriers may be overcome by, respectively, opening the BBB with MR image-guided focused ultrasound (FUS) and microbubbles and using highly compact “brain penetrating” nanoparticles (BPN) coated with a dense polyethylene glycol corona that prevents adhesion to ECM components. Here, we tested whether this combined approach could be utilized to deliver systemically administered DNA-bearing BPN (DNA-BPN) across the BBB and mediate localized, robust, and sustained transgene expression in the rat brain. Systemically administered DNA-BPN delivered through the BBB with FUS led to dose-dependent transgene expression only in the FUS-treated region that was evident as early as 24 h post administration and lasted for at least 28 days. In the FUS-treated region ~42% of all cells, including neurons and astrocytes, were transfected, while less than 6% were transfected in the contralateral non-FUS treated hemisphere. Importantly, this was achieved without any sign of toxicity or astrocyte activation. We conclude that the image-guided delivery of DNA-BPN with FUS and microbubbles constitutes a safe and non-invasive strategy for targeted gene therapy to the brain. PMID:26732553

Transcranial cavitation-mediated ultrasound therapy at sub-MHz frequency via temporal interference modulation

Science.gov (United States)

Sun, Tao; Sutton, Jonathan T.; Power, Chanikarn; Zhang, Yongzhi; Miller, Eric L.; McDannold, Nathan J.

2017-10-01

Sub-megahertz transmission is not usually adopted in pre-clinical small animal experiments for focused ultrasound (FUS) brain therapy due to the large focal size. However, low frequency FUS is vital for preclinical evaluations due to the frequency-dependence of cavitation behavior. To maximize clinical relevance, a dual-aperture FUS system was designed for low-frequency (274.3 kHz) cavitation-mediated FUS therapy. Combining two spherically curved transducers provides significantly improved focusing in the axial direction while yielding an interference pattern with strong side lobes, leading to inhomogeneously distributed cavitation activities. By operating the two transducers at slightly offset frequencies to modulate this interference pattern over the period of sonication, the acoustic energy was redistributed and resulted in a spatially homogenous treatment profile. Simulation and pressure field measurements in water were performed to assess the beam profiles. In addition, the system performance was demonstrated in vivo in rats via drug delivery through microbubble-mediated blood-brain barrier disruption. This design resulted in a homogenous treatment profile that was fully contained within the rat brain at a clinically relevant acoustic frequency.

Combined photothermal therapy and magneto-motive ultrasound imaging using multifunctional nanoparticles

Science.gov (United States)

Mehrmohammadi, Mohammad; Ma, Li L.; Chen, Yun-Sheng; Qu, Min; Joshi, Pratixa; Chen, Raeanna M.; Johnston, Keith P.; Emelianov, Stanislav

2010-02-01

Photothermal therapy is a laser-based non-invasive technique for cancer treatment. Photothermal therapy can be enhanced by employing metal nanoparticles that absorb the radiant energy from the laser leading to localized thermal damages. Targeting of nanoparticles leads to more efficient uptake and localization of photoabsorbers thus increasing the effectiveness of the treatment. Moreover, efficient targeting can reduce the required dosage of photoabsorbers; thereby reducing the side effects associated with general systematic administration of nanoparticles. Magnetic nanoparticles, due to their small size and response to an external magnetic field gradient have been proposed for targeted drug delivery. In this study, we investigate the applicability of multifunctional nanoparticles (e.g., magneto-plasmonic nanoparticles) and magneto-motive ultrasound imaging for image-guided photothermal therapy. Magneto-motive ultrasound imaging is an ultrasound based imaging technique capable of detecting magnetic nanoparticles indirectly by utilizing a high strength magnetic field to induce motion within the magnetically labeled tissue. The ultrasound imaging is used to detect the internal tissue motion. Due to presence of the magnetic component, the proposed multifunctional nanoparticles along with magneto-motive ultrasound imaging can be used to detect the presence of the photo absorbers. Clearly the higher concentration of magnetic carriers leads to a monotonic increase in magneto-motive ultrasound signal. Thus, magnetomotive ultrasound can determine the presence of the hybrid agents and provide information about their location and concentration. Furthermore, the magneto-motive ultrasound signal can indicate the change in tissue elasticity - a parameter that is expected to change significantly during the photothermal therapy. Therefore, a comprehensive guidance and assessment of the photothermal therapy may be feasible through magneto-motive ultrasound imaging and

Integrated ultrasound and magnetic resonance imaging for simultaneous temperature and cavitation monitoring during focused ultrasound therapies.

Science.gov (United States)

Arvanitis, Costas D; McDannold, Nathan

2013-11-01

Ultrasound can be used to noninvasively produce different bioeffects via viscous heating, acoustic cavitation, or their combination, and these effects can be exploited to develop a wide range of therapies for cancer and other disorders. In order to accurately localize and control these different effects, imaging methods are desired that can map both temperature changes and cavitation activity. To address these needs, the authors integrated an ultrasound imaging array into an MRI-guided focused ultrasound (MRgFUS) system to simultaneously visualize thermal and mechanical effects via passive acoustic mapping (PAM) and MR temperature imaging (MRTI), respectively. The system was tested with an MRgFUS system developed for transcranial sonication for brain tumor ablation in experiments with a tissue mimicking phantom and a phantom-filled ex vivo macaque skull. In experiments on cavitation-enhanced heating, 10 s continuous wave sonications were applied at increasing power levels (30-110 W) until broadband acoustic emissions (a signature for inertial cavitation) were evident. The presence or lack of signal in the PAM, as well as its magnitude and location, were compared to the focal heating in the MRTI. Additional experiments compared PAM with standard B-mode ultrasound imaging and tested the feasibility of the system to map cavitation activity produced during low-power (5 W) burst sonications in a channel filled with a microbubble ultrasound contrast agent. When inertial cavitation was evident, localized activity was present in PAM and a marked increase in heating was observed in MRTI. The location of the cavitation activity and heating agreed on average after registration of the two imaging modalities; the distance between the maximum cavitation activity and focal heating was -3.4 ± 2.1 mm and -0.1 ± 3.3 mm in the axial and transverse ultrasound array directions, respectively. Distortions and other MRI issues introduced small uncertainties in the PAM�

Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

Science.gov (United States)

Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

2014-09-10

Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

TU-EF-210-04: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy

Energy Technology Data Exchange (ETDEWEB)

Farahani, K. [National Cancer Institute (United States)

2015-06-15

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

TU-EF-210-04: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy

International Nuclear Information System (INIS)

Farahani, K.

2015-01-01

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare

Non-Thermal High-Intensity Focused Ultrasound for Breast Cancer Therapy

Science.gov (United States)

2013-07-01

Comet assay reveals DNA strand breaks induced by ultrasonic cavitation in vitro, Ultrasound in medicine & biology 1995; 21: 841-8. 3. Dalecki D...doxorubicin, focused ultrasound , HIFU, prostate cancer I. INTRODUCTION Pulsed high-intensity focused ultrasound (pFUS) is able to create acoustic cavitation ... ultrasound for breast cancer therapy PRINCIPAL INVESTIGATOR: Chang Ming (Charlie) Ma, Ph.D

TU-B-210-00: MR-Guided Focused Ultrasound Therapy in Oncology

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.

Ultrasound-controlled neuronavigator-guided brain surgery.

Science.gov (United States)

Koivukangas, J; Louhisalmi, Y; Alakuijala, J; Oikarinen, J

1993-07-01

The development of a unique neurosurgical navigator is described and a preliminary series of seven cases of intracerebral lesions approached with the assistance of this neuronavigation system under ultrasound control is presented. The clinical series included five low-grade astrocytomas, one chronic intracerebral hematoma, and one porencephalic cyst. Management procedures included biopsy in all cases, drainage of the hematoma, and endoscopy and fenestration for the cyst. The features of the neuronavigation system are interactive reconstructions of preoperative computerized tomography and magnetic resonance imaging data, corresponding intraoperative ultrasound images, versatility of the interchangeable end-effector instruments, graphic presentation of instruments on the reconstructed images, and voice control of the system. The principle of a common axis in the reconstructed images served to align the navigational pointer, biopsy guide, endoscope guide, ultrasound transducer, and surgical microscope to the brain anatomy. Intraoperative ultrasound imaging helped to verify the accuracy of the neuronavigator and check the results of the procedures. The arm of the neuronavigation system served as a holder for instruments, such as the biopsy guide, endoscope guide, and ultrasound transducer, in addition to functioning as a navigational pointer. Also, the surgical microscope was aligned with the neuronavigator for inspection and biopsy of the hematoma capsule to rule out tumor etiology. Voice control freed the neurosurgeon from manual exercises during start-up and calibration of the system.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles

Science.gov (United States)

Burgess, M. T.; Apostolakis, I.; Konofagou, E. E.

2018-03-01

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

Science.gov (United States)

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction

Directory of Open Access Journals (Sweden)

Yali Xu

2016-01-01

Full Text Available Objective. Blood-brain barrier (BBB is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p<0.01. Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4±1, grade 2 while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Ultrasound-based guidance of intensity-modulated radiation therapy

International Nuclear Information System (INIS)

Fung, Albert Y.C.; Ayyangar, Komanduri M.; Djajaputra, David; Nehru, Ramasamy M.; Enke, Charles A.

2006-01-01

In ultrasound-guided intensity-modulated radiation therapy (IMRT) of prostate cancer, ultrasound imaging ascertains the anatomical position of patients during x-ray therapy delivery. The ultrasound transducers are made of piezoelectric ceramics. The same crystal is used for both ultrasound production and reception. Three-dimensional (3D) ultrasound devices capture and correlate series of 2-dimensional (2D) B-mode images. The transducers are often arranged in a convex array for focusing. Lower frequency reaches greater depth, but results in low resolution. For clear image, some gel is usually applied between the probe and the skin contact surface. For prostate positioning, axial and sagittal scans are performed, and the volume contours from computed tomography (CT) planning are superimposed on the ultrasound images obtained before radiation delivery at the linear accelerator. The planning volumes are then overlaid on the ultrasound images and adjusted until they match. The computer automatically deduces the offset necessary to move the patient so that the treatment area is in the correct location. The couch is translated as needed. The currently available commercial equipment can attain a positional accuracy of 1-2 mm. Commercial manufacturer designs differ in the detection of probe coordinates relative to the isocenter. Some use a position-sensing robotic arm, while others have infrared light-emitting diodes or pattern-recognition software with charge-couple-device cameras. Commissioning includes testing of image quality and positional accuracy. Ultrasound is mainly used in prostate positioning. Data for 7825 daily fractions of 234 prostate patients indicated average 3D inter-fractional displacement of about 7.8 mm. There was no perceivable trend of shift over time. Scatter plots showed slight prevalence toward superior-posterior directions. Uncertainties of ultrasound guidance included tissue inhomogeneities, speckle noise, probe pressure, and inter

Efficacy of therapeutic ultrasound and exercise therapy in the ...

African Journals Online (AJOL)

Results: Findings of the study revealed no significant difference in VAS, ROM and WOMAC scores in the study and control groups. Conclusions: This study confirms that therapeutic ultrasound is of no additional benefit to exercise therapy in the management of chronic osteoarthritis. Key words: Ultrasound; Exercise; ...

A 1372-element Large Scale Hemispherical Ultrasound Phased Array Transducer for Noninvasive Transcranial Therapy

International Nuclear Information System (INIS)

Song, Junho; Hynynen, Kullervo

2009-01-01

Noninvasive transcranial therapy using high intensity focused ultrasound transducers has attracted high interest as a promising new modality for the treatments of brain related diseases. We describe the development of a 1372 element large scale hemispherical ultrasound phased array transducer operating at a resonant frequency of 306 kHz. The hemispherical array has a diameter of 31 cm and a 15.5 cm radius of curvature. It is constructed with piezoelectric (PZT-4) tube elements of a 10 mm in diameter, 6 mm in length and 1.4 mm wall thickness. Each element is quasi-air backed by attaching a cork-rubber membrane on the back of the element. The acoustic efficiency of the element is determined to be approximately 50%. The large number of the elements delivers high power ultrasound and offers better beam steering and focusing capability. Comparisons of sound pressure-squared field measurements with theoretical calculations in water show that the array provides good beam steering and tight focusing capability over an efficient volume of approximately 100x100x80 mm 3 with nominal focal spot size of approximately 2.3 mm in diameter at -6 dB. We also present its beam steering and focusing capability through an ex vivo human skull by measuring pressure-squared amplitude after phase corrections. These measurements show the same efficient volume range and focal spot sizes at -6 dB as the ones in water without the skull present. These results indicate that the array is sufficient for use in noninvasive transcranial ultrasound therapy.

Whole-brain radiation therapy for brain metastases: detrimental or beneficial?

International Nuclear Information System (INIS)

Gemici, Cengiz; Yaprak, Gokhan

2015-01-01

Stereotactic radiosurgery is frequently used, either alone or together with whole-brain radiation therapy to treat brain metastases from solid tumors. Certain experts and radiation oncology groups have proposed replacing whole-brain radiation therapy with stereotactic radiosurgery alone for the management of brain metastases. Although randomized trials have favored adding whole-brain radiation therapy to stereotactic radiosurgery for most end points, a recent meta-analysis demonstrated a survival disadvantage for patients treated with whole-brain radiation therapy and stereotactic radiosurgery compared with patients treated with stereotactic radiosurgery alone. However the apparent detrimental effect of adding whole-brain radiation therapy to stereotactic radiosurgery reported in this meta-analysis may be the result of inhomogeneous distribution of the patients with respect to tumor histologies, molecular histologic subtypes, and extracranial tumor stages between the groups rather than a real effect. Unfortunately, soon after this meta-analysis was published, even as an abstract, use of whole-brain radiation therapy in managing brain metastases has become controversial among radiation oncologists. The American Society of Radiation Oncology recently recommended, in their “Choose Wisely” campaign, against routinely adding whole-brain radiation therapy to stereotactic radiosurgery to treat brain metastases. However, this situation creates conflict for radiation oncologists who believe that there are enough high level of evidence for the effectiveness of whole-brain radiation therapy in the treatment of brain metastases

Ultrasound-mediated drug delivery to the brain: principles, progress and prospects

NARCIS (Netherlands)

Dasgupta, I.; Liu, M.; Ojha, T.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria

2016-01-01

The blood–brain barrier (BBB) limits drug delivery to the central nervous system. When combined with microbubbles, ultrasound can transiently permeate blood vessels in the brain. This approach, which can be referred to as sonoporation or sonopermeabilization, holds significant promise for shuttling

Ultrasound-guided interventional therapy for recurrent ovarian chocolate cysts.

Science.gov (United States)

Wang, Lu-Lu; Dong, Xiao-Qiu; Shao, Xiao-Hui; Wang, Si-Ming

2011-10-01

The aim of this study was to determine the effectiveness of ultrasound-guided interventional therapy in the treatment of postoperative recurrent chocolate cysts. The 198 patients enrolled in this study were divided into three groups. In group 1, the saline washing group, the cavity of the cyst was washed thoroughly with warm saline. In group 2, the ethanol short-time retention group, after washing with saline, the cyst was injected with 95% ethanol with a volume of half of the fluid aspirated from the cyst. Ten minutes later, the rest of the ethanol was aspirated. In group 3, the ethanol retention group, the procedures were the same as with the ethanol short-time retention group, except that 95% of the ethanol was retained in the cyst. An ultrasound examination was performed in the third, sixth and 12th months after therapy. The chocolate cyst cure rate was significantly higher in the ethanol retention group (96%, 66/69) than in the ethanol short-time retention group (82%, 56/68) and no case was cured in the first group (saline washing). We conclude that ultrasound-guided injection and 95% ethanol retention are an effective therapy for the treatment of postoperative recurrent chocolate cysts. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles.

Science.gov (United States)

Meairs, Stephen

2015-08-31

Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood-brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer's disease is presented.

Effectiveness of using ultrasound therapy and manual therapy in the conservative treatment of calcaneal spur – pilot study

Directory of Open Access Journals (Sweden)

Twarowska Natalia

2016-06-01

Full Text Available Introduction: Calcaneal spur is a pathology of the fibrocartilage enthesis of the Achilles tendon and plantar fascia or a pathology of the mixed enthesis of the flexor digitorum brevis muscle. Ultrasound therapy is commonly applied in the conservative treatment of a calcaneal spur. Foot muscle strengthening exercises, stretching exercises and soft tissue therapy are indicated as effective methods of conservative treatment. The aim of the study was to compare and assess the effects of ultrasound therapy and selected techniques of manual therapy on pain level and functional state in patients with calcaneal spur.

Cerebral blood flow and brain shrinkage seen on CT during ACTH therapy

International Nuclear Information System (INIS)

Futagi, Yasuyuki; Abe, Jiro; Kawahigashi, Kenji

1986-01-01

By means of the Doppler ultrasound method, the cerebral blood flow (CBF) was assessed in 21 children with epilepsy undergoing treatment with adrenocorticotrophic hormone (ACTH). The maximum reduction in the internal carotid velocity, as an index of CBF during therapy, was about 35 percent compared with the values before therapy. Furthermore, sequential computed tomography (CT) examinations of the same subjects were performed to evaluate the change in the area of the intracranial brain parenchyma during therapy. The maximum reduction in the parenchymal area during therapy was about 10 percent. This corresponds to a 20 percent reduction in CBF according to Poiseuille's law, however, the remaining reduction in CBF demonstrated by velocity measurement cannot be explained only by that mechanical vascular factor. From these findings, it is concluded that in order to elucidate the mechanism of the CBF reduction, physiological factors such as changes in metabolism during therapy should also be evaluated in addition to the mechanical and physical causes. (author)

Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles

Directory of Open Access Journals (Sweden)

Stephen Meairs

2015-08-01

Full Text Available Medical treatment options for central nervous system (CNS diseases are limited due to the inability of most therapeutic agents to penetrate the blood–brain barrier (BBB. Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer’s disease is presented.

Ultrasound-mediated microbubble enhancement of radiation therapy studied using three-dimensional high-frequency power Doppler ultrasound.

Science.gov (United States)

Kwok, Sheldon J J; El Kaffas, Ahmed; Lai, Priscilla; Al Mahrouki, Azza; Lee, Justin; Iradji, Sara; Tran, William Tyler; Giles, Anoja; Czarnota, Gregory J

2013-11-01

Tumor responses to high-dose (>8 Gy) radiation therapy are tightly connected to endothelial cell death. In the study described here, we investigated whether ultrasound-activated microbubbles can locally enhance tumor response to radiation treatments of 2 and 8 Gy by mechanically perturbing the endothelial lining of tumors. We evaluated vascular changes resulting from combined microbubble and radiation treatments using high-frequency 3-D power Doppler ultrasound in a breast cancer xenograft model. We compared treatment effects and monitored vasculature damage 3 hours, 24 hours and 7 days after treatment delivery. Mice treated with 2 Gy radiation and ultrasound-activated microbubbles exhibited a decrease in vascular index to 48 ± 10% at 24 hours, whereas vascular indices of mice treated with 2 Gy radiation alone or microbubbles alone were relatively unchanged at 95 ± 14% and 78 ± 14%, respectively. These results suggest that ultrasound-activated microbubbles enhance the effects of 2 Gy radiation through a synergistic mechanism, resulting in alterations of tumor blood flow. This novel therapy may potentiate lower radiation doses to preferentially target endothelial cells, thus reducing effects on neighboring normal tissue and increasing the efficacy of cancer treatments. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice.

Science.gov (United States)

Zhao, Bingxia; Chen, Yihan; Liu, Jinfeng; Zhang, Li; Wang, Jing; Yang, Yali; Lv, Qing; Xie, Mingxing

2018-01-12

To investigate the effects of the microbubble (MB) dose, mechanism index (MI) and sonication duration on blood-brain barrier (BBB) disruption induced by diagnostic ultrasound combined with MBs as well as to investigate the potential molecular mechanism. The extent of BBB disruption increased with MB dose, MI and sonication duration. A relatively larger extent of BBB disruption associated with minimal tissue damage was achieved by an appropriate MB dose and ultrasound exposure parameters with diagnostic ultrasound. Decreased expression of ZO-1, occludin and claudin-5 were correlated with disruption of the BBB, as confirmed by paracellular passage of the tracer lanthanum nitrate into the brain parenchyma after BBB disruption. These findings indicated that this technique is a promising tool for promoting brain delivery of diagnostic and therapeutic agents in the diagnosis and treatment of brain diseases. The extent of BBB disruption was qualitatively assessed by Evans blue (EB) staining and quantitatively analyzed by an EB extravasation measurement. A histological examination was performed to evaluate tissue damage. Expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5 was determined by western blotting analysis and immunohistofluorescence. Transmission electron microscopy was performed to observe ultrastructure changes of TJs after BBB disruption.

Segmentation of tumor ultrasound image in HIFU therapy based on texture and boundary encoding

International Nuclear Information System (INIS)

Zhang, Dong; Xu, Menglong; Quan, Long; Yang, Yan; Qin, Qianqing; Zhu, Wenbin

2015-01-01

It is crucial in high intensity focused ultrasound (HIFU) therapy to detect the tumor precisely with less manual intervention for enhancing the therapy efficiency. Ultrasound image segmentation becomes a difficult task due to signal attenuation, speckle effect and shadows. This paper presents an unsupervised approach based on texture and boundary encoding customized for ultrasound image segmentation in HIFU therapy. The approach oversegments the ultrasound image into some small regions, which are merged by using the principle of minimum description length (MDL) afterwards. Small regions belonging to the same tumor are clustered as they preserve similar texture features. The mergence is completed by obtaining the shortest coding length from encoding textures and boundaries of these regions in the clustering process. The tumor region is finally selected from merged regions by a proposed algorithm without manual interaction. The performance of the method is tested on 50 uterine fibroid ultrasound images from HIFU guiding transducers. The segmentations are compared with manual delineations to verify its feasibility. The quantitative evaluation with HIFU images shows that the mean true positive of the approach is 93.53%, the mean false positive is 4.06%, the mean similarity is 89.92%, the mean norm Hausdorff distance is 3.62% and the mean norm maximum average distance is 0.57%. The experiments validate that the proposed method can achieve favorable segmentation without manual initialization and effectively handle the poor quality of the ultrasound guidance image in HIFU therapy, which indicates that the approach is applicable in HIFU therapy. (paper)

Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy.

Science.gov (United States)

Hynynen, Kullervo; Jones, Ryan M

2016-09-07

Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

3D-printed adaptive acoustic lens as a disruptive technology for transcranial ultrasound therapy using single-element transducers

Science.gov (United States)

Maimbourg, Guillaume; Houdouin, Alexandre; Deffieux, Thomas; Tanter, Mickael; Aubry, Jean-François

2018-01-01

The development of multi-element arrays for better control of the shape of ultrasonic beams has opened the way for focusing through highly aberrating media, such as the human skull. As a result, the use of brain therapy with transcranial-focused ultrasound has rapidly grown. Although effective, such technology is expensive. We propose a disruptive, low-cost approach that consists of focusing a 1 MHz ultrasound beam through a human skull with a single-element transducer coupled with a tailored silicone acoustic lens cast in a 3D-printed mold and designed using computed tomography-based numerical acoustic simulation. We demonstrate on N  =  3 human skulls that adding lens-based aberration correction to a single-element transducer increases the deposited energy on the target 10 fold.

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping.

Science.gov (United States)

Deng, Lulu; O'Reilly, Meaghan A; Jones, Ryan M; An, Ran; Hynynen, Kullervo

2016-12-21

Focused ultrasound (FUS) phased arrays show promise for non-invasive brain therapy. However, the majority of them are limited to a single transmit/receive frequency and therefore lack the versatility to expose and monitor the treatment volume. Multi-frequency arrays could offer variable transmit focal sizes under a fixed aperture, and detect different spectral content on receive for imaging purposes. Here, a three-frequency (306, 612, and 1224 kHz) sparse hemispherical ultrasound phased array (31.8 cm aperture; 128 transducer modules) was constructed and evaluated for microbubble-mediated transcranial therapy and simultaneous cavitation mapping. The array is able to perform effective electronic beam steering over a volume spanning (-40, 40) and (-30, 50) mm in the lateral and axial directions, respectively. The focal size at the geometric center is approximately 0.9 (2.1) mm, 1.7 (3.9) mm, and 3.1 (6.5) mm in lateral (axial) pressure full width at half maximum (FWHM) at 1224, 612, and 306 kHz, respectively. The array was also found capable of dual-frequency excitation and simultaneous multi-foci sonication, which enables the future exploration of more complex exposure strategies. Passive acoustic mapping of dilute microbubble clouds demonstrated that the point spread function of the receive array has a lateral (axial) intensity FWHM between 0.8-3.5 mm (1.7-11.7 mm) over a volume spanning (-25, 25) mm in both the lateral and axial directions, depending on the transmit/receive frequency combination and the imaging location. The device enabled both half and second harmonic imaging through the intact skull, which may be useful for improving the contrast-to-tissue ratio or imaging resolution, respectively. Preliminary in vivo experiments demonstrated the system's ability to induce blood-brain barrier opening and simultaneously spatially map microbubble cavitation activity in a rat model. This work presents a tool to investigate optimal strategies for non

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Radiation Therapy for Gynecologic Cancers Radiation Therapy for Prostate Cancer top of page This page was reviewed on ... Abdomen Children's (Pediatric) Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding ... Images related to Ultrasound - Pelvis Sponsored by Please ...

Potential mechanism in sonodynamic therapy and focused ultrasound induced apoptosis in sarcoma 180 cells in vitro.

Science.gov (United States)

Tang, Wei; Liu, Quanhong; Wang, Xiaobing; Wang, Pan; Zhang, Jing; Cao, Bing

2009-12-01

Sonodynamic therapy employs a combination of ultrasound and a sonosensitizer to enhance the cytotoxic effect of ultrasound and promote apoptosis. However, the mechanism underlying the synergistic effect of ultrasound and hematoporphyrin is still unclear. In this study, we investigated mechanism of the induction of apoptosis by sonodynamic therapy in Sarcoma 180 cells. The cell suspension was treated by 1.75-MHz focused continuous ultrasound at an acoustic power (I(SATA)) of 1.4+/-0.07 W/cm(2) for 3 min in the absence or presence of 20 microg/ml hematoporphyrin. The proportion of apoptotic cells was determined by flow cytometry. We then analyzed the reactive oxygen species generation and localization by confocal microscopy. Western blotting and reverse transcriptase-polymerase chain reaction were used to analyze the expression of caspase-8, caspase-9, poly(ADP)-ribose polymerase, and nuclear factor-kappaB. The findings of our study indicate that ultrasound treatment induced the activation of nuclear factor-kappaB as an early stress response. When cells were pretreated with hematoporphyrin, the initial response to the therapy was the formation of (1)O(2) in the mitochondria. Our results primarily demonstrate that the mechanisms of induction of apoptosis by ultrasound and hematoporphyrin-sonodynamic therapies are very different. Our findings can provide a basis for explaining the synergistic effect of ultrasound and hematoporphyrin.

Subacute brain atrophy induced by radiation therapy to the malignant brain tumors

International Nuclear Information System (INIS)

Asai, Akio; Matsutani, Masao; Takakura, Kintomo.

1987-01-01

In order to analyze brain atrophy after radiation therapy to the brain tumors, we calculated a CSF-cranial volume ratio on CT scan as an index of brain atrophy, and estimated dementia-score by Hasegawa's method in 91 post-irradiated patients with malignant brain tumors. Radiation-induced brain atrophy was observed in 51 out of 91 patients (56 %) and dementia in 23 out of 47 patients (49 %). These two conditions were closely related, and observed significantly more often in aged and whole-brain-irradiated patients. As radiation-induced brain atrophy accompanied by dementia appeared 2 - 3 months after the completion of radiation therapy, it should be regarded as a subacute brain injury caused by radiation therapy. (author)

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

Directory of Open Access Journals (Sweden)

Habib Baghirov

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

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

Science.gov (United States)

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

2018-01-01

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

Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.

Science.gov (United States)

Kobus, Thiele; Vykhodtseva, Natalia; Pilatou, Magdalini; Zhang, Yongzhi; McDannold, Nathan

2016-02-01

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Dynamic contrast enhanced ultrasound for therapy monitoring

Energy Technology Data Exchange (ETDEWEB)

Hudson, John M. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Williams, Ross [Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Tremblay-Darveau, Charles; Sheeran, Paul S. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Milot, Laurent [Department of Medical Imaging, University of Toronto, Toronto, ON (Canada); Bjarnason, Georg A. [Department of Medical Oncology, University of Toronto, and Sunnybrook Odette Cancer Centre, Toronto, ON (Canada); Burns, Peter N., E-mail: burns@sri.utoronto.ca [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON (Canada)

2015-09-15

Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular. This papers reviews the principles and methodology of DCE-US, especially as applied to anti-angiogenic cancer therapies. Reproducibility is an important attribute of such a monitoring method: results are discussed. More recent technical advances in parametric and 3D DCE-US imaging are also summarised and illustrated.

Cranial Ultrasound/Head Ultrasound

Science.gov (United States)

... used to screen for brain conditions associated with prematurity, such as bleeding or brain tissue damage as ... or crying child will slow the examination process. Large patients are more difficult to image by ultrasound, ...

Review Paper: A Review on Brain Stimulation Using Low Intensity Focused Ultrasound

Directory of Open Access Journals (Sweden)

Ehsan Rezayat

2016-07-01

Full Text Available Brain stimulation techniques are important in both basic and clinical studies. Majority of well-known brain stimulating techniques have low spatial resolution or entail invasive processes. Low intensity focused ultrasound (LIFU seems to be a proper candidate for dealing with such deficiencies. This review recapitulates studies which explored the effects of LIFU on brain structures and its function, in both research and clinical areas. Although the mechanism of LIFU action is still unclear, its different effects from molecular level up to behavioral level can be explored in animal and human brain. It can also be coupled with brain imaging assessments in future research.

Quantitative analysis of normal fetal brain volume and flow by three-dimensional power Doppler ultrasound

Directory of Open Access Journals (Sweden)

Ju-Chun Hsu

2013-09-01

Conclusion: 3D ultrasound can be used to assess the fetal brain volume and blood flow development quantitatively. Our study indicates that the fetal brain vascularization and blood flow correlates significantly with the advancement of GA. This information may serve as a reference point for further studies of the fetal brain volume and blood flow in abnormal conditions.

Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.

Science.gov (United States)

Yang, Feng-Yi; Chang, Wen-Yuan; Chen, Jyh-Cheng; Lee, Lin-Chien; Hung, Yi-Shun

2014-04-15

The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption. Copyright © 2013 Elsevier Inc. All rights reserved.

Development, Characterization, and Implementation of a System for Focused Ultrasound-Mediated Blood-Brain Barrier Opening in Mice

Science.gov (United States)

Valdez, Michael Aaron

The blood-brain barrier BBB refers to the set of specialized endothelial cells that line the vasculature in the brain and effectively control movement of molecules into and out of the brain. While necessary for proper brain function, the BBB blocks 98% of drugs from entering the brain and is the most significant barrier to developing therapies for neurodegenerative diseases. Active transport allows some specific molecules to cross the BBB, but therapeutic development using this route has had limited success. A number of techniques have been used to bypass the BBB, but are often highly invasive and ineffective. Over the last two decades, a minimally invasive technique to transiently open the BBB has been under development that utilizes transcranial focused ultrasound (FUS) in combination with intravascular microbubble contrast agents. This method is often carried out in conjunction with magnetic resonance imaging (MRI) to guide and assess BBB opening and has been referred to as MRI guided FUS (MRgFUS). Because of the utility of mouse models of neurological disease and the exploratory nature of MRgFUS, systems that allow BBB opening in mice are a useful and necessary tool to develop and evaluate this method for clinical application. In this dissertation project, a custom built, cost-effective FUS system for opening the BBB in mice was developed, with the objective of using this device to deliver therapeutics to the brain. Being a custom device, it was necessary to evaluate the ultrasound output, verify in vivo safety, and anticipate the therapeutic effect. The scope of the work herein consists of the design, construction, and evaluation of system that fulfills these requirements. The final constructed system cost was an order of magnitude less than any commercially available MRgFUS system. At this low price point, the hardware could allow the implementation of the methodology in many more research areas than previously possible. Additionally, to anticipate the

High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

Science.gov (United States)

Phenix, Christopher Peter; Togtema, Melissa; Pichardo, Samuel; Zehbe, Ingeborg; Curiel, Laura

2014-01-01

Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.

Beacon signal in transcranial color coded ultrasound: A sign for brain death

Directory of Open Access Journals (Sweden)

Mehmet Akif Topçuoğlu

2014-04-01

Full Text Available A widely under-recognized brain-death confirming transcranial ultrasonography pattern resembling the red-blue beacon signal was demonstrated. Familiarity to this distinct and characteristic ultrasonic pattern seems to be important in the perspective of point-of-care neurological ultrasound use and knobology.

Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity

International Nuclear Information System (INIS)

McDannold, N; Vykhodtseva, N; Hynynen, K

2006-01-01

Acoustic emission was monitored during focused ultrasound exposures in conjunction with an ultrasound contrast agent (Optison (registered) ) in order to determine if cavitation activity is associated with the induction of blood-brain barrier disruption (BBBD). Thirty-four locations were sonicated (frequency: 260 kHz) at targets 10 mm deep in rabbit brain (N = 9). The sonications were applied at peak pressure amplitudes ranging from 0.11 to 0.57 MPa (burst length: 10 ms; repetition frequency of 1 Hz; duration: 20 s). Acoustic emission was recorded with a focused passive cavitation detector. This emission was recorded at each location during sonications with and without Optison (registered) . Detectable wideband acoustic emission was observed only at 0.40 and 0.57 MPa. BBBD was observed in contrast MRI after sonication at 0.29-0.57 MPa. The appearance of small regions of extravasated erythrocytes appeared to be associated with this wideband emission signal. The results thus suggest that BBBD resulting from focused ultrasound pulses in the presence of Optison (registered) can occur without indicators for inertial cavitation in vivo, wideband emission and extravasation. If inertial cavitation is not responsible for the BBBD, other ultrasound/microbubble interactions are likely the source. A significant increase in the emission signal due to Optison (registered) at the second and third harmonics of the ultrasound driving frequency was found to correlate with BBBD and might be useful as an online method to indicate when the disruption occurs

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Imaging? Ultrasound waves are disrupted by air or gas; therefore ultrasound is not an ideal imaging technique ... page Additional Information and Resources RTAnswers.org Radiation Therapy for Gynecologic Cancers Radiation Therapy for Prostate Cancer ...

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

Science.gov (United States)

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models.

Directory of Open Access Journals (Sweden)

Scott B Raymond

Full Text Available Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP, across a large age range (9-26 months, with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

OpenAIRE

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

WE-G-12A-01: High Intensity Focused Ultrasound Surgery and Therapy

Energy Technology Data Exchange (ETDEWEB)

Farahani, K [National Cancer Institute, Rockville, MD (United States); O' Neill, B [The Methodist Hospital Research Institute, Houston, TX (United States)

2014-06-15

More and more emphasis is being made on alternatives to invasive surgery and the use of ionizing radiation to treat various diseases including cancer. Novel screening, diagnosis, treatment and monitoring of response to treatment are also hot areas of research and new clinical technologies. Ultrasound(US) has gained traction in all of the aforementioned areas of focus. Especially with recent advances in the use of ultrasound to noninvasively treat various diseases/organ systems. This session will focus on covering MR-guided focused ultrasound and the state of the art clinical applications, and the second speaker will survey the more cutting edge technologies e.g. Focused Ultrasound (FUS) mediated drug delivery, principles of cavitation and US guided FUS. Learning Objectives: Fundamental physics and physical limitations of US interaction with tissue and nanoparticles The alteration of tissue transport using focused ultrasound US control of nanoparticle drug carriers for targeted release The basic principles of MRI-guided focused ultrasound (MRgFUS) surgery and therapy the current state of the art clinical applications of MRgFUS requirements for quality assurance and treatment planning.

Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles

OpenAIRE

Meairs, Stephen

2015-01-01

Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood–brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This techni...

Low-Frequency Ultrasound Therapy in Combination Treatment of Patients with Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

YE.E. LAVRINENKO

2013-04-01

Results. The beginning of therapeutic effect was observed after 2 procedures of the ultrasound exposure. The maximum effect is appeared after 8–10 treatment sessions. The positive dynamics of complex treatment is improving the general state of health, a disappearance of asthenization, and a decrease in the symptoms of cardiovascular disorders, achieving faster compensation of carbohydrate metabolism. The course of treatment contributed to the hyperglycemia reduction in patients with newly detected type 2 DM. After ultrasound treatment, the authors noted a positive dynamics of clinical symptoms: an improvement of the general health status, a decrease in fatigue, an improvement of psycho-emotional indices, disappearance of pain in the right upper quadrant, and a decrease in liver size in all the patients under study. Conclusions. The use of low-frequency ultrasound therapy on cutaneous projection of the liver in patients with type 2 DM promotes the normalization both fasting and postprandial glycemia. The effect of low-frequency ultrasound on cutaneous projection of the liver is significantly decreasing parameters that characterize the pancreatic insulin synthesizing function (immunoreactive insulin, C-peptide in patients with newly diagnosed type 2 DM and a BMI > 25 kg/m2. Low-frequency ultrasound reduces the glucagon secretion and thereby positively affects the hepatic gluconeogenesis. Ultrasound therapy can be used in the complex treatment of patients with newly diagnosed type 2 DM.

pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

Science.gov (United States)

Feng, Qianhua; Zhang, Wanxia; Yang, Xuemei; Li, Yuzhen; Hao, Yongwei; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

2018-03-01

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO 2 generation and HMME release with spatial/temporal resolution. Afterward, the CO 2 bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO 2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thin-film sparse boundary array design for passive acoustic mapping during ultrasound therapy.

Science.gov (United States)

Coviello, Christian M; Kozick, Richard J; Hurrell, Andrew; Smith, Penny Probert; Coussios, Constantin-C

2012-10-01

A new 2-D hydrophone array for ultrasound therapy monitoring is presented, along with a novel algorithm for passive acoustic mapping using a sparse weighted aperture. The array is constructed using existing polyvinylidene fluoride (PVDF) ultrasound sensor technology, and is utilized for its broadband characteristics and its high receive sensitivity. For most 2-D arrays, high-resolution imagery is desired, which requires a large aperture at the cost of a large number of elements. The proposed array's geometry is sparse, with elements only on the boundary of the rectangular aperture. The missing information from the interior is filled in using linear imaging techniques. After receiving acoustic emissions during ultrasound therapy, this algorithm applies an apodization to the sparse aperture to limit side lobes and then reconstructs acoustic activity with high spatiotemporal resolution. Experiments show verification of the theoretical point spread function, and cavitation maps in agar phantoms correspond closely to predicted areas, showing the validity of the array and methodology.

Noninvasive treatment of deep venous thrombosis using pulsed ultrasound cavitation therapy (histotripsy) in a porcine model.

Science.gov (United States)

Maxwell, Adam D; Owens, Gabe; Gurm, Hitinder S; Ives, Kimberly; Myers, Daniel D; Xu, Zhen

2011-03-01

This study evaluated histotripsy as a noninvasive, image-guided method of thrombolysis in a porcine model of deep vein thrombosis. Histotripsy therapy uses short, high-intensity, focused ultrasound pulses to cause mechanical breakdown of targeted soft tissue by acoustic cavitation, which is guided by real-time ultrasound imaging. This is an in vivo feasibility study of histotripsy thrombolysis. Acute thrombi were formed in the femoral vein of juvenile pigs weighing 30-40 kg by balloon occlusion with two catheters and thrombin infusion. A 10-cm-diameter 1-MHz focused transducer was used for therapy. An 8-MHz ultrasound imager was used to align the clot with the therapy focus. Therapy consisted of five cycle pulses delivered at a rate of 1 kHz and peak negative pressure between 14 and 19 MPa. The focus was scanned along the long axis of the vessel to treat the entire visible clot during ultrasound exposure. The targeted region identified by a hyperechoic cavitation bubble cloud was visualized via ultrasound during treatment. Thrombus breakdown was apparent as a decrease in echogenicity within the vessel in 10 of 12 cases and in 7 cases improved flow through the vein as measured by color Doppler. Vessel histology found denudation of vascular endothelium and small pockets of hemorrhage in the vessel adventitia and underlying muscle and fatty tissue, but perforation of the vessel wall was never observed. The results indicate histotripsy has potential for development as a noninvasive treatment for deep vein thrombosis. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Potential and problems in ultrasound-responsive drug delivery systems

Directory of Open Access Journals (Sweden)

Zhao YZ

2013-04-01

Full Text Available Ying-Zheng Zhao,1,3 Li-Na Du,2 Cui-Tao Lu,1 Yi-Guang Jin,2 Shu-Ping Ge3 1Wenzhou Medical College, Wenzhou City, Zhejiang Province, 2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3St Christopher’s Hospital for Children/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. Keywords: ultrasound, targeted therapy, clinical application

NMR guided focused ultrasound for myoma therapy - results from the first radiology-gynecology expert meeting

International Nuclear Information System (INIS)

Beck, A.; Charite Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin; David, M.; Kroencke, T.; Charite Universitaetsmedizin Berlin, Campus Charite Mitte, Berlin

2013-01-01

The contribution on the results from the first radiology-gynecology expert meeting concerning NMR guided focused ultrasound (MRgFUS) for myoma therapy covers the following topics: structural prerequisites for MRgFUS therapy; required examinations before MRgFUS therapy; indication for MRgFUS therapy; success criteria for the MRgFUS therapy; contraindications; MRgFUS therapy for patients that want to have children; side effects and complications of MRgFUS therapy; post-examination after MRgFUS therapy.

Lipid nano-bubble combined with ultrasound for anti-keloids therapy.

Science.gov (United States)

Wang, Xiao Qing; Li, Zhou-Na; Wang, Qi-Ming; Jin, Hong-Yan; Gao, Zhonggao; Jin, Zhe-Hu

2018-03-01

Keloids were characterized by excessive growth of fibrous tissues, and shared several pathological characteristics with cancer. They did put physical and emotional stress on patients in that keloids could badly change appearance of patients. N-(4-hydroxyphenyl) retinamide (4HPR) showed cytotoxic activity on a wide variety of invasive-growth cells. Our work was aim to prepare N-(4-hydroxyphenyl) retinamide-loaded lipid microbubbles (4HPR-LM) combined with ultrasound for anti-keloid therapy. 4HPR-loaded liposomes (4HPR-L) were first prepared by film evaporation method, and then 4HPR-LM were manufactured by mixing 4HPR-L and perfluoropentane (PFP) with ultrasonic cavitation method. The mean particle size and entrapment efficiency 4HPR-LM were 113 nm and 95%, respectively. The anti-keloids activity of 4HPR-LM was assessed with BALB/c nude mice bearing subcutaneous xenograft keloids model. 4HPR-LM, combined with ultrasound, could significantly induce apoptosis of keloid fibroblasts in vitro and inhibited growth of keloids in vivo. Thus, 4HPR-LM could be considered as a promising agent for anti-keloids therapy.

A region-based segmentation method for ultrasound images in HIFU therapy

International Nuclear Information System (INIS)

Zhang, Dong; Liu, Yu; Yang, Yan; Xu, Menglong; Yan, Yu; Qin, Qianqing

2016-01-01

Purpose: Precisely and efficiently locating a tumor with less manual intervention in ultrasound-guided high-intensity focused ultrasound (HIFU) therapy is one of the keys to guaranteeing the therapeutic result and improving the efficiency of the treatment. The segmentation of ultrasound images has always been difficult due to the influences of speckle, acoustic shadows, and signal attenuation as well as the variety of tumor appearance. The quality of HIFU guidance images is even poorer than that of conventional diagnostic ultrasound images because the ultrasonic probe used for HIFU guidance usually obtains images without making contact with the patient’s body. Therefore, the segmentation becomes more difficult. To solve the segmentation problem of ultrasound guidance image in the treatment planning procedure for HIFU therapy, a novel region-based segmentation method for uterine fibroids in HIFU guidance images is proposed. Methods: Tumor partitioning in HIFU guidance image without manual intervention is achieved by a region-based split-and-merge framework. A new iterative multiple region growing algorithm is proposed to first split the image into homogenous regions (superpixels). The features extracted within these homogenous regions will be more stable than those extracted within the conventional neighborhood of a pixel. The split regions are then merged by a superpixel-based adaptive spectral clustering algorithm. To ensure the superpixels that belong to the same tumor can be clustered together in the merging process, a particular construction strategy for the similarity matrix is adopted for the spectral clustering, and the similarity matrix is constructed by taking advantage of a combination of specifically selected first-order and second-order texture features computed from the gray levels and the gray level co-occurrence matrixes, respectively. The tumor region is picked out automatically from the background regions by an algorithm according to a priori

A region-based segmentation method for ultrasound images in HIFU therapy

Energy Technology Data Exchange (ETDEWEB)

Zhang, Dong, E-mail: dongz@whu.edu.cn; Liu, Yu; Yang, Yan; Xu, Menglong; Yan, Yu [School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Qin, Qianqing [State Key Laboratory of Information Engineering in Surveying, Mapping and Remote Sensing, Wuhan University, Wuhan 430072 (China)

2016-06-15

Purpose: Precisely and efficiently locating a tumor with less manual intervention in ultrasound-guided high-intensity focused ultrasound (HIFU) therapy is one of the keys to guaranteeing the therapeutic result and improving the efficiency of the treatment. The segmentation of ultrasound images has always been difficult due to the influences of speckle, acoustic shadows, and signal attenuation as well as the variety of tumor appearance. The quality of HIFU guidance images is even poorer than that of conventional diagnostic ultrasound images because the ultrasonic probe used for HIFU guidance usually obtains images without making contact with the patient’s body. Therefore, the segmentation becomes more difficult. To solve the segmentation problem of ultrasound guidance image in the treatment planning procedure for HIFU therapy, a novel region-based segmentation method for uterine fibroids in HIFU guidance images is proposed. Methods: Tumor partitioning in HIFU guidance image without manual intervention is achieved by a region-based split-and-merge framework. A new iterative multiple region growing algorithm is proposed to first split the image into homogenous regions (superpixels). The features extracted within these homogenous regions will be more stable than those extracted within the conventional neighborhood of a pixel. The split regions are then merged by a superpixel-based adaptive spectral clustering algorithm. To ensure the superpixels that belong to the same tumor can be clustered together in the merging process, a particular construction strategy for the similarity matrix is adopted for the spectral clustering, and the similarity matrix is constructed by taking advantage of a combination of specifically selected first-order and second-order texture features computed from the gray levels and the gray level co-occurrence matrixes, respectively. The tumor region is picked out automatically from the background regions by an algorithm according to a priori

Antioxidant therapies in traumatic brain injury: a review

Directory of Open Access Journals (Sweden)

Romero-Rivera Hector Rolando

2017-09-01

Full Text Available Oxidative stress constitute one of the commonest mechanism of the secondary injury contributing to neuronal death in traumatic brain injury cases. The oxidative stress induced secondary injury blockade may be considered as to be a good alternative to improve the outcome of traumatic brain injury (TBI treatment. Due to absence of definitive therapy of traumatic brain injury has forced researcher to utilize unconventional therapies and its roles investigated in the improvement of management and outcome in recent year. Antioxidant therapies are proven effective in many preclinical studies and encouraging results and the role of antioxidant mediaction may act as further advancement in the traumatic brain injury management it may represent aonr of newer moadlaity in neurosurgical aramamentorium, this kind of therapy could be a good alternative or adjuct to the previously established neuroprotection agents in TBI.

Wound healing treatment by high frequency ultrasound, microcurrent, and combined therapy modifies the immune response in rats

Directory of Open Access Journals (Sweden)

Raciele I. G. Korelo

2016-01-01

Full Text Available BACKGROUND: Therapeutic high-frequency ultrasound, microcurrent, and a combination of the two have been used as potential interventions in the soft tissue healing process, but little is known about their effect on the immune system. OBJECTIVE: To evaluate the effects of therapeutic high frequency ultrasound, microcurrent, and the combined therapy of the two on the size of the wound area, peritoneal macrophage function, CD4+ and CD8+, T lymphocyte populations, and plasma concentration of interleukins (ILs. METHOD: Sixty-five Wistar rats were randomized into five groups, as follows: uninjured control (C, group 1, lesion and no treatment (L, group 2, lesion treated with ultrasound (LU, group 3, lesion treated with microcurrent (LM, group 4, and lesion treated with combined therapy (LUM, group 5. For groups 3, 4 and 5, treatment was initiated 24 hours after surgery under anesthesia and each group was allocated into three different subgroups (n=5 to allow for the use of the different therapy resources at on days 3, 7 and 14 Photoplanimetry was performed daily. After euthanasia, blood was collected for immune analysis. RESULTS: Ultrasound increased the phagocytic capacity and the production of nitric oxide by macrophages and induced the reduction of CD4+ cells, the CD4+/CD8+ ratio, and the plasma concentration of IL-1β. Microcurrent and combined therapy decreased the production of superoxide anion, nitric oxide, CD4+-positive cells, the CD4+/CD8+ ratio, and IL-1β concentration. CONCLUSIONS: Therapeutic high-frequency ultrasound, microcurrent, and combined therapy changed the activity of the innate and adaptive immune system during healing process but did not accelerate the closure of the wound.

Treatment of Movement Disorders With Focused Ultrasound

Directory of Open Access Journals (Sweden)

Paul S Fishman

2017-05-01

Full Text Available Although the use of ultrasound as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists or neurologists are familiar with this technology. Stereotactic brain lesioning had been widely used as a treatment for medically refractory patients with essential tremor (ET, Parkinson disease (PD, and dystonia but has been largely replaced by deep brain stimulation (DBS surgery, with advantages both in safety and efficacy. However, DBS is associated with complications including intracerebral hemorrhage, infection, and hardware malfunction. The occurrence of these complications has spurred interest in less invasive stereotactic brain lesioning methods including magnetic resonance imaging–guided high intensity–focused ultrasound (FUS surgery. Engineering advances now allow sound waves to be targeted noninvasively through the skull to a brain target. High intensities of sonic energy can create a coagulation lesion similar to that of older radiofrequency stereotactic methods, but without opening the skull, recent Food and Drug Administration approval of unilateral thalamotomy for treatment of ET. Clinical studies of stereotactic FUS for aspects of PD are underway. Moderate intensity, pulsed FUS has also demonstrated the potential to safely open the blood-brain barrier for localized delivery of therapeutics including proteins, genes, and cell-based therapy for PD and related disorders. The goal of this review is to provide basic and clinical neuroscientists with a level of understanding to interact with medical physicists, biomedical engineers, and radiologists to accelerate the application of this powerful technology to brain disease

Registration of human skull computed tomography data to an ultrasound treatment space using a sparse high frequency ultrasound hemispherical array

Energy Technology Data Exchange (ETDEWEB)

O’Reilly, Meaghan A., E-mail: moreilly@sri.utoronto.ca; Jones, Ryan M. [Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7 (Canada); Birman, Gabriel [Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5 (Canada); Hynynen, Kullervo [Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7 (Canada); Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9 (Canada)

2016-09-15

Purpose: Transcranial focused ultrasound (FUS) shows great promise for a range of therapeutic applications in the brain. Current clinical investigations rely on the use of magnetic resonance imaging (MRI) to monitor treatments and for the registration of preoperative computed tomography (CT)-data to the MR images at the time of treatment to correct the sound aberrations caused by the skull. For some applications, MRI is not an appropriate choice for therapy monitoring and its cost may limit the accessibility of these treatments. An alternative approach, using high frequency ultrasound measurements to localize the skull surface and register CT data to the ultrasound treatment space, for the purposes of skull-related phase aberration correction and treatment targeting, has been developed. Methods: A prototype high frequency, hemispherical sparse array was fabricated. Pulse-echo measurements of the surface of five ex vivo human skulls were made, and the CT datasets of each skull were obtained. The acoustic data were used to rigidly register the CT-derived skull surface to the treatment space. The ultrasound-based registrations of the CT datasets were compared to the gold-standard landmark-based registrations. Results: The results show on an average sub-millimeter (0.9 ± 0.2 mm) displacement and subdegree (0.8° ± 0.4°) rotation registration errors. Numerical simulations predict that registration errors on this scale will result in a mean targeting error of 1.0 ± 0.2 mm and reduction in focal pressure of 1.0% ± 0.6% when targeting a midbrain structure (e.g., hippocampus) using a commercially available low-frequency brain prototype device (InSightec, 230 kHz brain system). Conclusions: If combined with ultrasound-based treatment monitoring techniques, this registration method could allow for the development of a low-cost transcranial FUS treatment platform to make this technology more widely available.

Registration of human skull computed tomography data to an ultrasound treatment space using a sparse high frequency ultrasound hemispherical array.

Science.gov (United States)

O'Reilly, Meaghan A; Jones, Ryan M; Birman, Gabriel; Hynynen, Kullervo

2016-09-01

Transcranial focused ultrasound (FUS) shows great promise for a range of therapeutic applications in the brain. Current clinical investigations rely on the use of magnetic resonance imaging (MRI) to monitor treatments and for the registration of preoperative computed tomography (CT)-data to the MR images at the time of treatment to correct the sound aberrations caused by the skull. For some applications, MRI is not an appropriate choice for therapy monitoring and its cost may limit the accessibility of these treatments. An alternative approach, using high frequency ultrasound measurements to localize the skull surface and register CT data to the ultrasound treatment space, for the purposes of skull-related phase aberration correction and treatment targeting, has been developed. A prototype high frequency, hemispherical sparse array was fabricated. Pulse-echo measurements of the surface of five ex vivo human skulls were made, and the CT datasets of each skull were obtained. The acoustic data were used to rigidly register the CT-derived skull surface to the treatment space. The ultrasound-based registrations of the CT datasets were compared to the gold-standard landmark-based registrations. The results show on an average sub-millimeter (0.9 ± 0.2 mm) displacement and subdegree (0.8° ± 0.4°) rotation registration errors. Numerical simulations predict that registration errors on this scale will result in a mean targeting error of 1.0 ± 0.2 mm and reduction in focal pressure of 1.0% ± 0.6% when targeting a midbrain structure (e.g., hippocampus) using a commercially available low-frequency brain prototype device (InSightec, 230 kHz brain system). If combined with ultrasound-based treatment monitoring techniques, this registration method could allow for the development of a low-cost transcranial FUS treatment platform to make this technology more widely available.

A Numerical Investigation of the Time Reversal Mirror Technique for Trans-skull Brain Cancer Ultrasound Surgery

Directory of Open Access Journals (Sweden)

H. Zahedmanesh

2007-06-01

Full Text Available Introduction: The medical applications of ultrasound on human brain are highly limited by the phase and amplitude aberrations induced by the heterogeneities of the skull. However, it has been shown that time reversing coupled with amplitude compensation can overcome these aberrations. In this work, a model for 2D simulation of the time reversal mirror technique is proposed to study the possibility of targeting any point within the brain without the need for craniotomy and to calculate the acoustic pressure field and the resulting temperature distribution within the skull and brain during a High Intensity Focused Ultrasound (HIFU transcranial therapy. Materials and Methods: To overcome the sensitivity of the wave pattern to the heterogeneous geometry of the skull, a real MRI derived 2D model is constructed. The model should include the real geometry of brain and skull. The model should also include the couplant medium which has the responsibility of coupling the transducer to the skull for the penetration of ultrasound. The clinical substance used as the couplant is water. The acoustic and thermal parameters are derived from the references. Next, the wave propagation through the skull is computed based on the Helmholtz equation, with a 2D finite element analysis. The acoustic simulation is combined with a 2D thermal diffusion analysis based on Pennes Bioheat equation and the temperature elevation inside the skull and brain is computed. The numerical simulations were performed using the FEMLAB 3.2 software on a PC having 8 GB RAM and a 2.4 MHz dual CPU. Results: It is seen that the ultrasonic waves are exactly focalized at the location where the hydrophone has been previously implanted. There is no penetration into the sinuses and the waves are reflected from their surface because of the high discrepancy between the speed of sound in bone and air.  Under the focal pressure of 2.5 MPa and after 4 seconds of sonication the temperature at the focus

Intensity-Modulated Radiation Therapy for Primary Brain Tumors

Institute of Scientific and Technical Information of China (English)

Zhong-min Wang

2004-01-01

Radiation therapy has been used to treat primary brain tumors as standard primary and/or adjunctive therapies for decades. It is difficult for conventional radiotherapy to deliver a lethal dose of radiation to the tumors while sparing surrounding normal brain due to complicated structures and multifunction in human brain. With the understanding of radiation physics and computer technology, a number of novel and more precise radiotherapies have been developed in recent years. Intensity modulated radiotherapy (IMRT) is one of these strategies. The use of IMRT in the treatment of primary brain tumors is being increasing nowadays. It shows great promise for some of primary brain tumors and also presents some problems, This review highlights current IMRT in the treatment of mainly primary brain tumors.

General Ultrasound Imaging

Medline Plus

Full Text Available ... flat sections of the body. Advancements in ultrasound technology include three-dimensional (3-D) ultrasound that formats ... legs, neck and/or brain (in infants and children) or within various body organs such as the ...

Magnetic resonance guided focalized ultrasound thermo-ablation: A promising oncologic local therapy

International Nuclear Information System (INIS)

Iannessi, A.; Doyen, J.; Leysalle, A.; Thyss, A.

2014-01-01

Pain management of bone metastases is usually made using systemic and local therapy. Even though radiations are nowadays the gold standard for painful metastases, innovations regarding minimally invasive treatment approaches have been developed because of the existing non-responder patients [1]. Indeed, cementoplasty and thermo-ablations like radiofrequency or cryotherapy have shown to be efficient on pain [2-4]. Among thermo-therapy, magnetic resonance guided focalized ultrasound is now a new non-invasive weapon for bone pain palliation. (authors)

WE-B-210-02: The Advent of Ultrafast Imaging in Biomedical Ultrasound

International Nuclear Information System (INIS)

Tanter, M.

2015-01-01

In the last fifteen years, the introduction of plane or diverging wave transmissions rather than line by line scanning focused beams has broken the conventional barriers of ultrasound imaging. By using such large field of view transmissions, the frame rate reaches the theoretical limit of physics dictated by the ultrasound speed and an ultrasonic map can be provided typically in tens of micro-seconds (several thousands of frames per second). Interestingly, this leap in frame rate is not only a technological breakthrough but it permits the advent of completely new ultrasound imaging modes, including shear wave elastography, electromechanical wave imaging, ultrafast doppler, ultrafast contrast imaging, and even functional ultrasound imaging of brain activity (fUltrasound) introducing Ultrasound as an emerging full-fledged neuroimaging modality. At ultrafast frame rates, it becomes possible to track in real time the transient vibrations – known as shear waves – propagating through organs. Such “human body seismology” provides quantitative maps of local tissue stiffness whose added value for diagnosis has been recently demonstrated in many fields of radiology (breast, prostate and liver cancer, cardiovascular imaging, …). Today, Supersonic Imagine company is commercializing the first clinical ultrafast ultrasound scanner, Aixplorer with real time Shear Wave Elastography. This is the first example of an ultrafast Ultrasound approach surpassing the research phase and now widely spread in the clinical medical ultrasound community with an installed base of more than 1000 Aixplorer systems in 54 countries worldwide. For blood flow imaging, ultrafast Doppler permits high-precision characterization of complex vascular and cardiac flows. It also gives ultrasound the ability to detect very subtle blood flow in very small vessels. In the brain, such ultrasensitive Doppler paves the way for fUltrasound (functional ultrasound imaging) of brain activity with unprecedented

WE-B-210-02: The Advent of Ultrafast Imaging in Biomedical Ultrasound

Energy Technology Data Exchange (ETDEWEB)

Tanter, M. [Laboratoire Ondes et Acoustique (France)

2015-06-15

In the last fifteen years, the introduction of plane or diverging wave transmissions rather than line by line scanning focused beams has broken the conventional barriers of ultrasound imaging. By using such large field of view transmissions, the frame rate reaches the theoretical limit of physics dictated by the ultrasound speed and an ultrasonic map can be provided typically in tens of micro-seconds (several thousands of frames per second). Interestingly, this leap in frame rate is not only a technological breakthrough but it permits the advent of completely new ultrasound imaging modes, including shear wave elastography, electromechanical wave imaging, ultrafast doppler, ultrafast contrast imaging, and even functional ultrasound imaging of brain activity (fUltrasound) introducing Ultrasound as an emerging full-fledged neuroimaging modality. At ultrafast frame rates, it becomes possible to track in real time the transient vibrations – known as shear waves – propagating through organs. Such “human body seismology” provides quantitative maps of local tissue stiffness whose added value for diagnosis has been recently demonstrated in many fields of radiology (breast, prostate and liver cancer, cardiovascular imaging, …). Today, Supersonic Imagine company is commercializing the first clinical ultrafast ultrasound scanner, Aixplorer with real time Shear Wave Elastography. This is the first example of an ultrafast Ultrasound approach surpassing the research phase and now widely spread in the clinical medical ultrasound community with an installed base of more than 1000 Aixplorer systems in 54 countries worldwide. For blood flow imaging, ultrafast Doppler permits high-precision characterization of complex vascular and cardiac flows. It also gives ultrasound the ability to detect very subtle blood flow in very small vessels. In the brain, such ultrasensitive Doppler paves the way for fUltrasound (functional ultrasound imaging) of brain activity with unprecedented

Preoperative magnetic resonance and intraoperative ultrasound fusion imaging for real-time neuronavigation in brain tumor surgery.

Science.gov (United States)

Prada, F; Del Bene, M; Mattei, L; Lodigiani, L; DeBeni, S; Kolev, V; Vetrano, I; Solbiati, L; Sakas, G; DiMeco, F

2015-04-01

Brain shift and tissue deformation during surgery for intracranial lesions are the main actual limitations of neuro-navigation (NN), which currently relies mainly on preoperative imaging. Ultrasound (US), being a real-time imaging modality, is becoming progressively more widespread during neurosurgical procedures, but most neurosurgeons, trained on axial computed tomography (CT) and magnetic resonance imaging (MRI) slices, lack specific US training and have difficulties recognizing anatomic structures with the same confidence as in preoperative imaging. Therefore real-time intraoperative fusion imaging (FI) between preoperative imaging and intraoperative ultrasound (ioUS) for virtual navigation (VN) is highly desirable. We describe our procedure for real-time navigation during surgery for different cerebral lesions. We performed fusion imaging with virtual navigation for patients undergoing surgery for brain lesion removal using an ultrasound-based real-time neuro-navigation system that fuses intraoperative cerebral ultrasound with preoperative MRI and simultaneously displays an MRI slice coplanar to an ioUS image. 58 patients underwent surgery at our institution for intracranial lesion removal with image guidance using a US system equipped with fusion imaging for neuro-navigation. In all cases the initial (external) registration error obtained by the corresponding anatomical landmark procedure was below 2 mm and the craniotomy was correctly placed. The transdural window gave satisfactory US image quality and the lesion was always detectable and measurable on both axes. Brain shift/deformation correction has been successfully employed in 42 cases to restore the co-registration during surgery. The accuracy of ioUS/MRI fusion/overlapping was confirmed intraoperatively under direct visualization of anatomic landmarks and the error was surgery and is less expensive and time-consuming than other intraoperative imaging techniques, offering high precision and

Optical Methods and Instrumentation in Brain Imaging and Therapy

CERN Document Server

2013-01-01

This book provides a comprehensive up-to-date review of optical approaches used in brain imaging and therapy. It covers a variety of imaging techniques including diffuse optical imaging, laser speckle imaging, photoacoustic imaging and optical coherence tomography. A number of laser-based therapeutic approaches are reviewed, including photodynamic therapy, fluorescence guided resection and photothermal therapy. Fundamental principles and instrumentation are discussed for each imaging and therapeutic technique. Represents the first publication dedicated solely to optical diagnostics and therapeutics in the brain Provides a comprehensive review of the principles of each imaging/therapeutic modality Reviews the latest advances in instrumentation for optical diagnostics in the brain Discusses new optical-based therapeutic approaches for brain diseases

Radiation therapy of brain metastases

Energy Technology Data Exchange (ETDEWEB)

Sauer, R; Huenig, R [Kantonsspital Basel (Switzerland). Universitaetsinstitut fuer Medizinische Radiologie

1975-08-01

Experiences are reported obtained with radiation therapy of brain metastases in 121 patients during the last 15 years. The treatment to a lesser extent aimed at prolongation of survival but much more at the attempt to alleviate troubles and to spare pain. The indication thus involved medical points of view as well as ethical ones. The radiotherapy of cerebral metastases comprises the whole cranial volume and requires a focal dose of minimally 4,000 R within four weeks. In 53% of the patients, the regression of neurological symptoms was considerable, in 18% even complete, partly beginning already after a few days of treatment. The number of recurrences was small. Under conditions of rigorous indication, the radiation therapy of brain metastases offers a rewarding palliative measure.

Ultrasound imaging-guided intracardiac injection to develop a mouse model of breast cancer brain metastases followed by longitudinal MRI.

Science.gov (United States)

Zhou, Heling; Zhao, Dawen

2014-03-06

Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 months. It is critical to have suitable animal models to mimic the hemodynamic spread of the metastatic cells in the clinical scenario. Here, we are introducing the use of small animal ultrasound imaging to guide an accurate injection of brain tropical breast cancer cells into the left ventricle of athymic nude mice. Longitudinal MRI is used to assessing intracranial initiation and growth of brain metastases. Ultrasound-guided intracardiac injection ensures not only an accurate injection and hereby a higher successful rate but also significantly decreased mortality rate, as compared to our previous manual procedure. In vivo high resolution MRI allows the visualization of hyperintense multifocal lesions, as small as 310 µm in diameter on T2-weighted images at 3 weeks post injection. Follow-up MRI reveals intracranial tumor growth and increased number of metastases that distribute throughout the whole brain.

Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface

Directory of Open Access Journals (Sweden)

Brittany Mei Young

2014-07-01

Full Text Available This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n=8 or no therapy (n=6. Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test, and the Nine-Hole Peg Test as well as task-based fMRI scans were conducted before, during, after, and one month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy but not in the absence of therapy to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and nonlesioned hemisphere and that these brain changes are associated with changes in specific motor functions.

Ultrasound therapy applicators for controlled thermal modification of tissue

Science.gov (United States)

Burdette, E. Clif; Lichtenstiger, Carol; Rund, Laurie; Keralapura, Mallika; Gossett, Chad; Stahlhut, Randy; Neubauer, Paul; Komadina, Bruce; Williams, Emery; Alix, Chris; Jensen, Tor; Schook, Lawrence; Diederich, Chris J.

2011-03-01

Heat therapy has long been used for treatments in dermatology and sports medicine. The use of laser, RF, microwave, and more recently, ultrasound treatment, for psoriasis, collagen reformation, and skin tightening has gained considerable interest over the past several years. Numerous studies and commercial devices have demonstrated the efficacy of these methods for treatment of skin disorders. Despite these promising results, current systems remain highly dependent on operator skill, and cannot effectively treat effectively because there is little or no control of the size, shape, and depth of the target zone. These limitations make it extremely difficult to obtain consistent treatment results. The purpose of this study was to determine the feasibility for using acoustic energy for controlled dose delivery sufficient to produce collagen modification for the treatment of skin tissue in the dermal and sub-dermal layers. We designed and evaluated a curvilinear focused ultrasound device for treating skin disorders such as psoriasis, stimulation of wound healing, tightening of skin through shrinkage of existing collagen and stimulation of new collagen formation, and skin cancer. Design parameters were examined using acoustic pattern simulations and thermal modeling. Acute studies were performed in 201 freshly-excised samples of young porcine underbelly skin tissue and 56 in-vivo treatment areas in 60- 80 kg pigs. These were treated with ultrasound (9-11MHz) focused in the deep dermis. Dose distribution was analyzed and gross pathology assessed. Tissue shrinkage was measured based on fiducial markers and video image registration and analyzed using NIH Image-J software. Comparisons were made between RF and focused ultrasound for five energy ranges. In each experimental series, therapeutic dose levels (60degC) were attained at 2-5mm depth. Localized collagen changes ranged from 1-3% for RF versus 8-15% for focused ultrasound. Therapeutic ultrasound applied at high

A Split-and-Merge-Based Uterine Fibroid Ultrasound Image Segmentation Method in HIFU Therapy.

Directory of Open Access Journals (Sweden)

Menglong Xu

Full Text Available High-intensity focused ultrasound (HIFU therapy has been used to treat uterine fibroids widely and successfully. Uterine fibroid segmentation plays an important role in positioning the target region for HIFU therapy. Presently, it is completed by physicians manually, reducing the efficiency of therapy. Thus, computer-aided segmentation of uterine fibroids benefits the improvement of therapy efficiency. Recently, most computer-aided ultrasound segmentation methods have been based on the framework of contour evolution, such as snakes and level sets. These methods can achieve good performance, although they need an initial contour that influences segmentation results. It is difficult to obtain the initial contour automatically; thus, the initial contour is always obtained manually in many segmentation methods. A split-and-merge-based uterine fibroid segmentation method, which needs no initial contour to ensure less manual intervention, is proposed in this paper. The method first splits the image into many small homogeneous regions called superpixels. A new feature representation method based on texture histogram is employed to characterize each superpixel. Next, the superpixels are merged according to their similarities, which are measured by integrating their Quadratic-Chi texture histogram distances with their space adjacency. Multi-way Ncut is used as the merging criterion, and an adaptive scheme is incorporated to decrease manual intervention further. The method is implemented using Matlab on a personal computer (PC platform with Intel Pentium Dual-Core CPU E5700. The method is validated on forty-two ultrasound images acquired from HIFU therapy. The average running time is 9.54 s. Statistical results showed that SI reaches a value as high as 87.58%, and normHD is 5.18% on average. It has been demonstrated that the proposed method is appropriate for segmentation of uterine fibroids in HIFU pre-treatment imaging and planning.

Value of combined exercise and ultrasound as an adjunct to compression therapy in chronic venous leg ulcers

Directory of Open Access Journals (Sweden)

Rehab A.E Sallam

2017-01-01

Conclusion Combined prescription of exercises and ultrasound as an adjunct to compression therapy would be a more effective means of promoting chronic venous ulcer healing, when standard compression therapy have failed. It is safe, easy and well tolerated and should be considered as adjunctive therapy in patients with venous leg ulcers.

Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy.

Science.gov (United States)

Stride, E P; Coussios, C C

2010-01-01

Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art.

The science of ultrasound therapy for fracture healing

Directory of Open Access Journals (Sweden)

Della Rocca Gregory

2009-01-01

Full Text Available Fracture healing involves a complex interplay of cellular processes, culminating in bridging of a fracture gap with bone. Fracture healing can be compromised by numerous exogenous and endogenous patient factors, and intense research is currently going on to identify modalities that can increase the likelihood of successful healing. Low-intensity pulsed ultrasound (LIPUS has been proposed as a modality that may have a benefit for increasing reliable fracture healing as well as perhaps increasing the rate of fracture healing. We conducted a review to establish basic scince evidence of therapeutic role of lipus in fracture healing. An electronic search without language restrictions was accomplished of three databases (PubMed, Embase, Cinahl for ultrasound-related research in osteocyte and chondrocyte cell culture and in animal fracture models, published from inception of the databases through December, 2008. Studies deemed to be most relevant were included in this review. Multiple in vitro and animal in vivo studies were identified. An extensive body of literature exists which delineates the mechanism of action for ultrasound on cellular and tissue signaling systems that may be related to fracture healing. Research on LIPUS in animal fracture models has demonstrated promising results for acceleration of fracture healing and for promotion of fracture healing in compromised tissue beds. A large body of cellular and animal research exists which reveals that LIPUS may be beneficial for accelerating normal fracture healing or for promoting fracture healing in compromised tissue beds. Further investigation of the effects of LIPUS in human fracture healing is warranted for this promising new therapy.

Application of a drug delivery system using ultrasound and nano/microbubbles for anti-angiogenic therapy

International Nuclear Information System (INIS)

Horie, Sachiko; Kodama, Tetsuya; Sato, Yasushi

2017-01-01

The drug delivery system using ultrasound and nano/microbubbles is a molecular delivery approach using the mechanism of sonoporation. With sonoporation, an endothelium-derived negative-feedback regulator of angiogenesis, Vasohibin-1 (VASH1), was introduced specifically into tumor vessels. We found VASH1 in tumor vessels induce normalization of tumor vessels and inhibited tumor growth. A recent topic regarding tumor angiogenesis is vascular normalization. Tumor vessels are abnormal or immature that cause hyperpermeability and impaired blood flow. Tumor vascular normalization improves blood flow and tissue hypoxia, which increase the effectiveness of chemotherapy and radiotherapy and reduce tumor cell malignancy. In this review, application of drug delivery system using ultrasound for an anti-angiogenic therapy, a tumor vessel normalization therapy to treat cancer, is summarized. (author)

Ultrasound therapy for recalcitrant diabetic foot ulcers: results of a randomized, double-blind, controlled, multicenter study.

Science.gov (United States)

Ennis, William J; Foremann, Phil; Mozen, Neal; Massey, Joi; Conner-Kerr, Teresa; Meneses, Patricio

2005-08-01

An estimated 15% of patients with diabetes will develop a foot ulcer sometime in their life, making them 30 to 40 times more likely to undergo amputation due to a non-healing foot ulcer than the non-diabetic population. To determine the safety and efficacy of a new, non-contact, kilohertz ultrasound therapy for the healing of recalcitrant diabetic foot ulcers - as well as to evaluate the impact on total closure and quantitative bacterial cultures and the effect on healing of various levels of sharp/surgical debridement - a randomized, double-blinded, sham-controlled, multicenter study was conducted in hospital-based and private wound care clinics. Patients (55 met criteria for efficacy analysis) received standard of care, which included products that provide a moist environment, offloading diabetic shoes and socks, debridement, wound evaluation, and measurement. The "therapy" was either active 40 KHz ultrasound delivered by a saline mist or a "sham device" which delivered a saline mist without the use of ultrasound. After 12 weeks of care, the proportion of wounds healed (defined as complete epithelialization without drainage) in the active ultrasound therapy device group was significantly higher than that in the sham control group (40.7% versus 14.3%, P = 0.0366, Fisher's exact test). The ultrasound treatment was easy to use and no difference in the number and type of adverse events between the two treatment groups was noted. Of interest, wounds were debrided at baseline followed by a quantitative culture biopsy. The results of these cultures demonstrated a significant bioburden (greater than 10(5)) in the majority of cases, despite a lack of clinical signs of infection. Compared to control, this therapeutic modality was found to increase the healing rate of recalcitrant, diabetic foot ulcers.

Obstacles to Brain Tumor Therapy: Key ABC Transporters

Directory of Open Access Journals (Sweden)

Juwina Wijaya

2017-11-01

Full Text Available The delivery of cancer chemotherapy to treat brain tumors remains a challenge, in part, because of the inherent biological barrier, the blood–brain barrier. While its presence and role as a protector of the normal brain parenchyma has been acknowledged for decades, it is only recently that the important transporter components, expressed in the tightly knit capillary endothelial cells, have been deciphered. These transporters are ATP-binding cassette (ABC transporters and, so far, the major clinically important ones that functionally contribute to the blood–brain barrier are ABCG2 and ABCB1. A further limitation to cancer therapy of brain tumors or brain metastases is the blood–tumor barrier, where tumors erect a barrier of transporters that further impede drug entry. The expression and regulation of these two transporters at these barriers, as well as tumor derived alteration in expression and/or mutation, are likely obstacles to effective therapy.

General Ultrasound Imaging

Medline Plus

Full Text Available ... baby in pregnant women and the brain and hips in infants. It’s also used to help guide ... and parathyroid glands scrotum (testicles) brain in infants hips in infants spine in infants Ultrasound is also ...

Modeling localized delivery of Doxorubicin to the brain following focused ultrasound enhanced blood-brain barrier permeability

International Nuclear Information System (INIS)

Nhan, Tam; Burgess, Alison; Hynynen, Kullervo; Lilge, Lothar

2014-01-01

Doxorubicin (Dox) is a well-established chemotherapeutic agent, however it has limited efficacy in treating brain malignancies due to the presence of the blood-brain barrier (BBB). Recent preclinical studies have demonstrated that focused ultrasound induced BBB disruption (BBBD) enables efficient delivery of Dox to the brain. For future treatment planning of BBBD-based drug delivery, it is crucial to establish a mathematical framework to predict the effect of transient BBB permeability enhancement on the spatiotemporal distribution of Dox at the targeted area. The constructed model considers Dox concentrations within three compartments (plasma, extracellular, intracellular) that are governed by various transport processes (e.g. diffusion in interstitial space, exchange across vessel wall, clearance by cerebral spinal fluid, uptake by brain cells). By examining several clinical treatment aspects (e.g. sonication scheme, permeability enhancement, injection mode), our simulation results support the experimental findings of optimal interval delay between two consecutive sonications and therapeutically-sufficient intracellular concentration with respect to transfer constant K trans range of 0.01–0.03 min −1 . Finally, the model suggests that infusion over a short duration (20–60 min) should be employed along with single-sonication or multiple-sonication at 10 min interval to ensure maximum delivery to the intracellular compartment while attaining minimal cardiotoxicity via suppressing peak plasma concentration. (paper)

Photodynamic Therapy for Malignant Brain Tumors.

Science.gov (United States)

Akimoto, Jiro

2016-01-01

Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area.

Magnetic resonance–guided interstitial high-intensity focused ultrasound for brain tumor ablation

Science.gov (United States)

MacDonell, Jacquelyn; Patel, Niravkumar; Rubino, Sebastian; Ghoshal, Goutam; Fischer, Gregory; Burdette, E. Clif; Hwang, Roy; Pilitsis, Julie G.

2018-01-01

Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors’ interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery. PMID:29385926

Therapy of malignant brain tumors

International Nuclear Information System (INIS)

Jellinger, K.

1987-01-01

The tumors of the brain claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper dis-posability for rational management and therapeutic strategies. The primary aim of the present book is to serve these purposes. With 8 chapters, two of them are indexed for INIS, the collective of competent authors deal on the biology, pathology and immunology of malignant brain tumors of adults and of children including relevant basic and recent data of experimental research; further on the available methods of therapy: neurosurgery, radiology and chemotherapy, the fundamental principals of their efficacy and the differing models of single respective combined application, in comprehensive critical form. 111 figs

Therapy of malignant brain tumors

Energy Technology Data Exchange (ETDEWEB)

Jellinger, K [ed.

1987-01-01

The tumors of the brain claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper dis-posability for rational management and therapeutic strategies. The primary aim of the present book is to serve these purposes. With 8 chapters, two of them are indexed for INIS, the collective of competent authors deal on the biology, pathology and immunology of malignant brain tumors of adults and of children including relevant basic and recent data of experimental research; further on the available methods of therapy: neurosurgery, radiology and chemotherapy, the fundamental principals of their efficacy and the differing models of single respective combined application, in comprehensive critical form. 111 figs.

Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

Directory of Open Access Journals (Sweden)

Quan Jiang

2016-01-01

Full Text Available Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain--a primate study.

Science.gov (United States)

Hynynen, Kullervo; McDannold, Nathan; Clement, Greg; Jolesz, Ferenc A; Zadicario, Eyal; Killiany, Ron; Moore, Tara; Rosen, Douglas

2006-08-01

MRI-guided and monitored focused ultrasound thermal surgery of brain through intact skull was tested in three rhesus monkeys. The aim of this study was to determine the amount of skull heating in an animal model with a head shape similar to that of a human. The ultrasound beam was generated by a 512 channel phased array system (Exablate 3000, InSightec, Haifa, Israel) that was integrated within a 1.5-T MR-scanner. The skin was pre-cooled by degassed temperature controlled water circulating between the array surface and the skin. Skull surface temperature was measured with invasive thermocouple probes. The results showed that by applying surface cooling the skin and skull surface can be protected, and that the brain surface temperature becomes the limiting factor. The MRI thermometry was shown to be useful in detecting the tissue temperature distribution next to the bone, and it should be used to monitor the brain surface temperature. The acoustic intensity values during the 20 s sonications were adequate for thermal ablation in the human brain provided that surface cooling is used.

Noninvasive, localized, and transient brain drug delivery using focused ultrasound and microbubbles

Science.gov (United States)

Choi, James J.

In the United States, Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancer caused 72,432, 19,566 and 12,886 deaths in 2006, respectively. Whereas the number of deaths due to major disorders such as heart disease, stroke, and prostate cancer have decreased since 2006, deaths attributed to AD, PD, and brain cancer have not. Treatment options for patients with CNS disorders remain limited despite significant advances in knowledge of CNS disease pathways and development of neurologically potent agents. One of the major obstacles is that the cerebral microvasculature is lined by a specialized and highly regulated blood-brain barrier (BBB) that prevents large agents from entering the brain extracellular space. The purpose of this dissertation is to design a noninvasive, localized, and transient BBB opening system using focused ultrasound (FUS) and determine ultrasound and microbubble conditions that can effectively and safely deliver large pharmacologically-relevant-sized agents to the brain. To meet this end, an in vivo mouse brain drug delivery system using a stereotactic-based targeting method was developed. FUS was applied noninvasively through the intact skin and skull, which allowed for long-term and high-throughput studies. With this system, more than 150 mice were exposed to one of 31 distinct acoustic and microbubble conditions. The feasibility of delivering a large MRI contrast agent was first demonstrated in vivo in both wild-type and transgenic Alzheimer's disease model (APP/PS1) mice. A wide range of acoustic and microbubble conditions were then evaluated for their ability to deliver agents to a target region. Interestingly, the possible design space of parameters was found to be vast and different conditions resulted in distinct spatial distributions and doses delivered. In particular, BBB opening was shown to be dependent on the microbubble diameter, acoustic pressure, pulse repetition frequency (PRF), and pulse length (PL). Each set of

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... sexes without x-ray exposure. Risks For standard diagnostic ultrasound , there are no known harmful effects on ... and Resources RTAnswers.org Radiation Therapy for Gynecologic Cancers Radiation Therapy for Prostate Cancer top of page ...

Clinical considerations for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr.

1990-01-01

The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the US in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should not be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam cases gamma rays to be generated when it interacts with tissue, they think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue

Vectorization of ultrasound-responsive nanoparticles in placental mesenchymal stem cells for cancer therapy.

Science.gov (United States)

Paris, Juan L; de la Torre, Paz; Victoria Cabañas, M; Manzano, Miguel; Grau, Montserrat; Flores, Ana I; Vallet-Regí, María

2017-05-04

A new platform constituted by engineered responsive nanoparticles transported by human mesenchymal stem cells is here presented as a proof of concept. Ultrasound-responsive mesoporous silica nanoparticles are coated with polyethylenimine to favor their effective uptake by decidua-derived mesenchymal stem cells. The responsive-release ability of the designed nanoparticles is confirmed, both in vial and in vivo. In addition, this capability is maintained inside the cells used as carriers. The migration capacity of the nanoparticle-cell platform towards mammary tumors is assessed in vitro. The efficacy of this platform for anticancer therapy is shown against mammary tumor cells by inducing the release of doxorubicin only when the cell vehicles are exposed to ultrasound.

The impact of standing wave effects on transcranial focused ultrasound disruption of the blood-brain barrier in a rat model

International Nuclear Information System (INIS)

O'Reilly, Meaghan A; Huang Yuexi; Hynynen, Kullervo

2010-01-01

Microbubble-mediated disruption of the blood-brain barrier (BBB) for targeted drug delivery using focused ultrasound shows great potential as a therapy for a wide range of brain disorders. This technique is currently at the pre-clinical stage and important work is being conducted in animal models. Measurements of standing waves in ex vivo rat skulls were conducted using an optical hydrophone and a geometry dependence was identified. Standing waves could not be eliminated through the use of swept frequencies, which have been suggested to eliminate standing waves. Definitive standing wave patterns were detected in over 25% of animals used in a single study. Standing waves were successfully eliminated using a wideband composite sharply focused transducer and a reduced duty cycle. The modified pulse parameters were used in vivo to disrupt the BBB in a rat indicating that, unlike some other bioeffects, BBB disruption is not dependent on standing wave conditions. Due to the high variability of standing waves and the inability to correctly estimate in situ pressures given standing wave conditions, attempts to minimize standing waves should be made in all future work in this field to ensure that results are clinically translatable.

Intraoperative ultrasound in determining the extent of resection of parenchymal brain tumors - a comparative study with computed tomography and histopathology

International Nuclear Information System (INIS)

Chacko, A.G.; Rajshekhar, V.; Kumar, N.K.S.; Athyal, R.; Chacko, G.

2003-01-01

Radical excision of parenchymal brain tumours is generally associated with a better long-term outcome; however, it is difficult to ascertain the extent of resection at surgery. We used intra-operative ultrasound [IOUS] to help detect residual tumour and define the tumour-brain interface. Thirty-five patients with parenchymal brain lesions including 11 low-grade and 22 high-grade tumours and 2 inflammatory granulomata were included in the study. The IOUS was used to localize tumours not seen on the surface, define their margins and assess the extent of resection at the end of surgery. Multiple samples from the tumour-brain interface which were reported as tumour or normal tissue an IOUS were submitted to histopathology. The IOUS findings were compared with a postoperative contrast enhanced computed tomogram [CT] and with histopathology. All tumours irrespective of histology were hyperechoic an IOUS. IOUS was useful in localizing those tumours not seen on the surface of the brain. In 71.4 % of cases IOUS was useful in defining their margins, however in the remaining cases the margins were ill-defined. The tumour margins were ill-defined in those treated previously by radiation. With regard to the extent of excision, after excluding the cases who were irradiated, it was found that in the 28 patients who had parenchymal neoplasms, there was concordance between the ultrasound findings and the postoperative CT scan in 23 cases. Of the 79 samples taken from the tumor-brain interface which were reported as tumour on ultrasound, 66 had histopathological evidence of tumour while 13 samples were negative for tumour. On the other hand, in the tissue sent from 17 sites where the IOUS showed no residual tumour, 2 were positive for tumour on histopathology while 15 were negative. In conclusion, IOUS is a cheap and useful real-time tool for localizing tumours not seen on the brain surface, for defining their margins and for determining the extent of resection. (author)

Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation.

Science.gov (United States)

Nomikou, N; Feichtinger, G A; Saha, S; Nuernberger, S; Heimel, P; Redl, H; McHale, A P

2018-01-01

Gene-activated matrix (GAM)-based therapeutics for tissue regeneration are limited by efficacy, the lack of spatiotemporal control and availability of target cells, all of which impact negatively on their translation to the clinic. Here, an advanced ultrasound-responsive GAM is described containing target cells that facilitates matrix-assisted sonoporation (MAS) to induce osteogenic differentiation. Ultrasound-responsive GAMs consisting of fibrin/collagen hybrid-matrices containing microbubbles, bone morphogenetic protein BMP2/7 coexpression plasmids together with C2C12 cells were treated with ultrasound either in vitro or following parenteral intramuscular implantation in vivo. Using direct measurement for alkaline phosphatase activity, von Kossa staining and immunohistochemical analysis for osteocalcin expression, MAS-stimulated osteogenic differentiation was confirmed in the GAMs in vitro 7 days after treatment with ultrasound. At day 30 post-treatment with ultrasound, ectopic osteogenic differentiation was confirmed in vivo using X-ray microcomputed tomography and histological analysis. Osteogenic differentiation was indicated by the presence of ectopic bone structures in all animals treated with MAS. In addition, bone volumes in this group were statistically greater than those in the control groups. This novel approach of incorporating a MAS capability into GAMs could be exploited to facilitate ex vivo gene transfer with subsequent surgical implantation or alternatively provide a minimally invasive means of stimulating in situ transgene delivery for osteoinductive gene-based therapies. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... in the abdomen, arms, legs, neck and/or brain (in infants and children) or within various body organs ... or uterine cancers A transvaginal ultrasound is usually performed to view ...

[Timing of Brain Radiation Therapy Impacts Outcomes in Patients with 
Non-small Cell Lung Cancer Who Develop Brain Metastases].

Science.gov (United States)

Wang, Yang; Fang, Jian; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Ma, Xiangjuan; Han, Jindi; Chen, Xiaoling; Tian, Guangming; Wu, Di; Han, Sen; Long, Jieran

2016-08-20

Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; Pbrain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; Pbrain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

Science.gov (United States)

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Progetto EURAMET: HLT03 DUTy - Dosimetria per terapie ultrasonore. Confronto tra metodi di misura - EURAMET: HLT03 DUTy - Dosimetry for ultrasound therapy. Intercomparison of methods

Directory of Open Access Journals (Sweden)

Giovanni Durando

2016-03-01

Full Text Available La mancanza di una definizione della dose ultrasonora rende di fatto impossibile la valutazione della più appropriata “quantità” energia ceduta ai tessuti dal fascio ultrasonoro emesso da un trasduttore durante una terapia. Il progetto di ricerca “Dosimetry for Ultrasound Therapy - DUTy”, finanziato dal programma di ricerca EURAMET EMRP, aveva tra i suoi principali obiettivi, oltre al confronto interlaboratorio che validasse le capacità metrologiche dei laboratori partecipanti, la ricerca della definizione di dose ultrasonora che consentisse la definizione di un piano terapeutico specifico per ogni paziente. ------ Standardized and traceable dose has not yet been developed for medical ultrasound applications. This means that the ‘amount’ of ultrasound required for a particular therapy cannot be calculated and that the ‘amount’ actually delivered quantified. The aim of EURAMET EMRP project “Dosimetry for Ultrasound Therapy - DUTy” project was developing the metrological infrastructure (definitions, validated measurement and modelling methods which underpins the specification of dose for therapeutic ultrasound applications allowing appropriate treatment planning and risk assessment.

Contrast ultrasound-guided photothermal therapy using gold nanoshelled microcapsules in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Wang, Shumin [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Ordos Center Hospital, Ordos, Inner Mongolia 017000 (China); Dai, Zhifei [Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871 (China); Ke, Hengte [Nanomedicine and Biosensor Laboratory, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001 (China); Qu, Enze [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Qi, Xiaoxu; Zhang, Kuo [Department of Laboratory Animal Science, Peking University Health Science Center, Beijing 100019 (China); Wang, Jinrui, E-mail: jinrui_wang@sina.com [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China)

2014-01-15

Objectives: The purpose of this study was to test whether dual functional gold nano-shelled microcapsules (GNS-MCs) can be used as an ultrasound imaging enhancer and as an optical absorber for photothermal therapy (PTT) in a rodent model of breast cancer. Methods: GNS-MCs were fabricated with an inner air and outer gold nanoshell spherical structure. Photothermal cytotoxicity of GNS-MCs was tested with BT474 cancer cells in vitro and non-obese diabetes-SCID (NOD/SCID) mice with breast cancer. GNS-MCs were injected into the tumor under ultrasound guidance and treated with near-infrared (NIR) laser irradiation. The photothermal ablative effectiveness of GNS-MCs was evaluated by measuring the surface and internal temperature of the tumor as well as the size of the tumor using histological confirmation. Results: NIR laser irradiation resulted in significant tumor cell death in GNS-MCs-treated BT474 cells in vitro. GNS-MCs were able to serve as an ultrasound enhancer to guide the intratumoral injection of GNS-MCs and ensure their uniform distribution. In vivo studies revealed that NIR laser irradiation increased the intratumoral temperature to nearly 70 °C for 8 min in GNS-MCs-treated mice. Tumor volumes decreased gradually and tumors were completely ablated in 6 out of 7 mice treated with GNS-MCs and laser irradiation by 17 days after treatment. Conclusion: This study demonstrates that ultrasound-guided PTT with theranostic GNS-MCs is a promising technique for in situ treatment of breast cancer.

A CT-ultrasound-coregistered augmented reality enhanced image-guided surgery system and its preliminary study on brain-shift estimation

International Nuclear Information System (INIS)

Huang, C H; Hsieh, C H; Lee, J D; Huang, W C; Lee, S T; Wu, C T; Sun, Y N; Wu, Y T

2012-01-01

With the combined view on the physical space and the medical imaging data, augmented reality (AR) visualization can provide perceptive advantages during image-guided surgery (IGS). However, the imaging data are usually captured before surgery and might be different from the up-to-date one due to natural shift of soft tissues. This study presents an AR-enhanced IGS system which is capable to correct the movement of soft tissues from the pre-operative CT images by using intra-operative ultrasound images. First, with reconstructing 2-D free-hand ultrasound images to 3-D volume data, the system applies a Mutual-Information based registration algorithm to estimate the deformation between pre-operative and intra-operative ultrasound images. The estimated deformation transform describes the movement of soft tissues and is then applied to the pre-operative CT images which provide high-resolution anatomical information. As a result, the system thus displays the fusion of the corrected CT images or the real-time 2-D ultrasound images with the patient in the physical space through a head mounted display device, providing an immersive augmented-reality environment. For the performance validation of the proposed system, a brain phantom was utilized to simulate brain-shift scenario. Experimental results reveal that when the shift of an artificial tumor is from 5mm ∼ 12mm, the correction rates can be improved from 32% ∼ 45% to 87% ∼ 95% by using the proposed system.

Interference-free ultrasound imaging during HIFU therapy, using software tools

Science.gov (United States)

Vaezy, Shahram (Inventor); Held, Robert (Inventor); Sikdar, Siddhartha (Inventor); Managuli, Ravi (Inventor); Zderic, Vesna (Inventor)

2010-01-01

Disclosed herein is a method for obtaining a composite interference-free ultrasound image when non-imaging ultrasound waves would otherwise interfere with ultrasound imaging. A conventional ultrasound imaging system is used to collect frames of ultrasound image data in the presence of non-imaging ultrasound waves, such as high-intensity focused ultrasound (HIFU). The frames are directed to a processor that analyzes the frames to identify portions of the frame that are interference-free. Interference-free portions of a plurality of different ultrasound image frames are combined to generate a single composite interference-free ultrasound image that is displayed to a user. In this approach, a frequency of the non-imaging ultrasound waves is offset relative to a frequency of the ultrasound imaging waves, such that the interference introduced by the non-imaging ultrasound waves appears in a different portion of the frames.

Insufficient scientific evidence for efficacy of widely used electrotherapy, laser therapy, and ultrasound treatment in physiotherapy

NARCIS (Netherlands)

Bouter, L M

2000-01-01

The Dutch Health Council recently published a report on the efficacy of electrotherapy, laser therapy and ultrasound treatment for musculoskeletal disorders. The assessment was based on three systematic reviews, including 169 randomized clinical trials, and focused on a best-evidence synthesis.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... and Resources RTAnswers.org Radiation Therapy for Gynecologic Cancers Radiation Therapy for Prostate Cancer top of page This page was reviewed on ... with caption Pediatric Content Some imaging tests and treatments have special pediatric considerations. ... Images related to Ultrasound - Pelvis Sponsored by Please ...

Hyperbaric oxygen therapy in spontaneous brain abscess patients

DEFF Research Database (Denmark)

Bartek, Jiri; Jakola, Asgeir S; Skyrman, Simon

2016-01-01

BACKGROUND: There is a need to improve outcome in patients with brain abscesses and hyperbaric oxygen therapy (HBOT) is a promising treatment modality. The objective of this study was to evaluate HBOT in the treatment of intracranial abscesses. METHOD: This population-based, comparative cohort...... study included 40 consecutive adult patients with spontaneous brain abscess treated surgically between January 2003 and May 2014 at our institution. Twenty patients received standard therapy with surgery and antibiotics (non-HBOT group), while the remaining 20 patients also received adjuvant HBOT (HBOT...... group). RESULTS: Resolution of brain abscesses and infection was seen in all patients. Two patients had reoperations after HBOT initiation (10 %), while nine patients (45 %) in the non-HBOT group underwent reoperations (p = 0.03). Of the 26 patients who did not receive HBOT after the first surgery, 15...

Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

Science.gov (United States)

Aryal, Muna; Arvanitis, Costas D.; Alexander, Phillip M.; McDannold, Nathan

2014-01-01

The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB. PMID:24462453

High Intensity Focused Ultrasound for Cancer Therapy--harnessing its non-linearity

International Nuclear Information System (INIS)

Haar, Gail ter

2008-01-01

In medicine in general, and for cancer treatments in particular, there is a drive to find effective non-invasive therapies. High Intensity Focused Ultrasound (HIFU) represents one such technique. In principle, it is simple--a high energy ultrasound beam is brought to a tight focus within a target which may lie several centimetres below the skin surface (for example, in a tumour of the liver), and is used to destroy a selected tissue volume. The main mechanism for cell killing in a HIFU beam is heat. Ultrasound energy absorption is frequency dependent, the higher frequencies being absorbed most strongly. Significant thermal advantage may therefore be gained from non-linear propagation, which generates higher harmonics, in tissue. Acoustic cavitation and thermal exsolution of gas (boiling) also contribute to tissue damage. This activity leads to the local mechanical disruption of cells. In addition, the non-linear oscillation of these bubbles leads to enhanced energy deposition. The acoustic emissions from such bubbles are characteristic of their behaviour and may be correlated to some extent with the appearance of the disruption produced. The more widespread clinical acceptance of HIFU is awaiting faster, and more efficient, energy delivery and treatment monitoring. A better understanding of the nonlinear aspects of HIFU propagation in tissue is thus important if this technique is to benefit more patients

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.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... arteries and veins in the abdomen, arms, legs, neck and/or brain (in infants and children) or ... diagnose symptoms experienced by women such as: pelvic pain abnormal vaginal bleeding other menstrual problems Ultrasound exams ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... abdomen, arms, legs, neck and/or brain (in infants and children) or within various body organs such ... and monitoring of pregnant women and their unborn babies. Ultrasound provides real-time imaging, making it a ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... legs, neck and/or brain (in infants and children) or within various body organs such as the ... tumors other disorders of the urinary bladder In children, pelvic ultrasound can help evaluate: pelvic masses pelvic ...

Quantitative Ultrasound Measurements at the Heel

DEFF Research Database (Denmark)

Daugschies, M.; Brixen, K.; Hermann, P.

2015-01-01

Calcaneal quantitative ultrasound can be used to predict osteoporotic fracture risk, but its ability to monitor therapy is unclear possibly because of its limited precision. We developed a quantitative ultrasound device (foot ultrasound scanner) that measures the speed of sound at the heel...... with the foot ultrasound scanner reduced precision errors by half (p quantitative ultrasound measurements is feasible. (E-mail: m.daugschies@rad.uni-kiel.de) (C) 2015 World Federation for Ultrasound in Medicine & Biology....

Radiosurgery for brain metastases: is whole brain radiation therapy necessary?

International Nuclear Information System (INIS)

Forstner, Julie M.; Sneed, Penny K.; Lamborn, Kathleen R.; Shu, H.-K.G.; McDermott, Michael W.; Park, Elaine; Ho, Maria; Chang, Susan; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

1996-01-01

Purpose: Because whole brain radiotherapy (WBRT) carries a significant risk of dementia in long-term survivors, it is desirable to determine if some patients with brain metastases may be managed with radiosurgery (RS) alone, reserving WBRT for salvage therapy as needed. To begin to approach this problem, we retrospectively reviewed freedom from brain failure/progression (Brain FFP) and survival of patients with newly-diagnosed solitary or multiple brain metastases treated with Gamma Knife RS ± WBRT. Materials and Methods: All patients treated at our institution with Gamma Knife RS for newly-diagnosed solitary or multiple (2-8) brain metastases from September 1991 through December 1995 were reviewed. Whether or not WBRT was given depended on physician preference and referral patterns. Brain FFP was measured from the date of RS until development of a new brain metastasis or progression of a treated metastasis, with censoring at the time of the last imaging study. Survival was measured from the date of RS until death or last clinical follow-up. Actuarial curves were estimated using the Kaplan-Meier method and compared with the log rank test. Multivariate analyses to adjust for known prognostic variables (age, KPS, history of extracranial metastases, and total target volume) were performed using the Cox proportional hazards model. Results: From September 1991-December 1995, 90 patients with newly-diagnosed brain metastases underwent RS. Three patients treated palliatively to a small component of their intracranial disease were excluded, leaving 54 treated with RS alone and 33 treated with RS + WBRT. Age ranged from 31-83 years (median, 59 years), KPS from 60-100 (median, 90), and total target volume from 0.15-26.1 cm 3 (median, 5.5 cm 3 ). Fifty patients had a history of extracranial metastases. Results are shown below. In the RS alone group, (22(54)) patients (41%) had a brain failure and (20(54)) (37%) died without evidence of brain failure. In the RS + WBRT group

Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

Energy Technology Data Exchange (ETDEWEB)

Tamai, I.; Takei, T. (National Sagamihara Hospital, Kanagawa (Japan)); Oota, H.; Maekawa, K.

1981-07-01

Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in infants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therapy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by high doses of ACTH and in cases where brain atrophy had already been observed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time.

In vitro characterization of perfluorocarbon droplets for focused ultrasound therapy

Energy Technology Data Exchange (ETDEWEB)

Schad, Kelly C; Hynynen, Kullervo, E-mail: khynynen@sri.utoronto.c [Imaging Research, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto (Canada)

2010-09-07

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment is difficult as bioeffects can occur outside of the target region. Spatial control of bubbles can be achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to gas bubbles. This study was undertaken to determine the acoustic parameters for bubble production by droplet conversion and how it depends on the acoustic conditions and droplet physical parameters. Lipid-encapsulated droplets containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to 7.2 {mu}m in diameter and diluted to a concentration of 8 x 10{sup 6} droplets mL{sup -1}. The droplets were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure under flow conditions through an acoustically transparent vessel. The sonications were 10 ms in duration at frequencies of 0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was measured with an active transducer operating in pulse-echo mode and simultaneous measurements of broadband acoustic emissions were performed with passive acoustic detection. The results show that droplets cannot be converted at low frequency without broadband emissions occurring. However, the pressure threshold for droplet conversion decreased with increasing frequency, exposure and droplet size. The pressure threshold for broadband emissions was independent of the droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz, respectively. In summary, we have demonstrated that droplet conversion is feasible for clinically relevant sized droplets and acoustic exposures.

In vitro characterization of perfluorocarbon droplets for focused ultrasound therapy

International Nuclear Information System (INIS)

Schad, Kelly C; Hynynen, Kullervo

2010-01-01

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment is difficult as bioeffects can occur outside of the target region. Spatial control of bubbles can be achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to gas bubbles. This study was undertaken to determine the acoustic parameters for bubble production by droplet conversion and how it depends on the acoustic conditions and droplet physical parameters. Lipid-encapsulated droplets containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to 7.2 μm in diameter and diluted to a concentration of 8 x 10 6 droplets mL -1 . The droplets were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure under flow conditions through an acoustically transparent vessel. The sonications were 10 ms in duration at frequencies of 0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was measured with an active transducer operating in pulse-echo mode and simultaneous measurements of broadband acoustic emissions were performed with passive acoustic detection. The results show that droplets cannot be converted at low frequency without broadband emissions occurring. However, the pressure threshold for droplet conversion decreased with increasing frequency, exposure and droplet size. The pressure threshold for broadband emissions was independent of the droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz, respectively. In summary, we have demonstrated that droplet conversion is feasible for clinically relevant sized droplets and acoustic exposures.

In vitro characterization of perfluorocarbon droplets for focused ultrasound therapy

Science.gov (United States)

Schad, Kelly C.; Hynynen, Kullervo

2010-09-01

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment is difficult as bioeffects can occur outside of the target region. Spatial control of bubbles can be achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to gas bubbles. This study was undertaken to determine the acoustic parameters for bubble production by droplet conversion and how it depends on the acoustic conditions and droplet physical parameters. Lipid-encapsulated droplets containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to 7.2 µm in diameter and diluted to a concentration of 8 × 106 droplets mL-1. The droplets were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure under flow conditions through an acoustically transparent vessel. The sonications were 10 ms in duration at frequencies of 0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was measured with an active transducer operating in pulse-echo mode and simultaneous measurements of broadband acoustic emissions were performed with passive acoustic detection. The results show that droplets cannot be converted at low frequency without broadband emissions occurring. However, the pressure threshold for droplet conversion decreased with increasing frequency, exposure and droplet size. The pressure threshold for broadband emissions was independent of the droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz, respectively. In summary, we have demonstrated that droplet conversion is feasible for clinically relevant sized droplets and acoustic exposures.

Technological progress in radiation therapy for brain tumors

LENUS (Irish Health Repository)

Vernimmen, Frederik Jozef

2014-01-01

To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological ad- vancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better un- derstanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Li-near Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

MR-Guided Pulsed High-Intensity Focused Ultrasound Enhancement of Gene Therapy Combined With Androgen Deprivation and Radiotherapy for Prostate Cancer Treatment

Science.gov (United States)

2009-09-01

ultrasound . J. Acoust. Soc.Am. 72 1926-1932, (1982) (7) Neppiras E A. Acoustic cavitation . Physics reports 61(3): 159-251, (1980) (8) ter Haar G R, Daniels...Guided Pulsed High-Intensity Focused Ultrasound Enhancement of 5b. GRANT NUMBER W81XWH-08-1-0469 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...failing to This work is aimed to study MR guided high intensity focused ultrasound (MRgHIFU) enhancement of gene therapy for Prostate Cancer. The

BBB disruption with unfocused ultrasound alone-A paradigm shift

Science.gov (United States)

Kyle, Al

2012-10-01

One paradigm for ultrasound-enabled blood brain barrier disruption uses image guided focused ultrasound and preformed microbubble agents to enable drug delivery to the brain. We propose an alternative approach: unguided, unfocused ultrasound with no adjunctive agent. Compared with the focused approach, the proposed method affects a larger region of the brain, and is aimed at treatment of regional neurological disease including glioblastoma multiforme (GBM). Avoidance of image guidance and focusing reduces cost for equipment and staff training. Avoidance of adjunctive agents also lowers cost and is enabled by a longer exposure time. Since 2004, our group has worked with two animal models, three investigators in four laboratories to safely deliver five compounds, increasing the concentration of large molecule markers in brain tissue two fold or more. Safety and effectiveness data for four studies have been presented at the Ultrasound Industry Association meetings in 2007 and 2010. This paper describes new safety and effectiveness results for a fifth study. We present evidence of delivery of large molecules - including Avastin-to the brains of a large animal model correlated with acoustic pressure, and summarize the advantages and disadvantages of this novel approach.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

Energy Technology Data Exchange (ETDEWEB)

Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

2016-04-01

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

International Nuclear Information System (INIS)

Lee, Katrina; Lenards, Nishele; Holson, Janice

2016-01-01

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

Science.gov (United States)

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

2016-01-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

Brain Injury After Proton Therapy or Carbon Ion Therapy for Head-and-Neck Cancer and Skull Base Tumors

International Nuclear Information System (INIS)

Miyawaki, Daisuke; Murakami, Masao; Demizu, Yusuke; Sasaki, Ryohei; Niwa, Yasue; Terashima, Kazuki; Nishimura, Hideki; Hishikawa, Yoshio; Sugimura, Kazuro

2009-01-01

Purpose: To assess the incidence of early delayed or late morbidity of Brain after particle therapy for skull base tumors and head-and-neck cancers. Methods and Materials: Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volume of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months. Results: Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between Brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses. Conclusion: Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between Brain lobes with and without RIBCs.

Effect of Electroconvulsive Therapy on Cognitive Functions of Rats with Depression-Like Disorders Induced by Ultrasound Exposure.

Science.gov (United States)

Ushakova, V M; Zubkov, E A; Morozova, A Y; Gorlova, A V; Pavlov, D A; Inozemtsev, A N; Chekhonin, V P

2017-09-01

We studied the effect of electroconvulsive therapy on cognitive functions in rats with depression-like disorder caused by exposure to ultrasound of varying frequency (20-45 kHz). Object recognition and Morris water-maze tests revealed no negative effects of the therapy on memory. Moreover, positive effect of therapy was demonstrated that manifested in amelioration of memory disturbances in depression-like disorders in these behavioral tests. The results of this study do not support the idea about side effects of electroconvulsive therapy, in particular, development of transient amnesia, and are a prerequisite for a more thorough study of internal mechanisms of the effect of the therapy on cognitive sphere.

Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

International Nuclear Information System (INIS)

Adam, Jean-Francois

2005-01-01

High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size 2 ) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal energy, for a

Subacute posteromedial impingement of the ankle in athletes: MR imaging evaluation and ultrasound guided therapy

International Nuclear Information System (INIS)

Messiou, Christina; Robinson, Philip; O'Connor, Philip J.; Grainger, Andrew

2006-01-01

To describe the use of MR imaging and efficacy of ultrasound-guided steroid injection in the diagnosis and management of athletes with clinical posteromedial impingement of the ankle. A retrospective analysis of imaging findings on MR was undertaken in nine elite athletes with clinical posteromedial ankle impingement. MR studies from six professional athletes with posterolateral pain were also reviewed as an imaging control group. The two reviewing radiologists were blinded to the clinical details and the proportion of control and study subjects. The nine study athletes also underwent diagnostic ultrasound and ultrasound-guided injection of steroid and anaesthetic into the posteromedial capsular abnormality. Follow-up was by telephone interview. Posteromedial capsular thickening was seen only in athletes with posteromedial impingement (7/9). Posteromedial synovitis was present in all athletes with posteromedial impingement; however, posterior and posterolateral synovitis was also seen in these athletes. Mild posteromedial synovitis was present in two control athletes. Ultrasound identified abnormal posteromedial soft tissue thickening deep to tibialis posterior between the medial malleolus and talus in all nine athletes. After injection all athletes returned to their previous level of sport, with eight of the nine not experiencing any residual or recurrent symptoms. If MR imaging excludes significant coexistent abnormality, ultrasound can localise posteromedial soft tissue abnormality and guide injection therapy, allowing return to athletic activity without surgical intervention. (orig.)

Feasibility study of a single-element transcranial focused ultrasound system for blood-brain barrier opening

Science.gov (United States)

Marquet, Fabrice; Tung, Yao-Sheng; Teichert, Tobias; Ferrera, Vincent P.; Konofagou, Elisa E.

2012-10-01

The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent CNS disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. The study addresses the focusing properties of single-element transducers at intermediate frequencies (500 kHz) through primate and human skulls, targeting clinically relevant targets extracted from 3D brain atlases such as the hippocampus and the basal ganglia, which are typically affected by early Alzheimer's and Parkinson's disease, respectively. A preliminary in vivo study was performed to study the frequency dependence of BBB opening parameters in mice. Then, feasibility of transcranial ME-FUS BBB opening in non-human primates was demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (custom made 4-5 μm and Definity®). 3T MRI was used to confirm the BBB disruption and to assess brain damage.

Opening the Blood-Brain Barrier with MR Imaging-guided Focused Ultrasound: Preclinical Testing on a Trans-Human Skull Porcine Model.

Science.gov (United States)

Huang, Yuexi; Alkins, Ryan; Schwartz, Michael L; Hynynen, Kullervo

2017-01-01

Purpose To develop and test a protocol in preparation for a clinical trial on opening the blood-brain barrier (BBB) with magnetic resonance (MR) imaging-guided focused ultrasound for the delivery of chemotherapy drugs to brain tumors. Materials and Methods The procedures were approved by the institutional animal care committee. A trans-human skull porcine model was designed for the preclinical testing. Wide craniotomies were applied in 11 pigs (weight, approximately 15 kg). A partial human skull was positioned over the animal's brain. A modified clinical MR imaging-guided focused ultrasound brain system was used with a 3.0-T MR unit. The ultrasound beam was steered during sonications over a 3 × 3 grid at 3-mm spacing. Acoustic power levels of 3-20 W were tested. Bolus injections of microbubbles at 4 μL/kg were tested for each sonication. Levels of BBB opening, hemorrhage, and cavitation signal were measured with MR imaging, histologic examination, and cavitation receivers, respectively. A cavitation safety algorithm was developed on the basis of logistic regression of the measurements and tested to minimize the risk of hemorrhage. Results BBB openings of approximately 1 cm 3 in volume were visualized with gadolinium-enhanced MR imaging after sonication at an acoustic power of approximately 5 W. Gross examination of histologic specimens helped confirm Evans blue (bound to macromolecule albumin) extravasation, and hematoxylin-eosin staining helped detect only scattered extravasation of red blood cells. In cases where cavitation signals were higher than thresholds, sonications were terminated immediately without causing hemorrhage. Conclusion With a trans-human skull porcine model, this study demonstrated BBB opening with a 230-kHz system in preparation for a clinical trial. © RSNA, 2016 Online supplemental material is available for this article.

Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

International Nuclear Information System (INIS)

Tamai, Isamu; Takei, Tadao; Oota, Hideomi; Maekawa, Kihei.

1981-01-01

Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in intants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therepy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by hight doses of ACTH and in cases where brain atrophy had already been obserbed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time. (author)

Understanding Acoustic Cavitation Initiation by Porous Nanoparticles: Toward Nanoscale Agents for Ultrasound Imaging and Therapy.

Science.gov (United States)

Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Goodwin, Andrew P

2016-08-23

Ultrasound is widely applied in medical diagnosis and therapy due to its safety, high penetration depth, and low cost. In order to improve the contrast of sonographs and efficiency of the ultrasound therapy, echogenic gas bodies or droplets (with diameters from 200 nm to 10 µm) are often used, which are not very stable in the bloodstream and unable to penetrate into target tissues. Recently, it was demonstrated that nanobubbles stabilized by nanoparticles can nucleate ultrasound responsive microbubbles under reduced acoustic pressures, which is very promising for the development of nanoscale (ultrasound agents. However, there is still very little understanding about the effects of nanoparticle properties on the stabilization of nanobubbles and nucleation of acoustic cavitation by these nanobubbles. Here, a series of mesoporous silica nanoparticles with sizes around 100 nm but with different morphologies were synthesized to understand the effects of nanoparticle porosity, surface roughness, hydrophobicity, and hydrophilic surface modification on acoustic cavitation inception by porous nanoparticles. The chemical analyses of the nanoparticles showed that, while the nanoparticles were prepared using the same silica precursor (TEOS) and surfactant (CTAB), they revealed varying amounts of carbon impurities, hydroxyl content, and degrees of silica crosslinking. Carbon impurities or hydrophobic modification with methyl groups is found to be essential for nanobubble stabilization by mesoporous silica nanoparticles. The acoustic cavitation experiments in the presence of ethanol and/or bovine serum albumin (BSA) demonstrated that acoustic cavitation is predominantly nucleated by the nanobubbles stabilized at the nanoparticle surface not inside the mesopores. Finally, acoustic cavitation experiments with rough and smooth nanoparticles were suggested that a rough nanoparticle surface is needed to largely preserve surface nanobubbles after coating the surface with hydrophilic

Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.

Science.gov (United States)

Liu, Zheng; Gao, Shunji; Zhao, Yang; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

2012-02-01

Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Ultrasound-enhanced nanotherapy of pancreatic cancer

Science.gov (United States)

Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

2010-03-01

The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

Anticoagulant therapy for venous thromboembolism detected by Doppler ultrasound in patients with metastatic colorectal cancer receiving bevacizumab

Directory of Open Access Journals (Sweden)

Suenaga M

2015-01-01

Full Text Available Mitsukuni Suenaga, Nobuyuki Mizunuma, Eiji Shinozaki, Satoshi Matsusaka, Masato Ozaka, Mariko Ogura, Keisho Chin, Toshiharu Yamaguchi Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan Background: Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev. We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings.Methods: Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E, thrombus >40 mm in diameter (S, thrombus involving the superior vena cava (C, and decreased blood flow (V.Results: Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9% by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%. Of these 56 patients, 11 (19.6% received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%, as well as V in two (18.2%, S + V + C in one (9.1%, E + S + V in one (9.1%, E + C in one (9.1%, E in one (9.1%, and C in one (9.1%. All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%. Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%, but there were no treatment

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

Science.gov (United States)

Lee, Katrina; Lenards, Nishele; Holson, Janice

2016-01-01

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Temporal regularization of ultrasound-based liver motion estimation for image-guided radiation therapy

Energy Technology Data Exchange (ETDEWEB)

O’Shea, Tuathan P., E-mail: tuathan.oshea@icr.ac.uk; Bamber, Jeffrey C.; Harris, Emma J. [Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS foundation Trust, Sutton, London SM2 5PT (United Kingdom)

2016-01-15

Purpose: Ultrasound-based motion estimation is an expanding subfield of image-guided radiation therapy. Although ultrasound can detect tissue motion that is a fraction of a millimeter, its accuracy is variable. For controlling linear accelerator tracking and gating, ultrasound motion estimates must remain highly accurate throughout the imaging sequence. This study presents a temporal regularization method for correlation-based template matching which aims to improve the accuracy of motion estimates. Methods: Liver ultrasound sequences (15–23 Hz imaging rate, 2.5–5.5 min length) from ten healthy volunteers under free breathing were used. Anatomical features (blood vessels) in each sequence were manually annotated for comparison with normalized cross-correlation based template matching. Five sequences from a Siemens Acuson™ scanner were used for algorithm development (training set). Results from incremental tracking (IT) were compared with a temporal regularization method, which included a highly specific similarity metric and state observer, known as the α–β filter/similarity threshold (ABST). A further five sequences from an Elekta Clarity™ system were used for validation, without alteration of the tracking algorithm (validation set). Results: Overall, the ABST method produced marked improvements in vessel tracking accuracy. For the training set, the mean and 95th percentile (95%) errors (defined as the difference from manual annotations) were 1.6 and 1.4 mm, respectively (compared to 6.2 and 9.1 mm, respectively, for IT). For each sequence, the use of the state observer leads to improvement in the 95% error. For the validation set, the mean and 95% errors for the ABST method were 0.8 and 1.5 mm, respectively. Conclusions: Ultrasound-based motion estimation has potential to monitor liver translation over long time periods with high accuracy. Nonrigid motion (strain) and the quality of the ultrasound data are likely to have an impact on tracking

Stereotactic Radiosurgery: Treatment of Brain Metastasis Without Interruption of Systemic Therapy

Energy Technology Data Exchange (ETDEWEB)

Shen, Colette J.; Kummerlowe, Megan N.; Redmond, Kristin J. [Department of Radiation Oncology, Johns Hopkins Hospital, Baltimore, Maryland (United States); Rigamonti, Daniele [Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland (United States); Johns Hopkins Aramco Healthcare, Dhahran (Saudi Arabia); Lim, Michael K. [Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland (United States); Kleinberg, Lawrence R., E-mail: kleinla@jhmi.edu [Department of Radiation Oncology, Johns Hopkins Hospital, Baltimore, Maryland (United States)

2016-06-01

Purpose: To evaluate the prevalence, outcomes, and toxicities of concurrent delivery of systemic therapy with stereotactic radiosurgery (SRS) for treatment of brain metastases. Methods and Materials: We conducted a retrospective review of 193 patients treated at our institution with SRS without prior whole-brain radiation therapy (WBRT) for brain metastases between 2009 and 2014. Outcome metrics included administration of concurrent systemic therapy, myelosuppression, neurotoxicity, and survival. Results: One hundred ninety-three patients with a median age of 61 years underwent a total of 291 SRS treatments. Thirty-seven percent of SRS treatments were delivered concurrently with systemic therapy, of which 46% were with conventional myelosuppressive chemotherapy, and 54% with targeted and immune therapy agents. Myelosuppression was minimal after treatment with both systemic therapy and SRS, with 14% grade 3-4 toxicity for lymphopenia and 4-9% for leukopenia, neutropenia, anemia, and thrombocytopenia. Neurotoxicity was also minimal after combined therapy, with no grade 4 and <5% grade 3 toxicity, 34% dexamethasone requirement, and 4% radiation necrosis, all similar to treatments with SRS alone. Median overall survival was similar after SRS alone (14.4 months) versus SRS with systemic therapy (12.9 months). In patients with a new diagnosis of primary cancer with brain metastasis, early treatment with concurrent systemic therapy and SRS correlated with improved survival versus SRS alone (41.6 vs 21.5 months, P<.05). Conclusions: Systemic therapy can be safely given concurrently with SRS for brain metastases: our results suggest minimal myelosuppression and neurotoxicity. Concurrent therapy is an attractive option for patients who have both intracranial and extracranial metastatic disease and may be particularly beneficial in patients with a new diagnosis of primary cancer with brain metastasis.

General Ultrasound Imaging

Science.gov (United States)

... spleen pancreas kidneys bladder uterus , ovaries , and unborn child ( fetus ) in pregnant patients eyes thyroid and parathyroid glands scrotum (testicles) brain in infants hips in infants spine in infants Ultrasound is also used to: guide ...

Stem cell therapies in preclinical models of stroke. Is the aged brain microenvironment refractory to cell therapy?

Science.gov (United States)

Sandu, Raluca Elena; Balseanu, Adrian Tudor; Bogdan, Catalin; Slevin, Mark; Petcu, Eugen; Popa-Wagner, Aurel

2017-08-01

Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF+BM-MSC or G-CSF+BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains. While the middle aged brain does not seem to impair drug and cell therapies, in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. Copyright © 2017. Published by Elsevier Inc.

Radiation therapy of 9L rat brain tumors

International Nuclear Information System (INIS)

Henderson, S.D.; Kimler, B.F.; Morantz, R.A.

1981-01-01

The effects of radiation therapy on normal rats and on rats burdened with 9L brain tumors have been studied. The heads of normal rats were x-irradiated with single exposures ranging from 1000 R to 2700 R. Following acute exposures greater than 2100 R, all animals died in 8 to 12 days. Approximately 30% of the animals survived beyond 12 days over the range of 1850 to 1950 R; following exposures less than 1850 R, all animals survived the acute radiation effects, and median survival times increased with decreasing exposure. Three fractionated radiation schedules were also studied: 2100 R or 3000 R in 10 equal fractions, and 3000 R in 6 equal fractions, each schedule being administered over a 2 week period. The first schedule produced a MST of greater than 1 1/2 years; the other schedules produced MSTs that were lower. It was determined that by applying a factor of 1.9, similar survival responses of normal rats were obtained with single as with fractionated radiation exposures. Animals burdened with 9L gliosarcoma brain tumors normally died of the disease process within 18 to 28 days ater tumor inoculation. Both single and fractionated radiation therapy resulted in a prolongation of survival of tumor-burdened rats. This prolongation was found to be linearly dependent upon the dose; but only minimally dependent upon the time after inoculation at which therapy was initiated, or upon the fractionation schedule that was used. As with normal animals, similar responses were obtained with single as with fractionated exposures when a factor (1.9) was applied. All tumor-bearing animals died prior to the time that death was observed in normal, irradiated rats. Thus, the 9L gliosarcoma rat brain tumor model can be used for the pre-clinical experimental investigation of new therapeutic schedules involving radiation therapy and adjuvant therapies

Brain hypothermia therapy for childhood acute encephalopathy based on clinical evidence

OpenAIRE

IMATAKA, GEORGE; ARISAKA, OSAMU

2015-01-01

Although previous studies have reported on the effectiveness of brain hypothermia therapy in childhood acute encephalopathy, additional studies in this field are necessary. In this review, we discussed brain hypothermia therapy methods for two clinical conditions for which sufficient evidences are currently available in the literature. The first condition is known as hypoxic-ischemic encephalopathy and occurs in newborns and the second condition is acute encephalopathy which occurs in adults ...

The comparison of manual lymph drainage and ultrasound therapy on the leg swelling caused by wearing high heels.

Science.gov (United States)

Lee, Dong-Yeop; Han, Ji-Su; Jang, Eun-Ji; Seo, Dong-Kwon; Hong, Ji-Heon; Lee, Sang-Sook; Lee, Dong-Geol; Yu Lee, Jae-Ho

2014-01-01

One of the major symptoms when women are wearing high heels for a long time is leg swelling. The purpose of this study was to compare the effect of manual lymph drainage with ultrasound therapy. The forty-five healthy women of twenties were participated in this study and divided randomly into three groups; manual lymph drainage group (n=15), ultrasound therapy group (n=15) and control group (n=15). Swelling was measured before wearing the high heels (10 cm-height), after one-hour of wearing the high heels, wearing the high heels of one-hour after the intervention of 15 minutes. Also swelling was calculated by using a tape measure, volumeter and body composition analyzer. Statistical analysis of the comparison between the three groups was performed by one-way ANOVA. Also comparison to the mean value in swelling according to the time was performed by repeated measure ANOVA. As the result of this study, a significant changes have emerged within each of manual lymph drainage, ultrasound therapy and control group (p 0.05). But the mean value of manual lymph drainage group showed the tendency of fast recovering before causing swelling. Therefore, we consider that the clinical treatment of manual lymph drainage and ongoing studies will be made since manual lymph drainage is very effective in releasing the leg swelling caused by wearing high heels and standing for a long time at work.

EVALUATION OF ULTRASOUND REMISSION CRITERIA IN PATIENTS WITH RHEUMATOID ARTHRITIS DURING TOCILIZUMAB THERAPY

OpenAIRE

Rita Aleksandrovna Osipyants; D E Karateev; E Yu Panasyuk; G V Lukina; A V Smirnov; S I Glukhova; E N Aleksandrova; A V Volkov; E L Nasonov

2013-01-01

Objective: to study the association of ultrasound (US) remission criteria with the clinical and laboratory indicators of inflammatory activity, functional status, and X-ray changes in patients with rheumatoid arthritis (RA) during tocilizumab (TCZ) therapy.Subjects and methods. The trial included 36 patients with RA (meeting the 1987 American College of Rheumatology (ACR) criteria) who had received TCZ for 6 months. The authors made a clinical and laboratory assessment of RA activity (DAS28-C...

Ultrasound Assessment of Carotid Plaque Echogenicity Response to Statin Therapy: A Systematic Review and Meta-Analysis

Science.gov (United States)

Ibrahimi, Pranvera; Jashari, Fisnik; Bajraktari, Gani; Wester, Per; Henein, Michael Y.

2015-01-01

Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS). Results: Nine out of 580 identified studies including 566 patients’ carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%–36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months. Conclusions: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL. PMID:25984600

General Ultrasound Imaging

Medline Plus

Full Text Available ... arteries and veins in the abdomen, arms, legs, neck and/or brain (in infants and children) or ... used to help physicians evaluate symptoms such as: pain swelling infection Ultrasound is a useful way of ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... ovaries , and unborn child ( fetus ) in pregnant patients eyes thyroid and parathyroid glands scrotum (testicles) brain in ... Any portions that are not wiped off will dry quickly. The ultrasound gel does not usually stain ...

MRI of the foetal brain

International Nuclear Information System (INIS)

Rich, P.; Jones, R.; Britton, J.; Foote, S.; Thilaganathan, B.

2007-01-01

Ultrasound examinations for foetal brain abnormalities have been a part of the routine antenatal screening programme in the UK for many years. In utero brain magnetic resonance imaging (MRI) is now being used increasingly successfully to clarify abnormal ultrasound findings, often resulting in a change of diagnosis or treatment plan. Interpretation requires an understanding of foetal brain development, malformations and acquired diseases. In this paper we will outline the technique of foetal MRI, relevant aspects of brain development and provide illustrated examples of foetal brain pathology

MO-AB-210-00: Diagnostic Ultrasound Imaging Quality Control and High Intensity Focused Ultrasound Therapy Hands-On Workshop

International Nuclear Information System (INIS)

2015-01-01

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrations with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant 5R25NS

MO-AB-210-00: Diagnostic Ultrasound Imaging Quality Control and High Intensity Focused Ultrasound Therapy Hands-On Workshop

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrations with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant 5R25NS

General Ultrasound Imaging

Medline Plus

Full Text Available ... organs and to examine a baby in pregnant women and the brain and hips in infants. It’s ... modality for the diagnosis and monitoring of pregnant women and their unborn babies. Ultrasound provides real-time ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... spleen pancreas kidneys bladder uterus , ovaries , and unborn child ( fetus ) in pregnant patients eyes thyroid and parathyroid glands scrotum (testicles) brain in infants hips in infants spine in infants Ultrasound is also used to: guide ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... organs and to examine a baby in pregnant women and the brain and hips in infants. It’s ... Transvaginal ultrasound. The transducer is inserted into a woman's vagina to view the uterus and ovaries. top ...

Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

Science.gov (United States)

2015-01-01

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

Science.gov (United States)

Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

2014-03-25

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

Science.gov (United States)

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-07

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual

High power phased array prototype for clinical high intensity focused ultrasound : applications to transcostal and transcranial therapy.

Science.gov (United States)

Pernot, M; Aubry, J -F; Tanter, M; Marquet, F; Montaldo, G; Boch, A -L; Kujas, M; Seilhean, D; Fink, M

2007-01-01

Bursts of focused ultrasound energy three orders of magnitude more intense than diagnostic ultrasound became during the last decade a noninvasive option for treating cancer from breast to prostate or uterine fibroid. However, many challenges remain to be addressed. First, the corrections of distortions induced on the ultrasonic therapy beam during its propagation through defocusing obstacles like skull bone or ribs remain today a technological performance that still need to be validated clinically. Secondly, the problem of motion artifacts particularly important for the treatment of abdominal parts becomes today an important research topic. Finally, the problem of the treatment monitoring is a wide subject of interest in the growing HIFU community. For all these issues, the potential of new ultrasonic therapy devices able to work both in Transmit and Receive modes will be emphasized. A review of the work under achievement at L.O.A. using this new generation of HIFU prototypes on the monitoring, motion correction and aberrations corrections will be presented.

Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

Science.gov (United States)

Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

2016-11-01

Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.

Therapeutic ultrasound

International Nuclear Information System (INIS)

Crum, Lawrence A

2004-01-01

The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

Impact of Focused Ultrasound-enhanced Drug Delivery on Survival in Rats with Glioma

Science.gov (United States)

Treat, Lisa Hsu; Zhang, Yongzhi; McDannold, Nathan; Hynynen, Kullervo

2009-04-01

Malignancies of the brain remain difficult to treat with chemotherapy because the selective permeability of the blood-brain barrier (BBB) blocks many potent agents from reaching their target. Previous studies have illustrated the feasibility of drug and antibody delivery across the BBB using MRI-guided focused ultrasound. In this study, we investigated the impact of focused ultrasound-enhanced delivery of doxorubicin on survival in rats with aggressive glioma. Sprague-Dawley rats were implanted with 9 L gliosarcoma cells in the brain. Eight days after implantation, each rat received one of the following: (1) no treatment (control), (2) a single treatment with microbubble-enhanced MRI-guided focused ultrasound (FUS only), (3) a single treatment with i.v. liposomal doxorubicin (DOX only), or (4) a single treatment with microbubble-enhanced MRI-guided focused ultrasound and concurrent i.v. injections of liposomal doxorubicin (FUS+DOX). The survival time from implantation to death or euthanasia was recorded. We observed a modest but significant increase in median survival time in rats treated with combined MRI-guided focused ultrasound chemotherapy, compared to chemotherapy alone (p0.10). Our study demonstrates for the first time a therapeutic benefit achieved with ultrasound-enhanced drug delivery across the blood-brain barrier. This confirmation of efficacy in an in vivo tumor model indicates that targeted drug delivery using MRI-guided focused ultrasound has the potential to have a major impact on the treatment of patients with brain tumors and other neurological disorders.

Radiation therapy of brain tumor

International Nuclear Information System (INIS)

Sung, K. J.; Lee, D. H.; Park, C. Y.

1980-01-01

One hundred and six cases of brain tumors were treated at the Yonsei Cancer Center from January 1972 to August 1978 by Co-60 teletherapy unit. We analyses their clinical findings, histopathological findings, treatment and results. In those cases which computerized tomography had been used before and after radiation therapy, changes in tumor size and the presence of edema or necrosis following treatment was evaluated. 1. Among 106 cases, 90 cases were primary brain tumors and 16 cases were metastatic brain tumors. Pituitary tumors (38), glioma (34) and pinealoma (10) composed of most of primary brain tumors. 2. Post treatment follow-up was possible in 38 cases more than 1 years. Four among 11 cases of giloma expired and survivors had considerable neurological symptoms except 2 cases. Sixty five percent (12/20) of pituitary tumors showed improvement of visual symptoms and all cases (7) of pinealoma which post treatment follow-up was possible, showed remarkable good response. 3. Findings of CT scan after radiation treatment were compatible with results of clinical findings and post treatment follow-up. It showed complete regression of tumor mass in one case of pinealoma and medulloblastoma. One case of pituitary tumor showed almost complete regression of tumor mass. It also showed large residual lesion in cases of glioblastoma multiforme and cystic astrocytoma.

Synergistic effects of Combined Therapy: nonfocused ultrasound plus Aussie current for noninvasive body contouring.

Science.gov (United States)

Canela, Vivianne Carvalho; Crivelaro, Cinthia Nicoletti; Ferla, Luciane Zacchi; Pelozo, Gisele Marques; Azevedo, Juliana; Liebano, Richard Eloin; Nogueira, Caroline; Guidi, Renata Michelini; Grecco, Clóvis; Sant'Ana, Estela

2018-01-01

Nowadays, there are several noninvasive technologies being used for improving of body contouring. The objectives of this pilot study were to verify the effectiveness of the Heccus ® device, emphasizing the synergism between nonfocused ultrasound plus Aussie current in the improvement of body contour, and to determine if the association of this therapy with whole-body vibration exercises can have additional positive effects in the results of the treatments. Twenty healthy women aged 20-40 years participated in the study. Ten patients received Combined Therapy treatment (G1) and the other 10 participants received Combined Therapy with additional vibratory platform treatment (G2). Anthropometric and standardized photography analysis, ultrasonography, cutometry and self-adminestered questionnaires of tolerance and satisfaction levels with the treatment were used. Compared with baseline values, reduction of fat thickness was observed by ultrasonography in the posterior thigh area in the G1 group ( P <0.05) and in the buttocks ( P <0.05) and the posterior thigh areas ( P <0.05) in the G2. All the treated areas in both groups showed reduction in cellulite degree in the buttocks, G1 ( P <0.05) and G2 ( P <0.05), and in posterior thigh areas, G1 ( P <0.05) and G2 ( P <0.05). Optimal improvement of skin firmness (G1, P <0.0001; G2, P =0.0034) in the treated areas was observed in both groups. We conclude that the synergistic effects of the Combined Therapy (nonfocused ultrasound plus Aussie current) might be a good option with noninvasive body contouring treatment for improving the aspect of the cellulite, skin firmness and localized fat. If used in association with the whole-body vibratory platform, the results can be better, especially in the treatment of localized fat. Further studies with larger sample size should be performed to confirm these results.

HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy.

Science.gov (United States)

Yan, Sijing; Lu, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

2016-08-18

This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.

Prostate Ultrasound

Medline Plus

Full Text Available ... needle biopsies and fluid aspiration. Risks For standard diagnostic ultrasound , there are no known harmful effects on ... and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top of page This page was reviewed on ...

Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim.

Science.gov (United States)

Wei, Karin; Feldmann, Robert E; Brascher, Anne-Kathrin; Benrath, Justus

2014-12-01

This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants. Wiley Periodicals, Inc.

Blue-Light Therapy following Mild Traumatic Brain Injury: Effects on White Matter Water Diffusion in the Brain

Directory of Open Access Journals (Sweden)

Sahil Bajaj

2017-11-01

Full Text Available Mild traumatic brain injury (mTBI is a common and often inconspicuous wound that is frequently associated with chronic low-grade symptoms and cognitive dysfunction. Previous evidence suggests that daily blue wavelength light therapy may be effective at reducing fatigue and improving sleep in patients recovering from mTBI. However, the effects of light therapy on recovering brain structure remain unexplored. In this study, we analyzed white matter diffusion properties, including generalized fractional anisotropy, and the quantity of water diffusion in isotropic (i.e., isotropic diffusion and anisotropic fashion (i.e., quantitative anisotropy, QA for fibers crossing 11 brain areas known to be significantly affected following mTBI. Specifically, we investigated how 6 weeks of daily morning blue light exposure therapy (compared to an amber-light placebo condition impacted changes in white matter diffusion in individuals with mTBI. We observed a significant impact of the blue light treatment (relative to the placebo on the amount of water diffusion (QA for multiple brain areas, including the corpus callosum, anterior corona radiata, and thalamus. Moreover, many of these changes were associated with improvements in sleep latency and delayed memory. These findings suggest that blue wavelength light exposure may serve as one of the potential non-pharmacological treatments for facilitating structural and functional recovery following mTBI; they also support the use of QA as a reliable neuro-biomarker for mTBI therapies.

MO-AB-210-02: Ultrasound Imaging and Therapy-Hands On Workshop

International Nuclear Information System (INIS)

Sammet, S.

2015-01-01

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrations with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant 5R25NS

MO-AB-210-01: Ultrasound Imaging and Therapy-Hands On Workshop

International Nuclear Information System (INIS)

Lu, Z.

2015-01-01

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrations with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant 5R25NS

MO-AB-210-02: Ultrasound Imaging and Therapy-Hands On Workshop

Energy Technology Data Exchange (ETDEWEB)

Sammet, S. [University of Chicago Medical Center (United States)

2015-06-15

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrations with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant 5R25NS

MO-AB-210-01: Ultrasound Imaging and Therapy-Hands On Workshop

Energy Technology Data Exchange (ETDEWEB)

Lu, Z. [University of Chicago (United States)

2015-06-15

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrations with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant 5R25NS

Thermal therapy for breast tumors by using a cylindrical ultrasound phased array with multifocus pattern scanning: a preliminary numerical study

International Nuclear Information System (INIS)

Ho, C-S; Ju, K-C; Cheng, T-Y; Chen, Y-Y; Lin, W-L

2007-01-01

The purpose of this study is to investigate the feasibility of using a 1 MHz cylindrical ultrasound phased array with multifocus pattern scanning to produce uniform heating for breast tumor thermal therapy. The breast was submerged in water and surrounded by the cylindrical ultrasound phased array. A multifocus pattern was generated and electrically scanned by the phased array to enlarge the treatment lesion in single heating. To prevent overheating normal tissues, a large planning target volume (PTV) would be divided into several planes with several subunits on each plane and sequentially treated with a cooling phase between two successive heatings of the subunit. Heating results for different target temperatures (T tgt ), blood perfusion rates and sizes of the PTV have been studied. Furthermore, a superficial breast tumor with different water temperatures was also studied. Results indicated that a higher target temperature would produce a slightly larger thermal lesion, and a higher blood perfusion rate would not affect the heating lesion size but increase the heating time significantly. The acoustic power deposition and temperature elevations in ribs can be minimized by orienting the acoustic beam from the ultrasound phased array approximately parallel to the ribs. In addition, a large acoustic window on the convex-shaped breast surface for the proposed ultrasound phased array and the cooling effect of water would prevent the skin overheating for the production of a lesion at any desired location. This study demonstrated that the proposed cylindrical ultrasound phased array can provide effective heating for breast tumor thermal therapy without overheating the skin and ribs within a reasonable treatment time

Diffuse brain calcification after radiation therapy in infantile cerebral malignant glioma

International Nuclear Information System (INIS)

Hondo, Hiroaki; Tanaka, Ryuichi; Yamada, Nobuhisa; Takeda, Norio

1987-01-01

We reported a case of infantile cerebral malignant glioma, which showed extensive intracranial calcification following radiation therapy, and reviewed the literature. A 4-month-old female infant was admitted to our hospital because of vomiting, enlargement of the head and convulsive seizures. Computerized tomography (CT) scans demonstrated a heterogeneously contrast-enhanced mass in the right temporo-parieto-occipital region and marked obstructive hydrocephalus. Subsequent to ventriculo-peritoneal shunt, biopsy was performed. The surgical specimen revealed anaplastic glioma. She then underwent whole brain irradiation with 1800 rads before subtotal removal and 3000 rads postoperatively. Calcification was first identified in the right frontal region and left basal ganglia 2.5 months after radiation therapy. At the age of 14 months, CT scans demonstrated extensive intracranial calcification in the cerebral hemispheres, basal ganglias, thalami, pons and cerebellum. A biopsy specimen of the frontal lobe revealed calcospherites of various sizes within and beside the walls of small vessels, but no tumor cells were observed. Cranial radiation therapy is a standard modality for treatment of children with neoplasm in the central nervous system. Since, however this therapy possibly causes long-term complications on the developing brain, it is important to plan radiation therapy for the brain tumor carefully. (author)

Controlled ultrasound-induced blood-brain barrier disruption using passive acoustic emissions monitoring.

Directory of Open Access Journals (Sweden)

Costas D Arvanitis

Full Text Available The ability of ultrasonically-induced oscillations of circulating microbubbles to permeabilize vascular barriers such as the blood-brain barrier (BBB holds great promise for noninvasive targeted drug delivery. A major issue has been a lack of control over the procedure to ensure both safe and effective treatment. Here, we evaluated the use of passively-recorded acoustic emissions as a means to achieve this control. An acoustic emissions monitoring system was constructed and integrated into a clinical transcranial MRI-guided focused ultrasound system. Recordings were analyzed using a spectroscopic method that isolates the acoustic emissions caused by the microbubbles during sonication. This analysis characterized and quantified harmonic oscillations that occur when the BBB is disrupted, and broadband emissions that occur when tissue damage occurs. After validating the system's performance in pilot studies that explored a wide range of exposure levels, the measurements were used to control the ultrasound exposure level during transcranial sonications at 104 volumes over 22 weekly sessions in four macaques. We found that increasing the exposure level until a large harmonic emissions signal was observed was an effective means to ensure BBB disruption without broadband emissions. We had a success rate of 96% in inducing BBB disruption as measured by in contrast-enhanced MRI, and we detected broadband emissions in less than 0.2% of the applied bursts. The magnitude of the harmonic emissions signals was significantly (P<0.001 larger for sonications where BBB disruption was detected, and it correlated with BBB permeabilization as indicated by the magnitude of the MRI signal enhancement after MRI contrast administration (R(2 = 0.78. Overall, the results indicate that harmonic emissions can be a used to control focused ultrasound-induced BBB disruption. These results are promising for clinical translation of this technology.

Study on medical economic evaluation methods for metastatic brain tumors therapy

International Nuclear Information System (INIS)

Takura, Tomoyuki; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Uetsuka, Yoshio

2010-01-01

Treatment design for metastatic brain tumors is required to firstly care about the life and function for which the patient hopes because it is terminal care. Therefore, to discuss the value of the therapy, a viewpoint of the quality of life (QOL) and the socioeconomic factors other than the survival rate is important. However, examination that applies these factors to the therapy needs to be carried out more thoroughly. With this in mind, we discuss cost effectiveness of therapy for metastatic brain tumor, through a pilot study on gamma knife therapy. We studied 18 patients (mean age 61.6 years old) undergoing therapy for metastatic brain tumors. The health rate QOL was assessed by the profile-type measure SF-36 (Short-Form 36-Item Ver1.2) and the preference-based measure EQ-5D (EuroQoL-5D), before and six months after gamma knife therapy. Cost-utility-analysis (yen/Qaly) was carried out from quality adjusted life years (Qalys) and medical fee claims. In addition, we made a correlation analysis of the irradiation procedure and the gains attained. The observation by SF-36 for six months was useful for metastatic brain tumor. As a result, the QOL indicators showed increased mental health (MH: p=0.040) and role emotional (RE: p=0.029) with significant difference. In the measurement of EQ-5D, it was added only for one month based on the significant difference (p=0.022) from the pre-therapy QOL. The utilities that were analyzed became 0.052±0.175 standard deviation (SD) (score), and Qalys were 0.135. Because the cost was 721.4±5.2 SD (thousand yen), the performance of cost-utility-analysis was estimated as 5,330,000 (yen/Qaly). In addition, positive correlation (r=0.845/p=0.034) was found between the EQ-5D utility score and the tumor irradiation energy (mJ), etc. We established a new value over and above mere survival rate concerning metastatic brain tumor therapy. The socioeconomics and efficacy of therapy are more difficult to discuss in this disease than in other

Prostate Ultrasound

Medline Plus

Full Text Available ... top of page Additional Information and Resources RTAnswers.org Radiation Therapy for Prostate Cancer top of page ... to Ultrasound - Prostate Sponsored by Please note RadiologyInfo.org is not a medical facility. Please contact your ...

Wii-habilitation as balance therapy for children with acquired brain injury.

Science.gov (United States)

Tatla, Sandy K; Radomski, Anna; Cheung, Jessica; Maron, Melissa; Jarus, Tal

2014-02-01

To evaluate the effectiveness of the Nintendo Wii compared to traditional balance therapy in improving balance, motivation, and functional ability in children undergoing acute rehabilitation after brain injury. A non-concurrent, randomized multiple baseline single-subject research design was used with three participants. Data were analyzed by visual inspection of trend lines. Daily Wii balance training was equally motivating to traditional balance therapy for two participants and more motivating for one participant. While improvements in dynamic balance were observed, the results for static balance remain inconclusive. All participants demonstrated improvements in functional ability. Wii balance therapy is a safe, feasible, and motivating intervention for children undergoing acute rehabilitation after an acquired brain injury. Further research to examine the effectiveness of Wii balance therapy in this population is warranted.

Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

Directory of Open Access Journals (Sweden)

A. I. Neimark

2014-01-01

Full Text Available Objective: to evaluate the efficiency and safety of using the luteinizing hormone releasing hormone leuprorelin with the Atrigel delivery system in doses of 7.5, 22.5, and 45 mg as an adjuvant regimen in high- and moderate-risk cancer patients who have received high-intensity focused ultrasound (HIFU therapy.Subjects and methods. Moderate- and high-risk locally advanced prostate cancer (PC patients treated with HIFU (n = 28 and HIFU in combination with hormone therapy during 6 months (n = 31 were examined.Results. The investigation has shown that leuprorelin acetate monotherapy used within 6 months after HIFU therapy can achieve the highest reduction in prostate-specific antigen levels and positively affect the symptoms of the disease. HIFU in combination with androgen deprivation substantially diminishes the clinical manifestations of the disease and improves quality of life in HIFU-treated patients with PC, by reducing the degree of infravesical obstruction (according to uroflowmetric findings and IPSS scores, and causes a decrease in prostate volume as compared to those who have undergone HIFU only. Treatment with leuprorelin having the Atrigel delivery system has demonstrated the low incidence of adverse reactions and good tolerability.

Pulsed focused ultrasound combined with micro-bubble contrast agent can open the blood-brain barrier of gliblastoma patients and improve the efficacy of Temozolomide treatment

Directory of Open Access Journals (Sweden)

Qian DONG

2017-06-01

Full Text Available Objective This research examined the effect of microbubble contrast agent plus ultrasound on the permeability of blood-brain barrier, and explored whether it affects the efficacy of chemotherapeutic drugs on cerebral glioblastoma. Methods Wistar rats were divided into three groups to find the optimal concentration of ultrasonic contrast agent. To identify the best ultrasound mode that affected the permeability of blood brain barrier, we employed transmission electron microscopy for study of brain ultrastructure. Western blotting was used to detect the tight junction protein claudin-5. Evans blue staining of brain tissues was utilized to identify the best ultrasonic contrast agent concentration and mode. Rat glioma cells (line 9L were injected into Wistar rats. After temozolomide chemotherapy, the tumor size was measured and the tumor marker GFAP in serum was detected by ELISA. Results The best contrast agent concentration which increases permeability of BBB in rats was found to be 1ml/kg and the best ultrasound mode was intermittently- triggered pulses lasting for 10min (with interval was set at 400ms. More Evans blue passed the blood-brain barrier in ultrasonic cavitation effect group than in control group (P<0.05. After temozolomide chemotherapy, more tumor marker GFAP was detected in ultrasonic cavitation effect group than in control group (P<0.05. Conclusion The permeability of BBB was increased and more temozolomide went through BBB when the rats were subjected to intermittently triggered ultrasonic pulses and were injected at contrast agent at 1ml/kg, which could help to achieve better therapeutic efficacy for glioblastoma. DOI: 10.11855/j.issn.0577-7402.2017.05.06

CT and Ultrasound Guided Stereotactic High Intensity Focused Ultrasound (HIFU)

Science.gov (United States)

Wood, Bradford J.; Yanof, J.; Frenkel, V.; Viswanathan, A.; Dromi, S.; Oh, K.; Kruecker, J.; Bauer, C.; Seip, R.; Kam, A.; Li, K. C. P.

2006-05-01

To demonstrate the feasibility of CT and B-mode Ultrasound (US) targeted HIFU, a prototype coaxial focused ultrasound transducer was registered and integrated to a CT scanner. CT and diagnostic ultrasound were used for HIFU targeting and monitoring, with the goals of both thermal ablation and non-thermal enhanced drug delivery. A 1 megahertz coaxial ultrasound transducer was custom fabricated and attached to a passive position-sensing arm and an active six degree-of-freedom robotic arm via a CT stereotactic frame. The outer therapeutic transducer with a 10 cm fixed focal zone was coaxially mounted to an inner diagnostic US transducer (2-4 megahertz, Philips Medical Systems). This coaxial US transducer was connected to a modified commercial focused ultrasound generator (Focus Surgery, Indianapolis, IN) with a maximum total acoustic power of 100 watts. This pre-clinical paradigm was tested for ability to heat tissue in phantoms with monitoring and navigation from CT and live US. The feasibility of navigation via image fusion of CT with other modalities such as PET and MRI was demonstrated. Heated water phantoms were tested for correlation between CT numbers and temperature (for ablation monitoring). The prototype transducer and integrated CT/US imaging system enabled simultaneous multimodality imaging and therapy. Pre-clinical phantom models validated the treatment paradigm and demonstrated integrated multimodality guidance and treatment monitoring. Temperature changes during phantom cooling corresponded to CT number changes. Contrast enhanced or non-enhanced CT numbers may potentially be used to monitor thermal ablation with HIFU. Integrated CT, diagnostic US, and therapeutic focused ultrasound bridges a gap between diagnosis and therapy. Preliminary results show that the multimodality system may represent a relatively inexpensive, accessible, and simple method of both targeting and monitoring HIFU effects. Small animal pre-clinical models may be translated to large

Noninvasive Blood-Brain Barrier Opening in Live Mice

Science.gov (United States)

Choi, James J.; Pernot, Mathieu; Small, Scott; Konofagou, Elisa E.

2006-05-01

Most therapeutic agents cannot be delivered to the brain because of brain's natural defense: the Blood-Brain Barrier (BBB). It has recently been shown that Focused Ultrasound (FUS) can produce reversible and localized BBB opening in the brain when applied in the presence of ultrasound contrast agents post-craniotomy in rabbits [1]. However, a major limitation of ultrasound in the brain is the strong phase aberration and attenuation of the skull bone, and, as a result, no study of trans-cranial ultrasound-targeted drug treatment in the brain in vivo has been reported as of yet. In this study, the feasibility of BBB opening in the hippocampus of wildtype mice using FUS through the intact skull and skin was investigated. In order to investigate the effect of the skull, simulations of ultrasound wave propagation (1.5 MHz) through the skull using μCT data, and needle hydrophone measurements through an ex-vivo skull were made. The pressure field showed minimal attenuation (18% of the pressure amplitude) and a well-focused pattern through the left and right halves of the parietal bone. In experiments in vivo, the brains of four mice were sonicated through intact skull and skin. Ultrasound sonications (burst length: 20 ms; duty cycle: 20%; acoustic pressure range: 2.0 to 2.7 MPa) was applied 5 times for 30 s per shot with a 30 s delay between shots. Prior to sonication, ultrasound contrast agents (Optison; 10 μL) were injected intravenously. Contrast material enhanced high resolution MR Imaging (9.4 Tesla) was able to distinguish opening of large vessels in the region of the hippocampus. These results demonstrate the feasibility of locally opening the BBB in the mouse hippocampus using focused ultrasound through intact skull and skin. Future investigations will deal with optimization and reproducibility of the technique as well as application on Alzheimer's-model mice.

Ultrasound in sports medicine-A critical evaluation

International Nuclear Information System (INIS)

Allen, Gina M.; Wilson, David J.

2007-01-01

This article will discuss the aspects of sports medicine where ultrasound imaging has advantages when compared to MRI looking at the strengths and weaknesses of ultrasound in the context of diagnosis and management. It will also assess the use of ultrasound in therapy including guided injections and current thoughts on novel forms of treatment. We will particularly emphasise the role of ultrasound imaging in the management of injuries of tendon, ligament and muscle

Vascular Structure Identification in Intraoperative 3D Contrast-Enhanced Ultrasound Data

Directory of Open Access Journals (Sweden)

Elisee Ilunga-Mbuyamba

2016-04-01

Full Text Available In this paper, a method of vascular structure identification in intraoperative 3D Contrast-Enhanced Ultrasound (CEUS data is presented. Ultrasound imaging is commonly used in brain tumor surgery to investigate in real time the current status of cerebral structures. The use of an ultrasound contrast agent enables to highlight tumor tissue, but also surrounding blood vessels. However, these structures can be used as landmarks to estimate and correct the brain shift. This work proposes an alternative method for extracting small vascular segments close to the tumor as landmark. The patient image dataset involved in brain tumor operations includes preoperative contrast T1MR (cT1MR data and 3D intraoperative contrast enhanced ultrasound data acquired before (3D-iCEUS s t a r t and after (3D-iCEUS e n d tumor resection. Based on rigid registration techniques, a preselected vascular segment in cT1MR is searched in 3D-iCEUS s t a r t and 3D-iCEUS e n d data. The method was validated by using three similarity measures (Normalized Gradient Field, Normalized Mutual Information and Normalized Cross Correlation. Tests were performed on data obtained from ten patients overcoming a brain tumor operation and it succeeded in nine cases. Despite the small size of the vascular structures, the artifacts in the ultrasound images and the brain tissue deformations, blood vessels were successfully identified.

Safety and Efficacy of Ultrasound-Guided Fiducial Marker Implantation for CyberKnife Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Hyun; Hong, Seong; Sook; Kim, Jung Hoon; Park, Hyun Jeong; Chang, Yun Woo; Chang, A Ram [Soonchunhyang University Seoul Hospital, Seoul (Korea, Republic of); Kwon, Seok Beom [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

2012-06-15

To evaluate the safety and technical success rate of an ultrasound-guided fiducial marker implantation in preparation for CyberKnife radiation therapy. We retrospectively reviewed 270 percutaneous ultrasound-guided fiducial marker implantations in 77 patients, which were performed from June 2008 through March 2011. Of 270 implantations, 104 were implanted in metastatic lymph nodes, 96 were in the liver, 39 were in the pancreas, and 31 were in the prostate. During and after the implantation, major and minor procedure-related complications were documented. We defined technical success as the implantation enabling adequate treatment planning and CT simulation. The major and minor complication rates were 1% and 21%, respectively. One patient who had an implantation in the liver suffered severe abdominal pain, biloma, and pleural effusion, which were considered as major complication. Abdominal pain was the most common complication in 11 patients (14%). Among nine patients who had markers inserted in the prostate, one had transient hematuria for less than 24 hours, and the other experienced transient voiding difficulty. Of the 270 implantations, 261 were successful (97%). The reasons for unsuccessful implantations included migration of fiducial markers (five implantations, 2%) and failure to discriminate the fiducial markers (three implantations, 1%). Among the unsuccessful implantation cases, six patients required additional procedures (8%). The symptomatic complications following ultrasound-guided percutaneous implantation of fiducial markers are relatively low. However, careful consideration of the relatively higher rate of migration and discrimination failure is needed when performing ultrasound-guided percutaneous implantations of fiducial markers.

Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study.

Directory of Open Access Journals (Sweden)

Kuo-Chen Wei

Full Text Available The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI-monitored focused ultrasound (FUS-induced blood-brain barrier (BBB disruption to enhance Temozolomide (TMZ delivery for improving Glioblastoma Multiforme (GBM treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI, animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

Science.gov (United States)

Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

2018-04-01

Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

[Deep brain stimulation in movement disorders: evidence and therapy standards].

Science.gov (United States)

Parpaley, Yaroslav; Skodda, Sabine

2017-07-01

The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice. Georg Thieme Verlag KG Stuttgart · New York.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

Science.gov (United States)

Menendez-Castro, Carlos; Zapke, Maren; Fahlbusch, Fabian; von Goessel, Heiko; Rascher, Wolfgang; Jüngert, Jörg

2017-07-06

Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

Learning-based prediction of gestational age from ultrasound images of the fetal brain.

Science.gov (United States)

Namburete, Ana I L; Stebbing, Richard V; Kemp, Bryn; Yaqub, Mohammad; Papageorghiou, Aris T; Alison Noble, J

2015-04-01

We propose an automated framework for predicting gestational age (GA) and neurodevelopmental maturation of a fetus based on 3D ultrasound (US) brain image appearance. Our method capitalizes on age-related sonographic image patterns in conjunction with clinical measurements to develop, for the first time, a predictive age model which improves on the GA-prediction potential of US images. The framework benefits from a manifold surface representation of the fetal head which delineates the inner skull boundary and serves as a common coordinate system based on cranial position. This allows for fast and efficient sampling of anatomically-corresponding brain regions to achieve like-for-like structural comparison of different developmental stages. We develop bespoke features which capture neurosonographic patterns in 3D images, and using a regression forest classifier, we characterize structural brain development both spatially and temporally to capture the natural variation existing in a healthy population (N=447) over an age range of active brain maturation (18-34weeks). On a routine clinical dataset (N=187) our age prediction results strongly correlate with true GA (r=0.98,accurate within±6.10days), confirming the link between maturational progression and neurosonographic activity observable across gestation. Our model also outperforms current clinical methods by ±4.57 days in the third trimester-a period complicated by biological variations in the fetal population. Through feature selection, the model successfully identified the most age-discriminating anatomies over this age range as being the Sylvian fissure, cingulate, and callosal sulci. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

Science.gov (United States)

Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

2015-05-01

Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques.

Science.gov (United States)

McDannold, Nathan; Arvanitis, Costas D; Vykhodtseva, Natalia; Livingstone, Margaret S

2012-07-15

The blood-brain barrier (BBB) prevents entry of most drugs into the brain and is a major hurdle to the use of drugs for brain tumors and other central nervous system disorders. Work in small animals has shown that ultrasound combined with an intravenously circulating microbubble agent can temporarily permeabilize the BBB. Here, we evaluated whether this targeted drug delivery method can be applied safely, reliably, and in a controlled manner on rhesus macaques using a focused ultrasound system. We identified a clear safety window during which BBB disruption could be produced without evident tissue damage, and the acoustic pressure amplitude where the probability for BBB disruption was 50% and was found to be half of the value that would produce tissue damage. Acoustic emission measurements seem promising for predicting BBB disruption and damage. In addition, we conducted repeated BBB disruption to central visual field targets over several weeks in animals trained to conduct complex visual acuity tasks. All animals recovered from each session without behavioral deficits, visual deficits, or loss in visual acuity. Together, our findings show that BBB disruption can be reliably and repeatedly produced without evident histologic or functional damage in a clinically relevant animal model using a clinical device. These results therefore support clinical testing of this noninvasive-targeted drug delivery method.

Scalp Dose Evaluation According Radiation Therapy Technique of Whole Brain Radiation Therapy

International Nuclear Information System (INIS)

Jang, Joon Yung; Park, Soo Yun; Kim, Jong Sik; Choi, Byeong Gi; Song, Gi Won

2011-01-01

Opposing portal irradiation with helmet field shape that has been given to a patient with brain metastasis can cause excess dose in patient's scalp, resulting in hair loss. For this reason, this study is to quantitatively analyze scalp dose for effective prevention of hair loss by comparing opposing portal irradiation with scalp-shielding shape and tomotherapy designed to protect patient's scalp with conventional radiation therapy. Scalp dose was measured by using three therapies (HELMET, MLC, TOMO) after five thermo-luminescence dosimeters were positioned along center line of frontal lobe by using RANDO Phantom. Scalp dose and change in dose distribution were compared and analyzed with DVH after radiation therapy plan was made by using Radiation Treatment Planning System (Pinnacle3, Philips Medical System, USA) and 6 MV X-ray (Clinac 6EX, VARIAN, USA). When surface dose of scalp by using thermo-luminescence dosimeters was measured, it was revealed that scalp dose decreased by average 87.44% at each point in MLC technique and that scalp dose decreased by average 88.03% at each point in TOMO compared with HELMET field therapy. In addition, when percentage of volume (V95%, V100%, V105% of prescribed dose) was calculated by using Dose Volume Histogram (DVH) in order to evaluate the existence or nonexistence of hotspot in scalp as to three therapies (HELMET, MLC, TOMO), it was revealed that MLC technique and TOMO plan had good dose coverage and did not have hot spot. Reducing hair loss of a patient who receives whole brain radiotherapy treatment can make a contribution to improve life quality of the patient. It is expected that making good use of opposing portal irradiation with scalp-shielding shape and tomotherapy to protect scalp of a patient based on this study will reduce hair loss of a patient.

Scalp Dose Evaluation According Radiation Therapy Technique of Whole Brain Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Jang, Joon Yung; Park, Soo Yun; Kim, Jong Sik; Choi, Byeong Gi; Song, Gi Won [Dept. of Radiation Oncology, Samsung Medical Center, Seoul (Korea, Republic of)

2011-09-15

Opposing portal irradiation with helmet field shape that has been given to a patient with brain metastasis can cause excess dose in patient's scalp, resulting in hair loss. For this reason, this study is to quantitatively analyze scalp dose for effective prevention of hair loss by comparing opposing portal irradiation with scalp-shielding shape and tomotherapy designed to protect patient's scalp with conventional radiation therapy. Scalp dose was measured by using three therapies (HELMET, MLC, TOMO) after five thermo-luminescence dosimeters were positioned along center line of frontal lobe by using RANDO Phantom. Scalp dose and change in dose distribution were compared and analyzed with DVH after radiation therapy plan was made by using Radiation Treatment Planning System (Pinnacle3, Philips Medical System, USA) and 6 MV X-ray (Clinac 6EX, VARIAN, USA). When surface dose of scalp by using thermo-luminescence dosimeters was measured, it was revealed that scalp dose decreased by average 87.44% at each point in MLC technique and that scalp dose decreased by average 88.03% at each point in TOMO compared with HELMET field therapy. In addition, when percentage of volume (V95%, V100%, V105% of prescribed dose) was calculated by using Dose Volume Histogram (DVH) in order to evaluate the existence or nonexistence of hotspot in scalp as to three therapies (HELMET, MLC, TOMO), it was revealed that MLC technique and TOMO plan had good dose coverage and did not have hot spot. Reducing hair loss of a patient who receives whole brain radiotherapy treatment can make a contribution to improve life quality of the patient. It is expected that making good use of opposing portal irradiation with scalp-shielding shape and tomotherapy to protect scalp of a patient based on this study will reduce hair loss of a patient.

Copper oxide loaded PLGA nanospheres: towards a multifunctional nanoscale platform for ultrasound-based imaging and therapy

Science.gov (United States)

Perlman, Or; Weitz, Iris S.; Sivan, Sarit S.; Abu-Khalla, Hiba; Benguigui, Madeleine; Shaked, Yuval; Azhari, Haim

2018-05-01

Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for

Impact of statin therapy on coronary plaque composition: A systematic review and meta-analysis of virtual histology intravascular ultrasound studies

NARCIS (Netherlands)

M. Banach (Maciej); C. Serban (Corina); A. Sahebkar (Amirhossein); D.P. Mikhailidis (Dimitri P.); S. Ursoniu (Sorin); K.K. Ray (Kausik K.); J. Rysz (Jacek); P.P. Toth (Peter); P. Muntner (Paul); S. Mosteoru (Svetlana); H.M. Garcia-Garcia (Hector); G.K. Hovingh (Kees); J.J.P. Kastelein (John); P.W.J.C. Serruys (Patrick)

2015-01-01

textabstractBackground: Virtual histology intravascular ultrasound (VH-IVUS) imaging is an innovative tool for the morphological evaluation of coronary atherosclerosis. Evidence for the effects of statin therapy on VH-IVUS parameters have been inconclusive. Consequently, we performed a systematic

Low-intensity pulsed ultrasound: Nonunions

Directory of Open Access Journals (Sweden)

Dijkman Bernadette

2009-01-01

Full Text Available Nonunions occur in 5-10% of fractures and are characterized by the failure to heal without further intervention. Low intensity pulsed ultrasound therapy has been developed as an alternative to surgery in the treatment of nonunions. We describe a systematic review on trials of low-intensity pulsed ultrasound therapy for healing of nonunions. We searched the electronic databases Medline and the Cochrane library for articles on ultrasound and healing of nonunions published up to 2008. Trials selected for the review met the following criteria: treatment of at least one intervention group with low intensity pulsed ultrasound; inclusion of patients (humans with one or more nonunions (defined as "established" or as a failure to heal for a minimum of eight months after initial injury; and assessment of healing and time to healing, as determined radiographically. The following data were abstracted from the included studies: sample size, ultrasound treatment characteristics, nonunion location, healing rate, time to fracture healing, fracture age, and demographic information. We found 79 potentially eligible publications, of which 14 met our inclusion criteria. Of these, eight studies were used for data abstraction. Healing rates averaged 87%, (range 65.6%-100% among eight trials. Mean time to healing was 146.5 days, (range 56-219 days. There is evidence from trials that low-intensity pulsed ultrasound may be an effective treatment for healing of nonunions. More homogeneous and larger controlled series are needed to further investigate its efficacy.

The study of low level laser irradiation therapy on brain infarction with SPECT

Institute of Scientific and Technical Information of China (English)

Xiao Xuechang; Jia Shaowei; Zleng Xiyuan

2000-01-01

Objective: Effect of rCBF and brain function on ILIB treating brain infarction will be investigated by SPECT brain perfusion imaging. Method: 3 1 patients with brain infarction, 17 patients were treated by ILIB on standard pharmaceutial treatment. SPECT brain perfusion imaging was performed before and after ILIB therapy with comparison of oneself. They were quantified with BFCR% model effect during ILIB in 14 patients were observed. Result: ILIB 30 rnme SPECT showed the improvement of rCBF and cerebral function in 14 patients with brain infarction, and in 17 patients locus were prominence than mirror regions att er ILIB therapy, both are higher singnitficant difference ( t=4.4052, P＜0.0001 ), but mirror regions were not singnificant difference before and after ILIB (t=1.6995, P＞0.05). BFCR% quantitative results of locus were higher mirror regions, and higher singnificant difference (t=4.5278 p＜0.0001 )。 Conclusion: ILIB can improve the rCBF and cerebral function of patients with brain infarction, and provoke function of brain cells. Some new evidence was provided for ILIB treatment of cerebral ischemia

Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies

NARCIS (Netherlands)

Banach, Maciej; Serban, Corina; Sahebkar, Amirhossein; Mikhailidis, Dimitri P.; Ursoniu, Sorin; Ray, Kausik K.; Rysz, Jacek; Toth, Peter P.; Muntner, Paul; Mosteoru, Svetlana; García-García, Hector M.; Hovingh, G. Kees; Kastelein, John J. P.; Serruys, Patrick W.

2015-01-01

Virtual histology intravascular ultrasound (VH-IVUS) imaging is an innovative tool for the morphological evaluation of coronary atherosclerosis. Evidence for the effects of statin therapy on VH-IVUS parameters have been inconclusive. Consequently, we performed a systematic review and meta-analysis

The effect of ultrasound on thromboembolic model of brain stroke in rat

Directory of Open Access Journals (Sweden)

Shabanzadeh A

2007-08-01

Full Text Available Background: Ultrasound (US has been used in neuroprotection after cerebral ischemia; however, its use is controversial. Application of US in combination with fibrinolytic agents may improve fibrinolytic effects. In this study the effects of US, alone or in combination with tissue plasminogen activator (tPA, on brain ischemic injury were examined and we studied whether US is protective in the brain injured by ischemia under normothermic conditions. Methods: We performed two studies. In the first study, rectal and brain temperatures were compared. In the second study, we studied whether US alone or in combination with tPA is neuroprotective in thromboembolic stroke. To induce focal cerebral ischemia, a clot was formed in a catheter. Once the clot had formed, the catheter was advanced 17 mm in the internal carotid artery until its tip was 1-2 mm away from the origin of the middle cerebral artery (MCA. The preformed clot in the catheter was then injected, and the catheter was removed. The wound was then closed and the infarction volume, edema and neurological deficits were measured after MCA occlusion. Results: The temperature in the brain was approximately 0.50 ºC lower than the rectal temperature. In the control, US+low tPA, low tPA, US+high tPA and, high tPA groups, the infarct volume (% was 34.56±4.16, 17.09±6.72, 21.25±7.8, 13.5±10.72 and 20.61±6.17 (mean ±SD at 48 h after MCA occlusion, respectively. The results indicate that US alone reduces the infarct volume by 30% compared to that of the control group (P<0.05. US improved neurological deficits and reduced brain edema significantly (p<0.05. Conclusions: This study indicate that US appears to have a protective effect, alone and in combination with tPA, in an embolic model of stroke.

[Music therapy and "brain music": state of the art, problems and perspectives].

Science.gov (United States)

Fedotchev, A I; Radchenko, G S

2013-01-01

Recent literature on the problem of interaction between music and the brain is reviewed and summarized. Mechanisms and effects of two most popular music therapy applications are picked out, including music listening and music making. Special attention is paid to relatively new line of investigations that is called "music of the brain" and deals with transformation of bioelectric processes of human organism into music. Unresolved questions of music therapy are identified and some promising lines of future investigations are delineated.

Image-guided procedures in brain biopsy.

Science.gov (United States)

Fujita, K; Yanaka, K; Meguro, K; Narushima, K; Iguchi, M; Nakai, Y; Nose, T

1999-07-01

Image-guided procedures, such as computed tomography (CT)-guided stereotactic and ultrasound-guided methods, can assist neurosurgeons in localizing the relevant pathology. The characteristics of image-guided procedures are important for their appropriate use, especially in brain biopsy. This study reviewed the results of various image-guided brain biopsies to ascertain the advantages and disadvantages. Brain biopsies assisted by CT-guided stereotactic, ultrasound-guided, Neuronavigator-guided, and the combination of ultrasound and Neuronavigator-guided procedures were carried out in seven, eight, one, and three patients, respectively. Four patients underwent open biopsy without a guiding system. Twenty of 23 patients had a satisfactory diagnosis after the initial biopsy. Three patients failed to have a definitive diagnosis after the initial procedure, one due to insufficient volume sampling after CT-guided procedure, and two due to localization failure by ultrasound because the lesions were nonechogenic. All patients who underwent biopsy using the combination of ultrasound and Neuronavigator-guided methods had a satisfactory result. The CT-guided procedure provided an efficient method of approaching any intracranial target and was appropriate for the diagnosis of hypodense lesions, but tissue sampling was sometimes not sufficient to achieve a satisfactory diagnosis. The ultrasound-guided procedure was suitable for the investigation of hyperdense lesions, but was difficult to localize nonechogenic lesions. The combination of ultrasound and Neuronavigator methods improved the diagnostic accuracy even in nonechogenic lesions such as malignant lymphoma. Therefore, it is essential to choose the most appropriate guiding method for brain biopsy according to the radiological nature of the lesions.

Additional Effect of Static Ultrasound and Diadynamic Currents on Myofascial Trigger Points in a Manual Therapy Program for Patients With Chronic Neck Pain: A Randomized Clinical Trial.

Science.gov (United States)

Dibai-Filho, Almir Vieira; de Oliveira, Alessandra Kelly; Girasol, Carlos Eduardo; Dias, Fabiana Rodrigues Cancio; Guirro, Rinaldo Roberto de Jesus

2017-04-01

To assess the additional effect of static ultrasound and diadynamic currents on myofascial trigger points in a manual therapy program to treat individuals with chronic neck pain. A single-blind randomized trial was conducted. Both men and women, between ages 18 and 45, with chronic neck pain and active myofascial trigger points in the upper trapezius were included in the study. Subjects were assigned to 3 different groups: group 1 (n = 20) was treated with manual therapy; group 2 (n = 20) was treated with manual therapy and static ultrasound; group 3 (n = 20) was treated with manual therapy and diadynamic currents. Individuals were assessed before the first treatment session, 48 hours after the first treatment session, 48 hours after the tenth treatment session, and 4 weeks after the last session. There was no group-versus-time interaction for Numeric Rating Scale, Neck Disability Index, Pain-Related Self-Statement Scale, pressure pain threshold, cervical range of motion, and skin temperature (F-value range, 0.089-1.961; P-value range, 0.106-0.977). Moreover, we found no differences between groups regarding electromyographic activity (P > 0.05). The use of static ultrasound or diadynamic currents on myofascial trigger points in upper trapezius associated with a manual therapy program did not generate greater benefits than manual therapy alone.

Multi-Channel RF System for MRI-Guided Transurethral Ultrasound Thermal Therapy

Science.gov (United States)

Yak, Nicolas; Asselin, Matthew; Chopra, Rajiv; Bronskill, Michael

2009-04-01

MRI-guided transurethral ultrasound thermal therapy is an approach to treating localized prostate cancer which targets precise deposition of thermal energy within a confined region of the gland. This treatment requires a system incorporating a heating applicator with multiple planar ultrasound transducers and associated RF electronics to control individual elements independently in order to achieve accurate 3D treatment. We report the design, construction, and characterization of a prototype multi-channel system capable of controlling 16 independent RF signals for a 16-element heating applicator. The main components are a control computer, microcontroller, and a 16-channel signal generator with 16 amplifiers, each incorporating a low-pass filter and transmitted/reflected power detection circuit. Each channel can deliver from 0.5 to 10 W of electrical power and good linearity from 3 to 12 MHz. Harmonic RF signals near the Larmor frequency of a 1.5 T MRI were measured to be below -30 dBm and heating experiments within the 1.5 T MR system showed no significant decrease in SNR of the temperature images. The frequency and power for all 16 channels could be changed in less than 250 ms, which was sufficiently rapid for proper performance of the control algorithms. A common backplane design was chosen which enabled an inexpensive, modular approach for each channel resulting in an overall system with minimal footprint.

Targeted therapy of animal eyes with tumors by laser-generated focused ultrasound (Conference Presentation)

Science.gov (United States)

Lee, Taehwa; Luo, Wei; Demirci, Hakan; Guo, L. Jay

2016-03-01

Cavitation therapy based on high-amplitude focused ultrasound (e.g., Histotripsy) has shown great promise in clinical trials. The technique realizes localized treatments of tissues and diseased cells by controlling cavitation zones, which can be even smaller than its acoustic spot sizes. Also, the short pressure pulse used in the technique can minimize the unwanted heat accumulation, which the conventional piezoelectric transducers suffer from due to low operating frequencies and relatively long acoustic pulses. However, this modality requires bulky system composed of array of piezoelectric elements and electric amplifiers in order to obtain high pressure amplitude. Moreover, especially when treating an area much smaller than the acoustic spot size, this approach may be vulnerable to nucleation sites within the focal volume, which can potentially induce cavitation and thus enlarge the total treatment area. Here, we show targeted cell-level therapy by using laser generated ultrasound. By employing a concave lens coated by a carbon nanotube (CNT)-polymer composite, high-amplitude acoustic pressure can be obtained at a tight focal spot (small focal spot, comparable to cavitation zone, lead to controlled cavitation treatment. Such feature can be exploited for treating intraocular tumors but without harming other parts of the eye (e.g. healthy retina and choroid) and therefore preserve the vision of the patients. We demonstrate that the localized disruption effects can be used for cell-level surgery to remove cells and to kill cells. Some experimental examples are shown using animal eyeballs.

General Ultrasound Imaging

Medline Plus

Full Text Available ... that allows the physician to see and evaluate blood flow through arteries and veins in the abdomen, arms, legs, neck and/or brain (in infants and children) or within various body organs such as the liver or kidneys. There are three types of Doppler ultrasound: Color Doppler uses a computer ...

First steps towards ultrasound-based motion compensation for imaging and therapy: calibration with an optical system and 4D PET imaging

Directory of Open Access Journals (Sweden)

Julia eSchwaab

2015-11-01

Full Text Available Target motion, particularly in the abdomen, due to respiration or patient movement is still a challenge in many diagnostic and therapeutic processes. Hence, methods to detect and compensate this motion are required. Diagnostic ultrasound represents a non-invasive and dose-free alternative to fluoroscopy, providing more information about internal target motion than respiration belt or optical tracking.The goal of this project is to develop an ultrasound based motion tracking for real time motion correction in radiation therapy and diagnostic imaging, notably in 4D positron emission tomography (PET. In this work, a workflow is established to enable the transformation of ultrasound tracking data to the coordinates of the treatment delivery or imaging system – even if the ultrasound probe is moving due to respiration. It is shown that the ultrasound tracking signal is equally adequate for 4D PET image reconstruction as the clinically used respiration belt and provides additional opportunities in this concern. Furthermore, it is demonstrated that the ultrasound probe being within the PET field of view generally has no relevant influence on the image quality. The accuracy and precision of all the steps in the calibration workflow for ultrasound tracking based 4D PET imaging are found to be in an acceptable range for clinical implementation. Eventually, we show in vitro that an ultrasound based motion tracking in absolute room coordinates with a moving US-transducer is feasible.

Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: a short-term study.

Science.gov (United States)

Baseri, Babak; Choi, James J; Tung, Yao-Sheng; Konofagou, Elisa E

2010-09-01

As a potentially viable method of brain drug delivery, the safety profile of blood-brain barrier (BBB) opening using focused ultrasound (FUS) and ultrasound contrast agents (UCA) needs to be established. In this study, we provide a short-term (30-min or 5-h survival) histological assessment of murine brains undergoing FUS-induced BBB opening. Forty-nine mice were intravenously injected with Definity microbubbles (0.05 microL/kg) and sonicated under the following parameters: frequency of 1.525 MHz, pulse length of 20 ms, pulse repetition frequency of 10 Hz, peak rarefactional acoustic pressures of 0.15-0.98 MPa and two 30-s sonication intervals with an intermittent 30-s delay. The BBB opening threshold was found to be 0.15-0.3 MPa based on fluorescence and magnetic resonance imaging of systemically injected tracers. Analysis of three histological measures in hematoxylin and eosin-stained sections revealed the safest acoustic pressure to be within the range of 0.3-0.46 MPa in all examined time periods post sonication. Across different pressure amplitudes, only the samples 30 min post opening showed significant difference (p < 0.05) in the average number of distinct damaged sites, microvacuolated sites, dark neurons and sites with extravasated erythrocytes. Enhanced fluorescence around severed microvessels was also noted and found to be associated with the largest tissue effects, whereas mildly diffuse BBB opening with uniform fluorescence in the parenchyma was associated with no or mild tissue injury. Region-specific areas of the sonicated brain (thalamus, hippocampal fissure, dentate gyrus and CA3 area of hippocampus) exhibited variation in fluorescence intensity based on the position, orientation and size of affected vessels. The results of this short-term histological analysis demonstrated the feasibility of a safe FUS-UCA-induced BBB opening under a specific set of sonication parameters and provided new insights on the mechanism of BBB opening.

A review of endocrine late effects in children after brain tumor therapy

International Nuclear Information System (INIS)

Marx, M.; Langer, T.; Beck, J.D.; Doerr, H.G.

1999-01-01

Background: Advances in the therapy of malignant brain tumors in children have led to a significant improvement in survival rates over the last few decades. As a result, the recognition and treatment of late effects have become more important. In addition to secondary tumors and deficiencies in cognitive and intellectual skills, the resulting endocrine disturbances play an important role. Method: Own data and literature review. Results: Deviations from the normal growth hormone secretion are usually recognized first and are most common, and have already been observed after conventional whole brain irradiation with 18 G. With some delay, other hypothalamopituitary deficiencies may occur, including panhypopituitarism. Puberty may come too early or too late or may not appear at all. Girls in particular, frequently experience an early and rapid pubertal development after brain tumor therapy, which may lead to further reduction in height due to an accelerated bone maturation. Functional disturbances of the thyroid and adrenal glands due to hypothalamic or pituitary deficiency are less common, and usually seen only after a radiation dose of over 40 Gy. Conclusion: Survivors of childhood brain tumors must be considered as long-term survivors, in whom the first therapy-induced long-term side effects appear almost immediately after the end of therapy. Maximum quality of life for the individual patient can only be achieved by long-term care and close cooperation of specialists in the different medical disciplines involved. (orig.) [de

Pharmacokinetic analysis of 111 in-labeled liposomal Doxorubicin in murine glioblastoma after blood-brain barrier disruption by focused ultrasound.

Directory of Open Access Journals (Sweden)

Feng-Yi Yang

Full Text Available The goal of this study was to evaluate the pharmacokinetics of targeted and untargeted (111In-doxorubicin liposomes after these have been intravenously administrated to tumor-bearing mice in the presence of blood-brain barrier disruption (BBB-D induced by focused ultrasound (FUS. An intracranial brain tumor model in NOD-scid mice using human brain glioblastoma multiforme (GBM 8401 cells was developed in this study. (111In-labeled human atherosclerotic plaque-specific peptide-1 (AP-1-conjugated liposomes containing doxorubicin (Lipo-Dox; AP-1 Lipo-Dox were used as a microSPECT probe for radioactivity measurements in the GBM-bearing mice. Compared to the control tumors treated with an injection of (111In-AP-1 Lipo-Dox or (111In-Lipo-Dox, the animals receiving the drugs followed by FUS exhibited enhanced accumulation of the drug in the brain tumors (p<0.05. Combining sonication with drugs significantly increased the tumor-to-normal brain doxorubicin ratio of the target tumors compared to the control tumors. The tumor-to-normal brain ratio was highest after the injection of (111In-AP-1 Lipo-Dox with sonication. The (111In-liposomes micro-SPECT/CT should be able to provide important information about the optimum therapeutic window for the chemotherapy of brain tumors using sonication.

Children's (Pediatric) Abdominal Ultrasound Imaging

Medline Plus

Full Text Available ... abdomen, arms, legs, neck and/or brain (in infants and children) or within various body organs such ... abdomen help determine causes of vomiting in young infants Because ultrasound provides real-time images, images that ...

Preliminary results on the feasibility of using ultrasound to monitor intrafractional motion during radiation therapy for pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Omari, Eenas A.; Erickson, Beth; Noid, George; Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 (United States); Ehlers, Christopher; Quiroz, Francisco [Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 (United States); Cooper, David T.; Lachaine, Martin [Elekta Ltd., Montreal, Québec H3A 2J5 (Canada)

2016-09-15

Purpose: Substantial intrafraction organ motion during radiation therapy (RT) for pancreatic cancer is well recognized as a major limiting factor for accurate delivery of RT. The aim of this work is to determine the feasibility of monitoring the intrafractional motion of the pancreas or surrounding structures using ultrasound for RT delivery. Methods: Transabdominal ultrasound (TAUS) and 4DCT data were acquired on ten pancreatic cancer patients during radiation therapy process in a prospective study. In addition, TAUS and MRI were collected for five healthy volunteers. The portal vein (PV) and the head of the pancreas (HP) along with other structures were contoured on these images. Volume changes, distance between the HP and PV, and motion difference between the HP and PV were measured to examine whether PV can be used as a motion surrogate for HP. TAUS images were acquired and processed using a research version of the Clarity autoscan ultrasound system (CAUS). Motion monitoring was performed with the ultrasound probe mounted on an arm fixed to the couch. Video segments of the monitoring sessions were captured. Results: On TAUS, PV is better visualized than HP. The measured mean volume deviation for all patients for the HP and PV was 1.4 and 0.6 ml, respectively. The distance between the HP and PV was close to a constant with 0.22 mm mean deviation throughout the ten breathing phases. The mean of the absolute motion difference for all patients was 1.7 ± 0.8 mm in LR, 1.5 ± 0.5 mm in AP, and 2.3 ± 0.7 mm in SI, suggesting that the PV is a good surrogate for HP motion estimation. By using this surrogate, the HP motion tracking using TAUS was demonstrated. Conclusions: Large intrafractional organ motion due to respiratory and/or bowel motion is a limiting factor in administering curative radiation doses to pancreatic tumors. The authors investigate the use of real-time ultrasound to track pancreas motion. Due to the poor visibility of the pancreas head on an

Preliminary results on the feasibility of using ultrasound to monitor intrafractional motion during radiation therapy for pancreatic cancer

International Nuclear Information System (INIS)

Omari, Eenas A.; Erickson, Beth; Noid, George; Li, X. Allen; Ehlers, Christopher; Quiroz, Francisco; Cooper, David T.; Lachaine, Martin

2016-01-01

Purpose: Substantial intrafraction organ motion during radiation therapy (RT) for pancreatic cancer is well recognized as a major limiting factor for accurate delivery of RT. The aim of this work is to determine the feasibility of monitoring the intrafractional motion of the pancreas or surrounding structures using ultrasound for RT delivery. Methods: Transabdominal ultrasound (TAUS) and 4DCT data were acquired on ten pancreatic cancer patients during radiation therapy process in a prospective study. In addition, TAUS and MRI were collected for five healthy volunteers. The portal vein (PV) and the head of the pancreas (HP) along with other structures were contoured on these images. Volume changes, distance between the HP and PV, and motion difference between the HP and PV were measured to examine whether PV can be used as a motion surrogate for HP. TAUS images were acquired and processed using a research version of the Clarity autoscan ultrasound system (CAUS). Motion monitoring was performed with the ultrasound probe mounted on an arm fixed to the couch. Video segments of the monitoring sessions were captured. Results: On TAUS, PV is better visualized than HP. The measured mean volume deviation for all patients for the HP and PV was 1.4 and 0.6 ml, respectively. The distance between the HP and PV was close to a constant with 0.22 mm mean deviation throughout the ten breathing phases. The mean of the absolute motion difference for all patients was 1.7 ± 0.8 mm in LR, 1.5 ± 0.5 mm in AP, and 2.3 ± 0.7 mm in SI, suggesting that the PV is a good surrogate for HP motion estimation. By using this surrogate, the HP motion tracking using TAUS was demonstrated. Conclusions: Large intrafractional organ motion due to respiratory and/or bowel motion is a limiting factor in administering curative radiation doses to pancreatic tumors. The authors investigate the use of real-time ultrasound to track pancreas motion. Due to the poor visibility of the pancreas head on an

Synergistic effects of Combined Therapy: nonfocused ultrasound plus Aussie current for noninvasive body contouring

Directory of Open Access Journals (Sweden)

Canela VC

2018-04-01

Full Text Available Vivianne Carvalho Canela,1 Cinthia Nicoletti Crivelaro,1 Luciane Zacchi Ferla,1 Gisele Marques Pelozo,1 Juliana Azevedo,2 Richard Eloin Liebano,3 Caroline Nogueira,4,5 Renata Michelini Guidi,4,5 Clóvis Grecco,4 Estela Sant’Ana4 1Ibramed Center for Education and Advanced Training (CEFAI, Amparo, SP, Brazil; 2CDE Medical Imaging Department, Brazilian College of Radiology (CBR, Amparo, SP, Brazil; 3Department of Physiotherapy, Federal University of São Carlos (UFSCar, São Carlos, SP, Brazil; 4Research, Development and Innovation Department, Ibramed Research Group (IRG, IBRAMED, Amparo, SP, Brazil; 5Biomedical Engineering Department, Faculty of Electrical Engineering and Computing, University of Campinas (UNICAMP, Campinas, SP, Brazil Background and objectives: Nowadays, there are several noninvasive technologies being used for improving of body contouring. The objectives of this pilot study were to verify the effectiveness of the Heccus® device, emphasizing the synergism between nonfocused ultrasound plus Aussie current in the improvement of body contour, and to determine if the association of this therapy with whole-body vibration exercises can have additional positive effects in the results of the treatments.Subjects and methods: Twenty healthy women aged 20–40 years participated in the study. Ten patients received Combined Therapy treatment (G1 and the other 10 participants received Combined Therapy with additional vibratory platform treatment (G2. Anthropometric and standardized photography analysis, ultrasonography, cutometry and self-adminestered questionnaires of tolerance and satisfaction levels with the treatment were used.Results: Compared with baseline values, reduction of fat thickness was observed by ultrasonography in the posterior thigh area in the G1 group (P<0.05 and in the buttocks (P<0.05 and the posterior thigh areas (P<0.05 in the G2. All the treated areas in both groups showed reduction in cellulite degree in the

Ultrasound applicability in Speech Language Pathology and Audiology.

Science.gov (United States)

Barberena, Luciana da Silva; Brasil, Brunah de Castro; Melo, Roberta Michelon; Mezzomo, Carolina Lisbôa; Mota, Helena Bolli; Keske-Soares, Márcia

2014-01-01

To present recent studies that used the ultrasound in the fields of Speech Language Pathology and Audiology, which evidence possibilities of the applicability of this technique in different subareas. A bibliographic research was carried out in the PubMed database, using the keywords "ultrasonic," "speech," "phonetics," "Speech, Language and Hearing Sciences," "voice," "deglutition," and "myofunctional therapy," comprising some areas of Speech Language Pathology and Audiology Sciences. The keywords "ultrasound," "ultrasonography," "swallow," "orofacial myofunctional therapy," and "orofacial myology" were also used in the search. Studies in humans from the past 5 years were selected. In the preselection, duplicated studies, articles not fully available, and those that did not present direct relation between ultrasound and Speech Language Pathology and Audiology Sciences were discarded. The data were analyzed descriptively and classified subareas of Speech Language Pathology and Audiology Sciences. The following items were considered: purposes, participants, procedures, and results. We selected 12 articles for ultrasound versus speech/phonetics subarea, 5 for ultrasound versus voice, 1 for ultrasound versus muscles of mastication, and 10 for ultrasound versus swallow. Studies relating "ultrasound" and "Speech Language Pathology and Audiology Sciences" in the past 5 years were not found. Different studies on the use of ultrasound in Speech Language Pathology and Audiology Sciences were found. Each of them, according to its purpose, confirms new possibilities of the use of this instrument in the several subareas, aiming at a more accurate diagnosis and new evaluative and therapeutic possibilities.

MO-FG-CAMPUS-JeP3-04: Feasibility Study of Real-Time Ultrasound Monitoring for Abdominal Stereotactic Body Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Su, Lin; Kien Ng, Sook; Zhang, Ying; Herman, Joseph; Wong, John; Ding, Kai [Department of Radiation Oncology, John Hopkins University, Baltimore, MD (United States); Ji, Tianlong [Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, Liaoning (China); Iordachita, Iulian [Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD (United States); Tutkun Sen, H.; Kazanzides, Peter; Lediju Bell, Muyinatu A. [Department of Computer Science, Johns Hopkins University, Baltimore, MD (United States)

2016-06-15

Purpose: Ultrasound is ideal for real-time monitoring in radiotherapy with high soft tissue contrast, non-ionization, portability, and cost effectiveness. Few studies investigated clinical application of real-time ultrasound monitoring for abdominal stereotactic body radiation therapy (SBRT). This study aims to demonstrate the feasibility of real-time monitoring of 3D target motion using 4D ultrasound. Methods: An ultrasound probe holding system was designed to allow clinician to freely move and lock ultrasound probe. For phantom study, an abdominal ultrasound phantom was secured on a 2D programmable respiratory motion stage. One side of the stage was elevated than another side to generate 3D motion. The motion stage made periodic breath-hold movement. Phantom movement tracked by infrared camera was considered as ground truth. For volunteer study three healthy subjects underwent the same setup for abdominal SBRT with active breath control (ABC). 4D ultrasound B-mode images were acquired for both phantom and volunteers for real-time monitoring. 10 breath-hold cycles were monitored for each experiment. For phantom, the target motion tracked by ultrasound was compared with motion tracked by infrared camera. For healthy volunteers, the reproducibility of ABC breath-hold was evaluated. Results: Volunteer study showed the ultrasound system fitted well to the clinical SBRT setup. The reproducibility for 10 breath-holds is less than 2 mm in three directions for all three volunteers. For phantom study the motion between inspiration and expiration captured by camera (ground truth) is 2.35±0.02 mm, 1.28±0.04 mm, 8.85±0.03 mm in LR, AP, SI directly, respectively. The motion monitored by ultrasound is 2.21±0.07 mm, 1.32±0.12mm, 9.10±0.08mm, respectively. The motion monitoring error in any direction is less than 0.5 mm. Conclusion: The volunteer study proved the clinical feasibility of real-time ultrasound monitoring for abdominal SBRT. The phantom and volunteer ABC

MO-FG-CAMPUS-JeP3-04: Feasibility Study of Real-Time Ultrasound Monitoring for Abdominal Stereotactic Body Radiation Therapy

International Nuclear Information System (INIS)

Su, Lin; Kien Ng, Sook; Zhang, Ying; Herman, Joseph; Wong, John; Ding, Kai; Ji, Tianlong; Iordachita, Iulian; Tutkun Sen, H.; Kazanzides, Peter; Lediju Bell, Muyinatu A.

2016-01-01

Purpose: Ultrasound is ideal for real-time monitoring in radiotherapy with high soft tissue contrast, non-ionization, portability, and cost effectiveness. Few studies investigated clinical application of real-time ultrasound monitoring for abdominal stereotactic body radiation therapy (SBRT). This study aims to demonstrate the feasibility of real-time monitoring of 3D target motion using 4D ultrasound. Methods: An ultrasound probe holding system was designed to allow clinician to freely move and lock ultrasound probe. For phantom study, an abdominal ultrasound phantom was secured on a 2D programmable respiratory motion stage. One side of the stage was elevated than another side to generate 3D motion. The motion stage made periodic breath-hold movement. Phantom movement tracked by infrared camera was considered as ground truth. For volunteer study three healthy subjects underwent the same setup for abdominal SBRT with active breath control (ABC). 4D ultrasound B-mode images were acquired for both phantom and volunteers for real-time monitoring. 10 breath-hold cycles were monitored for each experiment. For phantom, the target motion tracked by ultrasound was compared with motion tracked by infrared camera. For healthy volunteers, the reproducibility of ABC breath-hold was evaluated. Results: Volunteer study showed the ultrasound system fitted well to the clinical SBRT setup. The reproducibility for 10 breath-holds is less than 2 mm in three directions for all three volunteers. For phantom study the motion between inspiration and expiration captured by camera (ground truth) is 2.35±0.02 mm, 1.28±0.04 mm, 8.85±0.03 mm in LR, AP, SI directly, respectively. The motion monitored by ultrasound is 2.21±0.07 mm, 1.32±0.12mm, 9.10±0.08mm, respectively. The motion monitoring error in any direction is less than 0.5 mm. Conclusion: The volunteer study proved the clinical feasibility of real-time ultrasound monitoring for abdominal SBRT. The phantom and volunteer ABC

Feasibility study of local ultrasound hyperthermia in cancer therapy

International Nuclear Information System (INIS)

Jones, K.G.; Straube, W.; Emami, B.; Perez, C.A.

1987-01-01

This paper describes a retrospective analysis of patients treated at Washington University for recurrent or persistent cancer with Ultrasound Hyperthermia between October 1984 and June 1986. Fifteen of 102 lesions were treated during this time period with Ultrasound Hyperthermia instead of microwave hyperthermia due to the size of the lesion needing heat at depths greater than 4 cm. Also, the patients' lesion could not be implanted for interstitial microwave hyperthermia. Fourteen of the treated patients received concomitant radiotherapy, while one received concomitant Bleomycin. There were 79 total hyperthermia treatments delivered, of which 67 achieved a therapeutic temperature of 43 0 C for 60 minutes. During 15/79 treatments, patients experienced pain; of which 11/15 lead to poor heating. Only one treatment of the twelve poor treatments was secondary to technical difficulties. Complete local control was accomplished in seven patients, a partial response in four patients. The results of therapeutic heating and its relationship to the site of treatment and local control are presented, along with phantom studies of Ultrasound microwave hyperthermia reemphasizing the feasibility of using Ultrasound Hyperthermia

A case of lung adenocarcinoma with multiple intracranial hemorrhages of brain metastases after whole-brain radiation therapy

International Nuclear Information System (INIS)

Nakamichi, Shinji; Hirano, Satoshi; Asao, Tetsuhiko; Takeda, Yuichiro; Sugiyama, Haruhito; Kobayashi, Nobuyuki

2011-01-01

Whole-brain radiation therapy (WBRT) is widely applied in cases of brain metastases of non-small cell lung cancer (NSCLC). However, there are few case reports on hemorrhages of brain metastases occurring after WBRT. A 63-year-old woman was given a diagnosis of stage IV (T4N0M1b) lung adenocarcinoma about 4 years previously, and received chemotherapy regimens and gamma knife radiosurgery. However, her brain metastases exacerbated and she received WBRT in November 2010 and docetaxel monotherapy in December 2010. Two weeks after completing WBRT, she experienced dysarthria and an MRI showed multiple hemorrhages within brain metastases. Over a period of careful observation, these hemorrhages repeatedly alternated between improvement and exacerbation. Radiotherapy for metastatic brain tumors is considered to suppress hemorrhagic events of brain metastases. However, multiple intracranial hemorrhages of brain metastases occurred after WBRT in the present case. The accumulation of further studies of similar cases is necessary to identify the exact mechanism of these hemorrhages. (author)

SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Obeid, L; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Rhone-Alpes (France); Tessier, A [Centre Hospitalier Universitaire, La Tronche, Rhone-Alpes (France); Vautrin, M; Benkebil, M [DOSIsoft, Cachan, Ile de France (France); Sihanath, R [Centre Hospitalier Universitaire, La Tronche, Rhone- Alpes (France)

2014-06-01

Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator) were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.

Tanscranial Threshold of Inertial Cavitation Induced by Diagnosticc Ultrasound and Microbubbles

NARCIS (Netherlands)

Liu, J.; Gao, S.; Porter, T.R.; Everbach, C; Shi, W.; Vignon, F.; Powers, J.; Lof, J.; Turner, J.; Xie, F.

2011-01-01

Background: Inertial cavitation may cause hazardous bioeffects whileusing ultrasound and microbubble mediated thrombolysis. The purposeof this study was to investigate the influence of ultrasound pulselength and temporal bone on inertial cavitation thresholds within the brain utilizing transtemporal

Brain MRS glutamine as a biomarker to guide therapy of hyperammonemic coma.

Science.gov (United States)

O'Donnell-Luria, Anne H; Lin, Alexander P; Merugumala, Sai K; Rohr, Frances; Waisbren, Susan E; Lynch, Rebecca; Tchekmedyian, Vatche; Goldberg, Aaron D; Bellinger, Andrew; McFaline-Figueroa, J Ricardo; Simon, Tracey; Gershanik, Esteban F; Levy, Bruce D; Cohen, David E; Samuels, Martin A; Berry, Gerard T; Frank, Natasha Y

2017-05-01

Acute idiopathic hyperammonemia in an adult patient is a life-threatening condition often resulting in a rapid progression to irreversible cerebral edema and death. While ammonia-scavenging therapies lower blood ammonia levels, in comparison, clearance of waste nitrogen from the brain may be delayed. Therefore, we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine levels, the major reservoir of ammonia, in a gastric bypass patient with hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia-scavenging agents, sodium phenylacetate and sodium benzoate. Improvement in mental status mirrored brain glutamine levels, as coma persisted for 48h after plasma ammonia normalized. We hypothesize that the slower clearance for brain glutamine levels accounts for the delay in improvement following initiation of treatment in cases of chronic hyperammonemia. We propose MRS to monitor brain glutamine as a noninvasive approach to be utilized for diagnostic and therapeutic monitoring purposes in adult patients presenting with idiopathic hyperammonemia. Copyright © 2017 Elsevier Inc. All rights reserved.

MRI T2 relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy

OpenAIRE

Kunigiri, Girish; Jayakumar, P. N.; Janakiramaiah, N.; Gangadhar, B. N.

2007-01-01

Background: Although electroconvulsive therapy (ECT) causes no structural brain damage, recent studies reported altered brain perfusion acutely following ECT. This is in keeping with brain edema which was noted in animal experiments following electroconvulsive shock. Aim: This study examined alteration in magnetic resonance imaging (MRI) T2 relaxation time, a measure of brain edema, and its relation to therapeutic efficacy, orientation and memory impairment with ECT. Materials and Methods: Fi...

Exercise therapy in multiple sclerosis and its effects on function and the brain

DEFF Research Database (Denmark)

Dalgas, Ulrik

2017-01-01

to clinically relevant improvements in physical function, but should be considered an adjunct to specific task-based training. Exercise has also shown positive effects on the brain, including improvements in brain volume and cognition. In summary, exercise therapy is a safe and potent nonpharmacological...... intervention in MS, with beneficial effects on both functional capacity and the brain....

Boron neutron capture therapy: Brain Tumor Treatment Evaluation Program

International Nuclear Information System (INIS)

Griebenow, M.L.; Dorn, R.V. III; Gavin, P.R.; Spickard, J.H.

1988-01-01

The United States (US) Department of Energy (DOE) recently initiated a focused, multidisciplined program to evaluate Boron Neutron Capture Therapy (BNCT) for the treatment of brain tumors. The program, centered at the DOE/endash/Idaho National Engineering Laboratory (INEL), will develop the analytical, diagnostic and treatment tools, and the database required for BNCT technical assessment. The integrated technology will be evaluated in a spontaneously-occurring canine brain-tumor model. Successful animal studies are expected to lead to human clinical trials within four to five years. 2 refs., 3 figs

Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

Science.gov (United States)

Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

2014-02-01

Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

Submicron-bubble-enhanced focused ultrasound for blood-brain barrier disruption and improved CNS drug delivery.

Directory of Open Access Journals (Sweden)

Ching-Hsiang Fan

Full Text Available The use of focused ultrasound (FUS with microbubbles has been proven to induce transient blood-brain barrier opening (BBB-opening. However, FUS-induced inertial cavitation of microbubbles can also result in erythrocyte extravasations. Here we investigated whether induction of submicron bubbles to oscillate at their resonant frequency would reduce inertial cavitation during BBB-opening and thereby eliminate erythrocyte extravasations in a rat brain model. FUS was delivered with acoustic pressures of 0.1-4.5 MPa using either in-house manufactured submicron bubbles or standard SonoVue microbubbles. Wideband and subharmonic emissions from bubbles were used to quantify inertial and stable cavitation, respectively. Erythrocyte extravasations were evaluated by in vivo post-treatment magnetic resonance susceptibility-weighted imaging, and finally by histological confirmation. We found that excitation of submicron bubbles with resonant frequency-matched FUS (10 MHz can greatly limit inertial cavitation while enhancing stable cavitation. The BBB-opening was mainly caused by stable cavitation, whereas the erythrocyte extravasation was closely correlated with inertial cavitation. Our technique allows extensive reduction of inertial cavitation to induce safe BBB-opening. Furthermore, the safety issue of BBB-opening was not compromised by prolonging FUS exposure time, and the local drug concentrations in the brain tissues were significantly improved to 60 times (BCNU; 18.6 µg versus 0.3 µg by using chemotherapeutic agent-loaded submicron bubbles with FUS. This study provides important information towards the goal of successfully translating FUS brain drug delivery into clinical use.

Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

Science.gov (United States)

Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

2014-01-01

Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

Directory of Open Access Journals (Sweden)

Vera ePaefgen

2015-09-01

Full Text Available Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given.

Blood-Brain Barrier Opening in Behaving Non-Human Primates via Focused Ultrasound with Systemically Administered Microbubbles

Science.gov (United States)

Downs, Matthew E.; Buch, Amanda; Karakatsani, Maria Eleni; Konofagou, Elisa E.; Ferrera, Vincent P.

2015-10-01

Over the past fifteen years, focused ultrasound coupled with intravenously administered microbubbles (FUS) has been proven an effective, non-invasive technique to open the blood-brain barrier (BBB) in vivo. Here we show that FUS can safely and effectively open the BBB at the basal ganglia and thalamus in alert non-human primates (NHP) while they perform a behavioral task. The BBB was successfully opened in 89% of cases at the targeted brain regions of alert NHP with an average volume of opening 28% larger than prior anesthetized FUS procedures. Safety (lack of edema or microhemorrhage) of FUS was also improved during alert compared to anesthetized procedures. No physiological effects (change in heart rate, motor evoked potentials) were observed during any of the procedures. Furthermore, the application of FUS did not disrupt reaching behavior, but in fact improved performance by decreasing reaction times by 23 ms, and significantly decreasing touch error by 0.76 mm on average.

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.

Science.gov (United States)

Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

2017-07-01

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

Directory of Open Access Journals (Sweden)

Cuiyuan Huang

2017-07-01

Full Text Available Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

Energy Technology Data Exchange (ETDEWEB)

Lee, Seung Heon; Lee, Kyu Chan; Choi, Jin Ho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yun Mi [Gachon University Gil Hospital, Incheon (Korea, Republic of)

2012-06-15

To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Nine patients with multiple ({>=}4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10- 12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

Children's (Pediatric) Abdominal Ultrasound Imaging

Medline Plus

Full Text Available ... young children. It is also valuable for evaluating the brain, spinal cord and hip joints in newborns and infants. Risks For standard diagnostic ultrasound , there are no known harmful effects on humans. top of page What are the limitations of ...

Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

Science.gov (United States)

Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

2012-01-01

Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia. PMID:25337108

Occupational therapy in patients after the brain injury with neglect syndrome

OpenAIRE

Říhová, Petra

2015-01-01

OF BACHELOR THESIS Title of bachelor thesis: Occupational therapy in patients after the brain injury with neglect syndrome This bachelor thesis is focused on summarizing the knowledge of the neglect syndrome, very interesting phenomenon accompanying brain injury. Thesis provides information about prevalence, etiopathogenesis, classification, clinical presentation and course of the disease. Special attention is devoted to diagnostic and therapeutic procedures and description of occupational th...

Management of melanoma brain metastases in the era of targeted therapy.

Science.gov (United States)

Shapiro, Daniela Gonsalves; Samlowski, Wolfram E

2011-01-01

Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy." These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

Management of Melanoma Brain Metastases in the Era of Targeted Therapy

International Nuclear Information System (INIS)

Shapiro, D. G.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.

2011-01-01

Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy."These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

Ultrasound motion tracking for radiation therapy; Ultraschallbewegungstracking fuer die Strahlentherapie

Energy Technology Data Exchange (ETDEWEB)

Jenne, J. [Fraunhofer-Institut fuer Bildgestuetzte Medizin MEVIS, Bremen (Germany); Mediri GmbH, Heidelberg (Germany); Schwaab, J. [Mediri GmbH, Heidelberg (Germany)

2015-11-15

In modern radiotherapy the radiation dose can be applied with an accuracy in the range of 1-2 mm provided that the exact position of the target is known. If, however, the target (the tumor) is located in the lungs or the abdomen, respiration or peristalsis can cause substantial movement of the target. Various methods for intrafractional motion detection and compensation are currently under consideration or are already applied in clinical practice. Sonography is one promising option, which is now on the brink of clinical implementation. Ultrasound is particularly suited for this purpose due to the high soft tissue contrast, real-time capability, the absence of ionizing radiation and low acquisition costs. Ultrasound motion tracking is an image-based approach, i.e. the target volume or an adjacent structure is directly monitored and the motion is tracked automatically on the ultrasound image. Diverse algorithms are presently available that provide the real-time target coordinates from 2D as well as 3D images. Definition of a suitable sonographic window is not, however, trivial and a gold standard for positioning and mounting of the transducer has not yet been developed. Furthermore, processing of the coordinate information in the therapy unit and the dynamic adaptation of the radiation field are challenging tasks. It is not clear whether ultrasound motion tracking will become established in the clinical routine although all technical prerequisites can be considered as fulfilled, such that exciting progress in this field of research is still to be expected. (orig.) [German] In der modernen Strahlentherapie kann die Dosis mit einer Genauigkeit von 1-2 mm appliziert werden, sofern die Position der Zielstruktur genau bekannt ist. Liegt diese Zielstruktur (der Tumor) jedoch in der Lunge oder im Abdomen, koennen u. a. die Atmung oder die Peristaltik zu einer substanziellen Bewegung des Zielvolumens fuehren. Verschiedene Methoden zur intrafraktionellen Bewegungsdetektion

MRI tracing non-invasive TiO2-based nanoparticles activated by ultrasound for multi-mechanism therapy of prostatic cancer

Science.gov (United States)

Yuan, Pu; Song, Dongkui

2018-03-01

To reduce the side effects of chemotherapy and achieve effective and safe therapy for prostate cancer, herein a simple but multi-functional TiO2:Gd@DOX/FA system activated by ultrasound was developed for the MRI-guided multi-mechanism therapy of prostate cancer. TiO2 nanoparticles served as a sonosensitizer as well as a nanocarrier with the pH-responsive release of DOX. The doping of Gd was not only able to endow the TiO2 with magnetic resonance imaging (MRI) ability, but also further improve the sonodynamic ability of the TiO2. The characterization of the as-prepared TiO2:Gd@DOX/FA showed sensitive pH-responsive drug release, high reactive oxygen species (ROS) production, T 1-MRI contrast performance and excellent biocompatibility. The cytotoxicity assay in vitro showed cell death up to 91.68% after 48 h incubation induced by the TiO2:Gd@DOX + ultrasound group. Meanwhile, in the in vivo synergistic therapy studies, the tumor sizes of all the nanomedicine groups were smaller than for the free DOX (V:V 0 = 4.2). More importantly, the body showed nearly no weight loss. This safety was also confirmed by the H&E staining, biodistribution experiment and serum biochemistry results. Altogether, TiO2:Gd@DOX/FA significantly reduced the side effects of DOX, augmented the levels of ROS and achieved effective and safe therapy, indicating its potential for the multi-mechanism therapy of prostate cancer. There is no conflict of interest in this study and no funding has been received for it. We received the approval of the Research Ethics Committee before conducting this study.

Dose-volume considerations in stereotaxic brain radiation therapy

International Nuclear Information System (INIS)

Houdek, P.V.; Schwade, J.G.; Pisciotta, V.J.; Medina, A.J.; Lewin, A.A.; Abitbol, A.A.; Serago, C.F.

1988-01-01

Although brain radiation therapy experience suggests that a gain in the therapeutic ratio may be achieved by optimizing the dose-volume relationship, no practical system for quantitative assessment of dose-volume data has been developed. This presentation describes the rationale for using the integral dose function for this purpose and demonstrates that with the use of a conventional treatment planning computer and a series of computed tomographic scans, first-order optimization of the dose-volume function can be accomplished in two steps: first, high-dose volume is minimized by selecting an appropriate treatment technique and tumor margin, and then dosage is maximized by calculating the brain tolerance dose as a function of the irradiated volume

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

OpenAIRE

Zhou Weihua; Mukherjee Purna; Kiebish Michael A; Markis William T; Mantis John G; Seyfried Thomas N

2007-01-01

Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and su...

Possible alternation of the blood-brain barrier by boron-neutron capture therapy

International Nuclear Information System (INIS)

Hatanaka, H.; Moritani, M.; Camillo, M.

1991-01-01

In the course of re-assessment of boron-neutron capture therapy (BNCT) for malignant brain tumors, fractionation of neutron irradiation has been proposed. The authors have used BNCT with a single fraction technique during the past 21 years and now decided to study some effects of fractionation. Twenty-two healthy mouse brains were irradiated with thermal neutrons after boron-10 injection (mercaptoundecahydrododecaborate). A second dose of boron-10 was administered and its uptake in the boron-neutron-capture-irradiated brains was determined. A tendency towards increased boron uptake in the moderately BNCT-treated brains was noticed, which may result in increased brain damage if fractionated neutron irradiation is used. (orig.)

Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Zamenhof, R.G.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Clement, S.D.; Harling, O.K.; Yanch, J.C.

1990-01-01

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated

Low-frequency quantitative ultrasound imaging of cell death in vivo

International Nuclear Information System (INIS)

Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J.; Papanicolau, Naum; Tadayyon, Hadi; Lee, Justin; Zubovits, Judit; Sadeghian, Alireza; Karshafian, Raffi; Al-Mahrouki, Azza; Giles, Anoja; Kolios, Michael C.

2013-01-01

Purpose: Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models.Methods: Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy.Results: Ultrasound-based spectroscopic biomarkers indicated significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r 2 = 0.71, 0.82; p < 0.001).Conclusions: In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant frequency, in

Low-frequency quantitative ultrasound imaging of cell death in vivo

Energy Technology Data Exchange (ETDEWEB)

Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J. [Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Papanicolau, Naum; Tadayyon, Hadi [Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Lee, Justin [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Zubovits, Judit [Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Sadeghian, Alireza [Department of Computer Science, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Karshafian, Raffi [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Al-Mahrouki, Azza; Giles, Anoja [Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Kolios, Michael C. [Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada and Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada)

2013-08-15

Purpose: Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models.Methods: Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy.Results: Ultrasound-based spectroscopic biomarkers indicated significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r{sup 2}= 0.71, 0.82; p < 0.001).Conclusions: In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant frequency

Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

Science.gov (United States)

Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

2015-03-01

There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

Children's (Pediatric) Abdominal Ultrasound Imaging

Medline Plus

Full Text Available ... particularly valuable for evaluating abdominal, pelvic or scrotal pain in young children. It is also valuable for evaluating the brain, spinal cord and hip joints in newborns and infants. Risks For standard diagnostic ultrasound , there are no known harmful effects on ...

SU-E-J-114: Towards Integrated CT and Ultrasound Guided Radiation Therapy Using A Robotic Arm with Virtual Springs

Energy Technology Data Exchange (ETDEWEB)

Ding, K; Zhang, Y; Sen, H; Lediju Bell, M; Goldstein, S; Kazanzides, P; Iordachita, I; Wong, J [Johns Hopkins University, Baltimore, MD (United States)

2014-06-01

Purpose: Currently there is an urgent need in Radiation Therapy for noninvasive and nonionizing soft tissue target guidance such as localization before treatment and continuous monitoring during treatment. Ultrasound is a portable, low cost option that can be easily integrated with the LINAC room. We are developing a cooperatively controlled robot arm that has high intrafraction reproducibility with repositioning of the ultrasound probe. In this study, we introduce virtual springs (VS) to assist with interfraction probe repositioning and we compare the soft tissue deformation introduced by VS to the deformation that would exist without them. Methods: Three metal markers were surgically implanted in the kidney of one dog. The dog was anesthetized and immobilized supine in an alpha cradle. The reference ultrasound probe position and force to ideally visualize the kidney was defined by an experienced ultrasonographer using the Clarity ultrasound system and robot sensor. For each interfraction study, the dog was removed from the cradle and re-setup based on CBCT with bony anatomy alignment to mimic regular patient setup. The ultrasound probe was automatically returned to the reference position using the robot. To accommodate the soft tissue anatomy changes between each setup the operator used the VS feature to adjust the probe and obtain an ultrasound image that matched the reference image. CBCT images were acquired and each interfraction marker location was compared with the first interfraction Result. Results: Analysis of the marker positions revealed that the kidney was displaced by 18.8 ± 6.4 mm without VS and 19.9 ± 10.5 mm with VS. No statistically significant differences were found between two procedures. Conclusion: The VS feature is necessary to obtain matching ultrasound images, and they do not introduce further changes to the tissue deformation. Future work will focus on automatic VS based on ultrasound feedback. Supported in part by: NCI R01 CA161613

SU-E-J-114: Towards Integrated CT and Ultrasound Guided Radiation Therapy Using A Robotic Arm with Virtual Springs

International Nuclear Information System (INIS)

Ding, K; Zhang, Y; Sen, H; Lediju Bell, M; Goldstein, S; Kazanzides, P; Iordachita, I; Wong, J

2014-01-01

Purpose: Currently there is an urgent need in Radiation Therapy for noninvasive and nonionizing soft tissue target guidance such as localization before treatment and continuous monitoring during treatment. Ultrasound is a portable, low cost option that can be easily integrated with the LINAC room. We are developing a cooperatively controlled robot arm that has high intrafraction reproducibility with repositioning of the ultrasound probe. In this study, we introduce virtual springs (VS) to assist with interfraction probe repositioning and we compare the soft tissue deformation introduced by VS to the deformation that would exist without them. Methods: Three metal markers were surgically implanted in the kidney of one dog. The dog was anesthetized and immobilized supine in an alpha cradle. The reference ultrasound probe position and force to ideally visualize the kidney was defined by an experienced ultrasonographer using the Clarity ultrasound system and robot sensor. For each interfraction study, the dog was removed from the cradle and re-setup based on CBCT with bony anatomy alignment to mimic regular patient setup. The ultrasound probe was automatically returned to the reference position using the robot. To accommodate the soft tissue anatomy changes between each setup the operator used the VS feature to adjust the probe and obtain an ultrasound image that matched the reference image. CBCT images were acquired and each interfraction marker location was compared with the first interfraction Result. Results: Analysis of the marker positions revealed that the kidney was displaced by 18.8 ± 6.4 mm without VS and 19.9 ± 10.5 mm with VS. No statistically significant differences were found between two procedures. Conclusion: The VS feature is necessary to obtain matching ultrasound images, and they do not introduce further changes to the tissue deformation. Future work will focus on automatic VS based on ultrasound feedback. Supported in part by: NCI R01 CA161613

The effect of androgen deprivation on the early changes in prostate volume following transperineal ultrasound guided interstitial therapy for localized carcinoma of the prostate

Energy Technology Data Exchange (ETDEWEB)

Whittington, Richard; Broderick, Gregory A; Arger, Peter; Malkowicz, S Bruce; Epperson, Robert D; Arjomandy, Bijan; Kassaee, Alireza

1999-07-15

Purpose: To determine the change in volume of the prostate as a result of neoadjuvant androgen deprivation prior to prostate implant and in the early postimplant period following transperineal ultrasound guided palladium-103 brachytherapy for early-stage prostate cancer. Methods and Materials: Sixty-nine men received 3 to 6 months of androgen deprivation therapy followed by treatment planning ultrasound followed 4 to 8 weeks later by palladium-103 implant of the prostate. All patients had clinical and radiographic stage T1c-T2b adenocarcinoma of the prostate. A second ultrasound study was carried out 11 to 13 days following the implant to determine the change in volume of the prostate as a result of the implant. The prehormonal and preimplant volumes were compared to the postimplant volume to determine the effect of hormones and brachytherapy on prostate volume. Results: The median decrease in prostate volume as a result of androgen deprivation was 33% among the 54 patients with prostate volume determinations prior to hormonal therapy. The reduction in volume was greatest in the quartile of men with the largest initial gland volume (59%) and least in the quartile of men with smallest glands (10%). The median reduction in prostate volume between the treatment planning ultrasound and the follow-up study after implant was 3%, but 23 (33%) patients had an increase in prostate volume, including 16 (23%) who had an increase in volume >20%; 11 of these patients (16%) had an increase in volume >30%. The time course of development and resolution of this edema is not known. The severity of the edema was not related to initial or preimplant prostate volume or duration of hormonal therapy. Conclusions: Prostate edema may significantly affect the dose delivered to the prostate following transperineal ultrasound guided brachytherapy. The effect on the actual delivered dose will be greater when shorter lived isotopes are used. It remains to be observed whether this edema will

Music Therapy, Acquired Brain Injury and Interpersonal Communication Competencies

DEFF Research Database (Denmark)

Hald, Søren

2012-01-01

that music is a useful tool to stimulate interaction since musical interaction can be engaged at almost any cognitive and physical level and still be meaningful (Baker & Tamplin, 2006; Gilbertson, 2005; Hald, 2011). In addition, music therapy researchers specialising in ABI have found that: - Music therapy......Acquired brain injury (ABI) often affects physical, cognitive and psychological aspects of a person's functioning (Bateman, et al., 2010). Psychosocial problems associated with ABI may be the major challenge facing the rehabilitation process (Morton & Wehman, 1995) Consequently, interventions...... is a powerful means to improve communication, general behavior, and musical behavior (Purdie, Hamilton & Baldwin, 1997). - Music therapy can increase emotional stability, clarify thoughts, stimulate spontaneous interaction, and increase motivation and cooperation (Nayak, Wheeler, Shiflett & Agostinelli, 2000...

Focused ultrasound-facilitated brain drug delivery using optimized nanodroplets: vaporization efficiency dictates large molecular delivery

Science.gov (United States)

Wu, Shih-Ying; Fix, Samantha M.; Arena, Christopher B.; Chen, Cherry C.; Zheng, Wenlan; Olumolade, Oluyemi O.; Papadopoulou, Virginie; Novell, Anthony; Dayton, Paul A.; Konofagou, Elisa E.

2018-02-01

Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization with potentially improved in vivo stability, drug payload, and minimal interference outside of the focal zone compared with microbubbles. While the feasibility of blood-brain barrier (BBB) opening using nanodroplets has been previously reported, characterization of the associated delivery has not been achieved. It was hypothesized that the outcome of drug delivery was associated with the droplet’s sensitivity to acoustic energy, and can be modulated with the boiling point of the liquid core. Therefore, in this study, octafluoropropane (OFP) and decafluorobutane (DFB) nanodroplets were used both in vitro for assessing their relative vaporization efficiency with high-speed microscopy, and in vivo for delivering molecules with a size relevant to proteins (40 kDa dextran) to the murine brain. It was found that at low pressures (300-450 kPa), OFP droplets vaporized into a greater number of microbubbles compared to DFB droplets at higher pressures (750-900 kPa) in the in vitro study. In the in vivo study, successful delivery was achieved with OFP droplets at 300 kPa and 450 kPa without evidence of cavitation damage using ¼ dosage, compared to DFB droplets at 900 kPa where histology indicated tissue damage due to inertial cavitation. In conclusion, the vaporization efficiency of nanodroplets positively impacted the amount of molecules delivered to the brain. The OFP droplets due to the higher vaporization efficiency served as better acoustic agents to deliver large molecules efficiently to the brain compared with the DFB droplets.

Effects of hormone therapy on brain structure

OpenAIRE

Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay

2016-01-01

Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42?56 years, within 5?36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 ?g/d transdermal 17?-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active ...

Quantitative head ultrasound measurements to determine thresholds for preterm neonates requiring interventional therapies following intraventricular hemorrhage

Science.gov (United States)

Kishimoto, Jessica; Fenster, Aaron; Salehi, Fateme; Romano, Walter; Lee, David S. C.; de Ribaupierre, Sandrine

2016-04-01

Dilation of the cerebral ventricles is a common condition in preterm neonates with intraventricular hemorrhage (IVH). This post hemorrhagic ventricle dilation (PHVD) can lead to lifelong neurological impairment through ischemic injury due to increased intracranial pressure and without treatment, can lead to death. Clinically, 2D ultrasound (US) through the fontanelles ('soft spots') of the patients are serially acquired to monitor the progression of the ventricle dilation. These images are used to determine when interventional therapies such as needle aspiration of the built up cerebrospinal fluid (CSF) ('ventricle tap', VT) might be indicated for a patient; however, quantitative measurements of the growth of the ventricles are often not performed. There is no consensus on when a neonate with PHVD should have an intervention and often interventions are performed after the potential for brain damage is quite high. Previously we have developed and validated a 3D US system to monitor the progression of ventricle volumes (VV) in IVH patients. We will describe the potential utility of quantitative 2D and 3D US to monitor and manage PHVD in neonates. Specifically, we will look to determine image-based measurement thresholds for patients who will require VT in comparison to patients with PHVD who resolve without intervention. Additionally, since many patients who have an initial VT will require subsequent interventions, we look at the potential for US to determine which PHVD patients will require additional VT after the initial one has been performed.

Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

International Nuclear Information System (INIS)

Ebi, Junko; Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio

2013-01-01

Purpose: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. Methods and Materials: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. Results: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). Conclusions: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients

Gallbladder ascariasis in Kosovo - focus on ultrasound and conservative therapy: a case series.

Science.gov (United States)

Ismaili-Jaha, Vlora; Toro, Halim; Spahiu, Lidvana; Azemi, Mehmedali; Hoxha-Kamberi, Teuta; Avdiu, Muharrem; Spahiu-Konjusha, Shqipe; Jaha, Luan

2018-01-13

Ascaris lumbricoides is one of the most common intestinal infections in developing countries, including Kosovo. In contrast to migration to the bile duct, migration of the worm to the gallbladder, due to the narrow and tortuous nature of the cystic duct, is rare. When it does occur, it incites acalculous cholecystitis. This case series describes a 16-month-old Albanian girl, a 22-month-old Albanian girl, a 4-year-old Albanian girl, and a 10-year-old Albanian boy. Here we report our experience with gallbladder ascariasis including clinical manifestations, diagnostic procedures, and treatment. Fever, diarrhea and vomiting, dehydration, pale appearance, and weakness were the manifestations of the primary disease. In all patients, a physical examination revealed reduced turgor and elasticity of the skin. Abdomen was at the level of the chest, soft, with minimal palpatory pain. The liver and spleen were not palpable. A laboratory examination was not specific except for eosinophilia. There were no pathogenic bacteria in coproculture but Ascaris was found in all patients. At an ultrasound examination in all cases we found single, long, linear echogenic structure without acoustic shadowing containing a central, longitudinal anechoic tube with characteristic movement within the gallbladder. Edema of the gallbladder wall was suggestive of associated inflammation. There were no other findings on adjacent structures and organs. All patients received mebendazole 100 mg twice a day for 3 days. They also received symptomatic therapy for gastroenteritis. Because of elevated markers of inflammation all patients were treated with antibiotics, assuming acute cholecystitis, although ultrasound was able to confirm cholecystitis in only two of our four patients. Since the length of stay was dependent on the primary pathology it was 7 to 10 days. At control ultrasounds on 14th day, third and sixth month, all patients were free of ascariasis. Gallbladder ascariasis should be considered in

Brain expansion in patients with type II diabetes following insulin therapy: a preliminary study with longitudinal voxel-based morphometry.

Science.gov (United States)

Chen, Zhiye; Li, Jinfeng; Sun, Jie; Ma, Lin

2014-01-01

We performed a longitudinal analysis based on magnetic resonance (MR) imaging to investigate the brain structural and perfusion changes caused by insulin therapy in patients with type II diabetes. High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo images and flow-sensitive alternating inversion recovery (FAIR) images were obtained from 11 patients with type II diabetes before and 1 year after initiation of insulin therapy and 11 normal controls. Brain volume changes were investigated by a longitudinal voxel-based morphometry (VBM), and perfusion changes were evaluated by FAIR imaging between baseline and follow-up data. Significant regional gray matter (GM) expansion located in bilateral frontal, parietal, and left occipital lobes, and regional white matter (WM) expansion was shown in left precentral subcortical WM and right angular subcortical WM after insulin therapy (P Brain hyperperfusion was detected in bilateral frontal cortex, left occipital cortex, and right temporal cortex after insulin therapy (P brain expansion and hyperperfusion were demonstrated 1 year after initiation of insulin therapy, and insulin therapy could contribute to the brain volume gainment in the patients with type II diabetes. Copyright © 2013 by the American Society of Neuroimaging.

Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

Science.gov (United States)

Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

2013-12-28

Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

Constraint-induced movement therapy for children with acquired brain injury

DEFF Research Database (Denmark)

Schmidt Pedersen, Kristina; Pallesen, H.; Kristensen, H. K.

2016-01-01

An estimated 125-137 Danish children with acquired brain injury (ABI) require rehabilitation annually, 30-40 of these at a highly specialized level. Constraint-induced movement therapy (CIMT) has shown significant effects in increasing function in children with cerebral palsy. More knowledge of h...

Effectiveness of Animal Assisted Therapy after brain injury: A bridge to improved outcomes in CRT.

Science.gov (United States)

Stapleton, Mary

2016-06-18

Animal Assisted Therapy (AAT) has been widely used as a complementary therapy in mental health treatment especially to remediate social skill deficits. The goal of AAT is to improve social, emotional, and cognitive functioning. The purpose of this article is to draw upon the literature on AAT and explore specific applications to cognitive rehabilitation therapy (CRT) and social skills training. This study provides a systematic review of most of the available literature on ATT and assesses that potential uses of ATT for brain injury rehabilitation. Although the efficacy of AAT is not currently well documented by rigorous research, (Kazin, 2010) anecdotal evidence suggests that brain injury survivors may benefit from the combination of AAT and cognitive rehabilitation techniques. Acquired Brain Injury (ABI) survivors with cognitive impairments can benefit from AAT as part of a comprehensive and holistic rehabilitation treatment plan.

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

Science.gov (United States)

Sanchez-Martin, Manuel

2008-09-01

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

An Experimental Protocol for Assessing the Performance of New Ultrasound Probes Based on CMUT Technology in Application to Brain Imaging.

Science.gov (United States)

Matrone, Giulia; Ramalli, Alessandro; Savoia, Alessandro Stuart; Quaglia, Fabio; Castellazzi, Gloria; Morbini, Patrizia; Piastra, Marco

2017-09-24

The possibility to perform an early and repeatable assessment of imaging performance is fundamental in the design and development process of new ultrasound (US) probes. Particularly, a more realistic analysis with application-specific imaging targets can be extremely valuable to assess the expected performance of US probes in their potential clinical field of application. The experimental protocol presented in this work was purposely designed to provide an application-specific assessment procedure for newly-developed US probe prototypes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology in relation to brain imaging. The protocol combines the use of a bovine brain fixed in formalin as the imaging target, which ensures both realism and repeatability of the described procedures, and of neuronavigation techniques borrowed from neurosurgery. The US probe is in fact connected to a motion tracking system which acquires position data and enables the superposition of US images to reference Magnetic Resonance (MR) images of the brain. This provides a means for human experts to perform a visual qualitative assessment of the US probe imaging performance and to compare acquisitions made with different probes. Moreover, the protocol relies on the use of a complete and open research and development system for US image acquisition, i.e. the Ultrasound Advanced Open Platform (ULA-OP) scanner. The manuscript describes in detail the instruments and procedures involved in the protocol, in particular for the calibration, image acquisition and registration of US and MR images. The obtained results prove the effectiveness of the overall protocol presented, which is entirely open (within the limits of the instrumentation involved), repeatable, and covers the entire set of acquisition and processing activities for US images.

Dependence of the effectiveness of thrombolytic therapy at ischemic stroke from clinical and paraclinical predictors

Directory of Open Access Journals (Sweden)

Іванна Михайлівна Мельнічек

2015-12-01

Full Text Available The aim of the work. The aim of the work is an assessment of informativeness of several clinical and paraclinical predictors in prognostics of the results of effectiveness of thrombolytic therapy at the most acute period of ishemic stroke with the further definition of the most significant ones for achieving the least neurologic deficiency.Methods of research: There were retrospectively considered 61 patients 60,5±7,8 years old with ishemic stroket who sucsessfully underwent thrombolytic therapy as an intravenous administration of Actilyse. These patients demonstrated the next factors of gemostasis: prothrombin time, prothrombin index, fibrinogen. For the research there were also used the scales of neurological deficiency activisation (Rankin and NIHSS; ultrasound of the magistral arteries and extracranial CT of brain; methods of mathematical statistics (the definition of chances and confidence intervals ratio, Pirson and Student criteria, verification of hypothesis about the law of distribution and equality of the mean values in the both samplings.Results. There were defined the most informative factors in prognostication of the good result after thrombolytic therapy. There was formed the list of output factors that the results of actilyse thrombolytic therapy effectiveness in Lviv region are depending on. There was grounded the necessity of laboratory data monitoring in patients with stroke for receiving the best results of thrombolytic therapy.There was established that thrombolytic therapy of ishemic stroke must begin as early as possible (in computed tomography department if possible for receiving the maximal effectiveness. There was detected that ultrasound of magistral vessels that supply brain with blood is necessary for all patients who are candidates for thrombolytic therapy because the stenosis of the vessel lumen more than 60 % significantly worsens an effectiveness of treatment

Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies.

Science.gov (United States)

Vonder Haar, Cole; Peterson, Todd C; Martens, Kris M; Hoane, Michael R

2016-06-01

With the numerous failures of pharmaceuticals to treat traumatic brain injury in humans, more researchers have become interested in combination therapies. This is largely due to the multimodal nature of damage from injury, which causes excitotoxicity, oxidative stress, edema, neuroinflammation and cell death. Polydrug treatments have the potential to target multiple aspects of the secondary injury cascade, while many previous therapies focused on one particular aspect. Of specific note are vitamins, minerals and nutrients that can be utilized to supplement other therapies. Many of these have low toxicity, are already FDA approved and have minimal interactions with other drugs, making them attractive targets for therapeutics. Over the past 20 years, interest in supplementation and supraphysiologic dosing of nutrients for brain injury has increased and indeed many vitamins and nutrients now have a considerable body of the literature backing their use. Here, we review several of the prominent therapies in the category of nutraceutical treatment for brain injury in experimental models, including vitamins (B2, B3, B6, B9, C, D, E), herbs and traditional medicines (ginseng, Gingko biloba), flavonoids, and other nutrients (magnesium, zinc, carnitine, omega-3 fatty acids). While there is still much work to be done, several of these have strong potential for clinical therapies, particularly with regard to polydrug regimens. This article is part of a Special Issue entitled SI:Brain injury and recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

HIFU Monitoring and Control with Dual-Mode Ultrasound Arrays

Science.gov (United States)

Casper, Andrew Jacob

The biological effects of high-intensity focused ultrasound (HIFU) have been known and studied for decades. HIFU has been shown capable of treating a wide variety of diseases and disorders. However, despite its demonstrated potential, HIFU has been slow to gain clinical acceptance. This is due, in part, to the difficulty associated with robustly monitoring and controlling the delivery of the HIFU energy. The non-invasive nature of the surgery makes the assessment of treatment progression difficult, leading to long treatment times and a significant risk of under treatment. This thesis research develops new techniques and systems for robustly monitoring HIFU therapies for the safe and efficacious delivery of the intended treatment. Systems and algorithms were developed for the two most common modes of HIFU delivery systems: single-element and phased array applicators. Delivering HIFU with a single element transducer is a widely used technique in HIFU therapies. The simplicity of a single element offers many benefits in terms of cost and overall system complexity. Typical monitoring schemes rely on an external device (e.g. diagnostic ultrasound or MRI) to assess the progression of therapy. The research presented in this thesis explores using the same element to both deliver and monitor the HIFU therapy. The use of a dual-mode ultrasound transducer (DMUT) required the development of an FPGA based single-channel arbitrary waveform generator and high-speed data acquisition unit. Data collected from initial uncontrolled ablations led to the development of monitoring and control algorithms which were implemented directly on the FPGA. Close integration between the data acquisition and arbitrary waveform units allowed for fast, low latency control over the ablation process. Results are presented that demonstrate control of HIFU therapies over a broad range of intensities and in multiple in vitro tissues. The second area of investigation expands the DMUT research to an

The role of computed tomography in evaluation of a white matter edema during postoperative brain radiation therapy

International Nuclear Information System (INIS)

Thalacker, U.; Somogyi, A.; Nemeth, G.; Liszka, G.

1998-01-01

The aim of our study was to determine on CT whether a relation exists between a radiation induced brain edema, treated with diuretics and its corresponding Houndsfield Units (HU). Seventy-five patients (age 20 to 65 years), suffering from headaches but without hypertension, brain tumors or cerebral arteriosclerosis were examined as a reference group. The second group consisted of 20 patients with brain tumors, which underwent brain surgery. HU of the white matter were measured before radiation and after 10, 20, 30, 40 and 50 Gy. The third group consisted of 64 patients with brain tumors, that underwent postsurgical radiation therapy. Prior to radiation therapy 40 mg furosemide per os were given. CT-examinations, intensified diuretic therapy and follow-up examinations were performed as in group 2. If, despite therapy, the HU decreased, infusion of mannites was added. The second and third group of patients recieved radiation therapy with telecobalt and/or a linear accelerator (6 and 9 MeV X-ray). In the first group white matter density was >30 HU. In the second group white matter density was between 25 and 29 HU prior to diuretic therapy. Under 25 HU a continuous headache, vertigo and confusion ensued. Diuretic therapy was intensified until the measured values reached 25 to 29 HU. Forty-seven of 64 patients in the third group had 25 to 29 HU prior to radiation therapy. Despite prophylactic diuretic therapy in 28 cases density decreased to 20 to 24 HU. Improvement was achived with an additional glycerine per os. The measured values reached again 25 to 29 HU. In 1 case the values dropped under 20 HU. Additional mannite infusion was necessary. In 17 to 64 patients white matter density was >30 HU prior to radiation therapy, dropping to 25 to 29 HU during radiation. Prophylactic diuretic administration kept the values in this range. A correlation between age of the patient, radiation source, total dose, tumor histology and degree of change in HU was not found. (orig

Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

2006-03-15

Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

New three-dimensional moving field radiation therapy for brain tumors

Energy Technology Data Exchange (ETDEWEB)

Mitsuyama, Fuyuki; Kanno, Tetsuo; Nagata, Yutaka; Koga, Sukehiko [Fujita-Gakuen Health Univ., Toyoake, Aichi (Japan); Jain, V K

1992-06-01

A new modified rotation radiation method called 'three-dimensional moving field radiation therapy' is described. The new method uses rotation in many planes while maintaining the same isocenter to achieve a good spatial dose distribution. This delivers a high dose to tumors and spares the surrounding normal structures. This easy method can be carried out using the equipment for conventional rotation radiation therapy. The new method was superior to the one plane rotation radiation therapy using a physical phantom with film, a chemical phantom using the iodine-starch reaction, and a new biological model using tumor cells. Treatment of six brain tumors irradiated with total air doses of 50-60 Gy caused no hair loss or radiation necrosis. (author).

Real-Time Ultrasound-Guided Catheter Navigation for Approaching Deep-Seated Brain Lesions: Role of Intraoperative Neurosonography with and without Fusion with Magnetic Resonance Imaging.

Science.gov (United States)

Manjila, Sunil; Karhade, Aditya; Phi, Ji Hoon; Scott, R Michael; Smith, Edward R

2017-01-01

Brain shift during the exposure of cranial lesions may reduce the accuracy of frameless stereotaxy. We describe a rapid, safe, and effective method to approach deep-seated brain lesions using real-time intraoperative ultrasound placement of a catheter to mark the dissection trajectory to the lesion. With Institutional Review Board approval, we retrospectively reviewed the radiographic, pathologic, and intraoperative data of 11 pediatric patients who underwent excision of 12 lesions by means of this technique. Full data sets were available for 12 lesions in 11 patients. Ten lesions were tumors and 2 were cavernous malformations. Lesion locations included the thalamus (n = 4), trigone (n = 3), mesial temporal lobe (n = 3), and deep white matter (n = 2). Catheter placement was successful in all patients, and the median time required for the procedure was 3 min (range 2-5 min). There were no complications related to catheter placement. The median diameter of surgical corridors on postresection magnetic resonance imaging was 6.6 mm (range 3.0-12.1 mm). Use of real-time ultrasound guidance to place a catheter to aid in the dissection to reach a deep-seated brain lesion provides advantages complementary to existing techniques, such as frameless stereotaxy. The catheter insertion technique described here provides a quick, accurate, and safe method for reaching deep-seated lesions. © 2017 S. Karger AG, Basel.

The role of stereotactic radiation therapy and whole-brain radiotherapy in the treatment of multiple brain metastases

International Nuclear Information System (INIS)

Chen Xiujun; Xiao Jianping; Li Xiangpan; Jiang Xuesong; Zhang Ye; Xu Yingjie; Dai Jianrong; Li Yexiong

2012-01-01

Objective: To summarize the results of stereotactic radiation therapy (SRT) with or without whole-brain radiotherapy (WBRT) in the treatment of multiple brain metastasis. Methods: From May 1995 to April 2010, totally 98 newly diagnosed multiple (2 - 13 lesions) brain metastases patients were treated in our centre. Forty-four patients were treated with SRT alone and 54 with SRT + WBRT. Dose fractionation schemes were 15 -26 Gy in 1 fraction or 24.0 -52.5 Gy in 2 - 15 fractions with 3.5 - 12.0 Gy per fraction, depending on the tumor volume, location, and history of prior irradiation. Kaplan-Meier and Cox proportional hazards regression analyses were used for survival analysis. The median age of the whole group was 55 years. The survival time was calculated from the date of radiation treatment to the day of death by any cause. Results: The median follow-up time for the whole group was 12 months, and the follow-up rate was 100%. The median overall survival time was 13.5 months for the whole group, there was no difference between SRT alone group and SRT + WBRT group (13.0 months vs. 13.5 months, χ 2 =0.31, P =0.578). The Karnofsky Performance Score (KPS) at the time of treatment (χ 2 =6.25, P =0.012), the interval between the diagnosis of the primary tumor and brain metastases (χ 2 =7.34, P =0.025) and the status of extracranial metastases (χ 2 =4.20, P =0.040) were independent prognosis factors for survival in multivariate analyses. Conclusions: Stereotactic radiation therapy is an effective and alternative treatment choice for multiple brain metastases. (authors)

Preliminary assessment of one-dimensional MR elastography for use in monitoring focused ultrasound therapy

International Nuclear Information System (INIS)

Yuan Le; Glaser, Kevin J; Rouviere, Olivier; Gorny, Krzysztof R; Chen, Shigao; Manduca, Armando; Ehman, Richard L; Felmlee, Joel P

2007-01-01

The purpose of this work is to assess a fast technique that measures tissue stiffness and temperature during focused ultrasound thermal therapy (FUS). A one-dimensional (1D) MR elastography (MRE) pulse sequence was evaluated for the purpose of obtaining rapid measurements of thermally induced changes in tissue stiffness and temperature for monitoring FUS treatments. The accuracy of the 1D measurement was studied by comparing tissue displacements measured by 1D MRE with those measured by the well-established 2D MRE pulse sequence. The reproducibility of the 1D MRE measurement was assessed, in gel phantoms and ex vivo porcine tissue, for varied FUS intensity levels (31.5-199.9 W cm -2 ) and over a range of displacements at the focus (0.1-1 μm). Temperature elevations in agarose gel phantoms were measured using 1D MRE and calibrated using fiberoptic-thermometer-based measurements. The 1D MRE displacement measurements are highly correlated with those obtained with the 2D technique (R 2 = 0.88-0.93), indicating that 1D MRE can successfully measure tissue displacement. Ten repeated trials at each FUS power level yielded a minimum detectable displacement change of 0.2 μm in phantoms and 0.4 μm in tissue (at 95% confidence level). The 1D MRE temperature measurements correlated well with temperature changes measured simultaneously with fiberoptic thermometers (R 2 = 0.97). The 1D MRE technique is capable of detecting tissue displacements as low as 0.4 μm, which is an order of magnitude smaller than 5 μm displacements expected during FUS therapy (Le et al 2005 AIP Conf. Proc.: Ther. Ultrasound 829 186-90). Additionally, 1D MRE was shown to provide adequate measurements of temperature elevations in tissue. These findings indicate that 1D MRE may be an effective tool for monitoring FUS treatments

Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study.

Science.gov (United States)

Resnick, S M; Espeland, M A; Jaramillo, S A; Hirsch, C; Stefanick, M L; Murray, A M; Ockene, J; Davatzikos, C

2009-01-13

To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

Ultrasound-guided drug delivery in cancer

Energy Technology Data Exchange (ETDEWEB)

Chowdhury, Sayan Mullick; Lee, Tae Hwa; Willmann, Jugen K. [Dept. of Radiology, Stanford University School of Medicine, Stanford (United States)

2017-07-15

Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Freund, Derek; Zhang, Rui, E-mail: rzhang@marybird.com [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States); Sanders, Mary [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Newhauser, Wayne [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States)

2015-04-13

Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

Directory of Open Access Journals (Sweden)

Derek Freund

2015-04-01

Full Text Available Cancer of the brain and central nervous system (CNS is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT compared to passively scattered proton therapy (PSPT and intensity modulated proton therapy (IMPT. Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

Synergistic effects of Combined Therapy: nonfocused ultrasound plus Aussie current for noninvasive body contouring

Science.gov (United States)

Canela, Vivianne Carvalho; Crivelaro, Cinthia Nicoletti; Ferla, Luciane Zacchi; Pelozo, Gisele Marques; Azevedo, Juliana; Liebano, Richard Eloin; Nogueira, Caroline; Guidi, Renata Michelini; Grecco, Clóvis; Sant’Ana, Estela

2018-01-01

Background and objectives Nowadays, there are several noninvasive technologies being used for improving of body contouring. The objectives of this pilot study were to verify the effectiveness of the Heccus® device, emphasizing the synergism between nonfocused ultrasound plus Aussie current in the improvement of body contour, and to determine if the association of this therapy with whole-body vibration exercises can have additional positive effects in the results of the treatments. Subjects and methods Twenty healthy women aged 20–40 years participated in the study. Ten patients received Combined Therapy treatment (G1) and the other 10 participants received Combined Therapy with additional vibratory platform treatment (G2). Anthropometric and standardized photography analysis, ultrasonography, cutometry and self-adminestered questionnaires of tolerance and satisfaction levels with the treatment were used. Results Compared with baseline values, reduction of fat thickness was observed by ultrasonography in the posterior thigh area in the G1 group (Pcellulite degree in the buttocks, G1 (Ptreatment for improving the aspect of the cellulite, skin firmness and localized fat. If used in association with the whole-body vibratory platform, the results can be better, especially in the treatment of localized fat. Further studies with larger sample size should be performed to confirm these results. PMID:29731654

Electroconvulsive therapy, hypertensive surge, blood-brain barrier breach, and amnesia

DEFF Research Database (Denmark)

Andrade, Chittaranjan; Bolwig, Tom G

2014-01-01

Preclinical and clinical evidence show that electroconvulsive therapy (ECT)-induced intraictal surge in blood pressure may result in a small, transient breach in the blood-brain barrier, leading to mild cerebral edema and a possible leach of noxious substances from blood into brain tissues...... convincing evidence of benefits. It is concluded that there is insufficient support, at present, for the hypothesis that the hypertensive surge during ECT and the resultant blood-brain barrier breach contribute meaningfully to ECT-induced cognitive deficits. Future research should address the subset....... These changes may impair neuronal functioning and contribute to the mechanisms underlying ECT-induced cognitive deficits. Some but not all clinical data on the subject suggest that blood pressure changes during ECT correlate with indices of cognitive impairment. In animal models, pharmacological manipulations...

Inferring common cognitive mechanisms from brain blood-flow lateralisation data obtained with functional transcranial Doppler ultrasound.

Directory of Open Access Journals (Sweden)

Georg eMeyer

2014-06-01

Full Text Available Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV lateralisation data, obtained with functional TransCranial Doppler (fTCD ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralisation Index (LI for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG at two difficulty levels.In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training.CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated.The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques.

Therapeutic Ultrasound Examination of Follicular Reserve, and Ovarian Tissue Angiogenesis in Mice, 14 Days after Heterotopic Transplantation

Directory of Open Access Journals (Sweden)

N Abtahi

2014-06-01

Results: The study results showed that the CD31 angiogenic factor was expressed more in the irradiated animals than in control group animals and ultrasound-therapy resulted in better follicular preservation. Conclusion: The ultrasound therapy can improve preservation of ovarian follicle .This is probably due to acceleration of angiogenesis and increase in production of growth factors by low intensity pulse ultrasound.

Musculoskeletal ultrasound: how to treat calcific tendinitis of the rotator cuff by ultrasound-guided single-needle lavage technique.

Science.gov (United States)

Lee, Kenneth S; Rosas, Humberto G

2010-09-01

The purpose of this video article is to illustrate the ultrasound appearance of calcium deposition in the rotator cuff and provide a detailed step-by-step protocol for performing the ultrasound-guided single-needle lavage technique for the treatment of calcific tendinitis with emphasis on patient positioning, necessary supplies, real-time lavage technique, and steroid injection into the subacromial subdeltoid bursa. Musculoskeletal ultrasound is well established as a safe, cost-effective imaging tool in diagnosing and treating common musculoskeletal disorders. Calcific tendinitis of the rotator cuff is a common disabling cause of shoulder pain. Although most cases are self-limiting, a subset of patients is refractory to conservative therapy and requires treatment intervention. Ultrasound-guided lavage is an effective and safe minimally-invasive treatment not readily offered in the United States as an alternative to surgery, perhaps because of the limited prevalence of musculoskeletal ultrasound programs and limited training. On completion of this video article, the participant should be able to develop an appropriate diagnostic and therapeutic algorithm for the treatment of calcific tendinitis of the rotator cuff using ultrasound.

A Comparison of daily megavoltage CT and ultrasound image guided radiation therapy for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Peng Cheng; Kainz, Kristofer; Lawton, Colleen; Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 (United States)

2008-12-15

In order to quantify the differences between ultrasound-imaging and megavoltage-CT (MVCT) daily prostate localization in prostate-cancer radiotherapy and their dosimetric impacts, daily shifts were analyzed for a total of 140 prostate cancer patients; 106 positioned using ultrasound-based imaging [B-mode Acquisition and Targeting (BAT)], and 34 using the MVCT from a TomoTherapy Hi-Art unit. The shifts indicated by the two systems were compared statistically along the right/left (R/L), superior/inferior (S/I), and anterior/posterior (A/P) directions. The systematic and random variations among the daily alignments were calculated. Margins to account for these shifts were estimated. The mean shifts and standard deviations along the R/L, S/I, and A/P directions were -0.11{+-}3.80, 0.67{+-}4.67, and 2.71{+-}6.31 mm for BAT localizations and -0.98{+-}5.13, 0.27{+-}3.35, and 1.00{+-}4.22 mm for MVCT localizations, respectively. The systematic and random variations in daily shifts based on MVCT were generally smaller than those based on BAT, especially along the A/P direction. A t-test showed this difference to be statistically significant. The planning target volume margins in the A/P direction estimated to account for daily variations were 8.81 and 14.66 mm based on MVCT and BAT data, respectively. There was no statistically significant difference in the daily prostate movement pattern between the first few fractions and the remaining fractions. Dosimetric comparison of MVCT and BAT prostate alignments was performed for seven fractions from a patient. The degradation from the plan caused by the MVCT alignment is trivial, while that by BAT is substantial. The MVCT technique results in smaller variations in daily shifts than ultrasound imaging, indicating that MVCT is more reliable and precise for prostate localization. Ultrasound-based localization may overestimate the daily prostate motion, particularly in the A/P direction, negatively impacting prostate dose coverage

A Comparison of daily megavoltage CT and ultrasound image guided radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Peng Cheng; Kainz, Kristofer; Lawton, Colleen; Li, X. Allen

2008-01-01

In order to quantify the differences between ultrasound-imaging and megavoltage-CT (MVCT) daily prostate localization in prostate-cancer radiotherapy and their dosimetric impacts, daily shifts were analyzed for a total of 140 prostate cancer patients; 106 positioned using ultrasound-based imaging [B-mode Acquisition and Targeting (BAT)], and 34 using the MVCT from a TomoTherapy Hi-Art unit. The shifts indicated by the two systems were compared statistically along the right/left (R/L), superior/inferior (S/I), and anterior/posterior (A/P) directions. The systematic and random variations among the daily alignments were calculated. Margins to account for these shifts were estimated. The mean shifts and standard deviations along the R/L, S/I, and A/P directions were -0.11±3.80, 0.67±4.67, and 2.71±6.31 mm for BAT localizations and -0.98±5.13, 0.27±3.35, and 1.00±4.22 mm for MVCT localizations, respectively. The systematic and random variations in daily shifts based on MVCT were generally smaller than those based on BAT, especially along the A/P direction. A t-test showed this difference to be statistically significant. The planning target volume margins in the A/P direction estimated to account for daily variations were 8.81 and 14.66 mm based on MVCT and BAT data, respectively. There was no statistically significant difference in the daily prostate movement pattern between the first few fractions and the remaining fractions. Dosimetric comparison of MVCT and BAT prostate alignments was performed for seven fractions from a patient. The degradation from the plan caused by the MVCT alignment is trivial, while that by BAT is substantial. The MVCT technique results in smaller variations in daily shifts than ultrasound imaging, indicating that MVCT is more reliable and precise for prostate localization. Ultrasound-based localization may overestimate the daily prostate motion, particularly in the A/P direction, negatively impacting prostate dose coverage and rectal

Ultrasound Imaging of Mouse Fetal Intracranial Hemorrhage Due to Ischemia/Reperfusion

Directory of Open Access Journals (Sweden)

Kenichi Funamoto

2017-05-01

Full Text Available Despite vast improvement in perinatal care during the 30 years, the incidence rate of neonatal encephalopathy remains unchanged without any further Progress towards preventive strategies for the clinical impasse. Antenatal brain injury including fetal intracranial hemorrhage caused by ischemia/reperfusion is known as one of the primary triggers of neonatal injury. However, the mechanisms of antenatal brain injury are poorly understood unless better predictive models of the disease are developed. Here we show a mouse model for fetal intracranial hemorrhage in vivo developed to investigate the actual timing of hypoxia-ischemic events and their related mechanisms of injury. Intrauterine growth restriction mouse fetuses were exposed to ischemia/reperfusion cycles by occluding and opening the uterine and ovarian arteries in the mother. The presence and timing of fetal intracranial hemorrhage caused by the ischemia/reperfusion were measured with histological observation and ultrasound imaging. Protein-restricted diet increased the risk of fetal intracranial hemorrhage. The monitoring of fetal brains by ultrasound B-mode imaging clarified that cerebral hemorrhage in the fetal brain occurred after the second ischemic period. Three-dimensional ultrasound power Doppler imaging visualized the disappearance of main blood flows in the fetal brain. These indicate a breakdown of cerebrovascular autoregulation which causes the fetal intracranial hemorrhage. This study supports the fact that the ischemia/reperfusion triggers cerebral hemorrhage in the fetal brain. The present method enables us to noninvasively create the cerebral hemorrhage in a fetus without directly touching the body but with repeated occlusion and opening of the uterine and ovarian arteries in the mother.

Ultrasound cylindrical phased array for transoesophageal thermal therapy: initial studies

International Nuclear Information System (INIS)

Melodelima, David; Lafon, Cyril; Prat, Frederic; Birer, Alain; Cathignol, Dominique

2002-01-01

This work was undertaken to investigate the feasibility of constructing a cylindrical phased array composed of 64 elements spread around the periphery (OD 10.6 mm) for transoesophageal ultrasound thermotherapy. The underlying operating principle of this applicator is to rotate a plane ultrasound beam electronically. For this purpose, eight adjacent transducers were successively excited with appropriate delay times so as to generate a plane wave. The exposure direction was changed by exciting a different set of eight elements. For these feasibility studies, we used a cylindrical prototype (OD 10.6 mm) composed of 16 elementary transducers distributed over a quarter of the cylinder, all operating at 4.55 MHz. The active part was mechanically reinforced by a rigid damper structure behind the transducers. It was shown that an ultrasound field similar to that emitted by a plane transducer could be generated. Ex vivo experiments on pig's liver demonstrated that the ultrasound beam could be accurately rotated to generate sector-based lesions to a suitable depth (up to 19 mm). Throughout these experiments, exposures lasting 20 s were delivered at an acoustic intensity of 17 W cm -2 . By varying the power from exposure to exposure, the depth of the lesion at different angles could be controlled

Ultrasound-guided drug delivery in cancer

Directory of Open Access Journals (Sweden)

Sayan Mullick Chowdhury

2017-07-01

Full Text Available Recent advancements in ultrasound and microbubble (USMB mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

The short-term effects of TENS plus therapeutic ultrasound combinations in chronic neck pain.

Science.gov (United States)

Sayilir, Selcuk

2018-05-01

To investigate the effects of TENS plus therapeutic ultrasound combinations on symptom relief, physical functionality, perceived stress levels, daytime sleepiness and neck mobility in patients with chronic neck pain (CNP). A total of 64 patients were divided into two groups as the TENS plus ultrasound group (n = 39) and the control CNP group (n = 25). The therapy comprised TENS and therapeutic ultrasound applications for 10 sessions. The control subjects were discouraged from using analgesics but were allowed to use paracetamol daily, if necessary. The Neck Disability Index (NDI), Epworth Sleepiness Scale (ESS), Perceived Stress Scale (PSS), visual analog scale (VAS) and tragus-wall/chin-manubrium distances were recorded at the baseline and after therapy. Significant improvements were detected in the TENS plus ultrasound group compared to the control CNP subjects in respect of VAS, PSS and NDI scores after the TENS plus therapeutic ultrasound therapies (all p stress levels and improving functionality in the short-term of CNP. Copyright © 2018 Elsevier Ltd. All rights reserved.

Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging.

Science.gov (United States)

O'Reilly, Meaghan Anne; Jones, Ryan Matthew; Barrett, Edward; Schwab, Anthony; Head, Elizabeth; Hynynen, Kullervo

2017-01-01

Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits. Methods: Aged dogs naturally accumulate plaques and show associated cognitive declines. Low-frequency ultrasound was used to open the BBB unilaterally in aged beagles (9-11yrs, n=10) in accordance with institutionally approved protocols. Animals received either a single treatment or four weekly treatments. Magnetic resonance imaging(MRI) was used to guide the treatments and assess the tissue effects. The animals underwent neurological testing during treatment follow-up, and a follow-up MRI exam 1 week following the final treatment. Results: The permeability of the BBB was successfully increased in all animals (mean enhancement: 19±11% relative to untreated hemisphere). There was a single adverse event in the chronic treatment group that resolved within 24 hrs. Follow-up MRI showed the BBB to be intact with no evidence of tissue damage in all animals. Histological analysis showed comparable levels of microhemorrhage between the treated and control hemispheres in the prefrontal cortex (single/repeat treatment: 1.0±1.4 vs 0.4±0.5/5.2±1.8 vs. 4.0±2.0). No significant differences were observed in beta-amyloid load (single/repeat: p=0.31/p=0.98) although 3/5 animals in each group showed lower Aβ loads in the treated hemisphere. Conclusion: Whole-hemisphere opening of the BBB was well tolerated in the aged large animal brain. The treatment volumes and frequencies

Updates on ultrasound research in implant dentistry: a systematic review of potential clinical indications.

Science.gov (United States)

Bhaskar, Vaishnavi; Chan, Hsun-Liang; MacEachern, Mark; Kripfgans, Oliver D

2018-05-23

Ultrasonography has shown promising diagnostic value in dental implant imaging research; however, exactly how ultrasound was used and at what stage of implant therapy it can be applied has not been systematically evaluated. Therefore, the aim of this review is to investigate potential indications of ultrasound use in the three implant treatment phases, namely planning, intraoperative and postoperative phase. Eligible manuscripts were searched in major databases with a combination of key words related to the use of ultrasound imaging in implant therapy. An initial search yielded 414 articles, after further review, 28 articles were finally included for this systematic review. Ultrasound was found valuable, though at various development stages, for evaluating (1) soft tissues, (2) hard tissues (3) vital structures and (4) implant stability. B-mode, the main function to image anatomical structures of interest, has been evaluated in pre-clinical and clinical studies. Quantitative ultrasound parameters, e.g. sound speed and amplitude, are being developed to evaluate implant-bone stability, mainly in simulation and pre-clinical studies. Ultrasound could be potentially useful in all 3 treatment phases. In the planning phase, ultrasound could evaluate vital structures, tissue biotype, ridge width/density, and cortical bone thickness. During surgery, it can provide feedback by identifying vital structures and bone boundary. At follow-up visits, it could evaluate marginal bone level and implant stability. Understanding the current status of ultrasound imaging research for implant therapy would be extremely beneficial for accelerating translational research and its use in dental clinics.

Prognosis of patients treated with whole brain radiation therapy for metastatic gestational trophoblastic disease

International Nuclear Information System (INIS)

Schechter, Naomi R.; Mychalczak, Borys; Jones, Walter; Spriggs, David

1996-01-01

Purpose/Objective: To evaluate the effect of multiple treatment and disease related variables on the local control and survival of patients receiving whole brain radiation therapy for metastatic gestational trophoblastic disease. Materials and Methods: Between November 1967 and December 1994, 21 patients were treated at our institution for gestational trophoblastic disease metastatic to the brain. 29% ((6(21))) were diagnosed with their brain metastases before the onset of chemotherapy (early group). 79% ((15(21))) developed their brain metastases during or after the administration of first-line chemotherapy (late group). All patients were treated with whole brain radiation therapy. The total dose ranged from 200 cGy to 3600 cGy (median 2200 cGy). Sixteen patients (76%) received concurrent systemic chemotherapy. None of the patients received intrathecal chemotherapy as a component of their initial treatment. Survival and local control were calculated from the date of diagnosis of brain metastases. Follow-up ranged from 11 months to 170 months with a median of 77 months. Results: The median overall survival was 21 months, with 2- and 5-year actuarial survivals of 46% and 31%, respectively. Neither survival nor local control was significantly affected by age at diagnosis of brain metastases (<35 vs. ≥35 years), time of presentation of brain metastases (early vs. late), or use of concurrent chemotherapy. The total dose of radiation (<2200 cGy vs. ≥2200 cGy) significantly affected initial local control, but not survival. The 5-year actuarial local control of the initial brain metastases with ≥2200 cGy was 91%, as compared to 24% with <2200 cGy (p=0.05). Survival was significantly affected by control of disease at extracranial sites. The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100% and 83%, respectively, as compared to 8% and 0% for the 12 whose extracranial disease was not controlled (p=0

Non-invasive brain-to-brain interface (BBI: establishing functional links between two brains.

Directory of Open Access Journals (Sweden)

Seung-Schik Yoo

Full Text Available Transcranial focused ultrasound (FUS is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI. In conjunction with the use of brain-to-computer interface (BCI techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat, thus creating a brain-to-brain interface (BBI. The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.

CLINICAL FIELD NOTE - ULTRASOUND THERAPY: GETTING IT ...

African Journals Online (AJOL)

user

Incorporating this vital information has led to a turn around in the evidence of ultrasound research ... in clinical practice, there has not been enough research evidence to support its .... Parameters: 1W/cm , 50% duty cycle (pulsed), 15 minutes,. 2 with a 5cm ... New England Journal of Medicine 317: 141-145. Gam, A.N., F.

Perspectives of boron-neutron capture therapy of malignant brain tumors

Science.gov (United States)

Kanygin, V. V.; Kichigin, A. I.; Krivoshapkin, A. L.; Taskaev, S. Yu.

2017-09-01

Boron neutron capture therapy (BNCT) is characterized by a selective effect directly on the cells of malignant tumors. The carried out research showed the perspective of the given kind of therapy concerning malignant tumors of the brain. However, the introduction of BNCT into clinical practice is hampered by the lack of a single protocol for the treatment of patients and the difficulty in using nuclear reactors to produce a neutron beam. This problem can be solved by using a compact accelerator as a source of neutrons, with the possibility of installation in a medical institution. Such a neutron accelerator for BNCT was developed at Budker Institute of Nuclear Physics, Novosibirsk. A neutron beam was obtained on this accelerator, which fully complies with the requirements of BNCT, as confirmed by studies on cell cultures and experiments with laboratory animals. The conducted experiments showed the relative safety of the method with the absence of negative effects on cell cultures and living organisms, and also confirmed the effectiveness of BNCT for malignant brain tumors.

Improved survival in rats with glioma using MRI-guided focused ultrasound and microbubbles to disrupt the blood-brain barrier and deliver Doxil

Science.gov (United States)

Aryal, Muna; Zhi Zhang, Yong; Vykhodtseva, Natalia; Park, Juyoung; Power, Chanikarn; McDannold, Nathan

2012-02-01

Blood-brain-barrier (BBB) limits the transportation of most neuropeptides, proteins (enzymes, antibodies), chemotherapeutic agents, and genes that have therapeutic potential for the treatment of brain diseases. Different methods have been used to overcome this limitation, but they are invasive, non-targeted, or require the development of new drugs. We have developed a method that uses MRI-guided focused ultrasound (FUS) combined with circulating microbubbles to temporarily open BBB in and around brain tumors to deliver chemotherapy agents. Here, we tested whether this noninvasive technique could enhance the effectiveness of a chemotherapy agent (Doxil). Using 690 kHz FUS transducer and microbubble (Definity), we induced BBB disruption in intracranially-implanted 9L glioma tumors in rat's brain in three weekly sessions. Animals who received BBB disruption and Doxil had a median survival time of 34.5 days, which was significantly longer than that found in control animals which is 16, 18.5, 21 days who received no treatment, BBB disruption only and Doxil only respectively This work demonstrates that FUS technique has promise in overcoming barriers to drug delivery, which are particularly stark in the brain due to the BBB.

Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy

International Nuclear Information System (INIS)

Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R.; Wong, Eric T.; Uhlmann, Erik J.; Sengupta, Soma; Kasper, Ekkehard M.

2015-01-01

Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1–3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V 24 (9 cc vs. 44 cc, p < 0.0000) and V 30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia

Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era: The University of Rochester Experience.

Science.gov (United States)

Bates, James E; Youn, Paul; Peterson, Carl R; Usuki, Kenneth Y; Walter, Kevin A; Okunieff, Paul; Milano, Michael T

2017-10-01

Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy. We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed. Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS. This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

Non-rigid registration of 3D ultrasound for neurosurgery using automatic feature detection and matching.

Science.gov (United States)

Machado, Inês; Toews, Matthew; Luo, Jie; Unadkat, Prashin; Essayed, Walid; George, Elizabeth; Teodoro, Pedro; Carvalho, Herculano; Martins, Jorge; Golland, Polina; Pieper, Steve; Frisken, Sarah; Golby, Alexandra; Wells, William

2018-06-04

The brain undergoes significant structural change over the course of neurosurgery, including highly nonlinear deformation and resection. It can be informative to recover the spatial mapping between structures identified in preoperative surgical planning and the intraoperative state of the brain. We present a novel feature-based method for achieving robust, fully automatic deformable registration of intraoperative neurosurgical ultrasound images. A sparse set of local image feature correspondences is first estimated between ultrasound image pairs, after which rigid, affine and thin-plate spline models are used to estimate dense mappings throughout the image. Correspondences are derived from 3D features, distinctive generic image patterns that are automatically extracted from 3D ultrasound images and characterized in terms of their geometry (i.e., location, scale, and orientation) and a descriptor of local image appearance. Feature correspondences between ultrasound images are achieved based on a nearest-neighbor descriptor matching and probabilistic voting model similar to the Hough transform. Experiments demonstrate our method on intraoperative ultrasound images acquired before and after opening of the dura mater, during resection and after resection in nine clinical cases. A total of 1620 automatically extracted 3D feature correspondences were manually validated by eleven experts and used to guide the registration. Then, using manually labeled corresponding landmarks in the pre- and post-resection ultrasound images, we show that our feature-based registration reduces the mean target registration error from an initial value of 3.3 to 1.5 mm. This result demonstrates that the 3D features promise to offer a robust and accurate solution for 3D ultrasound registration and to correct for brain shift in image-guided neurosurgery.

The effect of music therapy on mood and anxiety-depression: an observational study in institutionalised patients with traumatic brain injury.

Science.gov (United States)

Guétin, S; Soua, B; Voiriot, G; Picot, M-C; Hérisson, C

2009-02-01

A previous study (carried out in 2003-2004) had included 34 patients with traumatic brain injury in order to study the feasibility and usefulness of music therapy in patients with this type of injury. To evaluate the effect of music therapy on mood, anxiety and depression in institutionalised patients with traumatic brain injury. A prospective, observational study. Thirteen patients with traumatic brain injury were included in the present study and took part in individual, weekly, 1-hour music therapy sessions over a period of 20 weeks. Each session was divided into two 30-minute periods - one devoted to listening to music (receptive music therapy) and the other to playing an instrument (active music therapy). The assessment criteria (measured at weeks 1, 5, 10, 15 and 20) were mood (on the face scale) and anxiety-depression (on the Hospital Anxiety and Depression [HAD] Scale). Mood was assessed immediately before and after the first music therapy session and every fifth session. Music therapy enabled a significant improvement in mood, from the first session onwards. This short-term effect was confirmed by the immediate changes in the scores after music therapy sessions (from 4.6+/-3.2 to 2.6+/-2; pMusic therapy also led to a significant reduction in anxiety-depression (pstudy (week 20). These results confirm the usefulness of music therapy in the treatment of anxiety-depression and mood in patients with traumatic brain injury. Music therapy could usefully form an integral part of the management programme for these patients.

Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

Science.gov (United States)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2013-02-01

The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

Science.gov (United States)

Zhu, Hai-tao; Bian, Chen; Yuan, Ji-chao; Liao, Xiao-jun; Liu, Wei; Zhu, Gang; Feng, Hua; Lin, Jiang-kai

2015-06-15

Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

Ultrasound based evaluation of hepatic steatosis and fibrosis in hepatitis c non-responders

International Nuclear Information System (INIS)

Sohail, S.; Aziz, S.

2013-01-01

To determine the accuracy of ultrasound in the diagnosis and grading of steatosis and fibrosis in Hepatitis C (HCV) patients not responding to ribavarin-interferon therapy. Study Design: A cross-sectional, analytical study. Place and Duration of Study: Radiology Department, Civil Hospital, Karachi, from March 2008 to August 2010. Methodology: Patients with positive HCV RNA despite 24 weeks ribavarin-interferon therapy (non-responders) were subjected to ultrasound and biopsy prior to institution of pegylated interferon therapy for detection and grading of steatosis and fibrosis. Using histopathology as the gold standard, sensitivity, specificity, negative and positive predictive values for ultrasound were determined. Results: The sensitivity of ultrasound for hepatic steatosis was 90.9% for no steatosis (NS), 100% for moderate and gross steatosis and 84.4% for mild steatosis with 100% specificity. The senitivity for fibrosis was 25% for no fibrosis, 100% for mild fibrosis, 89.74% for moderate fibrosis and 100% for gross fibrosis. The overall accuracy for detection of steatosis was 95.39% and that for fibrosis was 98.02%. Hepatic vein showed increased dampening of flow with advancing grades of steatosis and fibrosis. Conclusion: Ultrasound has a high accuracy in the diagnosis and grading of steatosis and fibrosis in HCV nonresponders. Mild fibrosis may confound the diagnosis of mild steatosis. (author)

Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

Science.gov (United States)

Dukart, Juergen; Regen, Francesca; Kherif, Ferath; Colla, Michael; Bajbouj, Malek; Heuser, Isabella; Frackowiak, Richard S.; Draganski, Bogdan

2014-01-01

There remains much scientific, clinical, and ethical controversy concerning the use of electroconvulsive therapy (ECT) for psychiatric disorders stemming from a lack of information and knowledge about how such treatment might work, given its nonspecific and spatially unfocused nature. The mode of action of ECT has even been ascribed to a “barbaric” form of placebo effect. Here we show differential, highly specific, spatially distributed effects of ECT on regional brain structure in two populations: patients with unipolar or bipolar disorder. Unipolar and bipolar disorders respond differentially to ECT and the associated local brain-volume changes, which occur in areas previously associated with these diseases, correlate with symptom severity and the therapeutic effect. Our unique evidence shows that electrophysical therapeutic effects, although applied generally, take on regional significance through interactions with brain pathophysiology. PMID:24379394

[Possibilities of magnetic-laser therapy in comprehensive treatment of patients with brain concussion in acute period].

Science.gov (United States)

Zubkova, O V; Samosiuk, I Z; Polishchuk, O V; Shul'ga, N M; Samosiuk, N I

2012-01-01

The efficacy of magnetic-laser therapy used according to the method developed by us was studied in patients having the brain concussion (BC) in an acute period. The study was based on the dynamics of values of the evoked vestibular potentials and the disease clinical course. It was shown that following the magnetic-laser therapy in combination with traditional pharmacotherapy in BC acute period, the statistically significant positive changes were registered in the quantitative characteristics of the evoked vestibular brain potentials that correlated with the dynamics of the disease clinical course. The data obtained substantiate the possibility of using the magnetic-laser therapy in patients with a mild craniocereblal injury in an acute period.

Intraluminal ultrasound guidance of transverse laser coronary atherectomy

Science.gov (United States)

Aretz, H. Thomas; Martinelli, Michael A.; LeDet, Earl G.; Sedlacek, Tomas; Hatch, G. F.; Gregg, Richard E.

1990-07-01

A coronary laser atherectomy system combining laser delivery and ultrasonic imaging capability is described. The system is being developed by Intra-Sonix, Inc. to treat severe stenoses. The imaging system provides the clinician with the guidance needed to remove substantial plaque without perforation. The ultrasound transducers and laser optics are mounted in a small (less than 4 F), flexible catheter, that is deliverable over a standard guidewire (0.016 inch). The laser and ultrasound beams are directed at the artery wall to permit debulking of lesions and ultrasonic depth profiling of the tissue structure throughout the thickness of the artery. This allows the physician to determine the level of therapy to be applied and to monitor the plaque removal as the therapy progresses. The precise location of the ultrasound and laser beams in the artery is determined by a navigation system. Navigation data are processed electronically in conjunction with ultrasound data to produce real-time cross-sectional and longitudinal images of the artery wall at selected locations, which are updated as the catheter progresses through the vessel lumen. Results of in vitro tests on human atherosclerotic arteries and early in vivo experiments in a canine-human xenograft model showing image construction and radial laser delivery are discussed.

Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

Science.gov (United States)

Du, Enming; Hu, Xunwu; Roy, Sona; Wang, Peng; Deasy, Kieran; Mochizuki, Toshiaki; Zhang, Ye

2017-05-30

The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Zamenhof, R.G.; Clement, S.D.; Harling, O.K.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Yanch, J.C.

1990-01-01

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction

[Ultrasound physiotherapy treatment of prostatitis].

Science.gov (United States)

Talberg, P I; Andryukhin, M I; Mazina, S E; Nikolaev, A L

2016-12-01

Develop a method of treatment of prostatitis based on the use of a standard antibiotic, immunomodulatory therapy, and transrectal ultrasound physiotherapy. The dynamics of the accumulation of the antibiotic was investigated in male rats. Sonication was performed immediately before the administration of the antibiotic and its accumulation in the process at 10, 20, 40, 60, 80, 100 min after dosing. The clinical study included 138 patients with chronic prostatitis. Patients of the experimental group, in addition to standard therapy, 10 sessions of transrectal ultrasound physical therapy was performed. The efficacy of treatment was assessed after 14 and 28 days after initiation. and its discussion. Experiments on laboratory animals have shown that the highest concentration and the residence time of antibiotic in the prostate tissue is noted ultrasonic treatment in the period of maximum blood concentration of the test drug. The data obtained allow to determine that the ultrasonic treatment must be performed considering the pharmacokinetics of the antibiotic. In conducting clinical trials on day 14 of treatment and clinical manifestations of prostatitis bacterial microflora in prostatic secretions were no patients in both groups. In 15% of patients of the experimental group the number of leukocytes decreased to the normal range. After 28 days the amount of leukocytes was normal in 51% of patients in the control and 85% in the experimental group. In animal experiments defined the optimal time interval separating the moment of injection of the antibiotic from the beginning of sonication. Clinical studies have shown that the transrectal ultrasound exposure during the period of maximum concentration of the antibiotic in the blood, improves patient outcomes by 33.8%.

Ultrasound Vector Flow Imaging: Part II: Parallel Systems

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt; Nikolov, Svetoslav Ivanov; Yu, Alfred C. H.

2016-01-01

The paper gives a review of the current state-of-theart in ultrasound parallel acquisition systems for flow imaging using spherical and plane waves emissions. The imaging methods are explained along with the advantages of using these very fast and sensitive velocity estimators. These experimental...... ultrasound imaging for studying brain function in animals. The paper explains the underlying acquisition and estimation methods for fast 2-D and 3-D velocity imaging and gives a number of examples. Future challenges and the potentials of parallel acquisition systems for flow imaging are also discussed....

EVALUATION OF ULTRASOUND REMISSION CRITERIA IN PATIENTS WITH RHEUMATOID ARTHRITIS DURING TOCILIZUMAB THERAPY

Directory of Open Access Journals (Sweden)

Rita Aleksandrovna Osipyants

2013-01-01

Full Text Available Objective: to study the association of ultrasound (US remission criteria with the clinical and laboratory indicators of inflammatory activity, functional status, and X-ray changes in patients with rheumatoid arthritis (RA during tocilizumab (TCZ therapy.Subjects and methods. The trial included 36 patients with RA (meeting the 1987 American College of Rheumatology (ACR criteria who had received TCZ for 6 months. The authors made a clinical and laboratory assessment of RA activity (DAS28-CRP, and SDAI, functional impairments (HAQ index and US verification of wrist joint synovitis (a Voluson-i device, GE, 4-13-MHz linear transducer at baseline and 6 months after therapy. No signs of grey-scale (B-mode and power Doppler (PD synovitis (B = 0; PD = 0 or minimal B-mode synovitis, and not more one PD hypervascular signal (В ≤1; PD ≤1 were arbitrarily taken as US remission criteria. Destruction changes were evaluated by hand and foot X-ray using the Sharp method modified by van der Heijde (SHS.Results. After 6 months of therapy, about 80% of the patients in clinical remission retained moderate or significant synovitis, as evidenced by US studies. There were no clinical differences in clinical activity indices and functional impairments between the patients who were and were not in US remission (p > 0.05. The 12-month follow-up SHS score was significantly higher with the preservation of 6-month therapy signs of B-mode synovitis and PD hypervascularization (of not more than one signal than that in US remission (p < 0.05. There was no relationship of X-ray progression to the clinical and functional statuses (p > 0.05.Conclusion. Subclinical synovitis is observed even in clinical remission of RA. Destruction progression is significantlyrelated to synovitis persistence, as shown by ultrasonography.

A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

Energy Technology Data Exchange (ETDEWEB)

Caravatta, Luciana; Deodato, Francesco; Ferro, Marica [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Massaccesi, Mariangela [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Cilla, Savino [Medical Physics Unit, Fondazione di Ricerca e Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Padula, Gilbert D.A. [Department of Radiation Oncology, The Lacks Cancer Center Saint Mary' s Health Care, Grand Rapids, Michigan (United States); Mignogna, Samantha; Tambaro, Rosa [Department of Palliative Therapies, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Carrozza, Francesco [Department of Oncology, A. Cardarelli Hospital, Campobasso (Italy); Flocco, Mariano [Madre Teresa di Calcutta Hospice, Larino (Italy); Cantore, Giampaolo [Department of Neurological Sciences, Istituto Neurologico Mediterraneo Neuromed, Istituto di Ricovero e Cura a Carattere Scientifico, Pozzilli (Italy); Scapati, Andrea [Department of Radiation Oncology, ' San Francesco' Hospital, Nuoro (Italy); Buwenge, Milly [Department of Radiotherapy, Mulago Hospital, Kampala (Uganda); and others

2012-11-15

Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

Brain-in-Brain Artifact (BIBA) in a Patient with Hydranencepaly: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Oh, Sang Young; Kim, You Me; Lee, Seung Ha; Lee, Young Seok [College of Medicine Dankook University Hospital, Cheonan (Korea, Republic of)

2011-03-15

Hydranencephaly is a condition that is characterized by an absent brain mantle along with the subadjacent white matter, with replacement of the cerebral hemispheres by a thin-walled membranous sac containing CSF. During brain sonograpy in a neonate with hydranencephaly, we have found a brain-in-brain appearance as an unusual sonographic artifact. We report here on this interesting sonographic artifact in a neonate with hydranencephaly, and this artifact was due to multipath reflection artifact of the ultrasound beam/wave, and we explain the underlying physics

Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.

Science.gov (United States)

Wang, Chung-Hsin; Kang, Shih-Tsung; Lee, Ya-Hsuan; Luo, Yun-Ling; Huang, Yu-Fen; Yeh, Chih-Kuang

2012-02-01

Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to trigger targeted acoustic droplet vaporization (ADV) which resulted in both mechanical cancer cell destruction by inertial cavitation and chemical treatment through localized drug release. HIFU insonation showed a 56.8% decrease in cell viability with aptamer-conjugated droplets, representing a 4.5-fold increase in comparison to non-conjugated droplets. In addition, the fully-vaporized droplets resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or partially vaporized droplets. Optical studies clearly illustrated the transient changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In conclusion, our fabricated droplets functioned as a hybrid chemical and mechanical strategy for the specific destruction of cancer cells upon ultrasound-mediated ADV, while simultaneously providing ultrasound imaging capability. Copyright © 2011 Elsevier Ltd. All rights reserved.

An online three-class Transcranial Doppler ultrasound brain computer interface.

Science.gov (United States)

Goyal, Anuja; Samadani, Ali-Akbar; Guerguerian, Anne-Marie; Chau, Tom

2016-06-01

Brain computer interfaces (BCI) can provide communication opportunities for individuals with severe motor disabilities. Transcranial Doppler ultrasound (TCD) measures cerebral blood flow velocities and can be used to develop a BCI. A previously implemented TCD BCI system used verbal and spatial tasks as control signals; however, the spatial task involved a visual cue that awkwardly diverted the user's attention away from the communication interface. Therefore, vision-independent right-lateralized tasks were investigated. Using a bilateral TCD BCI, ten participants controlled online, an on-screen keyboard using a left-lateralized task (verbal fluency), a right-lateralized task (fist motor imagery or 3D-shape tracing), and unconstrained rest. 3D-shape tracing was generally more discernible from other tasks than was fist motor imagery. Verbal fluency, 3D-shape tracing and unconstrained rest were distinguished from each other using a linear discriminant classifier, achieving a mean agreement of κ=0.43±0.17. These rates are comparable to the best offline three-class TCD BCI accuracies reported thus far. The online communication system achieved a mean information transfer rate (ITR) of 1.08±0.69bits/min with values reaching up to 2.46bits/min, thereby exceeding the ITR of previous online TCD BCIs. These findings demonstrate the potential of a three-class online TCD BCI that does not require visual task cues. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Computational exploration of wave propagation and heating from transcranial focused ultrasound for neuromodulation

Science.gov (United States)

Mueller, Jerel K.; Ai, Leo; Bansal, Priya; Legon, Wynn

2016-10-01

Objective. While ultrasound is largely established for use in diagnostic imaging, its application for neuromodulation is relatively new and crudely understood. The objective of the present study was to investigate the effects of tissue properties and geometry on the wave propagation and heating in the context of transcranial neuromodulation. Approach. A computational model of transcranial-focused ultrasound was constructed and validated against empirical data. The models were then incrementally extended to investigate a number of issues related to the use of ultrasound for neuromodulation, including the effect on wave propagation of variations in geometry of skull and gyral anatomy as well as the effect of multiple tissue and media layers, including scalp, skull, CSF, and gray/white matter. In addition, a sensitivity analysis was run to characterize the influence of acoustic properties of intracranial tissues. Finally, the heating associated with ultrasonic stimulation waveforms designed for neuromodulation was modeled. Main results. The wave propagation of a transcranially focused ultrasound beam is significantly influenced by the cranial domain. The half maximum acoustic beam intensity profiles are insensitive overall to small changes in material properties, though the inclusion of sulci in models results in greater peak intensity values compared to a model without sulci (1%-30% greater). Finally, heating using currently employed stimulation parameters in humans is highest in bone (0.16 °C) and is negligible in brain (4.27 × 10-3 °C) for a 0.5 s exposure. Significance. Ultrasound for noninvasive neuromodulation holds great promise and appeal for its non-invasiveness, high spatial resolution and deep focal lengths. Here we show gross brain anatomy and biological material properties to have limited effect on ultrasound wave propagation and to result in safe heating levels in the skull and brain.

Development of Flexible Capacitive Ultrasound Transducers and the Use of Ultrasound for Bone Repair

Science.gov (United States)

Wentzell, Scott A.

Ultrasound is a widely applicable technique for therapy in the biomedical arena. However, conventional ultrasound transducers are not conducive for non-planar surfaces. Therefore, we developed flexible transducers capable of performing ultrasound and evaluated their use in biomedical applications. Flexible capacitive ultrasound transducers based on micrometer-thick dielectric tapes were developed and fabricated. These transducers were able to be made by hand at low-cost while still demonstrating good tolerances in center operating frequency. Intensities of up to 120 mW/cm2 were recorded and operation was dependent upon the applied AC and DC voltages along with the thickness of the dielectric insulation. These capacitive ultrasound transducers were used to stimulate MC3T3-E1 murine osteoblast cells to investigate the effects of low-frequency ultrasound on osteogenic gene expression and anabolic signaling pathways. After stimulation by 94.5 kHz continuous wave ultrasound for 20 minutes, significant increases in the activation of the Wnt signaling pathway and concentration of intracellular calcium were observed. Daily stimulation by ultrasound showed a trend of increased osteogenic gene expression across the phases of matrix deposition, maturation and calcification by osteoblasts. Finally, the heating of osteoblasts for stimulating osteoclastogenic responses was investigated. The application of increased temperatures of 42 and 47 degrees Celsius for 5 minutes showed significant increases in the RANKL/OPG ratio in media conditioned by osteoblasts. However, the altered RANKL/OPG ratio was not able to generate increases in osteoclastogenesis for RAW 264.7 murine macrophage cells culture in the condition media. This was possibly due to high overall osteoprotegerin expression, or unwanted inducement of M1 and M2 macrophage activation in the cell population. The overall work of this thesis demonstrates the development of novel capacitive transducers. These conformable

The role of stereotactic radiation therapy in the management of children with brain tumors.

Science.gov (United States)

Lew, C M; LaVally, B

1995-10-01

Conventional radiation therapy plays an important role in the management of intracranial tumors in children. For certain tumors radiation therapy serves as the primary mode of treatment, and for others it plays an adjuvant role with surgery and/or chemotherapy. Improvements in long-term survival rates have focused attention on the long-term sequelae of brain tumors and their treatment, and the sequelae, in turn, have become important targets for clinical investigation. Long-term side effects of particular concern in children include cranial nerve damage, memory and intellectual deficits, pituitary-hypothalamic dysfunction, demyelinization of brain tissue, and secondary malignancies. A new form of radiation therapy, stereotactic radiotherapy (SRT), merges the technologies of stereotactic surgery and conventional fractionated radiotherapy. The intent is to deliver maximum tumoricidal doses to the target while limiting the dose to normal surrounding brain tissue. The key feature of SRT is a noninvasive, relocatable immobilization system to assure accurate and reproducible positioning during planning and treatment. The headframes used for children have been modified to address their specific needs. The complexities of this process require careful preparation of patients and their families and the participation of many disciplines. Long-term follow-up will be essential to evaluate the effectiveness of this innovative treatment.

Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes.

Science.gov (United States)

Espeland, Mark A; Brinton, Roberta Diaz; Manson, JoAnn E; Yaffe, Kristine; Hugenschmidt, Christina; Vaughan, Leslie; Craft, Suzanne; Edwards, Beatrice J; Casanova, Ramon; Masaki, Kamal; Resnick, Susan M

2015-09-29

To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65-79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial. The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes. Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of -18.6 mL (95% confidence interval [CI] -29.6, -7.6). For women without diabetes, this mean decrement was -0.4 (95% CI -3.8, 3.0) (interaction p=0.002). This interaction was evident for total gray matter (pNeurology.

The impact of group occupational therapy using a cueing system on executive function of preschool-aged children with brain lesions.

Science.gov (United States)

Seo, Sang-Min

2018-02-01

[Purpose] This study investigates the effects of group occupational therapy using a cueing system on the executive function of preschool-aged children with brain lesions. [Subjects and Methods] Six preschool-aged children with brain lesions participated in this study. A 24-session occupational therapy program (1 session/week, 50 minutes/session) designed based on a cueing system was administered to examine the changes in the participants' executive function. The behavior rating inventory of executive function-preschool (BRIEF-P) was used to check the magnitude of improvement of executive functions after therapy. [Results] A Wilcoxon signed rank test revealed that occupational therapy significantly improved all domains, indices, and the global executive composite in the BRIEF-P. [Conclusion] The occupational therapy intervention incorporating a type of cognitive behavioral approach known as the cueing system may assist improving executive functions in preschool-aged children with brain lesions.

Music-based cognitive remediation therapy for patients with traumatic brain injury.

Science.gov (United States)

Hegde, Shantala

2014-01-01

Traumatic brain injury (TBI) is one of the common causes of disability in physical, psychological, and social domains of functioning leading to poor quality of life. TBI leads to impairment in sensory, motor, language, and emotional processing, and also in cognitive functions such as attention, information processing, executive functions, and memory. Cognitive impairment plays a central role in functional recovery in TBI. Innovative methods such as music therapy to alleviate cognitive impairments have been investigated recently. The role of music in cognitive rehabilitation is evolving, based on newer findings emerging from the fields of neuromusicology and music cognition. Research findings from these fields have contributed significantly to our understanding of music perception and cognition, and its neural underpinnings. From a neuroscientific perspective, indulging in music is considered as one of the best cognitive exercises. With "plasticity" as its veritable nature, brain engages in producing music indulging an array of cognitive functions and the product, the music, in turn permits restoration and alters brain functions. With scientific findings as its basis, "neurologic music therapy" (NMT) has been developed as a systematic treatment method to improve sensorimotor, language, and cognitive domains of functioning via music. A preliminary study examining the effect of NMT in cognitive rehabilitation has reported promising results in improving executive functions along with improvement in emotional adjustment and decreasing depression and anxiety following TBI. The potential usage of music-based cognitive rehabilitation therapy in various clinical conditions including TBI is yet to be fully explored. There is a need for systematic research studies to bridge the gap between increasing theoretical understanding of usage of music in cognitive rehabilitation and application of the same in a heterogeneous condition such as TBI.

Can ultrasound be used to stimulate nerve tissue?

Directory of Open Access Journals (Sweden)

Norton Stephen J

2003-03-01

Full Text Available Abstract Background The stimulation of nerve or cortical tissue by magnetic induction is a relatively new tool for the non-invasive study of the brain and nervous system. Transcranial magnetic stimulation (TMS, for example, has been used for the functional mapping of the motor cortex and may have potential for treating a variety of brain disorders. Methods and Results A new method of stimulating active tissue is proposed by propagating ultrasound in the presence of a magnetic field. Since tissue is conductive, particle motion created by an ultrasonic wave will induce an electric current density generated by Lorentz forces. An analytical derivation is given for the electric field distribution induced by a collimated ultrasonic beam. An example shows that peak electric fields of up to 8 V/m appear to be achievable at the upper range of diagnostic intensities. This field strength is about an order of magnitude lower than fields typically associated with TMS; however, the electric field gradients induced by ultrasound can be quite high (about 60 kV/m2 at 4 MHz, which theoretically play a more important role in activation than the field magnitude. The latter value is comparable to TMS-induced gradients. Conclusion The proposed method could be used to locally stimulate active tissue by inducing an electric field in regions where the ultrasound is focused. Potential advantages of this method compared to TMS is that stimulation of cortical tissue could be highly localized as well as achieved at greater depths in the brain than is currently possible with TMS.

Evaluation of electrical aversion therapy for inappropriate sexual behaviour after traumatic brain injury: a single case experimental design study

Science.gov (United States)

ter Mors, Bert Jan; van Heugten, Caroline M; van Harten, Peter N

2012-01-01

Inappropriate sexual behaviour after acquired brain injury is a severe complication. Evidence for effective treatment is not available. Electrical aversion therapy (EAT) is a behavioural therapeutic option used in persons with intellectual disabilities, which might be suitable for brain-injured individuals for whom other therapies are not effective. The effect of EAT in brain injury has not been investigated previously. A single case experimental design was used. In an ABBA (baseline-treatment-treatment-withdrawal) design the frequency of the target behaviour (ie, inappropriate sexual behaviour) in a 40-year-old man was measured daily. A total of 551 measurements were recorded. A significant reduction of the target behaviour was seen after the first treatment phase (baseline 12.18 (2.59) vs 3.15 (3.19) mean target behaviours daily); this reduction remained stable over time. We conclude that EAT was effective in this patient with inappropriate sexual behaviour due to severe brain injury. EAT can therefore be considered in therapy resistant inappropriate sexual behaviour in brain-injured patients. PMID:22922913

Intensive treatment with ultrasound visual feedback for speech sound errors in childhood apraxia

Directory of Open Access Journals (Sweden)

Jonathan L Preston

2016-08-01

Full Text Available Ultrasound imaging is an adjunct to traditional speech therapy that has shown to be beneficial in the remediation of speech sound errors. Ultrasound biofeedback can be utilized during therapy to provide clients additional knowledge about their tongue shapes when attempting to produce sounds that are in error. The additional feedback may assist children with childhood apraxia of speech in stabilizing motor patterns, thereby facilitating more consistent and accurate productions of sounds and syllables. However, due to its specialized nature, ultrasound visual feedback is a technology that is not widely available to clients. Short-term intensive treatment programs are one option that can be utilized to expand access to ultrasound biofeedback. Schema-based motor learning theory suggests that short-term intensive treatment programs (massed practice may assist children in acquiring more accurate motor patterns. In this case series, three participants ages 10-14 diagnosed with childhood apraxia of speech attended 16 hours of speech therapy over a two-week period to address residual speech sound errors. Two participants had distortions on rhotic sounds, while the third participant demonstrated lateralization of sibilant sounds. During therapy, cues were provided to assist participants in obtaining a tongue shape that facilitated a correct production of the erred sound. Additional practice without ultrasound was also included. Results suggested that all participants showed signs of acquisition of sounds in error. Generalization and retention results were mixed. One participant showed generalization and retention of sounds that were treated; one showed generalization but limited retention; and the third showed no evidence of generalization or retention. Individual characteristics that may facilitate generalization are discussed. Short-term intensive treatment programs using ultrasound biofeedback may result in the acquisition of more accurate motor

A data-driven approach for evaluating multi-modal therapy in traumatic brain injury.

Science.gov (United States)

Haefeli, Jenny; Ferguson, Adam R; Bingham, Deborah; Orr, Adrienne; Won, Seok Joon; Lam, Tina I; Shi, Jian; Hawley, Sarah; Liu, Jialing; Swanson, Raymond A; Massa, Stephen M

2017-02-16

Combination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint. Data was curated and analyzed in a linked workflow involving non-linear principal component analysis followed by hypothesis testing with a linear mixed model. Results revealed significant benefits of the neurotrophic agent LM11A-31 on learning and memory outcomes after traumatic brain injury. In addition, modulations of LM11A-31 effects by co-administration of minocycline and by the type of physical therapy applied reached statistical significance. These results suggest a combinatorial effect of drug and physical therapy interventions that was not evident by univariate analysis. The study designs and analytic techniques applied here form a structured, unbiased, internally validated workflow that may be applied to other combinatorial studies, both in animals and humans.

Novel ultrasound-responsive chitosan/perfluorohexane nanodroplets for image-guided smart delivery of an anticancer agent: Curcumin.

Science.gov (United States)

Baghbani, Fatemeh; Chegeni, Mahdieh; Moztarzadeh, Fathollah; Hadian-Ghazvini, Samaneh; Raz, Majid

2017-05-01

Ultrasound-responsive nanodroplets are a class of new emerging smart drug delivery systems which provide image-guided nano-therapy of various diseases, especially cancers. Here, we developed multifunctional smart curcumin-loaded chitosan/perfluorohexane nanodroplets for contrast-ultrasound imaging and on-demand drug delivery. The nanodroplets were synthesized via nanoemulsion process. The optimal formulation with the size of 101.2nm and 77.8% curcumin entrapment was chosen for release study and cytotoxicity evaluation. Sonication at the frequency of 1MHz, 2W/cm 2 for 4min triggered the release of 63.5% of curcumin from optimal formulation (Cur-NDs-2). Ultrasound aided release study indicated that the concentration of perfluorohexane and the degree of acoustic droplet vaporization play important role in ultrasound-active drug release. B-mode ultrasound imaging confirmed strong ultrasound contrast of chitosan nanodroplets even at low concentrations via droplet to bubble transition. Finally, cytotoxicity of the ultrasound-responsive nanodroplets in the presence of ultrasound was evaluated in-vitro on 4T1 human breast cancer cells. Cell growth inhibitory effects of curcumin-loaded nanodroplets significantly increased by ultrasound exposure. According to the obtained results, these ultrasound responsive curcumin-loaded chitosan/perfluorohexane nanodroplets have a great potential for imaged-guided cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Intracavitary ultrasound phased arrays for prostate thermal therapies: MRI compatibility and in vivo testing.

Science.gov (United States)

Hutchinson, E B; Hynynen, K

1998-12-01

A 62 element MRI-compatible linear phased array was designed and constructed to investigate the feasibility of using transrectal ultrasound for the thermal therapeutic treatment of prostate cancer and benign prostatic hyperplasia. An aperiodic design technique developed in a previous study was used in the design of this array, which resulted in reduced grating lobe levels by using an optimized random distribution of unequally sized elements. The element sizes used in this array were selected to be favorable for both grating lobe levels as determined by array aperiodicity and array efficiency as determined by width to thickness ratios. The heating capabilities and MRI compatibility of the array were tested with in vivo rabbit thigh muscle heating experiments using MRI temperature monitoring. The array produced therapeutic temperature elevations in vivo at depths of 3-6 cm and axial locations up to 3 cm off the central axis and increased the size of the heated volume with electronic scanning of a single focus. The ability of this array to be used for ultrasound surgery was demonstrated by creating necrosed tissue lesions in vivo using short high-power sonications. The ability of the array to be used for hyperthermia was demonstrated by inducing therapeutic temperature elevations for longer exposures. Based on the acoustic and heating performance of this array, it has the potential to be clinically useful for delivering thermal therapies to the prostate and other target volumes close to body cavities.

Primate study suggests pentobarbital may help protect the brain during radiation therapy

International Nuclear Information System (INIS)

Skolnick, A.

1990-01-01

Radiation therapy, an often indispensable treatment for a wide range of brain tumors, is a double-edged sword, especially when used to treat children. Research reported at the 72nd Annual Meeting of the Endocrine Society, in Atlanta, Ga., now suggests that pentobarbital and perhaps other barbiturates may help protect the brain from radiation-induced damage, especially to the pituitary and hypothalmus, where such damage can lead to serious, life-long problems for children. Jeffrey J. Olson, MD, now assistant professor of neurosurgery at Emory University School of Medicine, Atlanta, reported the results of a study of the radioprotective effects of pentobarbital on the brain of a primate, which he and colleagues at the National Institute of Neurological Disorders and Stroke recently completed

Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

Science.gov (United States)

Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

2017-05-25

In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

Changes in functional connectivity correlate with behavioral gains in stroke patients after therapy using a brain-computer interface device

Directory of Open Access Journals (Sweden)

Brittany Mei Young

2014-07-01

Full Text Available Brain-computer interface (BCI technology is being incorporated into new stroke rehabilitation devices, but little is known about brain changes associated with its use. We collected anatomical and functional MRI of 9 stroke patients with persistent upper extremity motor impairment before, during, and after therapy using a BCI system. Subjects were asked to perform finger tapping of the impaired hand during fMRI. Action Research Arm Test (ARAT, 9-Hole Peg Test (9-HPT, and Stroke Impact Scale (SIS domains of Hand Function (HF and Activities of Daily Living (ADL were also assessed. Group-level analyses examined changes in whole-brain task-based functional connectivity (FC to seed regions in the motor network observed during and after BCI therapy. Whole-brain FC analyses seeded in each thalamus showed FC increases from baseline at mid-therapy and post-therapy (p< 0.05. Changes in FC between seeds at both the network and the connection levels were examined for correlations with changes in behavioral measures. Average motor network FC was increased post-therapy, and changes in average network FC correlated (p < 0.05 with changes in performance on ARAT (R2=0.21, 9-HPT (R2=0.41, SIS HF (R2=0.27, and SIS ADL (R2=0.40. Multiple individual connections within the motor network were found to correlate in change from baseline with changes in behavioral measures. Many of these connections involved the thalamus, with change in each of four behavioral measures significantly correlating with change from baseline FC of at least one thalamic connection. These preliminary results show changes in FC that occur with the administration of rehabilitative therapy using a BCI system. The correlations noted between changes in FC measures and changes in behavioral outcomes indicate that both adaptive and maladaptive changes in FC may develop with this therapy and also suggest a brain-behavior relationship that may be stimulated by the neuromodulatory component of BCI therapy.

Non-Invasive In Vivo Ultrasound Temperature Estimation

Science.gov (United States)

Bayat, Mahdi

New emerging technologies in thermal therapy require precise monitoring and control of the delivered thermal dose in a variety of situations. The therapeutic temperature changes in target tissues range from few degrees for releasing chemotherapy drugs encapsulated in the thermosensitive liposomes to boiling temperatures in complete ablation of tumors via cell necrosis. High intensity focused ultrasound (HIFU) has emerged as a promising modality for noninvasive surgery due to its ability to create precise mechanical and thermal effects at the target without affecting surrounding tissues. An essential element in all these procedures, however, is accurate estimation of the target tissue temperature during the procedure to ensure its safety and efficacy. The advent of diagnostic imaging tools for guidance of thermal therapy was a key factor in the clinical acceptance of these minimally invasive or noninvasive methods. More recently, ultrasound and magnetic resonance (MR) thermography techniques have been proposed for guidance, monitoring, and control of noninvasive thermal therapies. MR thermography has shown acceptable sensitivity and accuracy in imaging temperature change and it is currently FDA-approved on clinical HIFU units. However, it suffers from limitations like cost of integration with ultrasound therapy system and slow rate of imaging for real time guidance. Ultrasound, on the other hand, has the advantage of real time imaging and ease of integration with the therapy system. An infinitesimal model for imaging temperature change using pulse-echo ultrasound has been demonstrated, including in vivo small-animal imaging. However, this model suffers from limitations that prevent demonstration in more clinically-relevant settings. One limitation stems from the infinitesimal nature of the model, which results in spatial inconsistencies of the estimated temperature field. Another limitation is the sensitivity to tissue motion and deformation during in vivo, which

Occupational, Physical, and Speech Therapy Treatment Activities During Inpatient Rehabilitation for Traumatic Brain Injury.

Science.gov (United States)

Beaulieu, Cynthia L; Dijkers, Marcel P; Barrett, Ryan S; Horn, Susan D; Giuffrida, Clare G; Timpson, Misti L; Carroll, Deborah M; Smout, Randy J; Hammond, Flora M

2015-08-01

To describe the use of occupational therapy (OT), physical therapy (PT), and speech therapy (ST) treatment activities throughout the acute rehabilitation stay of patients with traumatic brain injury. Multisite prospective observational cohort study. Inpatient rehabilitation settings. Patients (N=2130) admitted for initial acute rehabilitation after traumatic brain injury. Patients were categorized on the basis of admission FIM cognitive scores, resulting in 5 fairly homogeneous cognitive groups. Not applicable. Percentage of patients engaged in specific activities and mean time patients engaged in these activities for each 10-hour block of time for OT, PT, and ST combined. Therapy activities in OT, PT, and ST across all 5 cognitive groups had a primary focus on basic activities. Although advanced activities occurred in each discipline and within each cognitive group, these advanced activities occurred with fewer patients and usually only toward the end of the rehabilitation stay. The pattern of activities engaged in was both similar to and different from patterns seen in previous practice-based evidence studies with different rehabilitation diagnostic groups. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of volumetric modulated arc therapy and intensity modulated radiation therapy for whole brain hippocampal sparing treatment plans based on radiobiological modeling

Directory of Open Access Journals (Sweden)

Ethan Kendall

2018-01-01

Full Text Available Introduction: In this article, we report the results of our investigation on comparison of radiobiological aspects of treatment plans with linear accelerator-based intensity-modulated radiation therapy and volumetric-modulated arc therapy for patients having hippocampal avoidance whole-brain radiation therapy. Materials and Methods: In this retrospective study using the dose-volume histogram, we calculated and compared biophysical indices of equivalent uniform dose, tumor control probability, and normal tissue complication probability (NTCP for 15 whole-brain radiotherapy patients. Results and Discussions: Dose-response models for tumors and critical structures were separated into two groups: mechanistic and empirical. Mechanistic models formulate mathematically with describable relationships while empirical models fit data through empirical observations to appropriately determine parameters giving results agreeable to those given by mechanistic models. Conclusions: Techniques applied in this manuscript could be applied to any other organs or types of cancer to evaluate treatment plans based on radiobiological modeling.

Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

Science.gov (United States)

Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

2016-09-01

We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

Change in brain and lesion volumes after CEE therapies

Science.gov (United States)

Espeland, Mark A.; Hogan, Patricia E.; Resnick, Susan M.; Bryan, R. Nick; Robinson, Jennifer G.; Goveas, Joseph S.; Davatzikos, Christos; Kuller, Lewis H.; Williamson, Jeff D.; Bushnell, Cheryl D.; Shumaker, Sally A.

2014-01-01

Objectives: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen–based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. Methods: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. Results: Total brain volume decreased an average of 3.22 cm3/y in the active arm and 3.07 cm3/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm3/y (p = 0.88). Conclusions: Conjugated equine estrogen–based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings. PMID:24384646

Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

Directory of Open Access Journals (Sweden)

Prat Frederic

2008-06-01

Full Text Available Abstract Background Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap. Methods Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm2 for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to in vivo studies on pig esophagi. Results Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases. Conclusion This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.

P32INCREASED PERCENTAGE RESECTION OF TUMOUR VOLUME USING NEURONAVIGATIONAL 3D INTRAOPERATIVE ULTRASOUND: A SINGLE UNIT EXPERIENCE

OpenAIRE

Vaqas, B.; O'Neill, K.; Awad, M.

2014-01-01

INTRODUCTION: The use of intraoperative 3D navigational ultrasound (Sonowand) offers a relatively inexpensive method of obtaining imaging of intrinsic brain tumours during resection which takes in account brain shift during surgery and also allows better visualisation of the tumour margin to help control resection. We designed a study to measure the volume of tumour resection in 25 consecutive Sonowand cases compared to 25 matched non-ultrasound guided controls. METHOD: A retrospective consec...

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

International Nuclear Information System (INIS)

Mundinger, F.

1985-01-01

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

MR-guided focused ultrasound: a potentially disruptive technology.

Science.gov (United States)

Bradley, William G

2009-07-01

A disruptive technology is a technological innovation that overturns the existing dominant technologies in a market. Magnetic resonance (MR)-guided focused ultrasound (MRgFUS) is a noninvasive procedure based on the combination of real-time MR anatomic guidance, MR thermometry, and high-intensity focused ultrasound. Several hundred transducer elements become convergent at a point under MR guidance, leading to heating and coagulation necrosis. Outside the focal point, there is no significant heating. There is no need to break the skin for procedures in the body or to perform a craniotomy for procedures in the brain. This lack of invasiveness is what makes MRgFUS so disruptive compared with surgery. At present, MRgFUS has been used for the ablation of uterine fibroids, breast tumors, painful bony metastases, and liver tumors. In the brain, it has been used for the ablation of glioblastomas and for functional neurosurgery. Phantom and animal studies suggest future applications for prostate cancer and acute stroke treatment.

TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

International Nuclear Information System (INIS)

Christensen, D.

2015-01-01

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

Energy Technology Data Exchange (ETDEWEB)

Christensen, D. [University of Utah (United States)

2015-06-15

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases : Research protocol CAR-study B

NARCIS (Netherlands)

Schimmel, W.C.M.; Verhaak, E.; Hanssens, Patrick E. J.; Gehring, K.; Sitskoorn, M.M.

2018-01-01

Background Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is

Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

Science.gov (United States)

Chu, Po-Chun; Chai, Wen-Yen; Tsai, Chih-Hung; Kang, Shih-Tsung; Yeh, Chih-Kuang; Liu, Hao-Li

2016-09-15

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

Science.gov (United States)

Minami, Yasunori; Kudo, Masatoshi

2009-12-31

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

Gadolinium neutron capture therapy for brain tumors. Biological aspects

International Nuclear Information System (INIS)

Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

1994-01-01

This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

Institute of Scientific and Technical Information of China (English)

Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

2004-01-01

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P＜0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P＜0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P＜0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS ＜70 (P＜0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

Candle soot nanoparticles-polydimethylsiloxane composites for laser ultrasound transducers

Science.gov (United States)

Chang, Wei-Yi; Huang, Wenbin; Kim, Jinwook; Li, Sibo; Jiang, Xiaoning

2015-10-01

Generation of high power laser ultrasound strongly demands the advanced materials with efficient laser energy absorption, fast thermal diffusion, and large thermoelastic expansion capabilities. In this study, candle soot nanoparticles-polydimethylsiloxane (CSNPs-PDMS) composite was investigated as the functional layer for an optoacoustic transducer with high-energy conversion efficiency. The mean diameter of the collected candle soot carbon nanoparticles is about 45 nm, and the light absorption ratio at 532 nm wavelength is up to 96.24%. The prototyped CSNPs-PDMS nano-composite laser ultrasound transducer was characterized and compared with transducers using Cr-PDMS, carbon black (CB)-PDMS, and carbon nano-fiber (CNFs)-PDMS composites, respectively. Energy conversion coefficient and -6 dB frequency bandwidth of the CSNPs-PDMS composite laser ultrasound transducer were measured to be 4.41 × 10-3 and 21 MHz, respectively. The unprecedented laser ultrasound transduction performance using CSNPs-PDMS nano-composites is promising for a broad range of ultrasound therapy applications.

Intraluminal laser atherectomy with ultrasound and electromagnetic guidance

Science.gov (United States)

Gregory, Kenton W.; Aretz, H. Thomas; Martinelli, Michael A.; LeDet, Earl G.; Hatch, G. F.; Gregg, Richard E.; Sedlacek, Tomas; Haase, Wayne C.

1991-05-01

The MagellanTM coronary laser atherectomy system is described. It uses high- resolution ultrasound imaging and electromagnetic sensing to provide real-time guidance and control of laser therapy in the coronary arteries. The system consists of a flexible catheter, an electromagnetic navigation antenna, a sensor signal processor and a computer for image processing and display. The small, flexible catheter combines an ultrasound transducer and laser delivery optics, aimed at the artery wall, and an electromagnetic receiving sensor. An extra-corporeal electromagnetic transmit antenna, in combination with catheter sensors, locates the position of the ultrasound and laser beams in the artery. Navigation and ultrasound data are processed electronically to produce real-time, transverse, and axial cross-section images of the artery wall at selected locations. By exploiting the ability of ultrasound to image beneath the surface of artery walls, it is possible to identify candidate treatment sites and perform safe radial laser debulking of atherosclerotic plaque with reduced danger of perforation. The utility of the system in plaque identification and ablation is demonstrated with imaging and experimental results.

Effects of hormone therapy on brain structure

Science.gov (United States)

Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay; Miller, Virginia M.

2016-01-01

Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42–56 years, within 5–36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Results: Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = −0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Conclusions: Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. Classification of evidence: This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. PMID:27473135

Psychomotor skills in medical ultrasound imaging: an analysis of the core skill set.

Science.gov (United States)

Nicholls, Delwyn; Sweet, Linda; Hyett, Jon

2014-08-01

Sonographers use psychomotor skills to perform medical ultrasound examinations. Psychomotor skills describe voluntary movements of the limb, joints, and muscles in response to sensory stimuli and are regulated by the motor neural cortex in the brain. We define a psychomotor skill in relation to medical ultrasound imaging as "the unique mental and motor activities required to execute a manual task safely and efficiently for each clinical situation." Skills in clinical ultrasound practice may be open or closed; most skills used in medical ultrasound imaging are open. Open skills are both complex and multidimensional. Visuomotor and visuospatial psychomotor skills are central components of medical ultrasound imaging. Both types of skills rely on learners having a visual exemplar or standard of performance with which to reference their skill performance and evaluate anatomic structures. These are imperative instructional design principles when teaching psychomotor skills. © 2014 by the American Institute of Ultrasound in Medicine.

A comparative analysis of analgesic efficacy of ultrasound and shock wave therapy in the treatment of patients with inflammation of the attachment of the plantar fascia in the course of calcaneal spurs.

Science.gov (United States)

Krukowska, Jolanta; Wrona, Jacek; Sienkiewicz, Monika; Czernicki, Jan

2016-09-01

Troublesome heel spur is a nuisance condition that affects people of all ages. Treatment of patients with heel spur is a difficult and lengthy process requiring patience from both the patient and the therapist. Sometimes, the only and ultimate method of treatment is surgery, although spurs tend to recur. The aim of the study is a comparative analysis of the analgesic efficacy of ultrasound and shock wave therapy in patients with heel spur. The cause of pain in the course of calcaneal spur is inflammation of the attachment of the plantar fascia, which plays an important role in the process of walking and is seriously strained during different types of movement. Treatment of patients is a difficult and lengthy process. The study was conducted on a group of 47 patients of both sexes, aged 38-60 years (mean 51.3) with a plantar calcaneal spur confirmed by X-ray images. Patients were randomly assigned into two groups using a simple randomization: Group 1-ultrasound therapy group (a series of ten treatments) and Group 2-the radial shock wave group (series of four treatments). In all patients, pain intensity was assessed three times: before therapy, after the first and second weeks of treatment. A version of Laitinen's pain assessment questionnaire and the Huskisson visual analogue scale (VAS) were used. Of the group of studied respondents, 47 patients of both sexes and aged 38-60 years (mean age 51.3) with a heel spur (confirmed on X-rays), who had pain for at least a month, were randomly included in the study. The patients were classified into: Group 1-US therapeutic group (a series of ten treatments) and Group 2-with RSWT (a series of five treatments). Pain intensity was assessed three times: before the treatment, after the first and second week of the treatment with the application of the VAS and the Leitinen Pain Questionnaire. However, a decrease in pain sensation was reported in all test intervals, and its largest decrease occurred in both groups within 1�

Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy

Directory of Open Access Journals (Sweden)

Wu S

2016-12-01

Full Text Available San-Gang Wu,1,* Jia-Yuan Sun,2,* Qin Tong,3 Feng-Yan Li,2 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 3Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China *These authors contributed equally to this work Objective: The objectives of this study were to describe the distribution of brain metastases (BM in breast cancer patients and investigate the risk factors for perihippocampal metastases (PHM. Patients and methods: Retrospective analysis of the clinicopathological characteristics and patterns of BM was performed. Associations between clinicopathological characteristics and PHM (the hippocampus plus 5 mm margin were evaluated using logistic regression analyses. Results: A total of 1,356 brain metastatic lesions were identified in 192 patients. Patients with 1–3 BM, 4–9 BM, and ≥10 BM accounted for 63.0%, 18.8%, and 18.2%, respectively. There were only 7 (3.6% patients with hippocampal metastases (HM and 14 (7.3% patients with PHM. On logistic regression, the number of BM was an independent risk factor for PHM. Patients with ≥10 BM had a significantly higher risk of PHM compared with those with <10 BM. Breast cancer subtype (BCS was not associated with PHM. The number of BM was significantly correlated with various BCSs. Patients with hormone receptor (HR+/human epidermal growth factor receptor 2 (HER2+, HR-/HER2+, and HR-/HER2- subtypes had a higher probability of ≥10 BM, relative to patients with an HR+/HER2- subtype. Conclusion: Our study suggests that a low incidence of PHM may be acceptable to perform hippocampal-sparing whole-brain radiation therapy for breast cancer patients

MaLT - Combined Motor and Language Therapy Tool for Brain Injury Patients Using Kinect.

Science.gov (United States)

Wairagkar, Maitreyee; McCrindle, Rachel; Robson, Holly; Meteyard, Lotte; Sperrin, Malcom; Smith, Andy; Pugh, Moyra

2017-03-23

The functional connectivity and structural proximity of elements of the language and motor systems result in frequent co-morbidity post brain injury. Although rehabilitation services are becoming increasingly multidisciplinary and "integrated", treatment for language and motor functions often occurs in isolation. Thus, behavioural therapies which promote neural reorganisation do not reflect the high intersystem connectivity of the neurologically intact brain. As such, there is a pressing need for rehabilitation tools which better reflect and target the impaired cognitive networks. The objective of this research is to develop a combined high dosage therapy tool for language and motor rehabilitation. The rehabilitation therapy tool developed, MaLT (Motor and Language Therapy), comprises a suite of computer games targeting both language and motor therapy that use the Kinect sensor as an interaction device. The games developed are intended for use in the home environment over prolonged periods of time. In order to track patients' engagement with the games and their rehabilitation progress, the game records patient performance data for the therapist to interrogate. MaLT incorporates Kinect-based games, a database of objects and language parameters, and a reporting tool for therapists. Games have been developed that target four major language therapy tasks involving single word comprehension, initial phoneme identification, rhyme identification and a naming task. These tasks have 8 levels each increasing in difficulty. A database of 750 objects is used to programmatically generate appropriate questions for the game, providing both targeted therapy and unique gameplay every time. The design of the games has been informed by therapists and by discussions with a Public Patient Involvement (PPI) group. Pilot MaLT trials have been conducted with three stroke survivors for the duration of 6 to 8 weeks. Patients' performance is monitored through MaLT's reporting facility

Near-infrared spectroscopy can reveal increases in brain activity related to animal-assisted therapy.

Science.gov (United States)

Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

2017-08-01

[Purpose] Previous studies have indicated that animal-assisted therapy can promote recovery of psychological, social, and physiological function in mental disorders. This study was designed as a pilot evaluation of the use of near-infrared spectroscopy to objectively identify changes in brain activity that could mediate the effect of animal-assisted therapy. [Subjects and Methods] The participants were 20 healthy students (10 males and 10 females; age 19-21 years) of the Faculty of Agriculture, Saga University. Participants were shown a picture of a Tokara goat or shack (control) while prefrontal cortical oxygenated haemoglobin levels (representing neural activity) were measured by near-infrared spectroscopy. [Results] The prefrontal cortical near-infrared spectroscopy signal was significantly higher during viewing of the animal picture than during a rest condition or during viewing of the control picture. [Conclusion] Our results suggest that near-infrared spectroscopy can be used to objectively identify brain activity changes during human mentation regarding animals; furthermore, these preliminary results suggest the efficacy of animal-assisted therapy could be related to increased activation of the prefrontal cortex.

Non-invasive transcranial ultrasound therapy based on a 3D CT scan: protocol validation and in vitro results

International Nuclear Information System (INIS)

Marquet, F; Pernot, M; Aubry, J-F; Montaldo, G; Tanter, M; Fink, M; Marsac, L

2009-01-01

A non-invasive protocol for transcranial brain tissue ablation with ultrasound is studied and validated in vitro. The skull induces strong aberrations both in phase and in amplitude, resulting in a severe degradation of the beam shape. Adaptive corrections of the distortions induced by the skull bone are performed using a previous 3D computational tomography scan acquisition (CT) of the skull bone structure. These CT scan data are used as entry parameters in a FDTD (finite differences time domain) simulation of the full wave propagation equation. A numerical computation is used to deduce the impulse response relating the targeted location and the ultrasound therapeutic array, thus providing a virtual time-reversal mirror. This impulse response is then time-reversed and transmitted experimentally by a therapeutic array positioned exactly in the same referential frame as the one used during CT scan acquisitions. In vitro experiments are conducted on monkey and human skull specimens using an array of 300 transmit elements working at a central frequency of 1 MHz. These experiments show a precise refocusing of the ultrasonic beam at the targeted location with a positioning error lower than 0.7 mm. The complete validation of this transcranial adaptive focusing procedure paves the way to in vivo animal and human transcranial HIFU investigations.

Non-invasive transcranial ultrasound therapy based on a 3D CT scan: protocol validation and in vitro results

Energy Technology Data Exchange (ETDEWEB)

Marquet, F; Pernot, M; Aubry, J-F; Montaldo, G; Tanter, M; Fink, M [Laboratoire Ondes et Acoustique, ESPCI, Universite Paris VII, UMR CNRS 7587, 10 rue Vauquelin, 75005 Paris (France); Marsac, L [Supersonic Imagine, Les Jardins de la Duranne, 510 rue Rene Descartes, 13857 Aix-en-Provence (France)], E-mail: fabrice.marquet@espci.org

2009-05-07

A non-invasive protocol for transcranial brain tissue ablation with ultrasound is studied and validated in vitro. The skull induces strong aberrations both in phase and in amplitude, resulting in a severe degradation of the beam shape. Adaptive corrections of the distortions induced by the skull bone are performed using a previous 3D computational tomography scan acquisition (CT) of the skull bone structure. These CT scan data are used as entry parameters in a FDTD (finite differences time domain) simulation of the full wave propagation equation. A numerical computation is used to deduce the impulse response relating the targeted location and the ultrasound therapeutic array, thus providing a virtual time-reversal mirror. This impulse response is then time-reversed and transmitted experimentally by a therapeutic array positioned exactly in the same referential frame as the one used during CT scan acquisitions. In vitro experiments are conducted on monkey and human skull specimens using an array of 300 transmit elements working at a central frequency of 1 MHz. These experiments show a precise refocusing of the ultrasonic beam at the targeted location with a positioning error lower than 0.7 mm. The complete validation of this transcranial adaptive focusing procedure paves the way to in vivo animal and human transcranial HIFU investigations.

Application of Ultrasonic Techniques for Brain Injury Diagnosis

International Nuclear Information System (INIS)

Kasili, P.M.; Mobley, J.; Norton, S.J.; Vo-Dinh, T.

1999-01-01

In this work, we evaluate methods for detecting brain injury using ultrasound. We have used simulations of ultrasonic fields in the head to model the phase distortion of the skull. In addition we present experimental data from the crania of large animals. The experimental data help us understand and evaluate the performance of different transducers in acquiring the backscatter data from the brain through the skull. Both the simulations and acquired data illustrate the superiority of lower-frequency (<= 1 MHz) ultrasonic fields for transcranial acquisition of signals from inside the brain. Additionally, the experimental work shows that the higher-frequency (5 MHz) ultrasound can also be useful in acquiring clean nearfield data to help detect the position of the inner boundary of the skull

Imaging the premature brain: ultrasound or MRI?

Energy Technology Data Exchange (ETDEWEB)

Vries, Linda S. de; Benders, Manon J.N.L.; Groenendaal, Floris [UMC Utrecht, Department of Neonatology, Wilhelmina Children' s Hospital, PO Box 85090, Utrecht (Netherlands)

2013-09-15

Neuroimaging of preterm infants has become part of routine clinical care, but the question is often raised on how often cranial ultrasound should be done and whether every high risk preterm infant should at least have one MRI during the neonatal period. An increasing number of centres perform an MRI either at discharge or around term equivalent age, and a few centres have access to a magnet in or adjacent to the neonatal intensive care unit and are doing sequential MRIs. In this review, we try to discuss when best to perform these two neuroimaging techniques and the additional information each technique may provide. (orig.)

Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

Energy Technology Data Exchange (ETDEWEB)

Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho [Dept. of Radiology, Saga Medical School (Japan); Matsui, Makoto; Kuroda, Yasuo [Dept. of Neurology, Saga Medical School (Japan)

2001-12-01

We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

International Nuclear Information System (INIS)

Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho; Matsui, Makoto; Kuroda, Yasuo

2001-01-01

We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

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

Therapeutic Ultrasound Bypasses Canonical Syndecan-4 Signaling to Activate Rac1*S⃞

Science.gov (United States)

Mahoney, Claire M.; Morgan, Mark R.; Harrison, Andrew; Humphries, Martin J.; Bass, Mark D.

2009-01-01

The application of pulsed, low intensity ultrasound is emerging as a potent therapy for the treatment of complex bone fractures and tissue damage. Ultrasonic stimuli accelerate fracture healing by up to 40% and enhance tendon and ligament healing by promoting cell proliferation, migration, and matrix synthesis through an unresolved mechanism. Ultrasound treatment also induces closure of nonunion fractures, at a success rate (85% of cases) similar to that of surgical intervention (68-96%) while avoiding the complications associated with surgery. The regulation of cell adhesion necessary for wound healing depends on cooperative engagement of the extracellular matrix receptors, integrin and syndecan, as exemplified by the wound healing defects observed in syndecan- and integrin-knock-out mice. This report distinguishes the influence of ultrasound on signals downstream of the prototypic fibronectin receptors, α5β1 integrin and syndecan-4, which cooperate to regulate Rac1 and RhoA. Ultrasonic stimulation fails to activate integrins or induce cell spreading on poor, electrostatic ligands. By contrast, ultrasound treatment overcomes the necessity of engagement or expression of syndecan-4 during the process of focal adhesion formation, which normally requires simultaneous engagement of both receptors. Ultrasound exerts an influence downstream of syndecan-4 and PKCα to specifically activate Rac1, itself a critical regulator of tissue repair, and to a lesser extent RhoA. The ability of ultrasound to bypass syndecan-4 signaling, which is known to facilitate efficient tissue repair, explains the reduction in healing times observed in ultrasound-treated patients. By substituting for one of the key axes of adhesion-dependent signaling, ultrasound therapy has considerable potential as a clinical technique. PMID:19147498

Effect of body mass index on shifts in ultrasound-based image-guided intensity-modulated radiation therapy for abdominal malignancies

International Nuclear Information System (INIS)

Choi, Mehee; Fuller, Clifton D.; Wang, Samuel J.; Siddiqi, Ather; Wong, Adrian; Thomas, Charles R.; Fuss, Martin

2009-01-01

Background and purpose: We investigated whether corrective shifts determined by daily ultrasound-based image-guidance correlate with body mass index (BMI) of patients treated with image-guided intensity-modulated radiation therapy (IG-IMRT) for abdominal malignancies. The utility of daily image-guidance, particularly for patients with BMI > 25.0, is examined. Materials and methods: Total 3162 ultrasound-directed shifts were performed in 86 patients. Direction and magnitude of shifts were correlated with pretreatment BMI. Bivariate statistical analysis and analysis of set-up correction data were performed using systematic and random error calculations. Results: Total 2040 daily alignments were performed. Average 3D vector of set-up correction for all patients was 12.1 mm/fraction. Directional and absolute shifts and 3D vector length were significantly different between BMI cohorts. 3D displacement averaged 4.9 mm/fraction and 6.8mm/fraction for BMI ≤ 25.0 and BMI > 25.0, respectively. Systematic error in all axes and 3D vector was significantly greater for BMI > 25.0. Differences in random error were not statistically significant. Conclusions: Set-up corrections derived from daily ultrasound-based IG-IMRT of abdominal tumors correlated with BMI. Daily image-guidance may improve precision of IMRT delivery with benefits assessed for the entire population, particularly patients with increased habitus. Requisite PTV margins suggested in the absence of daily image-guidance are significantly greater in patients with BMI > 25.0.

Retrospective study on therapy options of brain metastases: surgery versus stereotactic radiotherapy with the linear accelerator

International Nuclear Information System (INIS)

Fortunati, M.K.S.

2001-04-01

Background: in the therapy of brain metastases there has been a great progress in the last years. It was shown, that more aggressive therapies can not only extend the survival of the patients, but also improve quality of life. The major question of this study was, whether surgery or stereotactic radiotherapy with the linear accelerator show better results in behalf of the survival. Beside this major question many parameters regarding the patient or his primary cancer were examined. Methods: from the 1st of January 1995 until the 30th of June 2000 233 patients with one or more brain metastases have been treated in the Wagner Jauregg Landesnervenkrankenhaus Oberoesterreich (WJ LNKH OeO). The LINAC has been established on the 1st of July 1997. The patients have been distributed in three groups: 1. LINAC-group: 81 patients have been treated from the 1st of July 1997 until the 30th of June 2000 with the LINAC. 2. Surgery-group: 81 patients have been operated from the 1st of July 1997 until the 30th June 2000. 3 Control-group: 71 patients have been operated from the 1st of January 1995 until the 30th of June 1997, before the LINAC has been established on the 1st of July 1997. Results: There are shown the mean survival times. Therapy options (0,05): LINAC-group: 377 days. Surgery-group: 195 days. Control-group: 285 days. Primary cancer (0,05): unknown primary: 203 days. Cancer of the colon tract: 218 days. Breast cancer: 314 days. Melanoma: 162 days. Kidney: 466 days. Lung 261 days. Others: 439 days. Metastases in one/in both hemispheres (0,05): in one hemisphere 310 days, in both 184 days. All the other parameters (age, sex, Karnofsky-Index, period between diagnose of the primary and the brain metastases, primary cancer therapy, extra cerebral metastases, number of metastases, localization of metastases supra- or infratentoriell, dose/effect relationship in the LINAC-group, whole brain radiotherapy) showed interesting differences, but the results were not statistically

Intracavitary ultrasound phased arrays for thermal therapies

Science.gov (United States)

Hutchinson, Erin

Currently, the success of hyperthermia and thermal surgery treatments is limited by the technology used in the design and fabrication of clinical heating devices and the completeness of the thermometry systems used for guidance. For both hyperthermia and thermal surgery, electrically focused ultrasound generated by phased arrays provides a means of controlling localized energy deposition in body tissues. Intracavitary applicators can be used to bring the energy source close to a target volume, such as the prostate, thereby minimizing normal tissue damage. The work performed in this study was aimed at improving noninvasive prostate thermal therapies and utilized three research approaches: (1) Acoustic, thermal and optimization simulations, (2) Design and fabrication of multiple phased arrays, (3) Ex vivo and in vivo experimental testing of the heating capabilities of the phased arrays. As part of this study, a novel aperiodic phased array design was developed which resulted in a 30- 45% reduction in grating lobe levels when compared to conventional phased arrays. Measured acoustic fields generated by the constructed aperiodic arrays agreed closely with the fields predicted by the theoretical simulations and covered anatomically appropriate ranges. The power capabilities of these arrays were demonstrated to be sufficient for the purposes of hyperthermia and thermal surgery. The advantage of using phased arrays in place of fixed focus transducers was shown by demonstrating the ability of electronic scanning to increase the size of the necrosed tissue volume while providing a more uniform thermal dose, which can ultimately reduce patient treatment times. A theoretical study on the feasibility of MRI (magnetic resonance imaging) thermometry for noninvasive temperature feedback control was investigated as a means to improve transient and steady state temperature distributions achieved in hyperthermia treatments. MRI guided ex vivo and in vivo experiments demonstrated

Near-infrared spectroscopy can reveal increases in brain activity related to animal-assisted therapy

OpenAIRE

Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

2017-01-01

[Purpose] Previous studies have indicated that animal-assisted therapy can promote recovery of psychological, social, and physiological function in mental disorders. This study was designed as a pilot evaluation of the use of near-infrared spectroscopy to objectively identify changes in brain activity that could mediate the effect of animal-assisted therapy. [Subjects and Methods] The participants were 20 healthy students (10 males and 10 females; age 19?21 years) of the Faculty of Agricultur...

Synthesis of Laboratory Ultrasound Contrast Agents

Directory of Open Access Journals (Sweden)

Jaemin Oh

2013-10-01

Full Text Available Ultrasound Contrast Agents (UCAs were developed to maximize reflection contrast so that organs can be seen clearly in ultrasound imaging. UCAs increase the signal to noise ratio (SNR by linear and non-linear mechanisms and thus help more accurately visualize the internal organs and blood vessels. However, the UCAs on the market are not only expensive, but are also not optimized for use in various therapeutic research applications such as ultrasound-aided drug delivery. The UCAs fabricated in this study utilize conventional lipid and albumin for shell formation and perfluorobutane as the internal gas. The shape and density of the UCA bubbles were verified by optical microscopy and Cryo SEM, and compared to those of the commercially available UCAs, Definity® and Sonovue®. The size distribution and characteristics of the reflected signal were also analyzed using a particle size analyzer and ultrasound imaging equipment. Our experiments indicate that UCAs composed of spherical microbubbles, the majority of which were smaller than 1 um, were successfully synthesized. Microbubbles 10 um or larger were also identified when different shell characteristics and filters were used. These laboratory UCAs can be used for research in both diagnoses and therapies.

Hyperglycemia and ultrasound in radiotherapy of experimental tumors (a preliminary paper)

International Nuclear Information System (INIS)

Muratkhodzhaev, N.K.; Prus, E.S.; Zakirkhodzhaev, U.D.; Kutlimuratov, A.B.

1984-01-01

Experimental studies have shown that all the types of effects, as compared with the control, result in inhibition of the tumor growth; X-ray therapy decelerates the tumor growth, but its combination with hyperglycemia produced a more vivid effect. Inhibition of the tumor growth, as compared with that in the control group, was observed under a combined effect of hyperglycemia with ultrasound, though it was noticeably weaker than under other effects. Application of a complex effect including hyperglycemia, ultrasound, X-ray therapy turned to be most effective, the succession of their application playing an important role for the antitumoral effect of the used factors

Machine Learning Classification to Identify the Stage of Brain-Computer Interface Therapy for Stroke Rehabilitation Using Functional Connectivity

Directory of Open Access Journals (Sweden)

Rosaleena Mohanty

2018-05-01

Full Text Available Interventional therapy using brain-computer interface (BCI technology has shown promise in facilitating motor recovery in stroke survivors; however, the impact of this form of intervention on functional networks outside of the motor network specifically is not well-understood. Here, we investigated resting-state functional connectivity (rs-FC in stroke participants undergoing BCI therapy across stages, namely pre- and post-intervention, to identify discriminative functional changes using a machine learning classifier with the goal of categorizing participants into one of the two therapy stages. Twenty chronic stroke participants with persistent upper-extremity motor impairment received neuromodulatory training using a closed-loop neurofeedback BCI device, and rs-functional MRI (rs-fMRI scans were collected at four time points: pre-, mid-, post-, and 1 month post-therapy. To evaluate the peak effects of this intervention, rs-FC was analyzed from two specific stages, namely pre- and post-therapy. In total, 236 seeds spanning both motor and non-motor regions of the brain were computed at each stage. A univariate feature selection was applied to reduce the number of features followed by a principal component-based data transformation used by a linear binary support vector machine (SVM classifier to classify each participant into a therapy stage. The SVM classifier achieved a cross-validation accuracy of 92.5% using a leave-one-out method. Outside of the motor network, seeds from the fronto-parietal task control, default mode, subcortical, and visual networks emerged as important contributors to the classification. Furthermore, a higher number of functional changes were observed to be strengthening from the pre- to post-therapy stage than the ones weakening, both of which involved motor and non-motor regions of the brain. These findings may provide new evidence to support the potential clinical utility of BCI therapy as a form of stroke

Ultrasound pregnancy

Science.gov (United States)

Pregnancy sonogram; Obstetric ultrasonography; Obstetric sonogram; Ultrasound - pregnancy; IUGR - ultrasound; Intrauterine growth - ultrasound; Polyhydramnios - ultrasound; Oligohydramnios - ultrasound; ...

Calcification of the bilateral basal ganglia after radiation therapy for childhood brain tumors

Energy Technology Data Exchange (ETDEWEB)

Kubo, Osami; Tajika, Yasuhiko; Sakairi, Mitsuhiko; Katahira, Masako; Shimizu, Takashi; Kitamura, Koichi

1987-12-01

Calcification of the basal ganglia subsequent to radiation therapy for childhood brain tumors has rarely been reported. Three cases of this calcification subsequent to radiation are presented here. Case 1 is a 7 year-old boy who underwent irradiation of 5000 rads locally for craniopharyngioma at the age of 4 years. Case 2 is a 4 year-old boy who was treated with irradiation of 4500 rads locally for cerebellar medulloblastoma at the age of 1 year. Case 3 is a 15 year-old girl who was treated with irradiation of 5000 rads to the brain and 3000 rads locally for suprasellar germinoma at the age of 11 years. In all these cases, the interval between radiation and evidence of calcification as detected only by CT scan, was more than 3 years and 2 cases are experiencing mild mental retardation. These findings suggest the possibility of long-term complications due to radiation therapy.

Boron neutron capture therapy for malignant brain tumor and future potential

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Hatanaka, Hiroshi.

1994-01-01

This paper presents therapeutic experience with boron neutron capture therapy (BNCT) for malignant brain tumors. Nine patients who survived for 10 years or more as of 1986 are given in a table. A review of the 9 patients concluded that physical dose of 15 Gy is required. In addition, the following factors are defined to be the most important: (1) to determine tumor size and depth as accurately as possible, (2) to measure neutron doses in the deepest site of the tumor during irradiation, (3) to measure the content of boron within the tumor, and to deliver neutron beams as deeply as possible. Finally, the importance of knowing RBE of alpha particles for tumor cells of the human brain is emphasized. (N.K.)

A comparison of portable ultrasound and fully-equipped clinical ultrasound unit in the thyroid size measurement of the Indo-Pacific bottlenose dolphin.

Directory of Open Access Journals (Sweden)

Brian C W Kot

Full Text Available Measurement of thyroid size and volume is a useful clinical parameter in both human and veterinary medicine, particularly for diagnosing thyroid diseases and guiding corrective therapy. Procuring a fully-equipped clinical ultrasound unit (FCUS may be difficult in most veterinary settings. The present study evaluated the inter-equipment variability in dolphin thyroid ultrasound measurements between a portable ultrasound unit (PUS and a FCUS; for both units, repeatability was also assessed. Thyroid ultrasound examinations were performed on 15 apparently healthy bottlenose dolphins with both PUS and FCUS under identical scanning conditions. There was a high level of agreement between the two ultrasound units in dolphin thyroid measurements (ICC = 0.859-0.976. A high intra-operator repeatability in thyroid measurements was found (PUS: ICC = 0.854-0.984, FCUS: ICC = 0.709-0.954. As a conclusion, no substantial inter-equipment variability was found between PUS and FCUS in dolphin thyroid size measurements under identical scanning conditions, supporting further application of PUS for quantitative analyses of dolphin thyroid gland in both research and clinical practices at aquarium settings.

Multiple sessions of liposomal doxorubicin delivery via focused ultrasound mediated blood-brain barrier disruption: a safety study.

Science.gov (United States)

Aryal, Muna; Vykhodtseva, Natalia; Zhang, Yong-Zhi; McDannold, Nathan

2015-04-28

Transcranial MRI-guided focused ultrasound is a rapidly advancing method for delivering therapeutic and imaging agents to the brain. It has the ability to facilitate the passage of therapeutics from the vasculature to the brain parenchyma, which is normally protected by the blood-brain barrier (BBB). The method's main advantages are that it is both targeted and noninvasive, and that it can be easily repeated. Studies have shown that liposomal doxorubicin (Lipo-DOX), a chemotherapy agent with promise for tumors in the central nervous system, can be delivered into the brain across BBB. However, prior studies have suggested that doxorubicin can be significantly neurotoxic, even at small concentrations. Here, we studied whether multiple sessions of Lipo-DOX administered after FUS-induced BBB disruption (FUS-BBBD) induces severe adverse events in the normal brain tissues. First, we used fluorometry to measure the doxorubicin concentrations in the brain after FUS-BBBD to ensure that a clinically relevant doxorubicin concentration was achieved in the brain. Next, we performed three weekly sessions with FUS-BBBD±Lipo-DOX administration. Five to twelve targets were sonicated each week, following a schedule described previously in a survival study in glioma-bearing rats (Aryal et al., 2013). Five rats received three weekly sessions where i.v. injected Lipo-DOX was combined with FUS-BBBD; an additional four rats received FUS-BBBD only. Animals were euthanized 70days from the first session and brains were examined in histology. We found that clinically-relevant concentrations of doxorubicin (4.8±0.5μg/g) were delivered to the brain with the sonication parameters (0.69MHz; 0.55-0.81MPa; 10ms bursts; 1Hz PRF; 60s duration), microbubble concentration (Definity, 10μl/kg), and the administered Lipo-DOX dose (5.67mg/kg) used. The resulting concentration of Lipo-DOX was reduced by 32% when it was injected 10min after the last sonication compared to cases where the agent was

Ultrasound techniques in the evaluation of the mediastinum, part 2

DEFF Research Database (Denmark)

Jenssen, Christian; Annema, Jouke Tabe; Clementsen, Paul

2015-01-01

and inoperable lung cancer (e.g., surgery vs. combined chemoradiation therapy). Tissue sampling is often indicated for accurate nodal staging. Recent international lung cancer staging guidelines clearly state that endosonography should be the initial tissue sampling test over surgical staging. Mediastinal nodes...... can be sampled from the airways [endobronchial ultrasound combined with transbronchial needle aspiration (EBUS-TBNA)] or the esophagus [endoscopic ultrasound fine needle aspiration (EUS-FNA)]. EBUS and EUS have a complementary diagnostic yield and in combination virtually all MLNs can be biopsied...... and mediastinal staging of lung cancer. A specific emphasis will be on learning mediastinal endosonography. Part 1 deals with an introduction into ultrasound techniques, MLN anatomy and diagnostic reach of ultrasound techniques and part 2 with the clinical work up of neoplastic and inflammatory mediastinal...

Animal study assessing safety of an acoustic coupling fluid that holds the potential to avoid surgically induced artifacts in 3D ultrasound guided operations

International Nuclear Information System (INIS)

Jakola, Asgeir S; Jørgensen, Arve; Selbekk, Tormod; Michler, Ralf-Peter; Solheim, Ole; Torp, Sverre H; Sagberg, Lisa M; Aadahl, Petter; Unsgård, Geirmund

2014-01-01

Use of ultrasound in brain tumor surgery is common. The difference in attenuation between brain and isotonic saline may cause artifacts that degrade the ultrasound images, potentially affecting resection grades and safety. Our research group has developed an acoustic coupling fluid that attenuates ultrasound energy like the normal brain. We aimed to test in animals if the newly developed acoustic coupling fluid may have harmful effects. Eight rats were included for intraparenchymal injection into the brain, and if no adverse reactions were detected, 6 pigs were to be included with injection of the coupling fluid into the subarachnoid space. Animal behavior, EEG registrations, histopathology and immunohistochemistry were used in assessment. In total, 14 animals were included, 8 rats and 6 pigs. We did not detect any clinical adverse effects, seizure activity on EEG or histopathological signs of tissue damage. The novel acoustic coupling fluid intended for brain tumor surgery appears safe in rats and pigs under the tested circumstances

Efficacy of Ablation Therapy for Secondary Hyperparathyroidism by Ultrasound Guided Percutaneous Thermoablation.

Science.gov (United States)

Zhao, Junfeng; Qian, Linxue; Zu, Yuan; Wei, Ying; Hu, Xiangdong

2016-05-01

The objective of this study was to explore the value of ultrasound-guided percutaneous microwave thermoablation to treat secondary hyperparathyroidism (SHPT). One hundred and thirty-eight parathyroid glands from 56 patients with SHPT were ablated in this study. All the parathyroid glands were evaluated by real-time contrast-enhanced ultrasound before, during and after ablation. Changes in serum parathyroid hormone (sPTH) levels were measured before treatment and at 1 h, 1 wk, 1 mo and 6 mo after thermoablation treatment. All 56 cases had a 1-mo follow-up, and 34 cases had a 6-mo follow-up. The sPTH level of the 54 cases 1 mo after ablation was significantly lower than that before (p 0.05). Ultrasound-guided percutaneous microwave thermoablation is a feasible and effective non-surgical alternative treatment for SHPT patients. Copyright © 2016. Published by Elsevier Inc.

Carotid Doppler ultrasound findings in patients with left ventricular assist devices.

Science.gov (United States)

Cervini, Patrick; Park, Soon J; Shah, Dipesh K; Penev, Irina E; Lewis, Bradley D

2010-12-01

Left ventricular assist devices (LVADs) have been used to treat advanced heart failure refractory to medical management, as bridge therapy to myocardial recovery, as bridge therapy to cardiac transplantation, or as destination therapy for patients with unfavorable transplant candidacy. Neurologic complications are some of the most common and devastating complications in these patients. Preoperative carotid ultrasound is, therefore, a standard evaluation in patients at risk for cerebrovascular disease. Postoperative carotid artery Doppler sonography is performed in those patients with neurologic symptoms. It is likely, therefore, that sonographers, radiologists, and other physicians working in a center where LVADs are implanted will likely encounter a carotid artery Doppler study in this patient group. To our knowledge, the carotid Doppler findings in these patients have never been published. We review the Doppler ultrasound findings in 6 patients after LVAD insertion.

A brief history of ultrasound in rheumatology: where we were.

Science.gov (United States)

Grassi, Walter; Filippucci, Emilio

2014-01-01

Ultrasonography in the '70s was a well-known and widely used method within several medical specialties but not in rheumatology. Initial development of the field was led by radiologists who mainly investigated the potential of ultrasound in the assessment of large joints. In the late '80s, the first studies supporting the role of ultrasound in the detection of soft tissue changes and bone erosions in the hands of patients with rheumatoid arthritis were published. In the '90s, the dramatic improvement of spatial resolution due to the new generation high frequency probes opened up new avenues for the exploration of otherwise undetectable anatomical details. Ultrasound research during this period was enhanced by the growing use of colour Doppler and power Doppler and by the first prototypes of three dimensional ultrasound. Over the last 10 years, the buzz words in ultrasound research in rheumatology have been standardisation, early diagnosis and therapy monitoring.

IPEM Report No 84: Guidelines for the Testing and Calibration of Physiotherapy Ultrasound Machines

Energy Technology Data Exchange (ETDEWEB)

Duck, Francis A

2003-01-21

Institute of Physics and Engineering in Medicine York: IPEM (2001) 67 pp, 20.00 British Pounds, ISBN: 0-904181-98-7. This 67-page soft-cover report has been prepared by an expert group within the Institute of Physics and Engineering in Medicine (IPEM) to provide detailed guidance on the testing and calibration of ultrasound therapy devices. Physiotherapists have long used external energy sources to supplement massage and manipulation for musculo-skeletal therapy. Whilst, recently, there has been a general reduction in use of electrotherapy using radio-frequency radiation, microwaves and interferential devices, ultrasound therapy still remains central to physiotherapy practice. There is now robust evidence that, at least for some injuries, ultrasound accelerates the repair of injured tissue. This has been particularly well demonstrated for bone fracture repair. Managed therapy relies on well-calibrated radiation sources. Unfortunately, there has been less than adequate management of ultrasound output in the past. Several well-documented situations have occurred for which faulty ultrasound equipment has continued in clinical use, either generating no output at all, or, more seriously, operating at maximum power all the time. This report reminds those responsible for managing ultrasound equipment of the need for testing and calibration, and gives detailed advice on procedures for carrying this out. These details are contained in 12 annexes forming the majority of the text. Each annex presents a self-contained aspect of one aspect of testing or calibration, such as the measurement of acoustic power, or an example protocol for machine testing. Each is sufficiently detailed to allow novice technical staff to follow the recommended procedure, or to allow a department to plan to introduce ultrasound field calibration into its practice. Other annexes contain useful additional material, not included in the earlier IPSM Report 58. A procedure for the measurement of effective

Target volumes in radiation therapy of childhood brain tumours

International Nuclear Information System (INIS)

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

2001-01-01

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

Bursting neurons and ultrasound avoidance in crickets

Directory of Open Access Journals (Sweden)

Gary eMarsat

2012-07-01

Full Text Available Decision making in invertebrates often relies on simple neural circuits composed of only a few identified neurons. The relative simplicity of these circuits makes it possible to identify the key computation and neural properties underlying decisions. In this review, we summarize recent research on the neural basis of ultrasound avoidance in crickets, a response that allows escape from echolocating bats. The key neural property shaping behavioral output is high-frequency bursting of an identified interneuron, AN2, which carries information about ultrasound stimuli from receptor neurons to the brain. AN2's spike train consists of clusters of spikes –bursts– that may be interspersed with isolated, non-burst spikes. AN2 firing is necessary and sufficient to trigger avoidance steering but only high-rate firing, such as occurs in bursts, evokes this response. AN2 bursts are therefore at the core of the computation involved in deciding whether or not to steer away from ultrasound. Bursts in AN2 are triggered by synaptic input from nearly synchronous bursts in ultrasound receptors. Thus the population response at the very first stage of sensory processing –the auditory receptor- already differentiates the features of the stimulus that will trigger a behavioral response from those that will not. Adaptation, both intrinsic to AN2 and within ultrasound receptors, scales the burst-generating features according to the stimulus statistics, thus filtering out background noise and ensuring that bursts occur selectively in response to salient peaks in ultrasound intensity. Furthermore AN2’s sensitivity to ultrasound varies adaptively with predation pressure, through both developmental and evolutionary mechanisms. We discuss how this key relationship between bursting and the triggering of avoidance behavior is also observed in other invertebrate systems such as the avoidance of looming visual stimuli in locusts or heat avoidance in beetles.

Non-invasive estimation of temperature using diagnostic ultrasound during HIFU therapy

Science.gov (United States)

Georg, O.; Wilkens, V.

2017-03-01

The use of HIFU for thermal ablation of human tissues requires safe real-time monitoring of the lesion formation during the treatment to avoid damage of the surrounding healthy tissues and to control temperature rise. Besides MR imaging, several methods have been proposed for temperature imaging using diagnostic ultrasound, and echoshift estimation (using speckle tracking) is the most promising and commonly used technique. It is based on the thermal dependence of the ultrasound echo that accounts for two different physical phenomena: local change in speed of sound and thermal expansion of the propagating medium due to changes in temperature. In our experiments we have used two separate transducers: HIFU exposure was performed using a 1.06 MHz single element focusing transducer of 64 mm aperture and 63.2 mm focal length; the ultrasound diagnostic probe of 11 MHz operated in B-mode for image guidance. The temperature measurements were performed in an agar-based tissue-mimicking phantom. To verify the obtained results, numerical modeling of the acoustic and temperature fields was carried out using KZK and Pennes Bioheat equations, as well as measurements with thermocouples were performed.

Soothing the threatened brain: leveraging contact comfort with emotionally focused therapy.

Directory of Open Access Journals (Sweden)

Susan M Johnson

Full Text Available Social relationships are tightly linked to health and well-being. Recent work suggests that social relationships can even serve vital emotion regulation functions by minimizing threat-related neural activity. But relationship distress remains a significant public health problem in North America and elsewhere. A promising approach to helping couples both resolve relationship distress and nurture effective interpersonal functioning is Emotionally Focused Therapy for couples (EFT, a manualized, empirically supported therapy that is strongly focused on repairing adult attachment bonds. We sought to examine a neural index of social emotion regulation as a potential mediator of the effects of EFT. Specifically, we examined the effectiveness of EFT for modifying the social regulation of neural threat responding using an fMRI-based handholding procedure. Results suggest that EFT altered the brain's representation of threat cues in the presence of a romantic partner. EFT-related changes during stranger handholding were also observed, but stranger effects were dependent upon self-reported relationship quality. EFT also appeared to increase threat-related brain activity in regions associated with self-regulation during the no-handholding condition. These findings provide a critical window into the regulatory mechanisms of close relationships in general and EFT in particular.