Arik Hananel - Academia.edu (original) (raw)

Papers by Arik Hananel

Research paper thumbnail of In vivo low frequency MR-guided thalamotomy with focused ultrasound: thermal vs mechanical lesioning in pig brain

Journal of Therapeutic Ultrasound, 2015

Research paper thumbnail of T1-weighted MRI as a substitute to CT for skull aberration correction in transcranial focused ultrasound: in vivo feasibility and in vitro comparison on human calvaria

Journal of Therapeutic Ultrasound, 2015

Research paper thumbnail of Thermal dose and radiation dose comparison based on cell survival

Journal of Therapeutic Ultrasound, 2015

Research paper thumbnail of Head phantoms for transcranial focused ultrasound

Medical physics, 2015

In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focuse... more In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focused ultrasound (tcMRgFUS), ex-vivo studies wlkiith whole human skulls are of great use in improving the underlying technology guiding the accurate and precise thermal ablation of clinically relevant targets in the human skull. Described here are the designs, methods for fabrication, and notes on utility of three different ultrasound phantoms to be used for brain focused ultrasound research. Three different models of phantoms are developed and tested to be accurate, repeatable experimental options to provide means to further this research. The three models are a cadaver, a gel-filled skull, and a head mold containing a skull and filled with gel that mimics the brain and the skin. Each was positioned in a clinical tcMRgFUS system and sonicated at 1100 W (acoustic) for 12 s at different locations. Maximum temperature rise as measured by MR thermometry was recorded and compared against clinica...

Research paper thumbnail of Trans-cranial focused ultrasound without hair shaving: feasibility study in an ex vivo cadaver model

Journal of therapeutic ultrasound, 2013

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound proc... more In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient's head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220- and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz.

Research paper thumbnail of The Journal of Therapeutic Ultrasound: broadening knowledge in a rapidly growing field

Journal of therapeutic ultrasound, 2013

The Journal of Therapeutic Ultrasound has been established to provide an open access, online venu... more The Journal of Therapeutic Ultrasound has been established to provide an open access, online venue for the exponentially growing body of work in biomedical ultrasound therapy.

Research paper thumbnail of <title>MRI-guided focused ultrasound (MRgFUS) system for thermal ablation of prostate cancer: pre-clinical evaluation in canines</title>

Energy-based Treatment of Tissue and Assessment V, 2009

A transrectal MRgFUS system was tested in a canine prostate model. Focal volumes in each half of ... more A transrectal MRgFUS system was tested in a canine prostate model. Focal volumes in each half of the prostate were targeted, with high energy in one half of the gland for ablation and in the other with lower-energy sonications to test our ability to localize the focal spot before causing thermal tissue damage. All sonications (n=155) were readily observed with proton resonance frequency (PRF) MR temperature imaging, contrast enhanced MRI and histology. The prostate gland moved during the experiments, demonstrating the need for motion tracking. The resultant focal temperature changes during the experiments were 24.2 ± 8.2°C.

Research paper thumbnail of The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus

Journal of Therapeutic Ultrasound, 2013

Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non... more Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.

Research paper thumbnail of Focused ultrasound development and clinical adoption: 2013 update on the growth of the field

Journal of Therapeutic Ultrasound, 2014

The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significa... more The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significant growth, particularly over the past decade. The eventual widespread clinical adoption of this non-invasive therapeutic modality require continued progress, in a multitude of activities including technical, pre-clinical, and clinical research, regulatory approval and reimbursement, manufacturer growth, and other commercial and public sector investments into the field, all within a multi-stakeholder environment. We present here a snapshot of the field of focused ultrasound and describe how it has progressed over the past several decades. It is assessed using metrics which include quantity and breadth of academic work (presentations, publications), funding trends, manufacturer presence in the field, number of treated patients, number of indications reaching first-in-human status, and quantity and breadth of clinical indications.

Research paper thumbnail of International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions

International Journal of Hyperthermia, 2015

Abstract Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), ... more Abstract Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

Research paper thumbnail of Effects of human hair on trans-cranial focused ultrasound efficacy in an ex-vivo cadaver model

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound proc... more In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient's head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220-and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz.

Research paper thumbnail of Intracranial treatment envelope mapping of transcranial focused ultrasound

Research paper thumbnail of High-intensity Focused Ultrasound

Research paper thumbnail of T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided focused ultrasound

Physics in medicine and biology, Jan 7, 2014

Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimi... more Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve temperatures capable of inducing coagulative necrosis at acceptable power deposition levels. CT is usually used for this refocusing but requires a separate study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to determine whether MRI using an appropriate sequence would be a viable alternative to CT for planning ultrasound refocusing in TcMRgFUS. We tested three MRI pulse sequences (3D T1 weighted 3D volume interpolated breath hold examination (VIBE), proton density weighted 3D sampling perfection with applications optimized contrasts using different flip angle evolution and 3D true fast imaging with steady state precision T2-weighted imaging) on patients who have already had a CT scan performed. We made detailed measurements of the calvarial structure based on the MRI data and compared those so-called 'virt...

Research paper thumbnail of Intracranial inertial cavitation threshold and thermal ablation lesion creation using MRI-guided 220-kHz focused ultrasound surgery: preclinical investigation

Journal of Neurosurgery, 2015

obJeCt In biological tissues, it is known that the creation of gas bubbles (cavitation) during ul... more obJeCt In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology. MetHoDs Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600-14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140-300 W was used for long-duration sonications and 300-700 W for shortduration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions. results Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R 2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages. ConClusions This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.

Research paper thumbnail of MAGNETIC RESONANCE IMAGING-GUIDED FOCUSED ULTRASOUND FOR THERMAL ABLATION IN THE BRAIN

Neurosurgery, 2007

... Institute of Pathology, Sheba Medical Center, Tel Aviv, Israel (Nass). Insightec, Tel Aviv, I... more ... Institute of Pathology, Sheba Medical Center, Tel Aviv, Israel (Nass). Insightec, Tel Aviv, Israel (Zadicario) (Hananel). ... The system, ExAblate2000, is a focused ultrasound delivery system embedded within the MRI bed of a conventional diagnostic MRI scanner. ...

Research paper thumbnail of Potential of Magnetic Resonance-guided Focused Ultrasound for Intracranial Hemorrhage: An In Vivo Feasibility Study

Journal of Stroke and Cerebrovascular Diseases, 2014

Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality r... more Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept. The transcranial effectiveness of MRgFUS was tested ex vivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and sonicated in vivo with one 5-second pulse of 700 W through a bone window or with 3000 W when treated through an ex vivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images. In both in vivo porcine blood clot through a craniectomy model and the porcine clot in an ex vivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue. Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an in vivo porcine model of ICH and in 2 ex vivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.

Research paper thumbnail of Image-guided focused ultrasound: state of the technology and the challenges that lie ahead

Imaging in Medicine, 2013

Image-guided focused ultrasound: state of the technology and the challenges that lie ahead Image-... more Image-guided focused ultrasound: state of the technology and the challenges that lie ahead Image-guided focused ultrasound (FUS) is a noninvasive therapeutic technology platform that results from the marriage of FUS therapy and MR or ultrasound imaging. The thermal and mechanical mechanisms of ultrasound interaction with targeted tissue can produce a variety of localized biological effects that enable the treatment of a wide range of clinical conditions, from uterine fibroids to prostate and liver cancer, to neurological disorders. Coupling FUS therapy with either MR or ultrasound imaging enables precise targeting, planning, monitoring and confirmation of the treatment in real time. Future challenges remain to enable full clinical adoption of image-guided FUS. These include technical advancements to expand the FUS treatment envelope, accumulation of clinical evidence, insurance reimbursement and physician adoption. keywords: focused ultrasound n image-guided n MrI n therapeutic ultrasound n ultrasound imaging

Research paper thumbnail of In vivo low frequency MR-guided thalamotomy with focused ultrasound: thermal vs mechanical lesioning in pig brain

Journal of Therapeutic Ultrasound, 2015

Research paper thumbnail of T1-weighted MRI as a substitute to CT for skull aberration correction in transcranial focused ultrasound: in vivo feasibility and in vitro comparison on human calvaria

Journal of Therapeutic Ultrasound, 2015

Research paper thumbnail of Thermal dose and radiation dose comparison based on cell survival

Journal of Therapeutic Ultrasound, 2015

Research paper thumbnail of Head phantoms for transcranial focused ultrasound

Medical physics, 2015

In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focuse... more In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focused ultrasound (tcMRgFUS), ex-vivo studies wlkiith whole human skulls are of great use in improving the underlying technology guiding the accurate and precise thermal ablation of clinically relevant targets in the human skull. Described here are the designs, methods for fabrication, and notes on utility of three different ultrasound phantoms to be used for brain focused ultrasound research. Three different models of phantoms are developed and tested to be accurate, repeatable experimental options to provide means to further this research. The three models are a cadaver, a gel-filled skull, and a head mold containing a skull and filled with gel that mimics the brain and the skin. Each was positioned in a clinical tcMRgFUS system and sonicated at 1100 W (acoustic) for 12 s at different locations. Maximum temperature rise as measured by MR thermometry was recorded and compared against clinica...

Research paper thumbnail of Trans-cranial focused ultrasound without hair shaving: feasibility study in an ex vivo cadaver model

Journal of therapeutic ultrasound, 2013

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound proc... more In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient's head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220- and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz.

Research paper thumbnail of The Journal of Therapeutic Ultrasound: broadening knowledge in a rapidly growing field

Journal of therapeutic ultrasound, 2013

The Journal of Therapeutic Ultrasound has been established to provide an open access, online venu... more The Journal of Therapeutic Ultrasound has been established to provide an open access, online venue for the exponentially growing body of work in biomedical ultrasound therapy.

Research paper thumbnail of <title>MRI-guided focused ultrasound (MRgFUS) system for thermal ablation of prostate cancer: pre-clinical evaluation in canines</title>

Energy-based Treatment of Tissue and Assessment V, 2009

A transrectal MRgFUS system was tested in a canine prostate model. Focal volumes in each half of ... more A transrectal MRgFUS system was tested in a canine prostate model. Focal volumes in each half of the prostate were targeted, with high energy in one half of the gland for ablation and in the other with lower-energy sonications to test our ability to localize the focal spot before causing thermal tissue damage. All sonications (n=155) were readily observed with proton resonance frequency (PRF) MR temperature imaging, contrast enhanced MRI and histology. The prostate gland moved during the experiments, demonstrating the need for motion tracking. The resultant focal temperature changes during the experiments were 24.2 ± 8.2°C.

Research paper thumbnail of The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus

Journal of Therapeutic Ultrasound, 2013

Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non... more Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.

Research paper thumbnail of Focused ultrasound development and clinical adoption: 2013 update on the growth of the field

Journal of Therapeutic Ultrasound, 2014

The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significa... more The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significant growth, particularly over the past decade. The eventual widespread clinical adoption of this non-invasive therapeutic modality require continued progress, in a multitude of activities including technical, pre-clinical, and clinical research, regulatory approval and reimbursement, manufacturer growth, and other commercial and public sector investments into the field, all within a multi-stakeholder environment. We present here a snapshot of the field of focused ultrasound and describe how it has progressed over the past several decades. It is assessed using metrics which include quantity and breadth of academic work (presentations, publications), funding trends, manufacturer presence in the field, number of treated patients, number of indications reaching first-in-human status, and quantity and breadth of clinical indications.

Research paper thumbnail of International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions

International Journal of Hyperthermia, 2015

Abstract Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), ... more Abstract Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

Research paper thumbnail of Effects of human hair on trans-cranial focused ultrasound efficacy in an ex-vivo cadaver model

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound proc... more In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient's head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220-and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz.

Research paper thumbnail of Intracranial treatment envelope mapping of transcranial focused ultrasound

Research paper thumbnail of High-intensity Focused Ultrasound

Research paper thumbnail of T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided focused ultrasound

Physics in medicine and biology, Jan 7, 2014

Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimi... more Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve temperatures capable of inducing coagulative necrosis at acceptable power deposition levels. CT is usually used for this refocusing but requires a separate study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to determine whether MRI using an appropriate sequence would be a viable alternative to CT for planning ultrasound refocusing in TcMRgFUS. We tested three MRI pulse sequences (3D T1 weighted 3D volume interpolated breath hold examination (VIBE), proton density weighted 3D sampling perfection with applications optimized contrasts using different flip angle evolution and 3D true fast imaging with steady state precision T2-weighted imaging) on patients who have already had a CT scan performed. We made detailed measurements of the calvarial structure based on the MRI data and compared those so-called 'virt...

Research paper thumbnail of Intracranial inertial cavitation threshold and thermal ablation lesion creation using MRI-guided 220-kHz focused ultrasound surgery: preclinical investigation

Journal of Neurosurgery, 2015

obJeCt In biological tissues, it is known that the creation of gas bubbles (cavitation) during ul... more obJeCt In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology. MetHoDs Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600-14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140-300 W was used for long-duration sonications and 300-700 W for shortduration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions. results Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R 2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages. ConClusions This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.

Research paper thumbnail of MAGNETIC RESONANCE IMAGING-GUIDED FOCUSED ULTRASOUND FOR THERMAL ABLATION IN THE BRAIN

Neurosurgery, 2007

... Institute of Pathology, Sheba Medical Center, Tel Aviv, Israel (Nass). Insightec, Tel Aviv, I... more ... Institute of Pathology, Sheba Medical Center, Tel Aviv, Israel (Nass). Insightec, Tel Aviv, Israel (Zadicario) (Hananel). ... The system, ExAblate2000, is a focused ultrasound delivery system embedded within the MRI bed of a conventional diagnostic MRI scanner. ...

Research paper thumbnail of Potential of Magnetic Resonance-guided Focused Ultrasound for Intracranial Hemorrhage: An In Vivo Feasibility Study

Journal of Stroke and Cerebrovascular Diseases, 2014

Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality r... more Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept. The transcranial effectiveness of MRgFUS was tested ex vivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and sonicated in vivo with one 5-second pulse of 700 W through a bone window or with 3000 W when treated through an ex vivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images. In both in vivo porcine blood clot through a craniectomy model and the porcine clot in an ex vivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue. Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an in vivo porcine model of ICH and in 2 ex vivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.

Research paper thumbnail of Image-guided focused ultrasound: state of the technology and the challenges that lie ahead

Imaging in Medicine, 2013

Image-guided focused ultrasound: state of the technology and the challenges that lie ahead Image-... more Image-guided focused ultrasound: state of the technology and the challenges that lie ahead Image-guided focused ultrasound (FUS) is a noninvasive therapeutic technology platform that results from the marriage of FUS therapy and MR or ultrasound imaging. The thermal and mechanical mechanisms of ultrasound interaction with targeted tissue can produce a variety of localized biological effects that enable the treatment of a wide range of clinical conditions, from uterine fibroids to prostate and liver cancer, to neurological disorders. Coupling FUS therapy with either MR or ultrasound imaging enables precise targeting, planning, monitoring and confirmation of the treatment in real time. Future challenges remain to enable full clinical adoption of image-guided FUS. These include technical advancements to expand the FUS treatment envelope, accumulation of clinical evidence, insurance reimbursement and physician adoption. keywords: focused ultrasound n image-guided n MrI n therapeutic ultrasound n ultrasound imaging