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

ABSTRACT: 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.

SUBMITTER: MacDonell J

PROVIDER: S-EPMC5907801 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

MacDonell Jacquelyn J Patel Niravkumar N Rubino Sebastian S Ghoshal Goutam G Fischer Gregory G Burdette E Clif EC Hwang Roy R Pilitsis Julie G JG

Neurosurgical focus 20180201 2

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 s ...[more]

PMID: 29385926

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Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy.

Project description:ObjectiveThe purpose of this prospective multicenter study was to assess the safety and technical feasibility of volumetric Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) ablation for treatment of patients with symptomatic uterine fibroids.MethodsThirty-three patients with 36 fibroids were treated with volumetric MR-HIFU ablation. Treatment capability and technical feasibility were assessed by comparison of the Non-Perfused Volumes (NPVs) with MR thermal dose predicted treatment volumes. Safety was determined by evaluation of complications or adverse events and unintended lesions. Secondary endpoints were pain and discomfort scores, recovery time and length of hospital stay.ResultsThe mean NPV calculated as a percentage of the total fibroid volume was 21.7%. Correlation between the predicted treatment volumes and NPVs was found to be very strong, with a correlation coefficient r of 0.87. All patients tolerated the treatment well and were treated on an outpatient basis. No serious adverse events were reported and recovery time to normal activities was 2.3 ± 1.8 days.ConclusionThis prospective multicenter study proved that volumetric MR-HIFU is safe and technically feasible for the treatment of symptomatic uterine fibroids.Key points• Magnetic-resonance-guided high intensity focused ultrasound allows non-invasive treatment of uterine fibroids. • Volumetric feedback ablation is a novel technology that allows larger treatment volumes • MR-guided ultrasound ablation of uterine fibroids appears safe using volumetric feedback.

| S-EPMC3249029 | biostudies-literature

Efficacy, Efficiency, and Safety of Magnetic Resonance-Guided High-Intensity Focused Ultrasound for Ablation of Uterine Fibroids: Comparison with Ultrasound-Guided Method.

Project description:ObjectiveThe purpose of this study was to compare efficacy, sonication energy efficiency, treatment time and safety of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) and those of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of uterine fibroids.Materials and methodsThis study included 43 patients with 44 symptomatic uterine fibroids treated with MRgHIFU and 51 patients with 68 symptomatic uterine fibroids treated with USgHIFU. After therapy, contrast-enhanced MRI was conducted and complete ablation was defined as 100% non-perfused volume (NPV) of fibroids. Patients with completely ablated fibroids were selected for the comparison of the treatment data and sonication parameters between MRgHIFU and USgHIFU treated groups.ResultsThirteen completely ablated fibroids in 10 patients (23.3%, 10/43) were achieved with MRgHIFU and 28 completely ablated fibroids in 22 patients (43.1%, 22/51) were achieved with USgHIFU. In completely ablated fibroids, the energy-efficiency factor (EEF) was 5.1 ± 3.0 J/mm3 and 4.7 ± 2.5 J/mm3 in the MRgHIFU and USgHIFU, respectively (p = 0.165). There was a negative linear correlation between EEF and the NPV of fibroids for MRgHIFU (p = 0.016) and USgHIFU (p = 0.001). The mean treatment time was 174.5 ± 42.2 minutes and 114.4 ± 39.2 minutes in the MRgHIFU and USgHIFU procedures, respectively (p = 0.021). There were no severe adverse events and major complications after treatment.ConclusionMRgHIFU and USgHIFU are safe and effective with the equivalent energy efficiency for complete ablation of fibroids. USgHIFU has shorter treatment time than MRgHIFU.

| S-EPMC6005948 | biostudies-literature

Case Report: Desmoid tumor response to magnetic resonance-guided high intensity focused ultrasound over 4 years.

Project description:Desmoid tumors are a rare form of cancer, which show locally aggressive invasion of surrounding tissues and may occur anywhere in the body. Treatment options comprise conservative watch and wait strategies as tumors may show spontaneous regression as well as surgical resection, radiation therapy, nonsteroidal anti-inflammatory drugs (NSAID), chemotherapy, or local thermoablative approaches for progressive disease. The latter comprises cryotherapy, radiofrequency, microwave ablation, or thermal ablation with high intensity focused ultrasound (HIFU) as the only entirely non-invasive option. This report presents a case where a desmoid tumor at the left dorsal humerus was 2 times surgically resected and, after recurrence, thermally ablated with HIFU under magnetic resonance image-guidance (MR-HIFU). In our report, we analyze tumor volume and/or pain score during standard of care (2 years) and after HIFU treatment over a 4-year follow-up period. Results showed MR-HIFU treatment led to complete tumor remission and pain response.

| S-EPMC10289281 | biostudies-literature

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening.

Project description:Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

| S-EPMC6328789 | biostudies-literature

Focused ultrasound using a novel targeting method four-tract tractography for magnetic resonance–guided high-intensity focused ultrasound targeting

Project description:Abstract Magnetic resonance–guided high-intensity focused ultrasound thalamotomy is a Food and Drug Administration–approved treatment for essential tremor. The target, the ventral intermediate nucleus of the thalamus, is not visualized on standard, anatomic MRI sequences. Several recent reports have used diffusion tensor imaging to target the dentato-rubro-thalamic-tract. There is considerable variability in fibre tracking algorithms and what fibres are tracked. Targeting discrete white matter tracts with magnetic resonance–guided high-intensity focused ultrasound is an emerging precision medicine technique that has the promise to improve patient outcomes and reduce treatment times. We provide a technical overview and clinical benefits of our novel, easily implemented advanced tractography method: four-tract tractography. Our method is novel because it targets both the decussating and non-decussating dentato-rubro-thalamic-tracts while avoiding the medial lemniscus and corticospinal tracts. Our method utilizes Food and Drug Administration-approved software and is easily implementable into existing workflows. Initial experience using this approach suggests that it improves patient outcomes by reducing the incidence of adverse effects. Feltrin et al provide a technical note and clinical results from a novel targeting method for magnetic resonance guided high intensity focused ultrasound (MRgHIFU ) thalamotomy, 4 tract tractography. This approach improves the adverse effect profile of MRgHIFU while maintaining a sustained tremor response. Graphical Abstract Graphical abstract

| S-EPMC9897190 | biostudies-literature

Intracranial applications of magnetic resonance-guided focused ultrasound.

Project description:The ability to focus acoustic energy through the intact skull on to targets millimeters in size represents an important milestone in the development of neurotherapeutics. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel, noninvasive method, which--under real-time imaging and thermographic guidance--can be used to generate focal intracranial thermal ablative lesions and disrupt the blood-brain barrier. An established treatment for bone metastases, uterine fibroids, and breast lesions, MRgFUS has now been proposed as an alternative to open neurosurgical procedures for a wide variety of indications. Studies investigating intracranial MRgFUS range from small animal preclinical experiments to large, late-phase randomized trials that span the clinical spectrum from movement disorders, to vascular, oncologic, and psychiatric applications. We review the principles of MRgFUS and its use for brain-based disorders, and outline future directions for this promising technology.

| S-EPMC4121456 | biostudies-literature

Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model.

Project description:Clinical-grade doxorubicin encapsulated low temperature sensitive liposomes (LTSLs) were combined with a clinical magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) platform to investigate in vivo image-guided drug delivery. Plasma pharmacokinetics were determined in 3 rabbits. Fifteen rabbits with Vx2 tumors within superficial thigh muscle were randomly assigned into three treatment groups: 1) free doxorubicin, 2) LTSL and 3) LTSL + MR-HIFU. For the LTSL + MR-HIFU group, mild hyperthermia (40-41 °C) was applied to the tumors using an MR-HIFU system. Image-guided non-invasive hyperthermia was applied for a total of 30 min, completed within 1h after LTSL infusion. High-pressure liquid chromatography (HPLC) analysis of the harvested tumor and organ/tissue homogenates was performed to determine doxorubicin concentration. Fluorescence microscopy was performed to determine doxorubicin spatial distribution in the tumors. Sonication of Vx2 tumors resulted in accurate (mean = 40.5 ± 0.1 °C) and spatially homogenous (SD = 1.0 °C) temperature control in the target region. LTSL + MR-HIFU resulted in significantly higher tumor doxorubicin concentrations (7.6- and 3.4-fold greater compared to free doxorubicin and LTSL respectively, p<0.05, Newman-Keuls). This improved tumor concentration was achieved despite heating <25% of the tumor volume. Free doxorubicin and LTSL treatments appeared to deliver more drug in the tumor periphery as compared to the tumor core. In contrast, LTSL + MR-HIFU treatment suggested an improved distribution with doxorubicin found in both the tumor periphery and core. Doxorubicin bio-distribution in non-tumor organs/tissues was fairly similar between treatment groups. This technique has potential for clinical translation as an image-guided method to deliver drug to a solid tumor.

| S-EPMC3319290 | biostudies-literature

Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound.

Project description:PURPOSE:Objectives of this study were to: 1) develop iLTSL, a low temperature sensitive liposome co-loaded with an MRI contrast agent (ProHance® Gd-HP-DO3A) and doxorubicin, 2) characterise doxorubicin and Gd-HP-DO3A release from iLTSL and 3) investigate the ability of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) to induce and monitor iLTSL content release in phantoms and in vivo. METHODS:iLTSL was passively loaded with Gd-HP-DO3A and actively loaded with doxorubicin. Doxorubicin and Gd-HP-DO3A release was quantified by fluorescence and spectroscopic techniques, respectively. Release with MR-HIFU was examined in tissue-mimicking phantoms containing iLTSL and in a VX2 rabbit tumour model. RESULTS:iLTSL demonstrated consistent size and doxorubicin release kinetics after storage at 4°C for 7 days. Release of doxorubicin and Gd-HP-DO3A from iLTSL was minimal at 37°C but fast when heated to 41.3°C. The magnitude of release was not significantly different between doxorubicin and Gd-HP-DO3A over 10?min in HEPES buffer and plasma at 37°, 40° and 41.3°C (p?>?0.05). Relaxivity of iLTSL increased significantly (p?<?0.0001) from 1.95?±?0.05 to 4.01?±?0.1?mMs?¹ when heated above the transition temperature. Signal increase corresponded spatially and temporally to MR-HIFU-heated locations in phantoms. Signal increase was also observed in vivo after iLTSL injection and after each 10-min heating (41°C), with greatest increase in the heated tumour region. CONCLUSION:An MR imageable liposome formulation co-loaded with doxorubicin and an MR contrast agent was developed. Stability, imageability, and MR-HIFU monitoring and control of content release suggest that MR-HIFU combined with iLTSL may enable real-time monitoring and spatial control of content release.

| S-EPMC3417228 | biostudies-literature

Early health technology assessment of magnetic resonance-guided high intensity focused ultrasound ablation for the treatment of early-stage breast cancer.

Project description:Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) ablation is in development for minimally invasive treatment of breast cancer. Cost-effectiveness has not been assessed yet. An early health technology assessment was performed to estimate costs of MR-HIFU ablation, compared to breast conserving treatment (BCT).An MR-HIFU treatment model using the dedicated MR-HIFU breast system (Sonalleve, Philips Healthcare) was developed. Input parameters (treatment steps and duration) were based on the analysis of questionnaire data from an expert panel. MR-HIFU experts assessed face validity of the model. Data collected by questionnaires were compared to published data of an MR-HIFU breast feasibility study. Treatment costs for tumours of 1 to 3 cm were calculated.The model structure was considered of acceptable face validity by consulted experts, and questionnaire data and published data were comparable. Costs of MR-HIFU ablation were higher than BCT costs. MR-HIFU best-case scenario costs exceeded BCT costs with approximately €1000. Cooling times and breathing correction contributed most to treatment costs.MR-HIFU ablation is currently not a cost-effective alternative for BCT. MR-HIFU experience is limited, increasing uncertainty of estimations. The potential for cost-effectiveness increases if future research reduces treatment durations and might substantiate equal or improved results.

| S-EPMC5537939 | biostudies-other

Update on Clinical Magnetic Resonance-Guided Focused Ultrasound Applications.

Project description:In this review, several clinical applications of magnetic resonance (MR)-guided focused ultrasound (FUS) are updated. MR-guided FUS is used clinically for thermal ablation of uterine fibroids and bone metastases. Thousands of patients have successfully been treated. Transcranial MR-guided FUS has received CE certification for ablation of deep, central locations in the brain. Thermal ablation of specific parts of the thalamus can result in relief of the symptoms in a number of neurological disorders. Several approaches have been proposed for ablation of prostate and breast cancer and clinical trials should show the potential of MR-guided FUS for these and other applications.

| S-EPMC4621790 | biostudies-literature

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