Brain metastases (BM) are the most common site of metastases from systemic cancer, with an incidence of up to 170,000 new cases per year in North America. Untreated BM patients generally live less than two months. Treatment options are currently limited to resective surgery, radiation therapies and chemotherapy. Thermal ablation has been postulated as an alternative therapy, but available devices have significant limitations with respect to conformal spatial control of ablation pattern and access to some regions within the brain. This project proposes development of needle-based therapeutic ultrasound (NBTU) devices and integrated system to accurately target and induce conformal ablation patterns for treatment of tumors and validation in a large animal model. The initial project period resulted in the development of a complete set of tools that utilize real-time magnetic resonance imaging guided robot-assisted (MRgRA) delivery of interstitial NBTU as a neuroablative device, which culminated in two swine survival surgeries to date. This NBTU device offers advantages over transcranial HIFU in that all regions of the brain can be targeted, ablation volumes can be shaped three- dimensionally, and concurrent biopsy is possible. This competitive renewal project will focus on the need to modify the device to prepare for first-in-human trials and to validate the device in a significant animal study. The objectives of this project are to: 1) Develop directional therapeutic ultrasound probes that are configured to produce controlled intensity distribution of energy along both length and angle to allow for conformal ablation patterns based on tumor volume. 2) Optimize the robotic delivery device design to maximize its reachable workspace, and validate this capacity by performing ablations in various brain regions. 3) Improve the interface between the current FDA 510K approved TheraVision therapy planning and monitoring system, MR thermal imaging (MRTI), and MR-guided robotic assist device to allow for ?point and click? software use; and 4) In accordance with FDA requirements for a first in man trial, validate the clinically ready version of this system under appropriate design controls by performing survival swine studies that monitor safety and accuracy. An FDA IDE application will be filed in the final stages of this project to prepare for a future first-in-human clinical trial. Successful completion of this project will result in substantial technical and feasibility advancements over the current state-of-the-art for HIFU, including volumetric MR thermal imaging and customized NBTU probes and dosing strategies. This project will lead directly to delivery of a new high-precision treatment option for patients with brain metastases that will provide targeted tumor ablation with minimal collateral damage to surrounding non-targeted tissue.

Public Health Relevance

Nearly one-third of patients with systemic cancer develop brain metastases in the course of their treatment, which are rapidly fatal, and current treatment options are limited to resective surgery, radiation therapies, and chemotherapy. This project will optimize a novel magnetic resonance imaging guided robot-assisted (MRgRA) device combined with novel high intensity focused ultrasound (HIFU) interstitial needle-based therapeutic ultrasound (NBTU) devices producing tumor-conformal ablation patterns to provide a high-precision minimally invasive treatment option for patients with brain metastases. Successful completion of this project will lead to first-in-human clinical trials of a device that precisely targets therapeutic ultrasound under real-time MRI-based thermal dose monitoring to conformably ablate brain tumors and limit collateral damage to surrounding normal brain tissue.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
Program Officer
Baker, Houston
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Worcester Polytechnic Institute
Engineering (All Types)
Biomed Engr/Col Engr/Engr Sta
United States
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MacDonell, Jacquelyn; Patel, Niravkumar; Fischer, Gregory et al. (2018) Robotic Assisted MRI-Guided Interventional Interstitial MR Guided Focused Ultrasound Ablation in a Swine Model. Neurosurgery :
MacDonell, Jacquelyn; Patel, Niravkumar; Rubino, Sebastian et al. (2018) Magnetic resonance-guided interstitial high-intensity focused ultrasound for brain tumor ablation. Neurosurg Focus 44:E11
Ghoshal, Goutam; Gee, Lucy; Heffter, Tamas et al. (2018) A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies. Neurosurg Focus 44:E13
Mahoney, Emily C; Zeng, Andrew; Yu, Wilson et al. (2018) Ventral pallidum deep brain stimulation attenuates acute partial, generalized and tonic-clonic seizures in two rat models. Epilepsy Res 142:36-44
Wartenberg, Marek; Schornak, Joseph; Gandomi, Katie et al. (2018) Closed-Loop Active Compensation for Needle Deflection and Target Shift During Cooperatively Controlled Robotic Needle Insertion. Ann Biomed Eng 46:1582-1594
Kaszuba, Brian C; Walling, Ian; Gee, Lucy E et al. (2017) Effects of subthalamic deep brain stimulation with duloxetine on mechanical and thermal thresholds in 6OHDA lesioned rats. Brain Res 1655:233-241
Su, Hao; Shang, Weijian; Li, Gang et al. (2017) An MRI-Guided Telesurgery System Using a Fabry-Perot Interferometry Force Sensor and a Pneumatic Haptic Device. Ann Biomed Eng 45:1917-1928
Nycz, Christopher J; Gondokaryono, Radian; Carvalho, Paulo et al. (2017) Mechanical Validation of an MRI Compatible Stereotactic Neurosurgery Robot in Preparation for Pre-Clinical Trials. Rep U S 2017:1677-1684
Su, Hao; Iordachita, Iulian I; Tokuda, Junichi et al. (2017) Fiber Optic Force Sensors for MRI-Guided Interventions and Rehabilitation: A Review. IEEE Sens J 17:1952-1963
Su, Hao; Li, Gang; Rucker, D Caleb et al. (2016) A Concentric Tube Continuum Robot with Piezoelectric Actuation for MRI-Guided Closed-Loop Targeting. Ann Biomed Eng 44:2863-2873

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