The goal of this project is to develop an integrated system for MRI-guided precise targeting and accurate ablation of brain tumors by interstitial high intensity focused ultrasound (iHIFU). Between 25-40% of patients with systemic cancer suffer the effect of brain metastases (BM). Treatment of BMs is often multidisciplinary involving open surgery, stereotactic radiosurgery (SRS), whole brain radiation, and/or chemotherapy. A subset of patients are candidates for open surgery and/or SRS. Open surgery via craniotomy in appropriate patients allows for tissue diagnosis, rapid relief of symptoms, and local disease control. The advantage of SRS is that it is non-invasive and avoids complications associated with craniotomy. SRS, however, precludes tissue diagnosis and time to symptom relief is slower. The purpose of the proposed research is to provide a complete new set of tools offering the benefits of craniotomy less invasively by targeting and ablating tumors through an incision less than one inch. The complete set of tools to deliver this therapy thus requires adequate visualization, precise targeting (<1mm), and conformal ablation. The proposed approach is to combine real-time MR-guided robot-assisted delivery of iHIFU with MR thermal imaging (MRTI) feedback. The system uses an MR-compatible robotic manipulator capable of delivering a cannula with the accuracy, reproducibility and efficiency needed to make this therapy a reasonable adjunct, while interstitial high-intensity ultrasound allows for highly precise electronically configurable therapeutic ablation with capability for exact volume (size and shape) control in 3D, from very small (mm) to moderate (several cm) size, without harming nearby critical structures not involved with disease. The significance of the proposed approach is that it offers a less invasive alternative to craniotomy, which provides the advantage over SRS of allowing for tissue diagnosis as well as immediate tumor ablation in difficult to reach regions of the human brain. The clinical focus of the proposed work is on brain metastases (BM), which are solid, well-demarcated from surrounding tissue, and amenable to MR-guided ablations. It is anticipated that successful development of this novel and highly controllable ablation system will eventually lead to future approaches to treat other types of tumors such as meningiomas.
The aims of this project are to: 1) develop a MRI-compatible interstitial ultrasonic neuroablation instrument, 2) construct and evaluate an MRI-compatible manipulator for neuroablation instrument delivery and control, 3) develop and integrate computer-based 3D treatment planning and simulation tools, and 4) perform pre-clinical evaluations to confirm accuracy, optimize clinical workflow, and demonstrate successful ablative lesioning in clinically-relevant environment. Successful completion of this project will result in an experimental protocol in place with a veterinary hospital to use iHIFU as part of a treatment paradigm for canines with brain metastases, with human studies soon to follow.

Public Health Relevance

The proposed project will develop a novel robot-assisted system for highly precise and focused thermal treatment of brain tumors. The MRI-compatible robotic device combined with real-time anatomic and thermal imaging will enable precise delivery and monitoring of cannula-based interstitial high intensity focused ultrasound (iHIFU) to destroy the tumors without damaging nearby tissues. This approach will be less invasive and risky than open brain surgery through craniotomy, and will provide faster relief without destroying or harming nearby critical structures not involved with disease than stereotactic radiosurgery, the current methods of choice to treat brain tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
4R01CA166379-04
Application #
9052736
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Baker, Houston
Project Start
2013-05-17
Project End
2018-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Worcester Polytechnic Institute
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
041508581
City
Worcester
State
MA
Country
United States
Zip Code
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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