A non-invasive MR-compatible hyperthermia system for brain tumor treatment

About This Grant

PROJECT SUMMARY High-grade brain cancers have poor outcomes because radiation therapy (RT) dose escalation is limited by normal-brain toxicity and effective drug delivery is broadly limited by the blood-brain and blood-tumor barriers. This project addresses these limitations by developing Halo, a non-invasive, MR-compatible brain hyperthermia therapy (HT) system for adjuvant treatment of brain cancer. The long-term goal is to improve local tumor control and survival while reducing RT toxicity by enabling lower RT doses with adjuvant HT. HT uses localized tumor heating to 40 44°C for 1 hour to enhance RT, chemotherapy, and immunotherapy by inhibiting tumor DNA repair, increasing tumor perfusion and vascular permeability, and opening the blood-brain barrier to improve localized drug delivery. In randomized trials of brain tumors, interstitial HT with RT or chemoRT significantly improved outcomes, including more than doubling 2-year survival in glioblastoma patients. However, current brain HT technologies remain invasive and require hardware- and workflow-intensive procedures, substantially limiting widespread use in brain cancer care. The Halo system addresses these barriers using an external phased array of 72 microwave antennas around the head, operating at 915 MHz to focus heating at depth within the brain. In addition, patient-specific 3D HT treatment planning (HTP) software and MR thermometry will plan, monitor, and guide precise treatment delivery. A virtual head model database will support an in silico clinical trial across a range of tumor sizes and intracranial locations and will train and validate artificial intelligence-based tools for rapid tissue segmentation and temperature pattern prediction. Existing clinical HT hardware and software controls will be upgraded to drive the novel antenna array and improve clinical usability and translation. Validation will follow a staged, animal-sparing strategy. Computational modeling and anatomically realistic phantoms will be the primary tools for testing and optimizing Halo's performance. Building from this work, we will selectively deploy the HT platform in tumor-bearing minipigs as the critical bridge to human studies. Together, the computational, phantom, and minipig experiments will validate Hal's heating performance, compare HTP-predicted temperatures with MR thermometry, evaluate imaging endpoints, and assess tissue safety using histopathology, which are central to evaluating and optimizing the Halo system for clinical testing. Our team has extensive clinical HT experience, in silico and bench translational expertise, and an active industry collaboration supporting clinical application of this therapeutic device and overall strategy. Successful completion of this project will provide a dedicated, precise, easy-to-use, non-invasive, MR-compatible brain HT platform that can be integrated with RT, chemotherapy, and/or immunotherapy for advanced brain tumor care. This project directly addresses a pressing clinical need by advancing non-invasive brain cancer HT toward the clinical realm. Importantly, non-animal models cannot assess perfused brain/tumor heating, real-time MR thermometry, or tissue safety at the required scale and level of complexity. Therefore, their use is not feasible in this context.