Project Overview

Need for project: Neuropathological diagnoses of brain tumours require invasive neurosurgical biopsies that carry a risk of morbidity or mortalityto patients. There has been growing interest in the use of non-invasive liquid biopsies to sample cell-free circulating tumorDNA (ctDNA) for genomic and epigenomic analyses but the abundance of ctDNA in systemic circulation for brain tumourpatients is relatively lower than that for systemic cancer patients, limiting sensitivity in this population.

Goal of project: We aim to increase the sensitivity of non-invasive biopsy for the brain in a cohort of human subjects by increasing DNAshedding from the tumor into circulation using MRI guided focused ultrasound (MRgFUS). We hypothesize that sensitivity foridentifying genomic and epigenomic biomarkers will improve with the increased availability of ctDNA after the application ofMRgFUS

Project description: MRgFUS causes a significant increase in temperature in a defined focal plane of the multiple (up to 1024) ultrasound beams.We aim to thermally ablate the tumor margin with MRgFUS to disrupt the BBB and allow permeabilization of tumor cellmembranes and vessel walls for tumor DNA release into circulation. Plasma samples will be obtained from radiologicallydiagnosed tumor patients before and after MRgFUS and the accuracy in detecting genomic/epigenomic biomarkers will becompared.

Future impact: The overarching goal of this project is to shift the paradigm of brain tumor diagnoses from high-risk invasive procedures tonon-invasive diagnostic approaches with potentially additional advantages including the reaching of surgically inaccessiblebrain regions, capturing tumoral heterogeneity, serial monitoring for tumor progression, and distinguishing tumor frompseudoresponse, presudoprogression, or radiation necrosis.

Principal Investigator

Andres Lozano , University Health Network

Team Members

Daniel De Carvalho, Princess Margaret center – UHN

Gelareh Zadeh, University Health Network, Princess Margaret, University of Toronto

Partners and Donors

Canadian Cancer Society

Canadian Institutes of Health Research