Extracellular Impact of Ultrasound-induced Blood-brain Barrier Disruption

This study seeks to determine the impact of focused ultrasound (FUS) on the composition of the tumor extracellular microenvironment. Researchers will evaluate regions that are very abnormal, as well as regions that have less evidence of disease. A sub-portion of each of these areas will be targeted by focused ultrasound. Microdialysis catheters will then be placd into each region that has and has not been exposed to FUS (total of 4 catheters) to determine how FUS impacts the the brain and tumor extracellular metabolome, including concentration of routine drugs systemically administered prior to, and during surgery. Researchers hope that this information will help reveal the relative contribution of blood-derived compounds to the tumor microenvironment. If successful, microdialysis could be leveraged in the future to simultaneously evaluate pharmacokinetic and pharmacodynamic impacts of future candidate therapies, including those delivered with the aid of FUS.

This protocol performs FUS immediately prior to clinically indicated brain tumor resection. Accordingly, any drugs administered in the context of routine clinical care, such as Ancef, levetiracetam, and mannitol) and imaging agents (gadolinium and iopamidol) clinically available for pre-operative imaging via MRI or CT, respectively, will be quantified in plasma as well as the interstitial fluid of brain tumor and adjacent brain tissue within and outside the volume of FUS treatment. Patients with large (≥3cm) gliomas and no known contraindications to contrast agents or surgery will be recruited to undergo pre-operative Exablate 4000 Type-2 MR-guided FUS prior to intraoperative high molecular weight microdialysis and standard-of-care glioma resection. Intra-operative CT or O-arm will be obtained with contrast to document the location of catheters relative to tumor and region of blood brain barrier disruption following FUS prior to tumor resection.