Date of Award
Doctor of Philosophy (PhD)
Brainstem gliomas are tumors that occur in the brainstem, the brain region that connects the brain to the spinal cord and controls vital body functions. The critical anatomic location of the brainstem precludes surgical intervention and limits the use of invasive therapeutic techniques. Moreover, the frequently intact blood-brain barrier (BBB) of most brainstem gliomas prevents therapeutic agents from reaching the diseased site. The currently available techniques for brain drug delivery are either invasive (e.g., convection-enhanced delivery) or lack targeting to the diseased site (e.g., intranasal brain drug delivery). Novel techniques that can noninvasively overcome the BBB are critically needed for the treatment of brainstem glioma. Focused ultrasound combined with microbubbles can noninvasively induce temporal BBB disruption (FUS-BBBD) at the FUS-targeted brain region, allowing the trans-BBB delivery of intravenously injected agents. Focused ultrasound-mediated intranasal delivery (FUSIN) is a newly reported technique for brain drug delivery that integrates FUS and microbubbles to enhance the accumulation of intranasally administered agents at the FUS-targeted brain location with significantly lower systemic exposure than that of FUS-BBBD. The objective of this thesis was to evaluate the feasibility, safety, and efficacy of the two FUS-mediated techniques for drug delivery to the brainstem with the ultimate goal of providing a novel strategy for the treatment of brainstem gliomas.
Hong H. Chen
Guy G. Genin, Mark M. Meacham, Srikanth S. Singamaneni, Joshua B. J. Rubin,