טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentEilon Hazan
SubjectFunctional Imaging of MRI-Guided Transcranial Ultrasonic
Neuromodulation
DepartmentDepartment of Biomedical Engineering
Supervisors Full Professor Shoham Shy
Full Professor Kimmel Eitan
Full Thesis textFull thesis text - English Version


Abstract

Ultrasonic neuro-modulation phenomena were experimentally observed and studied for nearly a century, with recent discoveries on direct neural excitation and suppression sparking a new wave of investigations in models ranging from rodents to humans. Focusing the ultrasonic waves, using the FUS (Focused Ultrasound) technology, provides a fine, high resolution tool to selectively stimulate brain neural tissue, and Magnetic Resonance guided Focused Ultrasound (MRg-FUS) technology adds the important capability of guiding and monitoring the FUS during treatment. However, to date US neuromodulation using high resolution MRg-FUS wasn’t studied in rodents. In addition, measuring the effect of US neuromodulation using functional Magnetic Resonance Imaging was reported only in a single study.


In this study, we integrated a high-resolution small-animal 9.4 Tesla Bruker MRI system, with a 2.3 MHz Insightec phased-array FUS system, and applied it to study functional stimulation responses in the mouse brain. We developed and validated a method to target and verify the FUS location with submillimeter accuracy using MR thermometry. Next, we used a functional MRI (fMRI) protocol to measure the responses to the ultrasonic neuromodulation, as reflected in the cerebral blood oxygenation level-dependent (BOLD) signal. We analyzed the functional data of individual animals and the group using statistical parametric mapping regions of interest analyses. Our results demonstrate significant stimulus-locked hemodynamic responses, which were also monotonically modulated by the stimulus intensity. Surprisingly, we encountered two opposite types of hemodynamic responses which we speculate may indicate, in addition to neuromodulation, the involvement of other ultrasound induced phenomena. The new MRg-FUS platform can advance the study of region-specific brain responses to focused ultrasound, and be used to optimize the stimulation parameters and protocols.