Transcranial Functional Ultrasound Imaging Detects Focused Ultrasound Neuromodulation Induced Hemodynamic Changes in Mouse and Nonhuman Primate BrainsIn Vivo

Abstract

Focused ultrasound (FUS) is an emerging noinvasive technique for neuromodulation in the central nervous system (CNS). To evaluate the effects of FUS-induced neuromodulation, many studies used behavioral changes, functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). However, behavioral readouts are often not easily mapped to specific brain activity, EEG has low spatial resolution limited to the surface of the brain and fMRI requires a large importable scanner that limits additional readouts and manipulations. In this context, functional ultrasound imaging (fUSI) holds promise to directly monitor the effects of FUS neuromodulation with high spatiotemporal resolution in a large field of view, with a comparatively simple and flexible setup. fUSI uses ultrafast Power Doppler Imaging (PDI) to measure changes in cerebral blood volume, which correlates well with neuronal activity and local field potentials. We designed a setup that aligns a FUS transducer with a linear array to allow immediate subsequent monitoring of the hemodynamic response with fUSI during and after FUS neuromodulation. We established a positive correlation between FUS pressure and the size of the activated area, as well as changes in cerebral blood volume (CBV) and found that unilateral sonications produce bilateral hemodynamic changes with ipsilateral accentuation in mice. We further demonstrated the ability to perform fully noninvasive, transcranial FUS-fUSI in nonhuman primates for the first time by using a lower-frequency transducer configuration.

Functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice

“…We recently reported hemodynamic responses evoked by FUS in mice and nonhuman primates via transcranial fUS [41]. The study reported bilateral responses with center sonication and less localized hemodynamic responses with left or right sonication, which may be largely due to a large focal size of 1.68 MHz FUS transducer without in situ displacement targeting, and the presence of the skull.…”