Focused ultrasound (FUS) is a promising neuromodulation technique providing advantages such as non-invasiveness, high spatial resolution, and deep penetration depth. Functional ultrasound (fUS) in conjunction with FUS neuromodulation has demonstrated FUS-evoked brain activity via neurovascular coupling with high spatiotemporal resolution, but has been limited to 2-D (+ time). In this study, we present 4-D (x,y,z,t) functional ultrasound (fUS) using a 6.25-MHz row-column array (RCA) imaging transducer (RC6gV, Verasonics, USA) in conjunction with 1.5 MHz FUS in craniotomized mice. We employed orthogonal plane wave compounding with 42 plane waves (21 RC + 21 CR at angles evenly spaced between ± 5.5º), resulting in 310-Hz volume rate. Then, 160 IQ volumes were SVD-filtered and accumulated to generate volumetric power Doppler. We demonstrated volumetric power Doppler of the whole brain at 0.4-Hz frame rate. More importantly, we found 4-D fUS with RCA successfully revealed neurovascular responses evoked by 300 ms FUS pulses at 3 MPa. We observed significantly activated voxels in the posterior cingulate cortex, which is consistent with the location of FUS focus based on our numerical simulation (focal size : 0.59 × 0.59 × 4.91 mm, −6 dB volume : 1.42 mm3). We found 38.6 ± 6.3 % increases in cerebral blood volume (CBV) averaged within the activated volume. Our findings demonstrate that 4-D fUS with RCA can measure volumetric CBV changes elicited by FUS neuromodulation, which enables whole-brain neuroimaging of FUS-evoked hemodynamics.
Kim et al. (Wed,) studied this question.