Towards Transcranial Functional Ultrasound Imaging Through the Adult Skull

Functional ultrasound imaging (fUSI) is an emerging technology for assessing functional brain activity. To date, functional ultrasound without contrast agents has only been applied to human imaging during surgery with the skull removed or in neonates through a fontanel window. Here, we showcase a proof-of-concept study of contrast-free transcranial fUSI (tfUSI) through adult skulls. To achieve the high sensitivity and image quality required for tfUSI, we utilize several techniques including compound Barker coded excitation to boost signal-to-noise ratio, adaptive motion compensation and a head fixation device to minimize the effects of motion, and an eigen-based filtering approach to separate blood flow from tissue clutter. We assessed cerebrovascular reactivity induced by a breath hold by measuring cerebral blood volume with power Doppler imaging. We targeted the vasculature surrounding the midbrain in 13 healthy adult volunteers during a six minute task of alternating free breathing and breath holding periods. We showed that the power Doppler signal was correlated to the breath hold task ($\rho = 0.53 \pm 0.08$) and oxygen saturation ($\rho = 0.71 \pm 0.10$). Correlation coefficients were statistically significant for each subject (one-tailed $t$-test, $\alpha =0.01$). We also observed delayed vasodilation response in the power Doppler signal that reflected the expected delayed oxygen saturation drop from the breath hold. Delays to maximal signal were $47.69 \pm 23.7$ s for the first breath hold and $52.31 \pm 18.0$ s for the second breath hold. Our results demonstrate the utility of tfUSI for evaluating cerebrovascular reactivity and pave the way for further development to enable assessment of neural activation.