Label free, capillary-scale blood flow mapping in vivo reveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature

Non-invasive, low intensity focused ultrasound (FUS) is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported. The brains ability to provide targeted blood flow to electrically active regions involve a multitude of non-neuronal cell types and signaling pathways in the cerebral vasculature; an open question is whether persistent effects can be attributed, at least partly, to vascular mechanisms. Using a novel in vivo optical approach, we found that microvascular responses, unlike larger vessels which prior investigations have explored, exhibit persistent dilation following sonication without the use of microbubbles. This finding and approach offers a heretofore unseen aspect of the effects of FUS in vivo and indicate that concurrent changes in neurovascular function may partially underly persistent neuromodulatory effects.