First in human evaluation of non-invasive cranial nerve stimulation: DTI measures change in arterial perivascular space and nearby parenchyma

Motivation: We investigate using concurrent DTI during external neuromodulation of the trigeminal nerve to see if MRI can detect alterations in a portion of the glymphatic system. Goal(s): Using designs that demonstrate changes in near-infrared imaging of blood flow, we aim to non-invasively query the whole human brain during stimulation using DTI-based methods. Approach: We monitored the brain using DTI methods sensitive to changes in visible perivascular spaces. DTI-ALPS indices were also measured. Results: Whole-brain measurements confined to visible PVS show significantly increased MD and no difference in FA under stimulation compared to baseline. DTI-ALPS index was significantly higher during stimulation compared to baseline. Impact: Using DTI, external neuromodulation designed to induce changes in cerebrovascular pulsations in humans was shown to cause changes in perivascular spaces near brain arteries and nearby parenchyma, suggesting possibility for neuromodulation devices to serve therapeutic purpose for augmenting glymphatic clearance.