Global Mapping of Mouse CSF Flow via HEAP-METRIC Phase-contrast MRI

Roles of Cerebrospinal fluid (CSF) in brain waste clearance and homeostasis has been increasingly recognized, thus measuring its flow dynamics could provide important information about its function and perturbance. While phase-contrast MRI can be used for non-invasive flow mapping, so far its mapping of low velocity flow (such as mouse brain CSF) is not possible. Here we developed a novel generalized Hadamard encoding based multi-band acceleration scheme dubbed HEAP-METRIC (Hadamard Encoding APproach of Multi-band Excitation for short TR Imaging aCcelerating), and with significantly increased SNR per time, HEAP-METRIC phase-contrast MRI achieved fast and accurate mapping of slow (~102 micron/s) flow. Utilizing this novel method, we revealed a heterogeneous global pattern of CSF flow in the awake mouse brain with a averaged flow of ~200 micron/s, and further found isoflurane anesthesia reduced CSF flow that was accompanied by reduction of glymphatic function. Therefore, we developed the novel HEAP-METRIC phase-contrast MRI for mapping low velocity flow, and demonstrated its capability for global mapping of mouse CSF flow and its potential alterations related to various physiological or pathological conditions.