Whole‐brain mapping of mouse CSF flow via HEAP‐METRIC phase‐contrast MRI

PURPOSE: CSF plays important roles in clearing brain waste and homeostasis. However, mapping whole‐brain CSF flow in the rodents is difficult, primarily due to its assumed very low velocity. Therefore, we aimed to develop a novel phase‐contrast MRI method to map whole‐brain CSF flow in the mouse brain. METHODS: A novel generalized Hadamard encoding–based multi‐band scheme (dubbed HEAP‐METRIC, Hadamard Encoding APproach of Multi‐band Excitation for short TR Imaging aCcelerating) using complex Hadamard matrix was developed and incorporated into conventional phase contrast (PC)‐MRI to significantly increase SNR. RESULTS: Slow flow phantom imaging validated HEAP‐METRIC PC‐MRI’s ability to achieve fast and accurate mapping of slow flow velocities (~10(2) µm/s). With the SNR gain afforded by HEAP‐METRIC scheme, high‐resolution (0.08 × 0.08 mm in‐plane resolution and 36 0.4 mm slices) PC‐MRI was completed in 21 min for whole‐brain CSF flow mapping in the mouse. Using this novel method, we provide the first report of whole‐brain CSF flow in the awake mouse brain with an average flow velocity of ~200 µm/s. Furthermore, HEAP‐METRIC PC‐MRI revealed CSF flow was reduced by isoflurane anesthesia, accompanied by reduction of glymphatic function as measured by dynamic contrast‐enhanced MRI. CONCLUSION: We developed and validated a generalized HEAP‐METRIC PC‐MRI for mapping low velocity flow. With this method, we have achieved the first whole‐brain mapping of awake mouse CSF flow and have further revealed that anesthesia reduces CSF flow velocity.