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 (similar to 10(2) mu m/s). With the SNR gain afforded by HEAP-METRIC scheme, high-resolution (0.08 x 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 similar to 200 mu m/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.