Non-invasive magnetic resonance imaging techniques for visualizing brain waste clearance through cerebrospinal fluid pulsation and meningeal lymphatic vessels

Abstract

Brain waste clearance is crucial for maintaining neural function and preventing neurodegenerative disorders. This clearance process involves cerebrospinal fluid (CSF) circulation, the glymphatic system, and meningeal lymphatic vessels (mLVs). However, non-invasive imaging techniques for studying these clearance mechanisms have been limited, hindering a comprehensive understanding of their function and potential alterations in neurological conditions. This study focused on developing non-invasive MRI techniques to image CSF pulsatory circulation and mLVs, comprising three sub-studies. The first sub-study introduced IR-ALADDIN, a novel imaging technique using 2D interslice flow saturation MRI to visualize mLVs. IR-ALADDIN effectively demonstrated mLVs' morphology and flow characteristics, offering insights into brain waste clearance pathways. The second sub-study introduced CSFpulse, a method to quantify CSF pulsation using conventional EPI-based functional MRI. CSFpulse correlated significantly with phase contrast MRI stroke volume, presenting advantages over existing CSF pulsation measurement techniques. The third sub-study applied CSFpulse to investigate CSF dynamics in traumatic brain injury (TBI) patients. A significant decrease in CSF pulsation and correlation between global-BOLD and CSF inflow was observed after TBI, implying potential implications of CSF dynamics alteration for post-TBI brain dysfunction studies. In the fourth sub-study, we applied the previously proposed CSFpulse technique to functional MRI data of patients with Parkinson's disease. The analysis confirmed a significant enlargement of the fourth ventricle and an increase in cerebrospinal fluid flow caused by Parkinson's disease, with higher changes observed in patients who progressed to dementia after Parkinson's disease. In the final sub-study, we applied the proposed Inversion-Recovery ALADDIN technique to a group of patients with brain diseases. While the average speed of lymph was similar to that of the control group, the cross-sectional area of the lymphatic vessels significantly decreased in the disease group, ultimately confirming a tendency for the total flow of meningeal lymph to significantly decrease. These studies providing non-invasive and quantitative imaging techniques and application result of CSF pulsation measurement in TBI patients. They expand our understanding of brain waste clearance mechanisms, including mLVs flow and CSF dynamics, facilitating further investigations into neurological disorders related to neurofluids.