Noninvasive and remote measurement of sleep‐active glymphatic function in the human brain by dynamic impedance spectro‐tomography

Background Perivascular glymphatic exchange contributes to the clearance of amyloid β, tau, and α synuclein primarily during sleep. Glymphatic function has been assessed in human populations solely through neuroimaging, including contrast‐enhanced magnetic resonance imaging (CE‐MRI). Using a newly developed investigational medical device (IMD) to measure brain parenchymal resistance to fluid flow by dynamic impedance spectro‐tomography, we evaluated the performance of this putative measure of glymphatic function against “gold‐standard” CE‐MRI. Method Healthy 55‐65 y/o participants were enrolled in a cross‐over randomized control clinical trial encompassing one night of sleep/sleep deprivation followed by 4hr morning window of wake/sleep. Intravenous CE‐MRI was obtained prior to (T0) and following (T1) the 4hr window. Participants were instrumented with the IMD to measure continuous changes in brain parenchymal resistance (R). For the ROIs of interest, contrast enhancement (CE) was measured as the ratio of the T1/T0 MRI signal. The ratio CEp/CEd of anatomically proximal ROIs (CEp) to distal ROIs (CEd) was used to measure increasing (CEp/CEd ≤ 1) or decreasing (CEp/CEd > 1) net contrast movement. The predictive value of the R measured by the IMD, multiple EEG powerbands, and time spent in N2, N3 and REM sleep were tested against the CE‐MRI ROI ratios. Data from fourteen intervention periods were available for analysis. Result IMD parenchymal resistance R predicted IV CE‐MRI contrast movement through blood, cerebrospinal fluid, and interstitial brain compartments (Table 1, Figure 1). EEG slow power predicted contrast movement into more proximal ROIs only. Other powerbands and hypnogram sleep stages were not predictive of contrast movement. Conclusion EEG powerbands (increased slow, reduced beta) were weakly associated with increased glymphatic exchange measured by CE‐MRI. Parenchymal resistance R measured by the IMD were robust predictors of contrast movement from proximal (ventricles, subarachnoid) CSF compartments, through parenchymal compartments (gray matter, white matter). These findings begin to validate IMD‐derived parenchymal R as non‐imaging measure of glymphatic function. Detection of glymphatic impairment in real‐world settings may permit (i) early identification of individuals at‐risk for developing sleep‐related Alzheimer’s disease pathology, and (ii) enable precision targeted enhancement of glymphatic function to enhance glymphatic function and