Abstract
Recent modeling and experimental evidence suggests clearance of soluble metabolites from the brain can be driven by low frequency flow oscillations (LFOs) through the intramural periarterial drainage (IPAD) pathway. This study investigates the use of 4D flow MRI to derive LFOs from arterial and venous measures of blood flow. 3D radial 4D flow MRI data were acquired on a 3.0 T scanner and reconstructed using a low-rank constraint to produce time resolved measurements of blood flow. Physical phantom experiments were performed to validate the time resolved 4D flow against a standard 2D phase contrast (PC) approach. To evaluate the ability of 4D flow to distinguish physiologic flow changes from noise, healthy volunteers were scanned during a breath-hold (BH) maneuver and compared against 2D PC measures. Finally, flow measures were performed in intracranial arteries and veins of 112 participants including subjects diagnosed with Alzheimer's disease (AD) clinical syndrome (n = 23), and healthy controls (n = 89) on whom apolipoprotein ɛ4 positivity (APOE4+) and parental history of AD dementia (FH+) was known. To assess LFOs, flow range, standard deviation, demeaned temporal flow changes, and power spectral density were quantified from the time series. Group differences were assessed using ANOVA followed by Tukey-Kramer method for pairwise comparison for adjusted means (P < 0.05). Significantly lower LFOs as measured from flow variation range and standard deviations were observed in the arteries of AD subjects when compared to age-matched controls (P = 0.005, P = 0.011). Results suggest altered vascular function in AD subjects. 4D flow based spontaneous LFO measures might hold potential for longitudinal studies aimed at predicting cognitive trajectories in AD and study disease mechanisms.