Assessment of intracranial vascular flow oscillations in Alzheimer’s disease using real time 4D flow MRI

Abstract

AbstractBackgroundRecent models suggest clearance of soluble metabolites from the brain can be driven by low frequency flow oscillations (LFO) of vascular smooth muscle cells through the intramural periarterial drainage (IPAD) pathway. This work derives LFO from measures of blood flow variance using real time 4D flow MRI in the intracranial arteries of clinically diagnosed Alzheimer’s disease (AD) subjects.MethodsSubjects: Study groups are summarized in Figure 1. The APOE4+,FH+ group consisted of healthy late middle‐aged subjects with both APOE ε4 allele and parental family history of AD dementia positive. MRI: Volumetric, time‐resolved 4D flow MRI data were acquired on a 3.0T system (MR750, GE Healthcare) using a 32‐channel head coil (GE Healthcare). Images were reconstructed to a spatial resolution of 1.38mm isotropic and a temporal resolution of 4.3sec (scan time=7.1min). To evaluate the ability of 4D flow to distinguish physiologic flow changes from noise, healthy volunteers were scanned during a scan with breath‐holds (BH). LFO analysis: Flow waveforms in the internal carotid artery (ICA) and superior sagittal sinus (SSS) were recorded from the dynamic data. To quantify LFO demeaned temporal flow changes and standard deviations were calculated. Global atrophy was estimated as the ratio of CSF volume to brain volume. Group differences were assessed using ANOVA followed by Tukey‐Kramer method for pairwise comparison for adjusted means (P<0.05).ResultsFigure 2 shows an example of flow curves from a young volunteer during free breathing and a scan with BHs. Flow variance increased during the BH scan. The ICA flow variance normalized to the intracranial volume (ICV) and global atrophy, and ICA blood flow ranges were significantly larger in age‐matched controls compared to AD (P=0.025, P=0.024, P=0.004) (Figures 3&4). LFO from demeaned flow profiles are shown in Figure 5 for all subjects. The LFO in age‐matched controls were noticeable larger than in AD subjects. Finally, average flow rates in age‐matched controls were significantly larger than in AD subjects in the ICA (P=0.034) (Figure 6).ConclusionsSignificantly higher LFO, as measured by standard deviations, are measurable in age‐matched controls when compared to AD subjects suggesting decreased vascular compliance and vasomotion in AD.