Quantifying perivascular space in Alzheimer's disease by MRI relaxometry

Abstract Background The perivascular space (PVS) is a known key route of glymphatic clearance for the drainage of interstitial fluid and solutes such as soluble amyloid beta (Aβ) from the brain. Perivascular space dilation in aging could indicate abnormal protein accretion, such as Aβ accumulation. Recent studies indicate that dilation of PVS is associated with blocked cerebrospinal fluid (CSF) bulk flow, which is considered as free water. We propose to use MR T2 relaxometry‐based water compartment model for the quantification of free water in brain parenchyma and hence to infer the change of PVS. Method We filtered the 22 Aβ positive MCI subjects with three echo T2‐star data and amyloid PET from ADNI database. The three‐echo data was fitted to a two‐water compartment model (CSF and intro‐extracellular water), in which the water compartments were distinguished by the T2 relaxometry time. CSF fraction (CSFF) values were then extracted in the brain region masks generated from FreeSurfer. Mean CSFF for each subject was then calculated. The SUVr of cerebral cortex was used to evaluate brain amyloid load. Linear regression model between Aβ deposition and CSFF was built with age and gender controlled. Result The results from ADNI data show that CSFF is linearly related to the Aβ deposition in brain. Fig. 1 presents a map of CSFF and the amyloid PET for the same subject. Fig. 2 shows linear relationship (p<0.05) between CSFF and the SUVr in the cerebral cortex area. Conclusion The relation between CSFF and amyloid load in brain cortex shows that CSFF could be a potential biomarker for the amyloid clearance. The CSFF map reflects the percentage of free water in total volume at the water molecular level and can sensitively detect subtle PVS change.