DTI-ALPS-Plus: A New Technique for Measuring Glymphatic System Outflow with Enhanced Sensitivity to ISF and Robustness

Motivation: The ability of DTI-ALPS to reflect interstitial fluid (ISF) outflow remains controversial. Goal(s): To demonstrate the ISF's contribution to DTI-ALPS and propose a method to enhance its sensitivity to ISF dynamics and its robustness. Approach: The vein orientation was determined from SWI and voxels having medullary veins perpendicular to fiber orientation were semi-automatically selected to calculate DTI-ALPS (i.e., DTI-ALPS-Plus). Results: DTI-ALPS values decrease as the angle between the orientations of fiber tracts and medullary veins getting further away from 90o. In comparison with DTI-ALPS, DTI-ALPS-Plus shows significantly larger values, higher inter-observer and scan-rescan repeatability, and better performance in distinguishing AD from healthy controls. Impact: This work solves the problem of low inter-observer and scan-rescan repeatability in DTI-ALPS by semi-automatically selecting voxels having medullary veins perpendicular to fiber orientation (DTI-ALPS-Plus), which also enhances this method's sensitivity to ISF dynamics.