Abstract WMP63: Oxygen Metabolic Stress Attributes Intrinsic Vulnerability to Watershed Regions in Healthy Individuals

Abstract

Introduction: Physiological imaging studies in patients with severe steno-occlusive carotid disease (SSCD) reveal hemodynamic compromise as a mechanism underlying watershed infarcts (WI). However, it is unclear if the watershed region (WR) is intrinsically vulnerable in healthy individuals. We measured cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in healthy individuals to determine if the WR was under metabolic stress, and therefore an intrinsically vulnerable region. Methods: To define a common WR, we created an “average WI density map” using MRIs from patients with diffusion restriction ipsilateral to SSCD from a single academic center (7/10 to 8/20). WI density maps were created using 5%, 10% and 15% incidence thresholds. Maps were overlaid onto coregistered CBF and OEF maps generated from pseudo-continuous arterial spin labeling (pCASL) and asymmetric spin echo sequences, respectively, performed on healthy controls aged <55 with no vascular risk factors. OEF was normalized to whole brain values. White matter OEF and CBF was compared within vs. outside the WR using the Kruskal Wallis test. Results: 47 MRIs (mean age 62 years, 55 % females) were used to create average WI density maps using 3 thresholds (Fig A). Average CBF and OEF maps were created from 29 healthy volunteers (mean age 39 years, 59 % females). WI maps were superimposed on the CBF and OEF maps from healthy controls. OEF was higher (p<0.001), and CBF lower (p<0.001) within compared to outside the watershed regions, regardless of incidence threshold used (10% threshold shown in Fig. B-C). Conclusion: Increased OEF and decreased CBF suggest oxygen metabolic stress in the WR, suggesting that the deep white matter may be intrinsically vulnerable even in healthy individuals. Indeed, several brain pathologies (WI, white matter hyperintensities of presumed vascular origin, and multiple sclerosis lesions) are known to fall within this region.