Oxygen extraction efficiency and white matter lesion burden in older adults exhibiting radiological evidence of capillary shunting.

White matter lesions (WML) have been linked to cognitive decline in aging as well as in Alzheimer's disease. While hypoperfusion is frequently considered a cause of WMLs due to the resulting reduction in oxygen availability to brain tissue, such reductions could also be caused by impaired oxygen exchange. Here, we tested the hypothesis that venous hyperintense signal (VHS) in arterial spin labeling (ASL) magnetic resonance imaging (MRI) may represent a marker of impaired oxygen extraction in aging older adults. In participants aged 60-80 years (n = 30), we measured cerebral blood flow and VHS with arterial spin labeling, maximum oxygen extraction fraction (OEF max ) with dynamic susceptibility contrast, and WML volume with T 1 -weighted MRI. We found a significant interaction between OEF max and VHS presence on WML volume ( p  = 0.02), where lower OEF max was associated with higher WML volume in participants with VHS, and higher OEF max was associated with higher WML volume in participants without VHS. These results indicate that VHS in perfusion-weighted ASL data may represent a distinct cerebrovascular aging pattern involving oxygen extraction inefficiency as well as hypoperfusion.