Brain stress testing using blood oxygenation level-dependent (BOLD) MRI to evaluate changes in cerebrovascular reactivity (CVR) is of growing interest for evaluating white matter integrity. However, even under healthy conditions, the white matter BOLD-CVR response differs notably from that observed in the gray matter. The confluence of arterial hemodynamics and BOLD signal characteristics weighted by venous architecture unrelated to smooth-muscle mediated dilation/contraction play a significant role in defining the WM BOLD-signal response to hypercapnia. This caveat should be taken into account when attributing disease mechanisms and/or progression to presumed impaired WM BOLD-CVR.
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