Medullary vein architecture modulates the white matter BOLD cerebrovascular reactivity signal response to CO₂: observations from high-resolution T2^*weighted imaging at 7T

Abstract

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. In addition to actual arterial vascular control, the venous draining topology may influence the WM-CVR response leading to signal delays and dispersions. These types of alterations in hemodynamic parameters are sometimes linked with pathology, but may also arise from differences in normal venous architecture. In this work, high-resolution T2*-weighted anatomical images combined with BOLD imaging during a hypercapnic breathing protocol were acquired using a 7 tesla MRI system. Hemodynamic parameters including base CVR, hemodynamic lag, lag-corrected CVR, response onset and signal dispersion, and finally delta-CVR (corrected CVR minus base CVR) were calculated in 8 subjects. Parameter maps were spatially normalized and correlated against an MNI-registered white matter medullary vein atlas. Moderate correlations (Pearsons rho) were observed between medullary vessel frequency (MVF) and delta-CVR (0.52; 0.58 for total WM), MVF and hemodynamic lag (0.42; 0.54 for total WM), MVF and signal dispersion (0.44; 0.53 for total WM), and finally MVF and signal onset (0.43; 0.52 for total WM). Results indicate that, when assessed in the context of the WM venous architecture, changes in the response shape may only be partially reflective of the actual vascular reactivity response occurring further upstream by control vessels. This finding may have implications when attributing diseases mechanisms and/or progression to presumed impaired WM BOLD-CVR.

Quantifying cerebral blood arrival times using hypoxia-mediated arterial BOLD contrast

“…This is likely due to insensitivity towards arterial signals and true response onset times. The CVR based lag analysis is more highly influenced by vascular resistance mediated flow redistribution, differential sensitivity to CO 2 45 and vascular response rate 30 , as well as venous draining topology 37 ; (B) carpet plot results fitting the rising edge of the return to normoxia (top) during hypoxic experiments and the falling edge to baseline for hypercapnic experiments (bottom); the descending edge was chosen to do the limited onset contrast generated during the progressive CO 2 increase. Black traces represent the whole brain BOLD signal responses.…”

“…While this is may be less apparent when using the resting state signal, a hindrance to robust lag estimation arises due to the low CNR or blood-borne signals. Moreover, signals are subject to additional confounding contributions related to cerebral draining architecture which can influence local dHb concentrations 37 and obscure true blood arrival or transit times. Finally, resting-state and hypercapnia/hyperoxic BOLD signal changes are localized in veins.…”

“…Alternative ways of sorting (particularly for CO 2 -mediated changes) could be based on signal dispersion (defined as ‘Tau’ in the work of Poublanc et al 30 ). Using this approach, onset times could then also be fit explicitly using a gamma variate function 37 . Nevertheless, regions with limited (i.e.…”