Impaired dynamic cerebrovascular response to hypercapnia predicts development of white matter hyperintensities

Abstract

PurposeTo evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease.MethodsBlood oxygen level-dependent (BOLD) MRI CVR scans were acquired from forty-five subjects (age range: 50–90 years, 25 males) with moderate to severe white matter disease, at baseline and one-year follow-up. To calculate the dynamic (τ) and steady-state (ssCVR) components of the BOLD signal response, the PETCO2 signal waveform was convolved with an exponential decay function. The τ corresponding to the best fit between the convolved PETCO2 and BOLD signal defined the speed of response, and the slope of the regression between the convolved PETCO2 and BOLD signal defined ssCVR. ssCVR and τ were compared between normal-appearing white matter (NAWM) that remains stable over time and NAWM that progresses to white matter hyperintensities (WMHs).ResultsIn comparison to contralateral NAWM, NAWM that progressed to WMH had significantly lower ssCVR values by mean (SD) 46.5 (7.6)%, and higher τ values by 31.9 (9.6)% (both P < 0.01).ConclusionsVascular impairment in regions of NAWM that progresses to WMH consists not only of decreased magnitude of ssCVR, but also a pathological decrease in the speed of vascular response. These findings support the association between cerebrovascular dysregulation and the development of WMH.

BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

“…The current study demonstrates that WM CVR information is informative and robust: namely, conventional CVR and VTF‐AUC in WM were lower in WMH groups compared with healthy participants, and VTF‐TTP was lower in healthy participants, compared with the moderate WMH group in WM. These results support previous studies in people with WMH, which report that CBF and CVR are reduced in WMH vulnerable regions . Collectively, these findings suggest that CVR impairment in WM occurs due to potentially both timing and amplitude deficits, which aligns with the pathophysiology that shows smaller arteries and/or arterioles are subject to functionally impaired vasodilation in CSVD, whereas GM is less affected .…”

The efficiency of the brain connectome is associated with cerebrovascular reactivity in persons with white matter hyperintensities

“…Prior studies showed impaired white matter CVR is associated with disruption of white matter at the microstructural scale in participants with WMH (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016). Prior studies showed impaired white matter CVR is associated with disruption of white matter at the microstructural scale in participants with WMH (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016).…”

“…Impaired cerebrovascular autoregulation may also be contributing to chronic ischemia (Mikulis, 2013). Exhaustion of cerebrovascular reserve and the associated chronic ischemic injury to gray matter and white matter is hypothesized as the cause of disruption of both the network nodes and edges of the connectome respectively (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016). Exhaustion of cerebrovascular reserve and the associated chronic ischemic injury to gray matter and white matter is hypothesized as the cause of disruption of both the network nodes and edges of the connectome respectively (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016).…”

“…In patients with cerebrovascular disease, chronic ischemia may be caused by neurovascular uncoupling and an inability to increase blood flow in response to neural activity (Mikulis, 2013). Since impaired white matter CVR is associated with reduced FA (Sam, Conklin, Holmes, et al, 2016) threshold. In white matter, ischemic injury may be reducing the number of tracts in the network.…”

“…Using graph theory analysis, the global and local efficiency of the connectome was calculated (Rubinov & Sporns, 2010). Tractography depends on a FA threshold to terminate tracts, and since CVR and WMH are associated with altered FA, a secondary analysis was applied (Behrens & Jbabdi, 2009;Reginold et al, 2018;Sam, Conklin, Holmes, et al, 2016). As a control, we assessed the association between WMH volume with global and local efficiency which has been described in prior studies (Lawrence et al, 2014;Tuladhar, van Dijk, et al, 2016;Tuladhar, van Uden, et al, 2016;Valenti et al, 2017;Wiseman et al, 2018;Xu et al, 2018).…”