Abstract
In patients with carotid artery stenosis (CAS), the risk of stroke, its severity, and response to revascularization are strongly related to the availability of collateral blood flow. Unfortunately, there is poor agreement between observers in assessing collateral flow using flow-based imaging. We used changes in blood-oxygen-level-dependent (BOLD) MRI as a surrogate of changes in regional cerebral blood flow in response to a hypercapnic stimulus [i.e., cerebrovascular reactivity (CVR)] as indicating flow reserve ipsilateral to CAS. We hypothesized that some patients with hemodynamically significant CAS develop functional collateral flow as indicated by normalization of ipsilateral CVR. We identified 55 patients in our CVR database with various degrees of CAS assessed by angiography and classed them as <50% stenosis, 50–69% stenosis, 70–90% stenosis, >90% stenosis, and full occlusion. CVR was measured as the change in BOLD signal in response to changes in end-tidal partial pressure of CO2 (Δ BOLD/Δ PETCO2) and normalized voxel-wise relative to the mean and standard deviation of the CVR in the corresponding voxels of an atlas of 46 healthy controls (CVR z scores). CVR and z scores were then averaged over gray matter (GM) and white matter (WM) on each side of the middle cerebral artery (MCA) territory. As hypothesized, CVR varied for each severity of CAS. Ipsilateral MCA territory CVR was less than normal in each class, including that with <50% stenosis (Student t-test, two-tailed; p = 0.0014 for GM and p = 0.030 for WM), with a trend of decreasing average CVR with increasing stenosis. Remarkably, the considerable individual variability in MCA CVR included some patients with normal CVR in each class – including that with complete occlusion. We conclude that, in general, CAS depresses downstream vascular reserve, but the extent of collateralization is highly variable and not predictable from the degree of stenosis, including both <50% stenosis and complete occlusion. CVR may be the more reliable marker for recruitable collateral blood flow than degree of CAS.
Highlights
Stroke is the leading cause of disability and the third leading cause of death in North America, with approximately 85% of strokes ischemic in nature (Writing Group Members et al, 2016)
Differences in mean middle cerebral artery (MCA), cerebrovascular reactivity (CVR), and z scores between the percent stenosis categories are displayed in Figure 3 for both gray matter (GM) and white matter (WM)
The graphs present a relationship between percent stenosis and mean CVR and z scores
Summary
Stroke is the leading cause of disability and the third leading cause of death in North America, with approximately 85% of strokes ischemic in nature (Writing Group Members et al, 2016). Other than morphology of the lesion, most of these parameters are poorly related to the risk of stroke (Gupta et al, 2012; Reinhard et al, 2014). It has become clear over the last decade that the co-existence of recruitable collateral blood flow (Bang et al, 2008; Sheth et al, 2016; Tan et al, 2016) is one of the strongest predictors of stroke risk, in terms of its severity, prognosis (Lima et al, 2010; Menon et al, 2011), and response to therapy. Current tests of cerebral perfusion (CT and MR perfusion imaging) assess resting blood flow but provide no information about the availability of distal recruitable perfusion (Powers, 1991), i.e., collateral blood flow function, to compensate for an upstream flow obstruction such as from a clot or embolism (Fanou et al, 2015; Leng et al, 2016)
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