Evaluating Collateral Flow Territory Stability As A Novel Biomarker Of Recurrent Stroke In Patients With Symptomatic Intracranial Stenosis

Introduction: Intracranial (IC) collateral pathways provide important indicators of arterial steno-occlusion compensation, however evaluating the adequacy of these pathways is difficult with existing methods. Here, we modulated arterial partial pressure of CO 2 with mild hypercapnic respiratory stimuli to evaluate the stability of cerebral blood flow (CBF) territories in IC stenosis patients as a novel marker of collateralization adequacy. Methods: Symptomatic IC stenosis (n=20) and healthy (n=10) volunteers provided written consent and underwent noninvasive vessel-encoded arterial spin labeling. Separate magnetic labeling of the left ICA, right ICA, and vertebral arteries was performed, yielding 3 CBF territories. Scans were performed during normocapnia and hypercapnia (5% CO 2 ) and patients were monitored for recurrent stroke for a mean 1.6 years. The primary study variable was the CBF territory shifting index, defined as the percent of voxels changing from normocapnia to hypercapnia; the clinical endpoint was new non-cardioembolic stroke, TIA, or silent cerebral infarct. Significance was defined as two-sided p<0.05. Results: 10/20 patients experienced a clinical endpoint at or before follow-up. Shifting indices were significantly larger in patients meeting the clinical end-point (1.49±0.32) compared to controls (0.67±0.071; p<0.022) and patients not meeting the endpoint (0.67±0.12; p<0.0089) ( Fig. 1) . Using 1 standard error above the mean patient shifting index as a threshold, sensitivities and specificities for predicting the clinical endpoint were 70% (7 of 10) and 97% (29 of 30), respectively. Conclusion: Mild shifting of major CBF territories during hypercapnia may be elevated in IC stenosis patients at risk for recurrent stroke. This approach may provide a new marker of collateralization adequacy and risk of recurrent ischemic events. Figure 1: A. CBF territory shifting in a patient with left ICA stenosis. B. Boxplots of shifting indices.