Background— The collateral circulation plays a pivotal role in the pathophysiology of cerebral ischemia. Current knowledge of the collateral circulation remains sparse, largely because of prior limitations in methods for evaluation of these diminutive routes of cerebral blood flow. Summary of Review— Anatomic descriptions of the collateral circulation often focus on more proximal anastomoses at the circle of Willis, neglecting secondary collateral pathways provided by leptomeningeal vessels. Pathophysiological recruitment of collateral vessels likely depends on the temporal course of numerous compensatory hemodynamic, metabolic, and neural mechanisms. Subsequent endurance of these protective vascular pathways may determine the severity of ischemic injury. Characterization of the collateral circulation with advanced neuroimaging modalities that provide angiographic information and perfusion data may elucidate critical determinants of collateral blood flow. Such information on the status of the collateral circulation may be used to guide therapeutic interventions. Prognostication and risk stratification may also be improved by routine evaluation of collateral blood flow. Conclusions— Contemporary understanding of the collateral circulation may be greatly enhanced through further refinement of neuroimaging modalities that correlate angiographic findings with perfusion status, providing the basis for future therapeutic and prognostic applications.

Background and Purpose—: The purpose of this study was to provide the first correlative study of the hyperdense middle cerebral artery sign (HMCAS) and gradient-echo MRI blooming artifact (BA) with pathology of retrieved thrombi in acute ischemic stroke. Methods—: Noncontrast CT and gradient-echo MRI studies before mechanical thrombectomy in 50 consecutive cases of acute middle cerebral artery ischemic stroke were reviewed blinded to clinical and pathology data. Occlusions retrieved by thrombectomy underwent histopathologic analysis, including automated quantitative and qualitative rating of proportion composed of red blood cells (RBCs), white blood cells, and fibrin on microscopy of sectioned thrombi. Results—: Among 50 patients, mean age was 66 years and 48% were female. Mean (SD) proportion was 61% (±21) fibrin, 34% (±21) RBCs, and 4% (±2) white blood cells. Of retrieved clots, 22 (44%) were fibrin-dominant, 13 (26%) RBC-dominant, and 15 (30%) mixed. HMCAS was identified in 10 of 20 middle cerebral artery stroke cases with CT with mean Hounsfield Unit density of 61 (±8 SD). BA occurred in 17 of 32 with gradient-echo MRI. HMCAS was more commonly seen with RBC-dominant and mixed than fibrin-dominant clots (100% versus 67% versus 20%, P =0.016). Mean percent RBC composition was higher in clots associated with HMCAS (47% versus 22%, P =0.016). BA was more common in RBC-dominant and mixed clots compared with fibrin-dominant clots (100% versus 63% versus 25%, P =0.002). Mean percent RBC was greater with BA (42% versus 23%, P =0.011). Conclusions—: CT HMCAS and gradient-echo MRI BA reflect pathology of occlusive thrombus. RBC content determines appearance of HMCAS and BA, whereas absence of HMCAS or BA may indicate fibrin-predominant occlusive thrombi.

Background and Purpose—: Collaterals sustain the penumbra before recanalization and offset infarct growth, yet the influence of baseline collateral flow on recanalization after endovascular therapy remains relatively unexplored. Methods—: We analyzed consecutive patients who received endovascular therapy for acute cerebral ischemia from 2 distinct study populations. We assessed the relationship between pretreatment collateral grade and vascular recanalization (Thrombolysis In Myocardial Ischemia [TIMI] scale). In addition, we assessed infarct growth on serial MRI. Results—: A total of 222 patients was included, 138 from the United States and 84 from South Korea. Complete revascularization occurred in 14.1% (11 of 78) patients with poor pretreatment collateral grades, whereas it was observed in 25.2% (26 of 103) patients with good collaterals and 41.5% (17 of 41) patients with excellent collaterals ( P <0.001). This relationship was consistently observed in both study populations, although the mode of endovascular therapy was different between them. After adjustment for other factors, including mode of endovascular therapy, prior use of intravenous tissue plasminogen activator, and site of occlusion, pretreatment collateral grade was independently associated with recanalization. When revascularization was achieved, greater infarct growth occurred in patients with poor collaterals than in those with good collaterals ( P =0.012). Conclusions—: Our data indicate that angiographic collateral grade determines the recanalization rate after endovascular revascularization therapy. When therapeutic revascularization was achieved, beneficial effects were not observed in patients with poor collaterals. Angiographic collateral grade may therefore help guide treatment decision-making in acute cerebral ischemia.

Background: Collaterals may sustain penumbra prior to recanalisation yet the influence of baseline collateral flow on infarct growth following endovascular therapy remains unknown. Methods: Consecutive patients underwent serial diffusion and perfusion MRI before and after endovascular therapy for acute cerebral ischaemia. We assessed the relationship between MRI diffusion and perfusion lesion indices, angiographic collateral grade and infarct growth. Tmax perfusion lesion maps were generated and diffusion–perfusion mismatch regions were divided into Tmax ⩾4 s (severe delay) and Tmax ⩾2 but <4 s (mild delay). Results: Among 44 patients, collateral grade was poor in 7 (15.9%), intermediate in 20 (45.5%) and good in 17 (38.6%) patients. Although diffusion–perfusion mismatch volume was not different depending on the collateral grade, patients with good collaterals had larger areas of milder perfusion delay than those with poor collaterals (p = 0.005). Among 32 patients who underwent day 3–5 post-treatment MRIs, the degree of pretreatment collateral circulation (r = −0.476, p = 0.006) and volume of diffusion–perfusion mismatch (r = 0.371, p = 0.037) were correlated with infarct growth. Greatest infarct growth occurred in patients with both non-recanalisation and poor collaterals. Multiple regression analysis revealed that pretreatment collateral grade was independently associated with infarct growth. Conclusion: Our data suggest that angiographic collateral grade and penumbral volume interactively shape tissue fate in patients undergoing endovascular recanalisation therapy. These angiographic and MRI parameters provide complementary information about residual blood flow that may help guide treatment decision making in acute cerebral ischaemia.

Background and Purpose—: Endovascular strategies provide unique opportunity to correlate angiographic measures of collateral circulation at the time of endovascular therapy. We conducted systematic analyses of collaterals at conventional angiography on recanalization, reperfusion, and clinical outcomes in the endovascular treatment arm of the Interventional Management of Stroke (IMS) III trial. Methods—: Prospective evaluation of angiographic collaterals was conducted via central review of subjects treated with endovascular therapy in IMS III (n=331). Collateral grade before endovascular therapy was assessed with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale, blinded to all other data. Statistical analyses investigated the association between collaterals with baseline clinical variables, angiographic measures of recanalization, reperfusion and clinical outcomes. Results—: Adequate views of collateral circulation to the ischemic territory were available in 276 of 331 (83%) subjects. Collateral grade was strongly related to both recanalization of the occluded arterial segment ( P =0.0016) and downstream reperfusion ( P <0.0001). Multivariable analyses confirmed that robust angiographic collateral grade was a significant predictor of good clinical outcome (modified Rankin Scale score ≤2) at 90 days ( P =0.0353), adjusted for age, history of diabetes mellitus, National Institutes of Health Stroke Scale strata, and Alberta Stroke Program Early CT Score. The relationship between collateral flow and clinical outcome may depend on the degree of reperfusion. Conclusions—: More robust collateral grade was associated with better recanalization, reperfusion, and subsequent better clinical outcomes. These data, from the largest endovascular trial to date, suggest that collaterals are an important consideration in future trial design. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00359424.