Acute Ischemic Stroke Predictors of Reperfusion in Patients with

BACKGROUND AND PURPOSE: Ischemic stroke studies emphasize a difference between reperfusion and recanalization, but predictors of reperfusion have not been elucidated. The aim of this study was to evaluate the relationship between reperfusion and recanalization and identify predictors of reperfusion. MATERIALS AND METHODS: From the Dutch Acute Stroke Study, 178 patients were selected with an MCA territory deficit on admission CTP and day 3 follow-up CTP and CTA. Reperfusion was evaluated on CTP, and recanalization on CTA, follow-up imaging. Reperfusion percentages were calculated in patients with and without recanalization. Patient admission and treatment characteristics and admission CT imaging parameters were collected. Their association with complete reperfusion was analyzed by using univariate and multivariate logistic regression. RESULTS: Sixty percent of patients with complete recanalization showed complete reperfusion (relative risk, 2.60; 95% CI, 1.63– 4.13). Approximately one-third of patients showed some discrepancy between recanalization and reperfusion status. Lower NIHSS score (OR, 1.06; 95% CI, 1.01–1.11), smaller infarct core size (OR, 3.11; 95% CI, 1.46 – 6.66; and OR, 2.40; 95% CI, 1.14 –5.02), smaller total ischemic area (OR, 4.20; 95% CI, 1.91–9.22; and OR, 2.35; 95% CI, 1.12– 4.91), lower clot burden (OR, 1.35; 95% CI, 1.14 –1.58), distal thrombus location (OR, 3.02; 95% CI, 1.76 –5.20), and good collateral score (OR, 2.84; 95% CI, 1.34 – 6.02) significantly increased the odds of complete reperfusion. In multivariate analysis, only total ischemic area (OR, 6.12; 95% CI, 2.69 –13.93; and OR, 1.91; 95% CI, 0.91– 4.02) was an independent predictor of complete reperfusion. CONCLUSIONS: Recanalization and reperfusion are strongly associated but not always equivalent in ischemic stroke. A smaller total ischemic area is the only independent predictor of complete reperfusion. ABBREVIATIONS: DUST Dutch Acute Stroke Study; RR relative risk Patients with acute ischemic stroke presenting within 4.5 hours are treated with IV-rtPA to dissolve the thrombus and achieve revascularization. A recent consensus meeting on stroke imaging research (Acute Stroke Imaging Research Roadmap II) suggests that revascularization is a combination of 3 different mechanisms: 1) recanalization, referring to arterial patency; 2) reperfusion, which refers to antegrade microvascular perfusion; and 3) collateralization, which refers to microvascular perfusion via pial arteries or other anastomotic arterial channels that bypass the primary site of vessel occlusion. Recanalization, reperfusion, and collateralization can be evaluated by CTA and CTP, which are frequently used in dedicated stroke imaging protocols. An important reason to look at the revascularization mechanisms separately is the concept that recanalization of an arterial occlusion, as visualized on CTA, does not necessarily lead to complete reperfusion and improved clinical outcome. Furthermore, reperfusion can also occur without afferent vessel recanalization through collateralization of the ischemic area by collateral flow. Many previous studies, including those investigating intra-arterial therapy, consider recanalization to be synonymous with reperfusion. Other articles suggest that this assumption is not justified and found reperfusion to be a better predictor of follow-up infarct volume and clinical outcome than recanalization. Received August 11, 2014; accepted after revision December 11. From the Department of Radiology (A.D.H., J.W.D., J.M.N., T.v.S., I.C.v.d.S., W.P.Th.M.M., B.K.V.), University Medical Center Utrecht, Utrecht, the Netherlands; Department of Radiology (A.D.H.), Rijnstate Hospital, Arnhem, the Netherlands; and Julius Center for Health Sciences and Primary Care (Y.v.d.G.), Utrecht, the Netherlands. This work was supported by grants from the Netherlands Heart Foundation (2008 T034 and 2012 T061) and the Nuts Ohra Foundation (0903-012). Please address correspondence to Alexander D. Horsch, MD, MRCS, University Medical Center Utrecht, Heidelberglaan 100, HP E01.132, 3584 CX Utrecht, the Netherlands; e-mail: alexanderhorsch@gmail.com http://dx.doi. org/10.3174/ajnr.A4283 1056 Horsch Jun 2015 www.ajnr. org Although recanalization correlates well with improved reperfusion rates, it is unclear which other clinical and imaging factors influence reperfusion. Knowing which factors, available before treatment decisions, predict complete reperfusion could aid in decision-making. Treatment with IV-rtPA, good collateral scores and lesion geography (location of the infarct relative to penumbra), and structure (solitary or multiple infarct areas) have been related to reperfusion status assessed with CT or MR imaging. The aim of this study was to evaluate the relationship between reperfusion and recanalization and to investigate which clinical and CT imaging parameters, available on admission, can help predict complete reperfusion in patients with acute ischemic stroke. MATERIALS AND METHODS Study Design The Dutch Acute Stroke Study (DUST) is a large prospective multicenter cohort study, which aims to assess the additional value of CTP and CTA in predicting the outcome of patients with acute ischemic stroke. The study protocol has been published previously. In brief, inclusion criteria for this study were 18 years of age or older, suspected acute ischemic stroke of 9 hours’ duration, and an NIHSS score of 2 (or 1 if an indication for IV-rtPA was present). Exclusion criteria were known renal failure, contraindications to iodinated contrast material, and the presence of another diagnosis on admission NCCT that explained the symptoms. This study was approved by the local institutional ethics review boards of the participating centers. All patients or family gave signed informed consent unless a patient died before consent could be obtained. In that case, the need for consent was waived by the medical ethics committee. Patient Selection From the DUST data base, a consecutive series of patients included between May 2009 and August 2012 was selected from 9 centers. Additional inclusion criteria for this study were the following: 1) perfusion deficit in the MCA territory on admission CTP, and 2) available admission and follow-up CTP and CTA. Exclusion criteria were the following: 1) poor-quality CTP or CTA, 2) absence of 1 of the 2 ASPECTS levels on admission CTP, or 3) use of intra-arterial treatment. The inclusion process is clarified in the flow chart (Fig 1). Predictor Selection Clinical variables that were collected included age, sex, history of stroke, admission NIHSS score, IV-rtPA treatment, and time from symptom onset to treatment. Admission imaging variables included the following: infarct core size and total ischemic area from CTP ASPECTS levels and clot burden (clot burden score), thrombus location (ICA, MCA-M1 segment, MCA-M2 segment, and M2), and collateral score from CTA. Imaging Protocol NCCT, CTP, and CTA of the cervical and cerebral vessel were performed on admission. Multidetector CT scanners were used, with the number of detectors ranging from 40 to 320 (Brilliance 40, Brilliance 64, Brilliance iCT 256; Philips Healthcare, Best, the Netherlands; Sensation 64; Siemens, Erlangen, Germany; Aquilion ONE; Toshiba Medical Systems, Tokyo, Japan). NCCT was performed with 120 kV, 300 –375 mAs, and a section thickness of 5 mm. The CTP, performed with 80 kV and 150 mAs, involved successive gantry rotations in cine mode during intravenous administration of 40 mL of nonionic contrast material followed by 40 mL of saline with a flow of 6 mL/s. CTP coverage included at least the level of the basal ganglia to the lateral ventricles to be able to assess both ASPECTS levels. CTA was acquired from the aortic arch to the vertex with 50 –70 mL of contrast followed by 40 mL of saline, both with a flow of 6 mL/s. The individual CTA scan delay after intravenous injection was calculated from time-to-peak arterial enhancement on CTP or by trigger-based Hounsfield unit threshold measurement of contrast enhancement in the aortic arch. FIG 1. Inclusion flow chart. AJNR Am J Neuroradiol 36:1056 – 62 Jun 2015 www.ajnr. org 1057