Background Neurointerventionalists do not agree about the optimal imaging protocol when evaluating patients with acute stroke for potential endovascular revascularization. Preintervention cerebrovascular blood volume (CBV) has been shown to predict outcomes in patients undergoing intra-arterial stroke therapies.
Objective To determine whether CBV can predict hemorrhagic transformation and clinical outcomes in patients selected for endovascular therapy for acute ischemic middle cerebral artery (MCA) stroke using a CT perfusion (CTP)-based imaging protocol.
Methods We retrospectively reviewed cases of acute ischemic stroke due to MCA M1 segment occlusion and correlated favorable clinical outcomes (modified Rankin scale (mRS) ≤2) and radiographic outcomes with preintervention CBV values. All patients underwent whole-brain (320-detector-row) CTP imaging, and absolute CBV values of the affected and contralateral MCA territories were obtained separately for the cortical and basal ganglia regions.
Results Relative CBV (rCBV) of the MCA cortical regions was significantly lower in patients with poor clinical outcomes than in those with favorable clinical outcomes (0.87±0.21 vs 1.02±0.09, p=0.0003), and a negative correlation was found between rCBV values and mRS score severity. rCBV of the basal ganglia region was significantly lower in patients with hemorrhagic infarction (p=0.004) and parenchymal hematoma (p=0.04) than in those without hemorrhagic transformation.
Conclusions We found that cortical CBV loss is predictive of poor clinical outcomes, whereas basal ganglia CBV loss is predictive of hemorrhagic transformation but without translation into poor clinical outcomes. Our study findings support published results of baseline preintervention CBV as a predictor of outcomes in patients undergoing intra-arterial stroke therapies.
- CT perfusion
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Preintervention cerebral blood volume (CBV) values from CT perfusion (CTP) have been shown to be predictive of hemorrhagic transformation and clinical outcomes following endovascular therapy.1–3 However, conflicting data suggest that use of advanced imaging such as CTP may only delay recanalization without correlation with improved clinical outcomes.4
Neurointerventionalists do not agree about the optimal imaging protocol for evaluating patients with acute stroke for potential endovascular revascularization. We investigated the role of CBV as a predictor of hemorrhagic transformation and clinical outcomes in patients with acute stroke from middle cerebral artery (MCA) occlusion.
This study was approved by our local institutional review board. We retrospectively reviewed the medical records of patients with acute ischemic stroke treated by endovascular intra-arterial therapy between 1 January 2010 and 1 October 2013. The acute stroke imaging protocol at our institution includes clinical evaluation, immediately followed by non-contrast brain CT and whole-brain (320-detector-row) CTP imaging in combination with craniocervical CT angiography (CTA) for all patients with suspected acute ischemic stroke. We included cases of acute ischemic stroke due to MCA M1 segment occlusion that were documented on CTA and subsequently confirmed by DSA in patients treated with endovascular therapy. Cases (n=6) of subarachnoid hemorrhage or intraparenchymal hemorrhage from catheter or wire manipulation leading to vessel perforation that were recognized during the interventional procedure were excluded from analysis to allow isolated assessment of CTP-based prediction of outcome.
The following data were collected: age, sex, cerebrovascular risk factors, admission National Institutes of Health Stroke Scale score, time from symptom onset to CTP imaging, and use of intravenous recombinant tissue plasminogen activator in the emergency room. (The imaging protocol and details of imaging data collected are provided below.) Successful recanalization was defined as a Thrombolysis in Cerebral Infarction (TICI) score of 2b–3. Functional neurologic outcomes were quantified using the modified Rankin scale (mRS) at 90 days. Favorable outcome was defined as an mRS score of ≤2. Non-contrast head CT imaging obtained 24–36 h after the intervention was used to assess for hemorrhagic transformation. Intracranial hemorrhage (ICH) was classified as hemorrhagic infarction (HI) or parenchymal hematoma (PH) according to the European–Australasian Acute Stroke Study classification.5
All patients underwent 5 mm thick, non-contrast head CT imaging performed using the Aquilion ONE scanner (Toshiba Medical Systems, Nasu, Japan). CTP was performed using a 320-detector-row CT system (Aquilion ONE). Contrast medium infusion (50 mL, Optiray 350, Mallinckrodt, Missouri, USA) was performed at a rate of 5 mL/s via automated antecubital venous injection. CTP acquisition parameters were 80 kV tube voltage, 200 mA tube current, and 0.35 s rotation. Perfusion maps (cerebral blood flow (CBF), CBV, mean time to peak (mean transit time (MTT)), time to peak, and delay) were reconstructed using Vitrea software (V.6.4, Vital Images, Minnetonka, Minnesota, USA). On average, performing CTP and reconstructing perfusion maps takes 3–4 min. Perfusion maps are then immediately reviewed by the in-house on-call endovascular fellow, and the findings are discussed with the on-call endovascular neurosurgeon.
Thereafter, craniocervical CTA was performed using an infusion of contrast medium (80 mL, Omnipaque 350, GE Healthcare, Waukesha, Wisconsin, USA) at a rate of 4 mL/s, with scanning starting manually once the contrast medium reached the aortic arch. CTA images were reconstructed at 0.5 mm thickness.
Analysis of CTP maps was performed by two operators who were blinded to the final results. A freehand region of interest of increased MTT in the affected MCA territory was used to outline the total brain tissue at risk, with a mirrored region automatically generated on the CBV map, as previously described2 (figure 1). Absolute CBV values were recorded separately from two regions: (1) the MCA territory of the basal ganglia and (2) the supraganglionic territories (labeled as ‘cortical regions’), using standard anatomic regions from the Alberta Stroke Program Early CT score (ASPECTS) system for CTP interpretation.6 ,7 Relative CBV (rCBV) was calculated as the absolute CBV value of the affected hemisphere divided by the absolute CBV value of the contralateral (control) hemisphere.
Analysis of variables was performed using Fisher's exact test for categorical data and a two-tailed t test for continuous data. Analysis of covariance was used to evaluate the association between rCBV and mRS values. For all analyses, p<0.05 was considered statistically significant.
We identified 64 patients with stroke due to MCA M1 occlusion treated with endovascular therapy during the study period. Favorable clinical outcome was achieved in 21 (33%) cases. Demographic, clinical, and procedural characteristics of patients with favorable and poor clinical outcomes are shown in table 1. There was no statistical difference in those characteristics except for atrial fibrillation, which was more frequently seen in patients with poor versus favorable outcomes (53% vs 14%, respectively, p=0.003). TICI 2b–3 recanalization was achieved more often in patients with favorable outcome (95% of those cases) than in those with poor outcome (58%), p=0.003.
CBV values for both groups of patients are shown in table 1. Cortical rCBV was significantly lower in patients with poor clinical outcomes than in those with favorable clinical outcomes (0.87±0.21 and 1.02±0.09, p=0.0003), and a negative correlation was seen between rCBV values and mRS severity (r=−0.41, figure 2, left). rCBV of the basal ganglia was similar in patients with poor (0.9±0.11) and favorable (0.95±0.16, p=0.45) outcomes, and no correlation with mRS severity was seen (r=−0.065, figure 2, right).
CBV values in patients with and without hemorrhagic transformation are shown in table 2. There was no significant difference in rCBV of the cortical regions in patients without ICH versus patients with HI (p=0.83, figure 3, left) or PH (p=0.52, figure 3, left). rCBV of the basal ganglia region was significantly lower in patients with HI (p=0.004, figure 3, right) and PH (p=0.04, figure 3, right) than in patients without ICH.
The findings of our study support the previously published results of baseline preintervention CBV as a predictor of outcomes in patients undergoing intra-arterial stroke therapies. Rai et al1 measured the area of CBV abnormalities in patients with anterior circulation stroke and correlated those findings with functional outcomes at 3 months after intervention. A larger low CBV area was associated with increased mortality. Patients in whom the CBV perfusion deficit exceeded 1370 mm2 did not achieve favorable outcomes despite successful revascularization. Also, poor outcome and mortality could be predicted by CBV abnormality greater than one-third of the MCA distribution. Jain et al2 compared the values of MTT, CBF, and CBV in patients with and without hemorrhagic transformation. Only CBV values were predictive of hemorrhagic transformation. No specific threshold was used in either study to define the CBV deficit when the area representing a perfusion abnormality was selected for analysis.
Several points should be emphasized when interpreting the results of our study. First, because our institution uses CTP-based selection of patients with stroke for endovascular interventions, cases with profound CBV loss (such as CBV loss exceeding one-third of the MCA territory) were excluded from revascularization and thus were not available for analysis. It is possible that additional cases with more severe CBV deficit, if included in our study, would have resulted in a more powerful correlation with clinical outcomes. Because of selection bias, such a cohort is lacking.
Second, our analysis of CBV perfusion maps is different from that of previously published studies of perfusion maps with ASPECTS, in which semiquantitative analysis (perfusion deficit absent vs present) was used.8 ,9 Instead, our study provides quantitative analysis of CBV values for both the affected and contralateral (control) hemisphere. Because our cohort consisted entirely of patients with M1 segment MCA occlusion, we selected regions of the affected hemisphere corresponding to ASPECTS MCA territories. To our knowledge, separate analysis of cortical versus basal ganglia perfusion abnormalities has not been previously conducted. Interestingly, we found that cortical CBV loss is predictive of poor clinical outcomes, whereas basal ganglia CBV loss is predictive of hemorrhagic transformation but without translation into poor clinical outcomes.
Third, quantitative analysis of other perfusion maps (CBF, MTT) was not included in our study. We chose to focus exclusively on CBV on the basis of previously published data indicating its value as a predictor of clinical outcomes.1 ,2
The findings of our study support the previously published results of baseline preintervention CBV as a predictor of outcomes in patients undergoing intra-arterial stroke therapies. We found that cortical CBV loss is predictive of poor clinical outcomes, whereas basal ganglia CBV loss is predictive of hemorrhagic transformation but without translation into poor clinical outcomes.
The authors thank Paul H Dressel BFA for assistance with preparation of the illustrations and Debra J Zimmer for editorial assistance.
Contributors MM, KVS and AHS are responsible for concepts and design. All authors contributed intellectually. All authors acquired, analyzed, and interpreted the data. The manuscript was prepared by MM. All authors reviewed and critically revised the manuscript.
Competing interests EIL: shareholder/ownership interests–Intratech Medical Ltd, Mynx/Access Closure, Blockade Medical LLC; principal investigator: Covidien US SWIFT PRIME trials; other financial support–Abbott for carotid training for physicians. MM: educational grant–Toshiba; AHS: research grants (not related to this study)–National Institutes of Health (co-investigator: NINDS 1R01NS064592-01A1 and NIBIB 5 RO1 EB002873-07), University at Buffalo (Research Development Award); financial interests–Hotspur, Intratech Medical, StimSox, Valor Medical, Blockade Medical, Lazarus Effect; consultant–Codman & Shurtleff, Inc, Concentric Medical, Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra, Stryker Neurovascular, Pulsar Vascular; speakers’ bureaus–Codman & Shurtleff, Genentech; National Steering Committees for Penumbra 3D Separator Trial, Covidien SWIFT PRIME Trial; advisory board–Codman & Shurtleff, Covidien Vascular Therapies; honoraria–Abbott Vascular and Codman & Shurtleff, Inc for training other neurointerventionists in carotid stenting and for training physicians in endovascular stenting for aneurysms. KVS: consultant/speakers’ bureau/honoraria: Toshiba; speakers’ bureau/honoraria: ev3/Covidien, The Stroke Group.
Ethics approval This study was approved by the University at Buffalo institutional review board—project 403427-3.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data may be available as requested from the corresponding author.