Faculty Bibliography

BACKGROUND AND PURPOSE: Chronic hypoperfusion from athero-stenotic lesions is thought to lead to better collateral recruitment compared to cardioembolic strokes. It was sought to compare collateral flow in stroke patients with atrial fibrillation (AF) versus stroke patients with cervical atherosclerotic steno-occlusive disease (CASOD). METHOD: This was a retrospective review of a prospectively collected endovascular database. Patients with (i) anterior circulation large vessel occlusion stroke, (ii) pre-treatment computed tomography angiography (CTA) and (iii) intracranial embolism from AF or CASOD were included. CTA collateral patterns were evaluated and categorized into two groups: absent/poor collaterals (CTA collateral score 0-1) versus moderate/good collaterals (CTA collateral score 2-4). CT perfusion was also utilized for baseline core volume and evaluation of infarct growth. RESULTS: A total of 122 patients fitted the inclusion criteria, of whom 88 (72%) had AF and 34 (27%) CASOD. Patients with AF were older (P < 0.01) and less often males or smokers (P = 0.04 and P < 0.01 respectively). Baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were comparable between groups. Collateral scores were lower in the AF group (P = 0.01) with patients having poor collaterals in 28% of cases versus 9% in the CASOD group (P = 0.03). Mortality rates (20% vs. 0%; P = 0.02) were higher in the AF patients whilst rates of any parenchymal hemorrhage (6% vs. 26%; P < 0.01) were higher in the CASOD group. On multivariable analysis, CASOD was an independent predictor of moderate/good collaterals (odds ratio 4.70; 95% confidence interval 1.17-18.79; P = 0.03). CONCLUSIONS: Atheroembolic strokes seem to be associated with better collateral flow compared to cardioembolic strokes. This may in part explain the worse outcomes of AF-related stroke.

OBJECTIVE: To assess the utility of CT perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset. METHODS: We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 min after a baseline CTP. Patients were classified as 'target mismatch' if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up MRI. RESULTS: Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included; mean age 66 years, median NIHSS 16, median time from symptom onset to endovascular therapy 5.2 hours. Rate of reperfusion was 89%. In patients with target mismatch (n=131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of >/=8 points on the NIH Stroke Scale (83% vs 44%, p=0.002; adjusted OR=6.6; 95% CI 2.1-20.9). This association did not differ between patients treated within 6 hrs (OR = 6.4; 95% CI 1.5-27.8) and those treated beyond 6 hrs after symptom onset (OR = 13.7; 95% CI 1.4-140). INTERPRETATION: The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population

BACKGROUND AND PURPOSE: The purpose of this study is to evaluate the frequency and clinical utility of repeat cerebrovascular imaging with computed tomography angiography (CTA) of the head after contrast-enhanced magnetic resonance angiography (CE-MRA) of the head in acute stroke patients. MATERIALS AND METHODS: All stroke patients admitted to 2 academic medical centers from January 1, 2012 through December 31, 2014 were identified as part of prospective radiology database if they underwent CE-MRA of the head followed by subsequent CTA of the head within 7 days. Two vascular neurologists blinded to CTA results retrospectively reviewed medical records including documented indications for imaging studies and clinical changes in patients to determine necessity of CTA. RESULTS: Of 1355 acute stroke patients who underwent CE-MRA of the head, 195 (14%) patients underwent subsequent CTA of the head within 7 days, including 33 patients with nondiagnostic CE-MRA because of motion artifact. Of the remaining 162 (12%) patients, 69 (43%) were considered to have an unnecessary CTA of the head. Multivariable logistic regression analysis identified (1) absence of new neurologic examination changes [OR 7.29; 95% CI 1.92-27.63] and (2) same documented indication for both studies [OR 6.47; 95% CI 3.04-13.78] as significant predictors of an unnecessary CTA. Changes in clinical management after CTA were significantly more common in necessary CTAs compared with studies determined to be unnecessary (42% versus 7%, P < .0001). CONCLUSION: The utility of repeat cerebrovascular imaging with CTA of the head following a diagnostic CE-MRA is low when there is no change in neurologic examination or when ordered for the same indication.

The purpose of this study was to measure cerebrovascular reactivity (CVR) in chronic steno-occlusive disease using a novel approach that couples BOLD imaging with acetazolamide (ACZ) vasoreactivity (aczBOLD), to evaluate dynamic effects of ACZ on BOLD and to establish the relationship between aczBOLD and dynamic susceptibility contrast (DSC) perfusion MRI. Eighteen patients with unilateral chronic steno-occlusive disease of the anterior circulation underwent a 20-min aczBOLD imaging protocol, with ACZ infusion starting at 5 min of scan initiation. AczBOLD reactivity was calculated on a voxel-by-voxel basis to generate CVR maps for subsequent quantitative analyses. Reduced CVR was observed in the diseased vs. the normal hemisphere both by qualitative and quantitative assessment (gray matter (GM): 4.13% +/- 1.16% vs. 4.90% +/- 0.98%, P = 0.002; white matter (WM): 2.83% +/- 1.23% vs. 3.50% +/- 0.94%, P = 0.005). In all cases BOLD signal began increasing immediately following ACZ infusion, approaching a plateau at ~ 8.5 min after infusion, with the tissue volume of reduced augmentation increasing progressively with time, peaking at 2.60 min (time range above 95% of the maximum value: 0-4.43 min) for the GM and 1.80 min (time range above 95% of the maximum value: 1.40-3.53 min) for the WM. In the diseased hemisphere, aczBOLD CVR significantly correlated with baseline DSC time-to-maximum of the residue function (Tmax) (P = 0.008 for the WM) and normalized cerebral blood flow (P = 0.003 for the GM, and P = 0.001 for the WM). AczBOLD provides a novel, safe, easily implementable approach to CVR measurement in the routine clinical environments. Further studies can establish quantitative thresholds from aczBOLD towards identification of patients at heightened risk of recurrent ischemia and cognitive decline.

Importance: Endovascular therapy (ET) is typically not considered for patients with large baseline ischemic cores (irreversibly injured tissue). Computed tomographic perfusion (CTP) imaging may identify a subset of patients with large ischemic cores who remain at risk for significant infarct expansion and thus could still benefit from reperfusion to reduce their degree of disability. Objective: To compare the outcomes of patients with large baseline ischemic cores on CTP undergoing ET with the outcomes of matched controls who had medical care alone. Design, Setting, and Participants: A matched case-control study of patients with proximal occlusion after stroke (intracranial internal carotid artery and/or middle cerebral artery M1 and/or M2) on computed tomographic angiography and baseline ischemic core greater than 50 mL on CTP at a tertiary care center from May 1, 2011, through October 31, 2015. Patients receiving ET and controls receiving medical treatment alone were matched for age, baseline ischemic core volume on CTP, and glucose levels. Baseline characteristics and outcomes were compared. Main Outcomes and Measures: The primary outcome measure was the shift in the degree of disability among the treatment and control groups as measured by the modified Rankin Scale (mRS) (with scores ranging from 0 [fully independent] to 6 [dead]) at 90 days. Results: Fifty-six patients were matched across 2 equally distributed groups (mean [SD] age, 62.25 [13.92] years for cases and 58.32 [14.79] years for controls; male, 13 cases [46%] and 14 controls [50%]). Endovascular therapy was significantly associated with a favorable shift in the overall distribution of 90-day mRS scores (odds ratio, 2.56; 95% CI, 2.50-8.47; P = .04), higher rates of independent outcomes (90-day mRS scores of 0-2, 25% vs 0%; P = .04), and smaller final infarct volumes (mean [SD], 87 [77] vs 242 [120] mL; P < .001). One control (4%) and 2 treatment patients (7%) developed a parenchymal hematoma type 2 (P > .99). The rates of hemicraniectomy (2 [7%] vs 6 [21%]; P = .10) and 90-day mortality (7 [29%] vs 11 [48%]; P = .75) were numerically lower in the intervention arm. Sensitivity analysis for patients with a baseline ischemic core greater than 70 mL (12 pairs) revealed a significant reduction in final infarct volumes (mean [SD], 110 [65] vs 319 [147] mL; P < .001) but only a nonsignificant improvement in the overall distribution of mRS scores favoring the treatment group (P = .18). All 11 patients older than 75 years had poor outcomes (mRS score >3) at 90 days. Conclusions and Relevance: In properly selected patients, ET appears to benefit patients with large core and large mismatch profiles. Future prospective studies are warranted.

BACKGROUND AND PURPOSE: Cerebral thermoregulation remains poorly understood. Temperature dysregulation is deeply implicated in the potentiation of cerebrovascular ischemia. We present a multiphasic, MR thermographic study in a nonhuman primate model of MCA infarction, hypothesizing detectable brain temperature disturbances and brain-systemic temperature decoupling. MATERIALS AND METHODS: Three Rhesus Macaque nonhuman primates were sourced for 3-phase MR imaging: 1) baseline MR imaging, 2) 7-hour continuous MR imaging following minimally invasive, endovascular MCA stroke induction, and 3) poststroke day 1 MR imaging follow-up. MR thermometry was achieved by multivoxel spectroscopy (semi-localization by adiabatic selective refocusing) by using the proton resonance frequency chemical shift. The relationship of brain and systemic temperatures with time and infarction volumes was characterized by using a mixed-effects model. RESULTS: Following MCA infarction, progressive cerebral hyperthermia was observed in all 3 subjects, significantly outpacing systemic temperature fluctuations. Highly significant associations were observed for systemic, hemispheric, and global brain temperatures (F-statistic, P = .0005 for all regressions) relative to the time from stroke induction. Significant differences in the relationship between temperature and time following stroke onset were detected when comparing systemic temperatures with ipsilateral (P = .007), contralateral (P = .004), and infarction core (P = .003) temperatures following multiple-comparisons correction. Significant associations were observed between infarction volumes and both systemic (P