Publications

    Copen WA, Yoo AJ, Rost NS, Morais LT, Schaefer PW, González GR, Wu O. In patients with suspected acute stroke, CT perfusion-based cerebral blood flow maps cannot substitute for DWI in measuring the ischemic core. PLoS One 2017;12(11):e0188891.Abstract
    BACKGROUND: Neuroimaging may guide acute stroke treatment by measuring the volume of brain tissue in the irreversibly injured "ischemic core." The most widely accepted core volume measurement technique is diffusion-weighted MRI (DWI). However, some claim that measuring regional cerebral blood flow (CBF) with CT perfusion imaging (CTP), and labeling tissue below some threshold as the core, provides equivalent estimates. We tested whether any threshold allows reliable substitution of CBF for DWI. METHODS: 58 patients with suspected stroke underwent DWI and CTP within six hours of symptom onset. A neuroradiologist outlined DWI lesions. In CBF maps, core pixels were defined by thresholds ranging from 0%-100% of normal, in 1% increments. Replicating prior studies, we used receiver operating characteristic (ROC) curves to select thresholds that optimized sensitivity and specificity in predicting DWI-positive pixels, first using only pixels on the side of the brain where infarction was clinically suspected ("unilateral" method), then including both sides ("bilateral"). We quantified each method and threshold's accuracy in estimating DWI volumes, using sums of squared errors (SSE). For the 23 patients with follow-up studies, we assessed whether CBF-derived volumes inaccurately exceeded follow-up infarct volumes. RESULTS: The areas under the ROC curves were 0.89 (unilateral) and 0.90 (bilateral). Various metrics selected optimum CBF thresholds ranging from 29%-32%, with sensitivities of 0.79-0.81, and specificities of 0.83-0.85. However, for the unilateral and bilateral methods respectively, volume estimates derived from all CBF thresholds above 28% and 22% were less accurate than disregarding imaging and presuming every patient's core volume to be zero. The unilateral method with a 30% threshold, which recent clinical trials have employed, produced a mean core overestimation of 65 mL (range: -82-191), and exceeded follow-up volumes for 83% of patients, by up to 191 mL. CONCLUSION: CTP-derived CBF maps cannot substitute for DWI in measuring the ischemic core.
    Copen WA, Morais LT, Wu O, Schwamm LH, Schaefer PW, González GR, Yoo AJ. In Acute Stroke, Can CT Perfusion-Derived Cerebral Blood Volume Maps Substitute for Diffusion-Weighted Imaging in Identifying the Ischemic Core?. PLoS One 2015;10(7):e0133566.Abstract
    BACKGROUND AND PURPOSE: In the treatment of patients with suspected acute ischemic stroke, increasing evidence suggests the importance of measuring the volume of the irreversibly injured "ischemic core." The gold standard method for doing this in the clinical setting is diffusion-weighted magnetic resonance imaging (DWI), but many authors suggest that maps of regional cerebral blood volume (CBV) derived from computed tomography perfusion imaging (CTP) can substitute for DWI. We sought to determine whether DWI and CTP-derived CBV maps are equivalent in measuring core volume. METHODS: 58 patients with suspected stroke underwent CTP and DWI within 6 hours of symptom onset. We measured low-CBV lesion volumes using three methods: "objective absolute," i.e. the volume of tissue with CBV below each of six published absolute thresholds (0.9-2.5 mL/100 g), "objective relative," whose six thresholds (51%-60%) were fractions of mean contralateral CBV, and "subjective," in which two radiologists (R1, R2) outlined lesions subjectively. We assessed the sensitivity and specificity of each method, threshold, and radiologist in detecting infarction, and the degree to which each over- or underestimated the DWI core volume. Additionally, in the subset of 32 patients for whom follow-up CT or MRI was available, we measured the proportion of CBV- or DWI-defined core lesions that exceeded the follow-up infarct volume, and the maximum amount by which this occurred. RESULTS: DWI was positive in 72% (42/58) of patients. CBV maps' sensitivity/specificity in identifying DWI-positive patients were 100%/0% for both objective methods with all thresholds, 43%/94% for R1, and 83%/44% for R2. Mean core overestimation was 156-699 mL for objective absolute thresholds, and 127-200 mL for objective relative thresholds. For R1 and R2, respectively, mean±SD subjective overestimation were -11±26 mL and -11±23 mL, but subjective volumes differed from DWI volumes by up to 117 and 124 mL in individual patients. Inter-rater agreement regarding the presence of infarction on CBV maps was poor (kappa = 0.21). Core lesions defined by the six objective absolute CBV thresholds exceeded follow-up infarct volumes for 81%-100% of patients, by up to 430-1002 mL. Core estimates produced by objective relative thresholds exceeded follow-up volumes in 91% of patients, by up to 210-280 mL. Subjective lesions defined by R1 and R2 exceeded follow-up volumes in 18% and 26% of cases, by up to 71 and 15 mL, respectively. Only 1 of 23 DWI lesions (4%) exceeded final infarct volume, by 3 mL. CONCLUSION: CTP-derived CBV maps cannot reliably substitute for DWI in measuring core volume, or even establish which patients have DWI lesions.
    Wu O, Batista LM, Lima FO, Vangel MG, Furie KL, Greer DM. Predicting clinical outcome in comatose cardiac arrest patients using early noncontrast computed tomography. Stroke 2011;42(4):985-92.Abstract
    BACKGROUND AND PURPOSE: Early assessment of the likelihood of neurological recovery in comatose cardiac arrest survivors remains challenging. We hypothesize that quantitative noncontrast computed tomography (NCCT) combined with neurological assessments, are predictive of outcome. METHODS: We analyzed data sets acquired from comatose cardiac arrest patients who underwent CT within 72 hours of arrest. Images were semiautomatically segmented into anatomic regions. Median Hounsfield units (HU) were measured regionally and in the whole brain (WB). Outcome was based on the 6-month modified Rankin Scale (mRS) score. Logistic regression was used to combine Glasgow Coma Scale (GCS) score measured on Day 3 post arrest (GCS_Day3) with imaging to predict poor outcome (mRS>4). RESULTS: WB HU (P=0.02) and the ratio of HU in the putamen to the posterior limb of the internal capsule (PLIC) (P=0.004) from 175 datasets from 151 patients were univariate predictors of poor outcome. Thirty-three patients underwent hypothermia treatment. Multivariate analysis showed that combining median HU in the putamen (P=0.0006) and PLIC (P=0.007) was predictive of poor outcome. Combining WB HU and GCS_Day3 resulted in 72% [61% to 80%] sensitivity and 100% [73% to 100%] specificity for predicting poor outcome in 86 patients with measurable GCS_Day3. This was an improvement over prognostic performance based on GCS_Day3≤8 (98% sensitive but 71% specific). DISCUSSION: Combining density changes on CT with GCS_Day3 may be useful for predicting poor outcome in comatose cardiac arrest patients who are neither rapidly improving nor deteriorating. Improved prognostication with CT compared with neurological assessments can be achieved in patients treated with hypothermia.