Sean P. Symons

CT Angiography “Spot Sign” Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage

Background and Purpose— Morbidity and mortality in spontaneous intracerebral hemorrhage (ICH) are correlated with hematoma progression. We hypothesized that the presence of tiny, enhancing foci (“spot sign”) within acute hematomas is associated with hematoma expansion. Methods— We prospectively studied 39 consecutive patients with spontaneous ICH by computed tomography angiography within 3 hours of symptom onset. Scans were reviewed by 3 readers. Patients were dichotomized according to the presence or absence of the spot sign. Clinical and radiological outcomes were compared between groups. The predictive value of this sign was assessed in a multivariate analysis. Results— Thirteen patients (33%) demonstrated 31 enhancing foci. Baseline clinical variables were similar in both groups. Hematoma expansion occurred in 11 patients (28%) on follow-up. Seventy-seven percent of patients with and 4% without hematoma expansion demonstrated the spot sign (P<0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for expansion were 91%, 89%, 77%, 96%, and 8.5, respectively. Interobserver agreement was high (&kgr;=0.92 to 0.94). In patients with the spot sign, mean volume change was greater (P=0.008), extravasation more common (P=0.0005), and median hospital stay longer (P=0.04), and fewer patients achieved a good outcome (modified Rankin Scale score <2), although the latter was not significant (P=0.16). No differences in hydrocephalus (P=1.00), surgical intervention (P=1.00), or death (P=0.60) were noted between groups. In multiple regression, the spot sign independently predicted hematoma expansion (P=0.0003). Conclusions— The computed tomography angiography spot sign is associated with the presence and extent of hematoma progression. Fewer patients achieve a good clinical outcome and hospital stay was longer. Further studies are warranted to validate the ability of this sign to predict clinical outcomes.

CT Angiography Clot Burden Score and Collateral Score: Correlation with Clinical and Radiologic Outcomes in Acute Middle Cerebral Artery Infarct

BACKGROUND AND PURPOSE: Clot extent, location, and collateral integrity are important determinants of outcome in acute stroke. We hypothesized that a novel clot burden score (CBS) and collateral score (CS) are important determinants of clinical and radiologic outcomes and serve as useful additional stroke outcome predictors. MATERIALS AND METHODS: One hundred twenty-one patients with anterior circulation infarct presenting within 3 hours of stroke onset were reviewed. The Spearman correlation was performed to assess the correlation between CBS and CS and clinical and radiologic outcome measures. Patients were dichotomized by using a 90-day modified Rankin scale (mRS) score. Uni- and multivariate logistic regression models were used to assess variables predicting favorable clinical and radiologic outcomes. Receiver operating characteristic and intraclass correlation coefficient (ICC) analyses were performed. Diagnostic performance of a CBS threshold of >6 was assessed. RESULTS: There were 85 patients (mean age, 70 ± 14.5 years). Patients with higher CBS and CS demonstrated smaller pretreatment perfusion defects and final infarct volume and better clinical outcome (all, P < .01). CBS (P = .009) and recanalization (P = .015) independently predicted favorable outcome. A CBS >6 predicted good clinical outcome with an area under the curve of 0.75 (95% confidence interval [CI], 0.65–0.84; P = .0001), sensitivity of 73.0 (95% CI, 55.9–86.2), and specificity of 64.6 (95% CI, 49.5–77.8). The recanalization rate with intravenous recombinant tissue plasminogen activator was higher in patients with CBS >6 (P = .04; odds ratio, 3.2; 95% CI, 1.1–9.4). The ICC was 0.97 (95% CI, 0.95–0.98) and 0.87 (95% CI, 0.80–0.91) for CBS and CS, respectively. CONCLUSIONS: CBS and CS are useful additional markers predicting clinical and radiologic outcomes.

Identification of Penumbra and Infarct in Acute Ischemic Stroke Using Computed Tomography Perfusion–Derived Blood Flow and Blood Volume Measurements

Background and Purpose— We investigated whether computed tomography (CT) perfusion–derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. Methods— Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL · 100 g−1 · min−1 that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. Results— For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3±3.75 mL · 100 g−1 · min−1) than penumbra (25.0±3.82 mL · 100 g−1 · min−1). CBV in the penumbra (2.15±0.43 mL · 100 g−1) was significantly higher than contralateral (1.78±0.30 mL · 100 g−1) and infarcted tissue (1.12±0.37 mL · 100 g−1). Logistic regression using an interaction term (CBF×CBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1±5.67 mL · 100 g−1 · min−1 and 1.17±0.41 mL · 100 g−1, respectively. Conclusions— We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Hemorrhagic Transformation of Ischemic Stroke: Prediction with CT Perfusion

PURPOSE To determine whether admission computed tomography (CT) perfusion-derived permeability-surface area product (PS) maps differ between patients with hemorrhagic acute stroke and those with nonhemorrhagic acute stroke. MATERIALS AND METHODS This prospective study was institutional review board approved, and all participants gave written informed consent. Forty-one patients who presented with acute stroke within 3 hours after stroke symptom onset underwent two-phase CT perfusion imaging, which enabled PS measurement. Patients were assigned to groups according to whether they had hemorrhage transformation (HT) at follow-up magnetic resonance (MR) imaging and CT and/or whether they received tissue plasminogen activator (TPA) treatment. Clinical, demographic, and CT perfusion variables were compared between the HT and non-HT patient groups. Associations between PS and HT were tested at univariate and multivariate logistic regression analyses and receiver operating characteristic (ROC) analysis. RESULTS HT developed in 23 (56%) patients. Patients with HT had higher National Institutes of Health Stroke Scale (NIHSS) scores (P = .005), poorer outcomes (P = .001), and a higher likelihood of having received TPA (P = .005) compared with patients without HT. Baseline blood flow (P = .17) and blood volume (P = .11) defects and extent of flow reduction (P = .27) were comparable between the two groups. The mean PS for the HT group, 0.49 mL x min(-1) x (100 g)(-1), was significantly higher than that for the non-HT group, 0.09 mL x min(-1) x (100 g)(-1) (P < .0001). PS (odds ratio, 3.5; 95% confidence interval [CI]: 1.69, 7.06; P = .0007) and size of hypoattenuating area at nonenhanced admission CT (odds ratio, 0.4; 95% CI: 0.2, 0.7; P = .002) were the only independent variables associated with HT at stepwise multivariate analysis. The mean area under the ROC curve was 0.918 (95% CI: 0.828, 1.00). The PS threshold of 0.23 mL x min(-1) x (100 g)(-1) had 77% sensitivity and 94% specificity for detection of HT. CONCLUSION Admission PS measurement appears promising for distinguishing patients with acute stroke who are likely from those who are not likely to develop HT. SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/250/3/867/DC1.

Alberta Stroke Program Early CT Scoring of CT Perfusion in Early Stroke Visualization and Assessment

BACKGROUND AND PURPOSE: Qualitative CT perfusion (CTP) assessment by using the Alberta Stroke Program Early CT Score (ASPECTS) allows rapid calculation of infarct extent for middle cerebral artery infarcts. Published thresholds exist for noncontrast CT (NCCT) ASPECTS, which may distinguish outcome/complication risk, but early ischemic signs are difficult to detect. We hypothesized that different ASPECTS thresholds exist for CTP parameters versus NCCT and that these may be superior at predicting clinical and radiologic outcome in the acute setting. MATERIALS AND METHODS: Thirty-six baseline acute stroke NCCT and CTP studies within 3 hours of symptoms were blindly reviewed by 3 neuroradiologists, and ASPECTS were assigned. Treatment response was defined as major neurologic improvement when a ≥8-point National Institutes of Health Stroke Scale improvement at 24 hours occurred. Follow-up NCCT ASPECTS and 90-day modified Rankin score (mRS) were radiologic and clinical reference standards. Receiver operating characteristic curves derived optimal thresholds for outcome. RESULTS: Cerebral blood volume and NCCT ASPECTS had similar radiologic correlations (0.6 and 0.5, respectively) and best predicted infarct size in the absence of major neurologic improvement. A NCCT ASPECT threshold of 7 and a cerebral blood volume threshold of 8 discriminated patients with poor follow-up scans (P < .0002 and P = .0001) and mRS ≤2 (P = .001 and P < .001). Only cerebral blood volume predicted major neurologic improvement (P = .02). Interobserver agreement was substantial (intraclass correlation coefficient, 0.69). Cerebral blood volume ASPECTS sensitivity, specificity, positive predictive value, and negative predictive value for clinical outcome were 60%, 100%, 100%, and 45%, respectively. No patients with cerebral blood volume ASPECTS <8 achieved good clinical outcome. CONCLUSION: Cerebral blood volume ASPECTS is equivalent to NCCT for predicting radiologic outcome but may have an additional benefit in predicting patients with major neurologic improvement.

In Vivo 3D High-Spatial-Resolution MR Imaging of Intraplaque Hemorrhage

PURPOSE To apply magnetic resonance (MR) imaging of intraplaque hemorrhage (IPH), as compared with histologic analysis as the reference standard, to detect T1 hyperintense intraplaque signal and to test the hypothesis that T1 hyperintense material represents blood products (methemoglobin). MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. Eleven patients undergoing carotid endarterectomy were examined with MR imaging of IPH, and MR images were assessed for T1 hyperintense intraplaque signal. A total of 160 images per patient were available for coregistration with corresponding histologic slices. Because of endarterectomy specimen size and degradation and processing artifacts, only 97 images were coregistered to corresponding histologic slices. A grid that consisted of 16 segments was overlaid on images for correlation of MR images and histologic slices. Only one of 16 segments was chosen randomly per slide and used in the analysis. Agreement between MR images and histologic slices was measured with the Cohen kappa statistic. RESULTS Strong agreement was seen between MR images and histologic slices, with T1-weighted high signal intensity corresponding to hemorrhagic material (kappa = 0.7-0.8). There was a low 2% false-negative rate for the detection of hemorrhage on the basis of T1-weighted hyperintensity (two of 97 measured segments). The results of diagnostic tests for T1 hyperintense detection of hemorrhage were as follows: sensitivity of 100%, specificity of 80%, positive predictive value of 70%, and negative predictive value of 100% for reader 1 and sensitivity of 94%, specificity of 88%, positive predictive value of 78%, and negative predictive value of 97% for reader 2. CONCLUSION With its high spatial resolution, MR imaging of IPH permits detection of plaque hemorrhage location, resulting in strong agreement between imaging and histologic findings.

Renal safety of CT angiography and perfusion imaging in the emergency evaluation of acute stroke.

BACKGROUND AND PURPOSE: Multimodal CT imaging with contrast-enhanced CT angiography (CTA) and CT perfusion (CTP) is increasingly being used to guide emergency management of acute stroke. However, little has been reported about the safety of intravenous contrast administration associated with these studies in the acute stroke population, including cases in which baseline creatinine values are unknown. We investigated the incidence of contrast-induced nephropathy (CIN), defined as a 25% or more increase in baseline creatinine levels within 72 hours of contrast administration and chronic kidney disease in patients receiving CTA±CTP at our regional stroke center. MATERIALS AND METHODS: We analyzed 198 patients who underwent contrast CT studies for evaluation of acute ischemic or hemorrhagic stroke at our center (2003–2007). Through retrospective chart abstraction, we analyzed serial creatinine levels (baseline to day 3) and later values (≥day 4) where available. The incidences of CIN and/or chronic kidney disease were documented. After power analysis, CIN and non-CIN groups were compared by using the unpaired t test, Wilcoxon rank sum test, or Fisher exact test. RESULTS: None of the 198 patients developed chronic kidney disease or required dialysis. Of 175 patients with serial creatinine measurements between baseline and day 3, 5 (2.9%) developed CIN. The incidence of CIN was 2% in patients who were scanned before a baseline creatinine level was available. CONCLUSION: The incidence of renal sequelae is relatively low in acute stroke patients undergoing emergent multimodal CT scanning. Prompt CTA/CTP imaging of acute stroke, if indicated, need not be delayed in those with no history of renal impairment.

Pseudoprogression following chemoradiotherapy for glioblastoma multiforme.

PURPOSE Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis. MATERIALS/METHODS All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups. RESULTS Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p = 0.0286). CONCLUSIONS Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.

White Matter Thresholds for Ischemic Penumbra and Infarct Core in Patients with Acute Stroke: CT Perfusion Study

PURPOSE To prospectively determine the parameters derived at admission computed tomographic (CT) perfusion imaging admission that best differentiate ischemic white matter that recovers from that which infarcts, with the latter retrospectively defined at a CT examination performed without contrast material (unenhanced CT) 5-7 days after the event. MATERIALS AND METHODS Ethics committee approval and informed consent were obtained. Thirty patients with stroke underwent unenhanced CT, CT angiography, and CT perfusion studies at admission. Additionally, CT angiography was performed 24 hours after the stroke, and an unenhanced CT study was performed 5-7 days after the stroke. Five patients were excluded; the remaining patients (10 men, 15 women; mean age, 70 years +/- 13 [standard deviation]) were separated into those with recanalization (n = 16) and those without recanalization (n = 9) at 24 hours. For patients with recanalization, the final infarct was outlined on unenhanced CT images obtained 5-7 days after the event and was superimposed on coregistered maps from the CT perfusion study performed at admission. Ischemic white matter tissue (cerebral blood flow [CBF] < 14 mL/min/100 g) was identified at the admission CT perfusion study, and the penumbra was defined as the difference between the ischemic region and the infarct region. RESULTS Infarct regions showed a matched decrease in CBF and cerebral blood volume (CBV) at admission, whereas penumbra regions showed a significant (P < .05) decrease in CBF but no change in CBV (P > .05) from contralateral values. A threshold CBF . CBV value of 8.14 was the most sensitive (95%, 20 of 21 regions) and specific (94%, 32 of 34 regions) parameter for differentiating between regions of ischemic white matter that recovered and regions of ischemic white matter that infarcted. CONCLUSION The product of CBF and CBV derived from CT perfusion data provided the best differentiation between regions of ischemic white matter that infarcted and regions of ischemic white matter that recovered 5-7 days after a stroke.

Postcontrast CT Extravasation Is Associated With Hematoma Expansion in CTA Spot Negative Patients

BACKGROUND AND PURPOSE The purpose of this study was to assess the effect of postcontrast CT (PCCT) leakage (PCL) on hematoma growth in CTA spot negative patients. METHODS A retrospective study of 61 patients presenting within 6 hours of primary ICH onset imaged with CT angiography (CTA) and PCCT. Presence of CTA spot sign and PCL were documented. PCL was defined as the presence of contrast extravasation on the PCCT study at a location remote from the CTA spot sign if present. Hematoma expansion was defined as >6 mL or 30% hematoma enlargement. Patients were dichotomized by CTA spot sign presence and PCL and compared for baseline demographic data, hematoma size, and growth using the unpaired t test and Mann-Whitney test for continuous and categorical data, respectively. A probability value <0.05 was considered significant. RESULTS PCL was present in 11/61 patients (18%), occurring in 5 without a spot sign (45%). Spot negative PCL patients demonstrated larger absolute (P=0.02) and percentage hematoma growth (P=0.02) compared to those without PCL. The mean volume and percent increase was 6.7 mL and 26%, respectively. Inclusion of PCL together with CTA spot sign as risk factor for hematoma expansion increased sensitivity from 0.78 (95% CI; 0.52 to 0.94) to 0.94 (95% CI; 0.72 to 1.00) and NPV from 0.90 (95% CI; 0.76 to 0.97) to 0.97 (95% CI; 0.85 to 1.00). CONCLUSIONS Inclusion of PCCT in the investigation of ICH patients allows detection of PCL which, together with the CTA spot sign, increases sensitivity and negative predictive value for predicting hematoma expansion. This finding should be validated in larger studies.