Benison C. Lau

Blood-brain barrier permeability assessed by perfusion ct predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke

Symptomatic hemorrhagic transformation and malignant edema are the most feared complications of cerebral infarction, particularly after systemic thrombolysis; why are patients prone to develop them? These investigators retrospectively analyzed data obtained from 32 patients and gave special attention to the permeability of the blood-brain barrier (as measured by perfusion CT). Six patients developed SHT and/or ME and most had received either intravenous or intra-arterial tPA plus mechanical clot retrieval. Abnormal admission BBB permeability measurements were 100% sensitive and 79% specific in identifying patients who developed these dreaded complications. Also, all of these patients were older than 65 years of age. BACKGROUND AND PURPOSE: SHT and ME are feared complications in patients with acute ischemic stroke. They occur >10 times more frequently in tPA-treated versus placebo-treated patients. Our goal was to evaluate the sensitivity and specificity of admission BBBP measurements derived from PCT in predicting the development of SHT and ME in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively analyzed a dataset consisting of 32 consecutive patients with acute ischemic stroke with appropriate admission and follow-up imaging. We calculated admission BBBP by using delayed-acquisition PCT data and the Patlak model. Collateral flow was assessed on the admission CTA, while recanalization and reperfusion were assessed on the follow-up CTA and PCT, respectively. SHT and ME were defined according to ECASS III criteria. Clinical data were obtained from chart review. In our univariate and forward selection−based multivariate analysis for predictors of SHT and ME, we incorporated both clinical and imaging variables, including age, admission NIHSS score, admission blood glucose level, admission blood pressure, time from symptom onset to scanning, treatment type, admission PCT–defined infarct volume, admission BBBP, collateral flow, recanalization, and reperfusion. Optimal sensitivity and specificity for SHT and ME prediction were calculated by using ROC analysis. RESULTS: In our sample of 32 patients, 3 developed SHT and 3 developed ME. Of the 3 patients with SHT, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device; of the 3 patients with ME, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device. Admission BBBP measurements above the threshold were 100% sensitive and 79% specific in predicting SHT and ME. Furthermore, all patients with SHT and ME—and only those with SHT and ME—had admission BBBP measurements above the threshold, were older than 65 years of age, and received tPA. Admission BBBP, age, and tPA were the independent predictors of SHT and ME in our forward selection−based multivariate analysis. Of these 3 variables, only BBBP measurements and age were known before making the decision of administering tPA and thus are clinically meaningful. CONCLUSIONS: Admission BBBP, a pretreatment measurement, was 100% sensitive and 79% specific in predicting SHT and ME.

Radiation Dose Reduction Strategy for CT Protocols: Successful Implementation in Neuroradiology Section

PURPOSE To retrospectively quantify the effect of systematic use of tube current modulation for neuroradiology computed tomographic (CT) protocols on patient dose and image quality. MATERIALS AND METHODS This HIPAA-compliant study had institutional review board approval, with waiver of informed consent. The authors evaluated the effect of dose modulation on four types of neuroradiologic CT studies: brain CT performed without contrast material (unenhanced CT) in adult patients, unenhanced brain CT in pediatric patients, adult cervical spine CT, and adult cervical and intracranial CT angiography. For each type of CT study, three series of 100 consecutive studies were reviewed: 100 studies performed without dose modulation, 100 studies performed with z-axis dose modulation, and 100 studies performed with x-y-z-axis dose modulation. For each examination, the weighted volume CT dose index (CTDI(vol)) and dose-length product (DLP) were recorded and noise was measured. Each study was also reviewed for image quality. Continuous variables (CTDI(vol), DLP, noise) were compared by using t tests, and categorical variables (image quality) were compared by using Wilcoxon rank-sum tests. RESULTS For unenhanced CT of adult brains, the CTDI(vol) and DLP, respectively, were reduced by 60.9% and 60.3%, respectively, by using z-axis dose modulation and by 50.4% and 22.4% by using x-y-z-axis dose modulation. Significant dose reductions (P < .001) were also observed for pediatric unenhanced brain CT, cervical spine CT, and adult cervical and intracranial CT angiography performed with each dose modulation technique. Image quality and noise were unaffected by the use of either dose modulation technique (P > .05). CONCLUSION Use of dose-modulation techniques for neuroradiology CT examinations affords significant dose reduction while image quality is maintained.

Dynamic Perfusion CT Assessment of the Blood-Brain Barrier Permeability: First Pass versus Delayed Acquisition

BACKGROUND AND PURPOSE: The Patlak model has been applied to first-pass perfusion CT (PCT) data to extract information on blood-brain barrier permeability (BBBP) to predict hemorrhagic transformation in patients with acute stroke. However, the Patlak model was originally described for the delayed steady-state phase of contrast circulation. The goal of this study was to assess whether the first pass or the delayed phase of a contrast bolus injection better respects the assumptions of the Patlak model for the assessment of BBBP in patients with acute stroke by using PCT. MATERIALS AND METHODS: We retrospectively identified 125 consecutive patients (29 with acute hemispheric stroke and 96 without) who underwent a PCT study by using a prolonged acquisition time up to 3 minutes. The Patlak model was applied to calculate BBBP in ischemic and nonischemic brain tissue. Linear regression of the Patlak plot was performed separately for the first pass and for the delayed phase of the contrast bolus injection. Patlak linear regression models for the first pass and the delayed phase were compared in terms of their respective square root mean squared errors (√MSE) and correlation coefficients (R) by using generalized estimating equations with robust variance estimation. RESULTS: BBBP values calculated from the first pass were significantly higher than those from the delayed phase, both in nonischemic brain tissue (2.81 mL × 100 g−1 × min−1 for the first pass versus 1.05 mL × 100 g−1 × min−1 for the delayed phase, P < .001) and in ischemic tissue (7.63 mL × 100 g−1 × min−1 for the first pass versus 1.31 mL × 100 g−1 × min−1 for the delayed phase, P < .001). Compared with regression models from the first pass, Patlak regression models obtained from the delayed data were of better quality, showing significantly lower √MSE and higher R. CONCLUSION: Only the delayed phase of PCT acquisition respects the assumptions of linearity of the Patlak model in patients with and without stroke.

Visual Grading System for Vasospasm Based on Perfusion CT Imaging: Comparisons with Conventional Angiography and Quantitative Perfusion CT

Background: The purpose of this study was to compare simple visual grading of perfusion CT (PCT) maps to a more quantitative, threshold-based interpretation of PCT parameters in the characterization of presence and severity of vasospasm. Methods: Thirty-three patients with acute subarachnoid hemorrhage were enrolled in a prospective study and underwent a total of 40 paired PCT and digital subtraction angiography (DSA) examinations. A neuroradiologist and a neurologist reviewed the PCT mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume maps independently; they evaluated five anatomical regions (frontal, temporal, parietal, occipital/thalami, and basal ganglia/insula) and graded them for abnormality (0 if normal, 1 if abnormal in <50% of the region, and 2 if abnormal in ≧50% of the region). A third neuroradiologist blinded to the PCT results reviewed the DSA examinations and assessed 19 segments for the presence or absence of vasospasm. Correlation between PCT and DSA scores was assessed, as well as the sensitivity and specificity of PCT compared to DSA used as a gold standard. Results: MTT (R2 = 0.939) and CBF (R2 = 0.907) scores correlated best with DSA scores (p < 0.001). MTT scoring had a sensitivity of 92% and a specificity of 86% compared to DSA; CBF scoring had a sensitivity of 75% and a specificity of 95%. The interobserver agreement between neuroradiologist and neurologist was found to have kappa = 0.789 for MTT and 0.658 for CBF. Conclusion: We propose a user-friendly visual grading system for PCT maps in patients with suspected vasospasm. This visual approach compares favorably to the results of DSA. Sensitive MTT maps should be used for screening, and specific CBF maps for confirmation of vasospasm.

Carotid plaque computed tomography imaging in stroke and nonstroke patients.

To identify a set of computed tomographic (CT) features of carotid atherosclerotic plaques that is significantly associated with ischemic stroke.

17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status

Background and Purpose— Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. Methods— We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. Results— Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. Conclusions— This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.

Optimal Brain Perfusion CT Coverage in Patients with Acute Middle Cerebral Artery Stroke

BACKGROUND AND PURPOSE: PCT has emerged as an alternative to MR imaging for the assessment of patients with suspected acute stroke. However, 1 disadvantage of PCT is its limited anatomic coverage, which may impact the characterization of hemispheric ischemic strokes. The purpose of this study was to determine the optimal brain CT coverage required to accurately estimate the size of the infarct core relative to the MCA territory and the infarct-penumbra mismatch, by using a criterion standard of these parameters measured on PCT with 80-mm z-axis coverage. MATERIALS AND METHODS: Fifty-one patients with acute ischemic hemispheric stroke underwent PCT scanning (2 boluses, total coverage of 80 mm, 16 × 5 mm sections) within the first 24 hours of symptom onset and a follow-up NCCT of the brain between 3 days and 3 months after the initial stroke CT study. The volumes of PCT infarct and penumbra for each possible extent of z-axis coverage derived from the individual PCT sections were recorded (beginning with 5 mm of z-axis coverage above the orbits and then increasing the coverage in 5-mm increments in the z-axis up to 80 mm above the orbits). The infarct-penumbra mismatch and the size of the infarction relative to the MCA territory were calculated for each extent of z-axis coverage. Using the 80-mm z-axis coverage as the criterion standard, we calculated the accuracy of the values of the relative PCT infarct size and mismatch that were obtained by using more limited z-axis coverage. The impact of different levels of PCT z-axis coverage on the eligibility for reperfusion treatment was assessed. RESULTS: On the admission PCT, by using 80-mm of z-axis coverage, the mean perfusion infarct core volume was 45.9 ± 44.0 cm3 (range, 0–170 cm3) and the mean penumbra volume was 64.5 ± 64.4 cm3 (range, 0–226 cm3). The mean perfusion infarct core/MCA territory ratio was 19.6% ± 16.2% (range, 0.1%–56%). The penumbra / (infarct + penumbra) ratio was 68.6% ± 23.6% (range, 16.4%–100%). The final infarct volume on follow-up NCCT was 115.4 ± 157.3 cm3 (range, 1.79–647.4 cm3). The minimal z-axis PCT coverage required to obtain values similar to those obtained with 80-mm z-axis coverage was 75 mm for a mismatch of 0.5, fifty millimeters for a mismatch of 0.2, and 55 mm for a size of PCT infarct relative to the MCA territory. CONCLUSIONS: Seventy-five millimeters is the minimal PCT coverage required to use PCT as a tool to select patients with acute stroke for reperfusion therapy by using a mismatch of 0.5. A z-axis coverage of 50 mm was sufficient for a mismatch of 0.2; and 55 mm, for the size of PCT infarct relative to MCA territory (one-third or more).

Clinical risk factors and CT imaging features of carotid atherosclerotic plaques as predictors of new incident carotid ischemic stroke: A retrospective cohort study

BACKGROUND AND PURPOSE: Parameters other than luminal narrowing are needed to predict the risk of stroke more reliably, particularly in patients with <70% stenosis. The goal of our study was to identify clinical risk factors and CT features of carotid atherosclerotic plaques, in a retrospective cohort of patients free of stroke at baseline, that are independent predictors of incident stroke on follow-up. MATERIALS AND METHODS: We identified a retrospective cohort of patients admitted to our emergency department with suspected stroke between 2001–2007 who underwent a stroke work-up including a CTA of the carotid arteries that was subsequently negative for acute stroke. All patients also had to receive a follow-up brain study at least 2 weeks later. From a random sample, we reviewed charts and imaging studies of patients with subsequent new stroke on follow-up as well as those who remained stroke-free. All patients were classified either as “new carotid infarct patients” or “no-new carotid infarct patients” based on the Causative Classification for Stroke. Independently, the baseline CTA studies were processed using a custom, CT-based automated computer classifier algorithm that quantitatively assesses a set of carotid CT features (wall thickness, plaque ulcerations, fibrous cap thickness, lipid-rich necrotic core, and calcifications). Univariate and multivariate statistical analyses were used to identify any significant differences in CT features between the patient groups in the sample. Subsequent ROC analysis allowed comparison to the classic NASCET stenosis rule in identifying patients with incident stroke on follow-up. RESULTS: We identified a total of 315 patients without a new carotid stroke between baseline and follow-up, and 14 with a new carotid stroke between baseline and follow-up, creating the main comparison groups for the study. Statistical analysis showed age and use of antihypertensive drugs to be the most significant clinical variables, and maximal carotid wall thickness was the most relevant imaging variable. The use of age ≥75 years, antihypertensive medication use, and a maximal carotid wall thickness of at least 4 mm was able to successfully identify 10 of the 14 patients who developed a new incident infarct on follow-up. ROC analysis showed an area under the ROC curve of 0.706 for prediction of new stroke with this new model. CONCLUSIONS: Our new paradigm of using age ≥75 years, history of hypertension, and carotid maximal wall thickness of >4 mm identified most of the patients with subsequent new carotid stroke in our study. It is simple and may help clinicians choose the patients at greatest risk of developing a carotid infarct, warranting validation with a prospective observational study.

Accuracy and anatomical coverage of perfusion CT assessment of the blood-brain barrier permeability: one bolus versus two boluses.

Purpose: To assess whether blood-brain barrier permeability (BBBP) values, extracted with the Patlak model from the second perfusion CT (PCT) contrast bolus, are significantly lower than the values extracted from the first bolus in the same patient. Materials and Methods: 125 consecutive patients (29 with acute hemispheric stroke and 96 without stroke) who underwent a PCT study using a prolonged acquisition time up to 3 min were retrospectively identified. The Patlak model was applied to calculate the rate of contrast leakage out of the vascular compartment. Patlak plots were created from the arterial and parenchymal time enhancement curves obtained in multiple regions of interest drawn in ischemic brain tissue and in nonischemic brain tissue. The slope of a regression line fit to the Patlak plot was used as an indicator of BBBP. Square roots of the mean squared errors and correlation coefficients were used to describe the quality of the linear regression model. This was performed separately for the first and the second PCT bolus. Results from the first and the second bolus were compared in terms of BBBP values and the quality of the linear model fitted to the Patlak plot, using generalized estimating equations with robust variance estimation. Results: BBBP values from the second bolus were not lower than BBBP values from the first bolus in either nonischemic brain tissue [estimated mean with 95% confidence interval: 1.42 (1.10–1.82) ml·100 g–1·min–1 for the first bolus versus 1.64 (1.31–2.05) ml·100 g–1·min–1 for the second bolus, p = 1.00] or in ischemic tissue [1.04 (0.97–1.12) ml·100 g–1·min–1 for the first bolus versus 1.19 (1.11–1.28) ml·100 g–1·min–1 for the second bolus, p = 0.79]. Compared to regression models from the first bolus, the Patlak regression models obtained from the second bolus were of similar or slightly better quality. This was true both in nonischemic and ischemic brain tissue. Conclusion: The contrast material from the first bolus of contrast for PCT does not negatively influence measurements of BBBP values from the second bolus. The second bolus can thus be used to increase anatomical coverage of BBBP assessment using PCT.

Contrast Delay on Perfusion CT as a Predictor of New, Incident Infarct A Retrospective Cohort Study

Background and Purpose— The purpose of this study was to determine if the assessment of intracranial collateral circulation by CT angiography and/or perfusion CT (PCT) can predict the risk of future ischemic stroke in a large, retrospective cohort study. Methods— We identified 135 consecutive patients who underwent CT angiography of the head and neck and PCT of the brain at baseline and with subsequent follow-up brain imaging. Clinical and demographic information and carotid wall features were collected. Collateral circulation was assessed anatomically at CT angiography and functionally by measuring the mean transit time delay at PCT. The clinical, carotid, CT angiography, and PCT variables were compared between those with and without new incident infarct at follow-up imaging using mixed effect logistic statistical models. Results— During the follow-up period, 15 patients developed a new infarct and 120 patients did not. Clinical features associated with the stroke risk were age, hypertension, hyperlipidemia, and atrial fibrillation. The carotid features associated with stroke risk were wall thickness. Anatomic assessment of collaterals on CT angiography was not associated with stroke risk, whereas the functional assessment of collaterals (mean transit time delay on PCT) was associated with stroke risk. In a multivariate model, age, atrial fibrillation, and mean transit time delay (OR, 22.8; P<0.001) were the only covariates that were independent predictors of future ischemic stroke. Conclusions— The mean transit time delay on PCT contains important physiological information and should not be discarded. Along with age and atrial fibrillation, this functional assessment of intracranial collateral circulation predicts the risk of future hemispheric infarct.