CT angiography and CT perfusion improve prediction of infarct volume in patients with anterior circulation stroke.

INTRODUCTION: We investigated whether baseline CT angiography (CTA) and CT perfusion (CTP) in acute ischemic stroke could improve prediction of infarct presence and infarct volume on follow-up imaging. METHODS: We analyzed 906 patients with suspected anterior circulation stroke from the prospective multicenter Dutch acute stroke study (DUST). All patients underwent baseline non-contrast CT, CTA, and CTP and follow-up non-contrast CT/MRI after 3 days. Multivariable regression models were developed including patient characteristics and non-contrast CT, and subsequently, CTA and CTP measures were added. The increase in area under the curve (AUC) and R (2) was assessed to determine the additional value of CTA and CTP. RESULTS: At follow-up, 612 patients (67.5%) had a detectable infarct on CT/MRI; median infarct volume was 14.8 mL (interquartile range (IQR) 2.8-69.6). Regarding infarct presence, the AUC of 0.82 (95% confidence interval (CI) 0.79-0.85) for patient characteristics and non-contrast CT was improved with addition of CTA measures (AUC 0.85 (95% CI 0.82-0.87); p < 0.001) and was even higher after addition of CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001) and combined CTA/CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001). For infarct volume, adding combined CTA/CTP measures (R (2) = 0.58) was superior to patient characteristics and non-contrast CT alone (R (2) = 0.44) and to addition of CTA alone (R (2) = 0.55) or CTP alone (R (2) = 0.54; all p < 0.001). CONCLUSION: In the acute stage, CTA and CTP have additional value over patient characteristics and non-contrast CT for predicting infarct presence and infarct volume on follow-up imaging. These findings could be applied for patient selection in future trials on ischemic stroke treatment.

Relation between stroke severity, patient characteristics and CT-perfusion derived blood-brain barrier permeability measurements in acute ischemic stroke.

PURPOSE: Increased blood-brain barrier permeability (BBBP) can result from ischemia. In this study the relation between stroke severity, patient characteristics and admission BBBP values measured with CT-perfusion (CTP) was investigated in acute ischemic stroke patients. METHODS: From prospective data of the Dutch Acute Stroke Study 149 patients with a middle cerebral artery stroke and extended CTP were selected. BBBP values were measured in the penumbra and infarct core as defined by CTP thresholds, and in the contra-lateral hemisphere. The relation between stroke (severity) variables and patient characteristics, including early CT signs, dense vessel sign (DVS), time to scan and National Institute of Health Stroke Score (NIHSS), and BBBP parameters in penumbra and infarct core was quantified with regression analysis. RESULTS: Early CT signs were related to higher BBBP values in the infarct core (B = 0.710), higher ipsi- to contra-lateral BBBP ratios (B = 0.326) and higher extraction ratios in the infarct core (B = 16.938). Females were found to have lower BBBP values in penumbra and infarct core (B = - 0.446 and - 0.776 respectively) and lower extraction ratios in the infarct core (B = - 10.463). If a DVS was present the ipsi- to contra-lateral BBBP ratios were lower (B = - 0.304). There was no relation between NIHSS or time to scan and BBBP values. CONCLUSION: Early CT signs are related to higher BBBP values in the infarct core, suggesting that only severe ischemic damage alters BBBP within the first hours after symptom onset.

The Prognostic Value of CT Angiography and CT Perfusion in Acute Ischemic Stroke.

BACKGROUND: CT angiography (CTA) and CT perfusion (CTP) are important diagnostic tools in acute ischemic stroke. We investigated the prognostic value of CTA and CTP for clinical outcome and determined whether they have additional prognostic value over patient characteristics and non-contrast CT (NCCT). METHODS: We included 1,374 patients with suspected acute ischemic stroke in the prospective multicenter Dutch acute stroke study. Sixty percent of the cohort was used for deriving the predictors and the remaining 40% for validating them. We calculated the predictive values of CTA and CTP predictors for poor clinical outcome (modified Rankin Scale score 3-6). Associations between CTA and CTP predictors and poor clinical outcome were assessed with odds ratios (OR). Multivariable logistic regression models were developed based on patient characteristics and NCCT predictors, and subsequently CTA and CTP predictors were added. The increase in area under the curve (AUC) value was determined to assess the additional prognostic value of CTA and CTP. Model validation was performed by assessing discrimination and calibration. RESULTS: Poor outcome occurred in 501 patients (36.5%). Each of the evaluated CTA measures strongly predicted outcome in univariable analyses: the positive predictive value (PPV) was 59% for Alberta Stroke Program Early CT Score (ASPECTS) ≤7 on CTA source images (OR 3.3; 95% CI 2.3-4.8), 63% for presence of a proximal intracranial occlusion (OR 5.1; 95% CI 3.7-7.1), 66% for poor leptomeningeal collaterals (OR 4.3; 95% CI 2.8-6.6), and 58% for a >70% carotid or vertebrobasilar stenosis/occlusion (OR 3.2; 95% CI 2.2-4.6). The same applied to the CTP measures, as the PPVs were 65% for ASPECTS ≤7 on cerebral blood volume maps (OR 5.1; 95% CI 3.7-7.2) and 53% for ASPECTS ≤7 on mean transit time maps (OR 3.9; 95% CI 2.9-5.3). The prognostic model based on patient characteristics and NCCT measures was highly predictive for poor clinical outcome (AUC 0.84; 95% CI 0.81-0.86). Adding CTA and CTP predictors to this model did not improve the predictive value (AUC 0.85; 95% CI 0.83-0.88). In the validation cohort, the AUC values were 0.78 (95% CI 0.73-0.82) and 0.79 (95% CI 0.75-0.83), respectively. Calibration of the models was satisfactory. CONCLUSIONS: In patients with suspected acute ischemic stroke, admission CTA and CTP parameters are strong predictors of poor outcome and can be used to predict long-term clinical outcome. In multivariable prediction models, however, their additional prognostic value over patient characteristics and NCCT is limited in an unselected stroke population.

Relation between reperfusion and hemorrhagic transformation in acute ischemic stroke.

INTRODUCTION: Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT. METHODS: From the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment. RESULTS: Inclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5-3.1). In patients treated with IV-rtPA (n = 203), the OR was 1.3 (95%CI 0.4-4.0), and in patients not treated with IV-rtPA (n = 96), the OR was 0.8 (95%CI 0.1-4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference -1 to 14 %). CONCLUSION: Our results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status.

Additional diagnostic value of computed tomography perfusion for detection of acute ischemic stroke in the posterior circulation.

BACKGROUND AND PURPOSE: Detection of acute infarction in the posterior circulation is challenging. We aimed to determine the additional value of tomograpy (CT) perfusion to noncontrast CT and CT angiography source images for infarct detection and localization in patients suspected of acute ischemic posterior circulation stroke. METHODS: Patients with suspected acute ischemic posterior circulation stroke were selected from the Dutch acute Stroke Trial (DUST) study. Patients underwent noncontrast CT, CT angiography, and CT perfusion within 9 hours after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and location of ischemia. Discrimination of 3 hierarchical logistic regression models (noncontrast CT [A], added CT angiography source images [B], and CT perfusion [C]) was compared with C-statistics. RESULTS: Of 88 patients, 76 (86%) had a clinical diagnosis of ischemic stroke on discharge and 42 patients (48%) showed a posterior circulation infarct on follow-up imaging. Model C (area under the curve from the receiver operating characteristic curve=0.86; 95% confidence interval, 0.77-0.94) predicted an infarct in the posterior circulation territory better than models A (area under the curve from the receiver operating characteristic curve=0.64; 95% confidence interval, 0.53-0.76; P(C versus A)<0.001) and B (area under the curve from the receiver operating characteristic curve=0.68; 95% confidence interval, 0.56-0.79; P(C versus B)<0.001). CONCLUSIONS: CT perfusion has significant additional diagnostic values to noncontrast CT and CT angiography source images for detecting ischemic changes in patients suspected of acute posterior circulation stroke.

3D movement correction of CT brain perfusion image data of patients with acute ischemic stroke.

INTRODUCTION: Head movement during CT brain perfusion (CTP) acquisition can deteriorate the accuracy of CTP analysis. Most CTP software packages can only correct in-plane movement and are limited to small ranges. The purpose of this study is to validate a novel 3D correction method for head movement during CTP acquisition. METHODS: Thirty-five CTP datasets that were classified as defective due to head movement were included in this study. All CTP time frames were registered with non-contrast CT data using a 3D rigid registration method. Location and appearance of ischemic area in summary maps derived from original and registered CTP datasets were qualitative compared with follow-up non-contrast CT. A quality score (QS) of 0 to 3 was used to express the degree of agreement. Furthermore, experts compared the quality of both summary maps and assigned the improvement score (IS) of the CTP analysis, ranging from -2 (much worse) to 2 (much better). RESULTS: Summary maps generated from corrected CTP significantly agreed better with appearance of infarct on follow-up CT with mean QS 2.3 versus mean QS 1.8 for summary maps from original CTP (P = 0.024). In comparison to original CTP data, correction resulted in a quality improvement with average IS 0.8: 17 % worsened (IS = -2, -1), 20 % remained unchanged (IS = 0), and 63 % improved (IS = +1, +2). CONCLUSION: The proposed 3D movement correction improves the summary map quality for CTP datasets with severe head movement.

Prediction of outcome in patients with suspected acute ischaemic stroke with CT perfusion and CT angiography: the Dutch acute stroke trial (DUST) study protocol.

BACKGROUND: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated. METHODS/DESIGN: The DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests. DISCUSSION: This study will provide insight in the added prognostic value of CTP and CTA parameters in outcome prediction of acute stroke patients. The prediction models that will be developed in this study may help guide future treatment decisions in the acute stage of ischaemic stroke.

Histopathologic composition of cerebral thrombi of acute stroke patients is correlated with stroke subtype and thrombus attenuation.

INTRODUCTION: We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke. METHODS: We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥ 15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r). RESULTS: Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35-90)), followed by dissection (35 (20-40), p = 0.05), cardioembolism (35 (5-45), p = 0.013) and unknown subtype (25 (2-40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = -0.368, p = 0.09) and fibrin (r = -0.073, p = 0.75). CONCLUSIONS: The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.

Radiation dose reduction in cerebral CT perfusion imaging using iterative reconstruction.

OBJECTIVES: To investigate whether iterative reconstruction (IR) in cerebral CT perfusion (CTP) allows for 50% dose reduction while maintaining image quality (IQ). METHODS: A total of 48 CTP examinations were reconstructed into a standard dose (150 mAs) with filtered back projection (FBP) and half-dose (75 mAs) with two strengths of IR (middle and high). Objective IQ (quantitative perfusion values, contrast-to-noise ratio (CNR), penumbra, infarct area and penumbra/infarct (P/I) index) and subjective IQ (diagnostic IQ on a four-point Likert scale and overall IQ binomial) were compared among the reconstructions. RESULTS: Half-dose CTP with high IR level had, compared with standard dose with FBP, similar objective (grey matter cerebral blood volume (CBV) 4.4 versus 4.3 mL/100 g, CNR 1.59 versus 1.64 and P/I index 0.74 versus 0.73, respectively) and subjective diagnostic IQ (mean Likert scale 1.42 versus 1.49, respectively). The overall IQ in half-dose with high IR level was scored lower in 26-31%. Half-dose with FBP and with the middle IR level were inferior to standard dose with FBP. CONCLUSION: With the use of IR in CTP imaging it is possible to examine patients with a half dose without significantly altering the objective and diagnostic IQ. The standard dose with FBP is still preferable in terms of subjective overall IQ in about one quarter of patients. KEY POINTS: • Computed tomography perfusion (CTP) is increasingly important in ischaemia imaging. • Radiation exposure of CTP is a drawback. • Iterative reconstruction (IR) allows reduction of radiation dose in unenhanced head CT. • CTP IR enables 50% dose reduction without altering objective and diagnostic quality.

Reliability of visual assessment of non-contrast CT, CT angiography source images and CT perfusion in patients with suspected ischemic stroke.

BACKGROUND AND PURPOSE: Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke. METHODS: We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement. RESULTS: Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps. CONCLUSION: Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging.

Optimisation of vascular input and output functions in CT-perfusion imaging using 256(or more)-slice multidetector CT.

OBJECTIVES: To evaluate the accuracy and reproducibility of CT-perfusion (CTP) by finding the optimal artery for the arterial input function (AIF) and re-evaluating the necessity of the venous output function (VOF). METHODS: Forty-four acute ischaemic stroke patients who underwent non-enhanced CT, CTP and CT-angiography using 256-slice multidetector computed tomography (MDCT) were evaluated. The anterior cerebral artery (ACA), middle cerebral artery (MCA), internal carotid artery (ICA) and basilar artery were selected as the AIF. Subsequently the resulting area under the time-enhancement curve of the AIF (AUCAIF) and quantitative perfusion measurements were analysed by repeated measures ANOVA and subsequently the paired t test. To evaluate reproducibility we examined if the VOF could be deleted by comparing the perfusion measurements using versus not using the VOF (paired t test). RESULTS: The AUCAIF and perfusion measurements resulting from the different AIFs showed significant group differences (all P < 0.0001). The ICA had the largest AUCAIF and resulted in the highest mean transient time (MTT) and lowest cerebral blood flow (CBF), whereas the basilar artery showed the lowest cerebral blood volume (CBV). Not using the VOF showed significantly higher CBV and CBF in 66 % of patients on the ipsilateral (P < 0.0001 and P = 0.007, respectively) and contralateral hemisphere (P < 0.0001 and P = 0.019, respectively). CONCLUSION: Selecting the ICA as the AIF and continuing the use of the VOF would improve the accuracy of CTP. KEY POINTS: • Perfusion imaging is an increasingly important aspect of multidetector computed tomography (MDCT). • Vascular input functions were evaluated for CT-perfusion using 256-slice MDCT. • Selecting different arterial input functions (AIFs) leads to variation in quantitative values. • Using the internal carotid artery for AIF provides optimal perfusion values. • Deleting the venous output function would be detrimental for validity.