Alexander D. Horsch

Timing-Invariant Reconstruction for Deriving High-Quality CT Angiographic Data from Cerebral CT Perfusion Data

PURPOSE To suggest a simple and robust technique used to reconstruct high-quality computed tomographic (CT) angiographic images from CT perfusion data and to compare it with currently used CT angiography techniques. MATERIALS AND METHODS Institutional review board approval was waived for this retrospective study, which included 25 consecutive patients who had had a stroke. Temporal maximum intensity projection (tMIP) CT angiographic images were created by using prior temporal filtering as a timing-insensitive technique to produce CT angiographic images from CT perfusion data. The temporal filter strength was optimized to gain maximal contrast-to-noise ratios (CNRs) in the circle of Willis. The resulting timing-invariant (TI) CT angiography was compared with standard helical CT angiography, the arterial phase of dynamic CT angiography, and nonfiltered tMIP CT angiography. Vascular contrast, image noise, and CNR were measured. Four experienced observers scored all images for vascular noise, vascular contour, detail of small and medium arteries, venous superimposition, and overall image quality in a blinded side-by-side comparison. Measurements were compared with a paired t test; P ≤ .05 indicated a significant difference. RESULTS On average, optimized temporal filtering in TI CT angiography increased CNR by 18% and decreased image noise by 18% at the expense of a decrease in vascular contrast of 3% when compared with nonfiltered tMIP CT angiography. CNR, image noise, vascular noise, vascular contour, detail visibility of small and medium arteries, and overall image quality of TI CT angiograms were superior to those of standard CT angiography, tMIP CT angiography, and the arterial phase of dynamic CT angiography at a vascular contrast that was similar to that of standard CT angiography. Venous superimposition was similar for all techniques. Image quality of the arterial phase of dynamic CT angiography was rated inferior to that of standard CT angiography. CONCLUSION TI CT angiographic images constructed by using temporally filtered tMIP CT angiographic data have excellent image quality that is superior to that achieved with currently used techniques, but they suffer from modest venous superimposition.

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

BackgroundPrediction 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/designThe 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.DiscussionThis 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.

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.

Predictive Value of Thrombus Attenuation on Thin-Slice Non-Contrast CT for Persistent Occlusion after Intravenous Thrombolysis

Background: In stroke erythrocyte-rich thrombi are more sensitive to intravenous thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have higher density on non-contrast CT (NCCT). We investigated the relationship between thrombus density and recanalization and whether persistent occlusions can be predicted by Hounsfield unit (HU) measurements. Methods: In 88 IV-rtPA-treated patients with intracranial ICA or MCA occluding thrombus and follow-up imaging, thrombus and contralateral vessel attenuation measurements were performed on thin-slice NCCT. Mean absolute and relative HU were compared between patients with persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade 0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted for stroke subtype, clot burden score, occlusion site and time to thrombolysis) odds ratios for persistent occlusion were calculated. Additional prognostic value for persistent occlusion was estimated by adding HU measurements to the area under the curve (AUC) of known determinants and calculating optimal cut-off values. Results: Patients with persistent occlusion (n = 19) had significant lower mean HU (absolute 52.2 ± 9.5, relative 1.29 ± 0.20) compared to recanalization (absolute 63.1 ± 10.7, relative 1.54 ± 0.23, both p < 0.0001). Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6-6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per 0.20 relative HU decrease. Attenuation measurements significantly increased the AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative HU). Cut-off values of <56.5 absolute HU and <1.38 relative HU showed optimal predictive values for persistent occlusion. Conclusions: Thrombus density is related to recanalization rate. Lower absolute and relative HU are independently related to persistent occlusion and HU measurements significantly increase discriminative performances of known recanalization determinants.

A fast nonlinear regression method for estimating permeability in CT perfusion imaging

Blood–brain barrier damage, which can be quantified by measuring vascular permeability, is a potential predictor for hemorrhagic transformation in acute ischemic stroke. Permeability is commonly estimated by applying Patlak analysis to computed tomography (CT) perfusion data, but this method lacks precision. Applying more elaborate kinetic models by means of nonlinear regression (NLR) may improve precision, but is more time consuming and therefore less appropriate in an acute stroke setting. We propose a simplified NLR method that may be faster and still precise enough for clinical use. The aim of this study is to evaluate the reliability of in total 12 variations of Patlak analysis and NLR methods, including the simplified NLR method. Confidence intervals for the permeability estimates were evaluated using simulated CT attenuation-time curves with realistic noise, and clinical data from 20 patients. Although fixating the blood volume improved Patlak analysis, the NLR methods yielded significantly more reliable estimates, but took up to 12 x longer to calculate. The simplified NLR method was ~4 x faster than other NLR methods, while maintaining the same confidence intervals (CIs). In conclusion, the simplified NLR method is a new, reliable way to estimate permeability in stroke, fast enough for clinical application in an acute stroke setting.

Predictors of reperfusion in patients with acute ischemic stroke

BACKGROUND AND PURPOSE: Ischemic stroke studies emphasize a difference between reperfusion and recanalization, but predictors of reperfusion have not been elucidated. The aim of this study was to evaluate the relationship between reperfusion and recanalization and identify predictors of reperfusion. MATERIALS AND METHODS: From the Dutch Acute Stroke Study, 178 patients were selected with an MCA territory deficit on admission CTP and day 3 follow-up CTP and CTA. Reperfusion was evaluated on CTP, and recanalization on CTA, follow-up imaging. Reperfusion percentages were calculated in patients with and without recanalization. Patient admission and treatment characteristics and admission CT imaging parameters were collected. Their association with complete reperfusion was analyzed by using univariate and multivariate logistic regression. RESULTS: Sixty percent of patients with complete recanalization showed complete reperfusion (relative risk, 2.60; 95% CI, 1.63–4.13). Approximately one-third of patients showed some discrepancy between recanalization and reperfusion status. Lower NIHSS score (OR, 1.06; 95% CI, 1.01–1.11), smaller infarct core size (OR, 3.11; 95% CI, 1.46–6.66; and OR, 2.40; 95% CI, 1.14–5.02), smaller total ischemic area (OR, 4.20; 95% CI, 1.91–9.22; and OR, 2.35; 95% CI, 1.12–4.91), lower clot burden (OR, 1.35; 95% CI, 1.14–1.58), distal thrombus location (OR, 3.02; 95% CI, 1.76–5.20), and good collateral score (OR, 2.84; 95% CI, 1.34–6.02) significantly increased the odds of complete reperfusion. In multivariate analysis, only total ischemic area (OR, 6.12; 95% CI, 2.69–13.93; and OR, 1.91; 95% CI, 0.91–4.02) was an independent predictor of complete reperfusion. CONCLUSIONS: Recanalization and reperfusion are strongly associated but not always equivalent in ischemic stroke. A smaller total ischemic area is the only independent predictor of complete reperfusion.

Timing-Invariant CT Angiography Derived from CT Perfusion Imaging in Acute Stroke: A Diagnostic Performance Study

BACKGROUND AND PURPOSE: Timing-invariant (or delay-insensitive) CT angiography derived from CT perfusion data may obviate a separate cranial CTA in acute stroke, thus enhancing patient safety by reducing total examination time, radiation dose, and volume of contrast material. We assessed the diagnostic accuracy of timing-invariant CTA for detecting intracranial artery occlusion in acute ischemic stroke, to examine whether standard CTA can be omitted. MATERIALS AND METHODS: Patients with suspected ischemic stroke were prospectively enrolled and underwent CTA and CTP imaging at admission. Timing-invariant CTA was derived from the CTP data. Five neuroradiologic observers assessed all images for the presence and location of intracranial artery occlusion in a blinded and randomized manner. Sensitivity and specificity of timing-invariant CTA and standard CTA were calculated by using an independent expert panel as the reference standard. Interrater agreement was determined by using κ statistics. RESULTS: We included 108 patients with 47 vessel occlusions. Overall, standard CTA and timing-invariant CTA provided similar high diagnostic accuracy for occlusion detection with a sensitivity of 96% (95% CI, 90%–100%) and a specificity of 100% (99%–100%) for standard CTA and a sensitivity of 98% (95% CI, 94%–100%) and a specificity of 100% (95% CI, 100%–100%) for timing-invariant CTA. For proximal large-vessel occlusions, defined as occlusions of the ICA, basilar artery, and M1, the sensitivity and specificity were 100% (95% CI, 100%–100%) for both techniques. Interrater agreement was good for both techniques (mean κ value, 0.75 and 0.76). CONCLUSIONS: Timing-invariant CTA derived from CTP data provides diagnostic accuracy similar to that of standard CTA for the detection of artery occlusions in acute stroke.

Imaging Findings Associated with Space-Occupying Edema in Patients with Large Middle Cerebral Artery Infarcts.

BACKGROUND AND PURPOSE: Prominent space-occupying cerebral edema is a devastating complication occurring in some but not all patients with large MCA infarcts. It is unclear why differences in the extent of edema exist. Better knowledge of factors related to prominent edema formation could aid treatment strategies. This study aimed to identify variables associated with the development of prominent edema in patients with large MCA infarcts. MATERIALS AND METHODS: From the Dutch Acute Stroke Study (DUST), 137 patients were selected with large MCA infarcts on follow-up NCCT (3 ± 2 days after stroke onset), defined as ASPECTS ≤4. Prominent edema was defined as a midline shift of ≥5 mm on follow-up. Admission patient and treatment characteristics were collected. Admission CT parameters used were ASPECTS on NCCT and CBV and MTT maps, and occlusion site, clot burden, and collaterals on CTA. Permeability on admission CTP, and day 3 recanalization and reperfusion statuses were obtained if available. Unadjusted and adjusted (age and NIHSS) odds ratios were calculated for all variables in relation to prominent edema. RESULTS: Prominent edema developed in 51 patients (37%). Adjusted odds ratios for prominent edema were higher with lower ASPECTS on NCCT (adjusted odds ratio, 1.32; 95% CI, 1.13–1.55) and CBV (adjusted odds ratio, 1.26; 95% CI, 1.07–1.49), higher permeability (adjusted odds ratio, 2.35; 95% CI, 1.30–4.24), more proximal thrombus location (adjusted odds ratio, 3.40; 95% CI, 1.57–7.37), higher clot burden (adjusted odds ratio, 2.88; 95% CI, 1.11–7.45), and poor collaterals (adjusted odds ratio, 3.93; 95% CI, 1.78–8.69). CONCLUSIONS: Extensive proximal occlusion, poor collaterals, and larger ischemic deficits with higher permeability play a role in the development of prominent edema in large MCA infarcts.

CT perfusion analysis by nonlinear regression for predicting hemorrhagic transformation in ischemic stroke

PURPOSE Intravenous thrombolysis can improve clinical outcome in acute ischemic stroke patients but increases the risk of hemorrhagic transformation (HT). Blood-brain barrier damage, which can be quantified by the vascular permeability for contrast agents, is a potential predictor for HT. This study aimed to assess whether this prediction can be improved by measuring vascular permeability using a novel fast nonlinear regression (NLR) method instead of Patlak analysis. METHODS From a prospective ischemic stroke multicenter cohort study, 20 patients with HT on follow-up imaging and 40 patients without HT were selected. The permeability transfer constant K(trans) was measured in three ways; using standard Patlak analysis, Patlak analysis with a fixed offset, and the NLR method. In addition, the permeability-surface (PS) area product and the conventional perfusion parameters (blood volume, flow, and mean transit time) were measured using the NLR method. Relative values were calculated in two ways, i.e., by dividing the average in the infarct core by the average in the contralateral hemisphere, and by dividing the average in the ipsilateral hemisphere by the average in the contralateral hemisphere. Mann-Whitney U tests and receiver operating characteristic (ROC) analyses were performed to assess the discriminative power of each of the relative parameters. RESULTS Both the infarct-core and whole-hemisphere averaged relative K(trans) (rK(trans)) values, measured with the NLR method, were significantly higher in the patients who developed HT as compared with those who did not. The rK(trans) measured with standard Patlak analysis was not significantly different. The relative PS (rPS), measured with NLR, had the highest discriminative power (P = 0.002). ROC analysis of rPS showed an area under the curve (AUC) of 0.75 (95% confidence interval: 0.62-0.89) and a sensitivity of 0.75 at a specificity of 0.75. The AUCs of the Patlak rK(trans), the Patlak rK(trans) with fixed offset, and the NLR rK(trans) were 0.58, 0.66, and 0.67, respectively. CONCLUSIONS CT perfusion analysis may aid in predicting HT, but standard Patlak analysis did not provide estimates for rK(trans) that were significantly higher in the HT group. The rPS, measured in the infarct core with NLR, had superior discriminative power compared with K(trans) measured with either Patlak analysis with a fixed offset or NLR, and conventional perfusion parameters.

Residual High-Grade Stenosis After Recanalization of Extracranial Carotid Occlusion in Acute Ischemic Stroke

Background and Purpose— Residual stenosis after recanalization of an acute symptomatic extracranial occlusion of the internal carotid artery (ICA) might be an indication for carotid endarterectomy. We evaluated the proportion of residual high-grade stenosis (≥70%, near occlusions not included) on follow-up imaging in a consecutive series of patients with an acute symptomatic occlusion of the extracranial ICA. Methods— We included patients participating in the Dutch Acute Stroke Study (DUST), who had an acute symptomatic occlusion of the extracranial ICA that was diagnosed on computed tomographic angiography within 9 hours after onset of neurological symptoms. Follow-up imaging of the carotid artery had to be available within 7 days after admission. Results— Of the 1021 patients participating in DUST between May 2009 and May 2013, an acute symptomatic occlusion of the extracranial ICA was found in 126 (12.3%) patients. Follow-up imaging was available in 86 (68.3%) of these patients. At follow-up, a residual stenosis of <30% was found in 15 (17.4%; 95% confidence interval, 10.8–26.9) patients, a 30% to 49% stenosis in 3 (3.5%; 95% confidence interval, 0.8–10.2) patients, a 50% to 69% stenosis in 2 (2.3%; 95% confidence interval, 0.1–8.6) patients, and a ≥70% stenosis in 14 (16.3%; 95% confidence interval, 9.8–25.6) patients. A near or persistent occlusion was present in the remaining 52 (60.5%) patients. Conclusions— A residual high-grade stenosis of the extracranial ICA occurs in 1 of 6 patients with a symptomatic occlusion in the acute stage of cerebral ischemia. Because this may have implications for secondary prevention, we recommend follow-up imaging in these patients within a week after the event. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00880113.