CT perfusion measurement of postictal hypoperfusion: localization of the seizure onset zone and patterns of spread.

PURPOSE: Seizures are often followed by a period of transient neurological dysfunction and postictal alterations in cerebral blood flow may underlie these symptoms. Recent animal studies have shown reduced local cerebral blood flow at the seizure onset zone (SOZ) lasting approximately 1 h following seizures. Using arterial spin labelling (ASL) MRI, we observed postictal hypoperfusion at the SOZ in 75% of patients. The clinical implementation of ASL as a tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures blood flow and may circumvent the logistical limitations of MRI. Thus, we aimed to measure the extent of postictal hypoperfusion using CTP. METHODS: Fourteen adult patients with refractory focal epilepsy admitted for presurgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients also underwent a baseline scan after they were seizure-free for > 24 h. The acquired scans were qualitatively assessed by two reviewers by visual inspection and quantitatively assessed through a subtraction pipeline to identify areas of significant postictal hypoperfusion. RESULTS: Postictal blood flow reductions of > 15 ml/100 g-1/min-1 were seen in 12/13 patients using the quantitative method of analysis. In 10/12 patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ. In all patients, additional areas of scattered hypoperfusion were seen in areas corresponding to seizure spread. CONCLUSION: CTP can reliably measure postictal hypoperfusion which is maximal at the presumed SOZ.

Added value of multiphase CTA imaging for thrombus perviousness assessment.

PURPOSE: Thrombus perviousness has been associated with favorable functional outcome in acute ischemic stroke (AIS) patients. Measuring thrombus perviousness on CTA may be suboptimal due to potential delay in contrast agent arrival in occluded arteries at the moment of imaging. Dynamic sequences acquired over time can potentially overcome this issue. We investigate if dynamic CTA has added value in assessing thrombus perviousness. METHODS: Prospectively collected image data of AIS patients with proven occlusion of the anterior or posterior circulation with thin-slice multi-phase CTA (MCTA) and non-contrast CT were co-registered (n = 221). Thrombus attenuation increase (TAI; a perviousness measure) was measured for the arterial, venous, and delayed phase of the MCTA and time-invariant CTAs (TiCTA). Associations with favorable clinical outcome (90-day mRS ≤ 2) were assessed using univariate and multivariable regressions and calculating areas under receiver operating curves (AUC). RESULTS: TAI determined from the arterial phase CTA was superior in the association with favorable outcome with OR = 1.21 per 10 HU increase (95%CI 1.04-1.41, AUC 0.62, p = 0.014) compared to any other phase (venous 1.14(95%CI 1.01-1.30, AUC 0.58, p = 0.033), delayed 1.046(95%CI 0.919-1.19, AUC 0.53, p = 0.50)), and TiCTA (1.15(95%CI 1.02-1.30, AUC 0.60, p = 0.022). In the multivariable model, only TAI on arterial phase was significantly associated with favorable outcome (aOR 1.59, 95%CI 1.04-2.43, p = 0.032). CONCLUSION: Association between TAI with functional outcome was optimal on arterial-phase CTA such that dynamic CTA imaging has no additional benefits in current thrombus perviousness assessment, thereby suggesting that the delay of contrast arrival at the clot is a key variable for patient functional outcome.

Dynamic CTA-Derived Perfusion Maps Predict Final Infarct Volume: The Simple Perfusion Reconstruction Algorithm.

BACKGROUND AND PURPOSE: Infarct core volume measurement using CTP (CT perfusion) is a mainstay paradigm for stroke treatment decision-making. Yet, there are several downfalls with cine CTP technology that can be overcome by adopting the simple perfusion reconstruction algorithm (SPIRAL) derived from multiphase CTA. We compare SPIRAL with CTP parameters for the prediction of 24-hour infarction. MATERIALS AND METHODS: Seventy-two patients had admission NCCT, multiphase CTA, CTP, and 24-hour DWI. All patients had successful/quality reperfusion. Patient-level and cohort-level receiver operator characteristic curves were generated to determine accuracy. A 10-fold cross-validation was performed on the cohort-level data. Infarct core volume was compared for SPIRAL, CTP-time-to-maximum, and final DWI by Bland-Altman analysis. RESULTS: When we compared the accuracy in patients with early and late reperfusion for cortical GM and WM, there was no significant difference at the patient level (0.83 versus 0.84, respectively), cohort level (0.82 versus 0.81, respectively), or the cross-validation (0.77 versus 0.74, respectively). In the patient-level receiver operating characteristic analysis, the SPIRAL map had a slightly higher, though nonsignificant (P < .05), average receiver operating characteristic area under the curve (cortical GM/WM, r = 0.82; basal ganglia = 0.79, respectively) than both the CTP-time-to-maximum (cortical GM/WM = 0.82; basal ganglia = 0.78, respectively) and CTP-CBF (cortical GM/WM = 0.74; basal ganglia = 0.78, respectively) parameter maps. The same relationship was observed at the cohort level. The Bland-Altman plot limits of agreement for SPIRAL and time-to-maximum infarct volume were similar compared with 24-hour DWI. CONCLUSIONS: We have shown that perfusion maps generated from a temporally sampled helical CTA are an accurate surrogate for infarct core.

Quantitatively detecting postictal hypoperfusion in patients with focal epilepsy using CT perfusion: Determining cross-modality comparisons and electrode artifacts.

BACKGROUND: We previously showed that CT perfusion (CTP) and arterial spin labelled (ASL) MRI can localize the seizure onset zone in humans via postictal perfusion patterns. As a step towards improving the feasibility/ease of collecting postictal CBF data, we determined whether EEG electrodes need to be removed for CTP data collection and whether a cross-modality comparison between baseline ASL and postictal CTP data is possible. NEW METHOD: Five patients with epilepsy underwent postictal CTP scanning. Three patients had an interictal ASL scan; one patient had both an ASL and CTP interictal scan. Postictal CTP maps were quantitatively compared to 1) ASL maps averaged from 100 healthy controls, 2) each patient's baseline ASL map and 3) each patient's baseline CTP map. To assess for electrode artifacts, a phantom and one patient underwent CTP scanning with EEG electrodes in place. The acquired scans were assessed for artifacts and for postictal hypoperfusion. RESULTS: Focal postictal hypoperfusion was observable only in intra-modality comparisons (CTP to CTP) and not in cross-modality comparisons (CTP to ASL). EEG electrodes produced streaking artifact that decreased image quality and precluded quantitative analysis. COMPARISON WITH EXISTING METHODS(S): An intra-modality comparison of baseline CTP to postictal CTP was the only comparison method that showed localized hypoperfusion. CONCLUSIONS: Quantitative comparison between postictal CTP and baseline ASL scans is not feasible. Postictal hypoperfusion can be detected by CTP only when two CTP scans are collected and when metallic EEG electrodes are removed.

Permeability surface area product analysis in malignant brain edema prediction - A pilot study.

BACKGROUND AND PURPOSE: Using an extended CT perfusion acquisition (150s), we sought to determine the association between perfusion parameters and malignant edema after ischemic stroke. METHODS: Patients (from prospective study PROVE-IT, NCT02184936) with terminal internal carotid artery±proximal middle cerebral occlusion were involved. CTA was assessed for clot location and status of leptomeningeal collaterals. The following CTP parameters were calculated within the ischemic territory and contralaterally: permeability surface area product (PS), cerebral blood flow (CBF) and cerebral blood volume (CBV). PS was calculated using the adiabatic approximation to the Johnson and Wilson model. Outcome was evaluated by midline shift and infarction volume on follow-up imaging. RESULTS: Of 200 patients enrolled, 7 patients (3.5%) had midline shift≥5mm (2 excluded for poor-quality scans). Five patients with midline shift and 5 matched controls were analysed. There was no significant difference in mean PS, CBF and CBV within the ischemic territory between the two groups. A CBV threshold of 1.7ml/100g had the highest AUC=0.72, 95% CI=0.54-0.90 for early midline shift prediction, sensitivity and specificity were 0.83 and 0.67 respectively. CONCLUSION: Our preliminary results did not show significant differences in permeability surface area analysis if analysed for complete ischemic region. CBV parameter had the highest accuracy and there was a trend for the mean PS values for midline shift prediction.

Imaging, Intervention, and Workflow in Acute Ischemic Stroke: The Calgary Approach.

Five recently published clinical trials showed dramatically higher rates of favorable functional outcome and a satisfying safety profile of endovascular treatment compared with the previous standard of care in acute ischemic stroke with proximal anterior circulation artery occlusion. Eligibility criteria within these trials varied by age, stroke severity, imaging, treatment-time window, and endovascular treatment devices. This focused review provides an overview of the trial results and explores the heterogeneity in imaging techniques, workflow, and endovascular techniques used in these trials and the consequent impact on practice. Using evidence from these trials and following a case from start to finish, this review recommends strategies that will help the appropriate patient undergo a fast, focused clinical evaluation, imaging, and intervention.

Multimodal CT provides improved performance for lacunar infarct detection.

BACKGROUND AND PURPOSE: Lacunar infarcts account for approximately 25% of acute ischemic strokes. Compared with NCCT alone, the addition of CTP improves sensitivity for detection of infarcts overall. Our aim was to systematically evaluate the diagnostic benefit and interobserver reliability of an incremental CT protocol in lacunar infarction. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained. One hundred sixty-three patients presenting with a lacunar syndrome ≤4.5 hours from symptom onset were enrolled. Images were reviewed incrementally by 2 blinded readers in 3 separate sessions (NCCT only, NCCT/CTA, and NCCT/CTA/CTP). Diagnostic confidence was recorded on a 6-point scale with DWI/ADC as a reference. Logistic regression analysis calculated differences between actual and observed diagnoses, adjusted for confidence. Predictive effects of observed diagnostic accuracy and confidence score were quantified with the entropy r(2) value. Sensitivity, specificity, and confidence intervals were calculated accounting for multiple readers. Receiver operating characteristic analyses were compared among diagnostic strategies. Interobserver agreement was established with Cohen κ statistic. RESULTS: The final study cohort comprised 88 patients (50% male). DWI/ADC-confirmed lacunar infarction occurred in 59/88 (67%) with 36/59 (61%) demonstrating a concordant abnormal finding on CTP. Sensitivity for definite or probable presence of lacunar infarct increased significantly from 9.3% to 42.4% with incremental protocol use, though specificity was unchanged (range, 91.9%-95.3%). The observed diagnosis was significantly related to the actual diagnosis after adjusting for CTP confidence level (P = .04) and was 5.1 and 2.4 times more likely to confirm lacunar infarct than NCCT or CTA source images. CTP area under the curve (0.77) was significantly higher than that of CTA source images (0.68, P = .006) or NCCT (0.55, P < .001). CONCLUSIONS: CTP offers an improved diagnostic benefit over NCCT and CTA for the diagnosis of lacunar infarction.

Toward patient-tailored perfusion thresholds for prediction of stroke outcome.

BACKGROUND AND PURPOSE: Multiple patient-specific clinical and radiologic parameters impact traditional perfusion thresholds used to classify/determine tissue outcome. We sought to determine whether modified baseline perfusion thresholds calculated by integrating baseline perfusion and clinical factors better predict tissue fate and clinical outcome. MATERIALS AND METHODS: CTP within 4.5 hours of acute anterior circulation stroke onset and 5- to 7-day MR imaging were performed for 203 patients with stroke, divided into derivation (n = 114) and validation (n = 89) data bases. Affected regions were operationally classified as infarct and noninfarct according to baseline CTP and follow-up FLAIR imaging. Perfusion thresholds were derived for each of the infarct and noninfarct regions, without and with transformation by baseline clinical and radiologic variables by using a general linear mixed model. Performance of transformed and nontransformed perfusion thresholds for tissue fate and 90-day clinical outcome prediction was then tested in the derivation data base. Reproducibility of models was verified by using bootstrapping and validated in an independent cohort. RESULTS: Perfusion threshold transformation by clinical and radiologic baseline parameters significantly improved tissue fate prediction for both gray matter and white matter (P < .001). Transformed thresholds improved the 90-day outcome prediction for CBF and time-to-maximum (P < .001). Transformed relative CBF and absolute time-to-maximum values demonstrated maximal GM and WM accuracies in the derivation and validation cohorts (relative CBF GM: 91%, 86%; WM: 86%, 83%; absolute time-to-maximum 88%, 79%, and 80%, 76% respectively). CONCLUSIONS: Transformation of baseline perfusion parameters by patient-specific clinical and radiologic parameters significantly improves the accuracy of tissue fate and clinical outcome prediction.

Improving acute stroke management with computed tomography perfusion: a review of imaging basics and applications.

The inclusion of dynamic contrast-enhanced computed tomography (CT) or CT perfusion (CTP) scan into the imaging workup for acute stroke patients is widespread. Along with vessel occlusion status from CT angiography, CTP provides pathophysiological information a non-contrast CT cannot provide during the hyperacute stages of cerebral ischemia. Measurement of parenchymal perfusion at the capillary level can be used to characterize tissue viability, a target for thrombolysis. Further, CTP is useful for the detection of blood brain barrier disturbances with the permeability surface area product parameter (PS). Although new to stroke imaging, PS has diagnostic and prognostic implications for primary hemorrhage and secondary hemorrhagic transformation of ischemic stroke. The purpose of this article is to provide an overview of the CTP imaging concepts and their uses for imaging in stroke.

Early rate of contrast extravasation in patients with intracerebral hemorrhage.

BACKGROUND AND PURPOSE: For patients with ICH, knowing the rate of CT contrast extravasation may provide insight into the pathophysiology of hematoma expansion. This study assessed whether the PCT-derived PS can measure different rates of CT contrast extravasation for admission CTA spot signs, PCCT, PCL, and regions without extravasation in patients with ICH. MATERIALS AND METHODS: CT was performed at admission and at 24 hours for 16 patients with ICH with/without contrast extravasation seen on CTA and PCCT. PCT-PS was measured at admission. The Wilcoxon rank sum test with a Bonferroni correction was used to compare PS values from the following regions of interest: 1) spot sign lesions only (9 foci), 2) PCL lesions only (9 foci), 3) hematoma excluding extravasation, 4) regions contralateral to extravasation, 5) hematoma in patients without extravasation, and 6) an area contralateral to that in 5. Additionally, hematoma expansion was determined at 24 hours defined by NCCT. RESULTS: PS was 6.5 ± 1.60 mL · min(-1) × (100 g)(-1), 0.95 ± 0.39 mL · min(-1) × (100 g)(-1), 0.12 ± 0.39 mL · min(-1) × (100 g)(-1), 0.26 ± 0.09 mL · min(-1) × (100 g)(-1), 0.38 ± 0.26 mL · min(-1) × (100 g)(-1), and 0.09 ± 0.32 mL · min(-1) × (100 g)(-1) for the following: 1) spot sign lesions only (9 foci), 2) PCL lesions only (9 foci), 3) hematoma excluding extravasation, 4) regions contralateral to extravasation, 5) hematoma in patients without extravasation, and 6) an area contralateral to that in 5. PS values from spot sign lesions and PCL lesions were significantly different from each other and all other regions, respectively (P < .05). Hematoma volume increased from 34.1 ± 41.0 mL to 40.2 ± 46.1 mL in extravasation-positive patients and decreased from 19.8 ± 31.8 mL to 17.4 ± 27.3 mL in extravasation-negative patients. CONCLUSIONS: The PCT-PS parameter measures a higher rate of contrast extravasation for CTA spot sign lesions compared with PCL lesions and hematoma. Early extravasation was associated with hematoma expansion.

Effect of dipyridamole during acute stroke: exploring antithrombosis and neuroprotective benefits.

Currently, many stroke-prone individuals take antithrombotic drugs, which have known antiplatelet properties, to decrease stroke incidence. There is now evidence that this regimen could also reduce stroke severity through neuroprotective, nonplatelet mechanisms that include anti-inflammatory processes. Inflammation was found to play an important role in atherosclerosis/thrombosis development and acute stroke progression. In light of these findings, prevention strategies that target inflammatory mediators are under investigation. A common secondary stroke prevention therapeutic, dipyridamole, has shown promise for reducing stroke recurrence without increasing bleeding. In addition to its antiplatelet ability, dipyridamole has positive effects on vascular endothelium and inflammation. This review explores the effect of dipyridamole during acute stroke, revealing its potential use for improving poststroke clinical outcome.