Shervin Kamalian

CT cerebral blood flow maps optimally correlate with admission diffusion-weighted imaging in acute stroke but thresholds vary by postprocessing platform

Background and Purpose— Admission infarct core lesion size is an important determinant of management and outcome in acute (<9 hours) stroke. Our purposes were to: (1) determine the optimal CT perfusion parameter to define infarct core using various postprocessing platforms; and (2) establish the degree of variability in threshold values between these different platforms. Methods— We evaluated 48 consecutive cases with vessel occlusion and admission CT perfusion and diffusion-weighted imaging within 3 hours of each other. CT perfusion was acquired with a “second-generation” 66-second biphasic cine protocol and postprocessed using “standard” (from 2 vendors, “A-std” and “B-std”) and “delay-corrected” (from 1 vendor, “A-dc”) commercial software. Receiver operating characteristic curve analysis was performed comparing each CT perfusion parameter—both absolute and normalized to the contralateral uninvolved hemisphere—between infarcted and noninfarcted regions as defined by coregistered diffusion-weighted imaging. Results— Cerebral blood flow had the highest accuracy (receiver operating characteristic area under the curve) for all 3 platforms (P<0.01). The maximal areas under the curve for each parameter were: absolute cerebral blood flow 0.88, cerebral blood volume 0.81, and mean transit time 0.82 and relative Cerebral blood flow 0.88, cerebral blood volume 0.83, and mean transit time 0.82. Optimal receiver operating characteristic operating point thresholds varied significantly between different platforms (Friedman test, P<0.01). Conclusions— Admission absolute and normalized “second-generation” cine acquired CT cerebral blood flow lesion volumes correlate more closely with diffusion-weighted imaging-defined infarct core than do those of CT cerebral blood volume or mean transit time. Although limited availability of diffusion-weighted imaging for some patients creates impetus to develop alternative methods of estimating core, the marked variability in quantification among different postprocessing software limits generalizability of parameter map thresholds between platforms.

Cranial CT with Adaptive Statistical Iterative Reconstruction: Improved Image Quality with Concomitant Radiation Dose Reduction

Most state-of-the-art CT scanners have some type of iterative reconstruction program that allows for lower patient radiation exposure. At my institution we use it, when available, for most neuroimaging studies. Six levels in 100 CT iterative reconstruction studies were compared with conventional CT obtained previously in the same patients. SNR and CNR were computed and the studies were blindly and qualitatively evaluated. The results showed that iterative reconstruction studies had lower image noise and increased low-contrast resolution while allowing lower radiation doses without affecting spatial resolution. BACKGROUND AND PURPOSE: To safeguard patient health, there is great interest in CT radiation-dose reduction. The purpose of this study was to evaluate the impact of an iterative-reconstruction algorithm, ASIR, on image-quality measures in reduced-dose head CT scans for adult patients. MATERIALS AND METHODS: Using a 64-section scanner, we analyzed 100 reduced-dose adult head CT scans at 6 predefined levels of ASIR blended with FBP reconstruction. These scans were compared with 50 CT scans previously obtained at a higher routine dose without ASIR reconstruction. SNR and CNR were computed from Hounsfield unit measurements of normal GM and WM of brain parenchyma. A blinded qualitative analysis was performed in 10 lower-dose CT datasets compared with higher-dose ones without ASIR. Phantom data analysis was also performed. RESULTS: Lower-dose scans without ASIR had significantly lower mean GM and WM SNR (P = .003) and similar GM-WM CNR values compared with higher routine-dose scans. However, at ASIR levels of 20%–40%, there was no statistically significant difference in SNR, and at ASIR levels of ≥60%, the SNR values of the reduced-dose scans were significantly higher (P < .01). CNR values were also significantly higher at ASIR levels of ≥40% (P < .01). Blinded qualitative review demonstrated significant improvements in perceived image noise, artifacts, and GM-WM differentiation at ASIR levels ≥60% (P < .01). CONCLUSIONS: These results demonstrate that the use of ASIR in adult head CT scans reduces image noise and increases low-contrast resolution, while allowing lower radiation doses without affecting spatial resolution.

Virtual Monochromatic Reconstruction of Dual-Energy Unenhanced Head CT at 65–75 keV Maximizes Image Quality Compared with Conventional Polychromatic CT

PURPOSE To determine the virtual monochromatic imaging (VMI) energy levels that maximize brain parenchymal image quality in dual-energy unenhanced head computed tomography (CT) and to assess the improvement with this technique compared with conventional polychromatic scanning. MATERIALS AND METHODS Institutional review board approval was obtained with no informed consent required for this HIPAA-compliant retrospective analysis. Twenty-five consecutive unenhanced head CT scans were acquired with a 64-section dual-energy scanner with fast tube voltage switching (80-140 kVp). Scans were retrospectively reconstructed at VMI energy levels from 40 to 140 keV in 5-keV increments and were analyzed by using four quality indexes: gray matter (GM) signal-to-noise ratio (SNR), white matter (WM) SNR, GM-WM contrast-to-noise ratio (CNR), and posterior fossa artifact index (PFAI). Optimal mean values for each parameter were compared with those from 50 consecutive scans obtained with the same scanner in 120-kVp single-energy mode. Repeated-measures analysis of variance and Dunnett post hoc t test were then used to determine significance. RESULTS Maximal GM SNR, WM SNR, and GM-WM CNR values were observed at 65 keV, and minimal PFAI was observed at 75 keV. These values were significantly better than those of conventional polychromatic CT (P < .01); quality index improvement ratios (corrected for radiation dose) ranged from 17% to 50%. CONCLUSION Virtual monochromatic reconstruction of dual-energy unenhanced head CT scans at 65-75 keV (optimal energy levels) maximizes image quality compared with scans obtained with conventional polychromatic CT.

CT Perfusion Mean Transit Time Maps Optimally Distinguish Benign Oligemia from True “At-Risk” Ischemic Penumbra, but Thresholds Vary by Postprocessing Technique

BACKGROUND AND PURPOSE: Various CTP parameters have been used to identify ischemic penumbra. The purpose of this study was to determine the optimal CTP parameter and threshold to distinguish true “at-risk” penumbra from benign oligemia in acute stroke patients without reperfusion. MATERIALS AND METHODS: Consecutive stroke patients were screened and 23 met the following criteria: 1) admission scanning within 9 hours of onset, 2) CTA confirmation of large vessel occlusion, 3) no late clinical or radiographic evidence of reperfusion, 4) no thrombolytic therapy, 5) DWI imaging within 3 hours of CTP, and 6) either CT or MR follow-up imaging. CTP was postprocessed with commercial software packages, using standard and delay-corrected deconvolution algorithms. Relative cerebral blood flow, volume, and mean transit time (rCBF, rCBV and rMTT) values were obtained by normalization to the uninvolved hemisphere. The admission DWI and final infarct were transposed onto the CTP maps and receiver operating characteristic curve analysis was performed to determine optimal thresholds for each perfusion parameter in defining penumbra destined to infarct. RESULTS: Relative and absolute MTT identified penumbra destined to infarct more accurately than CBF or CBV*CBF (P < .01). Absolute and relative MTT thresholds for defining penumbra were 12s and 249% for the standard and 13.5s and 150% for the delay-corrected algorithms, respectively. CONCLUSIONS: Appropriately thresholded absolute and relative MTT-CTP maps optimally distinguish “at-risk” penumbra from benign oligemia in acute stroke patients with large-vessel occlusion and no reperfusion. The precise threshold values may vary, however, depending on the postprocessing technique used for CTP map construction.

Limited Reliability of Computed Tomographic Perfusion Acute Infarct Volume Measurements Compared With Diffusion-Weighted Imaging in Anterior Circulation Stroke

Background and Purpose— Diffusion-weighted imaging (DWI) can reliably identify critically ischemic tissue shortly after stroke onset. We tested whether thresholded computed tomographic cerebral blood flow (CT-CBF) and CT-cerebral blood volume (CT-CBV) maps are sufficiently accurate to substitute for DWI for estimating the critically ischemic tissue volume. Methods— Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation and on CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast:noise ratios of ischemic regions on the DWI and CT perfusion (CTP) images were measured. Correlation and Bland–Altman analyses were used to assess the reliability of CTP. Results— Mean contrast:noise ratios for DWI, CT-CBF, and CT-CBV were 4.3, 0.9, and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R2=0.87 for CT-CBF; R2=0.83 for CT-CBV; P<0.001). Bland–Altman analyses revealed little systemic bias (−2.6 mL) but high measurement variability (95% confidence interval, ±56.7 mL) between mean CT-CBF and DWI lesion volumes, and systemic bias (−26 mL) and high measurement variability (95% confidence interval, ±64.0 mL) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. Conclusions— The poor contrast:noise ratios of CT-CBV and CT-CBF compared with those of DWI result in large measurement error, making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than the number needed if DWI is used.

Good Outcome Rate of 35% in IV-tPA–Treated Patients With Computed Tomography Angiography Confirmed Severe Anterior Circulation Occlusive Stroke

Background and Purpose— To determine the effect of intravenous tissue plasminogen activator (IV-tPA) on outcomes in patients with severe major anterior circulation ischemic stroke. Methods— Prospectively, 649 patients with acute stroke had admission National Institutes of Health stroke scale (NIHSS) scores, noncontrast computed tomography (CT), CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale. IV-tPA treatment decisions were made before CTA, at the time of noncontrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as modified Rankin scale >2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed. Results— Of 649 patients, 188 (29%) patients presented with NIHSS>10, and 64 out of 188 (34%) patients received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes; however, a significant interaction existed between IV-tPA and occlusion (P<0.001). Of the patients who presented with NIHSS>10 with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17 out of 49 patients, 35%) than if they did not (13 out of 77 patients, 17%; P=0.031). The number needed to treat was 7 (95% confidence interval, 3–60). Conclusions— IV-tPA treatment resulted in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies.

Clot Length Distribution and Predictors in Anterior Circulation Stroke Implications for Intra-Arterial Therapy

Background and Purpose— Thin-section noncontrast computed tomography images can be used to measure hyperdense clot length in acute ischemic stroke. Clots ≥8 mm have a very low probability of intravenous tissue-type plasminogen activator recanalization and hence may benefit from a bridging intra-arterial approach. To understand the prevalence of such clots, we sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. Methods— Of 623 consecutive patients with acute ischemic stroke, 53 met inclusion criteria: presentation <8 hours from onset; intracranial internal carotid artery-terminus or proximal-middle cerebral artery occlusion; admission thin-slice noncontrast computed tomography (⩽2.5 mm); and no intravenous tissue-type plasminogen activator pretreatment. For each patient, hyperdense clot length was measured and recorded along with additional relevant imaging and clinical data. Results— Mean age was 70 years, and mean time to computed tomography was 213 minutes. Median baseline National Institutes of Health Stroke Scale was 16.5. Occlusions were located in the internal carotid artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean and median clot lengths (mm) of 18.5 (±14.2) and 16.1 (7.6–25.2), respectively. Occlusion location was the strongest predictor of clot length (multivariate, P=0.02). Clot length was ≥8 mm in 94%, 73%, and 22% of internal carotid artery-terminus, M1, and M2 occlusions, respectively. Conclusions— The majority of anterior circulation proximal occlusions are ≥8 mm long, helping to explain the low published rates of intravenous tissue-type plasminogen activator recanalization. Internal carotid artery-terminus occlusion is an excellent marker for clot length ≥8 mm; vessel-imaging status alone may be sufficient. Thin-section noncontrast computed tomography seems useful for patients with middle cerebral artery occlusion because of the wide variability of clot lengths.

Admission CT perfusion is an independent predictor of hemorrhagic transformation in acute stroke with similar accuracy to DWI.

Background: The utility of admission CT perfusion (CTP) to that of diffusion-weighted imaging (DWI) as a predictor of hemorrhagic transformation (HT) in acute stroke was compared. Methods: We analyzed the admission CTP and DWI scans of 96 consecutive stroke patients. HT was present in 22 patients (23%). Infarct core was manually segmented on the admission DWI. We determined the: (1) hypoperfused tissue volume in the ischemic hemisphere using a range of thresholds applied to multiple different CTP parameter maps, and (2) mean relative CTP (rCTP) voxel values within both the DWI-segmented lesions and the thresholded CTP parameter maps. Receiver operating characteristic area under curve (AUC) analysis and multivariate regression were used to evaluate the test characteristics of each set of volumes and mean rCTP parameter values as predictors of HT. Results: The hypoperfused tissue volumes with either relative cerebral blood flow (rCBF) <0.48 (AUC = 0.73), or relative mean transit time (rMTT) >1.3 (AUC = 0.70), had similar accuracy to the DWI-segmented core volume (AUC = 0.68, p = 0.2 and p = 0.1, respectively) as predictors of HT. The mean rMTT voxel values within the rMTT >1.3 segmented lesion (AUC = 0.71) had similar accuracy to the mean rMTT voxel values (AUC = 0.65, p = 0.24) and mean rCBF voxel values (AUC = 0.64, p = 0.22) within the DWI-segmented lesion. The only independent predictors of HT were: (1) mean rMTT with rMTT >1.3, and (2) mechanical thrombectomy. Conclusion: Admission CTP-based hypoperfused tissue volumes and thresholded mean voxel values are markers of HT in acute stroke, with similar accuracy to DWI. This could be of value when MRI cannot be obtained.

Admission Insular Infarction >25% Is the Strongest Predictor of Large Mismatch Loss in Proximal Middle Cerebral Artery Stroke

Background and Purpose— Previous univariate analyses have suggested that proximal middle cerebral artery infarcts with insular involvement have greater severity and are more likely to progress into surrounding penumbral tissue at risk. We hypothesized that a practical, simple scoring method to assess percent insular ribbon infarction (PIRI score) would improve prediction of penumbral loss over other common imaging biomarkers. Methods— Of consecutive acute stroke patients from 2003 to 2008, 45 with proximal middle cerebral artery–only occlusion met inclusion criteria, including available penumbral imaging. Infarct (diffusion-weighted imaging), tissue at risk (magnetic resonance mean transit time), and final infarct volume (magnetic resonance/computed tomography) were manually segmented. Diffusion-weighted imaging images were rated according to the 5-point PIRI score (0, normal; 1, <25%; 2, 25%–49%; 3, 50%–74%; 4, ≥75% insula involvement). Percent mismatch loss was calculated as an outcome measure of infarct progression. Receiver operating characteristic curve and multivariate analyses were performed. Results— Mean admission diffusion-weighted imaging infarct volume was 30.9 (±38.8) mL and median (interquartile range) PIRI score was 3 (0.75–4). PIRI score was significantly correlated with percent mismatch loss (P<0.0001). When percent mismatch loss was dichotomized based on its median value (30.0%), receiver operating characteristic curve area under curve was 0.89 (P=0.0001) with a 25% insula infarction optimal threshold. After adjusting for time to imaging and treatment, binary logistic regression, including dichotomized PIRI (25% threshold), age, National Institutes of Health Stroke Scale score, diffusion-weighted imaging infarct volume, and computed tomography angiography collateral score as covariates, revealed that only dichotomized insula score (P=0.03) and age (P=0.02) were independent predictors of large (68.2%) versus small (8.1%) mismatch loss. There was excellent interobserver agreement for dichotomized PIRI scoring (&kgr;=0.91). Conclusions— Admission insular infarction >25% is the strongest predictor of large mismatch loss in this cohort of proximal middle cerebral artery occlusive stroke. This outcome marker may help to identify treatment-eligible patients who are in greatest need of rapid reperfusion therapy.

Computed tomography imaging and angiography – principles

The evaluation of patients with diverse neurologic disorders was forever changed in the summer of 1973, when the first commercial computed tomography (CT) scanners were introduced. Until then, the detection and characterization of intracranial or spinal lesions could only be inferred by limited spatial resolution radioisotope scans, or by the patterns of tissue and vascular displacement on invasive pneumoencaphalography and direct carotid puncture catheter arteriography. Even the earliest-generation CT scanners - which required tens of minutes for the acquisition and reconstruction of low-resolution images (128×128 matrix) - could, based on density, noninvasively distinguish infarct, hemorrhage, and other mass lesions with unprecedented accuracy. Iodinated, intravenous contrast added further sensitivity and specificity in regions of blood-brain barrier breakdown. The advent of rapid multidetector row CT scanning in the early 1990s created renewed enthusiasm for CT, with CT angiography largely replacing direct catheter angiography. More recently, iterative reconstruction postprocessing techniques have made possible high spatial resolution, reduced noise, very low radiation dose CT scanning. The speed, spatial resolution, contrast resolution, and low radiation dose capability of present-day scanners have also facilitated dual-energy imaging which, like magnetic resonance imaging, for the first time, has allowed tissue-specific CT imaging characterization of intracranial pathology.