Bruno P. Soares

Reperfusion Is a More Accurate Predictor of Follow-Up Infarct Volume Than Recanalization: A Proof of Concept Using CT in Acute Ischemic Stroke Patients

Background and Purpose— The purpose of this study was to compare recanalization and reperfusion in terms of their predictive value for imaging outcomes (follow-up infarct volume, infarct growth, salvaged penumbra) and clinical outcome in acute ischemic stroke patients. Material and Methods— Twenty-two patients admitted within 6 hours of stroke onset were retrospectively included in this study. These patients underwent a first stroke CT protocol including CT-angiography (CTA) and perfusion-CT (PCT) on admission, and similar imaging after treatment, typically around 24 hours, to assess recanalization and reperfusion. Recanalization was assessed by comparing arterial patency on admission and posttreatment CTAs; reperfusion, by comparing the volumes of CBV, CBF, and MTT abnormality on admission and posttreatment PCTs. Collateral flow was graded on the admission CTA. Follow-up infarct volume was measured on the discharge noncontrast CT. The groups of patients with reperfusion, no reperfusion, recanalization, and no recanalization were compared in terms of imaging and clinical outcomes. Results— Reperfusion (using an MTT reperfusion index >75%) was a more accurate predictor of follow-up infarct volume than recanalization. Collateral flow and recanalization were not accurate predictors of follow-up infarct volume. An interaction term was found between reperfusion and the volume of the admission penumbra >50 mL. Conclusion— Our study provides evidence that reperfusion is a more accurate predictor of follow-up infarct volume in acute ischemic stroke patients than recanalization. We recommend an MTT reperfusion index >75% to assess therapy efficacy in future acute ischemic stroke trials that use perfusion-CT.

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.

Difference in Disease Burden and Activity in Pediatric Patients on Brain Magnetic Resonance Imaging at Time of Multiple Sclerosis Onset vs Adults

OBJECTIVE To compare initial brain magnetic resonance imaging (MRI) characteristics of children and adults at multiple sclerosis (MS) onset. DESIGN Retrospective analysis of features of first brain MRI available at MS onset in patients with pediatric-onset and adult-onset MS. SETTING A pediatric and an adult MS center. PATIENTS Patients with pediatric-onset <18 years) and adult-onset (> or =18 years) MS. MAIN OUTCOME MEASURES We evaluated initial and second (when available) brain MRI scans obtained at the time of first MS symptoms for lesions that were T2-bright, ovoid and well defined, large (> or =1cm), or enhancing. RESULTS We identified 41 patients with pediatric-onset MS and 35 patients with adult-onset MS. Children had a higher number of total T2- (median, 21 vs 6; P < .001) and large T2-bright areas (median, 4 vs 0; P < .001) than adults. Children more frequently had T2-bright foci in the posterior fossa (68.3% vs 31.4%; P = .001) and enhancing lesions (68.4% vs 21.2%; P < .001) than adults. On the second brain MRI, children had more new T2-bright (median, 2.5 vs 0; P < .001) and gadolinium-enhancing foci (P < .001) than adults. Except for corpus callosum involvement, race/ethnicity was not strongly associated with disease burden or lesion location on the first scan, although other associations cannot be excluded because of the width of the confidence intervals. CONCLUSION While it is unknown whether the higher disease burden, posterior fossa involvement, and rate of new lesions in pediatric-onset MS are explained by age alone, these characteristics have been associated with worse disability progression in adults.

MR and CT Monitoring of Recanalization, Reperfusion, and Penumbra Salvage. Everything That Recanalizes Does Not Necessarily Reperfuse!

Revascularization therapies for acute stroke patients aim to rescue the ischemic penumbra by restoring the patency of the occluded artery (“recanalization”) and the downstream capillary blood flow (“reperfusion”). This article reviews the definition of recanalization and reperfusion used in stroke clinical trials and their limitations and proposes a study design to determine the relative importance of recanalization, reperfusion, and collateral flow in evaluating the efficacy of revascularization therapies for acute ischemic stroke.

Automated versus manual post-processing of perfusion-CT data in patients with acute cerebral ischemia: influence on interobserver variability

IntroductionThe purpose of this study is to compare the variability of PCT results obtained by automatic selection of the arterial input function (AIF), venous output function (VOF) and symmetry axis versus manual selection.MethodsImaging data from 30 PCT studies obtained as part of standard clinical stroke care at our institution in patients with suspected acute hemispheric ischemic stroke were retrospectively reviewed. Two observers performed the post-processing of 30 CTP datasets. Each observer processed the data twice, the first time employing manual selection of AIF, VOF and symmetry axis, and a second time using automated selection of these same parameters, with the user being allowed to adjust them whenever deemed appropriate. The volumes of infarct core and of total perfusion defect were recorded. The cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and blood–brain barrier permeability (BBBP) values in standardized regions of interest were recorded. Interobserver variability was quantified using the Bland and Altmans approach.ResultsAutomated post-processing yielded lower coefficients of variation for the volume of the infarct core and the volume of the total perfusion defect (15.7% and 5.8%, respectively) compared to manual post-processing (31.0% and 12.2%, respectively). Automated post-processing yielded lower coefficients of variation for PCT values (11.3% for CBV, 9.7% for CBF, and 9.5% for MTT) compared to manual post-processing (23.7% for CBV, 32.8% for CBF, and 16.7% for MTT).ConclusionAutomated post-processing of PCT data improves interobserver agreement in measurements of CBV, CBF and MTT, as well as volume of infarct core and penumbra.

Carotid Atheroma Rupture Observed In Vivo and FSI-Predicted Stress Distribution Based on Pre-rupture Imaging

Atherosclerosis at the carotid bifurcation is a major risk factor for stroke. As mechanical forces may impact lesion stability, finite element studies have been conducted on models of diseased vessels to elucidate the effects of lesion characteristics on the stresses within plaque materials. It is hoped that patient-specific biomechanical analyses may serve clinically to assess the rupture potential for any particular lesion, allowing better stratification of patients into the most appropriate treatments. Due to a sparsity of in vivo plaque rupture data, the relationship between various mechanical descriptors such as stresses or strains and rupture vulnerability is incompletely known, and the patient-specific utility of biomechanical analyses is unclear. In this article, we present a comparison between carotid atheroma rupture observed in vivo and the plaque stress distribution from fluid–structure interaction analysis based on pre-rupture medical imaging. The effects of image resolution are explored and the calculated stress fields are shown to vary by as much as 50% with sub-pixel geometric uncertainty. Within these bounds, we find a region of pronounced elevation in stress within the fibrous plaque layer of the lesion with a location and extent corresponding to that of the observed site of plaque rupture.

Radiation dose reduction in pediatric CT-guided musculoskeletal procedures.

BackgroundComputed-tomography-guided interventions are attractive for tissue sampling of pediatric bone lesions; however, it comes with exposure to ionizing radiation, inherent to CT and magnified by multiple passes during needle localization.ObjectiveWe evaluate a method of CT-guided bone biopsy that minimizes ionizing radiation exposure by lowering CT scanner tube current (mAs) and voltage (kVp) during each localization scan.Materials and methodsWe retrospectively reviewed all CT-guided bone biopsies (n = 13) over a 1-year period in 12 children. Three blinded readers identified the needle tip on the reduced-dose CT images (mAs = 50, kVp = 80) during the final localization scan at biopsy and rated the image quality as high, moderate or low.ResultsThe image quality of the reduced-dose scans during biopsy was rated as either high or moderate, with needle tip visualized in 12 out of 13 biopsies. Twelve of 13 biopsies also returned sufficient sample for a pathological diagnosis. The average savings in exposure using the dose-reduction technique was 87%.ConclusionOur results suggest that a low mAs and kVp strategy for needle localization during CT-guided bone biopsy yields a large dose reduction and produces acceptable image quality without sacrificing yield for biopsy diagnosis.

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.

Novel Contrast-Enhanced Ultrasound Evaluation in Neonatal Hypoxic Ischemic Injury: Clinical Application and Future Directions

Sensitive, specific, and safe bedside evaluation of brain perfusion is key to the early diagnosis, treatment, and improved survival of neonates with hypoxic ischemic injury. Contrast‐enhanced ultrasound (US) imaging is a novel imaging technique in which intravenously injected gas‐filled microbubbles generate enhanced US echoes from an acoustic impedance mismatch. This article describes contrast‐enhanced US imaging in 2 neonates with hypoxic ischemic injury and future directions on developing quantitative contrast‐enhanced US techniques for improved characterization of perfusion abnormalities. The importance of studying the temporal evolution of brain perfusion in neonatal hypoxic ischemic injury is also highlighted.

Longitudinally extensive optic neuritis in pediatric patients

Extensive optic nerve demyelinating lesions on magnetic resonance imaging (MRI) in adults could indicate a diagnosis other than multiple sclerosis with worse prognosis such as neuromyelitis optica. We report the frequency of longitudinally extensive lesions in children with first events of optic neuritis. Subjects had brain or orbit MRI within 3 months of onset and were evaluated at the University of California, San Francisco, Pediatric Multiple Sclerosis Center. Lesion length, determined by T2 hyperintensity or contrast enhancement, was blindly graded as absent, focal or longitudinally extensive (at least 2 contiguous segments of optic nerve). Of 25 subjects, 9 (36%) had longitudinally extensive optic neuritis. Extensive lesions were not associated with non–multiple sclerosis versus multiple sclerosis diagnosis (P = 1.00). No association between age and lesion extent was observed (P = .26). Prospective studies are needed to determine if longitudinally extensive optic neuritis can predict visual outcome.