Beyond Diffusion Tensor MRI Methods for Improved Characterization of the Brain after Ischemic Stroke: A Review.

Ischemic stroke is a worldwide problem, with 15 million people experiencing a stroke annually. MR imaging is a valuable tool for understanding and assessing brain changes after stroke and predicting recovery. Of particular interest is the use of diffusion MR imaging in the nonacute stage 1-30 days poststroke. Thousands of articles have been published on the use of diffusion MR imaging in stroke, including several recent articles reviewing the use of DTI for stroke. The goal of this work was to survey and put into context the recent use of diffusion MR imaging methods beyond DTI, including diffusional kurtosis, generalized fractional anisotropy, spherical harmonics methods, and neurite orientation and dispersion models, in patients poststroke. Early studies report that these types of beyond-DTI methods outperform DTI metrics either in being more sensitive to poststroke changes or by better predicting outcome motor scores. More and larger studies are needed to confirm the improved prediction of stroke recovery with the beyond-DTI methods.

Carotid Artery Stiffness Accurately Predicts White Matter Hyperintensity Volume 20 Years Later: A Secondary Analysis of the Atherosclerosis Risk in the Community Study.

BACKGROUND AND PURPOSE: Arterial stiffness is a biomarker of cerebrovascular disease and dementia risk. Studies have shown an association between carotid artery stiffness and increased white matter hyperintensity volume and, as a result, reduced total brain volume on MR imaging, but none have had prolonged follow-up to fully evaluate the slow change seen in white matter hyperintensity volume and total brain volume with time. Our objective was to determine whether common carotid artery stiffness on sonography accurately predicts white matter hyperintensity volume and total brain volume on MR imaging more than 20 years later. MATERIALS AND METHODS: We performed a secondary analysis of the Atherosclerosis Risk in the Community study to compare 5 measurements of carotid artery stiffness, including strain, distensibility, compliance, Stiffness index, and pressure-strain elastic modulus, with the white matter hyperintensity volume and total brain volume on a follow-up MR imaging using linear regression. RESULTS: We included 1402 patients enrolled in the Atherosclerosis Risk in the Community study. There was a significant relationship between increasing carotid artery stiffness and both higher white matter hyperintensity volume and lower total brain volume on MR imaging, measured at a mean of 21.5 years later. In multivariable linear regression models, the carotid strain, distensibility, Stiffness index, and pressure-strain elastic modulus were associated with white matter hyperintensity volume. Only compliance was associated with total brain volume in the multivariate models. CONCLUSIONS: Sonography measurements of carotid artery stiffness are predictive of white matter hyperintensity volume and total brain volume on MR imaging more than 20 years later. The association is more robust for white matter hyperintensity volume than total brain volume. These findings support the role of arterial stiffness as a method for identifying patients at risk of developing white matter hyperintensity volume and as a potential mechanism leading to small-artery disease of the brain.

Vitamin D and Vulnerable Carotid Plaque.

BACKGROUND AND PURPOSE: MR imaging-detected carotid intraplaque hemorrhage indicates vulnerable plaque with high stroke risk. Angiotensin II stimulates intraplaque hemorrhage in animal models, and the angiotensin system is highly regulated by vitamin D. Our purpose was to determine whether low vitamin D levels predict carotid intraplaque hemorrhage in humans. MATERIALS AND METHODS: In this cross-sectional study, 65 patients with carotid disease underwent carotid MR imaging and blood draw. Systemic clinical confounders and local lumen imaging markers were recorded. To determine the association of low vitamin D levels with MR imaging detected intraplaque hemorrhage, we performed multivariable Poisson regression by using generalized estimating equations to account for up to 2 carotid arteries per patient and backward elimination of confounders. MR imaging detected intraplaque hemorrhage volume was also correlated with vitamin D levels and maximum plaque thickness. Thirty-five patients underwent carotid endarterectomy, and histology-detected intraplaque hemorrhage was correlated with vitamin D levels and total plaque area. RESULTS: Low vitamin D levels (<30 ng/mL, prevalence ratio = 2.05, P = .03) were a significant predictor of MR imaging detected intraplaque hemorrhage, along with plaque thickness (prevalence ratio = 1.40, P < .001). MR imaging detected intraplaque hemorrhage volume linearly correlated with plaque thickness (partial r = 0.45, P < .001) and low vitamin D levels (partial r = 0.26, P = .003). Additionally, histology-detected intraplaque hemorrhage area linearly correlated with plaque area (partial r = 0.46, P < .001) and low vitamin D levels (partial r = 0.22, P = .03). The association of intraplaque hemorrhage volume with low vitamin D levels was also higher with ischemic stroke. CONCLUSIONS: Low vitamin D levels and plaque thickness predict carotid intraplaque hemorrhage and outperform lumen markers of vulnerable plaque. This research demonstrates a significant link between low vitamin D levels and carotid intraplaque hemorrhage.

The cost-effectiveness of telestroke in the treatment of acute ischemic stroke.

OBJECTIVE: To conduct a cost-effectiveness analysis of telestroke--a 2-way, audiovisual technology that links stroke specialists to remote emergency department physicians and their stroke patients--compared to usual care (i.e., remote emergency departments without telestroke consultation or stroke experts). METHODS: A decision-analytic model was developed for both 90-day and lifetime horizons. Model inputs were taken from published literature where available and supplemented with western states' telestroke experiences. Costs were gathered using a societal perspective and converted to 2008 US dollars. Quality-adjusted life-years (QALYs) gained were combined with costs to generate incremental cost-effectiveness ratios (ICERs). In the lifetime horizon model, both costs and QALYs were discounted at 3% annually. Both one-way sensitivity analyses and Monte Carlo simulations were performed. RESULTS: In the base case analysis, compared to usual care, telestroke results in an ICER of $108,363/QALY in the 90-day horizon and $2,449/QALY in the lifetime horizon. For the 90-day and lifetime horizons, 37.5% and 99.7% of 10,000 Monte Carlo simulations yielded ICERs <$50,000/QALY, a ratio commonly considered acceptable in the United States. CONCLUSION: When a lifetime perspective is taken, telestroke appears cost-effective compared to usual care, since telestroke costs are upfront but benefits of improved stroke care are lifelong. If barriers to use such as low reimbursement rates and high equipment costs are reduced, telestroke has the potential to diminish the striking geographic disparities of acute stroke care in the United States.

The Causative Classification of Stroke system: an international reliability and optimization study.

BACKGROUND: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. METHODS: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. RESULTS: The κ value for causative classification was 0.80 (95% confidence interval [CI] 0.78-0.81) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.70 (95% CI 0.69-0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: κ = 0.81 (95% CI 0.79-0.82) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.79 (95% CI 0.78-0.80) for the 16-subtype CCS. The κ value for phenotypic classification was 0.79 (95% CI 0.77-0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93-0.98) for cardioembolism, 0.88 (95% CI 0.85-0.91) for small artery occlusion, and 0.79 (0.76-0.82) for other uncommon causes. CONCLUSIONS: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras.

Predicting ischaemic stroke subtype from presenting systolic blood pressure: the BASIC Project.

OBJECTIVE: We hypothesized that low presenting systolic blood pressure (SBP) predicted cardioembolic stroke aetiology. DESIGN: Active and passive surveillance were used to identify all ischaemic strokes as part of the Brain Attack Surveillance in Corpus Christi (BASIC) population-based study. Multinomial logistic regression was used to examine the association between stroke subtype and first documented SBP in the medical record. SETTING: Nueces County, TX, USA (313,645 residents in 2000). The community is urban with the majority of the population residing in the city of Corpus Christi. The area is served by seven adult acute care hospitals. PATIENTS: Three hundred and eight cases with completed ischaemic stroke and determined subtype aetiology between January 2000 and December 2002. RESULTS: Lower presenting SBP was associated with stroke subtype (P = 0.001). This association remained significant in the final model adjusted for age and history of coronary artery disease. The odds of cardioembolic versus small vessel occlusion increased by 20% (OR = 1.20, 95% CI: 1.07-1.35) for every 10 mmHg decrease in presenting SBP. Other covariates including race/ethnicity, gender, history of hypertension, and diabetes were neither significant predictors of stroke subtype, nor did they confound the association of SBP and stroke subtype. A 5 year increase in age increased the odds of cardioembolic subtype by 25% (OR = 1.25, 95% CI: 1.07-1.47). CONCLUSIONS: Lower initial SBP and older age at ischaemic stroke presentation were associated with cardioembolic stroke. Suspicion of cardioembolic stroke should be increased in those presenting with low SBP.