Medical Image Imputation from Image Collections

We present an algorithm for creating high resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a generative model that captures fine-scale anatomical structure across subjects in clinical image collections and derive an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago .Comment: Accepted at IEEE Transactions on Medical Imaging (\c{opyright} 2018 IEEE

Principles of precision medicine in stroke

The era of precision medicine has arrived and conveys tremendous potential, particularly for stroke neurology. The diagnosis of stroke, its underlying aetiology, theranostic strategies, recurrence risk and path to recovery are populated by a series of highly individualised questions. Moreover, the phenotypic complexity of a clinical diagnosis of stroke makes a simple genetic risk assessment only partially informative on an individual basis. The guiding principles of precision medicine in stroke underscore the need to identify, value, organise and analyse the multitude of variables obtained from each individual to generate a precise approach to optimise cerebrovascular health. Existing data may be leveraged with novel technologies, informatics and practical clinical paradigms to apply these principles in stroke and realise the promise of precision medicine. Importantly, precision medicine in stroke will only be realised once efforts to collect, value and synthesise the wealth of data collected in clinical trials and routine care starts. Stroke theranostics, the ultimate vision of synchronising tailored therapeutic strategies based on specific diagnostic data, demand cerebrovascular expertise on big data approaches to clinically relevant paradigms. This review considers such challenges and delineates the principles on a roadmap for rational application of precision medicine to stroke and cerebrovascular health

The TeleStroke Mimic (TM)‐Score: A Prediction Rule for Identifying Stroke Mimics Evaluated in a Telestroke Network

Background: Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation. Methods and Results: We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England–based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver‐operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM‐Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM‐Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77). Conclusions: SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision‐support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time‐critical telestroke evaluations

Medical Image Imputation From Image Collections

We present an algorithm for creating high-resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable the application of existing algorithms that were originally developed for high-resolution research scans to significantly undersampled scans. We introduce a generative model that captures a fine-scale anatomical structure across subjects in clinical image collections and derives an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms the state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago

Cognitive impairment after ischemic and hemorrhagic stroke: a scientific statement from the American Heart Association/American Stroke Association

Purpose: Cognitive impairment is a common consequence of stroke and has direct implications for poststroke functioning and quality of life, including the ability to maintain a job, live independently, sustain interpersonal relationships, and drive a vehicle. In this scientific statement, we critically appraise the literature on the prevalence, diagnosis, and management of poststroke cognitive impairment (PSCI) and provide a framework for clinical care while highlighting gaps that merit further study. Methods: We performed a scoping literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case-control studies, clinical guidelines, review articles, and editorials on the incidence and prevalence, natural history, diagnosis, and management of PSCI. Scoping reviews determine the scope of a body of literature on a given topic to indicate the volume of literature and the studies currently available and provide an overview of its focus. Results: PSCI is common after stroke, especially in the first year, and ranges from mild to severe. Although cognitive impairment is reversible in some cases early after stroke, up to one-third of individuals with stroke develop dementia within 5 years. The pathophysiology is not yet fully elucidated but is likely attributable to an acute stroke precipitating a series of pathological events, often in the setting of preexisting microvascular and neurodegenerative changes. Screening for associated comorbidities and interdisciplinary management are integral components of the care of individuals with PSCI. There is a need for prospective studies evaluating the individual trajectory of PSCI and the role of the acute vascular event in the predisposition for Alzheimer disease and related dementias, as well as high-quality, randomized clinical trials focused on PSCI management

Common NOTCH3 Variants and Cerebral Small-Vessel Disease.

BACKGROUND AND PURPOSE: The most common monogenic cause of cerebral small-vessel disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 gene mutations. It has been hypothesized that more common variants in NOTCH3 may also contribute to the risk of sporadic small-vessel disease. Previously, 4 common variants (rs10404382, rs1043994, rs10423702, and rs1043997) were found to be associated with the presence of white matter hyperintensity in hypertensive community-dwelling elderly. METHODS: We investigated the association of common single nucleotide polymorphisms (SNPs) in NOTCH3 in 1350 patients with MRI-confirmed lacunar stroke and 7397 controls, by meta-analysis of genome-wide association study data sets. In addition, we investigated the association of common SNPs in NOTCH3 with MRI white matter hyperintensity volumes in 3670 white patients with ischemic stroke. In each analysis, we considered all SNPs within the NOTCH3 gene, and within 50-kb upstream and downstream of the coding region. A total of 381 SNPs from the 1000 genome population with a mean allele frequency>0.01 were included in the analysis. A significance level of P<0.0015 was used, adjusted for the effective number of independent SNPs in the region using the Galwey method. RESULTS: We found no association of any common variants in NOTCH3 (including rs10404382, rs1043994, rs10423702, and rs1043997) with lacunar stroke or white matter hyperintensity volume. We repeated our analysis stratified for hypertension but again found no association. CONCLUSIONS: Our study does not support a role for common NOTCH3 variation in the risk of sporadic small-vessel disease.Collection of the UK Young Lacunar Stroke DNA Study (DNA lacunar) was primarily supported by the Wellcome Trust (WT072952) with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA lacunar samples, and Dr Traylor, was supported by a Stroke Association Grant (TSA 2013/01). Funding for the genotyping at Massachusetts General Hospital was provided by the Massachusetts General Hospital- Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke and the National Institute of Neurological Disorders and Stroke (U01 NS069208). Dr Rutten-Jacobs was supported by a project grant from the Stroke Association/British Heart Foundation grant (TSA BHF 2010/01). Dr Adib-Samii was supported by a Medical Research Council (United Kingdom) training fellowship. Drs Markus and Bevan were supported by the National Institute for Health Research Cambridge University Hospitals Comprehensive Biomedical Research Centre. Dr Markus was supported by a National Institute for Health Research Senior Investigator award. Dr Thijs was supported by a Clinical Investigator Grant from the scientific research fund, Fonds Wetenschappelijk Onderzoek Flanders. Dr Rost was supported by a National Institute of Neurological Disorders and Stroke grant (R01 NS082285-01).This is the final published version. It first appeared at http://stroke.ahajournals.org/content/46/6/1482.long

Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Background and purpose Functional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differences in microvascular integrity in individuals with acute ischaemic stroke.Methods A retrospective analysis of subjects with acute ischaemic stroke and brain MRI with diffusion-weighted (DWI) and dynamic-susceptibility contrast-enhanced (DSC) perfusion-weighted imaging obtained within 9 hours of last known well was performed. In the hemisphere contralateral to the acute infarct, normal-appearing white matter (NAWM) microvascular integrity was measured using the K-2 coefficient and apparent diffusion coefficient (ADC) values. Regression analyses for predictors of K-2 coefficient, DWI volume and good outcome (90-day modified Rankin scale (mRS) score &lt;2) were performed.Results 105 men and 79 women met inclusion criteria for analysis. Despite no difference in age, women had increased NAWM K-2 coefficient (1027.4 vs 692.7x10(-6)/s; p=0.006). In women, atrial fibrillation (beta=583.6; p=0.04) and increasing NAWM ADC (beta=4.4; p=0.02) were associated with increased NAWM K-2 coefficient. In multivariable regression analysis, the K-2 coefficient was an independent predictor of DWI volume in women (beta=0.007; p=0.01) but not men.Conclusions In women with acute ischaemic stroke, increased NAWM K-2 coefficient is associated with increased infarct volume and chronic white matter structural integrity. Prospective studies investigating sex-specific differences in white matter microvascular integrity are needed