Abstract

Stroke is one of the leading causes of death and disability worldwide. Reducing this disease burden through drug discovery and evaluation of stroke patient outcomes requires broader characterization of stroke pathophysiology, yet the underlying biologic and genetic factors contributing to outcomes are largely unknown. Remedying this critical knowledge gap requires deeper phenotyping, including large-scale integration of demographic, clinical, genomic, and imaging features. Such big data approaches will be facilitated by developing and running processing pipelines to extract stroke-related phenotypes at large scale. Millions of stroke patients undergo routine brain imaging each year, capturing a rich set of data on stroke-related injury and outcomes. The Stroke Neuroimaging Phenotype Repository (SNIPR) was developed as a multi-center centralized imaging repository of clinical computed tomography (CT) and magnetic resonance imaging (MRI) scans from stroke patients worldwide, based on the open source XNAT imaging informatics platform. The aims of this repository are to: (i) store, manage, process, and facilitate sharing of high-value stroke imaging data sets, (ii) implement containerized automated computational methods to extract image characteristics and disease-specific features from contributed images, (iii) facilitate integration of imaging, genomic, and clinical data to perform large-scale analysis of complications after stroke; and (iv) develop SNIPR as a collaborative platform aimed at both data scientists and clinical investigators. Currently, SNIPR hosts research projects encompassing ischemic and hemorrhagic stroke, with data from 2,246 subjects, and 6,149 imaging sessions from Washington University’s clinical image archive as well as contributions from collaborators in different countries, including Finland, Poland, and Spain. Moreover, we have extended the XNAT data model to include relevant clinical features, including subject demographics, stroke severity (NIH Stroke Scale), stroke subtype (using TOAST classification), and outcome [modified Rankin Scale (mRS)]. Image processing pipelines are deployed on SNIPR using containerized modules, which facilitate replicability at a large scale. The first such pipeline identifies axial brain CT scans from DICOM header data and image data using a meta deep learning scan classifier, registers serial scans to an atlas, segments tissue compartments, and calculates CSF volume. The resulting volume can be used to quantify the progression of cerebral edema after ischemic stroke. SNIPR thus enables the development and validation of pipelines to automatically extract imaging phenotypes and couple them with clinical data with the overarching aim of enabling a broad understanding of stroke progression and outcomes.

Highlights

  • Stroke is the second leading cause of death throughout the world, and the leading cause of long-term disability (George et al, 2017)

  • An endeavor is underway to describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical magnetic resonance imaging (MRI) in patients with acute ischemic stroke within the scope of the MRI-GENetics Interface Exploration (MRI-GENIE) study (Giese et al, 2017, 2020)

  • Louis School of Medicine (WUSTL)-affiliated hospital system can be imported directly from the clinical image repository or Picture Archiving and Communication System (PACS) using XNAT’s PACS query interface, which extracts the images from PACS, anonymizes them, and stores them to the Stroke Neuroimaging Phenotype Repository (SNIPR) file repository

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Summary

INTRODUCTION

Stroke is the second leading cause of death throughout the world, and the leading cause of long-term disability (George et al, 2017). An endeavor is underway to describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical magnetic resonance imaging (MRI) in patients with acute ischemic stroke within the scope of the MRI-GENetics Interface Exploration (MRI-GENIE) study (Giese et al, 2017, 2020) Another similar effort with focus on MRI data is Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery repository which tries to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. A big data approach is required to assess images at scale, including identifying quantitative image features and developing automated tools to extract them This imaging analysis can be coupled with analysis of clinical and genomics data from these subjects, facilitating large-scale genomic analysis of acute complications after stroke that are best represented by imaging features (Dhar et al, 2018). SNIPR enables coupling the imaging results with clinical data, with the overarching aim of enabling a broad understanding of stroke progression and outcomes

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