The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions.

BACKGROUND:Chronic lesion activity driven by smoldering inflammation is a pathological hallmark of progressive forms of multiple sclerosis (MS). OBJECTIVE:To develop a method for automatic detection of slowly expanding/evolving lesions (SELs) on conventional brain magnetic resonance imaging (MRI) and characterize such SELs in primary progressive MS (PPMS) and relapsing MS (RMS) populations. METHODS:We defined SELs as contiguous regions of existing T2 lesions showing local expansion assessed by the Jacobian determinant of the deformation between reference and follow-up scans. SEL candidates were assigned a heuristic score based on concentricity and constancy of change in T2- and T1-weighted MRIs. SELs were examined in 1334 RMS patients and 555 PPMS patients. RESULTS:Compared with RMS patients, PPMS patients had higher numbers of SELs (p = 0.002) and higher T2 volumes of SELs (p < 0.001). SELs were devoid of gadolinium enhancement. Compared with areas of T2 lesions not classified as SEL, SELs had significantly lower T1 intensity at baseline and larger decrease in T1 intensity over time. CONCLUSION:We suggest that SELs reflect chronic tissue loss in the absence of ongoing acute inflammation. SELs may represent a conventional brain MRI correlate of chronic active MS lesions and a candidate biomarker for smoldering inflammation in MS

Visual and Contextual Modeling for the Detection of Repeated Mild Traumatic Brain Injury.

Currently, there is a lack of computational methods for the evaluation of mild traumatic brain injury (mTBI) from magnetic resonance imaging (MRI). Further, the development of automated analyses has been hindered by the subtle nature of mTBI abnormalities, which appear as low contrast MR regions. This paper proposes an approach that is able to detect mTBI lesions by combining both the high-level context and low-level visual information. The contextual model estimates the progression of the disease using subject information, such as the time since injury and the knowledge about the location of mTBI. The visual model utilizes texture features in MRI along with a probabilistic support vector machine to maximize the discrimination in unimodal MR images. These two models are fused to obtain a final estimate of the locations of the mTBI lesion. The models are tested using a novel rodent model of repeated mTBI dataset. The experimental results demonstrate that the fusion of both contextual and visual textural features outperforms other state-of-the-art approaches. Clinically, our approach has the potential to benefit both clinicians by speeding diagnosis and patients by improving clinical care

Simultaneous lesion and neuroanatomy segmentation in Multiple Sclerosis using deep neural networks

Segmentation of both white matter lesions and deep grey matter structures is an important task in the quantification of magnetic resonance imaging in multiple sclerosis. Typically these tasks are performed separately: in this paper we present a single segmentation solution based on convolutional neural networks (CNNs) for providing fast, reliable segmentations of multimodal magnetic resonance images into lesion classes and normal-appearing grey- and white-matter structures. We show substantial, statistically significant improvements in both Dice coefficient and in lesion-wise specificity and sensitivity, compared to previous approaches, and agreement with individual human raters in the range of human inter-rater variability. The method is trained on data gathered from a single centre: nonetheless, it performs well on data from centres, scanners and field-strengths not represented in the training dataset. A retrospective study found that the classifier successfully identified lesions missed by the human raters. Lesion labels were provided by human raters, while weak labels for other brain structures (including CSF, cortical grey matter, cortical white matter, cerebellum, amygdala, hippocampus, subcortical GM structures and choroid plexus) were provided by Freesurfer 5.3. The segmentations of these structures compared well, not only with Freesurfer 5.3, but also with FSL-First and Freesurfer 6.0

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Getting the best outcomes from epilepsy surgery.

Neurosurgery is an underutilized treatment that can potentially cure drug-refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug-refractory focal epilepsies. Ann Neurol 2018;83:676-690

Validation of vessel size imaging (VSI) in high-grade human gliomas using magnetic resonance imaging, image-guided biopsies, and quantitative immunohistochemistry.

To evaluate the association between a vessel size index (VSIMRI) derived from dynamic susceptibility contrast (DSC) perfusion imaging using a custom spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence and quantitative estimates of vessel morphometry based on immunohistochemistry from image-guided biopsy samples. The current study evaluated both relative cerebral blood volume (rCBV) and VSIMRI in eleven patients with high-grade glioma (7 WHO grade III and 4 WHO grade IV). Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature. Measures of rCBV and VSIMRI were then compared to histological measures. We demonstrate good agreement between VSI measured by MRI and histology; VSIMRI = 13.67 μm and VSIHistology = 12.60 μm, with slight overestimation of VSIMRI in grade III patients compared to histology. rCBV showed a moderate but significant correlation with vessel density (r = 0.42, p = 0.03), and a correlation was also observed between VSIMRI and VSIHistology (r = 0.49, p = 0.01). The current study supports the hypothesis that vessel size measures using MRI accurately reflect vessel caliber within high-grade gliomas, while traditional measures of rCBV are correlated with vessel density and not vessel caliber

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

Dynamic low-level context for the detection of mild traumatic brain injury.

Mild traumatic brain injury (mTBI) appears as low contrast lesions in magnetic resonance (MR) imaging. Standard automated detection approaches cannot detect the subtle changes caused by the lesions. The use of context has become integral for the detection of low contrast objects in images. Context is any information that can be used for object detection but is not directly due to the physical appearance of an object in an image. In this paper, new low-level static and dynamic context features are proposed and integrated into a discriminative voxel-level classifier to improve the detection of mTBI lesions. Visual features, including multiple texture measures, are used to give an initial estimate of a lesion. From the initial estimate novel proximity and directional distance, contextual features are calculated and used as features for another classifier. This feature takes advantage of spatial information given by the initial lesion estimate using only the visual features. Dynamic context is captured by the proposed posterior marginal edge distance context feature, which measures the distance from a hard estimate of the lesion at a previous time point. The approach is validated on a temporal mTBI rat model dataset and shown to have improved dice score and convergence compared to other state-of-the-art approaches. Analysis of feature importance and versatility of the approach on other datasets are also provided