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Holmes, M. F.

Publications and source records attributed to Holmes, M. F..

6 recordsLinked to original sources

Deep Bayesian networks for uncertainty estimation and adversarial resistance of white matter hyperintensity segmentation

White matter hyperintensities (WMH) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation. MRI-based segmentation methods are often sensitive to acquisition protocols, scanners, noise-level, and image contrast, failing to generalize to other populations and out-of-distribution datasets. Given these concerns, we propose a novel Bayesian 3D Convolutional Neural Network (CNN) with a U-Net architecture that automatically segments WMH, provides uncertainty estimates of the segmentation output for quality control and is robust to changes in acquisition protocols. We also provide a second model to differentiate deep and periventricular WMH. 432 subjects were recruited to train the CNNs from four multi-site imaging studies. A separate test set of 158 subjects was used for evaluation, including an unseen multi-site study. We compared our model to two established state-of-the-art techniques (BIANCA and DeepMedic), highlighting its accuracy and efficiency. Our Bayesian 3D U-Net achieved the highest Dice similarity coefficient of 0.89 {+/-} 0.08 and the lowest modified Hausdorff distance of 2.98 {+/-} 4.40 mm. We further validated our models highlighting their robustness on clinical adversarial cases simulating data with low signal-to-noise ratio, low resolution, and different contrast (stemming from MRI sequences with different parameters). Our pipeline and models are available at: https://hypermapp3r.readthedocs.io

neuroscience↗

Investigating the Contribution of White Matter Hyperintensities and Cortical Thickness to Empathy in Neurodegenerative and Cerebrovascular Diseases

Introduction: Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Methods: 513 participants with Alzheimers Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia (FTD), Parkinsons Disease, or Cerebrovascular Disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. Results: A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex(female), global cognition, and right parietal and occipital WMH. Conclusions: Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.

neuroscience↗

Cortical thickness estimation in individuals with cerebral small vessel disease, focal atrophy, and chronic stroke lesions.

BackgroundRegional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases can be estimated using specialised neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood of misclassification errors and segmentation failures. PurposeThe main goal of this study was to examine a correction procedure developed for enhancing FreeSurfers cortical thickness estimation tool, particularly when applied to the most challenging MRI obtained from participants with chronic stroke and cerebrovascular disease, with varying degrees of neurovascular lesions and brain atrophy. MethodsIn 155 cerebrovascular disease patients enrolled in the Ontario Neurodegenerative Disease Research Initiative (ONDRI), FreeSurfer outputs were compared between a fully automated, unmodified procedure and a corrected procedure that accounted for potential sources of error due to atrophy and neurovascular lesions. Quality control (QC) measures were obtained from both procedures. Association between cortical thickness and global cognitive status as assessed by the Montreal Cognitive Assessment (MoCA) score was also investigated from both procedures. ResultsCorrected procedures increased Acceptable QC ratings from 18% to 76% for the cortical ribbon and from 38% to 92% for tissue segmentation. Corrected procedures reduced Fail ratings from 11% to 0% for the cortical ribbon and 62% to 8% for tissue segmentation. FreeSurfer-based segmentation of T1-weighted white matter hypointensities were significantly greater in the corrected procedure (5.8mL vs. 15.9mL, p<0.001). The unmodified procedure yielded no significant associations with global cognitive status, whereas the corrected procedure yielded positive associations between MoCA total score and clusters of cortical thickness in the left superior parietal (p=0.018) and left insula (p=0.04) regions. Further analyses with the corrected cortical thickness results and MoCA subscores showed a positive association between left superior parietal cortical thickness and Attention (p<0.001). ConclusionsThese findings suggest that correction procedures that account for brain atrophy and neurovascular lesions can significantly improve FreeSurfers segmentation results, reduce failure rates, and potentially increase sensitivity to examine brain-behaviour relationships. Future work will examine relationships between cortical thickness, cerebral small vessel disease, and neurodegenerative disease in the ONDRI study.

neuroscience↗

Improved segmentation of the intracranial and ventricular volumes in populations with cerebrovascular lesions and atrophy using 3D CNNs

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N=528 subjects for ICV, N=501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with vascular cognitive impairment and high white matter hyperintensity burden. Two of the three test sets came from studies not used in the training dataset. We assessed our algorithms relative to four state-of-the-art ICV extraction methods (MONSTR, BET, Deep Extraction, FreeSurfer), as well as a ventricular segmentation tool (FreeSurfer). Our multi-contrast models outperformed other methods across all evaluation metrics, with average Dice coefficients of 0.98 and 0.94 for ICV and ventricular segmentation respectively. Both models were also the most time efficient, segmenting the structures in orders of magnitude faster than some of the other available methods. Our networks showed an increased accuracy with the use of a conditional random field (CRF) as a post-processing step. We further validated both segmentation models, highlighting their robustness to images with lower resolution and signal-to-noise ratio, compared to tested techniques. The pipeline and models are available at: https://icvmapp3r.readthedocs.io and https://ventmapp3r.readthedocs.io to enable further investigation of the roles of ICV and ventricles in relation to normal aging and neurodegeneration in large multi-site studies.

neuroscience↗

An overview of the quality assurance and quality control of magnetic resonance imaging data for the Ontario Neurodegenerative Disease Research Initiative (ONDRI): pipeline development and neuroinformatics

Large scale research studies combining magnetic resonance imaging data generated at multiple sites on multiple vendor platforms are becoming more commonplace. The Ontario Neurodegenerative Disease Research Initiative (ONDRI - http://ondri.ca/), a project funded by the Ontario Brain Institute (OBI), is a recently established province-wide natural history study, which has recruited more than 500 participants from neurodegenerative disease groups including amyotrophic lateral sclerosis, fronto-temporal dementia, Parkinsons disease, Alzheimers disease, mild cognitive impairment, and cerebrovascular disease (previously referred to as the vascular cognitive impairment cohort). Because of its multi-site nature, all captured data must be standardized and meet minimum quality standards to reduce variability. The goal of the ONDRI imaging platform is to maximize data quality by implementing vendor-specific harmonized MR imaging protocols (consistent with the Canadi-an Dementia Imaging Protocol - http://www.cdip-pcid.ca/), monitoring protocol adherence, qualitatively assessing image quality, measuring signal-to-noise and contrast-to-noise, monitoring system stability, and applying corrections based on the analysis of images from two different phantoms regularly acquired at each site. To maximize image quality, this work describes the use of various automatic pipelines and manual assessment steps, integrated within an established informatics and databasing platform, the Stroke Patient Recovery Research Database (SPReD) built on the Extensible Neuroimaging Archive Toolkit (XNAT), and contained within the Brain-CODE (Centre for Ontario Data Exploration) framework. The purpose of the current paper is to describe the steps undertaken by ONDRI to achieve this high standard of data integrity. Data have been successfully collected for the past 4 years with the pipelines and assessments identifying deviations, allowing for timely interventions and assessment of image quality.

neuroscience↗

Ontario Neurodegenerative Disease Research Initiative (ONDRI): Structural MRI methods & outcome measures

The Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 year multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimers disease, mild cognitive impairment, Parkinsons disease, amyotrophic lateral sclerosis, frontotemporal dementia, and cerebrovascular disease patients. This heterogeneous cross-section of patients with complex neurodegenerative and neurovascular pathologies pose significant challenges for standard neuroimaging tools. To effectively quantify regional measures of normal and pathological brain tissue volumes, the ONDRI neuroimaging platform implemented a semi-automated MRI processing pipeline that was able to address many of the challenges resulting from this heterogeneity. This paper describes the comprehensive neuroimaging pipeline methods used to generate regional brain tissue volumes & neurovascular markers.

neuroscience↗