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Manera, A.

Publications and source records attributed to Manera, A..

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QRATER: a collaborative and centralized imaging quality control web-based application.

Quality control (QC) is an important part of all scientific analysis, including neuroscience. With manual curation considered the gold standard, there remains a lack of available tools that make manual neuroimaging QC accessible, fast, and easy. In this article we present Qrater, a containerized web-based python application that enables viewing and rating of previously generated QC images. A group of raters with varying amounts of experience in QC evaluated Qrater in three different tasks: QC of MRI raw acquisition (10,196 images), QC of non-linear registration to a standard template (10,196 images) and QC of skull segmentation (6,968 images). We measured the proportion of failed images, timing and intra- and inter-rater agreement. Raters spent vastly different amounts of time on each image depending on their experience and the task at hand. QC of MRI raw acquisition was the slowest. While an expert rater needed approximately one minute, trained raters spent 2-6 minutes evaluating an image. The fastest was the curation of a skull segmentation image, where expert raters spent on average 3 seconds per image before assigning a rating. Rating agreement also varied depending on the experience of the raters and the task at hand: trained raters inter-rater agreement with the experts gold standard ranged from fair to substantial in raw acquisition (Cohens chance corrected kappa agreement scores up to 0.72) and from fair to excellent in linear registration (kappa scores up to 0.82), while the experts inter-rater agreement of the skull segmentation task was excellent (kappa = 0.83). These results demonstrate that Qrater is a useful asset for QC tasks that rely on manual curation of images.

bioinformatics↗

White Matter Hyperintensities, Grey Matter Atrophy, and Cognitive Decline in Neurodegenerative Diseases

IntroductionWhite matter hyperintensities (WMHs) as seen on T2w and FLAIR scans represent small-vessel disease related changes in the brain. WMHs are associated with cognitive decline in the normal aging population in general and more specifically in patients with neurodegenerative diseases. In this study, we assessed the different spatial patterns and relationships between WMHs and grey matter (GM) atrophy in normal aging, individuals with mild cognitive impairment (MCI), Alzheimers dementia (AD), fronto-temporal dementia (FTD), and de novo Parkinsons disease (PD). MethodsImaging and clinical data were obtained from 3 large multi-center databases: The Alzheimers Disease Neuroimaging Initiative (ADNI), the frontotemporal lobar degeneration neuroimaging initiative (NIFD), and the Parkinsons Progression Markers Initiative (PPMI). WMHs and GM atrophy maps were measured in normal controls (N= 571), MCI (N= 577), AD (N= 222), FTD (N= 144), and PD (N= 363). WMHs were segmented using T1w and T2w/PD or FLAIR images and mapped onto 45 white matter tracts using the Yeh WM atlas. GM volume was estimated from the Jacobian determinant of the nonlinear deformation field required to map the subjects MRI to a standard template. The CerebrA atlas was used to obtain volume estimates in 84 GM regions. Mixed effects models were used to compare WMH in different WM tracts and volume of multiple GM structures between patients and controls, assess the relationship between regional WMHs and GM loss for each disease, and investigate their impact on cognition. ResultsMCI, AD, and FTD patients had significantly higher WMH loads than the matched controls. There was no significant difference in WMHs between PD and controls. For each cohort, significant interactions between WMH load and GM atrophy were found for several regions and tracts, reflecting additional contribution of WMH burden to GM atrophy. While these associations were more relevant for insular and parieto-occipital regions in MCI and AD cohorts, WMH burden in FTD subjects had greater impact on frontal and basal ganglia atrophy. Finally, we found additional contribution of WMH burden to cognitive deficits in AD and FTD subjects compared with matched controls, whereas their impact on cognitive performance in MCI and PD were not significantly different from controls. ConclusionsWMHs occur more extensively in MCI, AD, and FTD patients than age-matched normal controls. WMH burden on WM tracts also correlates with regional GM atrophy in regions anatomically and functionally related to those tracts, suggesting a potential involvement of WMHs in the neurodegenerative process.

neuroscience↗

MNI-FTD Templates: Unbiased Average Templates of Frontotemporal Dementia Variants

Standard anatomical templates are widely used in human neuroimaging processing pipelines to facilitate group level analyses and comparisons across different subjects and populations. The MNI-ICBM152 template is the most commonly used standard template, representing an average of 152 healthy young adult brains. However, in patients with neurodegenerative diseases such as frontotemporal dementia (FTD), the high levels of atrophy lead to significant differences between the brain shape of the individuals and the MNI-ICBM152 template. Such differences might inevitably lead to registration errors or subtle biases in downstream analyses and results. Disease-specific templates are therefore desirable to reflect the anatomical characteristics of the populations of interest and to reduce potential registration errors when processing data from such populations. Here, we present MNI-FTD136, MNI-bvFTD70, MNI-svFTD36, and MNI-pnfaFTD30, four unbiased average templates of 136 FTD patients, 70 behavioural variant (bv), 36 semantic variant (sv), and 30 progressive nonfluent aphasia (pnfa) variant FTD patients as well as a corresponding age matched average template of 133 healthy controls (MNI-CN133), along with probabilistic tissue maps for each template. The public availability of these templates will facilitate analyses of FTD cohorts and enable comparisons between different studies in a common standardized space appropriate to FTD populations.

neuroscience↗

Cerebral Atrophy in Amyotrophic Lateral Sclerosis Parallels the Pathological Distribution of TDP43

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a preferential involvement of both upper and lower motor neurons. Evidence from neuroimaging and post-mortem studies confirms additional involvement of brain regions extending beyond the motor cortex. The aim of this study was to assess the extent of cerebral disease in ALS cross-sectionally and longitudinally, and to compare the findings with a recently proposed disease-staging model of ALS pathology. Deformation-based morphometry (DBM) was used to identify the patterns of brain atrophy associated with ALS and to assess their relationship with clinical symptoms. Longitudinal T1-weighted MRI data and clinical measures were acquired at baseline, 4 months, and 8 months, from 66 ALS patients and 43 age-matched controls who participated in the Canadian ALS Neuroimaging Consortium (CALSNIC) study. Whole brain voxel-wise mixed-effects modelling analysis showed extensive atrophy patterns differentiating ALS patients from the normal controls. Cerebral atrophy was present in the motor cortex and corticospinal tract, involving both GM and WM, and to a lesser extent in non-motor regions. More specifically, the results showed significant bilateral atrophy in the motor cortex, the corticospinal tract including the internal capsule and brainstem, with an overall pattern of ventricular enlargement; along with significant progressive longitudinal atrophy in the precentral gyrus, frontal and parietal white matter, accompanied by ventricular and sulcal enlargement. Atrophy in the precentral gyrus was significantly associated with greater disability as quantified with the ALS Functional Rating Scale-Revised (ALSFRS-R) (p<0.0001). The pattern of atrophy observed using DBM was consistent with the Brettschneiders four stage pathological model of the disease. Deformation based morphometry provides a sensitive indicator of atrophy in ALS, and has potential as a biomarker of disease burden, in both gray and white matter.

neuroscience↗

Data-driven algorithm for the diagnosis of behavioral variant frontotemporal dementia

INTRODUCTIONBrain structural imaging is paramount for the diagnosis of behavioral variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. METHODSA total of 515 subjects from two different bvFTD databases (training and validation cohorts) were included to perform voxel-wise deformation-based morphometry analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from morphometric differences in isolation and together with bedside cognitive scores. RESULTSAverage ten-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In a separate validation cohort of genetically confirmed bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added cognitive scores. DISCUSSIONThe random forest classifier developed can accurately predict bvFTD at the individual subject level.

neuroscience↗