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Fonov, V.

Publications and source records attributed to Fonov, V..

17 recordsLinked to original sources

Brain Age Prediction: Deep Models Need a Hand to Generalize

Predicting brain age from T1-weighted MRI is a promising marker for understanding brain aging and its associated conditions. While deep learning models have shown success in reducing the Mean Absolute Error (MAE) of predicted brain age, concerns about robust and accurate generalization in new data limit their clinical applicability. The large number of trainable parameters, combined with limited medical imaging training data, contribute to this challenge, often resulting in a generalization gap where there is a significant discrepancy between model performance on training data versus unseen data. In this study, we assess a deep model, SFCN-reg, based on the VGG-16 architecture, and address the generalization gap through comprehensive preprocessing, extensive data augmentation, and model regularization. Using training data from the UK Biobank, we demonstrate substantial improvements in model performance. Specifically, our approach reduces the generalization MAE by 44% (from 5.25 to 2.96 years) in the Alzheimers Disease Neuroimaging Initiative dataset and by 22% (from 4.35 to 3.40 years) in the Australian Imaging, Biomarker and Lifestyle dataset. Furthermore, we achieve a 29% reduction in scan-rescan error (from 0.86 to 0.61 years) while enhancing the models robustness to registration errors. Feature importance maps highlight anatomical regions used to predict age. These results highlight the critical role of high-quality preprocessing and robust training techniques in improving accuracy and narrowing the generalization gap, both necessary steps towards the clinical use of brain age prediction models. Our study makes valuable contributions to neuroimaging research by offering a potential pathway to improve the clinical applicability of deep learning models.

neuroscience↗

Automatization and validation of the hippocampal-to-ventricle ratio in a clinical sample

BackgroundThe hippocampal-to-ventricle ratio (HVR) is a biomarker of medial temporal atrophy, particularly useful in the assessment of neurodegeneration in diseases such as Alzheimers disease (AD). To minimize subjectivity and inter-rater variability, an automated, accurate, precise, and reliable segmentation technique for the hippocampus (HC) and surrounding cerebro-spinal fluid (CSF) filled spaces -- such as the temporal horns of the lateral ventricles -- is essential. MethodsWe trained and evaluated three automated methods for the segmentation of both HC and CSF (Multi-Atlas Label Fusion (MALF), Nonlinear Patch-Based Segmentation (NLPB), and a Convolutional Neural Network (CNN)). We then evaluated these methods, including the widely used FreeSurfer technique, using baseline T1w MRIs of 1,641 participants from the AD Neuroimaging Initiative study with various degree of atrophy associated with their cognitive status on the spectrum from cognitively healthy to clinically probable AD. Our gold standard consisted in manual segmentation of HC and CSF from 80 cognitively healthy individuals. We calculated HC volumes and HVR and compared all methods in terms of segmentation reliability, similarity across methods, sensitivity in detecting between-group differences and associations with age, scores of the learning subtest of the Rey Auditory Verbal Learning Test (RAVLT) and the Alzheimers Disease Assessment Scale 13 (ADAS13) scores. ResultsCross validation demonstrated that the CNN method yielded more accurate HC and CSF segmentations when compared to MALF and NLPB, demonstrating higher volumetric overlap (Dice Kappa = 0.94) and correlation (rho = 0.99) with the manual labels. It was also the most reliable method in clinical data application, showing minimal failures. Our comparisons yielded high correlations between FreeSurfer, CNN and NLPB volumetric values. HVR yielded higher control:AD effect sizes than HC volumes among all segmentation methods, reinforcing the significance of HVR in clinical distinction. AssociationsThe positive association with age was significantly stronger for HVR compared to HC volumes on all methods except FreeSurfer. Memory associations with HC volumes or HVR were only significant for individuals with mild cognitive impairment. Finally, the HC volumes and HVR showed comparable negative associations with ADAS13, particularly in the mild cognitive impairment cohort. ConclusionThis study provides an evaluation of automated segmentation methods centered to estimate HVR, emphasizing the superior performance of a CNN-based algorithm. The findings underscore the pivotal role of accurate segmentation in HVR calculations for precise clinical applications, contributing valuable insights into medial temporal lobe atrophy in neurodegenerative disorders, especially AD. AuthorshipO_LISofia Fernandez-Lozano: Conceptualization, Methodology, Software, Investigation, Writing - Original Draft, Visualization. C_LIO_LIVladimir Fonov: Software, Data Curation. C_LIO_LIDorothee Schoemaker: Resources, Writing - Review & Editing. C_LIO_LIJens Pruessner: Resources, Writing - Review & Editing. C_LIO_LIOlivier Potvin: Resources, Writing - Review & Editing. C_LIO_LISimon Duchesne: Resources, Writing - Review & Editing. C_LIO_LID. Louis Collins: Conceptualization, Writing - Review & Editing, Supervision. C_LI

neuroscience↗

The FinnBrain Multimodal Neonatal Template and Atlas Collection: T1, T2, and DTI brain templates, and accompanying cortical and subcortical atlases

The accurate processing of neonatal and infant brain MRI data is crucially important for developmental neuroscience, but presents challenges that child and adult data do not. Tissue segmentation and image coregistration accuracy can be improved by optimizing template images and / or related segmentation procedures. Here, we describe the construction of the FinnBrain Neonate (FBN-125) template; a multi-contrast template with T1- and T2-weighted as well as diffusion tensor imaging derived fractional anisotropy and mean diffusivity images. The template is symmetric and aligned to the Talairach-like MNI 152 template and has high spatial resolution (0.5 mm3). In addition, we provide atlas labels, constructed from manual segmentations, for cortical grey matter, white matter, cerebrospinal fluid, brainstem, and cerebellum as well as the bilateral hippocampi, amygdalae, caudate nuclei, putamina, globi pallidi, and thalami. We provide this multi-contrast template along with the labelled atlases for the use of the neuroscience community in the hope that it will prove useful in advancing developmental neuroscience, for example, by helping to achieve reliable means for spatial normalization and measures of neonate brain structure via automated computational methods. Additionally, we provide standard co-registration files that will enable investigators to reliably transform their statistical maps to the adult MNI space, which has the potential to improve the consistency and comparability of neonatal studies or the use of adult MNI space atlases in neonatal neuroimaging.

neuroscience↗

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↗

DARQ: Deep learning of quality control for stereotaxic registration of human brain MRI

Linear registration to stereotaxic space is a common first step in many automated image-processing tools for analysis of human brain MRI scans. This step is crucial for the success of the subsequent image-processing steps. Several well-established algorithms are commonly used in the field of neuroimaging for this task, but none have a 100% success rate. Manual assessment of the registration is commonly used as part of quality control. To reduce the burden of this time-consuming step, we propose Deep Automated Registration Qc (DARQ), a fully automatic quality control method based on deep learning that can replace the human rater and accurately perform quality control assessment for stereotaxic registration of T1w brain scans. In a recently published study from our group comparing linear registration methods, we used a database of 9325 MRI scans and 64476 registrations from several publicly available datasets and applied seven linear registration tools to them. In this study, the resulting images that were assessed and labeled by a human rater are used to train a deep neural network to detect cases when registration failed. We further validated the results on an independent dataset of patients with multiple sclerosis, with manual QC labels available (n=1200). In terms of agreement with a manual rater, our automated QC method was able to achieve 89%accuracy and 85% true negative rate (equivalently 15% false positive rate) in detecting scans that should pass quality control in a balanced cross-validation experiments, and 96.1% accuracy and 95.5% true negative rate (or 4.5% FPR) when evaluated in a balanced independent sample, similar to manual QC rater (test-retest accuracy of 93%). The results show that DARQ is robust, fast, accurate, and generalizable in detecting failure in linear stereotaxic registrations and can substantially reduce QC time (by a factor of 20 or more) when processing large datasets.

neuroscience↗

CerebrA: Accurate registration and manual label correction of Mindboggle-101 atlas for MNI-ICBM152 template

Accurate anatomical atlases are recognized as important tools in brain-imaging research. They are widely used to estimate disease-specific changes and therefore, are of great relevance in extracting regional information on volumetric variations in clinical cohorts in comparison to healthy populations. The use of high spatial resolution magnetic resonance imaging and the improvement in data preprocessing methods have enabled the study of structural volume changes on a wide range of disorders, particularly in neurodegenerative diseases where different brain morphometry analyses are being broadly used in an effort to improve diagnostic biomarkers. In the present dataset, we introduce the Cerebrum Atlas (CerebrA) along with the MNI-ICBM2009c average template. MNI-ICBM2009c is the most recent version of the MNI-ICBM152 brain average, providing a higher level of anatomical details. Cerebra is based on an accurate non-linear registration of cortical and subcortical labelling from Mindboggle 101 to the symmetric MNI-ICBM2009c atlas, followed by manual editing.

neuroscience↗

Unsupervised domain adaptation for the automated segmentation of neuroanatomy in MRI: a deep learning approach

Neuroanatomical segmentation in T1-weighted magnetic resonance imaging of the brain is a prerequisite for quantitative morphological measurements, as well as an essential element in general pre-processing pipelines. While recent fully automated segmentation methods based on convolutional neural networks have shown great potential, these methods nonetheless suffer from severe performance degradation when there are mismatches between training (source) and testing (target) domains (e.g. due to different scanner acquisition protocols or due to anatomical differences in the respective populations under study). This work introduces a new method for unsupervised domain adaptation which improves performance in challenging cross-domain applications without requiring any additional annotations on the target domain. Using a previously validated state-of-the-art segmentation method based on a context-augmented convolutional neural network, we first demonstrate that networks with better domain generalizability can be trained using extensive data augmentation with label-preserving transformations which mimic differences between domains. Second, we incorporate unlabelled target domain samples into training using a self-ensembling approach, demonstrating further performance gains, and further diminishing the performance gap in comparison to fully-supervised training on the target domain.

bioinformatics↗

Disruption of Capn15 in mice leads to brain and eye deficits

The Small Optic Lobe (SOL) family of calpains are intracellular cysteine proteases that are expressed in the nervous system and play an important role in neuronal development in both Drosophila, where loss of this calpain leads to the eponymous small optic lobes, and in mouse and human, where loss of this calpain leads to eye anomalies. Some human individuals with biallelic variants in CAPN15 also have developmental delay and autism. However, neither the specific effect of the loss of the Capn15 protein on brain development nor the brain regions where this calpain is expressed in the adult is known. Here we show using small animal MRI that mice with the complete loss of Capn15 have smaller brains overall with larger decreases in the thalamus and subregions of the hippocampus. These losses are not seen in Capn15 conditional KO mice where Capn15 is knocked out only in excitatory neurons in the adult. Based on {beta}-galactosidase expression in an insert strain where lacZ is expressed under the control of the Capn15 promoter, we show that Capn15 is expressed in adult mice, particularly in neurons involved in plasticity such as the hippocampus, lateral amygdala and Purkinje neurons, and partially in other non-characterized cell types. The regions of the brain in the adult where Capn15 is expressed do not correspond well to the regions of the brain most affected by the complete knockout suggesting distinct roles of Capn15 in brain development and adult brain function.

neuroscience↗

MRI and cognitive scores complement each other to accurately predict Alzheimer’s dementia 2 to 7 years before clinical onset

BackgroundPredicting cognitive decline and the eventual onset of dementia in patients with Mild Cognitive Impairment (MCI) is of high value for patient management and potential cohort enrichment in pharmaceutical trials. We used cognitive scores and MRI biomarkers from a single baseline visit to predict the onset of dementia in an MCI population over a nine-year follow-up period.\n\nMethodAll MCI subjects from ADNI1, ADNI2, and ADNI-GO with available baseline cognitive scores and T1w MRI were included in the study (n=756). We built a Naive Bayes classifier for every year over a 9-year follow-up period and tested each one with Leave one out cross validation.\n\nResultsWe reached 87% prediction accuracy at five years follow-up with an AUC>0.85 from two to seven years (peaking at 0.92 at five years). Both cognitive test scores and MR biomarkers were needed to make the prognostic models highly sensitive and specific, especially for longer follow-ups. MRI features are more sensitive, while cognitive features bring specificity to the prediction.\n\nConclusionCombining cognitive scores and MR biomarkers yield accurate prediction years before onset of dementia. Such a tool may be helpful in selecting patients that would most benefit from lifestyle changes, and eventually early treatments that would slow cognitive decline and delay the onset of dementia.

neuroscience↗

SNIPE score can capture prodromal Alzheimer's in cognitively normal subjects

Capturing early changes in the brain related to Alzheimers disease may lead to models that successfully predict cognitive decline and the eventual onset of dementia, well ahead of onset of clinical symptoms. In this study we used both hippocampal volume and our hippocampal driven SNIPE score to show which marker better captures Alzheimers related changes in a large dataset of normal controls (N=515) from the ADNI study, comparing controls that remain cognitively stable and controls that progress to either MCI or Alzheimers dementia during 10 years of follow-up (median follow-up: 30 months). We measured hippocampal volume and SNIPE score and found that the effect size to differentiate between stable and progressor groups was significantly larger for SNIPE score than for volume. Our results also show that there is a significant age-related difference between groups for both markers, and the difference is greater with the SNIPE score. Our experiments show that considering high sensitivity of our SNIPE score regarding to early AD-related brain changes, this marker is a better candidate in comparison to hippocampal volume for predicting the future onset of dementia.

neuroscience↗

Unbiased Age-Appropriate Structural Brain Atlases for Chinese Pediatrics

In magnetic resonance imaging (MRI) studies of children brain development, structural brain atlases usually serve as important references of pediatric population in which individual images are spatially normalized into a common or standard stereotactic space. However, the existing popular children brain atlases (e.g., National Institutes of Health pediatric atlases, NIH-PD atlases) are made mostly based on MR images from Western populations, and are thus insufficient to characterize the brains of Chinese children due to the neuroanatomical differences that are relevant to genetic and environmental factors. By collecting high-quality T1- and T2- weighted MR images from 328 typically developing Chinese children aged from 6 to 12 years old, we created a set of age-appropriate Chinese pediatric (CHN-PD) atlases using an unbiased template construction algorithm. The CHN-PD atlases included the head/brain templates, the symmetric brain template, the gender-specific brain templates and the corresponding tissue probability atlases. Moreover, the atlases contained multiple age-specific templates with a one-year interval. A direct comparison of the CHN-PD and the NIH-PD atlases revealed remarkable anatomical differences bilaterally in the lateral frontal and parietal regions and somatosensory cortex. While applying the CHN-PD atlases to two independent Chinese pediatric datasets (N = 114 and N = 71, respectively), machine-learning regression approaches revealed higher prediction accuracy on brain ages than the usage of NIH-PD atlases. These results suggest that the CHN-PD brain atlases are necessary and important for future typical and atypical developmental studies in Chinese pediatric population. Currently, the CHN-PD atlases have been released on the NITRC website (https://www.nitrc.org/projects/chn-pd).

neuroscience↗

Deep learning of quality control for stereotaxic registration of human brain MRI

Linear registration to stereotaxic space is a common first step in many automated image-processing tools for analysis of human brain MRI scans. This step is crucial for the success of the following image-processing steps. Several well-established algorithms are commonly used in the field of neuroimaging for this task, but none of them has a 100% success rate. Manual assessment of the registration is commonly used as part of quality control.\n\nWe propose a completely automatic quality control method based on deep learning that replaces human rater and accurately performs quality control assessment for stereotaxic registration of T1w brain scans.\n\nIn a recently published study from our group comparing linear registration methods, we used a database of 9693 MRI scans from several publically available datasets and applied five linear registration tools. In this study, the resulting images that were assessed and labeled by a human rater are used to train a deep neural network to detect cases when registration failed.\n\nOur method was able to achieve 88% accuracy and 11% false positive rate in detecting scans that should pass quality control, better than a manual QC rater.

neuroscience↗

NeuroMTL iSEG challenge methods

We propose a tissue classification method for MRI scans of 6-month old infants, and used it to process the iSeg-2017 challenge data. The method relies on a deep-learning 3D U-Net network, trained with MRI scans of 216 infants, aged 6-24 months, from the ACE-IBIS longitudinal database.

neuroscience↗

Comparison of different methods for average anatomical templates creation: do we really gain anything from a diffeomorphic framework?

In the field of computation anatomy, the diffeomorphic framework is widely used to perform analysis of human brain anatomy in both healthy and diseased populations. While useful for analysis, the framework imposes certain implementation constraints that do not necessarily result in improved accuracy of inter-subject co-registration in case of average anatomical template (AAT) construction - a common technique used in large population studies. In this work, we evaluated several state-of-the-art non-diffeomorphic and diffeomorphic non-linear registration frameworks in terms of their ability to build AATs. While all methods generated well behaved transforms, we found that the diffeomorphic framework does not automatically guarantee an increase of accuracy in average anatomical template construction.

neuroscience↗

Voxel-wise T2 relaxometry of Normal Pediatric Brain Development in 326 healthy infants and toddlers.

Quantitative T2 data from an NIH-sponsored multi-center study of Normal Brain Development was used to perform automatic voxel-wise analysis of the changes in T2 evolution in the brain in healthy children within the age range from birth to 5 years. All data were non-linearly registered into a common coordinate space. The T2 parameters were estimated by 2 point fitting from the PD-weighted and T2-weighted image data, or by least-squares fitting of 4 data points when addition intermediate weighting images were available. The main result of this study is voxel-level map of monoexponential evolution of T2 in this age range indicating the delay (in months) and the rate (in 1/months) of development. The automatic maps are compared to manual region-of-interest based estimates of T2 evolution.

neuroscience↗

BIC Defacing Algorithm

Public distribution of imaging information from several MRI data processing projects at the BIC has lead to the development of this DEFACING algorithm that is used as part of anonymisation process. Key features of the algorithm include: the defacing should modify voxels associated with face of the subject, making a rendering of the face unrecognisable, it should work on data in the native scanner space and it should not significantly affect subsequent data processing outcome (model based registration, brain extraction, brain tissue classification and brain segmentation). The algorithm is implemented using the MINC library and source code is publicly available. The effect of the defacing algorithm on the data processing was verified using the ICBM database of 152 scans of young adults.

neuroscience↗

Network Connectivity Predicts Cortical Thinning and Cognitive Decline in Early Parkinson’s Disease

Parkinsons Disease (PD) is a progressive neurodegenerative disorder characterized by motor and cognitive deficits. The neurodegenerative process is thought to move stereotypically from the brainstem up to the cerebral cortex, possibly reflecting the spread of toxic alpha-synuclein molecules. Using a large, longitudinal, multi-center database of de novo PD patients, we tested whether focal reductions in cortical thickness could be explained by disease spread from a subcortical \"disease reservoir\" along the brains connectome. PD patients (n=105) and matched controls (n=57) underwent T1-MRI at entry and one year later. Over this period, PD patients demonstrated significantly greater loss of cortical thickness than healthy controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical regions with greater connectivity (measured functionally or structurally) to a \"disease reservoir\" evaluated via MRI at baseline demonstrated greater atrophy one year later. The atrophy pattern in the ventral frontal lobes resembled one described in certain cases of Alzheimers disease. Moreover, a multiple linear regression model suggested that cortical thinning was associated with impaired cognitive function at follow-up. Our findings suggest that disease propagation to the cortex in PD follows neural connectivity, and that disease spread to the cortex may herald the onset of cognitive impairment.

neuroscience↗