arXiv subjects

Murat Bilgel

Publications and source records attributed to Murat Bilgel.

8 recordsLinked to original sources

arXiv2026

GenFAR: A generalized representation of brain structure, derived from 49,246 multi-cohort MRIs via deep learning

Deep learning models for neuroimaging have largely been developed for individual tasks, limiting knowledge transfer across applications. Here we introduce GenFAR, a modular deep learning framework that learns general, clinically informed features from brain MRIs. We trained this modular architecture on 49,246 individuals across 11 cohorts, using 17 diverse classification and regression tasks spanning cognition, clinical, diagnosis, demographics, and biomarkers. This yields aggregated, focused feature sets that capture rich, clinically- and biologically-relevant brain representations. We developed a sequential learning approach where tasks progressively build on previously learned representations. Through an analysis of 5,000 task sequences, we identified an optimal sequence length of six tasks and introduced a Donor Score metric to quantify each task's contribution to downstream performance. This analysis revealed five consistently strong donor tasks (Age, AD/MCI, MMSE, Hypertension, Hyperlipidemia) that formed the base of our sequential model. We demonstrated the utility of our learned representation, in various tasks beyond those included in the training set, to serve as the foundation for specialized secondary predictors. We further showed that using the learned feature representation can substantially increase the sample efficiency of secondary deep learning training tasks and models, as well as improve their accuracy.

cs.CV↗

arXiv2026

Harmonizing MR Images Across 100+ Scanners: Multi-site Validation with Traveling Subjects and Real-world Protocols

Reliable harmonization of heterogeneous magnetic resonance~(MR) image datasets, especially those acquired in pragmatic clinical trials, is critical to advance multi-center neuroimaging studies and translational machine learning in healthcare. We present an enhanced and rigorously validated version of the HACA3 harmonization algorithm, which we refer to as HACA3$^+$, incorporating key methodological enhancements: (1)~an improved artifact encoder to better isolate and mitigate image artifacts, (2)~background and foreground-sensitive attention mechanisms to increase harmonization specificity, and (3)~extensive training using data spanning 100+ scanners from 64 independent sites, providing a broader diversity of scanners than other harmonization methods. Our study focuses on four commonly acquired MR image contrasts (T1-weighted, T2-weighted, proton density, \& fluid-attenuated inversion recovery), reflecting realistic clinical protocols. We perform inter-site harmonization experiments using traveling subjects to assess the generalization and robustness of the harmonization model. We compare the results of the publicly available version of HACA3 and our implementation, HACA3$^+$. Downstream relevance is further established through whole brain segmentation and image imputation. Finally, we justify each enhancement through an ablation experiment. Pre-trained weights and code for HACA3$^+$ are made publicly available at https://github.com/shays15/haca3-plus.

eess.IV↗

arXiv2026

Unsupervised learning of acquisition variability in structural connectomes via hybrid latent space modeling

Acquisition differences across sites, scanners, and protocols in dMRI introduce variability that complicates structural connectome analysis. This motivates deep learning models that can represent high-dimensional connectomes in a low-dimensional space while explicitly separating acquisition-related effects from biological variation. Conventional dimensionality reduction methods model all variance as continuous, so acquisition effects often get absorbed into a continuous latent space. Recent hybrid latent-space models combine discrete and continuous components to address this, but typically require manual capacity tuning to ensure the discrete component captures the intended variability. We introduce an unsupervised framework that removes this manual tuning by architecturally annealing encoder outputs before decoding, allowing the model to adaptively balance discrete and continuous latent variables during training. To evaluate it, we curated a dataset of N=7,416 structural connectomes derived from dMRI, spanning ages 2 to 102 and 13 studies with 25 unique acquisition-parameter combinations. Of these, 5,900 are cognitively unimpaired, 877 have mild cognitive impairment (MCI), and 639 have Alzheimer's disease (AD). We compare against a standard VAE, PCA with k-means clustering, and hybrid models that anneal only through the loss function. Our architectural annealing produces stronger site learning (ARI=0.53, p<0.05) than these baselines. Results show that a hybrid continuous-discrete latent space, with architectural rather than loss-based annealing, provides a useful unsupervised mechanism for capturing acquisition variability in dMRI: by jointly modeling smooth and categorical structure, the Joint-VAE recovers clusters aligned with scanner and protocol differences.

cs.LG↗

arXiv2023

HACA3: A Unified Approach for Multi-site MR Image Harmonization

The lack of standardization is a prominent issue in magnetic resonance (MR) imaging. This often causes undesired contrast variations in the acquired images due to differences in hardware and acquisition parameters. In recent years, image synthesis-based MR harmonization with disentanglement has been proposed to compensate for the undesired contrast variations. Despite the success of existing methods, we argue that three major improvements can be made. First, most existing methods are built upon the assumption that multi-contrast MR images of the same subject share the same anatomy. This assumption is questionable, since different MR contrasts are specialized to highlight different anatomical features. Second, these methods often require a fixed set of MR contrasts for training (e.g., both T1-weighted and T2-weighted images), limiting their applicability. Lastly, existing methods are generally sensitive to imaging artifacts. In this paper, we present Harmonization with Attention-based Contrast, Anatomy, and Artifact Awareness (HACA3), a novel approach to address these three issues. HACA3 incorporates an anatomy fusion module that accounts for the inherent anatomical differences between MR contrasts. Furthermore, HACA3 is also robust to imaging artifacts and can be trained and applied to any set of MR contrasts. HACA3 is developed and evaluated on diverse MR datasets acquired from 21 sites with varying field strengths, scanner platforms, and acquisition protocols. Experiments show that HACA3 achieves state-of-the-art performance under multiple image quality metrics. We also demonstrate the applicability and versatility of HACA3 on downstream tasks including white matter lesion segmentation and longitudinal volumetric analyses.

eess.IV↗

arXiv2022

Disentangling A Single MR Modality

Disentangling anatomical and contrast information from medical images has gained attention recently, demonstrating benefits for various image analysis tasks. Current methods learn disentangled representations using either paired multi-modal images with the same underlying anatomy or auxiliary labels (e.g., manual delineations) to provide inductive bias for disentanglement. However, these requirements could significantly increase the time and cost in data collection and limit the applicability of these methods when such data are not available. Moreover, these methods generally do not guarantee disentanglement. In this paper, we present a novel framework that learns theoretically and practically superior disentanglement from single modality magnetic resonance images. Moreover, we propose a new information-based metric to quantitatively evaluate disentanglement. Comparisons over existing disentangling methods demonstrate that the proposed method achieves superior performance in both disentanglement and cross-domain image-to-image translation tasks.

eess.IV↗

arXiv2021

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

q-bio.PE↗

arXiv2021

Disentangling Alzheimer's disease neurodegeneration from typical brain aging using machine learning

Neuroimaging biomarkers that distinguish between typical brain aging and Alzheimer's disease (AD) are valuable for determining how much each contributes to cognitive decline. Machine learning models can derive multi-variate brain change patterns related to the two processes, including the SPARE-AD (Spatial Patterns of Atrophy for Recognition of Alzheimer's Disease) and SPARE-BA (of Brain Aging) investigated herein. However, substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology toward disentangling the two. T1-weighted MRI images of 4,054 participants (48-95 years) with AD, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the iSTAGING (Imaging-based coordinate SysTem for AGIng and NeurodeGenerative diseases) consortium were analyzed. First, a subset of AD patients and CN adults were selected based purely on clinical diagnoses to train SPARE-BA1 (regression of age using CN individuals) and SPARE-AD1 (classification of CN versus AD). Second, analogous groups were selected based on clinical and molecular markers to train SPARE-BA2 and SPARE-AD2: amyloid-positive (A+) AD continuum group (consisting of A+AD, A+MCI, and A+ and tau-positive CN individuals) and amyloid-negative (A-) CN group. Finally, the combined group of the AD continuum and A-/CN individuals was used to train SPARE-BA3, with the intention to estimate brain age regardless of AD-related brain changes. Disentangled SPARE models derived brain patterns that were more specific to the two types of the brain changes. Correlation between the SPARE-BA and SPARE-AD was significantly reduced. Correlation of disentangled SPARE-AD was non-inferior to the molecular measurements and to the number of APOE4 alleles, but was less to AD-related psychometric test scores, suggesting contribution of advanced brain aging to these scores.

cs.LG↗

arXiv2016

A multivariate nonlinear mixed effects model for longitudinal image analysis: Application to amyloid imaging

It is important to characterize the temporal trajectories of disease-related biomarkers in order to monitor progression and identify potential points of intervention. This is especially important for neurodegenerative diseases, as therapeutic intervention is most likely to be effective in the preclinical disease stages prior to significant neuronal damage. Longitudinal neuroimaging allows for the measurement of structural, functional, and metabolic integrity of the brain over time at the level of voxels. However, commonly used longitudinal analysis approaches, such as linear mixed effects models, do not account for the fact that individuals enter a study at various disease stages and progress at different rates, and generally consider each voxelwise measure independently. We propose a multivariate nonlinear mixed effects model for estimating the trajectories of voxelwise neuroimaging biomarkers from longitudinal data that accounts for such differences across individuals. The method involves the prediction of a progression score for each visit based on a collective analysis of voxelwise biomarker data within an expectation-maximization framework that efficiently handles large amounts of measurements and variable number of visits per individual, and accounts for spatial correlations among voxels. This score allows individuals with similar progressions to be aligned and analyzed together, which enables the construction of a trajectory of brain changes as a function of an underlying progression or disease stage. Application of our method to studying images of beta-amyloid deposition, a hallmark of preclinical Alzheimer's disease, suggests that precuneus is the earliest cortical region to accumulate amyloid. The proposed method can be applied to other types of longitudinal imaging data, including metabolism, blood flow, tau, and structural imaging-derived measures.

stat.ME↗