arXiv subjects

Aaron Carass

Publications and source records attributed to Aaron Carass.

At least 19 recordsLinked to original sources

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

Solving a Nonlinear Blind Inverse Problem for Tagged MRI with Physics and Deep Generative Priors

Tagged MRI enables tracking internal tissue motion non-invasively. It encodes motion by modulating anatomy with periodic tags, which deform along with tissue. However, the entanglement between anatomy, tags and motion poses significant challenges for post-processing. The existence of tags and imaging blur hinders downstream tasks such as segmenting anatomy. Tag fading, due to T1-relaxation, disrupts the brightness constancy assumption for motion tracking. For decades, these challenges have been handled in isolation and sub-optimally. In contrast, we introduce a blind and nonlinear inverse framework for tagged MRI that, for the first time, unifies these tasks: anatomical image recovery, high-resolution cine image synthesis, and motion estimation. At its core, the synergy of MR physics and generative priors enables us to blindly estimate the unknown forward imaging models and high-resolution underlying anatomy, while simultaneously tracking 3D diffeomorphic Lagrangian motion over time. Experiments on tagged brain MRI demonstrate that our approach yields high-resolution anatomy images, cine images, and more accurate motion than specialized methods.

eess.IV↗

arXiv2026

Likelihood-Separable Diffusion Inference for Multi-Image MRI Super-Resolution

Diffusion models are the current state-of-the-art for solving inverse problems in imaging. Their impressive generative capability allows them to approximate sampling from a prior distribution, which alongside a known likelihood function permits posterior sampling without retraining the model. While recent methods have made strides in advancing the accuracy of posterior sampling, the majority focuses on single-image inverse problems. However, for modalities such as magnetic resonance imaging (MRI), it is common to acquire multiple complementary measurements, each low-resolution along a different axis. In this work, we generalize common diffusion-based inverse single-image problem solvers for multi-image super-resolution (MISR) MRI. We show that the DPS likelihood correction allows an exactly-separable gradient decomposition across independently acquired measurements, enabling MISR without constructing a joint operator, modifying the diffusion model, or increasing network function evaluations. We derive MISR versions of DPS, DMAP, DPPS, and diffusion-based PnP/ADMM, and demonstrate substantial gains over SISR across $4\times/8\times/16\times$ anisotropic degradations. Our results achieve state-of-the-art super-resolution of anisotropic MRI volumes and, critically, enable reconstruction of near-isotropic anatomy from routine 2D multi-slice acquisitions, which are otherwise highly degraded in orthogonal views.

cs.CV↗

arXiv2025

Diffusion-Driven Generation of Minimally Preprocessed Brain MRI

The purpose of this study is to present and compare three denoising diffusion probabilistic models (DDPMs) that generate 3D $T_1$-weighted MRI human brain images. Three DDPMs were trained using 80,675 image volumes from 42,406 subjects spanning 38 publicly available brain MRI datasets. These images had approximately 1 mm isotropic resolution and were manually inspected by three human experts to exclude those with poor quality, field-of-view issues, and excessive pathology. The images were minimally preprocessed to preserve the visual variability of the data. Furthermore, to enable the DDPMs to produce images with natural orientation variations and inhomogeneity, the images were neither registered to a common coordinate system nor bias field corrected. Evaluations included segmentation, Frechet Inception Distance (FID), and qualitative inspection. Regarding results, all three DDPMs generated coherent MR brain volumes. The velocity and flow prediction models achieved lower FIDs than the sample prediction model. However, all three models had higher FIDs compared to real images across multiple cohorts. In a permutation experiment, the generated brain regional volume distributions differed statistically from real data. However, the velocity and flow prediction models had fewer statistically different volume distributions in the thalamus and putamen. In conclusion this work presents and releases the first 3D non-latent diffusion model for brain data without skullstripping or registration. Despite the negative results in statistical testing, the presented DDPMs are capable of generating high-resolution 3D $T_1$-weighted brain images. All model weights and corresponding inference code are publicly available at https://github.com/piksl-research/medforj .

eess.IV↗

arXiv2025

MSRepaint: Multiple Sclerosis Repaint with Conditional Denoising Diffusion Implicit Model for Bidirectional Lesion Filling and Synthesis

In multiple sclerosis, lesions interfere with automated magnetic resonance imaging analyses such as brain parcellation and deformable registration, while lesion segmentation models are hindered by the limited availability of annotated training data. To address both issues, we propose MSRepaint, a unified diffusion-based generative model for bidirectional lesion filling and synthesis that restores anatomical continuity for downstream analyses and augments segmentation through realistic data generation. MSRepaint conditions on spatial lesion masks for voxel-level control, incorporates contrast dropout to handle missing inputs, integrates a repainting mechanism to preserve surrounding anatomy during lesion filling and synthesis, and employs a multi-view DDIM inversion and fusion pipeline for 3D consistency with fast inference. Extensive evaluations demonstrate the effectiveness of MSRepaint across multiple tasks. For lesion filling, we evaluate both the accuracy within the filled regions and the impact on downstream tasks including brain parcellation and deformable registration. MSRepaint outperforms the traditional lesion filling methods FSL and NiftySeg, and achieves accuracy on par with FastSurfer-LIT, a recent diffusion model-based inpainting method, while offering over 20 times faster inference. For lesion synthesis, state-of-the-art MS lesion segmentation models trained on MSRepaint-synthesized data outperform those trained on CarveMix-synthesized data or real ISBI challenge training data across multiple benchmarks, including the MICCAI 2016 and UMCL datasets. Additionally, we demonstrate that MSRepaint's unified bidirectional filling and synthesis capability, with full spatial control over lesion appearance, enables high-fidelity simulation of lesion evolution in longitudinal MS progression.

eess.IV↗

arXiv2025

Surrogate Supervision for Robust and Generalizable Deformable Image Registration

Objective: Deep learning-based deformable image registration has achieved strong accuracy, but remains sensitive to variations in input image characteristics such as artifacts, field-of-view mismatch, or modality difference. We aim to develop a general training paradigm that improves the robustness and generalizability of registration networks. Methods: We introduce surrogate supervision, which decouples the input domain from the supervision domain by applying estimated spatial transformations to surrogate images. This allows training on heterogeneous inputs while ensuring supervision is computed in domains where similarity is well defined. We evaluate the framework through three representative applications: artifact-robust brain MR registration, mask-agnostic lung CT registration, and multi-modal MR registration. Results: Across tasks, surrogate supervision demonstrated strong resilience to input variations including inhomogeneity field, inconsistent field-of-view, and modality differences, while maintaining high performance on well-curated data. Conclusions: Surrogate supervision provides a principled framework for training robust and generalizable deep learning-based registration models without increasing complexity. Significance: Surrogate supervision offers a practical pathway to more robust and generalizable medical image registration, enabling broader applicability in diverse biomedical imaging scenarios.

cs.CV↗

arXiv2025

Learn2Reg 2024: New Benchmark Datasets Driving Progress on New Challenges

Medical image registration is critical for clinical applications, and fair benchmarking of different methods is essential for monitoring ongoing progress in the field. To date, the Learn2Reg 2020-2023 challenges have released several complementary datasets and established metrics for evaluations. Building on this foundation, the 2024 edition expands the challenge's scope to cover a wider range of registration scenarios, particularly in terms of modality diversity and task complexity, by introducing three new tasks, including large-scale multi-modal registration and unsupervised inter-subject brain registration, as well as the first microscopy-focused benchmark within Learn2Reg. The new datasets also inspired new method developments, including invertibility constraints, pyramid features, keypoints alignment and instance optimisation. Visit Learn2Reg at https://learn2reg.grand-challenge.org.

eess.IV↗

arXiv2025

The Brain Resection Multimodal Image Registration (ReMIND2Reg) 2025 Challenge

Accurate intraoperative image guidance is critical for achieving maximal safe resection in brain tumor surgery, yet neuronavigation systems based on preoperative MRI lose accuracy during the procedure due to brain shift. Aligning post-resection intraoperative ultrasound (iUS) with preoperative MRI can restore spatial accuracy by estimating brain shift deformations, but it remains a challenging problem given the large anatomical and topological changes and substantial modality intensity gap. The ReMIND2Reg 2025 Challenge provides the largest public benchmark for this task, built upon the ReMIND dataset. It offers 99 training cases, 5 validation cases, and 10 private test cases comprising paired 3D ceT1 MRI, T2 MRI, and post-resection 3D iUS volumes. Data are provided without annotations for training, while validation and test performance are evaluated on manually annotated anatomical landmarks. Metrics include target registration error (TRE), robustness to worst-case landmark misalignment (TRE30), and runtime. By establishing a standardized evaluation framework for this clinically critical and technically complex problem, ReMIND2Reg aims to accelerate the development of robust, generalizable, and clinically deployable multimodal registration algorithms for image-guided neurosurgery.

cs.CV↗

arXiv2025

UNISELF: A Unified Network with Instance Normalization and Self-Ensembled Lesion Fusion for Multiple Sclerosis Lesion Segmentation

Automated segmentation of multiple sclerosis (MS) lesions using multicontrast magnetic resonance (MR) images improves efficiency and reproducibility compared to manual delineation, with deep learning (DL) methods achieving state-of-the-art performance. However, these DL-based methods have yet to simultaneously optimize in-domain accuracy and out-of-domain generalization when trained on a single source with limited data, or their performance has been unsatisfactory. To fill this gap, we propose a method called UNISELF, which achieves high accuracy within a single training domain while demonstrating strong generalizability across multiple out-of-domain test datasets. UNISELF employs a novel test-time self-ensembled lesion fusion to improve segmentation accuracy, and leverages test-time instance normalization (TTIN) of latent features to address domain shifts and missing input contrasts. Trained on the ISBI 2015 longitudinal MS segmentation challenge training dataset, UNISELF ranks among the best-performing methods on the challenge test dataset. Additionally, UNISELF outperforms all benchmark methods trained on the same ISBI training data across diverse out-of-domain test datasets with domain shifts and missing contrasts, including the public MICCAI 2016 and UMCL datasets, as well as a private multisite dataset. These test datasets exhibit domain shifts and/or missing contrasts caused by variations in acquisition protocols, scanner types, and imaging artifacts arising from imperfect acquisition. Our code is available at https://github.com/uponacceptance.

eess.IV↗

arXiv2025

Synthetic multi-inversion time magnetic resonance images for visualization of subcortical structures

Purpose: Visualization of subcortical gray matter is essential in neuroscience and clinical practice, particularly for disease understanding and surgical planning.While multi-inversion time (multi-TI) T$_1$-weighted (T$_1$-w) magnetic resonance (MR) imaging improves visualization, it is rarely acquired in clinical settings. Approach: We present SyMTIC (Synthetic Multi-TI Contrasts), a deep learning method that generates synthetic multi-TI images using routinely acquired T$_1$-w, T$_2$-weighted (T$_2$-w), and FLAIR images. Our approach combines image translation via deep neural networks with imaging physics to estimate longitudinal relaxation time (T$_1$) and proton density (PD) maps. These maps are then used to compute multi-TI images with arbitrary inversion times. Results: SyMTIC was trained using paired MPRAGE and FGATIR images along with T$_2$-w and FLAIR images. It accurately synthesized multi-TI images from standard clinical inputs, achieving image quality comparable to that from explicitly acquired multi-TI data.The synthetic images, especially for TI values between 400-800 ms, enhanced visualization of subcortical structures and improved segmentation of thalamic nuclei. Conclusion: SyMTIC enables robust generation of high-quality multi-TI images from routine MR contrasts. It generalizes well to varied clinical datasets, including those with missing FLAIR images or unknown parameters, offering a practical solution for improving brain MR image visualization and analysis.

eess.IV↗

arXiv2025

Beyond the LUMIR challenge: The pathway to foundational registration models

Medical image challenges have played a transformative role in advancing the field, catalyzing innovation and establishing new performance benchmarks. Image registration, a foundational task in neuroimaging, has similarly advanced through the Learn2Reg initiative. Building on this, we introduce the Large-scale Unsupervised Brain MRI Image Registration (LUMIR) challenge, a next-generation benchmark for unsupervised brain MRI registration. Previous challenges relied upon anatomical label maps, however LUMIR provides 4,014 unlabeled T1-weighted MRIs for training, encouraging biologically plausible deformation modeling through self-supervision. Evaluation includes 590 in-domain test subjects and extensive zero-shot tasks across disease populations, imaging protocols, and species. Deep learning methods consistently achieved state-of-the-art performance and produced anatomically plausible, diffeomorphic deformation fields. They outperformed several leading optimization-based methods and remained robust to most domain shifts. These findings highlight the growing maturity of deep learning in neuroimaging registration and its potential to serve as a foundation model for general-purpose medical image registration.

eess.IV↗

arXiv2025

Pretraining Deformable Image Registration Networks with Random Images

Recent advances in deep learning-based medical image registration have shown that training deep neural networks~(DNNs) does not necessarily require medical images. Previous work showed that DNNs trained on randomly generated images with carefully designed noise and contrast properties can still generalize well to unseen medical data. Building on this insight, we propose using registration between random images as a proxy task for pretraining a foundation model for image registration. Empirical results show that our pretraining strategy improves registration accuracy, reduces the amount of domain-specific data needed to achieve competitive performance, and accelerates convergence during downstream training, thereby enhancing computational efficiency.

cs.CV↗

arXiv2025

Brightness-Invariant Tracking Estimation in Tagged MRI

Magnetic resonance (MR) tagging is an imaging technique for noninvasively tracking tissue motion in vivo by creating a visible pattern of magnetization saturation (tags) that deforms with the tissue. Due to longitudinal relaxation and progression to steady-state, the tags and tissue brightnesses change over time, which makes tracking with optical flow methods error-prone. Although Fourier methods can alleviate these problems, they are also sensitive to brightness changes as well as spectral spreading due to motion. To address these problems, we introduce the brightness-invariant tracking estimation (BRITE) technique for tagged MRI. BRITE disentangles the anatomy from the tag pattern in the observed tagged image sequence and simultaneously estimates the Lagrangian motion. The inherent ill-posedness of this problem is addressed by leveraging the expressive power of denoising diffusion probabilistic models to represent the probabilistic distribution of the underlying anatomy and the flexibility of physics-informed neural networks to estimate biologically-plausible motion. A set of tagged MR images of a gel phantom was acquired with various tag periods and imaging flip angles to demonstrate the impact of brightness variations and to validate our method. The results show that BRITE achieves more accurate motion and strain estimates as compared to other state of the art methods, while also being resistant to tag fading.

eess.IV↗

arXiv2025

Correlation Ratio for Unsupervised Learning of Multi-modal Deformable Registration

In recent years, unsupervised learning for deformable image registration has been a major research focus. This approach involves training a registration network using pairs of moving and fixed images, along with a loss function that combines an image similarity measure and deformation regularization. For multi-modal image registration tasks, the correlation ratio has been a widely-used image similarity measure historically, yet it has been underexplored in current deep learning methods. Here, we propose a differentiable correlation ratio to use as a loss function for learning-based multi-modal deformable image registration. This approach extends the traditionally non-differentiable implementation of the correlation ratio by using the Parzen windowing approximation, enabling backpropagation with deep neural networks. We validated the proposed correlation ratio on a multi-modal neuroimaging dataset. In addition, we established a Bayesian training framework to study how the trade-off between the deformation regularizer and similarity measures, including mutual information and our proposed correlation ratio, affects the registration performance.

eess.IV↗

arXiv2025

ECLARE: Efficient cross-planar learning for anisotropic resolution enhancement

In clinical imaging, magnetic resonance (MR) image volumes are often acquired as stacks of 2D slices with decreased scan times, improved signal-to-noise ratio, and image contrasts unique to 2D MR pulse sequences. While this is sufficient for clinical evaluation, automated algorithms designed for 3D analysis perform poorly on multi-slice 2D MR volumes, especially those with thick slices and gaps between slices. Super-resolution (SR) methods aim to address this problem, but previous methods do not address all of the following: slice profile shape estimation, slice gap, domain shift, and non-integer or arbitrary upsampling factors. In this paper, we propose ECLARE (Efficient Cross-planar Learning for Anisotropic Resolution Enhancement), a self-SR method that addresses each of these factors. ECLARE uses a slice profile estimated from the multi-slice 2D MR volume, trains a network to learn the mapping from low-resolution to high-resolution in-plane patches from the same volume, and performs SR with anti-aliasing. We compared ECLARE to cubic B-spline interpolation, SMORE, and other contemporary SR methods. We used realistic and representative simulations so that quantitative performance against ground truth can be computed, and ECLARE outperformed all other methods in both signal recovery and downstream tasks. Importantly, as ECLARE does not use external training data it cannot suffer from domain shift between training and testing. Our code is open-source and available at https://www.github.com/sremedios/eclare.

cs.CV↗

arXiv2024

Unsupervised learning of spatially varying regularization for diffeomorphic image registration

Spatially varying regularization accommodates the deformation variations that may be necessary for different anatomical regions during deformable image registration. Historically, optimization-based registration models have harnessed spatially varying regularization to address anatomical subtleties. However, most modern deep learning-based models tend to gravitate towards spatially invariant regularization, wherein a homogenous regularization strength is applied across the entire image, potentially disregarding localized variations. In this paper, we propose a hierarchical probabilistic model that integrates a prior distribution on the deformation regularization strength, enabling the end-to-end learning of a spatially varying deformation regularizer directly from the data. The proposed method is straightforward to implement and easily integrates with various registration network architectures. Additionally, automatic tuning of hyperparameters is achieved through Bayesian optimization, allowing efficient identification of optimal hyperparameters for any given registration task. Comprehensive evaluations on publicly available datasets demonstrate that the proposed method significantly improves registration performance and enhances the interpretability of deep learning-based registration, all while maintaining smooth deformations.

cs.CV↗

arXiv2024

Unique MS Lesion Identification from MRI

Unique identification of multiple sclerosis (MS) white matter lesions (WMLs) is important to help characterize MS progression. WMLs are routinely identified from magnetic resonance images (MRIs) but the resultant total lesion load does not correlate well with EDSS; whereas mean unique lesion volume has been shown to correlate with EDSS. Our approach builds on prior work by incorporating Hessian matrix computation from lesion probability maps before using the random walker algorithm to estimate the volume of each unique lesion. Synthetic images demonstrate our ability to accurately count the number of lesions present. The takeaways, are: 1) that our method correctly identifies all lesions including many that are missed by previous methods; 2) we can better separate confluent lesions; and 3) we can accurately capture the total volume of WMLs in a given probability map. This work will allow new more meaningful statistics to be computed from WMLs in brain MRIs

eess.IV↗

arXiv2024

Bi-Directional MS Lesion Filling and Synthesis Using Denoising Diffusion Implicit Model-based Lesion Repainting

Automatic magnetic resonance (MR) image processing pipelines are widely used to study people with multiple sclerosis (PwMS), encompassing tasks such as lesion segmentation and brain parcellation. However, the presence of lesion often complicates these analysis, particularly in brain parcellation. Lesion filling is commonly used to mitigate this issue, but existing lesion filling algorithms often fall short in accurately reconstructing realistic lesion-free images, which are vital for consistent downstream analysis. Additionally, the performance of lesion segmentation algorithms is often limited by insufficient data with lesion delineation as training labels. In this paper, we propose a novel approach leveraging Denoising Diffusion Implicit Models (DDIMs) for both MS lesion filling and synthesis based on image inpainting. Our modified DDIM architecture, once trained, enables both MS lesion filing and synthesis. Specifically, it can generate lesion-free T1-weighted or FLAIR images from those containing lesions; Or it can add lesions to T1-weighted or FLAIR images of healthy subjects. The former is essential for downstream analyses that require lesion-free images, while the latter is valuable for augmenting training datasets for lesion segmentation tasks. We validate our approach through initial experiments in this paper and demonstrate promising results in both lesion filling and synthesis, paving the way for future work.

eess.IV↗