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Juan Eugenio Iglesias

Publications and source records attributed to Juan Eugenio Iglesias.

At least 19 recordsLinked to original sources

Uncertainty-Aware Cortical Surface Reconstruction and Spherical Registration for Heterogeneous Brain MRI

Surface-based cortical analysis is useful in many applications as it is a natural way to model the highly folded structure of the cerebral cortex, allowing quantities such as curvature and thickness to be easily calculated. Existing deep learning (DL) methods have focused on 1x1x1 mm3 T1-weighted (T1w) scans, thus replicating classical pipelines. Here we present a neural network that is trained exclusively on synthetic scans with random contrast and resolution. Consequently, it can be applied to almost any kind of magnetic resonance imaging (MRI) scan. In addition, our model provides vertex-wise uncertainty estimates of the predicted surface as well as a spherical registration to fsaverage space. Our model performs on par with other state-of-the-art DL methods on 1x1x1 mm3 T1w scans and outperforms the only other method capable of estimating cortical surfaces from low resolution, non-T1w scans. The predicted uncertainty, moreover, correlates with overall scan quality on low resolution scans and highlights areas of poor surface reconstruction on 1x1x1 mm3 T1w scans, suggesting that it can be used for quality control. Finally, the predicted spherical registrations prove comparable to other DL and classical registration methods. These qualities, when combined with the fast inference time, will provide the ability to analyze large, existing databases of clinical MRI scans, with the potential for finding disease-specific patterns that would otherwise be infeasible in a research setting.

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Towards Brain MRI Foundation Models for the Clinic: Findings from the FOMO25 Challenge

Clinical deployment of automated brain MRI analysis faces a fundamental challenge: clinical data is heterogeneous and noisy, and high-quality labels are prohibitively costly to obtain. Self-supervised learning (SSL) can address this by leveraging the vast amounts of unlabeled data produced in clinical workflows to train robust \textit{foundation models} that adapt out-of-domain with minimal supervision. However, the development of foundation models for brain MRI has been limited by small pretraining datasets and in-domain benchmarking focused on high-quality, research-grade data. To address this gap, we organized the FOMO25 challenge as a satellite event at MICCAI 2025. FOMO25 provided participants with a large pretraining dataset, FOMO60K, and evaluated models on data sourced directly from clinical workflows in few-shot and out-of-domain settings. Tasks covered infarct classification, meningioma segmentation, and brain age regression, and considered both models trained on FOMO60K (method track) and any data (open track). Nineteen foundation models from sixteen teams were evaluated using a standardized containerized pipeline. Results show that (a) self-supervised pretraining improves generalization on clinical data under domain shift, with the strongest models trained \textit{out-of-domain} surpassing supervised baselines trained \textit{in-domain}. (b) No single pretraining objective benefits all tasks: MAE favors segmentation, hybrid reconstruction-contrastive objectives favor classification, and (c) strong performance was achieved by small pretrained models, and improvements from scaling model size and training duration did not yield reliable benefits.

cs.CV↗

A large-scale heterogeneous 3D magnetic resonance brain imaging dataset for self-supervised learning

We present FOMO260K, a large-scale, heterogeneous dataset of 260,927 brain Magnetic Resonance Imaging (MRI) scans from 77,589 MRI sessions and 55,378 subjects, aggregated from 910 publicly available sources. The dataset includes both clinical- and research-grade images, multiple MRI sequences, and a wide range of anatomical and pathological variability, including scans with large brain anomalies. Minimal preprocessing was applied to preserve the original image characteristics while reducing entry barriers for new users. Companion code for self-supervised pretraining and finetuning is provided, along with pretrained models. FOMO260K is intended to support the development and benchmarking of self-supervised learning methods in medical imaging at scale.

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Learn2Synth: Learning Optimal Data Synthesis Using Hypergradients for Brain Image Segmentation

Domain randomization through synthesis is a powerful strategy to train networks that are unbiased with respect to the domain of the input images. Randomization allows networks to see a virtually infinite range of intensities and artifacts during training, thereby minimizing overfitting to appearance and maximizing generalization to unseen data. Although powerful, this approach relies on the accurate tuning of a large set of hyperparameters that govern the probabilistic distribution of the synthesized images. Instead of manually tuning these parameters, we introduce Learn2Synth, a novel procedure in which synthesis parameters are learned using a small set of real labeled data. Unlike methods that impose constraints to align synthetic data with real data (e.g., contrastive or adversarial techniques), which risk misaligning the image and its label map, we tune an augmentation engine such that a segmentation network trained on synthetic data has optimal accuracy when applied to real data. This approach allows the training procedure to benefit from real labeled examples, without ever using these real examples to train the segmentation network, which avoids biasing the network towards the properties of the training set. Specifically, we develop parametric and nonparametric strategies to enhance synthetic images in a way that improves the performance of the segmentation network. We demonstrate the effectiveness of this learning strategy on synthetic and real-world brain scans. Code is available at: https://github.com/HuXiaoling/Learn2Synth.

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Enhanced Portable Ultra Low-Field Diffusion Tensor Imaging with Bayesian Artifact Correction and Deep Learning-Based Super-Resolution

Portable, ultra-low-field (ULF) magnetic resonance imaging has the potential to expand access to neuroimaging but currently suffers from coarse spatial and angular resolutions and low signal-to-noise ratios. Diffusion tensor imaging (DTI), a sequence tailored to detect and reconstruct white matter tracts within the brain, is particularly prone to such imaging degradation due to inherent sequence design coupled with prolonged scan times. In addition, ULF DTI scans exhibit artifacting that spans both the space and angular domains, requiring a custom modelling algorithm for subsequent correction. We introduce a nine-direction, single-shell ULF DTI sequence, as well as a companion Bayesian bias field correction algorithm that possesses angular dependence and convolutional neural network-based superresolution algorithm that is generalizable across DTI datasets and does not require re-training (''DiffSR''). We show through a synthetic downsampling experiment and white matter assessment in real, matched ULF and high-field DTI scans that these algorithms can recover microstructural and volumetric white matter information at ULF. We also show that DiffSR can be directly applied to white matter-based Alzheimers disease classification in synthetically degraded scans, with notable improvements in agreement between DTI metrics, as compared to un-degraded scans. We freely disseminate the Bayesian bias correction algorithm and DiffSR with the goal of furthering progress on both ULF reconstruction methods and general DTI sequence harmonization. We release all code related to DiffSR for $\href{https://github.com/markolchanyi/DiffSR}{public \space use}$.

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Uncertainty Estimation for Pretrained Medical Image Registration Models via Transformation Equivariance

Accurate image registration is essential in many medical imaging applications, yet most deep registration networks provide little indication of when or where their predictions are unreliable. Existing uncertainty estimation approaches, such as Bayesian methods, ensembles, or MC-dropout, typically require architectural modifications or retraining, precluding their applicability to pretrained registration models. We propose an inference-time, model-agnostic uncertainty estimation framework that applies directly to any pretrained registration network. Our approach is grounded in the transformation equivariance property of image registration, which states that the underlying anatomical mapping should remain consistent under spatial perturbations of the input. Experiments across three pretrained registration models and four anatomical structures show that the resulting uncertainty maps consistently correlate with registration error and highlight unreliably aligned regions. This framework turns pretrained registration networks into risk-aware tools at test time, moving medical image registration closer to safe clinical and large-scale research deployment.

cs.CV↗

Improving Neuropathological Reconstruction Fidelity via AI Slice Imputation

Neuropathological analyses benefit from spatially precise volumetric reconstructions that enhance anatomical delineation and improve morphometric accuracy. Our prior work has shown the feasibility of reconstructing 3D brain volumes from 2D dissection photographs. However these outputs sometimes exhibit coarse, overly smooth reconstructions of structures, especially under high anisotropy (i.e., reconstructions from thick slabs). Here, we introduce a computationally efficient super-resolution step that imputes slices to generate anatomically consistent isotropic volumes from anisotropic 3D reconstructions of dissection photographs. By training on domain-randomized synthetic data, we ensure that our method generalizes across dissection protocols and remains robust to large slab thicknesses. The imputed volumes yield improved automated segmentations, achieving higher Dice scores, particularly in cortical and white matter regions. Validation on surface reconstruction and atlas registration tasks demonstrates more accurate cortical surfaces and MRI registration. By enhancing the resolution and anatomical fidelity of photograph-based reconstructions, our approach strengthens the bridge between neuropathology and neuroimaging. Our method is publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/mri_3d_photo_recon

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Deep generative priors for 3D brain analysis

Diffusion models have recently emerged as powerful generative models in medical imaging. However, it remains a major challenge to combine these data-driven models with domain knowledge to guide brain imaging problems. In neuroimaging, Bayesian inverse problems have long provided a successful framework for inference tasks, where incorporating domain knowledge of the imaging process enables robust performance without requiring extensive training data. However, the anatomical modeling component of these approaches typically relies on classical mathematical priors that often fail to capture the complex structure of brain anatomy. In this work, we present the first general-purpose application of diffusion models as priors for solving a wide range of medical imaging inverse problems. Our approach leverages a score-based diffusion prior trained extensively on diverse brain MRI data, paired with flexible forward models that capture common image processing tasks such as super-resolution, bias field correction, inpainting, and combinations thereof. We further demonstrate how our framework can refine outputs from existing deep learning methods to improve anatomical fidelity. Experiments on heterogeneous clinical and research MRI data show that our method achieves state-of-the-art performance producing consistent, high-quality solutions without requiring paired training datasets. These results highlight the potential of diffusion priors as versatile tools for brain MRI analysis.

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Reference-Free 3D Reconstruction of Brain Dissection Slabs via Learned Atlas Coordinates

Correlation of neuropathology with MRI has the potential to transfer microscopic signatures of pathology to in vivo scans. There is increasing interest in building these correlations from 3D reconstructed stacks of slab photographs, which are routinely taken during dissection at brain banks. These photographs bypass the need for ex vivo MRI, which is not widely accessible. However, existing methods either require a corresponding 3D reference (e.g., an ex vivo MRI scans, or a brain surface acquired with a structured light scanner) or a full stack of brain slabs, which severely limits applicability. Here we propose RefFree, a 3D reconstruction method for dissection photographs that does not require an external reference. RefFree coherently reconstructs a 3D volume for an arbitrary set of slabs (including a single slab) using predicted 3D coordinates in the standard atlas space (MNI) as guidance. To support RefFree's pipeline, we train an atlas coordinate prediction network that estimates the coordinate map from a 2D photograph, using synthetic photographs generated from digitally sliced 3D MRI data with randomized appearance for enhanced generalization. As a by-product, RefFree can propagate information (e.g., anatomical labels) from atlas space to one single photograph even without reconstruction. Experiments on simulated and real data show that, when all slabs are available, RefFree achieves performance comparable to existing classical methods but at substantially higher speed. Moreover, RefFree yields accurate reconstruction and registration for partial stacks or even a single slab. Our code is available at https://github.com/lintian-a/reffree.

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Learning to Upscale 3D Segmentations in Neuroimaging

Obtaining high-resolution (HR) segmentations from coarse annotations is a pervasive challenge in computer vision. Applications include inferring pixel-level segmentations from token-level labels in vision transformers, upsampling coarse masks to full resolution, and transferring annotations from legacy low-resolution (LR) datasets to modern HR imagery. These challenges are especially acute in 3D neuroimaging, where manual labeling is costly and resolutions continually increase. We propose a scalable framework that generalizes across resolutions and domains by regressing signed distance maps, enabling smooth, boundary-aware supervision. Crucially, our model predicts one class at a time, which substantially reduces memory usage during training and inference (critical for large 3D volumes) and naturally supports generalization to unseen classes. Generalization is further improved through training on synthetic, domain-randomized data. We validate our approach on ultra-high-resolution (UHR) human brain MRI (~100 μm), where most existing methods operate at 1 mm resolution. Our framework effectively upsamples such standard-resolution segmentations to UHR detail. Results on synthetic and real data demonstrate superior scalability and generalization compared to conventional segmentation methods. Code is available at: https://github.com/HuXiaoling/Learn2Upscale.

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Automated Segmentation of Coronal Brain Tissue Slabs for 3D Neuropathology

Advances in image registration and machine learning have recently enabled volumetric analysis of postmortem brain tissue from conventional photographs of coronal slabs, which are routinely collected in brain banks and neuropathology laboratories worldwide. One caveat of this methodology is the requirement of segmentation of the tissue from photographs, which currently requires costly manual intervention. In this article, we present a deep learning model to automate this process. The automatic segmentation tool relies on a U-Net architecture that was trained with a combination of 1,414 manually segmented images of both fixed and fresh tissue, from specimens with varying diagnoses, photographed at two different sites. Automated model predictions on a subset of photographs not seen in training were analyzed to estimate performance compared to manual labels, including both inter- and intra-rater variability. Our model achieved a median Dice score over 0.98, mean surface distance under 0.4mm, and 95\% Hausdorff distance under 1.60mm, which approaches inter-/intra-rater levels. Our tool is publicly available at surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools.

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Generating healthy counterfactuals with denoising diffusion bridge models

Generating healthy counterfactuals from pathological images holds significant promise in medical imaging, e.g., in anomaly detection or for application of analysis tools that are designed for healthy scans. These counterfactuals should represent what a patient's scan would plausibly look like in the absence of pathology, preserving individual anatomical characteristics while modifying only the pathological regions. Denoising diffusion probabilistic models (DDPMs) have become popular methods for generating healthy counterfactuals of pathology data. Typically, this involves training on solely healthy data with the assumption that a partial denoising process will be unable to model disease regions and will instead reconstruct a closely matched healthy counterpart. More recent methods have incorporated synthetic pathological images to better guide the diffusion process. However, it remains challenging to guide the generative process in a way that effectively balances the removal of anomalies with the retention of subject-specific features. To solve this problem, we propose a novel application of denoising diffusion bridge models (DDBMs) - which, unlike DDPMs, condition the diffusion process not only on the initial point (i.e., the healthy image), but also on the final point (i.e., a corresponding synthetically generated pathological image). Treating the pathological image as a structurally informative prior enables us to generate counterfactuals that closely match the patient's anatomy while selectively removing pathology. The results show that our DDBM outperforms previously proposed diffusion models and fully supervised approaches at segmentation and anomaly detection tasks.

cs.CV↗

CADD: Context aware disease deviations via restoration of brain images using normative conditional diffusion models

Applying machine learning to real-world medical data, e.g. from hospital archives, has the potential to revolutionize disease detection in brain images. However, detecting pathology in such heterogeneous cohorts is a difficult challenge. Normative modeling, a form of unsupervised anomaly detection, offers a promising approach to studying such cohorts where the ``normal'' behavior is modeled and can be used at subject level to detect deviations relating to disease pathology. Diffusion models have emerged as powerful tools for anomaly detection due to their ability to capture complex data distributions and generate high-quality images. Their performance relies on image restoration; differences between the original and restored images highlight potential abnormalities. However, unlike normative models, these diffusion model approaches do not incorporate clinical information which provides important context to guide the disease detection process. Furthermore, standard approaches often poorly restore healthy regions, resulting in poor reconstructions and suboptimal detection performance. We present CADD, the first conditional diffusion model for normative modeling in 3D images. To guide the healthy restoration process, we propose a novel inference inpainting strategy which balances anomaly removal with retention of subject-specific features. Evaluated on three challenging datasets, including clinical scans, which may have lower contrast, thicker slices, and motion artifacts, CADD achieves state-of-the-art performance in detecting neurological abnormalities in heterogeneous cohorts.

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Analysis of the MICCAI Brain Tumor Segmentation -- Metastases (BraTS-METS) 2025 Lighthouse Challenge: Brain Metastasis Segmentation on Pre- and Post-treatment MRI

Despite continuous advancements in cancer treatment, brain metastatic disease remains a significant complication of primary cancer and is associated with an unfavorable prognosis. One approach for improving diagnosis, management, and outcomes is to implement algorithms based on artificial intelligence for the automated segmentation of both pre- and post-treatment MRI brain images. Such algorithms rely on volumetric criteria for lesion identification and treatment response assessment, which are still not available in clinical practice. Therefore, it is critical to establish tools for rapid volumetric segmentations methods that can be translated to clinical practice and that are trained on high quality annotated data. The BraTS-METS 2025 Lighthouse Challenge aims to address this critical need by establishing inter-rater and intra-rater variability in dataset annotation by generating high quality annotated datasets from four individual instances of segmentation by neuroradiologists while being recorded on video (two instances doing "from scratch" and two instances after AI pre-segmentation). This high-quality annotated dataset will be used for testing phase in 2025 Lighthouse challenge and will be publicly released at the completion of the challenge. The 2025 Lighthouse challenge will also release the 2023 and 2024 segmented datasets that were annotated using an established pipeline of pre-segmentation, student annotation, two neuroradiologists checking, and one neuroradiologist finalizing the process. It builds upon its previous edition by including post-treatment cases in the dataset. Using these high-quality annotated datasets, the 2025 Lighthouse challenge plans to test benchmark algorithms for automated segmentation of pre-and post-treatment brain metastases (BM), trained on diverse and multi-institutional datasets of MRI images obtained from patients with brain metastases.

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UNSURF: Uncertainty Quantification for Cortical Surface Reconstruction of Clinical Brain MRIs

We propose UNSURF, a novel uncertainty measure for cortical surface reconstruction of clinical brain MRI scans of any orientation, resolution, and contrast. It relies on the discrepancy between predicted voxel-wise signed distance functions (SDFs) and the actual SDFs of the fitted surfaces. Our experiments on real clinical scans show that traditional uncertainty measures, such as voxel-wise Monte Carlo variance, are not suitable for modeling the uncertainty of surface placement. Our results demonstrate that UNSURF estimates correlate well with the ground truth errors and: \textit{(i)}~enable effective automated quality control of surface reconstructions at the subject-, parcel-, mesh node-level; and \textit{(ii)}~improve performance on a downstream Alzheimer's disease classification task.

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BraTS-PEDs: Results of the Multi-Consortium International Pediatric Brain Tumor Segmentation Challenge 2023

Pediatric central nervous system tumors are the leading cause of cancer-related deaths in children. The five-year survival rate for high-grade glioma in children is less than 20%. The development of new treatments is dependent upon multi-institutional collaborative clinical trials requiring reproducible and accurate centralized response assessment. We present the results of the BraTS-PEDs 2023 challenge, the first Brain Tumor Segmentation (BraTS) challenge focused on pediatric brain tumors. This challenge utilized data acquired from multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. BraTS-PEDs 2023 aimed to evaluate volumetric segmentation algorithms for pediatric brain gliomas from magnetic resonance imaging using standardized quantitative performance evaluation metrics employed across the BraTS 2023 challenges. The top-performing AI approaches for pediatric tumor analysis included ensembles of nnU-Net and Swin UNETR, Auto3DSeg, or nnU-Net with a self-supervised framework. The BraTSPEDs 2023 challenge fostered collaboration between clinicians (neuro-oncologists, neuroradiologists) and AI/imaging scientists, promoting faster data sharing and the development of automated volumetric analysis techniques. These advancements could significantly benefit clinical trials and improve the care of children with brain tumors.

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BraTS orchestrator : Democratizing and Disseminating state-of-the-art brain tumor image analysis

The Brain Tumor Segmentation (BraTS) cluster of challenges has significantly advanced brain tumor image analysis by providing large, curated datasets and addressing clinically relevant tasks. However, despite its success and popularity, algorithms and models developed through BraTS have seen limited adoption in both scientific and clinical communities. To accelerate their dissemination, we introduce BraTS orchestrator, an open-source Python package that provides seamless access to state-of-the-art segmentation and synthesis algorithms for diverse brain tumors from the BraTS challenge ecosystem. Available on GitHub (https://github.com/BrainLesion/BraTS), the package features intuitive tutorials designed for users with minimal programming experience, enabling both researchers and clinicians to easily deploy winning BraTS algorithms for inference. By abstracting the complexities of modern deep learning, BraTS orchestrator democratizes access to the specialized knowledge developed within the BraTS community, making these advances readily available to broader neuro-radiology and neuro-oncology audiences.

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Conditional diffusion models for guided anomaly detection in brain images using fluid-driven anomaly randomization

Supervised machine learning has enabled accurate pathology detection in brain MRI, but requires training data from diseased subjects that may not be readily available in some scenarios, for example, in the case of rare diseases. Reconstruction-based unsupervised anomaly detection, in particular using diffusion models, has gained popularity in the medical field as it allows for training on healthy images alone, eliminating the need for large disease-specific cohorts. These methods assume that a model trained on normal data cannot accurately represent or reconstruct anomalies. However, this assumption often fails with models failing to reconstruct healthy tissue or accurately reconstruct abnormal regions i.e., failing to remove anomalies. In this work, we introduce a novel conditional diffusion model framework for anomaly detection and healthy image reconstruction in brain MRI. Our weakly supervised approach integrates synthetically generated pseudo-pathology images into the modeling process to better guide the reconstruction of healthy images. To generate these pseudo-pathologies, we apply fluid-driven anomaly randomization to augment real pathology segmentation maps from an auxiliary dataset, ensuring that the synthetic anomalies are both realistic and anatomically coherent. We evaluate our model's ability to detect pathology, using both synthetic anomaly datasets and real pathology from the ATLAS dataset. In our extensive experiments, our model: (i) consistently outperforms variational autoencoders, and conditional and unconditional latent diffusion; and (ii) surpasses on most datasets, the performance of supervised inpainting methods with access to paired diseased/healthy images.

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