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.

Scalable Segmentation for Ultra-High-Resolution Brain MR Images

Although deep learning has shown great success in 3D brain MRI segmentation, achieving accurate and efficient segmentation of ultra-high-resolution brain images remains challenging due to the lack of labeled training data for fine-scale anatomical structures and high computational demands. In this work, we propose a novel framework that leverages easily accessible, low-resolution coarse labels as spatial references and guidance, without incurring additional annotation cost. Instead of directly predicting discrete segmentation maps, our approach regresses per-class signed distance transform maps, enabling smooth, boundary-aware supervision. Furthermore, to enhance scalability, generalizability, and efficiency, we introduce a scalable class-conditional segmentation strategy, where the model learns to segment one class at a time conditioned on a class-specific input. This novel design not only reduces memory consumption during both training and testing, but also allows the model to generalize to unseen anatomical classes. We validate our method through comprehensive experiments on both synthetic and real-world datasets, demonstrating its superior performance and scalability compared to conventional segmentation approaches.

End-to-end Cortical Surface Reconstruction from Clinical Magnetic Resonance Images

Surface-based cortical analysis is valuable for a variety of neuroimaging tasks, such as spatial normalization, parcellation, and gray matter (GM) thickness estimation. However, most tools for estimating cortical surfaces work exclusively on scans with at least 1 mm isotropic resolution and are tuned to a specific magnetic resonance (MR) contrast, often T1-weighted (T1w). This precludes application using most clinical MR scans, which are very heterogeneous in terms of contrast and resolution. Here, we use synthetic domain-randomized data to train the first neural network for explicit estimation of cortical surfaces from scans of any contrast and resolution, without retraining. Our method deforms a template mesh to the white matter (WM) surface, which guarantees topological correctness. This mesh is further deformed to estimate the GM surface. We compare our method to recon-all-clinical (RAC), an implicit surface reconstruction method which is currently the only other tool capable of processing heterogeneous clinical MR scans, on ADNI and a large clinical dataset (n=1,332). We show a approximately 50 % reduction in cortical thickness error (from 0.50 to 0.24 mm) with respect to RAC and better recovery of the aging-related cortical thinning patterns detected by FreeSurfer on high-resolution T1w scans. Our method enables fast and accurate surface reconstruction of clinical scans, allowing studies (1) with sample sizes far beyond what is feasible in a research setting, and (2) of clinical populations that are difficult to enroll in research studies. The code is publicly available at https://github.com/simnibs/brainnet.

From Low Field to High Value: Robust Cortical Mapping from Low-Field MRI

Three-dimensional reconstruction of cortical surfaces from MRI for morphometric analysis is fundamental for understanding brain structure. While high-field MRI (HF-MRI) is standard in research and clinical settings, its limited availability hinders widespread use. Low-field MRI (LF-MRI), particularly portable systems, offers a cost-effective and accessible alternative. However, existing cortical surface analysis tools are optimized for high-resolution HF-MRI and struggle with the lower signal-to-noise ratio and resolution of LF-MRI. In this work, we present a machine learning method for 3D reconstruction and analysis of portable LF-MRI across a range of contrasts and resolutions. Our method works "out of the box" without retraining. It uses a 3D U-Net trained on synthetic LF-MRI to predict signed distance functions of cortical surfaces, followed by geometric processing to ensure topological accuracy. We evaluate our method using paired HF/LF-MRI scans of the same subjects, showing that LF-MRI surface reconstruction accuracy depends on acquisition parameters, including contrast type (T1 vs T2), orientation (axial vs isotropic), and resolution. A 3mm isotropic T2-weighted scan acquired in under 4 minutes, yields strong agreement with HF-derived surfaces: surface area correlates at r=0.96, cortical parcellations reach Dice=0.98, and gray matter volume achieves r=0.93. Cortical thickness remains more challenging with correlations up to r=0.70, reflecting the difficulty of sub-mm precision with 3mm voxels. We further validate our method on challenging postmortem LF-MRI, demonstrating its robustness. Our method represents a step toward enabling cortical surface analysis on portable LF-MRI. Code is available at https://surfer.nmr.mgh.harvard.edu/fswiki/ReconAny

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.

Reference-Free 3D Reconstruction of Brain Dissection Photographs with Machine Learning

Correlation of neuropathology with MRI has the potential to transfer microscopic signatures of pathology to invivo scans. Recently, a classical registration method has been proposed, to build these correlations from 3D reconstructed stacks of dissection photographs, which are routinely taken at brain banks. These photographs bypass the need for exvivo MRI, which is not widely accessible. However, this method requires a full stack of brain slabs and a reference mask (e.g., acquired with a surface scanner), which severely limits the applicability of the technique. Here we propose RefFree, a dissection photograph reconstruction method without external reference. RefFree is a learning approach that estimates the 3D coordinates in the atlas space for every pixel in every photograph; simple least-squares fitting can then be used to compute the 3D reconstruction. As a by-product, RefFree also produces an atlas-based segmentation of the reconstructed stack. RefFree is trained on synthetic photographs generated from digitally sliced 3D MRI data, with randomized appearance for enhanced generalization ability. Experiments on simulated and real data show that RefFree achieves performance comparable to the baseline method without an explicit reference while also enabling reconstruction of partial stacks. Our code is available at https://github.com/lintian-a/reffree.

Learn2Synth: Learning Optimal Data Synthesis Using Hypergradients

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. While powerful, this approach relies on the accurate tuning of a large set of hyper-parameters governing 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 both parametric and nonparametric strategies to augment the synthetic images, enhancing the segmentation network's performance. Experimental results on both synthetic and real-world datasets demonstrate the effectiveness of this learning strategy. Code is available at: https://github.com/HuXiaoling/Learn2Synth.

A Constrast-Agnostic Method for Ultra-High Resolution Claustrum Segmentation

The claustrum is a band-like gray matter structure located between putamen and insula whose exact functions are still actively researched. Its sheet-like structure makes it barely visible in in vivo Magnetic Resonance Imaging (MRI) scans at typical resolutions and neuroimaging tools for its study, including methods for automatic segmentation, are currently very limited. In this paper, we propose a contrast- and resolution-agnostic method for claustrum segmentation at ultra-high resolution (0.35 mm isotropic); the method is based on the SynthSeg segmentation framework (Billot et al., 2023), which leverages the use of synthetic training intensity images to achieve excellent generalization. In particular, SynthSeg requires only label maps to be trained, since corresponding intensity images are synthesized on the fly with random contrast and resolution. We trained a deep learning network for automatic claustrum segmentation, using claustrum manual labels obtained from 18 ultra-high resolution MRI scans (mostly ex vivo). We demonstrated the method to work on these 18 high resolution cases (Dice score = 0.632, mean surface distance = 0.458 mm, and volumetric similarity = 0.867 using 6-fold Cross Validation (CV)), and also on in vivo T1-weighted MRI scans at typical resolutions (~1 mm isotropic). We also demonstrated that the method is robust in a test-retest setting and when applied to multimodal imaging (T2-weighted, Proton Density and quantitative T1 scans). To the best of our knowledge this is the first accurate method for automatic ultra-high resolution claustrum segmentation, which is robust against changes in contrast and resolution. The method is released at https://github.com/chiara-mauri/claustrum_segmentation and as part of the neuroimaging package Freesurfer (Fischl, 2012).

TV-based Deep 3D Self Super-Resolution for fMRI

While functional Magnetic Resonance Imaging (fMRI) offers valuable insights into cognitive processes, its inherent spatial limitations pose challenges for detailed analysis of the fine-grained functional architecture of the brain. More specifically, MRI scanner and sequence specifications impose a trade-off between temporal resolution, spatial resolution, signal-to-noise ratio, and scan time. Deep Learning (DL) Super-Resolution (SR) methods have emerged as a promising solution to enhance fMRI resolution, generating high-resolution (HR) images from low-resolution (LR) images typically acquired with lower scanning times. However, most existing SR approaches depend on supervised DL techniques, which require training ground truth (GT) HR data, which is often difficult to acquire and simultaneously sets a bound for how far SR can go. In this paper, we introduce a novel self-supervised DL SR model that combines a DL network with an analytical approach and Total Variation (TV) regularization. Our method eliminates the need for external GT images, achieving competitive performance compared to supervised DL techniques and preserving the functional maps.

Recon-all-clinical: Cortical surface reconstruction and analysis of heterogeneous clinical brain MRI

Surface-based analysis of the cerebral cortex is ubiquitous in human neuroimaging with MRI. It is crucial for cortical registration, parcellation, and thickness estimation. Traditionally, these analyses require high-resolution, isotropic scans with good gray-white matter contrast, typically a 1mm T1-weighted scan. This excludes most clinical MRI scans, which are often anisotropic and lack the necessary T1 contrast. To enable large-scale neuroimaging studies using vast clinical data, we introduce recon-all-clinical, a novel method for cortical reconstruction, registration, parcellation, and thickness estimation in brain MRI scans of any resolution and contrast. Our approach employs a hybrid analysis method that combines a convolutional neural network (CNN) trained with domain randomization to predict signed distance functions (SDFs) and classical geometry processing for accurate surface placement while maintaining topological and geometric constraints. The method does not require retraining for different acquisitions, thus simplifying the analysis of heterogeneous clinical datasets. We tested recon-all-clinical on multiple datasets, including over 19,000 clinical scans. The method consistently produced precise cortical reconstructions and high parcellation accuracy across varied MRI contrasts and resolutions. Cortical thickness estimates are precise enough to capture aging effects independently of MRI contrast, although accuracy varies with slice thickness. Our method is publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/recon-all-clinical, enabling researchers to perform detailed cortical analysis on the huge amounts of already existing clinical MRI scans. This advancement may be particularly valuable for studying rare diseases and underrepresented populations where research-grade MRI data is scarce.