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.

Beyond the LUMIR challenge: The pathway to foundational registration models

Medical image challenges have played a transformative role in advancing the field, catalyzing algorithmic innovation and establishing new performance standards across diverse clinical applications. Image registration, a foundational task in neuroimaging pipelines, has similarly benefited from the Learn2Reg initiative. Building on this foundation, we introduce the Large-scale Unsupervised Brain MRI Image Registration (LUMIR) challenge, a next-generation benchmark designed to assess and advance unsupervised brain MRI registration. Distinct from prior challenges that leveraged anatomical label maps for supervision, LUMIR removes this dependency by providing over 4,000 preprocessed T1-weighted brain MRIs for training without any label maps, encouraging biologically plausible deformation modeling through self-supervision. In addition to evaluating performance on 590 held-out test subjects, LUMIR introduces a rigorous suite of zero-shot generalization tasks, spanning out-of-domain imaging modalities (e.g., FLAIR, T2-weighted, T2*-weighted), disease populations (e.g., Alzheimer's disease), acquisition protocols (e.g., 9.4T MRI), and species (e.g., macaque brains). A total of 1,158 subjects and over 4,000 image pairs were included for evaluation. Performance was assessed using both segmentation-based metrics (Dice coefficient, 95th percentile Hausdorff distance) and landmark-based registration accuracy (target registration error). Across both in-domain and zero-shot tasks, deep learning-based methods consistently achieved state-of-the-art accuracy while producing anatomically plausible deformation fields. The top-performing deep learning-based models demonstrated diffeomorphic properties and inverse consistency, outperforming several leading optimization-based methods, and showing strong robustness to most domain shifts, the exception being a drop in performance on out-of-domain contrasts.

Multipath cycleGAN for harmonization of paired and unpaired low-dose lung computed tomography reconstruction kernels

Reconstruction kernels in computed tomography (CT) affect spatial resolution and noise characteristics, introducing systematic variability in quantitative imaging measurements such as emphysema quantification. Choosing an appropriate kernel is therefore essential for consistent quantitative analysis. We propose a multipath cycleGAN model for CT kernel harmonization, trained on a mixture of paired and unpaired data from a low-dose lung cancer screening cohort. The model features domain-specific encoders and decoders with a shared latent space and uses discriminators tailored for each domain.We train the model on 42 kernel combinations using 100 scans each from seven representative kernels in the National Lung Screening Trial (NLST) dataset. To evaluate performance, 240 scans from each kernel are harmonized to a reference soft kernel, and emphysema is quantified before and after harmonization. A general linear model assesses the impact of age, sex, smoking status, and kernel on emphysema. We also evaluate harmonization from soft kernels to a reference hard kernel. To assess anatomical consistency, we compare segmentations of lung vessels, muscle, and subcutaneous adipose tissue generated by TotalSegmentator between harmonized and original images. Our model is benchmarked against traditional and switchable cycleGANs. For paired kernels, our approach reduces bias in emphysema scores, as seen in Bland-Altman plots (p<0.05). For unpaired kernels, harmonization eliminates confounding differences in emphysema (p>0.05). High Dice scores confirm preservation of muscle and fat anatomy, while lung vessel overlap remains reasonable. Overall, our shared latent space multipath cycleGAN enables robust harmonization across paired and unpaired CT kernels, improving emphysema quantification and preserving anatomical fidelity.

Investigating the impact of kernel harmonization and deformable registration on inspiratory and expiratory chest CT images for people with COPD

Paired inspiratory-expiratory CT scans enable the quantification of gas trapping due to small airway disease and emphysema by analyzing lung tissue motion in COPD patients. Deformable image registration of these scans assesses regional lung volumetric changes. However, variations in reconstruction kernels between paired scans introduce errors in quantitative analysis. This work proposes a two-stage pipeline to harmonize reconstruction kernels and perform deformable image registration using data acquired from the COPDGene study. We use a cycle generative adversarial network (GAN) to harmonize inspiratory scans reconstructed with a hard kernel (BONE) to match expiratory scans reconstructed with a soft kernel (STANDARD). We then deformably register the expiratory scans to inspiratory scans. We validate harmonization by measuring emphysema using a publicly available segmentation algorithm before and after harmonization. Results show harmonization significantly reduces emphysema measurement inconsistencies, decreasing median emphysema scores from 10.479% to 3.039%, with a reference median score of 1.305% from the STANDARD kernel as the target. Registration accuracy is evaluated via Dice overlap between emphysema regions on inspiratory, expiratory, and deformed images. The Dice coefficient between inspiratory emphysema masks and deformably registered emphysema masks increases significantly across registration stages (p<0.001). Additionally, we demonstrate that deformable registration is robust to kernel variations.

Pitfalls of defacing whole-head MRI: re-identification risk with diffusion models and compromised research potential

Defacing is often applied to head magnetic resonance image (MRI) datasets prior to public release to address privacy concerns. The alteration of facial and nearby voxels has provoked discussions about the true capability of these techniques to ensure privacy as well as their impact on downstream tasks. With advancements in deep generative models, the extent to which defacing can protect privacy is uncertain. Additionally, while the altered voxels are known to contain valuable anatomical information, their potential to support research beyond the anatomical regions directly affected by defacing remains uncertain. To evaluate these considerations, we develop a refacing pipeline that recovers faces in defaced head MRIs using cascaded diffusion probabilistic models (DPMs). The DPMs are trained on images from 180 subjects and tested on images from 484 unseen subjects, 469 of whom are from a different dataset. To assess whether the altered voxels in defacing contain universally useful information, we also predict computed tomography (CT)-derived skeletal muscle radiodensity from facial voxels in both defaced and original MRIs. The results show that DPMs can generate high-fidelity faces that resemble the original faces from defaced images, with surface distances to the original faces significantly smaller than those of a population average face (p < 0.05). This performance also generalizes well to previously unseen datasets. For skeletal muscle radiodensity predictions, using defaced images results in significantly weaker Spearman's rank correlation coefficients compared to using original images (p < 10-4). For shin muscle, the correlation is statistically significant (p < 0.05) when using original images but not statistically significant (p > 0.05) when any defacing method is applied, suggesting that defacing might not only fail to protect privacy but also eliminate valuable information.

Brain age identification from diffusion MRI synergistically predicts neurodegenerative disease

Estimated brain age from magnetic resonance image (MRI) and its deviation from chronological age can provide early insights into potential neurodegenerative diseases, supporting early detection and implementation of prevention strategies. Diffusion MRI (dMRI), a widely used modality for brain age estimation, presents an opportunity to build an earlier biomarker for neurodegenerative disease prediction because it captures subtle microstructural changes that precede more perceptible macrostructural changes. However, the coexistence of macro- and micro-structural information in dMRI raises the question of whether current dMRI-based brain age estimation models are leveraging the intended microstructural information or if they inadvertently rely on the macrostructural information. To develop a microstructure-specific brain age, we propose a method for brain age identification from dMRI that minimizes the model's use of macrostructural information by non-rigidly registering all images to a standard template. Imaging data from 13,398 participants across 12 datasets were used for the training and evaluation. We compare our brain age models, trained with and without macrostructural information minimized, with an architecturally similar T1-weighted (T1w) MRI-based brain age model and two state-of-the-art T1w MRI-based brain age models that primarily use macrostructural information. We observe difference between our dMRI-based brain age and T1w MRI-based brain age across stages of neurodegeneration, with dMRI-based brain age being older than T1w MRI-based brain age in participants transitioning from cognitively normal (CN) to mild cognitive impairment (MCI), but younger in participants already diagnosed with Alzheimer's disease (AD). Approximately 4 years before MCI diagnosis, dMRI-based brain age yields better performance than T1w MRI-based brain ages in predicting transition from CN to MCI.

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.

Multi-Modality Conditioned Variational U-Net for Field-of-View Extension in Brain Diffusion MRI

An incomplete field-of-view (FOV) in diffusion magnetic resonance imaging (dMRI) can severely hinder the volumetric and bundle analyses of whole-brain white matter connectivity. Although existing works have investigated imputing the missing regions using deep generative models, it remains unclear how to specifically utilize additional information from paired multi-modality data and whether this can enhance the imputation quality and be useful for downstream tractography. To fill this gap, we propose a novel framework for imputing dMRI scans in the incomplete part of the FOV by integrating the learned diffusion features in the acquired part of the FOV to the complete brain anatomical structure. We hypothesize that by this design the proposed framework can enhance the imputation performance of the dMRI scans and therefore be useful for repairing whole-brain tractography in corrupted dMRI scans with incomplete FOV. We tested our framework on two cohorts from different sites with a total of 96 subjects and compared it with a baseline imputation method that treats the information from T1w and dMRI scans equally. The proposed framework achieved significant improvements in imputation performance, as demonstrated by angular correlation coefficient (p < 1E-5), and in downstream tractography accuracy, as demonstrated by Dice score (p < 0.01). Results suggest that the proposed framework improved imputation performance in dMRI scans by specifically utilizing additional information from paired multi-modality data, compared with the baseline method. The imputation achieved by the proposed framework enhances whole brain tractography, and therefore reduces the uncertainty when analyzing bundles associated with neurodegenerative.

Influence of Early through Late Fusion on Pancreas Segmentation from Imperfectly Registered Multimodal MRI

Multimodal fusion promises better pancreas segmentation. However, where to perform fusion in models is still an open question. It is unclear if there is a best location to fuse information when analyzing pairs of imperfectly aligned images. Two main alignment challenges in this pancreas segmentation study are 1) the pancreas is deformable and 2) breathing deforms the abdomen. Even after image registration, relevant deformations are often not corrected. We examine how early through late fusion impacts pancreas segmentation. We used 353 pairs of T2-weighted (T2w) and T1-weighted (T1w) abdominal MR images from 163 subjects with accompanying pancreas labels. We used image registration (deeds) to align the image pairs. We trained a collection of basic UNets with different fusion points, spanning from early to late, to assess how early through late fusion influenced segmentation performance on imperfectly aligned images. We assessed generalization of fusion points on nnUNet. The single-modality T2w baseline using a basic UNet model had a Dice score of 0.73, while the same baseline on the nnUNet model achieved 0.80. For the basic UNet, the best fusion approach occurred in the middle of the encoder (early/mid fusion), which led to a statistically significant improvement of 0.0125 on Dice score compared to the baseline. For the nnUNet, the best fusion approach was na\"ive image concatenation before the model (early fusion), which resulted in a statistically significant Dice score increase of 0.0021 compared to baseline. Fusion in specific blocks can improve performance, but the best blocks for fusion are model specific, and the gains are small. In imperfectly registered datasets, fusion is a nuanced problem, with the art of design remaining vital for uncovering potential insights. Future innovation is needed to better address fusion in cases of imperfect alignment of abdominal image pairs.

Beyond MR Image Harmonization: Resolution Matters Too

Magnetic resonance (MR) imaging is commonly used in the clinical setting to non-invasively monitor the body. There exists a large variability in MR imaging due to differences in scanner hardware, software, and protocol design. Ideally, a processing algorithm should perform robustly to this variability, but that is not always the case in reality. This introduces a need for image harmonization to overcome issues of domain shift when performing downstream analysis such as segmentation. Most image harmonization models focus on acquisition parameters such as inversion time or repetition time, but they ignore an important aspect in MR imaging -- resolution. In this paper, we evaluate the impact of image resolution on harmonization using a pretrained harmonization algorithm. We simulate 2D acquisitions of various slice thicknesses and gaps from 3D acquired, 1mm3 isotropic MR images and demonstrate how the performance of a state-of-the-art image harmonization algorithm varies as resolution changes. We discuss the most ideal scenarios for image resolution including acquisition orientation when 3D imaging is not available, which is common for many clinical scanners. Our results show that harmonization on low-resolution images does not account for acquisition resolution and orientation variations. Super-resolution can be used to alleviate resolution variations but it is not always used. Our methodology can generalize to help evaluate the impact of image acquisition resolution for multiple tasks. Determining the limits of a pretrained algorithm is important when considering preprocessing steps and trust in the results.