Predicting brain aging can help in the early detection and prognosis of neurodegenerative diseases. Longitudinal cohorts of healthy subjects scanned through magnetic resonance imaging (MRI) have been essential to understand the structural brain changes due to aging. However, these cohorts suffer from missing data due to logistic issues in the recruitment of subjects. This paper proposes a methodology for filling up missing data in longitudinal cohorts with anatomically plausible images that capture the subject-specific aging process. The proposed methodology is developed within the framework of diffeomorphic registration. First, two novel modules are introduced within Synthmorph, a fast, state-of-the-art deep learning-based diffeomorphic registration method, to simulate the aging process between the first and last available MRI scan for each subject in three-dimensional (3D). The use of image registration also makes the generated images plausible by construction. Second, we used six image similarity measurements to rearrange the generated images to the specific age range. Finally, we estimated the age of every generated image by using the assumption of linear brain decay in healthy subjects. The methodology was evaluated on 2662 T1-weighted MRI scans from 796 healthy participants from 3 different longitudinal cohorts: Alzheimer's Disease Neuroimaging Initiative, Open Access Series of Imaging Studies-3, and Group of Neuropsychological Studies of the Canary Islands (GENIC). In total, we generated 7548 images to simulate the access of a scan per subject every 6 months in these cohorts. We evaluated the quality of the synthetic images using six quantitative measurements and a qualitative assessment by an experienced neuroradiologist with state-of-the-art results. The assumption of linear brain decay was accurate in these cohorts (R2 ∈ [.924,.940]). The experimental results show that the proposed methodology can produce anatomically plausible aging predictions that can be used to enhance longitudinal datasets. Compared to deep learning-based generative methods, diffeomorphic registration is more likely to preserve the anatomy of the different structures of the brain, which makes it more appropriate for its use in clinical applications. The proposed methodology is able to efficiently simulate anatomically plausible 3D MRI scans of brain aging of healthy subjects from two images scanned at two different time points.

 Simulating prospective magnetic resonance imaging (MRI) scans from a given individual brain image is challenging, as it requires accounting for canonical changes in aging and/or disease progression while also considering the individual brain’s current status and unique characteristics. While current deep generative models can produce high-resolution anatomically accurate templates for population-wide studies, they cannot predict future aging trajectories for individuals. In this study, we introduce Individualized Brain Synthesis (InBrainSyn), a framework that synthesizes high resolution longitudinal MRI scans that simulate subject-specific neurodegeneration in both Alzheimer’s disease (AD) and normal aging. InBrainSyn uses a parallel transport algorithm to adapt the population-level aging trajectories learned by a generative deep template network to synthesize subject-specific aging. Diffeomorphic registration guarantees the anatomical plausibility of the synthesized images by design. Experimentally, we find that our model faithfully simulates both individualized aging and inter-cohort generations capturing neuroanatomical transitions between normal aging and AD on the OASIS-3 dataset. Overall, given only a single scan from an individual, InBrainSyn produces high-fidelity and anatomically plausible longitudinal aging trajectories of synthesized 3D spatiotemporal T1w MRI scans. The code is shared at https://github.com/Fjr9516/InBrainSyn. 

Alzheimer’s Disease (AD) and normal aging are both characterized by brain atrophy. The question of whether AD-related brain atrophy represents accelerated aging or a neurodegeneration process distinct from that in normal aging remains unresolved. Moreover, precisely disentangling AD-related brain atrophy from normal aging in a clinical context is complex. In this study, we propose a deformation-based morphometry framework to estimate normal aging and AD-specific atrophy patterns of subjects from morphological MRI scans. For this, we first leverage deep-learning-based methods to create age-dependent templates of cognitively normal (CN) subjects. These templates model the normal aging atrophy patterns in a CN population. Then, we use the learned diffeomorphic registration to estimate the one-year normal aging pattern at the voxel level. In the second step, we register the testing image to the 60-year-old CN template. Finally, normal aging and AD-specific scores are estimated by measuring the alignment of this registration with the one-year normal aging pattern. The methodology was developed and evaluated on the OASIS3 dataset with 1,014 T1-weighted MRI scans, which is a unique dataset focused on preclinical cohorts. Of these, 326 scans were from CNsubjects, and 688 scans were from individuals clinically diagnosed with AD at different stages of clinical severity defined by clinical dementia rating (CDR) scores. The results show that ventricles predominantly follow an accelerated normal aging pattern in subjects with AD. In turn, hippocampi and amygdala regions were affected by both normal aging and AD-specific factors. Interestingly, hippocampi and amygdala regions showed more of an accelerated normal aging pattern for subjects during the early clinical stages of the disease, while the AD-specific score increases in later clinical stages. Our code is freely available at https://github.com/Fjr9516/DBM_with_DL.

Significant advances have been made toward building accurate automatic segmentation models for adult gliomas. However, the performance of these models often degrades when applied to pediatric glioma due to their imaging and clinical differences (domain shift). Obtaining sufficient annotated data for pediatric glioma is typically difficult because of its rare nature. Also, manual annotations are scarce and expensive. In this work, we propose Domain-Adapted nnU-Net (DA-nnUNet) to perform unsupervised domain adaptation from adult glioma (source domain) to pediatric glioma (target domain). Specifically, we add a domain classifier connected with a gradient reversal layer (GRL) to a backbone nnU-Net. Once the classifier reaches a very high accuracy, the GRL is activated with the goal of transferring domain-invariant features from the classifier to the segmentation model while preserving segmentation accuracy on the source domain. The accuracy of the classifier slowly degrades to chance levels. No annotations are used in the target domain. The method is compared to 8 different supervised models using BraTS-Adult glioma (N=1251) and BraTS-PED glioma data (N=99). The proposed method shows notable performance enhancements in the tumor core (TC) region compared to the model that only uses adult data: ~32% better Dice scores and ~20 better 95th percentile Hausdorff distances. Moreover, our unsupervised approach shows no statistically significant difference compared to the practical upper bound model using manual annotations from both datasets in TC region. The code is shared at https://github.com/Fjr9516/DA_nnUNet.

Rigid registration aims to determine the translations and rotations necessary to align features in a pair of images. While recent machine learning methods have become state-of-the-art for linear and deformable registration across subjects, they have demonstrated limitations when applied to longitudinal (within-subject) registration, where achieving precise alignment is critical. Building on an existing framework for anatomy-aware, acquisition-agnostic affine registration, we propose a model optimized for longitudinal, rigid brain registration. By training the model with synthetic within-subject pairs augmented with rigid and subtle nonlinear transforms, the model estimates more accurate rigid transforms than previous cross-subject networks and performs robustly on longitudinal registration pairs within and across magnetic resonance imaging (MRI) contrasts.