MRI-based brain age estimation models aim to assess a subject's biological brain age based on information, such as neuroanatomical features. Various factors, including neurodegenerative diseases, can accelerate brain aging and measuring this phenomena could serve as a potential biomarker for clinical applications. While deep learning (DL)-based regression has recently attracted major attention, existing approaches often fail to capture the continuous nature of neuromorphological changes, potentially resulting in sub-optimal feature representation and results. To address this, we propose to use supervised contrastive learning with the recent Rank-N-Contrast (RNC) loss to estimate brain age based on widely used T1w structural MRI for the first time and leverage Grad-RAM to visually explain regression results. Experiments show that our proposed method achieves a mean absolute error (MAE) of 4.27 years and an $R^2$ of 0.93 with a limited dataset of training samples, significantly outperforming conventional deep regression with the same ResNet backbone while performing better or comparably with the state-of-the-art methods with significantly larger training data. Furthermore, Grad-RAM revealed more nuanced features related to age regression with the RNC loss than conventional deep regression. As an exploratory study, we employed the proposed method to estimate the gap between the biological and chronological brain ages in Alzheimer's Disease and Parkinson's disease patients, and revealed the correlation between the brain age gap and disease severity, demonstrating its potential as a biomarker in neurodegenerative disorders.

The human brain undergoes continuous transformations across the lifespan, representing a natural component of aging that does not inherently signal pathological conditions [1]. Neurodegenerative disorders such as dementia can compromise the brain structure and accelerate aging processes. Understanding and characterizing healthy brain aging patterns therefore becomes essential for distinguishing normal aging from pathological neurodegeneration, potentially enabling earlier detection of neurodegenerative diseases. The Brain Age-Gap (BAG), i.e. the discrepancy between predicted brain age and chronological age, has emerged as a robust biomarker that captures pathological brain processes and offers insights into the rate at which an individual's brain ages in comparison to others in the population [2, 3]. It is not only associated with various neurological disorders, such as Alzheimer's disease, cognitive impairment, and Autism Spectrum Disorder, but also serves as an indicator of all-cause mortality [4, 5, 6, 7, 8] Brain age estimation has been approached through both conventional and machine learning techniques, analyzing either the whole brain, specific regions, or localized patches [9, 10, 11]. One particular study presented a method using T1-weighted MRI to predict age through region-level and voxel-level metrics [12]. Regression-based machine learning has shown promise for the brain age prediction, with kernel regression applied to whole-brain MRI across diverse age ranges [13]. Various algorithms including Support Vector Regression and Binary Decision Trees have been compared for their brain age prediction capabilities [14]. Additional regression techniques such as Relevance Vector Regression, Twin Support Vector Regression, and Gaussian Process Regression have been explored across different imaging modalities for age estimation and mortality prediction [11, 15, 16, 17].

Accurate estimation of biological brain age from three dimensional (3D) T$_1$-weighted magnetic resonance imaging (MRI) is a critical imaging biomarker for identifying accelerated aging associated with neurodegenerative diseases. Effective brain age prediction necessitates training 3D models to leverage comprehensive insights from volumetric MRI scans, thereby fully capturing spatial anatomical context. However, optimizing deep 3D models remains challenging due to problems such as vanishing gradients. Furthermore, brain structural patterns differ significantly between sexes, which impacts aging trajectories and vulnerability to neurodegenerative diseases, thereby making sex classification crucial for enhancing the accuracy and generalizability of predictive models. To address these challenges, we propose a Deeply Supervised Multitask Autoencoder (DSMT-AE) framework for brain age estimation. DSMT-AE employs deep supervision, which involves applying supervisory signals at intermediate layers during training, to stabilize model optimization, and multitask learning to enhance feature representation. Specifically, our framework simultaneously optimizes brain age prediction alongside auxiliary tasks of sex classification and image reconstruction, thus effectively capturing anatomical and demographic variability to improve prediction accuracy. We extensively evaluate DSMT-AE on the Open Brain Health Benchmark (OpenBHB) dataset, the largest multisite neuroimaging cohort combining ten publicly available datasets. The results demonstrate that DSMT-AE achieves state-of-the-art performance and robustness across age and sex subgroups. Additionally, our ablation study confirms that each proposed component substantially contributes to the improved predictive accuracy and robustness of the overall architecture.

Brain aging is a complex and dynamic process, leading to functional and structural changes in the brain. These changes could lead to the increased risk of neurodegenerative diseases and cognitive decline. Accurate brain-age estimation utilizing neuroimaging data has become necessary for detecting initial signs of neurodegeneration. Here, we propose a novel deep learning approach using the Residual Neural Network 101 Version 2 (ResNet101V2) model to predict brain age from MRI scans. To train, validate and test our proposed model, we used a large dataset of 2102 images which were selected randomly from the International Consortium for Brain Mapping (ICBM). Next, we applied data preprocessing techniques, including normalizing the images and using outlier detection via Isolation Forest method. Then, we evaluated various pre-trained approaches (namely: MobileNetV2, ResNet50V2, ResNet101V2, Xception). The results demonstrated that the ResNet101V2 model has higher performance compared with the other models, attaining MAEs of 0.9136 and 0.8242 years for before and after using Isolation Forest process. Our method achieved a high accuracy in brain age estimation in ICBM dataset and it provides a reliable brain age prediction.

Brain aging involves structural and functional changes and therefore serves as a key biomarker for brain health. Combining structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) has the potential to improve brain age estimation by leveraging complementary data. However, fMRI data, being noisier than sMRI, complicates multimodal fusion. Traditional fusion methods often introduce more noise than useful information, which can reduce accuracy compared to using sMRI alone. In this paper, we propose a novel multimodal framework for biological brain age estimation, utilizing a sex-aware adversarial variational autoencoder (SA-AVAE). Our framework integrates adversarial and variational learning to effectively disentangle the latent features from both modalities. Specifically, we decompose the latent space into modality-specific codes and shared codes to represent complementary and common information across modalities, respectively. To enhance the disentanglement, we introduce cross-reconstruction and shared-distinct distance ratio loss as regularization terms. Importantly, we incorporate sex information into the learned latent code, enabling the model to capture sex-specific aging patterns for brain age estimation via an integrated regressor module. We evaluate our model using the publicly available OpenBHB dataset, a comprehensive multi-site dataset for brain age estimation. The results from ablation studies and comparisons with state-of-the-art methods demonstrate that our framework outperforms existing approaches and shows significant robustness across various age groups, highlighting its potential for real-time clinical applications in the early detection of neurodegenerative diseases.

Despite advances in deep learning for estimating brain age from structural MRI data, incorporating functional MRI data is challenging due to its complex structure and the noisy nature of functional connectivity measurements. To address this, we present the Multitask Adversarial Variational Autoencoder, a custom deep learning framework designed to improve brain age predictions through multimodal MRI data integration. This model separates latent variables into generic and unique codes, isolating shared and modality-specific features. By integrating multitask learning with sex classification as an additional task, the model captures sex-specific aging patterns. Evaluated on the OpenBHB dataset, a large multisite brain MRI collection, the model achieves a mean absolute error of 2.77 years, outperforming traditional methods. This success positions M-AVAE as a powerful tool for metaverse-based healthcare applications in brain age estimation.

Hypoxic-Ischemic Encephalopathy (HIE) affects 1 to 5 out of every 1,000 newborns, with 30% to 50% of cases resulting in adverse neurocognitive outcomes. However, these outcomes can only be reliably assessed as early as age 2. Therefore, early and accurate prediction of HIE-related neurocognitive outcomes using deep learning models is critical for improving clinical decision-making, guiding treatment decisions and assessing novel therapies. However, a major challenge in developing deep learning models for this purpose is the scarcity of large, annotated HIE datasets. We have assembled the first and largest public dataset, however it contains only 156 cases with 2-year neurocognitive outcome labels. In contrast, we have collected 8,859 normal brain black Magnetic Resonance Imagings (MRIs) with 0-97 years of age that are available for brain age estimation using deep learning models. In this paper, we introduce AGE2HIE to transfer knowledge learned by deep learning models from healthy controls brain MRIs to a diseased cohort, from structural to diffusion MRIs, from regression of continuous age estimation to prediction of the binary neurocognitive outcomes, and from lifespan age (0-97 years) to infant (0-2 weeks). Compared to training from scratch, transfer learning from brain age estimation significantly improves not only the prediction accuracy (3% or 2% improvement in same or multi-site), but also the model generalization across different sites (5% improvement in cross-site validation).

Brain age estimation involves predicting the biological age of individuals from their brain images, which offers valuable insights into the aging process and the progression of neurodegenerative diseases. Conducting large-scale datasets for medical image analysis is a challenging and time-consuming task. Existing approaches mostly depend on large datasets, which are hard to come by and expensive. These approaches also require sophisticated, resource-intensive models with a large number of parameters, necessitating a considerable amount of processing power. As a result, there is a vital need to develop innovative methods that can achieve robust performance with limited datasets and efficient use of computational resources. This paper proposes a novel slice-based dual-stream method called GDSM (Greedy Dual-Stream Model) for brain age estimation. This method addresses the limitations of large dataset requirements and computational resource intensiveness. The proposed method incorporates local and global aspects of the brain, thereby refining the focus on specific target regions. The approach employs four backbones to predict ages based on local and global features, complemented by a final model for age correction. Our method demonstrates a Mean Absolute Error (MAE) of 3.25 years on the test set of IBID, which only contains 289 subjects. To demonstrate the robustness of our approach for any small dataset, we analyzed the proposed method with the IXI dataset and achieved an MAE of 4.18 years on the test set of IXI. By leveraging dual-stream and greedy strategies, this approach achieves efficiency and robust performance, making it comparable with other state-of-the-art methods. The code for the GDSM model is available at https://github.com/iman2693/GDSM.

The integration of machine learning in medicine has significantly improved diagnostic precision, particularly in the interpretation of complex structures like the human brain. Diagnosing challenging conditions such as Alzheimer's disease has prompted the development of brain age estimation techniques. These methods often leverage three-dimensional Magnetic Resonance Imaging (MRI) scans, with recent studies emphasizing the efficacy of 3D convolutional neural networks (CNNs) like 3D ResNet. However, the untapped potential of Vision Transformers (ViTs), known for their accuracy and interpretability, persists in this domain due to limitations in their 3D versions. This paper introduces Triamese-ViT, an innovative adaptation of the ViT model for brain age estimation. Our model uniquely combines ViTs from three different orientations to capture 3D information, significantly enhancing accuracy and interpretability. Tested on a dataset of 1351 MRI scans, Triamese-ViT achieves a Mean Absolute Error (MAE) of 3.84, a 0.9 Spearman correlation coefficient with chronological age, and a -0.29 Spearman correlation coefficient between the brain age gap (BAG) and chronological age, significantly better than previous methods for brian age estimation. A key innovation of Triamese-ViT is its capacity to generate a comprehensive 3D-like attention map, synthesized from 2D attention maps of each orientation-specific ViT. This feature is particularly beneficial for in-depth brain age analysis and disease diagnosis, offering deeper insights into brain health and the mechanisms of age-related neural changes.

Brain age estimation is clinically important as it can provide valuable information in the context of neurodegenerative diseases such as Alzheimer's. Population graphs, which include multimodal imaging information of the subjects along with the relationships among the population, have been used in literature along with Graph Convolutional Networks (GCNs) and have proved beneficial for a variety of medical imaging tasks. A population graph is usually static and constructed manually using non-imaging information. However, graph construction is not a trivial task and might significantly affect the performance of the GCN, which is inherently very sensitive to the graph structure. In this work, we propose a framework that learns a population graph structure optimized for the downstream task. An attention mechanism assigns weights to a set of imaging and non-imaging features (phenotypes), which are then used for edge extraction. The resulting graph is used to train the GCN. The entire pipeline can be trained end-to-end. Additionally, by visualizing the attention weights that were the most important for the graph construction, we increase the interpretability of the graph. We use the UK Biobank, which provides a large variety of neuroimaging and non-imaging phenotypes, to evaluate our method on brain age regression and classification. The proposed method outperforms competing static graph approaches and other state-of-the-art adaptive methods. We further show that the assigned attention scores indicate that there are both imaging and non-imaging phenotypes that are informative for brain age estimation and are in agreement with the relevant literature.