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Rate of brain aging associates with future executive function in Asian children and older adults.

Cheng SF, Yue WL, Ng KK, Qian X, Liu S, Tan TWK, Nguyen KN, Leong RLF, Hilal S, Cheng CY, Tan AP, Law EC, Gluckman PD, Chen CL, Chong YS, Meaney MJ, Chee MWL, Yeo BTT, Zhou JH

pubmed logopapersJun 16 2025
Brain age has emerged as a powerful tool to understand neuroanatomical aging and its link to health outcomes like cognition. However, there remains a lack of studies investigating the rate of brain aging and its relationship to cognition. Furthermore, most brain age models are trained and tested on cross-sectional data from primarily Caucasian, adult participants. It is thus unclear how well these models generalize to non-Caucasian participants, especially children. Here, we tested a previously published deep learning model on Singaporean elderly participants (55-88 years old) and children (4-11 years old). We found that the model directly generalized to the elderly participants, but model finetuning was necessary for children. After finetuning, we found that the rate of change in brain age gap was associated with future executive function performance in both elderly participants and children. We further found that lateral ventricles and frontal areas contributed to brain age prediction in elderly participants, while white matter and posterior brain regions were more important in predicting brain age of children. Taken together, our results suggest that there is potential for generalizing brain age models to diverse populations. Moreover, the longitudinal change in brain age gap reflects developing and aging processes in the brain, relating to future cognitive function.

Default Mode Network Connectivity Predicts Individual Differences in Long-Term Forgetting: Evidence for Storage Degradation, not Retrieval Failure

Xu, Y., Prat, C. S., Sense, F., van Rijn, H., Stocco, A.

biorxiv logopreprintJun 16 2025
Despite the importance of memories in everyday life and the progress made in understanding how they are encoded and retrieved, the neural processes by which declarative memories are maintained or forgotten remain elusive. Part of the problem is that it is empirically difficult to measure the rate at which memories fade, even between repeated presentations of the source of the memory. Without such a ground-truth measure, it is hard to identify the corresponding neural correlates. This study addresses this problem by comparing individual patterns of functional connectivity against behavioral differences in forgetting speed derived from computational phenotyping. Specifically, the individual-specific values of the speed of forgetting in long-term memory (LTM) were estimated for 33 participants using a formal model fit to accuracy and response time data from an adaptive paired-associate learning task. Individual speeds of forgetting were then used to examine participant-specific patterns of resting-state fMRI connectivity, using machine learning techniques to identify the most predictive and generalizable features. Our results show that individual speeds of forgetting are associated with resting-state connectivity within the default mode network (DMN) as well as between the DMN and cortical sensory areas. Cross-validation showed that individual speeds of forgetting were predicted with high accuracy (r = .78) from these connectivity patterns alone. These results support the view that DMN activity and the associated sensory regions are actively involved in maintaining memories and preventing their decline, a view that can be seen as evidence for the hypothesis that forgetting is a result of storage degradation, rather than of retrieval failure.

An 11,000-Study Open-Access Dataset of Longitudinal Magnetic Resonance Images of Brain Metastases

Saahil Chadha, David Weiss, Anastasia Janas, Divya Ramakrishnan, Thomas Hager, Klara Osenberg, Klara Willms, Joshua Zhu, Veronica Chiang, Spyridon Bakas, Nazanin Maleki, Durga V. Sritharan, Sven Schoenherr, Malte Westerhoff, Matthew Zawalich, Melissa Davis, Ajay Malhotra, Khaled Bousabarah, Cornelius Deuschl, MingDe Lin, Sanjay Aneja, Mariam S. Aboian

arxiv logopreprintJun 16 2025
Brain metastases are a common complication of systemic cancer, affecting over 20% of patients with primary malignancies. Longitudinal magnetic resonance imaging (MRI) is essential for diagnosing patients, tracking disease progression, assessing therapeutic response, and guiding treatment selection. However, the manual review of longitudinal imaging is time-intensive, especially for patients with multifocal disease. Artificial intelligence (AI) offers opportunities to streamline image evaluation, but developing robust AI models requires comprehensive training data representative of real-world imaging studies. Thus, there is an urgent necessity for a large dataset with heterogeneity in imaging protocols and disease presentation. To address this, we present an open-access dataset of 11,884 longitudinal brain MRI studies from 1,430 patients with clinically confirmed brain metastases, paired with clinical and image metadata. The provided dataset will facilitate the development of AI models to assist in the long-term management of patients with brain metastasis.

Kernelized weighted local information based picture fuzzy clustering with multivariate coefficient of variation and modified total Bregman divergence measure for brain MRI image segmentation.

Lohit H, Kumar D

pubmed logopapersJun 16 2025
This paper proposes a novel clustering method for noisy image segmentation using a kernelized weighted local information approach under the Picture Fuzzy Set (PFS) framework. Existing kernel-based fuzzy clustering methods struggle with noisy environments and non-linear structures, while intuitionistic fuzzy clustering methods face limitations in handling uncertainty in real-world medical images. To address these challenges, we introduce a local picture fuzzy information measure, developed for the first time using Multivariate Coefficient of Variation (MCV) theory, enhancing robustness in segmentation. Additionally, we integrate non-Euclidean distance measures, including kernel distance for local information computation and modified total Bregman divergence (MTBD) measure for improving clustering accuracy. This combination enhances both local spatial consistency and global membership estimation, leading to precise segmentation. The proposed method is extensively evaluated on synthetic images with Gaussian, Salt and Pepper, and mixed noise, along with Brainweb, IBSR, and MRBrainS18 MRI datasets under varying Rician noise levels, and a CT image template. Furthermore, we benchmark our proposed method against two deep learning-based segmentation models, ResNet34-LinkNet and patch-based U-Net. Experimental results demonstrate significant improvements in segmentation accuracy, as validated by metrics such as Dice Score, Fuzzy Performance Index, Modified Partition Entropy, Average Volume Difference (AVD), and the XB index. Additionally, Friedman's statistical test confirms the superior performance of our approach compared to state-of-the-art clustering methods for noisy image segmentation. To facilitate reproducibility, the implementation of our proposed method is made publicly available at: Google Drive Repository.

Improving Prostate Gland Segmenting Using Transformer based Architectures

Shatha Abudalou

arxiv logopreprintJun 16 2025
Inter reader variability and cross site domain shift challenge the automatic segmentation of prostate anatomy using T2 weighted MRI images. This study investigates whether transformer models can retain precision amid such heterogeneity. We compare the performance of UNETR and SwinUNETR in prostate gland segmentation against our previous 3D UNet model [1], based on 546 MRI (T2weighted) volumes annotated by two independent experts. Three training strategies were analyzed: single cohort dataset, 5 fold cross validated mixed cohort, and gland size based dataset. Hyperparameters were tuned by Optuna. The test set, from an independent population of readers, served as the evaluation endpoint (Dice Similarity Coefficient). In single reader training, SwinUNETR achieved an average dice score of 0.816 for Reader#1 and 0.860 for Reader#2, while UNETR scored 0.8 and 0.833 for Readers #1 and #2, respectively, compared to the baseline UNets 0.825 for Reader #1 and 0.851 for Reader #2. SwinUNETR had an average dice score of 0.8583 for Reader#1 and 0.867 for Reader#2 in cross-validated mixed training. For the gland size-based dataset, SwinUNETR achieved an average dice score of 0.902 for Reader#1 subset and 0.894 for Reader#2, using the five-fold mixed training strategy (Reader#1, n=53; Reader#2, n=87) at larger gland size-based subsets, where UNETR performed poorly. Our findings demonstrate that global and shifted-window self-attention effectively reduces label noise and class imbalance sensitivity, resulting in improvements in the Dice score over CNNs by up to five points while maintaining computational efficiency. This contributes to the high robustness of SwinUNETR for clinical deployment.

Reaction-Diffusion Model for Brain Spacetime Dynamics.

Li Q, Calhoun VD

pubmed logopapersJun 16 2025
The human brain exhibits intricate spatiotemporal dynamics, which can be described and understood through the framework of complex dynamic systems theory. In this study, we leverage functional magnetic resonance imaging (fMRI) data to investigate reaction-diffusion processes in the brain. A reaction-diffusion process refers to the interaction between two or more substances that spread through space and react with each other over time, often resulting in the formation of patterns or waves of activity. Building on this empirical foundation, we apply a reaction-diffusion framework inspired by theoretical physics to simulate the emergence of brain spacetime vortices within the brain. By exploring this framework, we investigate how reaction-diffusion processes can serve as a compelling model to govern the formation and propagation of brain spacetime vortices, which are dynamic, swirling patterns of brain activity that emerge and evolve across both time and space within the brain. Our approach integrates computational modeling with fMRI data to investigate the spatiotemporal properties of these vortices, offering new insights into the fundamental principles of brain organization. This work highlights the potential of reaction-diffusion models as an alternative framework for understanding brain spacetime dynamics.

Classification of glioma grade and Ki-67 level prediction in MRI data: A SHAP-driven interpretation.

Bhuiyan EH, Khan MM, Hossain SA, Rahman R, Luo Q, Hossain MF, Wang K, Sumon MSI, Khalid S, Karaman M, Zhang J, Chowdhury MEH, Zhu W, Zhou XJ

pubmed logopapersJun 16 2025
This study focuses on artificial intelligence-driven classification of glioma and Ki-67 leveling using T2w-FLAIR MRI, exploring the association of Ki-67 biomarkers with deep learning (DL) features through explainable artificial intelligence (XAI) and SHapley Additive exPlanations (SHAP). This IRB-approved study included 101 patients with glioma brain tumor acquired MR images with the T2W-FLAIR sequence. We extracted DL bottleneck features using ResNet50 from glioma MR images. Principal component analysis (PCA) was deployed for dimensionality reduction. XAI was used to identify potential features. The XGBosst classified the histologic grades of the glioma and the level of Ki-67. We integrated potential DL features with patient demographics (age and sex) and Ki-67 biomarkers, utilizing SHAP to determine the model's essential features and interactions. Glioma grade classification and Ki-67 level predictions achieved overall accuracies of 0.94 and 0.91, respectively. It achieved precision scores of 0.92, 0.94, and 0.96 for glioma grades 2, 3, and 4, and 0.88, 0.94, and 0.97 for Ki-67 levels (low: 5%≤Ki-67<10%, moderate: 10%≤Ki-67≤20, and high: Ki-67>20%). Corresponding F1-scores were 0.95, 0.88, and 0.96 for glioma grades and 0.92, 0.93, and 0.87 for Ki-67 levels. SHAP analysis further highlighted a strong association between bottleneck DL features and Ki-67 biomarkers, demonstrating their potential to differentiate glioma grades and Ki-67 levels while offering valuable insights into glioma aggressiveness. This study demonstrates the precise classification of glioma grades and the prediction of Ki-67 levels to underscore the potential of AI-driven MRI analysis to enhance clinical decision-making in glioma management.

Biological age prediction in schizophrenia using brain MRI, gut microbiome and blood data.

Han R, Wang W, Liao J, Peng R, Liang L, Li W, Feng S, Huang Y, Fong LM, Zhou J, Li X, Ning Y, Wu F, Wu K

pubmed logopapersJun 15 2025
The study of biological age prediction using various biological data has been widely explored. However, single biological data may offer limited insights into the pathological process of aging and diseases. Here we evaluated the performance of machine learning models for biological age prediction by using the integrated features from multi-biological data of 140 healthy controls and 43 patients with schizophrenia, including brain MRI, gut microbiome, and blood data. Our results revealed that the models using multi-biological data achieved higher predictive accuracy than those using only brain MRI. Feature interpretability analysis of the optimal model elucidated that the substantial contributions of the frontal lobe, the temporal lobe and the fornix were effective for biological age prediction. Notably, patients with schizophrenia exhibited a pronounced increase in the predicted biological age gap (BAG) when compared to healthy controls. Moreover, the BAG in the SZ group was negatively and positively correlated with the MCCB and PANSS scores, respectively. These findings underscore the potential of BAG as a valuable biomarker for assessing cognitive decline and symptom severity of neuropsychiatric disorders.

Altered resting-state brain activity in patients with major depression disorder and bipolar disorder: A regional homogeneity analysis.

Han W, Su Y, Wang X, Yang T, Zhao G, Mao R, Zhu N, Zhou R, Wang X, Wang Y, Peng D, Wang Z, Fang Y, Chen J, Sun P

pubmed logopapersJun 15 2025
Major Depressive Disorder (MDD) and Bipolar Disorder (BD) exhibit overlapping depressive symptoms, complicating their differentiation in clinical practice. Traditional neuroimaging studies have focused on specific regions of interest, but few have employed whole-brain analyses like regional homogeneity (ReHo). This study aims to differentiate MDD from BD by identifying key brain regions with abnormal ReHo and using advanced machine learning techniques to improve diagnostic accuracy. A total of 63 BD patients, 65 MDD patients, and 70 healthy controls were recruited from the Shanghai Mental Health Center. Resting-state functional MRI (rs-fMRI) was used to analyze ReHo across the brain. We applied Support Vector Machine (SVM) and SVM-Recursive Feature Elimination (SVM-RFE), a robust machine learning model known for its high precision in feature selection and classification, to identify critical brain regions that could serve as biomarkers for distinguishing BD from MDD. SVM-RFE allows for the recursive removal of non-informative features, enhancing the model's ability to accurately classify patients. Correlations between ReHo values and clinical scores were also evaluated. ReHo analysis revealed significant differences in several brain regions. The study results revealed that, compared to healthy controls, both BD and MDD patients exhibited reduced ReHo in the superior parietal gyrus. Additionally, MDD patients showed decreased ReHo values in the Right Lenticular nucleus, putamen (PUT.R), Right Angular gyrus (ANG.R), and Left Superior occipital gyrus (SOG.L). Compared to the MDD group, BD patients exhibited increased ReHo values in the Left Inferior occipital gyrus (IOG.L). In BD patients only, the reduction in ReHo values in the right superior parietal gyrus and the right angular gyrus was positively correlated with Hamilton Depression Scale (HAMD) scores. SVM-RFE identified the IOG.L, SOG.L, and PUT.R as the most critical features, achieving an area under the curve (AUC) of 0.872, with high sensitivity and specificity in distinguishing BD from MDD. This study demonstrates that BD and MDD patients exhibit distinct patterns of regional brain activity, particularly in the occipital and parietal regions. The combination of ReHo analysis and SVM-RFE provides a powerful approach for identifying potential biomarkers, with the left inferior occipital gyrus, left superior occipital gyrus, and right putamen emerging as key differentiating regions. These findings offer valuable insights for improving the diagnostic accuracy between BD and MDD, contributing to more targeted treatment strategies.

GM-LDM: Latent Diffusion Model for Brain Biomarker Identification through Functional Data-Driven Gray Matter Synthesis

Hu Xu, Yang Jingling, Jia Sihan, Bi Yuda, Calhoun Vince

arxiv logopreprintJun 15 2025
Generative models based on deep learning have shown significant potential in medical imaging, particularly for modality transformation and multimodal fusion in MRI-based brain imaging. This study introduces GM-LDM, a novel framework that leverages the latent diffusion model (LDM) to enhance the efficiency and precision of MRI generation tasks. GM-LDM integrates a 3D autoencoder, pre-trained on the large-scale ABCD MRI dataset, achieving statistical consistency through KL divergence loss. We employ a Vision Transformer (ViT)-based encoder-decoder as the denoising network to optimize generation quality. The framework flexibly incorporates conditional data, such as functional network connectivity (FNC) data, enabling personalized brain imaging, biomarker identification, and functional-to-structural information translation for brain diseases like schizophrenia.
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