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Role of Brain Age Gap as a Mediator in the Relationship Between Cognitive Impairment Risk Factors and Cognition.

Tan WY, Huang X, Huang J, Robert C, Cui J, Chen CPLH, Hilal S

pubmed logopapersJul 22 2025
Cerebrovascular disease (CeVD) and cognitive impairment risk factors contribute to cognitive decline, but the role of brain age gap (BAG) in mediating this relationship remains unclear, especially in Southeast Asian populations. This study investigated the influence of cognitive impairment risk factors on cognition and examined how BAG mediates this relationship, particularly in individuals with varying CeVD burden. This cross-sectional study analyzed Singaporean community and memory clinic participants. Cognitive impairment risk factors were assessed using the Cognitive Impairment Scoring System (CISS), encompassing 11 sociodemographic and vascular factors. Cognition was assessed through a neuropsychological battery, evaluating global cognition and 6 cognitive domains: executive function, attention, memory, language, visuomotor speed, and visuoconstruction. Brain age was derived from structural MRI features using ensemble machine learning model. Propensity score matching balanced risk profiles between model training and the remaining sample. Structural equation modeling examined the mediation effect of BAG on CISS-cognition relationship, stratified by CeVD burden (high: CeVD+, low: CeVD-). The study included 1,437 individuals without dementia, with 646 in the matched sample (mean age 66.4 ± 6.0 years, 47% female, 60% with no cognitive impairment). Higher CISS was consistently associated with poorer cognitive performance across all domains, with the strongest negative associations in visuomotor speed (β = -2.70, <i>p</i> < 0.001) and visuoconstruction (β = -3.02, <i>p</i> < 0.001). Among the CeVD+ group, BAG significantly mediated the relationship between CISS and global cognition (proportion mediated: 19.95%, <i>p</i> = 0.01), with the strongest mediation effects in executive function (34.1%, <i>p</i> = 0.03) and language (26.6%, <i>p</i> = 0.008). BAG also mediated the relationship between CISS and memory (21.1%) and visuoconstruction (14.4%) in the CeVD+ group, but these effects diminished after statistical adjustments. Our findings suggest that BAG is a key intermediary linking cognitive impairment risk factors to cognitive function, particularly in individuals with high CeVD burden. This mediation effect is domain-specific, with executive function, language, and visuoconstruction being the most vulnerable to accelerated brain aging. Limitations of this study include the cross-sectional design, limiting causal inference, and the focus on Southeast Asian populations, limiting generalizability. Future longitudinal studies should verify these relationships and explore additional factors not captured in our model.

Deformation registration based on reconstruction of brain MRI images with pathologies.

Lian L, Chang Q

pubmed logopapersJul 1 2025
Deformable registration between brain tumor images and brain atlas has been an important tool to facilitate pathological analysis. However, registration of images with tumors is challenging due to absent correspondences induced by the tumor. Furthermore, the tumor growth may displace the tissue, causing larger deformations than what is observed in healthy brains. Therefore, we propose a new reconstruction-driven cascade feature warping (RCFW) network for brain tumor images. We first introduce the symmetric-constrained feature reasoning (SFR) module which reconstructs the missed normal appearance within tumor regions, allowing a dense spatial correspondence between the reconstructed quasi-normal appearance and the atlas. The dilated multi-receptive feature fusion module is further introduced, which collects long-range features from different dimensions to facilitate tumor region reconstruction, especially for large tumor cases. Then, the reconstructed tumor images and atlas are jointly fed into the multi-stage feature warping module (MFW) to progressively predict spatial transformations. The method was performed on the Multimodal Brain Tumor Segmentation (BraTS) 2021 challenge database and compared with six existing methods. Experimental results showed that the proposed method effectively handles the problem of brain tumor image registration, which can maintain the smooth deformation of the tumor region while maximizing the image similarity of normal regions.

Deformable image registration with strategic integration pyramid framework for brain MRI.

Zhang Y, Zhu Q, Xie B, Li T

pubmed logopapersJul 1 2025
Medical image registration plays a crucial role in medical imaging, with a wide range of clinical applications. In this context, brain MRI registration is commonly used in clinical practice for accurate diagnosis and treatment planning. In recent years, deep learning-based deformable registration methods have achieved remarkable results. However, existing methods have not been flexible and efficient in handling the feature relationships of anatomical structures at different levels when dealing with large deformations. To address this limitation, we propose a novel strategic integration registration network based on the pyramid structure. Our strategy mainly includes two aspects of integration: fusion of features at different scales, and integration of different neural network structures. Specifically, we design a CNN encoder and a Transformer decoder to efficiently extract and enhance both global and local features. Moreover, to overcome the error accumulation issue inherent in pyramid structures, we introduce progressive optimization iterations at the lowest scale for deformation field generation. This approach more efficiently handles the spatial relationships of images while improving accuracy. We conduct extensive evaluations across multiple brain MRI datasets, and experimental results show that our method outperforms other deep learning-based methods in terms of registration accuracy and robustness.

Automatic adult age estimation using bone mineral density of proximal femur via deep learning.

Cao Y, Ma Y, Zhang S, Li C, Chen F, Zhang J, Huang P

pubmed logopapersJul 1 2025
Accurate adult age estimation (AAE) is critical for forensic and anthropological applications, yet traditional methods relying on bone mineral density (BMD) face significant challenges due to biological variability and methodological limitations. This study aims to develop an end-to-end Deep Learning (DL) based pipeline for automated AAE using BMD from proximal femoral CT scans. The main objectives are to construct a large-scale dataset of 5151 CT scans from real-world clinical and cadaver cohorts, fine-tune the Segment Anything Model (SAM) for accurate femoral bone segmentation, and evaluate multiple convolutional neural networks (CNNs) for precise age estimation based on segmented BMD data. Model performance was assessed through cross-validation, internal clinical testing, and external post-mortem validation. SAM achieved excellent segmentation performance with a Dice coefficient of 0.928 and an average intersection over union (mIoU) of 0.869. The CNN models achieved an average mean absolute error (MAE) of 5.20 years in cross-validation (male: 5.72; female: 4.51), which improved to 4.98 years in the independent clinical test set (male: 5.32; female: 4.56). External validation on the post-mortem dataset revealed an MAE of 6.91 years, with 6.97 for males and 6.69 for females. Ensemble learning further improved accuracy, reducing MAE to 4.78 years (male: 5.12; female: 4.35) in the internal test set, and 6.58 years (male: 6.64; female: 6.37) in the external validation set. These findings highlight the feasibility of dl-driven AAE and its potential for forensic applications, offering a fully automated framework for robust age estimation.

The impact of multi-modality fusion and deep learning on adult age estimation based on bone mineral density.

Cao Y, Zhang J, Ma Y, Zhang S, Li C, Liu S, Chen F, Huang P

pubmed logopapersJul 1 2025
Age estimation, especially in adults, presents substantial challenges in different contexts ranging from forensic to clinical applications. Bone mineral density (BMD), with its distinct age-related variations, has emerged as a critical marker in this domain. This study aims to enhance chronological age estimation accuracy using deep learning (DL) incorporating a multi-modality fusion strategy based on BMD. We conducted a retrospective analysis of 4296 CT scans from a Chinese population, covering August 2015 to November 2022, encompassing lumbar, femur, and pubis modalities. Our DL approach, integrating multi-modality fusion, was applied to predict chronological age automatically. The model's performance was evaluated using an internal real-world clinical cohort of 644 scans (December 2022 to May 2023) and an external cadaver validation cohort of 351 scans. In single-modality assessments, the lumbar modality excelled. However, multi-modality models demonstrated superior performance, evidenced by lower mean absolute errors (MAEs) and higher Pearson's R² values. The optimal multi-modality model exhibited outstanding R² values of 0.89 overall, 0.88 in females, 0.90 in males, with the MAEs of 4.05 overall, 3.69 in females, 4.33 in males in the internal validation cohort. In the external cadaver validation, the model maintained favourable R² values (0.84 overall, 0.89 in females, 0.82 in males) and MAEs (5.01 overall, 4.71 in females, 5.09 in males), highlighting its generalizability across diverse scenarios. The integration of multi-modalities fusion with DL significantly refines the accuracy of adult age estimation based on BMD. The AI-based system that effectively combines multi-modalities BMD data, presenting a robust and innovative tool for accurate AAE, poised to significantly improve both geriatric diagnostics and forensic investigations.

TCDE-Net: An unsupervised dual-encoder network for 3D brain medical image registration.

Yang X, Li D, Deng L, Huang S, Wang J

pubmed logopapersJul 1 2025
Medical image registration is a critical task in aligning medical images from different time points, modalities, or individuals, essential for accurate diagnosis and treatment planning. Despite significant progress in deep learning-based registration methods, current approaches still face considerable challenges, such as insufficient capture of local details, difficulty in effectively modeling global contextual information, and limited robustness in handling complex deformations. These limitations hinder the precision of high-resolution registration, particularly when dealing with medical images with intricate structures. To address these issues, this paper presents a novel registration network (TCDE-Net), an unsupervised medical image registration method based on a dual-encoder architecture. The dual encoders complement each other in feature extraction, enabling the model to effectively handle large-scale nonlinear deformations and capture intricate local details, thereby enhancing registration accuracy. Additionally, the detail-enhancement attention module aids in restoring fine-grained features, improving the network's capability to address complex deformations such as those at gray-white matter boundaries. Experimental results on the OASIS, IXI, and Hammers-n30r95 3D brain MR dataset demonstrate that this method outperforms commonly used registration techniques across multiple evaluation metrics, achieving superior performance and robustness. Our code is available at https://github.com/muzidongxue/TCDE-Net.

Mamba-based deformable medical image registration with an annotated brain MR-CT dataset.

Wang Y, Guo T, Yuan W, Shu S, Meng C, Bai X

pubmed logopapersJul 1 2025
Deformable registration is essential in medical image analysis, especially for handling various multi- and mono-modal registration tasks in neuroimaging. Existing studies lack exploration of brain MR-CT registration, and face challenges in both accuracy and efficiency improvements of learning-based methods. To enlarge the practice of multi-modal registration in brain, we present SR-Reg, a new benchmark dataset comprising 180 volumetric paired MR-CT images and annotated anatomical regions. Building on this foundation, we introduce MambaMorph, a novel deformable registration network based on an efficient state space model Mamba for global feature learning, with a fine-grained feature extractor for low-level embedding. Experimental results demonstrate that MambaMorph surpasses advanced ConvNet-based and Transformer-based networks across several multi- and mono-modal tasks, showcasing impressive enhancements of efficacy and efficiency. Code and dataset are available at https://github.com/mileswyn/MambaMorph.

Semi-supervised temporal attention network for lung 4D CT ventilation estimation.

Xue P, Zhang J, Ma L, Li Y, Ji H, Ren T, Hu Z, Ren M, Zhang Z, Dong E

pubmed logopapersJul 1 2025
Computed tomography (CT)-derived ventilation estimation, also known as CT ventilation imaging (CTVI), is emerging as a potentially crucial tool for designing functional avoidance radiotherapy treatment plans and evaluating therapy responses. However, most conventional CTVI methods are highly dependent on deformation fields from image registration to track volume variations, making them susceptible to registration errors and resulting in low estimation accuracy. In addition, existing deep learning-based CTVI methods typically have the issue of requiring a large amount of labeled data and cannot fully utilize temporal characteristics of 4D CT images. To address these issues, we propose a semi-supervised temporal attention (S<sup>2</sup>TA) network for lung 4D CT ventilation estimation. Specifically, the semi-supervised learning framework involves a teacher model for generating pseudo-labels from unlabeled 4D CT images, to train a student model that takes both labeled and unlabeled 4D CT images as input. The teacher model is updated as the moving average of the instantly trained student, to prevent it from being abruptly impacted by incorrect pseudo-labels. Furthermore, to fully exploit the temporal information of 4D CT images, a temporal attention architecture is designed to effectively capture the temporal relationships across multiple phases in 4D CT image sequence. Extensive experiments on three publicly available thoracic 4D CT datasets show that our proposed method can achieve higher estimation accuracy than state-of-the-art methods, which could potentially be used for lung functional avoidance radiotherapy and treatment response modeling.

Association of Psychological Resilience With Decelerated Brain Aging in Cognitively Healthy World Trade Center Responders.

Seeley SH, Fremont R, Schreiber Z, Morris LS, Cahn L, Murrough JW, Schiller D, Charney DS, Pietrzak RH, Perez-Rodriguez MM, Feder A

pubmed logopapersJul 1 2025
Despite their exposure to potentially traumatic stressors, the majority of World Trade Center (WTC) responders-those who worked on rescue, recovery, and cleanup efforts on or following September 11, 2001-have shown psychological resilience, never developing long-term psychopathology. Psychological resilience may be protective against the earlier age-related cognitive changes associated with posttraumatic stress disorder (PTSD) in this cohort. In the current study, we calculated the difference between estimated brain age from structural magnetic resonance imaging (MRI) data and chronological age in WTC responders who participated in a parent functional MRI study of resilience (<i>N</i> = 97). We hypothesized that highly resilient responders would show the least brain aging and explored associations between brain aging and psychological and cognitive measures. WTC responders screened for the absence of cognitive impairment were classified into 3 groups: a WTC-related PTSD group (<i>n</i> = 32), a Highly Resilient group without lifetime psychopathology despite high WTC-related exposure (<i>n</i> = 34), and a Lower WTC-Exposed control group also without lifetime psychopathology (<i>n</i> = 31). We used <i>BrainStructureAges</i>, a deep learning algorithm that estimates voxelwise age from T1-weighted MRI data to calculate decelerated (or accelerated) brain aging relative to chronological age. Globally, brain aging was decelerated in the Highly Resilient group and accelerated in the PTSD group, with a significant group difference (<i>p</i> = .021, Cohen's <i>d</i> = 0.58); the Lower WTC-Exposed control group exhibited no significant brain age gap or group difference. Lesser brain aging was associated with resilience-linked factors including lower emotional suppression, greater optimism, and better verbal learning. Cognitively healthy WTC responders show differences in brain aging related to resilience and PTSD.

A Workflow-Efficient Approach to Pre- and Post-Operative Assessment of Weight-Bearing Three-Dimensional Knee Kinematics.

Banks SA, Yildirim G, Jachode G, Cox J, Anderson O, Jensen A, Cole JD, Kessler O

pubmed logopapersJul 1 2025
Knee kinematics during daily activities reflect disease severity preoperatively and are associated with clinical outcomes after total knee arthroplasty (TKA). It is widely believed that measured kinematics would be useful for preoperative planning and postoperative assessment. Despite decades-long interest in measuring three-dimensional (3D) knee kinematics, no methods are available for routine, practical clinical examinations. We report a clinically practical method utilizing machine-learning-enhanced software and upgraded C-arm fluoroscopy for the accurate and time-efficient measurement of pre-TKA and post-TKA 3D dynamic knee kinematics. Using a common C-arm with an upgraded detector and software, we performed an 8-s horizontal sweeping pulsed fluoroscopic scan of the weight-bearing knee joint. The patient's knee was then imaged using pulsed C-arm fluoroscopy while performing standing, kneeling, squatting, stair, chair, and gait motion activities. We used limited-arc cone-beam reconstruction methods to create 3D models of the femur and tibia/fibula bones with implants, which can then be used to perform model-image registration to quantify the 3D knee kinematics. The proposed protocol can be accomplished by an individual radiology technician in ten minutes and does not require additional equipment beyond a step and stool. The image analysis can be performed by a computer onboard the upgraded c-arm or in the cloud, before loading the examination results into the Picture Archiving and Communication System and Electronic Medical Record systems. Weight-bearing kinematics affects knee function pre- and post-TKA. It has long been exclusively the domain of researchers to make such measurements. We present an approach that leverages common, but digitally upgraded, imaging hardware and software to implement an efficient examination protocol for accurately assessing 3D knee kinematics. With these capabilities, it will be possible to include dynamic 3D knee kinematics as a component of the routine clinical workup for patients who have diseased or replaced knees.
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