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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.

AI-enhanced patient-specific dosimetry in I-131 planar imaging with a single oblique view.

Jalilifar M, Sadeghi M, Emami-Ardekani A, Bitarafan-Rajabi A, Geravand K, Geramifar P

pubmed logopapersJul 8 2025
This study aims to enhance the dosimetry accuracy in <sup>131</sup>I planar imaging by utilizing a single oblique view and Monte Carlo (MC) validated dose point kernels (DPKs) alongside the integration of artificial intelligence (AI) for accurate dose prediction within planar imaging. Forty patients with thyroid cancers post-thyroidectomy surgery and 30 with neuroendocrine tumors underwent planar and SPECT/CT imaging. Using whole-body (WB) planar images with an additional oblique view, organ thicknesses were estimated. DPKs and organ-specific S-values were used to estimate the absorbed doses. Four AI algorithms- multilayer perceptron (MLP), linear regression, support vector regression model, decision tree, convolution neural network, and U-Net were used for dose estimation. Planar image counts, body thickness, patient BMI, age, S-values, and tissue attenuation coefficients were imported as input into the AI algorithm. To provide the ground truth, the CT-based segmentation generated binary masks for each organ, and the corresponding SPECT images were used for GATE MC dosimetry. The MLP-predicted dose values across all organs represented superior performance with the lowest mean absolute error in the liver but higher in the spleen and salivary glands. Notably, MLP-based dose estimations closely matched ground truth data with < 15% differences in most tissues. The MLP-estimated dose values present a robust patient-specific dosimetry approach capable of swiftly predicting absorbed doses in different organs using WB planar images and a single oblique view. This approach facilitates the implementation of 2D planar imaging as a pre-therapeutic technique for a more accurate assessment of the administrated activity.

A novel framework for fully-automated co-registration of intravascular ultrasound and optical coherence tomography imaging data

Xingwei He, Kit Mills Bransby, Ahmet Emir Ulutas, Thamil Kumaran, Nathan Angelo Lecaros Yap, Gonul Zeren, Hesong Zeng, Yaojun Zhang, Andreas Baumbach, James Moon, Anthony Mathur, Jouke Dijkstra, Qianni Zhang, Lorenz Raber, Christos V Bourantas

arxiv logopreprintJul 8 2025
Aims: To develop a deep-learning (DL) framework that will allow fully automated longitudinal and circumferential co-registration of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) images. Methods and results: Data from 230 patients (714 vessels) with acute coronary syndrome that underwent near-infrared spectroscopy (NIRS)-IVUS and OCT imaging in their non-culprit vessels were included in the present analysis. The lumen borders annotated by expert analysts in 61,655 NIRS-IVUS and 62,334 OCT frames, and the side branches and calcific tissue identified in 10,000 NIRS-IVUS frames and 10,000 OCT frames, were used to train DL solutions for the automated extraction of these features. The trained DL solutions were used to process NIRS-IVUS and OCT images and their output was used by a dynamic time warping algorithm to co-register longitudinally the NIRS-IVUS and OCT images, while the circumferential registration of the IVUS and OCT was optimized through dynamic programming. On a test set of 77 vessels from 22 patients, the DL method showed high concordance with the expert analysts for the longitudinal and circumferential co-registration of the two imaging sets (concordance correlation coefficient >0.99 for the longitudinal and >0.90 for the circumferential co-registration). The Williams Index was 0.96 for longitudinal and 0.97 for circumferential co-registration, indicating a comparable performance to the analysts. The time needed for the DL pipeline to process imaging data from a vessel was <90s. Conclusion: The fully automated, DL-based framework introduced in this study for the co-registration of IVUS and OCT is fast and provides estimations that compare favorably to the expert analysts. These features renders it useful in research in the analysis of large-scale data collected in studies that incorporate multimodality imaging to characterize plaque composition.

AI lesion tracking in PET/CT imaging: a proposal for a Siamese-based CNN pipeline applied to PSMA PET/CT scans.

Hein SP, Schultheiss M, Gafita A, Zaum R, Yagubbayli F, Tauber R, Rauscher I, Eiber M, Pfeiffer F, Weber WA

pubmed logopapersJul 8 2025
Assessing tumor response to systemic therapies is one of the main applications of PET/CT. Routinely, only a small subset of index lesions out of multiple lesions is analyzed. However, this operator dependent selection may bias the results due to possible significant inter-metastatic heterogeneity of response to therapy. Automated, AI-based approaches for lesion tracking hold promise in enabling the analysis of many more lesions and thus providing a better assessment of tumor response. This work introduces a Siamese CNN approach for lesion tracking between PET/CT scans. Our approach is applied on the laborious task of tracking a high number of bone lesions in full-body baseline and follow-up [<sup>68</sup>Ga]Ga- or [<sup>18</sup>F]F-PSMA PET/CT scans after two cycles of [<sup>177</sup>Lu]Lu-PSMA therapy of metastatic castration resistant prostate cancer patients. Data preparation includes lesion segmentation and affine registration. Our algorithm extracts suitable lesion patches and forwards them into a Siamese CNN trained to classify the lesion patch pairs as corresponding or non-corresponding lesions. Experiments have been performed with different input patch types and a Siamese network in 2D and 3D. The CNN model successfully learned to classify lesion assignments, reaching an accuracy of 83 % in its best configuration with an AUC = 0.91. For corresponding lesions the pipeline accomplished lesion tracking accuracy of even 89 %. We proved that a CNN may facilitate the tracking of multiple lesions in PSMA PET/CT scans. Future clinical studies are necessary if this improves the prediction of the outcome of therapies.

Development and validation of an improved volumetric breast density estimation model using the ResNet technique.

Asai Y, Yamamuro M, Yamada T, Kimura Y, Ishii K, Nakamura Y, Otsuka Y, Kondo Y

pubmed logopapersJul 7 2025
&#xD;Temporal changes in volumetric breast density (VBD) may serve as prognostic biomarkers for predicting the risk of future breast cancer development. However, accurately measuring VBD from archived X-ray mammograms remains challenging. In a previous study, we proposed a method to estimate volumetric breast density using imaging parameters (tube voltage, tube current, and exposure time) and patient age. This approach, based on a multiple regression model, achieved a determination coefficient (R²) of 0.868. &#xD;Approach:&#xD;In this study, we developed and applied machine learning models-Random Forest, XG-Boost-and the deep learning model Residual Network (ResNet) to the same dataset. Model performance was assessed using several metrics: determination coefficient, correlation coefficient, root mean square error, mean absolute error, root mean square percentage error, and mean absolute percentage error. A five-fold cross-validation was conducted to ensure robust validation. &#xD;Main results:&#xD;The best-performing fold resulted in R² values of 0.895, 0.907, and 0.918 for Random Forest, XG-Boost, and ResNet, respectively, all surpassing the previous study's results. ResNet consistently achieved the lowest error values across all metrics. &#xD;Significance:&#xD;These findings suggest that ResNet successfully achieved the task of accurately determining VBD from past mammography-a task that has not been realised to date. We are confident that this achievement contributes to advancing research aimed at predicting future risks of breast cancer development by enabling high-accuracy time-series analyses of retrospective VBD.&#xD.

DHR-Net: Dynamic Harmonized registration network for multimodal medical images.

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

pubmed logopapersJul 5 2025
Although deep learning has driven remarkable advancements in medical image registration, deep neural network-based non-rigid deformation field generation methods demonstrate high accuracy in single-modality scenarios. However, multi-modal medical image registration still faces critical challenges. To address the issues of insufficient anatomical consistency and unstable deformation field optimization in cross-modal registration tasks among existing methods, this paper proposes an end-to-end medical image registration method based on a Dynamic Harmonized Registration framework (DHR-Net). DHR-Net employs a cascaded two-stage architecture, comprising a translation network and a registration network that operate in sequential processing phases. Furthermore, we propose a loss function based on the Noise Contrastive Estimation framework, which enhances anatomical consistency in cross-modal translation by maximizing mutual information between input and transformed image patches. This loss function incorporates a dynamic temperature adjustment mechanism that progressively optimizes feature contrast constraints during training to improve high-frequency detail preservation, thereby better constraining the topological structure of target images. Experiments conducted on the M&M Heart Dataset demonstrate that DHR-Net outperforms existing methods in registration accuracy, deformation field smoothness, and cross-modal robustness. The framework significantly enhances the registration quality of cardiac images while demonstrating exceptional performance in preserving anatomical structures, exhibiting promising potential for clinical applications.

Joint Shape Reconstruction and Registration via a Shared Hybrid Diffeomorphic Flow.

Shi H, Wang P, Zhang S, Zhao X, Yang B, Zhang C

pubmed logopapersJul 3 2025
Deep implicit functions (DIFs) effectively represent shapes by using a neural network to map 3D spatial coordinates to scalar values that encode the shape's geometry, but it is difficult to establish correspondences between shapes directly, limiting their use in medical image registration. The recently presented deformation field-based methods achieve implicit templates learning via template field learning with DIFs and deformation field learning, establishing shape correspondence through deformation fields. Although these approaches enable joint learning of shape representation and shape correspondence, the decoupled optimization for template field and deformation field, caused by the absence of deformation annotations lead to a relatively accurate template field but an underoptimized deformation field. In this paper, we propose a novel implicit template learning framework via a shared hybrid diffeomorphic flow (SHDF), which enables shared optimization for deformation and template, contributing to better deformations and shape representation. Specifically, we formulate the signed distance function (SDF, a type of DIFs) as a one-dimensional (1D) integral, unifying dimensions to match the form used in solving ordinary differential equation (ODE) for deformation field learning. Then, SDF in 1D integral form is integrated seamlessly into the deformation field learning. Using a recurrent learning strategy, we frame shape representations and deformations as solving different initial value problems of the same ODE. We also introduce a global smoothness regularization to handle local optima due to limited outside-of-shape data. Experiments on medical datasets show that SHDF outperforms state-of-the-art methods in shape representation and registration.

A novel few-shot learning framework for supervised diffeomorphic image registration network.

Chen K, Han H, Wei J, Zhang Y

pubmed logopapersJul 2 2025
Image registration is a key technique in image processing and analysis. Due to its high complexity, the traditional registration frameworks often fail to meet real-time demands in practice. To address the real-time demand, several deep learning networks for registration have been proposed, including the supervised and the unsupervised networks. Unsupervised networks rely on large amounts of training data to minimize specific loss functions, but the lack of physical information constraints results in the lower accuracy compared with the supervised networks. However, the supervised networks in medical image registration face two major challenges: physical mesh folding and the scarcity of labeled training data. To address these two challenges, we propose a novel few-shot learning framework for image registration. The framework contains two parts: random diffeomorphism generator (RDG) and a supervised few-shot learning network for image registration. By randomly generating a complex vector field, the RDG produces a series of diffeomorphism. With the help of diffeomorphism generated by RDG, one can use only a few image data (theoretically, one image data is enough) to generate a series of labels for training the supervised few-shot learning network. Concerning the elimination of the physical mesh folding phenomenon, in the proposed network, the loss function is only required to ensure the smoothness of deformation (no other control for mesh folding elimination is necessary). The experimental results indicate that the proposed method demonstrates superior performance in eliminating physical mesh folding when compared to other existing learning-based methods. Our code is available at this link https://github.com/weijunping111/RDG-TMI.git.

Robust brain age estimation from structural MRI with contrastive learning

Carlo Alberto Barbano, Benoit Dufumier, Edouard Duchesnay, Marco Grangetto, Pietro Gori

arxiv logopreprintJul 2 2025
Estimating brain age from structural MRI has emerged as a powerful tool for characterizing normative and pathological aging. In this work, we explore contrastive learning as a scalable and robust alternative to supervised approaches for brain age estimation. We introduce a novel contrastive loss function, $\mathcal{L}^{exp}$, and evaluate it across multiple public neuroimaging datasets comprising over 20,000 scans. Our experiments reveal four key findings. First, scaling pre-training on diverse, multi-site data consistently improves generalization performance, cutting external mean absolute error (MAE) nearly in half. Second, $\mathcal{L}^{exp}$ is robust to site-related confounds, maintaining low scanner-predictability as training size increases. Third, contrastive models reliably capture accelerated aging in patients with cognitive impairment and Alzheimer's disease, as shown through brain age gap analysis, ROC curves, and longitudinal trends. Lastly, unlike supervised baselines, $\mathcal{L}^{exp}$ maintains a strong correlation between brain age accuracy and downstream diagnostic performance, supporting its potential as a foundation model for neuroimaging. These results position contrastive learning as a promising direction for building generalizable and clinically meaningful brain representations.

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.
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