L. Brattain
Publications
Toward Personalized Digital Twins for Cognitive Decline Assessment: A Multimodal, Uncertainty-Aware Framework
Cognitive decline is highly heterogeneous across individuals, which complicates prognosis, trial design, and treatment planning. We present the Personalized Cognitive Decline Assessment Digital Twin (PCD-DT), a multimodal and uncertainty-aware framework for modeling patient-specific disease trajectories from sparse, noisy, and irregular longitudinal data. The framework combines three methodological components: (1) latent state-space models for individualized temporal dynamics, (2) multimodal fusion for clinical, biomarker, and imaging features, and (3) uncertainty-aware validation and adaptive updating for robust digital twin operation. We also outline how conditional generative models can support data augmentation and stress testing for underrepresented progression patterns. As a preliminary feasibility study, we analyze longitudinal TADPOLE trajectories and show clear separation between cognitively normal and Alzheimer's disease cohorts in ADAS13, ventricle volume, and hippocampal volume over five years. We further conduct a multimodal next-visit prediction ablation using an LSTM sequence model on 3{,}003 visit-pair sequences derived from TADPOLE, where the combined cognitive plus MRI configuration achieves the lowest standardized RMSE for both ADAS13 (0.4419) and ventricle volume (0.5842), outperforming a Last Observation Carried Forward baseline. A Bayesian tensor modeling component for high-dimensional imaging fusion is also discussed. These results support the feasibility of the proposed architecture while also highlighting the need for stronger uncertainty calibration and longer-horizon predictive evaluation. The PCD-DT framework provides a principled starting point for personalized in silico modeling in neurodegenerative disease. This work positions PCD-DT as a foundational step toward clinically deployable, uncertainty-aware digital twin systems.
Evaluating TabPFN for Mild Cognitive Impairment to Alzheimer's Disease Conversion in Data Limited Settings
Accurate prediction of conversion from Mild Cognitive Impairment (MCI) to Alzheimers Diseases (AD) is essential for early intervention, however, developing reliable conversion predictive models is difficult to develop due to limited longitudinal data availability We evaluate TabPFN (Tabular Pre-Trained Foundation Network) against traditional machine learning methods for predicting 3 year MCI to AD conversion using the TADPOLE dataset derived from ADNI. Using multimodal biomarker features extracted from demographics, APOE4, MRI volumes, CSF markers, and PET imaging, we conducted an experimental comparison across varying training set sizes (N=50 to 1000) and models including XGBoost, Random Forest, LightGBM, and Logistic Regression. TabPFN achieved one the highest performance (AUC=0.892), outperforming LightGBM (AUC=0.860) and demonstrating advantages in low data settings. At N=50 training samples, TabPFN maintained strong AUC while the traditional machine learning models struggles at small training samples. These findings demonstrate that foundation models are promising for disease prediction in data limited scenarios, such as Alzheimers diseases.
CognitiveTwin: Robust Multi-Modal Digital Twins for Predicting Cognitive Decline in Alzheimer's Disease
Predicting individual cognitive decline in Alzheimer's disease (AD) is difficult due to the heterogeneity of disease progression. Reliable clinical tools require not only high accuracy but also fairness across demographics and robustness to missing data. We present CognitiveTwin, a digital twin framework that predicts patient-specific cognitive trajectories. The model integrates multi-modal longitudinal data (cognitive scores, magnetic resonance imaging, positron emission tomography, cerebrospinal fluid biomarkers, and genetics). We use a Transformer-based architecture to fuse these modalities and a Deep Markov Model to capture temporal dynamics. We trained and evaluated the framework using data from 1,666 patients in the TADPOLE (Alzheimer's Disease Neuroimaging Initiative) dataset. We assessed the model for prediction error, demographic fairness, and robustness to missing-not-at-random (MNAR) data patterns. ognitiveTwin provides accurate and personalized predictions of cognitive decline. Its demonstrated fairness across patient demographics and resilience to clinical dropout make it a reliable tool for clinical trial enrichment and personalized care planning.
GeoVision-Enabled Digital Twin for Hybrid Autonomous-Teleoperated Medical Responses
Remote medical response systems are increasingly being deployed to support emergency care in disaster-affected and infrastructure-limited environments. Enabled by GeoVision capabilities, this paper presents a Digital Twin architecture for hybrid autonomous-teleoperated medical response systems. The proposed framework integrates perception and adaptive navigation with a Digital Twin, synchronized in real-time, that mirrors system states, environmental dynamics, patient conditions, and mission objectives. Unlike traditional ground control interfaces, the Digital Twin provides remote clinical and operational users with an intuitive, continuously updated virtual representation of the platform and its operational context, enabling enhanced situational awareness and informed decision-making.
Hybrid Diffusion Model for Breast Ultrasound Image Augmentation
We propose a hybrid diffusion-based augmentation framework to overcome the critical challenge of ultrasound data augmentation in breast ultrasound (BUS) datasets. Unlike conventional diffusion-based augmentations, our approach improves visual fidelity and preserves ultrasound texture by combining text-to-image generation with image-to-image (img2img) refinement, as well as fine-tuning with low-rank adaptation (LoRA) and textual inversion (TI). Our method generated realistic, class-consistent images on an open-source Kaggle breast ultrasound image dataset (BUSI). Compared to the Stable Diffusion v1.5 baseline, incorporating TI and img2img refinement reduced the Frechet Inception Distance (FID) from 45.97 to 33.29, demonstrating a substantial gain in fidelity while maintaining comparable downstream classification performance. Overall, the proposed framework effectively mitigates the low-fidelity limitations of synthetic ultrasound images and enhances the quality of augmentation for robust diagnostic modeling.