Rosemary He

Rosemary He, Gabriella Ang, Daniel Tward

Neurodegeneration as measured through magnetic resonance imaging (MRI) is recognized as a potential biomarker for diagnosing Alzheimer's disease (AD), but is generally considered less specific than amyloid or tau based biomarkers. Due to a large amount of variability in brain anatomy between different individuals, we hypothesize that leveraging MRI time series can help improve specificity, by treating each patient as their own baseline. Here we turn to conditional variational autoencoders to generate individualized MRI predictions given the subject's age, disease status and one previous scan. Using serial imaging data from the Alzheimer's Disease Neuroimaging Initiative, we train a novel architecture to build a latent space distribution which can be sampled from to generate future predictions of changing anatomy. This enables us to extrapolate beyond the dataset and predict MRIs up to 10 years. We evaluated the model on a held-out set from ADNI and an independent dataset (from Open Access Series of Imaging Studies). By comparing to several alternatives, we show that our model produces more individualized images with higher resolution. Further, if an individual already has a follow-up MRI, we demonstrate a usage of our model to compute a likelihood ratio classifier for disease status. In practice, the model may be able to assist in early diagnosis of AD and provide a counterfactual baseline trajectory for treatment effect estimation. Furthermore, it generates a synthetic dataset that can potentially be used for downstream tasks such as anomaly detection and classification.

Rosemary Y. He, Jeffrey N. Chiang

Trajectory forecasting in healthcare data has been an important area of research in precision care and clinical integration for computational methods. In recent years, generative AI models have demonstrated promising results in capturing short and long range dependencies in time series data. While these models have also been applied in healthcare, most of them only predict one value at a time, which is unrealistic in a clinical setting where multiple measures are taken at once. In this work, we extend the framework temporal fusion transformer (TFT), a multi-horizon time series prediction tool, and propose TFT-multi, an end-to-end framework that can predict multiple vital trajectories simultaneously. We apply TFT-multi to forecast 5 vital signs recorded in the intensive care unit: blood pressure, pulse, SpO2, temperature and respiratory rate. We hypothesize that by jointly predicting these measures, which are often correlated with one another, we can make more accurate predictions, especially in variables with large missingness. We validate our model on the public MIMIC dataset and an independent institutional dataset, and demonstrate that this approach outperforms state-of-the-art univariate prediction tools including the original TFT and Prophet, as well as vector regression modeling for multivariate prediction. Furthermore, we perform a study case analysis by applying our pipeline to forecast blood pressure changes in response to actual and hypothetical pressor administration.

Rosemary He, Ichiro Takeuchi

Alzheimer's Disease is challenging to diagnose due to our limited understanding of its mechanism and large heterogeneity among patients. Neurodegeneration is studied widely as a biomarker for clinical diagnosis, which can be measured from time series MRI progression. On the other hand, generative AI has shown promise in anomaly detection in medical imaging and used for tasks including tumor detection. However, testing the reliability of such data-driven methods is non-trivial due to the issue of double-dipping in hypothesis testing. In this work, we propose to solve this issue with selective inference and develop a reliable generative AI method for Alzheimer's prediction. We show that compared to traditional statistical methods with highly inflated p-values, selective inference successfully controls the false discovery rate under the desired alpha level while retaining statistical power. In practice, our pipeline could assist clinicians in Alzheimer's diagnosis and early intervention.