Vafaei, Fereydoon, authorAnderson, Charles, advisorKirby, Michael, committee memberBlanchard, Nathaniel, committee memberBurzynska, Agnieszka, committee member2023-06-012025-05-262023https://hdl.handle.net/10217/236681Machine Learning (ML) and Deep Learning (DL) are now considered as state-of-the-art assistive AI technologies that help neuroscientists, neurologists and medical professionals with early diagnosis of neurodegenerative diseases and cognitive decline as a consequence of unhealthy brain aging. Brain Age Prediction (BAP) is the process of estimating a person's biological age using Neuroimaging data, and the difference between the predicted age and the subject's chronological age, known as Delta, is regarded as a biomarker for healthy versus unhealthy brain aging. Accurate and efficient BAP is an important research topic, and hence ML/DL methods have been developed for this task. There are different modalities of Neuroimaging such as Magnetic Resonance Imaging (MRI) that have been used for BAP in the past. Diffusion Tensor Imaging (DTI) is an advanced quantitative Neuroimaging technology that gives insight into microstructure of White Matter tracts that connect different parts of the brain to function properly. DTI data is high-dimensional, and age-related microstructural changes in White Matter include non-linear patterns. In this study, we perform a series of analytical experiments using ML and DL methods to investigate the applicability of DTI data for BAP. We also investigate which Diffusivity Parameters, which are DTI metrics that reflect direction and magnitude of diffusion of water molecules in the brain, are relevant for BAP as a Supervised Learning task. Moreover, we propose, implement, and analyze a novel methodology that can detect age-related anomalies (high Deltas), and can overcome some of the major and fundamental limitations of the current supervised approach for BAP, such as "Chronological Age Label Inconsistency". Our proposed methodology, which combines Unsupervised Anomaly Detection (UAD) and supervised BAP, focuses on addressing a fundamental challenge in BAP which is how to interpret a model's error. Should a researcher interpret a model's error as an indication of unhealthy brain aging or the model's poor performance that should be eliminated? We argue that the underlying cause of this problem is the inconsistency of chronological age labels as the ground truth of the Supervised Learning task, which is the common basis of training ML/DL models. Our Unsupervised Learning methods and findings open a new possibility to detect irregularities and abnormalities in the aging brain using DTI scans, independent of inconsistent chronological age labels. The results of our proposed methodology show that combining label-independent UAD and supervised BAP provides a more reliable and methodical way for error analysis than the current supervised BAP approach when it is used in isolation. We also provide visualization and explanations on how our ML/DL methods make their decisions for BAP. Explainability and generalization of our ML/DL models are two important aspects of our study.born digitaldoctoral dissertationsengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.deep learningmachine learningunsupervised learningdiffusion tensor imagingbrain age predictionneuroimagingTextEmbargo Expires: 05/26/2025