Lori L. Beason-Held

Chenyu Gao, Michael E. Kim, Ho Hin Lee et al.

Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural MRI data has become an important task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest. The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 years for cognitively normal participants and MAE of 6.62 years for cognitively impaired participants, while the second method achieves MAE of 4.69 years for cognitively normal participants and MAE of 4.96 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.

Yihao Liu, Chenyu Gao, Lianrui Zuo et al.

Modern deep learning methods have achieved impressive results across tasks from disease classification, estimating continuous biomarkers, to generating realistic medical images. Most of these approaches are trained to model conditional distributions defined by a specific predictive direction with a specific set of input variables. We introduce MetaVoxel, a generative joint diffusion modeling framework that models the joint distribution over imaging data and clinical metadata by learning a single diffusion process spanning all variables. By capturing the joint distribution, MetaVoxel unifies tasks that traditionally require separate conditional models and supports flexible zero-shot inference using arbitrary subsets of inputs without task-specific retraining. Using more than 10,000 T1-weighted MRI scans paired with clinical metadata from nine datasets, we show that a single MetaVoxel model can perform image generation, age estimation, and sex prediction, achieving performance comparable to established task-specific baselines. Additional experiments highlight its capabilities for flexible inference.Together, these findings demonstrate that joint multimodal diffusion offers a promising direction for unifying medical AI models and enabling broader clinical applicability.

Chenyu Gao, Michael E. Kim, Karthik Ramadass et al.

Estimated brain age from magnetic resonance image (MRI) and its deviation from chronological age can provide early insights into potential neurodegenerative diseases, supporting early detection and implementation of prevention strategies. Diffusion MRI (dMRI) presents an opportunity to build an earlier biomarker for neurodegenerative disease prediction because it captures subtle microstructural changes that precede more perceptible macrostructural changes. However, the coexistence of macro- and micro-structural information in dMRI raises the question of whether current dMRI-based brain age estimation models are leveraging the intended microstructural information or if they inadvertently rely on the macrostructural information. To develop a microstructure-specific brain age, we propose a method for brain age identification from dMRI that mitigates the model's use of macrostructural information by non-rigidly registering all images to a standard template. Imaging data from 13,398 participants across 12 datasets were used for the training and evaluation. We compare our brain age models, trained with and without macrostructural information mitigated, with an architecturally similar T1-weighted (T1w) MRI-based brain age model and two recent, popular, openly available T1w MRI-based brain age models that primarily use macrostructural information. We observe difference between our dMRI-based brain age and T1w MRI-based brain age across stages of neurodegeneration, with dMRI-based brain age being older than T1w MRI-based brain age in participants transitioning from cognitively normal (CN) to mild cognitive impairment (MCI), but younger in participants already diagnosed with Alzheimer's disease (AD). Furthermore, dMRI-based brain age may offer advantages over T1w MRI-based brain age in predicting the transition from CN to MCI up to five years before diagnosis.

Chenyu Gao, Kaiwen Xu, Michael E. Kim et al.

Defacing is often applied to head magnetic resonance image (MRI) datasets prior to public release to address privacy concerns. The alteration of facial and nearby voxels has provoked discussions about the true capability of these techniques to ensure privacy as well as their impact on downstream tasks. With advancements in deep generative models, the extent to which defacing can protect privacy is uncertain. Additionally, while the altered voxels are known to contain valuable anatomical information, their potential to support research beyond the anatomical regions directly affected by defacing remains uncertain. To evaluate these considerations, we develop a refacing pipeline that recovers faces in defaced head MRIs using cascaded diffusion probabilistic models (DPMs). The DPMs are trained on images from 180 subjects and tested on images from 484 unseen subjects, 469 of whom are from a different dataset. To assess whether the altered voxels in defacing contain universally useful information, we also predict computed tomography (CT)-derived skeletal muscle radiodensity from facial voxels in both defaced and original MRIs. The results show that DPMs can generate high-fidelity faces that resemble the original faces from defaced images, with surface distances to the original faces significantly smaller than those of a population average face (p < 0.05). This performance also generalizes well to previously unseen datasets. For skeletal muscle radiodensity predictions, using defaced images results in significantly weaker Spearman's rank correlation coefficients compared to using original images (p < 10-4). For shin muscle, the correlation is statistically significant (p < 0.05) when using original images but not statistically significant (p > 0.05) when any defacing method is applied, suggesting that defacing might not only fail to protect privacy but also eliminate valuable information.