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1. Learning Multi-Modal Biomarker Representations via Globally Aligned Longitudinal Enrichments

   https://doi.org/10.1609/aaai.v34i01.5426  

   Lu, Lyujian; Elbeleidy, Saad; Baker, Lauren Zoe; Wang, Hua (June 2020, Proceedings of the AAAI Conference on Artificial Intelligence)

   Alzheimer's Disease (AD) is a chronic neurodegenerative disease that severely impacts patients' thinking, memory and behavior. To aid automatic AD diagnoses, many longitudinal learning models have been proposed to predict clinical outcomes and/or disease status, which, though, often fail to consider missing temporal phenotypic records of the patients that can convey valuable information of AD progressions. Another challenge in AD studies is how to integrate heterogeneous genotypic and phenotypic biomarkers to improve diagnosis prediction. To cope with these challenges, in this paper we propose a longitudinal multi-modal method to learn enriched genotypic and phenotypic biomarker representations in the format of fixed-length vectors that can simultaneously capture the baseline neuroimaging measurements of the entire dataset and progressive variations of the varied counts of follow-up measurements over time of every participant from different biomarker sources. The learned global and local projections are aligned by a soft constraint and the structured-sparsity norm is used to uncover the multi-modal structure of heterogeneous biomarker measurements. While the proposed objective is clearly motivated to characterize the progressive information of AD developments, it is a nonsmooth objective that is difficult to efficiently optimize in general. Thus, we derive an efficient iterative algorithm, whose convergence is rigorously guaranteed in mathematics. We have conducted extensive experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) data using one genotypic and two phenotypic biomarkers. Empirical results have demonstrated that the learned enriched biomarker representations are more effective in predicting the outcomes of various cognitive assessments. Moreover, our model has successfully identified disease-relevant biomarkers supported by existing medical findings that additionally warrant the correctness of our method from the clinical perspective. 

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2. Predicting Longitudinal Outcomes of Alzheimer’s Disease via a Tensor-Based Joint Classification and Regression Mode

   Brand L., Nichols K. (January 2020, The Proceedings of the 25th Pacific Symposium on Biocomputing (PSB 2020))

   Alzheimer's disease (AD) is a serious neurodegenerative condition that affects millions of people across the world. Recently machine learning models have been used to predict the progression of AD, although they frequently do not take advantage of the longitudinal and structural components associated with multi-modal medical data. To address this, we present a new algorithm that uses the multi-block alternating direction method of multipliers to optimize a novel objective that combines multi-modal longitudinal clinical data of various modalities to simultaneously predict the cognitive scores and diagnoses of the participants in the Alzheimer's Disease Neuroimaging Initiative cohort. Our new model is designed to leverage the structure associated with clinical data that is not incorporated into standard machine learning optimization algorithms. This new approach shows state-of-the-art predictive performance and validates a collection of brain and genetic biomarkers that have been recorded previously in AD literature. 

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3. Predicting Cognitive Declines Using Longitudinally Enriched Representations for Imaging Biomarkers

   https://doi.org/10.1109/CVPR42600.2020.00488  

   Lu, Lyujian; Wang, Hua; Elbeleidy, Saad; Nie, Feiping (June 2020, 2020 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR))

   With rapid progress in high-throughput genotyping and neuroimaging, researches of complex brain disorders, such as Alzheimer’s Disease (AD), have gained significant attention in recent years. Many prediction models have been studied to relate neuroimaging measures to cognitive status over the progressions when these disease develops. Missing data is one of the biggest challenge in accurate cognitive score prediction of subjects in longitudinal neuroimaging studies. To tackle this problem, in this paper we propose a novel formulation to learn an enriched representation for imaging biomarkers that can simultaneously capture both the information conveyed by baseline neuroimaging records and that by progressive variations of varied counts of available follow-up records over time. While the numbers of the brain scans of the participants vary, the learned biomarker representation for every participant is a fixed-length vector, which enable us to use traditional learning models to study AD developments. Our new objective is formulated to maximize the ratio of the summations of a number of L1-norm distances for improved robustness, which, though, is difficult to efficiently solve in general. Thus we derive a new efficient iterative solution algorithm and rigorously prove its convergence. We have performed extensive experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. A performance gain has been achieved to predict four different cognitive scores, when we compare the original baseline representations against the learned representations with enrichments. These promising empirical results have demonstrated improved performances of our new method that validate its effectiveness. 

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4. Learning Deeply Enriched Representations of Longitudinal Imaging-Genetic Data to Predict Alzheimer’s Disease Progression

   https://doi.org/10.1109/BIBM52615.2021.9669428  

   Seo, Hoon; Wang, Hua (December 2021, 2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM))

   Alzheimer’s Disease (AD) is a progressive memory disorder that causes irreversible cognitive declines, therefore early diagnosis is imperative to prevent the progression of AD. To this end, many biomarker analysis models have been presented for early AD detection. However, these models may not realize the full data potential due to their failure to integrate longitudinal (dynamic) phenotypic data with (static) genetic data. Sometimes, they may not fully utilize both labeled and unlabeled samples either. To overcome these limitations, we propose a semi-supervised enrichment learning method to learn a fixed-length vectorial representation for each participant, by which the static data record can be integrated with the dynamic data records. We have applied our new method on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort and achieved 75% accuracy on multiclass AD progression prediction by one year in advance. 

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5. Integrating Static and Dynamic Data for Improved Prediction of Cognitive Declines Using Augmented Genotype-Phenotype Representations

   Seo, Hoon; Brand, Lodewijk; Wang, Hua; Nie, Feiping (January 2021, Proceedings of the AAAI Conference on Artificial Intelligence)

   null (Ed.)

   Alzheimer’s Disease (AD) is a chronic neurodegenerative disease that causes severe problems in patients’ thinking, memory, and behavior. An early diagnosis is crucial to prevent AD progression; to this end, many algorithmic approaches have recently been proposed to predict cognitive decline. However, these predictive models often fail to integrate heterogeneous genetic and neuroimaging biomarkers and struggle to handle missing data. In this work we propose a novel objective function and an associated optimization algorithm to identify cognitive decline related to AD. Our approach is designed to incorporate dynamic neuroimaging data by way of a participant-specific augmentation combined with multimodal data integration aligned via a regression task. Our approach, in order to incorporate additional side-information, utilizes structured regularization techniques popularized in recent AD literature. Armed with the fixed-length vector representation learned from the multimodal dynamic and static modalities, conventional machine learning methods can be used to predict the clinical outcomes associated with AD. Our experimental results show that the proposed augmentation model improves the prediction performance on cognitive assessment scores for a collection of popular machine learning algorithms. The results of our approach are interpreted to validate existing genetic and neuroimaging biomarkers that have been shown to be predictive of cognitive decline. 

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