Ahmad Wisnu Mulyadi

Kwanseok Oh, Da-Woon Heo, Ahmad Wisnu Mulyadi et al.

Deep learning (DL) for predicting Alzheimer's disease (AD) has provided timely intervention in disease progression yet still demands attentive interpretability to explain how their DL models make definitive decisions. Recently, counterfactual reasoning has gained increasing attention in medical research because of its ability to provide a refined visual explanatory map. However, such visual explanatory maps based on visual inspection alone are insufficient unless we intuitively demonstrate their medical or neuroscientific validity via quantitative features. In this study, we synthesize the counterfactual-labeled structural MRIs using our proposed framework and transform it into a gray matter density map to measure its volumetric changes over the parcellated region of interest (ROI). We also devised a lightweight linear classifier to boost the effectiveness of constructed ROIs, promoted quantitative interpretation, and achieved comparable predictive performance to DL methods. Throughout this, our framework produces an ``AD-relatedness index'' for each ROI and offers an intuitive understanding of brain status for an individual patient and across patient groups with respect to AD progression.

Ahmad Wisnu Mulyadi, Heung-Il Suk

Extensive adoption of electronic health records (EHRs) offers opportunities for their use in various downstream clinical analyses. To accomplish this purpose, enriching an EHR cohort with external knowledge (e.g., standardized medical ontology and wealthy semantics) could help us reveal more comprehensive insights via a spectrum of informative relations among medical codes. Nevertheless, harnessing those beneficial interconnections was scarcely exercised, especially in the medication recommendation task. This study proposes a novel Knowledge-Induced Medicine Prescribing Network (KindMed) to recommend medicines by inducing knowledge from myriad medical-related external sources upon the EHR cohort and rendering interconnected medical codes as medical knowledge graphs (KGs). On top of relation-aware graph representation learning to obtain an adequate embedding over such KGs, we leverage hierarchical sequence learning to discover and fuse temporal dynamics of clinical (i.e., diagnosis and procedures) and medicine streams across patients' historical admissions to foster personalized recommendations. Eventually, we employ attentive prescribing that accounts for three essential patient representations, i.e., a summary of joint historical medical records, clinical progression, and the current clinical state of patients. We validated the effectiveness of our KindMed on the augmented real-world EHR cohorts, achieving improved recommendation performances against a handful of graph-driven baselines.

Ahmad Wisnu Mulyadi, Wonsik Jung, Kwanseok Oh et al.

Diagnosing Alzheimer's disease (AD) involves a deliberate diagnostic process owing to its innate traits of irreversibility with subtle and gradual progression. These characteristics make AD biomarker identification from structural brain imaging (e.g., structural MRI) scans quite challenging. Furthermore, there is a high possibility of getting entangled with normal aging. We propose a novel deep-learning approach through eXplainable AD Likelihood Map Estimation (XADLiME) for AD progression modeling over 3D sMRIs using clinically-guided prototype learning. Specifically, we establish a set of topologically-aware prototypes onto the clusters of latent clinical features, uncovering an AD spectrum manifold. We then measure the similarities between latent clinical features and well-established prototypes, estimating a "pseudo" likelihood map. By considering this pseudo map as an enriched reference, we employ an estimating network to estimate the AD likelihood map over a 3D sMRI scan. Additionally, we promote the explainability of such a likelihood map by revealing a comprehensible overview from two perspectives: clinical and morphological. During the inference, this estimated likelihood map served as a substitute over unseen sMRI scans for effectively conducting the downstream task while providing thorough explainable states.

Seungwoo Jeong, Wonjun Ko, Ahmad Wisnu Mulyadi et al.

Modeling non-Euclidean data is drawing extensive attention along with the unprecedented successes of deep neural networks in diverse fields. Particularly, a symmetric positive definite matrix is being actively studied in computer vision, signal processing, and medical image analysis, due to its ability to learn beneficial statistical representations. However, owing to its rigid constraints, it remains challenging to optimization problems and inefficient computational costs, especially, when incorporating it with a deep learning framework. In this paper, we propose a framework to exploit a diffeomorphism mapping between Riemannian manifolds and a Cholesky space, by which it becomes feasible not only to efficiently solve optimization problems but also to greatly reduce computation costs. Further, for dynamic modeling of time-series data, we devise a continuous manifold learning method by systematically integrating a manifold ordinary differential equation and a gated recurrent neural network. It is worth noting that due to the nice parameterization of matrices in a Cholesky space, training our proposed network equipped with Riemannian geometric metrics is straightforward. We demonstrate through experiments over regular and irregular time-series datasets that our proposed model can be efficiently and reliably trained and outperforms existing manifold methods and state-of-the-art methods in various time-series tasks.

Ahmad Wisnu Mulyadi, Eunji Jun, Heung-Il Suk

Electronic health records (EHR) consist of longitudinal clinical observations portrayed with sparsity, irregularity, and high-dimensionality, which become major obstacles in drawing reliable downstream clinical outcomes. Although there exist great numbers of imputation methods to tackle these issues, most of them ignore correlated features, temporal dynamics and entirely set aside the uncertainty. Since the missing value estimates involve the risk of being inaccurate, it is appropriate for the method to handle the less certain information differently than the reliable data. In that regard, we can use the uncertainties in estimating the missing values as the fidelity score to be further utilized to alleviate the risk of biased missing value estimates. In this work, we propose a novel variational-recurrent imputation network, which unifies an imputation and a prediction network by taking into account the correlated features, temporal dynamics, as well as the uncertainty. Specifically, we leverage the deep generative model in the imputation, which is based on the distribution among variables, and a recurrent imputation network to exploit the temporal relations, in conjunction with utilization of the uncertainty. We validated the effectiveness of our proposed model on two publicly available real-world EHR datasets: PhysioNet Challenge 2012 and MIMIC-III, and compared the results with other competing state-of-the-art methods in the literature.

Eunji Jun, Ahmad Wisnu Mulyadi, Jaehun Choi et al.

Electronic health records (EHR) are characterized as non-stationary, heterogeneous, noisy, and sparse data; therefore, it is challenging to learn the regularities or patterns inherent within them. In particular, sparseness caused mostly by many missing values has attracted the attention of researchers, who have attempted to find a better use of all available samples for determining the solution of a primary target task through the defining a secondary imputation problem. Methodologically, existing methods, either deterministic or stochastic, have applied different assumptions to impute missing values. However, once the missing values are imputed, most existing methods do not consider the fidelity or confidence of the imputed values in the modeling of downstream tasks. Undoubtedly, an erroneous or improper imputation of missing variables can cause difficulties in modeling as well as a degraded performance. In this study, we present a novel variational recurrent network that (i) estimates the distribution of missing variables allowing to represent uncertainty in the imputed values, (ii) updates hidden states by explicitly applying fidelity based on a variance of the imputed values during a recurrence (i.e., uncertainty propagation over time), and (iii) predicts the possibility of in-hospital mortality. It is noteworthy that our model can conduct these procedures in a single stream and learn all network parameters jointly in an end-to-end manner. We validated the effectiveness of our method using the public datasets of MIMIC-III and PhysioNet challenge 2012 by comparing with and outperforming other state-of-the-art methods for mortality prediction considered in our experiments. In addition, we identified the behavior of the model that well represented the uncertainties for the imputed estimates, which indicated a high correlation between the calculated MAE and the uncertainty.