Metabolic phenotyping with computed tomography deep learning for metabolic syndrome, osteoporosis and sarcopenia predicts mortality in adults

Abstract

Background: Computed tomography (CT) body compositions reflect age-related metabolic derangements. We aimed to develop a multi-outcome deep learning model using CT multi-level body composition parameters to detect metabolic syndrome (MS), osteoporosis and sarcopenia by identifying metabolic clusters simultaneously. We also investigated the prognostic value of metabolic phenotyping by CT model for long-term mortality.

Methods: The derivation set (n = 516; 75% train set, 25% internal test set) was constructed using age- and sex-stratified random sampling from two community-based cohorts. Data from participants in the individual health assessment programme (n = 380) were used as the external test set 1. Semi-automatic quantification of body compositions at multiple levels of abdominal CT scans was performed to train a multi-layer perceptron (MLP)-based multi-label classification model. External test set 2 to test the prognostic value of the model output for mortality was built using data from individuals who underwent abdominal CT in a tertiary-level institution (n = 10 141).

Results: The mean ages of the derivation and external sets were 62.8 and 59.7 years, respectively, without difference in sex distribution (women 50%) or body mass index (BMI; 23.9 kg/m2). Skeletal muscle density (SMD) and bone density (BD) showed a more linear decrement across age than skeletal muscle area. Alternatively, an increase in visceral fat area (VFA) was observed in both men and women. Hierarchical clustering based on multi-level CT body composition parameters revealed three distinctive phenotype clusters: normal, MS and osteosarcopenia clusters. The L3 CT-parameter-based model, with or without clinical variables (age, sex and BMI), outperformed clinical model predictions of all outcomes (area under the receiver operating characteristic curve: MS, 0.76 vs. 0.55; osteoporosis, 0.90 vs. 0.79; sarcopenia, 0.85 vs. 0.81 in external test set 1; P < 0.05 for all). VFA contributed the most to the MS predictions, whereas SMD, BD and subcutaneous fat area were features of high importance for detecting osteoporosis and sarcopenia. In external test set 2 (mean age 63.5 years, women 79%; median follow-up 4.9 years), a total of 907 individuals (8.9%) died during follow-up. Among model-predicted metabolic phenotypes, sarcopenia alone (adjusted hazard ratio [aHR] 1.55), MS + sarcopenia (aHR 1.65), osteoporosis + sarcopenia (aHR 1.83) and all three combined (aHR 1.87) remained robust predictors of mortality after adjustment for age, sex and comorbidities.

Conclusions: A CT body composition-based MLP model detected MS, osteoporosis and sarcopenia simultaneously in community-dwelling and hospitalized adults. Metabolic phenotypes predicted by the CT MLP model were associated with long-term mortality, independent of covariates.