Radiogenomics of Alzheimer's disease: exploring gene related metabolic imaging markers

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and considerably determined by genetic factors. Fluorodeoxyglucose positron emission tomography (FDG-PET) can reflect the functional state of glucose metabolism in the brain, and radiomic features of FDG-PET were considered as important imaging markers in AD. However, radiomic features are not highly interpretable, especially lack of explanation of underlying biological and molecular mechanisms. Therefore, this study used radiogenomics analysis to explore prognostic metabolic imaging markers by associating radiomics features and genetic data. In the study, we used the FDG-PET images and genotype data of 389 subjects (Cohort B) enrolled in the ADNI, including 109 AD, 134 healthy controls (HCs), 72 MCI non-converters (MCI-nc) and 74 MCI converters (MCI-c). Firstly, we performed a Genome-wide association study (GWAS) on the genotype data of 998 subjects (Cohort A), including 632 AD and 366 HCs after quality control (QC) steps to identify susceptibility loci as the gene features. Secondly, radiomics features were extracted from the preprocessed PET images. Thirdly, two-sample t-test, rank sum test and F-score were regarded as the feature selection step to select effective radiomic features. Fourthly, a support vector machine (SVM) was used to test the ability of the radiomic features to classify HCs, MCI and AD patients. Finally, we performed the Spearman correlation analysis on the genetic data and radiomic features. As a result, we identified rs429358 and rs2075650 as genome-wide significant signals. The radiomic approach achieved good classification abilities. Two prognostic FDG-PET radiomic features in the amygdala were proven to be correlated with the genetic data.