The accumulation of inter-muscular adipose tissue (IMAT) interdigitated between muscle fibers beneath the muscle fascia represents a main underlying mechanism by which chronic diseases cause physical disability and increase mortality. We recently reported that human IMAT has a unique gene expression pattern distinct from subcutaneous fat and skeletal muscle and directly modulates skeletal muscle insulin sensitivity. Herein we will determine whether computational integration of distinctive innovative non-invasive optoacoustic microscopy (MiROM), multispectral optoacoustic tomography (MSOT), and MRI imaging patterns with region-specific cellular compositions, spatial gene expression patterns and key metabolic fluxes of IMAT is capable of visualizing changes in human IMAT in response to lifestyle interventions. With this approach, we aim to develop a standardized tool for the non-invasive assessment of metabolic disease and the prediction of its progression or remission under personalized treatment strategies in humans.