In 2015, four million people worldwide died because of the aftermaths of obesity (7% of total deaths), and in 2030, half of humankind is expected to be overweight. Lifestyle interventions in subjects with obesity can prevent the development of obesity-induced metabolic dysfunction but need personalization in order to become effective for diabetes and cardiovascular disease prevention. Visceral adiposity and adipocyte hypertrophy are phenotypes strongly linked to metabolic dysfunction in subjects with obesity. Visceral adiposity can be non-invasively measured using Magnetic Resonance Imaging (MRI). Adipocyte size measurements are however nowadays only feasible using highly invasive biopsy procedures that cause severe patient discomfort, hold a risk for complications and are therefore rarely performed in the personalization of lifestyle interventions. The ProFatMRI research program (ERC-StG 677661) has been focusing on the development of an MRI platform to non-invasively assess fat microstructure.
In the present proof of concept (PoC) project, we enhanced and further developed lipid droplet size measurement approaches successfully developed within ProFatMRI into an effective and reproducible toolkit (FatVirtualBiopsy) for non-invasive human adipocyte size measurements. The present PoC project encompassed the technical development, evaluation and further technical adjustment of the adipocyte size measurement in the realistic setting of imaging human adipose, including both diffusion and relaxation mapping MRI techniques. Diffusion MRI-based techniques were proven to be overall highly sensitive to motion effects when measuring the large diameter of human adipocytes using the hardware of a clinical MRI system, showing moderate correlations to microscopy-based adipocyte size measurements. Relaxation mapping MRI-based techniques showed good correlation to microscopy-based adipocyte size measurements in ex vivo imaging of human adipose tissue. An efficient MR spectroscopy (MRS) technique was particularly developed for accelerated lipid relaxation time measurements and used in the performed ex vivo validation study, allowing the simultaneous assessment of both adipocyte size and adipose tissue fatty acid composition.
The present PoC project results provide the foundation towards a non-invasive imaging toolkit for measuring adipocyte size that can be integrated into clinical prevention, targeting a wide range of medical specialists involved in obesity treatment. The further in vivo validation of the FatVirtualBiopsy results will therefore contribute to transform the personalization of lifestyle interventions and drastically improve their effectiveness in subjects with obesity towards diabetes and cardiovascular disease prevention.
