METABOLIC IMAGING GROUP (MIG)

Head: Associate Professor S. Sendhil Velan

Research Overview

The goal of the Metabolic Imaging Group (MIG) is to conduct translational imaging research in the domain of metabolic diseases (Obesity, Diabetes, Nutrition and Metabolism) using Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS).   We have focused on the development of non-invasive imaging strategies for detecting early changes in lipid/glucose metabolism, quantifying adipose tissue depots and ectopic fat infiltration, and for assessing the modulation of lipid/glucose metabolism in response to an intervention.

We have ongoing projects to evaluate the fat partitioning, insulin resistance and metabolic dysfunction with interventions including Asian diets. We are also establishing quantitative imaging methods for fat quantity, fat quality, fat composition and detection of metabolites in various organs including abdomen, liver, skeletal muscle, kidney, pancreas  and brown / beige adipose tissues.   We also perform interventions including pharmacological, nutritional, exercise, calorie restriction, cold exposure etc. for improving the whole body metabolism and insulin sensitivity. 

From a methodological perspective, our research program includes:

•     Investigation of fundamental MR properties in intact tissues

•     Probing of metabolic pathways using labelled compounds

•     Development of quantitative acquisition / post-processing techniques for detecting new biomarkers for the metabolic syndrome that respond to biological  and clinical interventions and therapeutic procedures

•     Post-processing and quantitation of fat depots and metabolites

•     Multi-modal imaging (e.g. MRI-MRS, PET and MSOT) for exploring new biomarkers and to enhance the imaging capability

•     Metabolomics by solution state NMR and High Resolution Magic Angle Spinning Spectroscopy

Supporting Biological Tasks
• Assess mitochondrial function and bioenergetics in metabolic syndrome
• Tissue morphology  by histology, immunohistochemistry and other microscopic imaging
• Mechanisms  by gene expression analysis using RT-PCR and western blot analysis
• Oral glucose tolerance test (OGTT) to analyze glucose and insulin levels.

While increased whole body adiposity is associated with increased metabolic alterations, different fat depots have very different metabolic effects. Subcutaneous adipose depots play a protective role because of their ability to buffer the flux of free fatty acids in the form of metabolically inert triglycerides. Visceral adipose tissue and ectopic fat infiltration in the liver, pancreas, skeletal muscle and cardiac muscle are markers of dysfunctional subcutaneous adipose tissue and are associated with worsened metabolic health. Adipose tissue dysfunction is also marked by hypertrophic adipocytes. A hyperplastic adipose tissue morphology, on the other hand, indicates a higher residual capacity for adipose tissue expansion which can delay the onset of a lipotoxic lipid profile. In the above context, we have focussed on the quantification of individual adipose tissue compartments and ectopic fat using MRS and MRI, MR-based investigation of the fatty acid oxidation pathways using 13C labelled compounds, investigating the fundamental MR properties of white and brown adipose tissue and the development of novel MR-based markers for hypertrophic obesity. These methods have been used for studying the comorbidities of the metabolic syndrome, and for understanding the nexus between adipose tissue morphology, hepatic steatosis, intramyocellar lipid, coronary dysfunction, insulin resistance and type 2 diabetes.

We recently expanded our research in investigating the role of brown adipose tissue (BAT) in rodent models of obesity and diabetes by non-invasive imaging approach. Repartitioning of energy through activation of BAT is a potential strategy for treating obesity. We have ongoing effort in implementing imaging techniques that will be suitable to exploit the variation in size of lipid droplets in white, brown and beige adipose tissues.  To support our program we have implemented algorithms for quantitative image segmentation and metabolite quantification. 

We are actively translating the preclinical methodologies through the GUSTO, SPRESTO Translational Clinical Research (TCR) programs and other ongoing academic/industrial clinical research studies through Singapore Institute of Clinical Sciences, Clinical Imaging Research Centre, NUH/NUS and other partners. Within the GUSTO study we have been involved in identifying early developmental, genetic and ethnic factors that could influence children’s body composition and metabolic health. Within the SPRESTO study we have been trying to identify preconception body composition markers that are predictive of gestational diabetes during pregnancy. We also work closely with other clinical collaborators to evaluate the effect of exercise, dietary and pharmacological interventions on the body composition, assessed by MRI and MRS.

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