MRI of structural & functional changes associated with Western diet consumption

Lauren M. Smith, The University of Western Ontario

Abstract

The Western diet (WD) is a high-fat, high-sugar diet increasingly common in the Western world and is associated with adverse effects in many organs, though the mechanisms behind these changes are unclear. Magnetic resonance imaging (MRI) techniques that provide structural and functional information non-invasively were used to investigate the effect of the WD on the liver and placenta in a guinea pig model.

The WD leads to a manifestation of the metabolic syndrome in the liver known as non-alcoholic fatty liver disease (NAFLD). Fat-fraction MRI was used to confirm the onset of NAFLD in a guinea pig model fed a lifelong WD, and hyperpolarized [1-¹³C]pyruvate magnetic resonance spectroscopy (MRS) was used to observe abnormal pyruvate metabolism in the liver. Importantly, this study included ex vivo enzyme measurements that correlated with the MRS results, further validating its use in identifying potential biomarkers of metabolic disease.

While hyperpolarized MRS techniques were successfully applied in the liver, investigation of the placenta requires imaging, especially in the guinea pig where multiple fetoplacental units are common. A technical improvement to the hyperpolarized MRI acquisition technique involving an optimized flip angle scheme was shown to improve the signal-to-noise ratio, enabling it to be used more effectively for in vivo evaluation of pyruvate metabolism in pregnancy research.

Continuing to investigate the effect of the WD, diffusion-weighted MRI and T₂* maps were used to measure blood perfusion and oxygenation of the placenta in a guinea pig model. Lifelong maternal WD consumption led to decreased oxygen saturation in the placenta in conjunction with increased blood perfusion at mid-gestation, which eventually improved blood oxygenation in the placenta near term. Similar placental adaptations have previously been reported in other models, but this is the first study to propose a connection with maternal diet.

In conclusion, this dissertation contains applications of advanced MRI techniques to study the effect of the WD in multiple organs and provides an improved acquisition strategy for hyperpolarized MRI relevant to the study of metabolic disease. The findings presented here validate and further motivate the use of hyperpolarized and diffusion-weighted MRI in studies of metabolic disease.