Doctor of Philosophy
McKenzie, Charles A.
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.
Summary for Lay Audience
A high-fat and high-sugar diet, known as the Western diet (WD), is common in Western society and may lead to poor health outcomes. In this thesis, we investigate the effect of diet on the liver and placenta using magnetic resonance imaging (MRI) techniques.
The effect of diet on liver function was chosen as a focus because it is known that diets high in fat lead to the accumulation of fat in the liver and poor liver function. We used a specialized MRI technique in an animal model to investigate how diet affects the liver’s ability to break down simple sugars to generate energy. We found that guinea pigs fed a WD had fatty livers and displayed a metabolism pattern that has previously been associated with liver damage.
The MRI technique used to gain information on metabolism in the body is an emerging method that suffers from poor image quality and difficulty in image acquisition. Part of this thesis aimed to improve image quality using a modified version of this technique. The new method was shown to produce higher quality images in our guinea pig experiments.
Poor diet during pregnancy has been shown to lead to poorer outcomes for the infant. One way this happens is through placental damage that limits the placenta’s ability to function properly. To measure the effect of diet on placental function, advanced MRI techniques were used to measure oxygenation and blood flow in a guinea pig model. Mothers fed a WD had less oxygen in the placenta but, interestingly, more blood flow than mothers fed a control diet. We believe this data suggests that the placenta recognizes the low oxygen levels associated with poor diet and reacts by increasing blood flow through the placenta in an attempt to provide the fetus with sufficient oxygen.
The research in this thesis is important for demonstrating advanced MRI techniques to study changes associated with poor diet. These results promote more investigation using these techniques that may eventually be incorporated into clinical examinations.
Smith, Lauren M., "MRI of structural & functional changes associated with Western diet consumption" (2021). Electronic Thesis and Dissertation Repository. 7821.
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Available for download on Wednesday, June 01, 2022