Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

McKenzie, Charles A.

2nd Supervisor

de Vrijer, Barbra

Joint Supervisor

Abstract

Adipose tissue is crucial for providing heat and energy to infants, especially at transitions such as birth and therefore must begin developing in utero. This development may be altered due to an adverse uterine environment, increasing the risk of developing later-life metabolic diseases such as obesity. An early assessment of fetal adipose tissue development through lipid accumulation could be key to understanding metabolic programming and minimizing this risk.

Water-fat magnetic resonance imaging (MRI) can non-invasively measure the lipid concentration of tissues and can therefore monitor the development of adipose tissue via tissue lipid concentration. This work demonstrated the feasibility of measuring fetal adipose tissue volumes and lipid concentrations in the third trimester. Both measures increased with gestational age, indicating this technique is sensitive to the tissue expansion and accumulation of lipids within the adipose tissue, an important improvement over previous MRI techniques limited to volume measures only.

Two water-fat MRI techniques were compared for measuring fetal adipose tissue lipid concentration; modified two-point Dixon and chemical-shift encoded MRI. It was found that the two techniques produced reliable fetal adipose tissue lipid concentration measures; however, only chemical-shift encoded MRI is suitable for assessing the lipid concentration of the fetal liver.

A regional variability of fetal adipose tissue lipid concentrations was found, reflecting the different gestational ages that adipose tissue compartments begin developing. Two compartments that begin development simultaneously but contain one of the two main types of adipose tissue, brown (generates heat) and white (stores energy), also had different lipid concentrations. This is an encouraging result suggesting that water-fat MRI could be used to differentiate fetal brown and white adipose tissues.

In conclusion, this dissertation contains applications of water-fat MRI techniques to assess the lipid concentration of fetal adipose tissue. It highlights factors that affect lipid concentration, including gestational age and adipose tissue region and type. These factors, and the choice of water-fat MRI technique, are important considerations for future studies aiming to use fetal tissue lipid concentrations to assess fetal metabolic programming.

Summary for Lay Audience

Babies born to mothers with diseases like obesity and diabetes that affect how their body processes food are at an increased risk of developing these diseases later in life. Since increases in fat tissue are associated with these diseases, investigating the development of fat tissue before birth may provide information about a baby’s risk of developing these diseases. This thesis uses a special magnetic resonance imaging (MRI) technique, water-fat MRI, to measure the amount of fat tissue and the amount of fats within that tissue (fatty content).

Previous ultrasound and MRI techniques only measured the volume of fetal fat tissue, but with water-fat MRI, measuring the fatty content of the fetal fat was also possible. This fatty content increases through pregnancy, as one of the last parts of fetal fat tissue development includes the accumulation of fats in the fat tissue cells.

There are a few ways that water-fat MRI can be performed, and a comparison of two popular techniques is included. Both techniques can be used in the fetal fat tissue, but only one can be used in the fetal liver because of the effects of fetal liver blood cell production on the fatty content measurement.

During fetal fat tissue development, the accumulation of fats in different areas begins at different times during pregnancy. As a result, there was a higher fatty content in areas that begin developing earlier in pregnancy than in those that develop later in pregnancy.

The two main types of fat tissue are brown fat, which produces heat, and white fat, which stores energy. The fatty content was different between these two types of fat tissue.

The research in this thesis highlights the factors that will affect fatty content measurements, including the time during pregnancy and the area and type of fat tissue being measured. These results provide the information necessary to design future studies using water-fat MRI to study fetal fat tissue development, which may eventually provide insight into the development of early risks for later-life diseases affecting how the body processes food.

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