Water-fat magnetic resonance imaging for the assessment of human fetal adipose tissue

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

The application of in utero magnetic resonance imaging in the study of the metabolic and cardiovascular consequences of the developmental origins of health and disease

Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta\u27s transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD

Water-fat magnetic resonance imaging of adipose tissue compartments in the normal third trimester fetus

BACKGROUND: Assessment of fetal adipose tissue gives information about the future metabolic health of an individual, with evidence that the development of this tissue has regional heterogeneity. OBJECTIVE: To assess differences in the proton density fat fraction (PDFF) between fetal adipose tissue compartments in the third trimester using water-fat magnetic resonance imaging (MRI). MATERIALS AND METHODS: Water-fat MRI was performed in a 1.5-T scanner. Fetal adipose tissue was segmented into cheeks, thorax, abdomen, upper arms, forearms, thighs and lower legs. PDFF and R2* values were measured in each compartment. RESULTS: Twenty-eight women with singleton pregnancies were imaged between 28 and 38 weeks of gestation. At 30 weeks\u27 gestation (n=22), the PDFF was statistically different between the compartments (P CONCLUSION: Fetal adipose tissue accumulates lipids at a similar rate in all white adipose tissue compartments. PDFF variances between the compartments suggest that accumulation begins at different gestational ages, starting with cheeks, followed by extremities, trunk and abdomen. Additionally, MRI was able to detect differences in the PDFF between fetal brown adipose tissue and white adipose tissue

A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells

The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood–brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs