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Title: An image-based computation of microvascular dysfunction
Author: Zeller-Plumhoff, Berit
ISNI:       0000 0004 6061 2156
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2017
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The supply of oxygen in sufficient quantity is vital for the correct functioning of all organs, in particular for skeletal muscle during exercise. Disease is often associated with a reduction of the microvascular oxygen supply capability and is thought to relate to changes in the structure of blood vessel networks. Traditional methods of vascular perfusion or tissue staining for micro-computed tomography (μCT), as well as phase contrast-based synchrotron radiation computed tomography (SR CT) were used to image the microvasculature of the mouse soleus. These techniques were applied to an animal model of developmental conditioning to investigate the influence of maternal fat intake on the structure and oxygen exchange capability of the microvasculature in the adult offspring. Dams and their offspring were assigned either a standard chow diet (C) or a high-fat diet (HF), resulting in four groups: HFHF, HFC, CHF, CC. Tissue staining and vascular perfusion techniques were found insufficient for imaging capillaries. SR CT imaging enabled the visualization of red blood cells (RBCs) which allowed the determination quantitative measures of capillarization. An image-based model of muscle tissue oxygenation was further created. Quantitative measures in the CC group showed good agreement with values obtained by gold standard histology. RBC spacing was the only measure significantly different for the dietary groups (p < 0:05). By assessing the relationship between tissue oxygenation and the structural parameters, it was found that volume fraction (R2 = 0:63) and RBC spacing (R2 = 0:52) were the best predictors for muscle tissue oxygenation, followed by length density (R2 = 0:40). Fractal dimension (R2 = 0:28) and the 2D measures of capillary density (R2 = 0:30) and capillary-to-fibre ratio (R2 = 0:26) ranked last. SR CT further enabled the visualisation of fat, nerves and muscle spindles in the muscle. The mean muscle volume in the CC group was determined as 5:21-0:40mm3. The number of muscle fibres per SR CT cross-section in the medial region of the muscle was 1013-45. In the CC group an average of 11:8-0:7 muscle spindles per muscle was found with a mean of 3:7-0:1 intrafusal fibres per muscle spindle. The mean spacing between muscle spindles and the muscle boundary was 0:28-0:15 μm. No effect of offspring or maternal diet on spindle numbers was observed. Offspring high-fat diet lead to a significant increase in intramuscular adipose tissue (p < 0:05) and muscle volume (p < 0:0001).
Supervisor: Roose, Tiina Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available