Bone marrow Fat - A Novel Quantification Method and Potential Clinical Applications

Abstract

Ageing bone is characterised by increased marrow fat infiltration altering its composition and microstructure, thus predisposing the person to osteoporosis. Yet to date, non-invasive quantifications of marrow fat are limited to special MRI techniques, and clinical studies examining marrow fat in the ageing skeleton are scarce. Thus, the key aims of this thesis are to: · Validate a new non-invasive technique of marrow fat quantification using CT technology · Determine the effects of dietary fatty acids on marrow fat · Measure marrow fat content in different skeletal regions in healthy older men · Determine the effect of exercise and calcium on marrow fat. The imaging techniques employed in our animal and human studies were micro CT (µCT) and quantitative CT (QCT) respectively. All images were analysed with the imaging software Slice O Matic version 4.1 (Tomovision). Regions of interest [ROIs] were Volumes of interests (VOIs) of bone, fat and blood measured in µm3 or mm3. Individual tissue volumes, expressed as percentages of the total marrow volume, and ratios of tissue volumes were also used in the analysis. Global and local thresholds for individual tissue volumes were determined separately for µCT and QCT. Thresholds for µCT were those derived from the initial validation study, whereas those for QCT were based on previous published data. To account for partial volume averaging effects, further manual refinement of threshold ranges were undertaken by inspection of individual pixels and their neighbours. This manual process was carried out for both µCT and QCT to derive local thresholds for use in manual segmentation and computation of volumes. Our validation study showed that quantification of marrow fat using µCT was reliable and accurate compared to the gold standard technique- histology- when reliably defined thresholds were used. Good agreement between tissue volumes measured by histology and those computed by the imaging software was demonstrated. We applied this technique to quantify marrow fat in an animal model of senile osteoporosis, and showed that fatty acids (ω- 3 and ω-6) had dual effects on bone. With QCT studies, we confirmed the age related increase in marrow adiposity, and more significantly, different ratios between fat and bone in common fracture regions. Similarly, exercise affects marrow fat differently in different regions, and there was a trend to statistically significant changes to marrow fat with exercise. In conclusion, this body of work showed that quantification of marrow fat using CT is promising, and has future clinical implications. However, significantly more clinical studies are needed to confirm these findings and refine shortfalls in quantification capabilities

    Similar works