Description
Age-associated loss of skeletal muscle mass currently affects 50 million in the US with the number expected to quadruple by 2050. The concomitant loss of muscle strength cannot be accounted for completely by the widely believed primary causes of neural and muscle contractility in origin. Recent evidence suggest the extracellular matrix (ECM) plays an important role in loss of muscle quality. The ECM remodels with age, both in content and distribution, however the contribution of these changes to loss of muscle quality in humans has never been investigated comprehensively. This thesis is focused on evaluating imaging techniques to quantify the age related structural/compositional remodeling of the ECM. The ECM cannot be imaged by routine MRI techniques with TE in the milliseconds range. Protons in the ECM bound to large molecules result in extremely short signal decay times requiring special imaging sequences such as ultra-short echo time imaging (UTE). We integrate the use of UTE sequences and fat quantification sequences (IDEAL) to quantify macromolecular fraction (MMF) and fat fraction (FF) in the calf muscle of young (n=2) and senior (n=2) subjects. While collagen is speculated to be the main component of MMF, at least one study using a rat model suggests that MMF correlates with muscle fiber density. We hypothesize that by acquiring data at different ultra-low TEs (200 and 30 µs), we will be able to quantify macromolecular entities with different short T2 values and potentially identify their source. We use diffusion tensor imaging (DTI) to obtain indices that correlate to muscle fiber density and investigate their correlation to the different MMFs in both cohorts. Our results show that FF increases primarily in the plantarflexors and in the intermuscular region. MMF at 200 and 30 µs had a distribution that approximately followed muscle type enabling a tentative conclusion that these MMFs may reflect collagen. The shorter T2 MMF did not show such correlation implying a different origin. DTI indices correlation with MMF was not very strong but interestingly, MMF at 200 and 30 µs showed opposite correlations to those shown by the shorter T2, suggesting again a different origin.
