Utilising novel technologies to predict muscle loss and muscle quality

Abstract

Declines in skeletal muscle quantity and quality have been associated with functional decline in older adults. After 30 years of age, muscle mass decreases by 3-8 % per decade and is considered the primary determinant of age-related declines in strength. Losses in strength appear to exceed losses in muscle quantity, and there is increasing evidence that poor muscle quality, defined as the capacity of the muscle to perform a function and measured by muscle architecture, lipid infiltration, metabolism and nerve conductivity may have a greater impact on functional strength than quantity alone. People who experience multiple short periods of muscle disuse following immobilisation or bed rest due to injury or hospitalisation do not always regain full muscle strength. This is exacerbated in people with type 2 diabetes, overweight/obesity and particularly in the elderly. It is essential therefore that healthcare services use assistive technologies capable of objectively measuring both quantity and quality to improve outcomes. Current technology such as MRI and CT are highly accurate but expensive, inaccessible and not available to therapists in clinical practice. Developing a cheaper ‘bedside’ tool capable of predicting age-related changes, in both muscle quantity and quality, would assist both clinicians and researchers, not only in the understanding of age-related changes to interventions but in delivering more effective rehabilitation to optimise quality of life into old age. The experimental chapters in this thesis begin with Chapter 3, a validation study to develop an ultrasound model capable of measuring muscle quantity and quality in lower limb muscles, in old and young healthy participants. Muscle parameters were compared against the gold standard MRI mDIXON for agreement with fat fraction. Two multivariate ultrasound models capable of predicting fat fraction for the gastrocnemius medialis and vastus lateralis are presented showing muscle thickness, subcutaneous fat thickness (SFT), echointensity and age as key parameters. The model was stronger for older persons where SFT was the dominant variable, whereas both SFT and echointensity contributed in near equal portions in the younger group. Model development continues into Chapter 4, using a homogeneous group of weight stable, moderately active females and demonstrated an association between ultrasound lipid infiltration and functional strength outcomes. The differences in strength were not explained by muscle thickness alone suggesting lipid infiltration as a contributor to loss of muscle strength. Together these studies demonstrate the potential of ultrasound as a tool for taking real-time measurements of both muscle quantity and quality, regardless of age and sex. Chapter 5 introduces a new experimental model of muscle atrophy in prolonged endurance ocean rowing of sufficient duration for chronic muscular adaptation and it provided a platform to test the capability of the ultrasound model to detect change. An annual 3000-mile rowing race across the Atlantic Ocean from La Gomera, Canary Islands to Antigua, sees males and females of all ages competing each year incurring significant body and muscle loss. After 46 days at sea, ocean rowers lost 10 % body mass and using the ultrasound tool, a dimorphic muscular response to negative energy balance was detected, where calf muscles atrophied by 15.7 % while upper limb muscle mass was maintained. Muscle atrophy was not accompanied by an increase in fat fraction and SFT did not change. The rate of response was not different between old and young, or male and female. An unexpected and novel finding from this study described in Chapter 6 showed that, for the first time experimentally, there appears to be a voluntary limit to dietary intake in recreational endurance athletes of ~2.4 x RMR. In the final week and after 6 weeks of ocean rowing, TEE was able to meet energy intake. Given the chronic changes in body and muscle mass this suggested a time-rate of change response. Building on both of these findings, Chapter 7 attempts to both quantify the acute to chronic time-rate response of prolonged endurance by utilising daily ultrasound measurements and prospectively test the maximal dietary intake in recreational athletes. A 7-day sled-haul on the Greenland polar ice cap showed that it was not possible to maintain the planned level of energy intake and thus, body mass loss could not be prevented. Acute ultrasound measures of quantity and quality were highly responsive to acute fluctuations, perhaps due to fluid shift, and because of this far more variable and less reliable. Together, these studies have demonstrated the capability of ultrasound as a tool for measuring, and predicting change in muscle thickness, architecture and lipid infiltration in stable conditions and in response to chronic prolonged exercise. Applying the model in acute settings that are likely to induce non-skeletal muscular tissue changes such as fluid shift, may impact on accuracy of the ultrasound model and requires further validation. This is particularly pertinent in clinical situations that incur body mass change and fluid shifts e.g. ICU patients. It is therefore recommended, at this stage, that the model be used in weight stable, or adapted muscle not undergoing fluid shift. Through the ultrasound muscle quantity and quality model and prolonged endurance alimentary limit to energy intake, this thesis offers two distinct and novel contributions to the literature.