Measuring Muscle Mass and Strength in Obesity: a Review of Various Methods

MRI has replaced the computed tomography (CT) scan as the gold standard [32]. MRI creates images from emission of radiofrequency energy from the nuclei of hydrogen atoms generated by magnetic fields and the signal will differ depending on the type of tissue [32]. MRI protocols can be optimized to assess the contrast among muscle tissue and fat tissue [33]. It also allows for quantification of FFM components, e.g., skeletal muscle mass, specific organ mass and bone marrow adipose tissue [14, 32]. MRI can also separate the muscle tissue into two different components, muscle with intramuscular fat and fat-free muscle. New methods to separate extracellular and intracellular muscle compartments can be used to show the expansion of extracellular space in aging and development of sarcopenia [34]. MRI is the most valuable tool for clinical research studies, due to the ability to quantify body compartments, which cannot be measured by other techniques. Furthermore, it can be used to assess relatively small changes over time which is useful in both intervention and observational studies [15]. Additionally, MRI can be used for body composition profiling, which is mainly used to compartmentalize the fat tissue but also to assess the weight muscle ratio [35]. General limitations of MRI are the costs, need for technicians, space requirements and infeasibility for patients with claustrophobia or with MRI incompatible implanted devices (e.g., cardiac pacemaker) [14]. The main drawbacks in a population with class II/III obesity are weight limitation (approx. 200 kg) and radial size limit (approx. 60 cm) [36]. MRI has been validated in healthy populations by post mortem cadaver studies in which subjects with obesity were also included, but with a maximum body mass index (BMI) of 31 kg/m² (r = 0.97; Table 2). The results of test-retest and inter-observer reliability were highly correlated (respectively: 2.9%, r = 0.99 and 2.6%, r = 0.99) [33, 38]. There are MRI machines available with open configuration, eliminating the radial size limitations, and with higher maximal weight (approx. 290 kg) [39]. With these MRI machines, it might be possible to validate measurements of muscle mass in patients with morbid obesity. Finally, MRI can measure a single abdominal cross-sectional slice at the third lumbar vertebra (L3) level, which has been validated in individuals with obesity against total MRI imaging of the abdomen and allows for estimation of both visceral adiposity and skeletal muscle mass [19].

In 1971, the CT scan was the first clinically accepted body composition measurement tool and was used as a gold standard [34]. The CT scan uses an X-ray beam to make cross-sectional images of the body, which can estimate total body fat, visceral fat and skeletal muscle mass [40, 41]. A single cross-sectional image of the abdominal area at the level of the L3 has shown a high correlation with total body skeletal muscle mass and body adipose tissue, comparable to whole-body MRI results [42]. However, these studies have mainly been done in healthy populations and populations prone to wasting and thus might not be applicable in patients with obesity [43]. General limitations of CT are the costs, need for technicians and radiation exposure [14]. Obesity-related limitations are similar to MRI, as CT also has a weight limit (approx. 230 kg) and radial size limit (approx. 60 cm) [15]. The CT validity was also tested with cadaver dissection in non-obese individuals (r = 0.97; Table 2) [33]. The test-retest reliability showed a high correlation (1.4%, r = 0.999) [33, 44]. Currently, CT is rarely used to measure muscle mass.

DXA is the best alternative to the gold standard. Originally invented to assess bone mineral content, DXA is now frequently used to examine body composition and muscle mass. It uses two X-ray beams to separate fat, bone and lean tissue based on the tissue X-ray absorption [45]. DXA highly correlates to both MRI and CT measures of skeletal muscle mass [22, 46, 47]. The main limitation is that muscle is not quantified directly. Several assumptions are made to calculate the lean soft tissue mass or FFM, based on the different gray-tones in the DXA scan. There can also be interference from both dehydration and edema, which are not unusual in populations with obesity [48, 49]. The validity of the muscle measurements of the DXA compared to CT has been examined in non-obese volunteers (r = 0.96; Table 2) [50]. The test-retest reliability between measures of FFM, also showed a high correlation (r = 0.99) [47]. However, these studies excluded individuals who did not fit within the DXA field-of-view or exceeded the CT radial size [50]. A recent study has shown that half-body analysis is comparable to the whole-body analysis for FM, non-bone lean mass and fat percentage. This half-body analysis uses a symmetry assumption, in which the left part of the body should have the same fat and muscle distribution as the right part of the body. It can be used if patients do not fit in the DXA field-of-view [51, 52]. In short, the DXA can accurately predict the FFM, in both healthy individuals and individuals with obesity.

In ultrasonography (US), high-frequency sound waves travel through the skin and are reflected by the underlying tissues. The reflection is called the acoustic impedance and each tissue type has a unique impedance. The reflection, received by the transducer, is converted into electrical signals and then visualized on a monitor [53]. The ultrasound is a non-invasive, fast and inexpensive tool [53, 54]. Alterations in the muscle mass can also be measured with US [55]. The ultrasound is portable and therefore especially useful in critically ill patients at bedside [53]. There have been studies in healthy and older adults validating US in quantifying body composition, e.g., FM, especially visceral fat, and skeletal muscle thickness [55‐57]. FM measurements with US have been validated with DXA in non-obese individuals (r = 0.98; Table 2) [58]. Estimation of lean tissue mass with US has not been validated in populations with obesity. The most commonly used sonographic devices have a maximum measuring depth of approximately 12 cm [59]. This limits the use in persons with morbid obesity, in whom subcutaneous fat thickness of more than 12 cm is not uncommon. Using an ultrasound with a lower frequency can solve this problem, as the penetration increases, however this will decrease the resolution of the image [60]. Future research on US to measure lean tissue in populations with obesity is underway. Finally, it might also be possible to look at muscle quality, which has already been validated in healthy athletes and critically ill patients [61, 62].

MRI and CT have been the gold standard in measuring muscle mass for years. Both have a weight and radial size limit. Newer models have bigger radial size limits and there is even an open configuration MRI [34]. However, both MRI and CT are expensive and require trained personnel. Currently, the CT is rarely used for measuring muscle mass.

The DXA results (lean tissue mass and FFM) highly correlate with both MRI and CT measures of muscle mass and DXA is relatively cheap compared to MRI or CT [63]. DXA also has some limitations, e.g., need for trained personnel and (low levels of) radiation. DXA is already established and frequently used as an alternative to MRI to measure muscle mass. US to measure muscle is quite new and has not been tested in populations with obesity yet.

Circumference measurements are done with a flexible quilting tape, making the measurements safe, easy and at low-cost [73]. The accuracy of circumference measurements depends on the skills and training of the person taking the measurements and can differ between observers [74]. Arm, thigh, and calf circumference together with skinfold thickness (SFT) can be used to estimate skeletal muscle mass. A prediction equation was developed to estimate the skeletal muscle mass: skeletal muscle mass = height × [0.00744 × corrected arm girth² + 0.00088 × corrected thigh girth² + 0.0041 x corrected calf girth²] + 2.4 × sex − 0.048 x age + race × 7.8. The correction of the circumferences is done by subtracting π x SFT from the measured circumference [75]. The equation was validated with MRI in patients with class I and II obesity [76].

Creatinine is a breakdown product of creatinine phosphate and is released from muscle cells with a usually fairly constant rate in to the blood. The classic method for the estimation of total skeletal muscle mass is 24-h urinary creatinine excretion, with the equation of 17–20 kg of muscle mass per gram of creatinine [77, 78]. This equation has been validated in patients with advanced renal failure, children, adolescents, elderly people and patients with wasting conditions, but not in populations with obesity [78‐80]. One study also highlighted the relatively high day-to-day variability of creatinine excretion (approx. 4–8%) and some influential factors on the secretion of creatinine (e.g., diet, exercise, menstrual cycle). It shows a high validity compared to anthropometric methods [78]. Serum creatinine can estimate muscle mass when serum cystatin C is added to the equation.⁵⁰ The equation has been developed and validated in a diverse population, only excluding patients with chronic kidney disease (r = 0.93) [81]. However, it has not been specifically validated in populations with obesity. Another relatively new tool is the D₃-creatine dilution method. This method measures D₃-creatine and D₃-creatinine excretion in morning urine [82]. Creatine is needed for energy supply in the muscle and approximately 2% is converted into creatinine and excreted. With the D₃-creatine method, subjects will ingest a single dose of stable isotope-labeled D₃-creatine. D₃-creatine will be taken up into muscle tissue and the excreted D₃-creatinine will give an estimation of skeletal muscle creatine enrichment and thus total body creatine and total muscular mass [82‐84]. There is less variability compared to 24-h urinary creatinine excretion and less dependence on subject compliance [83]. This specific method of measuring D₃-creatine has yet to be validated in a population with obesity.