Voluntary activation of human knee extensors during isotonic shortening contractions.

PURPOSE: The interpolated twitch technique (ITT) is often used to assess voluntary activation during isometric contractions; however, this may have limited relevance to dynamic contractions. Although the ITT has been applied to relatively slow isokinetic contractions (< 150°/s), it has received limited consideration during unconstrained velocity (i.e., isotonic) contractions, despite their relevance to natural movements. Here, we explored the ITT during isotonic knee extension contractions using a modified dynamometer. METHODS: Young males (n = 6) and females (n = 4) performed isometric and isotonic knee extension contractions of sub-maximal and maximal intensities with doublet (150 Hz) muscle belly stimulations to assess voluntary activation. Following each voluntary isotonic contraction (velocity range ~ 35°/s to ~ 275°/s), resting potentiated doublets were evaluated during passive joint rotation at the same angular velocity achieved during voluntary efforts, to account for force-velocity characteristics. Correlations between voluntary activation and the proportion of maximal torque or power were evaluated for isometric and isotonic contractions, respectively. RESULTS: Isometric voluntary activation was strongly correlated with increasing torque output (r = 0.96, p < 0.001). Doublet torque during passive joint rotation displayed a hyperbolic relationship with increasing angular velocity (r = 0.98, p < 0.001). Isotonic voluntary activation was strongly correlated with increasing power output (r = 0.89, p < 0.001). During maximal effort contractions, no differences were observed in voluntary activation between isometric and isotonic conditions (89.4% vs. 89.2%, p = 0.904). CONCLUSIONS: The ITT is a valid approach to evaluate voluntary activation during an isotonic contraction using a modified dynamometer. Participants were able to achieve a similar high level of voluntary activation during isometric and isotonic contractions.

Methodological and Clinimetric Evaluation of Inspiratory Respiratory Muscle Ultrasound in the Critical Care Setting: A Systematic Review and Meta-Analysis.

OBJECTIVE: Significant variations exist in the use of respiratory muscle ultrasound in intensive care with no society-level consensus on the optimal methodology. This systematic review aims to evaluate, synthesize, and compare the clinimetric properties of different image acquisition and analysis methodologies. DATA SOURCES: Systematic search of five databases up to November 24, 2021. STUDY SELECTION: Studies were included if they enrolled at least 50 adult ICU patients, reported respiratory muscle (diaphragm or intercostal) ultrasound measuring either echotexture, muscle thickness, thickening fraction, or excursion, and evaluated at least one clinimetric property. Two independent reviewers assessed titles, abstracts, and full text against eligibility. DATA EXTRACTION: Study demographics, ultrasound methodologies, and clinimetric data. DATA SYNTHESIS: Sixty studies, including 5,025 patients, were included with 39 studies contributing to meta-analyses. Most commonly measured was diaphragm thickness (DT) or diaphragm thickening fraction (DTF) using a linear transducer in B-mode, or diaphragm excursion (DE) using a curvilinear transducer in M-mode. There are significant variations in imaging methodology and acquisition across all studies. Inter- and intrarater measurement reliabilities were generally excellent, with the highest reliability reported for DT (ICC, 0.98; 95% CI, 0.94-0.99). Pooled data demonstrated acceptable to excellent accuracy for DT, DTF, and DE to predicting weaning outcome after 48 to 72 hours postextubation (DTF AUC, 0.79; 95% CI, 0.73-0.85). DT imaging was responsive to change over time. Only three eligible studies were available for intercostal muscles. Intercostal thickening fraction was shown to have excellent accuracy of predicting weaning outcome after 48-hour postextubation (AUC, 0.84; 95% CI, 0.78-0.91). CONCLUSIONS: Diaphragm muscle ultrasound is reliable, valid, and responsive in ICU patients, but significant variation exists in the imaging acquisition and analysis methodologies. Future work should focus on developing standardized protocols for ultrasound imaging and consider further research into the role of intercostal muscle imaging.

Comparison of prolonged low-frequency force depression assessed using isometric torque and isotonic power following a dynamic fatiguing task.

PURPOSE: Prolonged low-frequency force depression (PLFFD) occurs following both dynamic and static fatiguing tasks, but it has been assessed predominately using measures of isometric torque. However, it is unknown whether PLFFD induced during dynamic tasks is adequately characterized by isometric torque, which excludes velocity and power. The purpose of this study was to compare PLFFD assessed using isometric torque and isotonic power following a concentric fatiguing task. METHODS: Young (18-31 years) males (n = 9) and females (n = 4) performed isotonic plantar flexion contractions until a ~ 75% reduction in peak power. Isotonic and isometric contractions were electrically evoked at 10 Hz and 50 Hz via tibial nerve stimulation. Isotonic and isometric PLFFD was assessed as the ratio of 10 to 50 Hz for power and torque, respectively. Recovery was assessed immediately, and at 2.5, 5, 10, 20, and 30 min after task termination. RESULTS: Relative to baseline, 10:50 Hz ratio assessed using isotonic power was reduced more than isometric torque (30 min 41 ± 17 vs. 25 ± 12% reduction, p = 0.001); however, both contraction modes displayed similar trajectories throughout recovery (p = 0.906). The larger reduction in isotonic 10:50 Hz ratio was due to greater impairments in 10 Hz power compared to 10 Hz isometric torque (30 min 38 ± 20 vs. 21 ± 11% reduction, p < 0.001). CONCLUSION: The similar trajectories of 10:50 Hz ratios throughout recovery indicate that PLFFD can be adequately characterized using either isometric torque or isotonic power.

Influence of Subcutaneous Adipose Tissue and Skeletal Muscle Thickness on Rectus Femoris Echo Intensity in Younger and Older Males and Females.

OBJECTIVES: Ultrasound measurements of muscle echo intensity are commonly used surrogates of muscle composition (eg, intramuscular adipose tissue). However, given that soundwaves are increasingly attenuated with tissue depth, the interpretation of echo intensity may be confounded by adipose and skeletal muscle thickness. Our objectives are to compare the associations between adipose or muscle tissue thickness and rectus femoris echo intensity in younger and older males and females. METHODS: Participants included in this analysis were derived from 3 previously published cohorts of younger (<45 years) and older (≥60 years) males and females. Ultrasound images of the rectus femoris were evaluated for muscle thickness, echo intensity, and subcutaneous adipose tissue thickness. RESULTS: Older adults (n: 49 males, 19 females) had a higher body mass index (P = .001) compared with younger adults (n: 37 males, 49 females). Muscle thickness was negatively associated with echo intensity in older males (r = -0.59) and females (r = -0.53), whereas no associations were observed in younger males (r = 0.00) or females (r = -0.11). Subcutaneous adipose tissue thickness displayed no associations with echo intensity in any group. CONCLUSIONS: Despite the known influence of subcutaneous adipose tissue thickness on beam attenuation, we observed no association with muscle echo intensity, indicating that adipose tissue correction may be required to better understand muscle echo intensity across differences in adiposity. The negative associations between muscle thickness and echo intensity in older, but not younger adults, suggests these associations may be related to the co-occurrence of skeletal muscle atrophy and intramuscular adipose tissue infiltration with advancing age.

Assessment of muscle mass using ultrasound with minimal versus maximal pressure compared with computed tomography in critically ill adult patients.

BACKGROUND: Preserved skeletal muscle mass identified using computed tomography (CT) predicts improved outcomes from critical illness; however, CT imaging have few limitations such that it involves a radiation dose and transferring patients out of the intensive care unit. This study aimed to assess in critically ill patients the relationship between muscle mass estimates obtained using minimally invasive ultrasound techniques with both minimal and maximal pressure compared with CT images at the third lumber vertebra level. METHODS: All patients were treated in a single Australian intensive care unit. Eligible patients had paired assessments, within a 72-h window, of muscle mass by ultrasound (quadriceps muscle layer thickness in centimetres, with maximal and minimal pressure) and CT axial cross-sectional area (cm2). Data are presented as mean (standard deviation), median (interquartile range), and frequencies [n (%)]. RESULTS: Thirty-five patients [mean (standard deviation) age = 55 (16) years, median (interquartile range) body mass index = 27 (25-32) kg/m2, and 26 (74%) men] contributed 41 paired measurements. Quadriceps muscle thickness measured using the maximal pressure technique was a strong independent predictor of lumbar muscle cross-sectional area. Within a multivariate mixed linear regression model and adjusting for sex, age, and body mass index, for every 1 cm increase in quadriceps muscle layer thickness, the lumbar muscle cross-sectional area increased by 35 cm2 (95% confidence interval = 11-59 cm2). Similar univariate associations were observed using minimal pressure; however, as per multivariate analysis, there was no strength in this relationship [8 cm2 (95% confidence interval = -5 to 22 cm2)]. CONCLUSION: Ultrasound assessment of the quadriceps muscle using maximal pressure reasonably predicts the skeletal muscle at the third lumbar vertebra level of critically ill patients. However, there is substantial uncertainty within these regression estimates, and this may reduce the current utility of this technique as a minimally invasive surrogate for CT assessment of skeletal muscle mass.

Differential effects of stimulation frequency on isometric and concentric isotonic contractile function in human quadriceps.

Electrically evoked contractions are used to assess the relationship between frequency input and contractile output to characterize inherent muscle function, and these have been done mostly with isometric contractions (i.e., no joint rotation). The purpose was to compare the electrically stimulated frequency and contractile function relationship during isometric (i.e., torque) with isotonic (i.e., concentric torque, angular velocity, and mechanical power) contractions. The knee extensors of 16 (5 female) young recreationally active participants were stimulated (∼1-2.5 s) at 14 frequencies from 1 to 100 Hz. This was done during four conditions, which were isometric and isotonic at loads of 0 (unloaded), 7.5%, and 15% isometric maximal voluntary contraction (MVC), and repeated on separate days. Comparisons across contractile parameters were made as a % of 100 Hz. Independent of the load, the mechanical power-frequency relationship was rightward shifted compared with isometric torque-frequency, concentric torque-frequency, and velocity-frequency relationships (all P ≤ 0.04). With increasing load (0%-15% MVC), the isotonic concentric torque-frequency relationship was shifted leftward systematically from 15 to 30 Hz (all P ≤ 0.04). Conversely, the same changes in load caused a rightward shift in the velocity-frequency relationship from 1 to 40 Hz (all P ≤ 0.03). Velocity was leftward shifted of concentric torque in the unloaded isotonic condition from 10 to 25 Hz (all P ≤ 0.03), but concentric torque was leftward shifted of velocity at 15% MVC isotonic condition from 10 to 50 Hz (all P ≤ 0.03). Therefore, isometric torque is not a surrogate to evaluate dynamic contractile function. Interpretations of evoked contractile function differ depending on contraction type, load, and frequency, which should be considered relative to the specific task.NEW & NOTEWORTHY In whole human muscle, we showed that the electrically stimulated power-frequency relationship was rightward shifted of the stimulated isometric torque-frequency relationship independent of isotonic load, indicating that higher stimulation frequencies are needed to achieve tetanus. Therefore, interpretations of evoked contractile function differ depending on contraction type (isometric vs. dynamic), load, and frequency. And thus, isometric measures may not be appropriate as a surrogate assessment when evaluating dynamic isotonic contractile function.

Influence of stimulation frequency on early and late phase rate of torque and velocity development.

The early (≤50 ms) rate of torque development (RTD) is dependent upon the speed of neuromuscular activation; however, few studies have evaluated the determinants of rate of velocity development (RVD), which may be load-dependent. The purpose here was to explore the relationship between stimulation frequency with the early and late (≥100 ms) phase isometric RTD and isotonic RVD. The knee extensors of 16 (five female) young recreationally active participants were stimulated using 14 frequencies from 1 to 100 Hz during isometric and isotonic ("unloaded" and 7.5% of the isometric maximal voluntary contraction [MVC]) contractions. Isometric RTD and isotonic RVD were evaluated for the early (0-50 ms) and late (0-100 ms) phases from torque and velocity onset, respectively. Sigmoid functions were fit and bilinear regressions were used to examine the slopes of the steep portion of the curve and the plateau frequency. RTD- and RVD-frequency relationships were well described by a sigmoid function (all r2 > 0.96). Compared with the late phase, early isometric RTD, and unloaded RVD displayed lower slopes (all P ≤ 0.001) and higher plateau frequencies (all P < 0.001). In contrast, early and late RVD of a moderately loaded isotonic contraction did not display different slopes (P = 0.055) or plateau frequencies (P = 0.690). Early isometric RTD and unloaded isotonic RVD are more dependent on changes in stimulation frequency compared with late phases. However, RVD for a moderately loaded isotonic contraction displayed similar responses for the early and late phases. Therefore, a high frequency of activation is critical for early torque and velocity generation but dependent upon the load for isotonic contractions.NEW & NOTEWORTHY We show that during an "unloaded" isotonic contraction, the early phase rate of velocity development is more dependent upon a high electrical activation frequency compared with the late phase, similar to isometric torque. However, early and late phase rates of velocity development of moderately loaded isotonic contractions display similar responses. These results indicate that the determinants of isotonic shortening function are dependent on the externally applied load, highlighting the importance of task-specificity of contraction.

Calcaneal tendon stiffness is not associated with dynamic time-dependent contractile output.

The ability to rapidly generate muscular torque and velocity is important in specialized activities and daily tasks of living. Tendon stiffness is one factor in the neuromuscular system that influences musculoskeletal torque transmission. Previous studies have reported weak-to-moderate correlations between tendon stiffness and rate of torque development (RTD). However, these correlations have been reported only for isometric contractions, which may not be relevant to contractions involving joint rotation (i.e., dynamic). The purpose was to investigate the effect of calcaneal tendon stiffness on the dynamic RTD and rate of velocity development (RVD) in plantar flexor muscles. Young adult males (n = 13) and females (n = 2) performed prone isometric- and isotonic-mode maximal voluntary plantar flexion contractions (MVC). Ultrasound imaging was used to quantify tendon morphological characteristics to estimate Young's elastic modulus (YM). Maximal voluntary and electrically evoked (300 Hz) isometric- and isotonic-mode (at 10% and 40% MVC loads) contractions were evaluated for RTD and RVD through a 25° ankle joint range of motion. YM was correlated with isometric RTD, but only for evoked contractions (RTD0-50 ms: r = 0.54, p = 0.02, RTD0-200 ms: r = 0.62, p = 0.01). Conversely, YM was not correlated with dynamic RTD (voluntary: r = -0.07-0.41, p = 0.06-0.40, evoked: r = -0.2-0.3, p = 0.14-0.24) nor RVD (voluntary: r = -0.08-0.24, p = 0.27-0.40, evoked: r = 0.12-0.3, p = 0.14-0.34). These correlations would indicate that calcaneal tendon stiffness is an important factor for rapid isometric torque development, but less so for isotonic contractions. The determinants of dynamic contractile rates are more complex and warrant further study.

Electrically Evoked Isotonic Plantar Flexion Contractions Are Impaired Less than Voluntary After a Dynamic Fatiguing Task.

PURPOSE: Evaluating central and peripheral processes responsible for reduced power after dynamic fatiguing tasks are often limited to isometric torque, which may not accurately reflect dynamic contractile performance. Here, we compare voluntary and electrically evoked peak power (and its determinants: dynamic torque and velocity) and rate of velocity development (RVD) before and after a dynamic fatiguing task using concentric Plantar flexion contractions. METHODS: Young (18-32 yr) males ( n = 11) and females ( n = 2) performed maximal-effort isotonic Plantar flexion contractions using a load of 20% isometric torque until an approximately 75% reduction in peak power. Voluntary and electrically evoked (300 Hz tibial nerve stimulation) contractions loaded to 20% and 40% isometric torque through 25° ankle joint range of motion were compared before and 0, 2.5, 5, and 10 min after task termination. RESULTS: At task termination, peak power and RVD of voluntary contractions at both loads were reduced more (~40% to 50% reduction) than electrically evoked (~25% to 35% reduction) contractions ( P < 0.001 and P = 0.003). Throughout the recovery period, electrically evoked peak power and RVD returned to baseline sooner (<5 min) than voluntary contractions, which were still depressed at 10 min. Reductions in peak power for the 20% load were equally due to impaired dynamic torque and velocity, whereas velocity was impaired more than dynamic torque ( P < 0.001) for the 40% load. CONCLUSIONS: The relative preservation of electrically evoked power and RVD compared with voluntary contractions at task termination and quicker recovery to baseline indicates that the reductions in dynamic contractile performance after task termination are due to both central and peripheral processes; however, the relative contribution of dynamic torque and velocity is load dependent.

Test-retest repeatability of electrically evoked isotonic power and isometric torque in the plantar flexors.

Electrically evoked isometric torque has good to excellent repeatability, but the degree of repeatability for electrically evoked isotonic power is unknown. We evaluated the test-retest repeatability of plantar flexion isometric torque and isotonic power evoked using brief tetanic trains at 10 and 50 Hz. Both torque and power had excellent (intraclass correlation coefficient >0.9) repeatability at low and high frequencies. Similar to isometric torque, electrically evoked isotonic power is a stable measure for studying dynamic muscle function.

Frequency-dependent coexistence of muscle fatigue and potentiation assessed by concentric isotonic contractions in human plantar flexors.

The purpose was to investigate whether postactivation potentiation (PAP) mitigates power (i.e., torque × angular velocity) loss during dynamic fatiguing contractions and subsequent recovery by enhancing either muscle torque or angular velocity in human plantar flexors. In 12 participants, electrically stimulated (1, 10, and 50 Hz) dynamic contractions were done during a voluntary isotonic fatiguing protocol until a 75% loss in voluntary peak power, and throughout 30 min of recovery. At the initial portion of fatigue (20% decrease), power responses of evoked low frequencies (1 and 10 Hz) were enhanced due to PAP (156% and 137%, respectively, P < 0.001), whereas voluntary maximal efforts were depressed due to fatiguing mechanisms. Following the fatiguing task, prolonged low-frequency force depression (PLFFD) was evident by reduced 10:50 Hz peak power ratios (21%-24%) from 3 min onward during the 30-min recovery (P < 0.005). Inducing PAP with maximal voluntary dynamic contractions during PLFFD enhanced the peak power responses of low frequencies (1 and 10 Hz) by 128%-160%, P < 0.01. This PAP response mitigated the effects of PLFFD as the 1:50 (P < 0.05) and 10:50 (P > 0.4) Hz peak power ratios were greater or not different from the prefatigue (baseline) values. In addition, PAP enhanced peak torque more than peak angular velocity during both baseline and fatigue measurements (P < 0.03). These results indicate that PAP can ameliorate PLFFD acutely when evaluated during concentric isotonic contractions and that peak torque is enhanced to a greater degree compared with peak angular velocity at baseline and in a fatigued state.NEW & NOTEWORTHY Postactivation potentiation (PAP) enhanced stimulated low frequencies (1 and 10 Hz) during muscle fatigue development when assessed with power (torque × angular velocity) in a voluntary isotonic fatiguing task. Following the task during 30 min of recovery, prolonged low-frequency force depression (PLFFD) was evident, and inducing PAP with brief maximal contractions during this state ameliorated the effects of PLFFD. PAP enhanced peak torque more than peak angular velocity during both baseline and fatiguing conditions.

Altered features of body composition in older adults with type 2 diabetes and prediabetes compared with matched controls.

BACKGROUND: Ageing is accompanied by muscle loss and fat gain, which may elevate the risk of type 2 diabetes (T2D). However, there is a paucity of data on the distribution of regional lean and fat tissue in older adults with T2D or prediabetes compared with healthy controls. The objective of this study was to compare regional body composition [by dual-energy x-ray absorptiometry (DXA)], muscle and subcutaneous adipose tissue (SAT) thicknesses (by ultrasound), and ultrasound-based muscle texture features in older adults with T2D or prediabetes compared with normoglycaemic controls. METHODS: Eighteen adults > 60 years with T2D or prediabetes (T2D group) were individually matched to normoglycaemic participants [healthy matched (HM) group] for age (±5 years), sex, and body fat (±2.5%). In a single study visit, all participants received a whole-body DXA scan and ultrasound assessment of the abdomen and anterior thigh. At these two landmarks, we used ultrasound to measure muscle and SAT thickness, as well as texture features of the rectus femoris and rectus abdominis. We also conducted an exploratory subanalysis on a subset of participants (n = 14/18 in the T2D group and n = 10/18 in the HM group) who underwent additional assessments including strength testing of the knee extensors (using a Biodex dynamometer), and a fasting blood sample for the measurement of circulating markers of glucose metabolism [glucose, insulin, c-peptide, and the homoeostatic model assessment of insulin resistance (HOMA-IR)]. RESULTS: The T2D group was 72 ± 8 years old (mean ± SD), predominantly male (n = 15/18; 83%), and overweight (BMI: 27.8 ± 4.2 kg/m2 , 33.2 ± 5.3% body fat). DXA-derived upper arm lean mass was 0.4 kg greater (P = 0.034), and leg fat mass was 1.4 kg lower (P = 0.048), in the T2D vs. HM group. Ultrasound-based texture features were distinct between the groups [rectus abdominis blob size: 0.07 ± 0.06 vs. 0.30 ± 0.43 cm2 , P = 0.045; rectus femoris local binary pattern (LBP) entropy: 4.65 ± 0.05 vs. 4.59 ± 0.08 A.U., P = 0.007]. When all participants who underwent additional assessments were pooled (n = 24), we observed that certain ultrasound-based muscle texture features correlated significantly with muscle strength (rectus abdominis histogram skew vs. power during an isokinetic contraction at 60°/s: r = 0.601, P = 0.003) and insulin resistance (rectus femoris LBP entropy vs. HOMA-IR: r = 0.419, P = 0.042). CONCLUSIONS: Our findings suggest a novel body composition phenotype specific to older adults with T2D or prediabetes. We are also the first to report that ultrasound-based texture features correspond with functional outcomes. Future larger scale studies are needed to uncover the mechanisms underpinning these regional body composition differences.

Association of strength, power, and function with muscle thickness, echo intensity, and lean tissue in older males.

Dual-energy X-ray absorptiometry (DXA) appendicular lean tissue is used to screen older adults for sarcopenia. However, emerging data indicates that ageing-related muscle atrophy largely occurs within specific muscles, which may be masked using appendicular lean tissue. Comparisons between appendicular lean tissue and site-specific measures of muscle in relation to strength and physical function are needed to advance our understanding of these features in the context of poor muscle function in aged adults. Our primary objective was to compare correlations between lean tissue and site-specific muscle characteristics in relation to strength and physical function in older males. Older males (≥65 years) were evaluated for muscle strength, physical function (6-minute walk and 30-second sit-to-stand), and muscle size (appendicular and site-specific) and composition (echo intensity) using DXA and ultrasound. Of the 32 older males (75.4 ± 7.9 years), 12 had low appendicular lean tissue. All DXA and ultrasound muscle characteristics were associated (r = 0.39 to 0.83, p < 0.05) with torque or power producing capabilities. Except for the knee flexors, no differences in correlation coefficients were observed between muscle thickness or regional lean tissue in relation to muscle strength. Neither DXA nor ultrasound muscle characteristics were associated with physical function. In older males, ultrasound-based muscle thickness and DXA lean tissue provided similar associations with strength. Novelty: Lean tissue and muscle thickness provide similar associations with strength. Muscle thickness can distinguish low and normal appendicular lean tissue in older adults.

Body size normalization of ultrasound measured anterior upper leg muscle thickness in younger and older males and females.

BACKGROUND: Ultrasound measurements of the anterior upper leg muscle thickness are often used to quantify muscle mass; however, the ideal normalization approach is unclear. Our primary objective was to examine how the anterior upper leg muscle thickness scales with indices of body size in younger and older adults. Our secondary objectives were to examine how normalization with body size alters the identification of low muscle thickness and associations with strength and physical function. METHODS: Younger (<45 years) males (n = 38) and females (n = 24) and older (≥60 years) males (n = 53) and females (n = 24) were evaluated for anthropometrics and anterior upper leg muscle thickness. Allometric models were used to examine how body size metrics scale with anterior upper leg muscle thickness. A subset of older males was evaluated for strength and function. RESULTS: Weight and BMI scaled with anterior upper leg muscle thickness with coefficients less than 1 (0.58 to 0.82, r2 = 0.15 to 0.31, p < 0.05) for both younger and older males and females. Compared to absolute anterior upper leg thickness, normalized indices identified a greater proportion of older adults with low muscle thickness (p < 0.05). Absolute muscle thickness provided stronger associations with strength compared to weight normalized indices. CONCLUSIONS: Scaling exponents less than 1 for weight and BMI for the anterior upper leg muscle thickness indicate that allometric normalization is the ideal approach to develop body size independent metrics. However, allometric normalization of muscle thickness increases the proportion of older adults classified as low muscle mass but decreased the associations with strength.

Age-related performance fatigability: a comprehensive review of dynamic tasks.

Adult aging is associated with a myriad of changes within the neuromuscular system, leading to reductions in contractile function of old adults. One of the consequences of these age-related neuromuscular adaptations is altered performance fatigability, which can limit the ability of old adults to perform activities of daily living. Whereas age-related fatigability during isometric tasks has been well characterized, considerably less is known about fatigability of old adults during dynamic tasks involving movement about a joint, which provides a more functionally relevant task compared with static contractions. This review provides a comprehensive summary of age-related fatigability during dynamic contractions, where the importance of task specificity is highlighted with a brief discussion of the potential mechanisms responsible for differences in fatigability between young and old adults. The angular velocity of the task is critical for evaluating age-related fatigability, as tasks that constrain angular velocity (i.e., isokinetic) produce equivocal age-related differences in fatigability, whereas tasks involving unconstrained velocity (i.e., isotonic-like) consistently induce greater fatigability for old compared with young adults. These unconstrained velocity tasks, which are more closely associated with natural movements, offer an excellent model to uncover the underlying age-related mechanisms of increased fatigability. Future work evaluating the mechanisms of increased age-related fatigability during dynamic tasks should be evaluated using contraction modes that are specific to the task (i.e., dynamic), rather than isometric, particularly for the assessment of spinal and supra spinal components. Advancing our understanding of age-related fatigability is likely to yield novel insights and approaches for improving mobility limitations in old adults.

Rectus Abdominis Muscle Thickness is a Valid Measure of Cross-Sectional Area: Implications for Ultrasound.

RATIONALE AND OBJECTIVES: The rectus abdominis muscle exhibits early and significant muscle atrophy, which has largely been characterized using ultrasound measured muscle thickness. However, the validity of rectus abdominis muscle thickness as a metric of muscle size has not been established, limiting precise interpretation of age-related changes. In a heterogeneous cohort of women and men, our objectives were to: (1) evaluate the association between rectus abdominis muscle thickness and cross-sectional area (CSA), and (2) examine if the visceral adipose tissue (VAT) compartment confounds the validity of rectus abdominis muscle thickness. MATERIALS AND METHODS: Abdominal computed tomography scans of the third lumbar vertebrae from clinical and healthy populations were used to evaluate rectus abdominis thickness and CSA, and VAT CSA. Computed tomography scans were utilized due to the limited field of view of ultrasound imaging to capture the rectus abdominis CSA. RESULTS: A total of 348 individuals (31% women) were included in this analysis, with a mean ± standard deviation age and body mass index of 51.2 ± 15.4 years and 28.0 ± 5.1 kg/m2, respectively. Significant correlations were observed between rectus abdominis thickness and CSA for women (r = 0.758; p < 0.001) and men (r = 0.688; p < 0.001). Independent of age, VAT CSA was negatively associated with rectus abdominis thickness in men (p = 0.011), but not women (p = 0.446). CONCLUSION: These data support the use of rectus abdominis muscle thickness as a measurement of muscle size in both women and men; however, the VAT compartment may confound its validity to a minor extent in men.

Associations between Pretreatment Body Composition Features and Clinical Outcomes among Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Blockade.

PURPOSE: High body mass index (BMI) may lead to improved immune-checkpoint blockade (ICB) outcomes in metastatic clear cell renal cell carcinoma (mccRCC). However, BMI is a crude body size measure. We investigated BMI and radiographically assessed body composition (BC) parameters association with mccRCC ICB outcomes. EXPERIMENTAL DESIGN: Retrospective study of ICB-treated patients with mccRCC. BMI and BC variables [skeletal muscle index (SMI) and multiple adiposity indexes] were determined using pretreatment CT scans. We examined the associations between BMI and BC variables with ICB outcomes. Therapeutic responses per RECIST v1.1 were determined. We compared whole-transcriptomic patterns with BC variables in a separate cohort of 62 primary tumor samples. RESULTS: 205 patients with mccRCC were included in the cohort (74% were male, 71% were overweight/obese, and 53% were classified as low SMI). High-BMI patients experienced longer overall survival (OS) than normal-weight patients [unadjusted HR, 0.66; 95% confidence interval (CI), 0.45-0.97; P = 0.035]. The only BC variable associated with OS was SMI [unadjusted HR comparing low vs. high SMI 1.65 (95% CI: 1.13-2.43); P = 0.009]. However, this OS association became nonsignificant after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium score and line of therapy. No OS association was seen for adiposity and no BC variable was associated with progression-free survival or radiological responses. Tumors from patients with low SMI displayed increased angiogenic, inflammatory, and myeloid signals. CONCLUSIONS: Our findings highlight the relevance of skeletal muscle in the BMI paradox. Future studies should investigate if addressing low skeletal muscle in metastatic patients treated with ICB can improve survival.

Muscle Composition Analysis of Ultrasound Images: A Narrative Review of Texture Analysis.

Skeletal muscle composition, often characterized by the degree of intramuscular adipose tissue, deteriorates with aging and disease and contributes to impairments in function and metabolism. Ultrasound can provide surrogate measures of muscle composition through measurement of echo intensity; however, there are several limitations associated with its analysis. More complex image processing features, broadly known as texture analysis, can also provide surrogates of muscle composition and may circumvent some of the limitations associated with muscle echo intensity. Here, texture features from the intensity histogram, gray-level co-occurrence matrix, run-length matrix, local binary pattern, blob analysis, texture anisotropy index and wavelet analysis are discussed. The purpose of this review was to provide a conceptual understanding of texture analysis as it pertains to muscle composition of ultrasound images.

Site-specific skeletal muscle echo intensity and thickness differences in subcutaneous adipose tissue matched older and younger adults.

BACKGROUND: Age-related deterioration of muscle mass does not occur uniformly across the body. However, there is limited knowledge on the uniformity of age-related muscle composition changes across the body. OBJECTIVE: Our primary objective was to evaluate muscle composition differences between younger and older adults across multiple muscle groups. METHODS: We re-analysed data from a previously published cohort to evaluate differences in ultrasound muscle composition (echo intensity) between younger (<45 years) and older (>60 years) adults, when matched for adipose tissue mass at the anterior upper arm, anterior upper leg and abdominal muscles. Analysis of echo intensity is confounded by subcutaneous adipose tissue (SAT) thickness overlaying the muscle; we accounted for these effects by matching older and younger adults (1:1), stratified by sex, for absolute SAT thickness at each landmark. RESULTS: From 96 adults (n = females), 58 (n = 34) were SAT matched at the anterior upper arm, 52 (n = 30) at the anterior upper leg and 60 (n = 30) at the abdominal region; thus, there were no age group differences in SAT thickness at each landmark. In comparison with younger adults, older adults presented with greater echo intensity at the anterior upper leg (females:40.3 ± 6.8 vs. 52.4 ± 7.6; males:35.7 ± 8.0 vs. 54.3 ± 9.8, p < .01) and abdominal (females:38.7 ± 27.6 vs. 73.4 ± 31.0; males:18.7 ± 15.2 vs. 60.9 ± 23.4, p < .01) muscles, but not anterior upper arm muscles (females:47.0 ± 6.5 vs. 53.2 ± 13.1; males:43.4 ± 8.9 vs. 48.9 ± 10.1, p = .18). CONCLUSIONS: Distinct age-related differences in trunk and lower limb muscle composition were evident compared to upper limb muscles; highlighting the importance of quantifying specific muscle groups when evaluating age-associated muscle characteristics.

Associations between skeletal muscle echo intensity and thickness in relation to glucose homeostasis in healthy and glucose impaired older males.

BACKGROUND: Aging-related changes in muscle composition and mass may predispose older adults to developing insulin resistance. Ultrasound echo intensity and thickness are surrogates of muscle composition and mass, however, their associations with glucose homeostasis are not well established. We examined how muscle echo intensity and thickness correlate with markers of glucose homeostasis in older (≥65 years) males with normal (n = 22) or impaired (n = 10) glucose control. METHODS: Echo intensity was measured for the biceps brachii, rectus abdominis, and rectus femoris. Muscle thickness was evaluated for the biceps brachii + brachioradialis, rectus abdominis, and rectus femoris + vastus intermedius. Glucose homeostasis was evaluated using a 2-h oral glucose tolerance test. RESULTS: In older males with normal glucose homeostasis, higher echo intensity of the rectus abdominis and rectus femoris was moderately (r = 0.36 to 0.59) associated with 2-h glucose. On the contrary, higher muscle echo intensity of the rectus abdominis, biceps brachii, and rectus femoris was moderately-to-strongly (r = -0.36 to -0.79) associated with indices of better glucose homeostasis in the impaired group. Rectus abdominis muscle thickness was moderately associated (r = 0.36) with better glucose tolerance in the normal glucose homeostasis; however, in the glucose impaired group, muscle thickness was associated with (r = 0.37 to 0.73) with poorer glucose homeostasis. CONCLUSIONS: Muscle echo intensity displays divergent associations with glucose homeostasis in older males with normal compared to impaired glucose control. Larger muscle thickness was associated with poorer glucose homeostasis in the glucose impaired group, but rectus abdominis muscle thickness was correlated with better homeostasis in healthy older males.