Diffusion-tensor magnetic resonance imaging (DT-MRI) offers objective measures of muscle characteristics, providing insights into age-related changes. We used DT-MRI to probe skeletal muscle microstructure and architecture in a large healthy-aging cohort, with the aim of characterizing age-related differences and comparing these to muscle strength. We recruited 94 participants (43 female; median age = 56, range = 22–89 years) and measured microstructure parameters—fractional anisotropy (FA) and mean diffusivity (MD)—in 12 thigh muscles, and architecture parameters—pennation angle, fascicle length, fiber curvature, and physiological cross-sectional area (PCSA)—in the rectus femoris (RF) and biceps femoris longus (BFL). Knee extension and flexion torques were also measured for comparison to architecture measures. FA and MD were associated with age (β = 0.33, p = 0.001, R2 = 0.10; and β = −0.36, p < 0.001, R2 = 0.12), and FA was negatively associated with Type I fiber proportions from the literature (β = −0.70, p = 0.024, and R2 = 0.43). Pennation angle, fiber curvature, fascicle length, and PCSA were associated with age in the RF (β = −0.22, 0.26, −0.23, and −0.31, respectively; p < 0.05), while in the BFL only curvature and fascicle length were associated with age (β = 0.36, and −0.40, respectively; p < 0.001). In the RF, pennation angle and PCSA were associated with strength (β = 0.29, and 0.46, respectively; p < 0.01); in the BFL, only PCSA was associated with strength (β = 0.43; p < 0.001). Our results show skeletal muscle architectural changes with aging and intermuscular differences in the microstructure. DT-MRI may prove useful for elucidating muscle changes in the early stages of sarcopenia and monitoring interventions aimed at preventing age-associated microstructural changes in muscle that lead to functional impairment.
Purpose: To develop an anomalous (non-Gaussian) diffusion model for characterizing skeletal muscle perfusion using multi-b-value DWI. Theory and methods: Fick’s first law was extended for describing tissue perfusion as anomalous superdiffusion, which is non-Gaussian diffusion exhibiting greater particle spread than that of the Gaussian case. This was accomplished using a space-fractional derivative that gives rise to a power-law relationship between mean squared displacement and time, and produces a stretched exponential signal decay as a function of b-value. Numerical simulations were used to estimate parameter errors under in vivo conditions, and examine the effect of limited SNR and residual fat signal. Stretched exponential DWI parameters, α and (Formula presented.), were measured in thigh muscles of 4 healthy volunteers at rest and following in-magnet exercise. These parameters were related to a stable distribution of jump-length probabilities and used to estimate microvascular volume fractions. Results: Numerical simulations showed low dispersion in parameter estimates within 1.5% and 1%, and bias errors within 3% and 10%, for α and (Formula presented.), respectively. Superdiffusion was observed in resting muscle, and to a greater degree following exercise. Resting microvascular volume fraction was between 0.0067 and 0.0139 and increased between 2.2-fold and 4.7-fold following exercise. Conclusions: This model captures superdiffusive molecular motions consistent with perfusion, using a parsimonious representation of the DWI signal, providing approximations of microvascular volume fraction comparable with histological estimates. This signal model demonstrates low parameter-estimation errors, and therefore holds potential for a wide range of applications in skeletal muscle and elsewhere in the body.
Throughout the body, muscle structure and function can be interrogated using a variety of noninvasive magnetic resonance imaging (MRI) methods. Recently, intravoxel incoherent motion (IVIM) MRI has gained momentum as a method to evaluate components of blood flow and tissue diffusion simultaneously. Much of the prior research has focused on highly vascularized organs, including the brain, kidney, and liver. Unique aspects of skeletal muscle, including the relatively low perfusion at rest and large dynamic range of perfusion between resting and maximal hyperemic states, may influence the acquisition, postprocessing, and interpretation of IVIM data. Here, we introduce several of those unique features of skeletal muscle; review existing studies of IVIM in skeletal muscle at rest, in response to exercise, and in disease states; and consider possible confounds that should be addressed for muscle-specific evaluations. Most studies used segmented nonlinear least squares fitting with a b-value threshold of 200 sec/mm2 to obtain IVIM parameters of perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D). In healthy individuals, across all muscles, the average ± standard deviation of D was 1.46 ± 0.30 × 10−3 mm2/sec, D* was 29.7 ± 38.1 × 10−3 mm2/sec, and f was 11.1 ± 6.7%. Comparisons of reported IVIM parameters in muscles of the back, thigh, and leg of healthy individuals showed no significant difference between anatomic locations. Throughout the body, exercise elicited a positive change of all IVIM parameters. Future directions including advanced postprocessing models and potential sequence modifications are discussed. Level of Evidence: 2. Technical Efficacy: Stage 2.
Skeletal muscle density, as determined by computed tomography (CT), has been shown to decline with age, resulting in increased frailty and morbidity. However, the mechanism underlying this decrease in muscle density remains elusive. We sought to investigate the role of intramyocellular lipid (IMCL) accumulation in the age-related decline in muscle density. Muscle density was measured using computerized tomography (CT), and IMCL content was quantified using in vivo proton magnetic resonance spectroscopy (1H-MRS). The study population consisted of 314 healthy participants (142 men, 32–98 years) of the Baltimore Longitudinal Study of Aging (BLSA). In addition to IMCL quantification, obesity-related covariates were measured, including body mass index (BMI), waist circumference, and circulating triglyceride concentration. Higher IMCL concentrations were significantly correlated with lower muscle density in older individuals, independent of age, sex, race, and the obesity-associated covariates (p < 0.01). Lower muscle density was also significantly associated with greater age-adjusted IMCL, a variable we constructed using LOESS regression (p < 0.05). Our results suggest that the accumulation of IMCL may be associated with a decrease in muscle density. This may serve to define a potential therapeutic target for treatment of age-associated decreased muscle function.
Background
Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females.
Methods
Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses.
Results
Mitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = − 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = − 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr.
Conclusions
These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.
Maximum oxidative capacity of skeletal muscle measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS) declines with age, and negatively affects whole-body aerobic capacity. However, it remains unclear whether the loss of oxidative capacity is caused by reduced volume and function of mitochondria or limited substrate availability secondary to impaired muscle perfusion. Therefore, we sought to elucidate the role of muscle perfusion on the age-related decline of muscle oxidative capacity and ultimately whole-body aerobic capacity. Muscle oxidative capacity was assessed by 31P-MRS post-exercise phosphocreatine recovery time (τPCr), with higher τPCr reflecting lower oxidative capacity, in 75 healthy participants (48 men, 22-89 years) of the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing study. Muscle perfusion was characterized as an index of blood volume at rest using a customized diffusion-weighted MRI technique and analysis method developed in our laboratory. Aerobic capacity (peak-VO2) was also measured during a graded treadmill exercise test in the same visit. Muscle oxidative capacity, peak-VO2, and resting muscle perfusion were significantly lower at older ages independent of sex, race, and body mass index (BMI). τPCr was significantly associated with resting muscle perfusion independent of age, sex, race, and BMI (p-value = 0.004, β = -0.34). τPCr was also a significant independent predictor of peak-VO2 and, in a mediation analysis, significantly attenuated the association between muscle perfusion and peak-VO2 (34% reduction for β in perfusion). These findings suggest that the age-associated decline in muscle oxidative capacity is partly due to impaired muscle perfusion and not mitochondrial dysfunction alone. Furthermore, our findings show that part of the decline in whole-body aerobic capacity observed with aging is also due to reduced microvascular blood volume at rest, representing a basal capacity of the microvascular system, which is mediated by muscle oxidative capacity. This finding suggests potential benefit of interventions that target an overall increase in muscle perfusion for the restoration of energetic capacity and mitochondrial function with aging.
Aging is associated with impaired endothelium-dependent vasodilation that leads to muscle perfusion impairment and contributes to organ dysfunction. Impaired muscle perfusion may result in inadequate delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationship between perfusion and muscle damage has been limited using traditional muscle perfusion measures, which are invasive and risky. To overcome this limitation, we optimized a diffusion-weighted MRI sequence and validated an intravoxel incoherent motion (IVIM) analysis based on Monte Carlo simulation to study muscle perfusion impairment with aging during post-exercise hyperemia.
Simulation results demonstrated that the bias of IVIM-derived perfusion fraction (f p ) and diffusion of water molecules in extra-vascular tissue (D) ranged from −3.3% to 14% and from −16.5% to 0.002%, respectively, in the optimized experimental condition. The dispersion in f p and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The mid-thigh of the left leg of four younger (21–30 year old) and four older (60–90 year old) healthy females was studied using the optimized protocol at baseline and at seven time increments occurring every 3.25 min following in-magnet dynamic knee extension exercise performed using a MR-compatible ergometer with a workload of 0.4 bar for 2.5 min. After exercise, both f p and D significantly increased in the rectus femoris (active muscle during exercise) but not in adductor magnus (inactive muscle), reflecting the fact that the local increase in perfusion with both groups showed a maximum value in the second post-exercise time-point.
A significantly greater increase in perfusion from the baseline (p < 0.05) was observed in the younger group (37 ± 12.05%) compared with the older group (17.57 ± 15.92%) at the first post-exercise measurement. This work establishes a reliable non-invasive method that can be used to study the effects of aging on dynamic changes in muscle perfusion as they relate to important measures of physical function.
BACKGROUND AND PURPOSE: Myelin water fraction (MWF) mapping permits direct visualization of myelination patterns in the developing brain and in pathology. MWF is conventionally measured through multiexponential T2 analysis which is very sensitive to noise, leading to inaccuracies in derived MWF estimates. Although noise reduction filters may be applied during postprocessing, conventional filtering can introduce bias and obscure small structures and edges. Advanced nonblurring filters, while effective, exhibit a high level of complexity and the requirement for supervised implementation for optimal performance. The purpose of this paper is to demonstrate the ability of the recently introduced nonlocal estimation of multispectral magnitudes (NESMA) filter to greatly improve the determination of MWF parameter estimates from gradient and spin echo (GRASE) imaging data.
METHODS: We evaluated the performance of the NESMA filter for MWF mapping from clinical GRASE imaging data of the human brain, and compared the results to those calculated from unfiltered images. Numerical and in vivo analyses of the brains of three subjects, representing different ages, were conducted.
RESULTS: Our results demonstrated the potential of the NESMA filter to permit high-quality in vivo MWF mapping. Indeed, NESMA permits substantial reduction of random variation in derived MWF estimates while preserving accuracy and detail.
CONCLUSIONS: In vivo estimation of MWF in the human brain from GRASE imaging data was markedly improved through use of the NESMA filter. The use of NESMA may contribute to the goal of high-quality MWF mapping in clinically feasible imaging times.