Time-dependent diffusion tensor imaging and diffusion modeling of age-related differences in the medial gastrocnemius and feasibility study of correlations to histopathology.

PURPOSE: Implement STEAM-DTI to model time-dependent diffusion eigenvalues using the random permeable barrier model (RPBM) to study age-related differences in the medial gastrocnemius (MG) muscle. Validate diffusion model-extracted fiber diameter for histological assessment. METHODS: Diffusion imaging at different diffusion times (Δ) was performed on seven young and six senior participants. Time-dependent diffusion eigenvalues (λ2 (t), λ3 (t), and D⊥ (t); average of λ2 (t) and λ3 (t)) were fit to the RPBM to extract tissue microstructure parameters. Biopsy of the MG tissue for histological assessment was performed on a subset of participants (four young, six senior). RESULTS: λ3 (t) was significantly higher in the senior cohort for the range of diffusion times. RPBM fits to λ2 (t) yielded fiber diameters in agreement to those from histology for both cohorts. The senior cohort had lower values of volume fraction of membranes, ζ, in fits to λ2 (t), λ3 (t), and D⊥ (t) (significant for fit to λ3 (t)). Fits of fiber diameter from RPBM to that from histology had the highest correlation for the fit to λ2 (t). CONCLUSION: The age-related patterns in λ2 (t) and λ3 (t) could tentatively be explained from RPBM fits; these patterns may potentially arise from a decrease in fiber asymmetry and an increase in permeability with age.

Compressed sensing velocity encoded phase contrast imaging: Monitoring skeletal muscle kinematics.

PURPOSE: This study implements a compressed sensing (CS) 3-directional velocity encoded phase contrast (VE-PC) imaging for studying skeletal muscle kinematics within 40 s. METHODS: Independent variable density random sampling in the phase encoding direction for each temporal frame was implemented for various combinations of CS-factors and views per segment. CS reconstruction was performed for the combined multicoil, temporal datasets using temporal Fourier transform followed by temporal principal component analysis sparsifying transformations. The method was tested on a flow phantom and in vivo, on velocity and strain rate of the medial gastrocnemius muscle of 11 subjects performing isometric contractions. RESULTS: For the flow phantom, velocity from 8 undersampled sequences matched very well with the flowmeter values over a range of velocities spanning in vivo muscle velocities. Bland-Altman plots of the peak strain rate eigenvalues comparing 7 undersampled sequences was in good agreement with the reference (full k-space) scan. CS-factor of 4 combined with views per segment of 4 (scan times reduced by 4) yielded images with no visual artifacts allowing and yielded velocities and strain rate maps in the lower leg muscle in 40 s. CONCLUSION: This study shows that a reduction in scan time of velocity encoded phase contrast imaging up to a factor of 4 is possible using the proposed CS reconstruction.

Magnetization transfer saturation imaging of human calf muscle: Reproducibility and sensitivity to regional and sex differences.

BACKGROUND: Magnetization transfer saturation (MTsat ) derives a semiquantitative index of magnetization transfer in faster acquisition times than quantitative magnetization transfer; the potential of MTsat for muscle imaging has not yet been explored. PURPOSE: To evaluate the potential of MTsat to identify regional and sex differences in calf muscle. STUDY TYPE: Prospective cohort study. PHANTOM/SUBJECTS: Vials with different agar and nickel nitrate concentrations providing a range of macromolecular fraction and T1 . Seven male subjects (25 ± 7 years) and seven female subjects (28 ± 14 years); three subjects were scanned in three separate sessions to assess reproducibility. FIELD STRENGTH/SEQUENCE: 3T, 3D fast low angle shot (FLASH) sequence with and without a magnetization transfer pulse; acquisition time of 4.12 minutes. ASSESSMENT: The effectiveness of two methods of fat suppression was evaluated using the fat unsuppressed sequence as the reference and MTsat maps derived with and without transmit field inhomogeneity corrections were compared. Statistical evaluation of MTsat differences between calf muscles and between male and female cohorts was made. STATISTICAL TESTS: Bland-Altman plots were used to assess fat suppression and B1+ correction. The coefficient of variation (CV) and the repeatability coefficient (RC) were calculated from the repeat sessions. Sex and regional differences were assessed using two-way factorial analyses of variance (ANOVAs) with Bonferroni-adjusted independent sample t-tests for post-hoc analyses. RESULTS: In phantoms, MTsat increased linearly with agar concentration and MTsat was independent of T1 (P = 0.229) evaluated in phantoms with two T1 s. The CV and RC of MTsat ranged between 2.65 to 5.03% and 0.13 to 0.38, respectively, in the different calf muscles. MTsat of the tibialis anterior was significantly higher than other muscles (P < 0.05). MTsat in male subjects was significantly higher than in female subjects (P = 0.009). DATA CONCLUSION: MTsat maps of calf muscle acquired under 5 minutes may have the potential to detect regional and sex differences. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1227-1237.

Diffusion tensor imaging and diffusion modeling: Application to monitoring changes in the medial gastrocnemius in disuse atrophy induced by unilateral limb suspension.

BACKGROUND: Diffusion tensor imaging (DTI) assesses underlying tissue microstructure, and has been applied to studying skeletal muscle. Unloading of the lower leg causes decreases in muscle force, mass, and muscle protein synthesis as well as changes in muscle architecture. PURPOSE: To monitor the change in DTI indices in the medial gastrocnemius (MG) after 4-week unilateral limb suspension (ULLS) and to explore the feasibility of extracting tissue microstructural parameters based on a two-compartment diffusion model. STUDY TYPE: Prospective cohort study. SUBJECTS: Seven moderately active subjects (29.1 ± 5.7 years). FIELD STRENGTH/SEQUENCE: 3T, single-shot fat-suppressed echo planar spin echo sequence. ASSESSMENT: Suspension-related changes in the DTI indices (eigenvalues: λ1 , λ2 , λ3 , fractional anisotropy; coefficient of planarity) were statistically analyzed. Changes in model-derived tissue parameters (muscle fiber circularity and diameter, intracellular volume fraction, and residence time) after suspension are qualitatively discussed. STATISTICAL TESTS: Changes in the DTI indices of the MG between pre- and postsuspension were assessed using repeated-measures two-way analysis of variance (ANOVA). RESULTS: All the eigenvalues (λ1 : P = 0.025, λ2 : P = 0.035, λ3 : P = 0.049) as well as anisotropic diffusion coefficient (P = 0.029) were significantly smaller post-ULLS. Diffusion modeling revealed that fibers were more circular (circularity index increased from 0.55 to 0.95) with a smaller diameter (diameter decreased from 82-60 µm) postsuspension. DATA CONCLUSION: We have shown that DTI indices change with disuse and modeling can relate these voxel level changes to changes in the tissue microarchitecture. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

Relationship of changes in strain rate indices estimated from velocity-encoded MR imaging to loss of muscle force following disuse atrophy.

PURPOSE: This study explores changes in strain rate (SR) (rate of regional deformation) parameters extracted from velocity-encoded MRI and their relationship to muscle force loss following 4-week unilateral lower limb suspension in healthy humans. METHODS: Two-dimensional SR maps were derived from three directional velocity-encoded MR phase-contrast images of the medial gastrocnemius in seven subjects. Atrophy-related and regional differences in the SR eigenvalues, angle between the SR and muscle fiber (SR-fiber angle), and strain rates in the fiber basis were statistically analyzed using analysis of variance and linear regression. RESULTS: During isometric contraction, SR in the fiber cross section (SRin-plane ) was significantly lower, and the SR-fiber angle was significantly higher postsuspension (P < 0.05). On multiple variable regression analysis, the volume of medial gastrocnemius, SRin-plane , and SR-fiber angle were significantly associated with force and changes in the, and the SR eigenvalues and shear SR were significantly associated with change in force with disuse. CONCLUSIONS: Changes in SR-fiber angle, SRin-plane , and shear SR as well as their ability to predict force and force changes may reflect the role of remodeling of the extracellular matrix in disuse atrophy and its functional consequence in reducing lateral transmission of force. Magn Reson Med 79:912-922, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Shear strain rate from phase contrast velocity encoded MRI: Application to study effects of aging in the medial gastrocnemius muscle.

BACKGROUND: Strain rate (SR) is a measure of the rate of regional deformation that can be computed by analyzing velocity-encoded phase-contrast 2D images. Recent studies have explored the changes in normal components of the strain tensor in aging muscle, while shear strain may also provide valuable information. PURPOSE: To compute the shear SR from velocity-encoded MRI of the lower leg and to study the correlation of SR parameters measured in the medial gastrocnemius (MG) to muscle force in a cohort of young and senior subjects. STUDY TYPE: Prospective cohort study. SUBJECTS: Six young (26.1 ± 2.3 years) and six senior (76.7 ± 8.3 years) healthy females; two other subjects were scanned on three separate occasions for repeatability studies. FIELD STRENGTH/SEQUENCE: 1.5T using a single oblique sagittal slice with velocity-encoding in three directions (velocity-encoded phase contrast gradient echo sequence). ASSESSMENT: Age-related and regional differences in the SR eigenvalues (SRfiber , SRin-plane ), normal SRs (SRff , SRcc ), and shear SRs (SRfc , SRfc_max ) were statistically analyzed. STATISTICAL TESTS: Difference between young and senior cohorts were assessed using two-way analysis of variance (ANOVAs). The coefficient of variation and repeatability coefficient were calculated from repeat studies. Univariate and stepwise multivariable linear regression was performed to identify predictors of force. RESULTS: During isometric plantarflexion contraction, SRs in the principal basis (SRfiber , SRin-plane ) and maximum shear SR (SRfc_max ) was significantly lower in the senior cohort (P < 0.05). On multiple variable regression, maximum shear SR (SRfc_max ) and normal SR in the fiber cross-section (SRcc ) were significantly associated with force (R = 0.681, F = 14.034, P < 0.001). DATA CONCLUSION: This study establishes that computation of shear strain is feasible and is a significant predictor of force variability with age. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1351-1357.

Exploration of male urethral sphincter complex using diffusion tensor imaging (DTI)-based fiber-tracking.

BACKGROUND: Urinary incontinence is a major clinical problem arising primarily from age-related degenerative changes to the sphincter muscles. However, the precise anatomy of the normal male sphincter muscles has yet to be established. Diffusion tensor imaging (DTI) may offer a unique insight into muscle microstructure and fiber architecture. PURPOSE: To explore the anatomy of the urethral sphincter muscles pertinent to urinary continence function using DT-MRI. STUDY TYPE: Prospective cohort study. SUBJECTS: Eleven normal male subjects (mean age: 25.4 years); two subjects were scanned in three separate sessions to assess reproducibility. FIELD STRENGTH/SEQUENCE: 3T; using a diffusion-weighted spin echo planar sequence. ASSESSMENT: DT parameters including fractional anisotropy (FA), primary (λ1 ), secondary (λ2 ), and tertiary (λ3 ) eigenvalues, Apparent diffusion coefficient and radial diffusivity were analyzed statistically, while tracked muscle fibers were assessed visually. STATISTICAL TESTS: Regional differences (sphincters and longitudinal muscle of the urethra) in the DTI indices were assessed by one-way analysis of variance. A Tukey post-hoc test was used to identify significant differences between muscle regions. RESULTS: Two sphincter muscles, one proximal near the base of the bladder, corresponding to the lisso-sphincter, and the other distal to the end of the prostate corresponding to the rhabdo-sphincter, surrounding a central urethral muscle fiber bundle, were clearly identified. FA was higher and λ3 lower in the proximal sphincter muscle compared to the central urethral muscle and the distal sphincter (P < 0.05). The average coefficient of variation ranged from 5-12% for the DTI indices. DATA CONCLUSION: Since DTI values are known to reflect underlying tissue microarchitecture, significant differences in DTI indices identified here between the muscles of the urethral complex may potentially arise from differences in tissue microarchitecture that may in turn be related to the specific function of the sphincter and other muscles. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1002-1011.

3D multimodal spatial fuzzy segmentation of intramuscular connective and adipose tissue from ultrashort TE MR images of calf muscle.

PURPOSE: To develop and evaluate an automated algorithm to segment intramuscular adipose (IMAT) and connective (IMCT) tissue from musculoskeletal MRI images acquired with a dual echo Ultrashort TE (UTE) sequence. THEORY AND METHODS: The dual echo images and calculated structure tensor images are the inputs to the multichannel fuzzy cluster mean (MCFCM) algorithm. Modifications to the basic multichannel fuzzy cluster mean include an adaptive spatial term and bias shading correction. The algorithm was tested on digital phantoms simulating IMAT/IMCT tissue under varying conditions of image noise and bias and on ten subjects with varying amounts of IMAT/IMCT. RESULTS: The MCFCM including the adaptive spatial term and bias shading correction performed better than the original MCFCM and adaptive spatial MCFCM algorithms. IMAT/IMCT was segmented from the unsmoothed simulated phantom data with a mean Dice coefficient of 0.933 ±0.001 when contrast-to-noise (CNR) was 140 and bias was varied between 30% and 65%. The algorithm yielded accurate in vivo segmentations of IMAT/IMCT with a mean Dice coefficient of 0.977 ±0.066. CONCLUSION: The proposed algorithm is completely automated and yielded accurate segmentation of intramuscular adipose and connective tissue in the digital phantom and in human calf data. Magn Reson Med 77:870-883, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Age-related differences in strain rate tensor of the medial gastrocnemius muscle during passive plantarflexion and active isometric contraction using velocity encoded MR imaging: potential index of lateral force transmission.

PURPOSE: The strain rate (SR) tensor measures the principal directions and magnitude of the instantaneous deformation; this study aims to track age-related changes in the 2D SR tensor in the medial gastrocnemius during passive joint rotation and active isometric contraction. METHODS: SR tensors were derived from velocity encoded magnetic resonance phase-contrast images in nine young (28 years) and eight senior (78 years) women. Strain rates along and in the cross-section of the fiber were calculated from the SR tensor and used to derive the out-plane SR. Age-related and regional differences in the SR eigenvalues, orientation, and the angle between the SR and muscle fiber (SR-fiber angle) were statistically analyzed. RESULTS: SR along the fiber was significantly different between the cohorts during isometric contraction with higher values in the young (P < 0.05). The SR-fiber angle was larger in the young for both motion types but this difference was not statistically significant. Significant regional differences in the SR indices was seen in passive joint rotation (P < 0.05) for both cohorts. CONCLUSION: SR mapping reflects age-related and regional differences during active and passive motion respectively; this may arise from differences in contractility (active motion) and elastic properties (active and passive motion).

Age-related differences in diffusion tensor indices and fiber architecture in the medial and lateral gastrocnemius.

PURPOSE: To investigate age related changes in diffusion tensor indices and fiber architecture of the medial and lateral gastrocnemius (MG and LG) muscles using diffusion tensor imaging (DTI). MATERIALS AND METHODS: The lower leg of five young and five senior subjects was scanned at 3 Tesla and DTI indices extracted using three methods: region of interest, histogram, and tract based. Tracked fibers were automatically edited to ensure physiologically relevant tracks. Pennation angles were measured with respect to the deep and superficial aponeuroses of both muscles. RESULTS: The three methods provided internally consistent measures of the DTI indices (correlation coefficient in the range of 0.90-0.99). The primary, secondary, and tertiary eigenvalues in the MG and LG increased significantly in the senior cohort (P < 0.05), while the small increase in fractional anisotropy with age was not significant (MG/LG: P = 0.39/0.85; 95% confidence interval: [-0.059/-0.056, 0.116/0.064]). Fiber lengths of MG fibers originating distally were significantly decreased in seniors (P < 0.05) while pennation angles decreased with age in the MG and LG but this was not significant. CONCLUSION: Fiber atrophy and increased fibrosis have opposing effects on the diffusion indices resulting in a complicated dependence with aging. Fiber architectural changes could play a role in determining aging muscle function.

Methodological improvements in voxel-based analysis of diffusion tensor images: applications to study the impact of apolipoprotein E on white matter integrity.

PURPOSE: To identify regional differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) using customized preprocessing before voxel-based analysis (VBA) in 14 normal subjects with the specific genes that decrease (apolipoprotein [APO] E ε2) and that increase (APOE ε4) the risk of Alzheimer's disease. MATERIALS AND METHODS: Diffusion tensor images (DTI) acquired at 1.5 Tesla were denoised with a total variation tensor regularization algorithm before affine and nonlinear registration to generate a common reference frame for the image volumes of all subjects. Anisotropic and isotropic smoothing with varying kernel sizes was applied to the aligned data before VBA to determine regional differences between cohorts segregated by allele status. RESULTS: VBA on the denoised tensor data identified regions of reduced FA in APOE ε4 compared with the APOE ε2 healthy older carriers. The most consistent results were obtained using the denoised tensor and anisotropic smoothing before statistical testing. In contrast, isotropic smoothing identified regional differences for small filter sizes alone, emphasizing that this method introduces bias in FA values for higher kernel sizes. CONCLUSION: Voxel-based DTI analysis can be performed on low signal to noise ratio images to detect subtle regional differences in cohorts using the proposed preprocessing techniques.

Age-associated differences in triceps surae muscle composition and strength - an MRI-based cross-sectional comparison of contractile, adipose and connective tissue.

BACKGROUND: In human skeletal muscles, the aging process causes a decrease of contractile and a concomitant increase of intramuscular adipose (IMAT) and connective (IMCT) tissues. The accumulation of non-contractile tissues may contribute to the significant loss of intrinsic muscle strength typically observed at older age but their in vivo quantification is challenging. The purpose of this study was to establish MR imaging-based methods to quantify the relative amounts of IMCT, IMAT and contractile tissues in young and older human cohorts, and investigate their roles in determining age-associated changes in skeletal muscle strength. METHODS: Five young (31.6 ± 7.0 yrs) and five older (83.4 ± 3.2 yrs) Japanese women were subject to a detailed MR imaging protocol, including Fast Gradient Echo, Quantitative Fat/Water (IDEAL) and Ultra-short Echo Time (UTE) sequences, to determine contractile muscle tissue and IMAT within the entire Triceps Surae complex, and IMCT within both heads of the Gastrocnemius muscle. Specific force was calculated as the ratio of isometric plantarflexor force and the physiological cross-sectional area of the Triceps Surae complex. RESULTS: In the older cohort, total Triceps Surae volume was smaller by 17.5%, while the relative amounts of Triceps Surae IMAT and Gastrocnemius IMCT were larger by 55.1% and 48.9%, respectively. Differences of 38.6% and 42.1% in plantarflexor force and specific force were observed. After subtraction of IMAT and IMCT from total muscle volume, differences in intrinsic strength decreased to 29.6%. CONCLUSIONS: Our data establishes that aging causes significant changes in skeletal muscle composition, with marked increases in non-contractile tissues. Such quantification of the remodeling process is likely to be of functional and clinical importance in elucidating the causes of the disproportionate age-associated decrease of force compared to that of muscle volume.

MRI Based Fiber Strain Mapping of the Medial Gastrocnemius Muscle at Submaximal Isometric Contractions at Different Ankle Angles.

Muscle force production is influenced by muscle fiber and aponeurosis architecture. This prospective cohort study utilizes special MR imaging sequences to examine the structure-function in-vivo in the Medial Gastrocnemius (MG) at three-ankle angles (dorsiflexion, neutral, and plantar flexion) and two sub-maximal levels of maximum voluntary contraction (25% and 50% MVC). The study was performed on 6 young male subjects. Muscle fiber and aponeurosis strain, fiber strain normalized to force, fiber length and pennation angle (at rest and peak contraction) were analyzed for statistical differences between ankle positions and %MVC. A two-way repeated measures ANOVA and post hoc Bonferroni-adjusted tests were conducted for normal data. A related samples test with Friedman's 2-way ANOVA by ranks with corrections for multiple comparisons was conducted for non-normal data. The dorsiflexed ankle position generated significantly higher force with lower fiber strain than neutral and plantarflexed positions. Sarcomere length extracted from muscle fiber length at each ankle angle was used to track the location on the Force-Length curve and showed the MG operates on the curve's ascending limb. Muscle force changes predicted from the F-L curve going from dorsi- to plantarflexion was less than that experimentally observed suggesting other determinants of force changes with ankle position.

Strain and Strain Rate Tensor Mapping of Medial Gastrocnemius at Submaximal Isometric Contraction and Three Ankle Angles.

INTRODUCTION: The aim of this study is to analyze the muscle kinematics of the medial gastrocnemius (MG) during submaximal isometric contractions and to explore the relationship between deformation and force generated at plantarflexed (PF), neutral (N) and dorsiflexed (DF) ankle angles. METHOD: Strain and Strain Rate (SR) tensors were calculated from velocity-encoded magnetic resonance phase-contrast images in six young men acquired during 25% and 50% Maximum Voluntary Contraction (MVC). Strain and SR indices as well as force normalized values were statistically analyzed using two-way repeated measures ANOVA for differences with force level and ankle angle. An exploratory analysis of differences between absolute values of longitudinal compressive strain (Eλ1) and radial expansion strains (Eλ2) and maximum shear strain (Emax) based on paired t-test was also performed for each ankle angle. RESULTS: Compressive strains/SRs were significantly lower at 25%MVC. Normalized strains/SR were significantly different between %MVC and ankle angles with lowest values for DF. Absolute values of Eλ2 and Emax were significantly higher than Eλ1 for DF suggesting higher deformation asymmetry and higher shear strain, respectively. CONCLUSIONS: In addition to the known optimum muscle fiber length, the study identified two potential new causes of increased force generation at dorsiflexion ankle angle, higher fiber cross-section deformation asymmetry and higher shear strains.

Effect of different ankle joint positions on medial gastrocnemius muscle fiber strains during isometric plantarflexion.

Muscle force production is influenced by muscle fiber and aponeurosis architecture. This prospective cohort study utilizes special MR imaging sequences to examine the structure-function in-vivo in the Medial Gastrocnemius (MG) at three-ankle angles (dorsiflexion, plantar flexion-low and high) and two sub-maximal levels of maximum voluntary contraction (25% and 50%MVC). The study was performed on 6 young male participants. Muscle fiber and aponeurosis strain, fiber strain normalized to force, fiber length and pennation angle (at rest and peak contraction) were analyzed for statistical differences between ankle positions and %MVC. A two-way repeated measures ANOVA and post hoc Bonferroni-adjusted tests were conducted for normal data. A related samples test with Friedman's 2-way ANOVA by ranks with corrections for multiple comparisons was conducted for non-normal data. The dorsiflexed ankle position generated significantly higher force with lower fiber strain than the plantarflexed positions. Sarcomere length extracted from muscle fiber length at each ankle angle was used to track the location on the Force-Length curve and showed the MG operates on the curve's ascending limb. Muscle force changes predicted from the F-L curve going from dorsi- to plantarflexion was less than that experimentally observed suggesting other determinants of force changes with ankle position.

Investigating the Correlation between Force Output, Strains, and Pressure for Active Skeletal Muscle Contractions.

Experimental observations suggest that the force output of the skeletal muscle tissue can be correlated to the intra-muscular pressure generated by the muscle belly. However, pressure often proves difficult to measure through in-vivo tests. Simulations on the other hand, offer a tool to model muscle contractions and analyze the relationship between muscle force generation and deformations as well as pressure outputs, enabling us to gain insight into correlations among experimentally measurable quantities such as principal and volumetric strains, and the force output. In this work, a correlation study is performed using Pearson's and Spearman's correlation coefficients on the force output of the skeletal muscle, the principal and volumetric strains experienced by the muscle and the pressure developed within the muscle belly as the muscle tissue undergoes isometric contractions due to varying activation profiles. The study reveals strong correlations between force output and the strains at all locations of the belly, irrespective of the type of activation profile used. This observation enables estimation on the contribution of various muscle groups to the total force by the experimentally measurable principal and volumetric strains in the muscle belly. It is also observed that pressure does not correlate well with force output due to stress relaxation near the boundary of muscle belly.

Spin Lattice (T1) and Magnetization Transfer Saturation (MTsat) Imaging to Monitor Age-Related Differences in Skeletal Muscle Tissue.

BACKGROUND: The aim was to compare spin-lattice relaxation (T1) mapping from sequences with no fat suppression and three fat suppression methods and Magnetization Transfer Saturation (MTsat) mapping, to identify regional and age-related differences in calf muscle. These differences may be of clinical significance in age-related loss of muscle force. METHODS: Ten young and seven senior subjects were imaged on a 3T MRI scanner using a 3D Fast Low Angle Shot sequence without and with different fat suppression and with MT saturation pulse. Bland-Altman plots were used to assess T1 maps using the fat unsuppressed sequence as the reference image. Age and regional differences in T1 and in MTsat were assessed using two-way factorial analyses of variance (ANOVAs) with Bonferroni-adjusted independent sample t-tests for post hoc analyses. RESULTS: A significant age-related increase in T1 and decrease in MTsat was seen in the calf muscles. The largest size effect was observed in the T1 sequence with fat saturation. CONCLUSIONS: T1 increase with age may reflect increase in inflammatory processes while the decrease in MTsat may indicate that magnetization transfer may also be associated with muscle fiber macromolecules. T1 and MTsat maps of calf muscle have the potential to detect regional and age-related compositional differences in calf muscle.

Multiscale modeling of passive material influences on deformation and force output of skeletal muscles.

Passive materials in human skeletal muscle tissues play an important role in force output of skeletal muscles. This paper introduces a multiscale modeling framework to investigate how age-associated variations on microscale passive muscle components, including microstructural geometry (e.g., connective tissue thickness) and material properties (e.g., anisotropy), influence the force output and deformations of the continuum skeletal muscle. We first define a representative volume element (RVE) for the microstructure of muscle and determine the homogenized macroscale mechanical properties of the RVE from the separate mechanical properties of the individual components of the RVE, including muscle fibers and connective tissue with its associated collagen fibers. The homogenized properties of the RVE are then used to define the elements of the continuum muscle model to evaluate the force output and deformations of the whole muscle. Conversely, the regional deformations of the continuum model are fed back to the RVE model to determine the responses of the individual microscale components. Simulations of muscle isometric contractions at a range of muscle lengths are performed to investigate the effects of muscle architectural changes (e.g., pennation angles) due to aging on force output and muscle deformation. The correlations between the pennation angle, the shear deformation in the microscale connective tissue (an indicator for the lateral force transmission), the angle difference between the fiber direction and principal strain direction and the resulting shear deformation at the continuum scale, as well as the force output of the skeletal muscle are also discussed.