Geoffrey G. Handsfield

Relationships of 35 lower limb muscles to height and body mass quantified using MRI

Skeletal muscle is the most abundant tissue in the body and serves various physiological functions including the generation of movement and support. Whole body motor function requires adequate quantity, geometry, and distribution of muscle. This raises the question: how do muscles scale with subject size in order to achieve similar function across humans? While much of the current knowledge of human muscle architecture is based on cadaver dissection, modern medical imaging avoids limitations of old age, poor health, and limited subject pool, allowing for muscle architecture data to be obtained in vivo from healthy subjects ranging in size. The purpose of this study was to use novel fast-acquisition MRI to quantify volumes and lengths of 35 major lower limb muscles in 24 young, healthy subjects and to determine if muscle size correlates with bone geometry and subject parameters of mass and height. It was found that total lower limb muscle volume scales with mass (R(2)=0.85) and with the height-mass product (R(2)=0.92). Furthermore, individual muscle volumes scale with total muscle volume (median R(2)=0.66), with the height-mass product (median R(2)=0.61), and with mass (median R(2)=0.52). Muscle volume scales with bone volume (R(2)=0.75), and muscle length relative to bone length is conserved (median s.d.=2.1% of limb length). These relationships allow for an arbitrary subjects individual muscle volumes to be estimated from mass or mass and height while muscle lengths may be estimated from limb length. The dataset presented here can further be used as a normative standard to compare populations with musculoskeletal pathologies.

Heterogeneity of muscle sizes in the lower limbs of children with cerebral palsy.

Cerebral palsy (CP) is associated with reduced muscle volumes, but previous studies have reported deficits in only a small number of muscles. The extent of volume deficits across lower limb muscles is not known. This study presents an imaging‐based assessment of muscle volume and length deficits in 35 lower limb muscles.

A 3D model of the Achilles tendon to determine the mechanisms underlying nonuniform tendon displacements

The Achilles is the thickest tendon in the body and is the primary elastic energy-storing component during running. The form and function of the human Achilles is complex: twisted structure, intratendinous interactions, and differential motor control from the triceps surae muscles make Achilles behavior difficult to intuit. Recent in vivo imaging of the Achilles has revealed nonuniform displacement patterns that are not fully understood and may result from complex architecture and musculotendon interactions. In order to understand which features of the Achilles tendon give rise to the nonuniform deformations observed in vivo, we used computational modeling to predict the mechanical contributions from different features of the tendon. The aims of this study are to: (i) build a novel computational model of the Achilles tendon based on ultrashort echo time MRI, (ii) compare simulated displacements with published in vivo ultrasound measures of displacement, and (iii) use the model to elucidate the effects of tendon twisting, intratendon sliding, retrocalcaneal insertion, and differential muscle forces on tendon deformation. Intratendon sliding and differential muscle forces were found to be the largest factors contributing to displacement nonuniformity between tendon regions. Elimination of intratendon sliding or muscle forces reduced displacement nonuniformity by 96% and 85%, respectively, while elimination of tendon twist and the retrocalcaneal insertion reduced displacement nonuniformity by only 35% and 3%. These results suggest that changes in the complex internal structure of the tendon alter the interaction between muscle forces and tendon behavior and therefore may have important implications on muscle function during movement.

Toward modeling locomotion using electromyography-informed 3D models: application to cerebral palsy

This position paper proposes a modeling pipeline to develop clinically relevant neuromusculoskeletal models to understand and treat complex neurological disorders. Although applicable to a variety of neurological conditions, we provide direct pipeline applicative examples in the context of cerebral palsy (CP). This paper highlights technologies in: (1) patient‐specific segmental rigid body models developed from magnetic resonance imaging for use in inverse kinematics and inverse dynamics pipelines; (2) efficient population‐based approaches to derive skeletal models and muscle origins/insertions that are useful for population statistics and consistent creation of continuum models; (3) continuum muscle descriptions to account for complex muscle architecture including spatially varying material properties with muscle wrapping; (4) muscle and tendon properties specific to CP; and (5) neural‐based electromyography‐informed methods for muscle force prediction. This represents a novel modeling pipeline that couples for the first time electromyography extracted features of disrupted neuromuscular behavior with advanced numerical methods for modeling CP‐specific musculoskeletal morphology and function. The translation of such pipeline to the clinical level will provide a new class of biomarkers that objectively describe the neuromusculoskeletal determinants of pathological locomotion and complement current clinical assessment techniques, which often rely on subjective judgment. WIREs Syst Biol Med 2017, 9:e1368. doi: 10.1002/wsbm.1368

Diminished Foot and Ankle Muscle Volumes in Young Adults With Chronic Ankle Instability

Background: Patients with chronic ankle instability (CAI) have demonstrated altered neuromuscular function and decreased muscle strength when compared with healthy counterparts without a history of ankle sprain. Up to this point, muscle volumes have not been analyzed in patients with CAI to determine whether deficits in muscle size are present following recurrent sprain. Purpose: To analyze intrinsic and extrinsic foot and ankle muscle volumes and 4-way ankle strength in young adults with and without CAI. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Five patients with CAI (mean age, 23.0 ± 4 years; 1 male, 4 females) and 5 healthy controls (mean age, 23.8 ± 4.5 years; 1 male, 4 females) volunteered for this study. Novel fast-acquisition magnetic resonance imaging (MRI) was used to scan from above the femoral condyles through the foot and ankle. The perimeter of each muscle was outlined on each axial slice and then the 2-dimensional area was multiplied by the slice thickness (5 mm) to calculate the muscle volume. Plantar flexion, dorsiflexion, inversion, and eversion isometric strength were measured using a handheld dynamometer. Patients with CAI were compared with healthy controls on all measures of muscle volume and strength. Extrinsic muscle volumes of patients with CAI were also compared with a normative database of healthy controls (n = 24) by calculating z scores for each muscle individually for each CAI subject. Results: The CAI group had smaller total shank, superficial posterior compartment, soleus, adductor hallucis obliqus, and flexor hallucis brevis muscle volumes compared with healthy controls as indicated by group means and associated 90% CIs that did not overlap. Cohen d effect sizes for the significant group differences were all large and ranged from 1.46 to 3.52, with 90% CIs that did not cross zero. The CAI group had lower eversion, dorsiflexion, and 4-way composite ankle strength, all with group means and associated 90% CIs that did not overlap. No other significant differences were identified. Conclusion: Patients with CAI demonstrate atrophy of intrinsic and extrinsic foot and ankle musculature accompanied by lower ankle strength. Clinical Relevance: Clinicians should be aware of the muscle atrophy and strength deficits when prescribing rehabilitation for patients with lateral ankle sprain or CAI.

Rapid Prediction of Personalised Muscle Mechanics: Integration with Diffusion Tensor Imaging

Diffusion Tensor Imaging (DTI) has been widely used to characterise the 3D fibre architecture in both neural and muscle mechanics. However, the computational expense associated with continuum models make their use in graphics and medical visualisation intractable. This study presents an integration of continuum muscle mechanics with partial least squares regression to create a fast mechano-statistical model. We use the human triceps surae muscle as an example informed though DTI. Our statistical models predicted muscle shape (within 0.063 mm RMS error), musculotendon force (within 1% error), and tissue strain (within 8% max error during contraction). Importantly, the presented framework may play a role in addressing computational cost of predicting detailed muscle information through popular rigid body solvers such as OpenSIM.

Soleus muscle weakness in Cerebral Palsy: muscle architecture revealed with Diffusion Tensor Imaging

Cerebral palsy (CP) is associated with movement disorders and reduced muscle size. This latter phenomenon has been observed by computing muscle volumes from conventional MRI, with most studies reporting significantly reduced volumes in leg muscles. This indicates impaired muscle growth, but without knowing muscle fiber orientation, it is not clear whether muscle growth in CP is impaired in the along-fiber direction (indicating shortened muscles and limited range of motion) or the cross-fiber direction (indicating weak muscles and impaired strength). Using Diffusion Tensor Imaging (DTI) we can determine muscle fiber orientation and construct 3D muscle architectures to examine along-fiber length and cross-sectional area separately. Such an approach has not been undertaken in CP. Here, we use advanced DTI sequences with fast imaging times to capture fiber orientations in the soleus muscle of children with CP and age-matched, able-bodied controls. Physiological cross sectional areas (PCSA) were reduced (37 ± 11%) in children with CP compared to controls, indicating impaired muscle strength. Along-fiber muscle lengths were not different between groups, but we observed large variance in length within CP group. This study is the first to demonstrate functional strength deficits using DTI and implicates impaired cross-sectional muscle growth in children with cerebral palsy.

Towards rapid prediction of personalised muscle mechanics: integration with diffusion tensor imaging

ABSTRACT Diffusion tensor imaging (DTI) has been widely used to characterise the 3D fascicle architecture in muscle mechanics. However, the computational expense associated with continuum models make their use in graphics and medical visualisation intractable. This study presents an integration of continuum muscle mechanics with partial least-squares regression to create a fast mechanostatistical model. We use the human gastrocnemius muscle (medial and lateral heads) as an example informed though DTI. Our statistical models predicted muscle shape (within 0.063 mm root-mean-square (RMS) error), musculotendon force (within 1% error), and tissue strain (within 8% max error during muscle contraction), compared to a finite-element model simulation. The technique presented here is a step towards integrating expensive continuum mechanics with fast rigid body solutions in biomechanics. While muscle force is a primary objective in rigid body solvers the additional information including 3D muscle shape and stress/strain fields may now be integrated. One of the key benefits is that muscle interaction with other soft tissues is accounted for, muscle moment arms are not estimated, and the detailed rich 3D continuum fascicle architecture is no longer simplified but plays a full role in biomechanics simulation. This has implications for musculoskeletal biomechanics, orthopaedics and medical visualisation.

Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms

Duchenne muscular dystrophy (DMD) is a progressive degenerative disease that results in fibrosis and atrophy of muscles. The main cause of death associated with DMD is failure of the diaphragm. The diaphragm is a dome-shaped muscle with a fiber microstructure that differs across regions of the muscle. However, no studies to our knowledge have examined spatial variations of muscle fibers in dystrophic diaphragm or how aging affects those variations in DMD. In this study, diaphragms were obtained from mdx and healthy mice at ages three, seven, and ten months in the dorsal, midcostal, and ventral regions. Through immunostaining and confocal imaging, we quantified sarcomere length, interstitial space between fibers, fiber branching, fiber cross sectional area (CSA), and fiber regeneration measured by centrally located nuclei. Because DMD is associated with chronic inflammation, we also investigated the number of macrophages in diaphragm muscle cross-sections. We saw regional differences in the number of regenerating fibers and macrophages during the progression of DMD in the mdx diaphragm. Additionally, the number of regenerating fibers increased with age, while CSA and the number of branching fibers decreased. Dystrophic diaphragms had shorter sarcomere lengths than age-matched controls. Our results suggest that the dystrophic diaphragm in the mdx mouse is structurally heterogeneous and remodels non-uniformly over time. Understanding regional changes in dystrophic diaphragms over time will facilitate the development of targeted therapies to prevent or minimize respiratory failure in DMD patients.