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Abstract

In this study we investigated the changes in fiber length and diffusion parameters as a consequence of passive lengthening and stretching of the calf muscles. We hypothesized that changes in radial diffusivity (RD) are caused by changes in the muscle fiber cross sectional area (CSA) as a consequence of lengthening and shortening of the muscle. Diffusion Tensor MRI (DT-MRI) measurements were made twice in five healthy volunteers, with the foot in three different positions (30° plantarflexion, neutral position and 15° dorsiflexion). The muscles of the calf were manually segmented on co-registered high resolution anatomical scans, and maps of RD and axial diffusivity (AD) were reconstructed from the DT-MRI data. Fiber tractography was performed and mean fiber length was calculated for each muscle group. Significant negative correlations were found between the changes in RD and changes in fiber length in the dorsiflexed and plantarflexed positions, compared with the neutral foot position. Changes in AD did not correlate with changes in fiber length. Assuming a simple cylindrical model with constant volume for the muscle fiber, the changes in the muscle fiber CSA were calculated from the changes in fiber length. In line with our hypothesis, we observed a significant positive correlation of the CSA with the measured changes in RD. In conclusion, we showed that changes in diffusion coefficients induced by passive muscle stretching and lengthening can be explained by changes in muscle CSA, advancing the physiological interpretation of parameters derived from skeletal muscle DT-MRI.

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... As in many preceding studies, DTI was used to measure diffusion along ( 1 ) and perpendicular to ( 2 and 3 ) muscle fibers. In agreement with almost all DTI studies that have investigated the effects of muscle length changes on diffusion (19,20,33,46,49,50), we observed a decrease in radial diffusion ( 2 and 3 ) and increase in fractional anisotropy with increasing muscle length. However, we also observed that increases in muscle length were accompanied by increases in 1 , while most other studies report no effect of muscle length change on axial diffusion. ...
... Human skeletal muscle fibers have diameters of~20 -90 m (39) and, because most of the muscle's volume is composed of intracellular space, DTI measures are probably most affected by fiber diameter. Our data, and those of others (12,33,46,50), are consistent with this hypothesis because we found a systematic decrease in both 2 and 3 with fascicle lengthening (Table 3). If muscle fibers were perfect cylinders and all diffusion occurred within fibers and not in the extracellular space, there would be a linear relationship between radial diffusivity ( 2 and 3 ) and fiber diameter squared (33). ...
... Our data, and those of others (12,33,46,50), are consistent with this hypothesis because we found a systematic decrease in both 2 and 3 with fascicle lengthening (Table 3). If muscle fibers were perfect cylinders and all diffusion occurred within fibers and not in the extracellular space, there would be a linear relationship between radial diffusivity ( 2 and 3 ) and fiber diameter squared (33). This suggests that the decrease in 2 and 3 reflects the reduction in the fiber diameter that would accompany increases in fiber length. ...
Article
There are few comprehensive investigations of the changes in muscle architecture that accompany muscle contraction or change in muscle length in vivo. For this study, we measured changes in the three-dimensional architecture of the human medial gastrocnemius at the whole-muscle level, the fascicle level and the fiber level using anatomical MRI and diffusion tensor imaging (DTI). Data were obtained from eight subjects under relaxed conditions at three muscle lengths. At the whole muscle level, a 5.1% increase in muscle belly length resulted in a reduction in both muscle width (mean change -2.5%) and depth (-4.8%). At the fascicle level, muscle architecture measurements obtained at 3,000 locations per muscle showed that for every millimeter increase in muscle-tendon length above the slack length, average fascicle length increased by 0.46 mm, pennation angle decreased by 0.27° (0.17° in the superficial part and 0.37° in the deep part) and fascicle curvature decreased by 0.18 /m. There was no evidence of systematic variation in architecture along the muscle's long axis at any muscle length. At the fiber level, analysis of the diffusion signal showed that passive lengthening of the muscle increased diffusion along fibers and decreased diffusion across fibers. Using these measurements across scales, we show that the complex shape changes that muscle fibers, whole muscles and aponeuroses of the medial gastrocnemius undergo in vivo cannot be captured by simple geometrical models. This justifies the need for more complex models that link microstructural changes in muscle fibers to macroscopic changes in architecture.
... Each volunteer was examined on the same day in two separate scanning sessions, with at least 30 min in between. The dataset was also used to assess fiber length by Mazzoli et al. [23]. ...
... Manual delineation of the muscles was done in the resulting 25 slices using ITK-SNAP [27] on the images obtained with the ankle in neutral position. The segmentations were then transferred to all six datasets (three positions x two measurements) by registering the down-sampled mDixon images to full resolution out-of-phase mDixon images using rigid registration followed by non-linear b-spline registration, as previously described by Mazzoli et al. [23]. ...
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Background The purpose of this study was to develop a DTI-based method to quantitatively assess fiber angles and changes therein in leg muscles in order to facilitate longitudinal studies on muscle fiber architectural adaptations in healthy subjects.Methods The upper legs of five volunteers were scanned twice on the same day. The right lower legs of five volunteers were scanned twice with the ankle in three positions, i.e. -15° dorsiflexion, 0° neutral position, and 30° plantarflexion. The MRI protocols consisted of a noise scan, a 3-point mDixon scan and a DTI scan. Fiber-angle color maps were generated for four muscles in the upper legs and two muscles in the lower leg. Voxel-wise fiber angles (θ) were calculated from the angle between the principal eigenvector of the diffusion tensor and a reference line defined between the origo and insertion points of each muscle. Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation (CV%), minimal detectable change (MDC), standard error (SE) and Friedman test were used for assessing the feasibility of this method and in order to have an indication of the repeatability and the sensitivity.ResultsBland-Altman analysis showed good repeatability (CV%
... In the last decade, diffusion-weighted MRI (DWI) has begun to be applied to study muscle tissue [23][24][25][26]. More specifically, diffusion tensor imaging (DTI) has proven to be a powerful technique for quantifying muscle anisotropy, enabling fiber orientation and curvature to be estimated and providing an alternative to cadaveric studies. ...
... A close agreement in terms of muscle fiber architecture was observed between the estimated fiber tracks and the cadaveric reference in both superficial and deep heads of the muscle , Fig 1c. Tissue diffusivity measurements also agreed well with values verified previously for other muscles [23,24,28], Table 4. ...
Article
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This study presents a modelling framework in which information on muscle fiber direction and orientation during contraction is derived from diffusion tensor imaging (DTI) and incorporated in a computational model of the surface electromyographic (EMG) signal. The proposed model makes use of the principle of reciprocity to simultaneously calculate the electric potentials produced at the recording electrode by charges distributed along an arbitrary number of muscle fibers within the muscle, allowing for a computationally efficient evaluation of extracellular motor unit action potentials. The approach is applied to the complex architecture of the first dorsal interosseous (FDI) muscle of the hand to simulate EMG during index finger flexion and abduction. Using diffusion tensor imaging methods, the results show how muscle fiber orientation and curvature in this intrinsic hand muscle change during flexion and abduction. Incorporation of anatomically accurate muscle architecture and other hand tissue morphologies enables the model to capture variations in extracellular action potential waveform shape across the motor unit population and to predict experimentally observed differences in EMG signal features when switching from index finger abduction to flexion. The simulation results illustrate how structural and electrical properties of the tissues comprising the volume conductor, in combination with fiber direction and curvature, shape the detected action potentials. Using the model, the relative contribution of motor units of different sizes located throughout the muscle under both conditions is examined, yielding a prediction of the detection profile of the surface EMG electrode array over the muscle crosssection.
... However, voluntary synchronization is imprecise, subject-dependent, and impractical for patients with pain. Retrospective gating can be applied using additional sensors 168 or self-gating approaches, 169 assuming that the timing variations have a negligible impact on kinematic estimates. Movement can be more precisely controlled by a physical apparatus, but this does not lead to realistic physical effort, which is often needed to reproduce the abnormal movement and/or the symptom being studied (eg, pain). ...
Article
Real‐time magnetic resonance imaging (RT‐MRI) allows for imaging dynamic processes as they occur, without relying on any repetition or synchronization. This is made possible by modern MRI technology such as fast‐switching gradients and parallel imaging. It is compatible with many (but not all) MRI sequences, including spoiled gradient echo, balanced steady‐state free precession, and single‐shot rapid acquisition with relaxation enhancement. RT‐MRI has earned an important role in both diagnostic imaging and image guidance of invasive procedures. Its unique diagnostic value is prominent in areas of the body that undergo substantial and often irregular motion, such as the heart, gastrointestinal system, upper airway vocal tract, and joints. Its value in interventional procedure guidance is prominent for procedures that require multiple forms of soft‐tissue contrast, as well as flow information. In this review, we discuss the history of RT‐MRI, fundamental tradeoffs, enabling technology, established applications, and current trends. Level of Evidence 5 Technical Efficacy Stage 1
... DTI-based muscle fiber tractography has been successfully used to show muscle architecture of human leg muscles in healthy and diseased subjects [25][26][27], human arm and shoulder muscles [28,29], pelvic floor [30,31], levator ani [32] and tongue [33]. However, this method still faces several challenges. ...
Article
Objectives To consider the tract-based analysis of DTI parameters in human muscle by assessing different fiber tracking stop criteria settings on diffusion parameters. Materials and methods 30 healthy volunteers underwent a 3 T MRI. Diffusion-weighted images were acquired to perform DTI and fiber tracking analysis for six thigh muscles. Whole thigh muscles were evaluated by fiber tractography using different fiber tracking stop parameters [FA (0.01–0.15) to (0.4–0.99); angle 10°–30°, step size 0.75 mm, 1.5 mm, 3 mm]. Diffusion and tractography-derived parameters per stop criterion were compared using a repeated measure ANOVA including Bonferroni-corrected post hoc tests. Results We found significant differences in all examined diffusion parameters between different stop criteria (main effect p < 0.001). We showed different influence of tracking parameters on diffusion parameters in examined muscles (main effect p ≤ 0.001). Conclusions Statistically significant differences in fiber tracking results using different stop criteria were shown. Fiber tracking stop criteria do have an important influence on study results and should be considered in the development of study protocols and comparison of studies. We recommend a FA minimum of 0.10 and a step size lower than voxel size, e.g., a half with a constant ratio between step size and angle of 10°/mm.
... The UTE and T1 had higher spatial resolution (smaller voxels) than the mDixon scans, leading to clearer delineations between aponeuroses and surrounding tissues. We chose these sequences and resolutions because T1-weighted 13,25 and mDixon scans 26,31,32 of similar resolution have been used previously in muscletendon research, so determining their validity provides the most practically useful information. From T1 and UTE scans, aponeuroses were usually discernible along the muscle's length, even in regions where aponeuroses were very thin. ...
Article
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Muscle performance is closely related to the structure and function of tendons and aponeuroses, the sheet-like, intramuscular parts of tendons. The architecture of aponeuroses has been difficult to study with magnetic resonance imaging (MRI) because these thin, collagen-rich connective tissues have very short transverse relaxation (T2) times and therefore provide a weak signal with conventional MRI sequences. Here, we validated measurements of aponeurosis dimensions from two MRI sequences commonly used in muscle-tendon research (mDixon and T1-weighted images), and an ultrashort echo time (UTE) sequence designed for imaging tissues with short T2 times. MRI -based measurements of aponeurosis width, length and area of 20 sheep leg muscles were compared to direct measurements made with three-dimensional (3D) quantitative microdissection. The errors in measurement of aponeurosis width relative to the mean width were 1.8% for UTE, 3.7% for T1 and 18.8% for mDixon. For aponeurosis length, the errors were 7.6% for UTE, 1.9% for T1 and 21.0% for mDixon. Measurements from T1 and UTE scans were unbiased, but mDixon scans systematically underestimated widths, lengths and areas of the aponeuroses. Using the same methods, we then found high inter-rater reliability (intra-class correlation coefficients > 0.92 for all measures) of measurements of the dimensions of the central aponeurosis of the human tibialis anterior muscle from T1-weighted scans. We conclude that valid and reliable measurements of aponeurosis dimensions can be obtained from UTE and from T1-weighted scans. When the goal is to study the macroscopic architecture of aponeuroses, UTE does not hold an advantage over T1-weighted imaging
... Additionally, changes in muscle ADC are rather unspecific. Changes in ADC and directional diffusivity in healthy human muscles have previously been reported to be dependent on exercise [62,63], training condition [64], active muscle contraction [65], and passive joint position [66,67]. Recent systematic evaluations of DWI in healthy human skeletal muscle have furthermore described the DWI parameters to be dependent on different technical issues during acquisition and post-processing, such as spatial resolution, diffusion-encoding parameters, signal-tonoise ratio, and phase-sensitive variations due to microcirculation [68][69][70][71]. ...
Article
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Neuromuscular diseases are characterized by progressive muscle degeneration and muscle weakness resulting in functional disabilities. While each of these diseases is individually rare, they are common as a group, and a large majority lacks effective treatment with fully market approved drugs. Magnetic resonance imaging and spectroscopy techniques (MRI and MRS) are showing increasing promise as an outcome measure in clinical trials for these diseases. In 2013, the European Union funded the COST (co-operation in science and technology) action BM1304 called MYO-MRI (www.myo-mri.eu), with the overall aim to advance novel MRI and MRS techniques for both diagnosis and quantitative monitoring of neuromuscular diseases through sharing of expertise and data, joint development of protocols, opportunities for young researchers and creation of an online atlas of muscle MRI and MRS. In this report, the topics that were discussed in the framework of working group 3, which had the objective to: Explore new contrasts, new targets and new imaging techniques for NMD are described. The report is written by the scientists who attended the meetings and presented their data. An overview is given on the different contrasts that MRI can generate and their application, clinical needs and desired readouts, and emerging methods.
... Diffusion magnetic resonance imaging (MRI) 11 is known to be sensitive to tissue microstructure, 12,13 including at cellular and subcellular length scales, 14 and has been used to investigate both muscle structure [15][16][17] and function. [18][19][20] The contrast mechanism underlying diffusion-weighted images relies on the random microscopic motion of water molecules 13 within the tissue microenvironment during a defined diffusion time (Δ). ...
Article
The investigation of age-related changes in muscle microstructure between developmental and healthy adult mice may help us to understand the clinical features of early-onset muscle diseases, such as Duchenne muscular dystrophy. We investigated the evolution of mouse hind-limb muscle microstructure using diffusion imaging of in vivo and in vitro samples from both actively growing and mature mice. Mean apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined as a function of diffusion time (Δ), age (7.5, 22 and 44 weeks) and diffusion gradient direction, applied parallel or transverse to the principal axis of the muscle fibres. We investigated a wide range of diffusion times with the goal of probing a range of diffusion lengths characteristic of muscle microstructure. We compared the diffusion time-dependent ADC of hind-limb muscles with histology. ADC was found to vary as a function of diffusion time in muscles at all stages of maturation. Muscle water diffusivity was higher in younger (7.5 weeks) than in adult (22 and 44 weeks) mice, whereas no differences were observed between the older ages. In vitro data showed the same diffusivity pattern as in vivo data. The highlighted differences in diffusion properties between young and mature muscles suggested differences in underlying muscle microstructure, which were confirmed by histological assessment. In particular, although diffusion was more restricted in older muscle, muscle fibre size increased significantly from young to adult age. The extracellular space decreased with age by only ~1%. This suggests that the observed diffusivity differences between young and adult muscles may be caused by increased membrane permeability in younger muscle associated with properties of the sarcolemma.
... However, a trade-off exists among spatial resolution, field-of-view and temporal resolution in these 3-D techniques. Alternatively, magnetic resonance imaging (MRI) allows the study of muscle contraction throughout the full length of the muscle (Dresner et al. 2001;Englund et al. 2011;Mazzoli et al. 2016;Moerman et al. 2012;Pappas et al. 2002;Zhong et al. 2008). While MRI measurements can provide detailed information about muscle structures, its ability to quantify muscle deformation during natural activities (e.g., gait) is limited. ...
Article
A need exists for biomarkers to diagnose, quantify and longitudinally follow facioscapulohumeral muscular dystrophy (FSHD) and many other neuromuscular disorders. Furthermore, the pathophysiological mechanisms leading to muscle weakness in most neuromuscular disorders are not completely understood. Dynamic ultrasound imaging (B-mode image sequences) in combination with speckle tracking is an easy, applicable and patient-friendly imaging tool to visualize and quantify muscle deformation. This dynamic information provides insight in the pathophysiological mechanisms and may help to distinguish the various stages of diseased muscle in FSHD. In this proof-of-principle study, we applied a speckle tracking technique to 2-D ultrasound image sequences to quantify the deformation of the tibialis anterior muscle in patients with FSHD and in healthy controls. The resulting deformation patterns were compared with muscle ultrasound echo intensity analysis (a measure of fat infiltration and dystrophy) and clinical outcome measures. Of the four FSHD patients, two patients had severe peroneal weakness and two patients had mild peroneal weakness on clinical examination. We found a markedly varied muscle deformation pattern between these groups: patients with severe peroneal weakness showed a different motion pattern of the tibialis anterior, with overall less displacement of the central tendon region, while healthy patients showed a non-uniform displacement pattern, with the central aponeurosis showing the largest displacement. Hence, dynamic muscle ultrasound of the tibialis anterior muscle in patients with FSHD revealed a distinctively different tissue deformation pattern among persons with and without tibialis anterior weakness. These findings could clarify the understanding of the pathophysiology of muscle weakness in FSHD patients. In addition, the change in muscle deformation shows good correlation with clinical measures and quantitative muscle ultrasound measurements. In conclusion, dynamic ultrasound in combination with speckle tracking allows the study of the effects of muscle pathology in relation to strength, force transmission and movement generation. Although further research is required, this technique can develop into a biomarker to quantify muscle disease severity.
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Diffusion tensor imaging (DTI) measures water diffusion in skeletal muscle tissue and allows for muscle assessment in a broad range of neuromuscular diseases. However, current DTI measurements, typically performed using pulsed gradient spin echo (PGSE) diffusion encoding, are limited to the assessment of non-contracted musculature, therefore providing limited insight into muscle contraction mechanisms and contraction abnormalities. In this study, we propose the use of an oscillating gradient spin echo (OGSE) diffusion encoding strategy for DTI measurements to mitigate the effect of signal voids in contracted muscle and to obtain reliable diffusivity values. Two OGSE sequences with encoding frequencies of 25 and 50 Hz were tested in the lower leg of five healthy volunteers with relaxed musculature and during active dorsiflexion and plantarflexion, and compared with a conventional PGSE approach. A significant reduction of areas of signal voids using OGSE compared with PGSE was observed in the tibialis anterior for the scans obtained in active dorsiflexion and in the soleus during active plantarflexion. The use of PGSE sequences led to unrealistically elevated axial diffusivity values in the tibialis anterior during dorsiflexion and in the soleus during plantarflexion, while the corresponding values obtained using the OGSE sequences were significantly reduced. Similar findings were seen for radial diffusivity, with significantly higher diffusivity measured in plantarflexion in the soleus muscle using the PGSE sequence. Our preliminary results indicate that DTI with OGSE diffusion encoding is feasible in human musculature and allows to quantitatively assess diffusion properties in actively contracting skeletal muscle. OGSE holds great potential to assess microstructural changes occurring in the skeletal muscle during contraction, and for non-invasive assessment of contraction abnormalities in patients with muscle diseases.
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Background The paraspinal muscles play an important role in the onset and progression of lower back pain. It would be of clinical interest to identify imaging biomarkers of the paraspinal musculature that are related to muscle function and strength. Diffusion tensor imaging (DTI) enables the microstructural examination of muscle tissue and its pathological changes. Purpose To investigate associations of DTI parameters of the lumbar paraspinal muscles with isometric strength measurements in healthy volunteers. Study Type Prospective. Subjects Twenty‐one healthy subjects (12 male, 9 female; age = 30.1 ± 5.6 years; body mass index [BMI] = 27.5 ± 2.6 kg/m²) were recruited. Field Strength/Sequence 3 T/single‐shot echo planar imaging (ss‐EPI) DTI in 24 directions; six‐echo 3D spoiled gradient echo sequence for chemical shift encoding‐based water–fat separation. Assessment Paraspinal muscles at the lumbar spine were examined. Erector spinae muscles were segmented bilaterally; cross‐sectional area (CSA), proton density fat fraction (PDFF), and DTI parameters were calculated. Muscle flexion and extension maximum isometric torque values [Nm] at the back were measured with an isokinetic dynamometer and the ratio of extension to flexion strength (E/F) calculated. Statistical Tests Pearson correlation coefficients; multivariate regression models. Results Significant positive correlations were found between the ratio of extension to flexion (E/F) strength and mean diffusivity (MD) (P = 0.019), RD (P = 0.02) and the eigenvalues (λ1: P = 0.026, λ2: P = 0.033, λ3: P = 0.014). In multivariate regression models λ3 of the erector spinae muscle λ3 and gender remained statistically significant predictors of E/F (R²adj = 0.42, P = 0.003). Data Conclusion DTI allowed the identification of muscle microstructure differences related to back muscle function that were not reflected by CSA and PDFF. DTI may potentially track subtle changes of back muscle tissue composition. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019.
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Skeletal muscles' primary function in the body is mechanical - to move and stabilize the skeleton. As such, their mechanical behavior is a key aspect of their physiology. Recent developments in medical imaging technology have enabled quantitative studies of passive muscle mechanics, ranging from measurements of intrinsic muscle mechanical properties, such as elasticity and viscosity, to 3D muscle architecture and dynamic muscle deformation and kinematics. In this review we summarize the principles and applications of contemporary imaging methods that have been used to study the passive mechanical behaviour of skeletal muscles. Elastography measurements can provide in vivo maps of passive muscle mechanical parameters, and both MRI and ultrasound methods are available (magnetic resonance elastography and ultrasound shear wave elastography, respectively). Both have been shown to differentiate between healthy muscle and muscles affected by a broad range of clinical conditions. Detailed muscle architecture can now be depicted using diffusion tensor imaging, which is particularly useful for computational modeling of muscle, but also has potential in assessing architectural changes in muscle disorders. More dynamic information about muscle mechanics can be obtained using a range of dynamic magnetic resonance imaging methods, which characterize the detailed internal muscle deformations during motion. There are several MRI techniques available (e.g. Phase-contrast MRI, Displacement encoded MRI, and 'tagged' MRI), each of which can be collected in synchrony with muscle motion, and post-processed to quantify muscle deformation. Together, these modern imaging techniques can characterize muscle motion, deformation, mechanical properties and architecture, providing complementary insights into skeletal muscle function.
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Biomechanical analysis of pelvic floor dysfunction requires knowledge of certain biomechanical parameters, such as muscle fiber direction, in order to adequately model function. Magnetic resonance (MR) diffusion tensor imaging (DTI) provides an estimate of overall muscle fiber directionality based on the mathematical description of water diffusivity. This work aimed at evaluating the concurrence between pubovisceralis muscle fiber representations obtained from DTI, and the maximum principal stress lines obtained through the finite element method. Seven datasets from axial T2-weighted images were used to build numerical models, and muscle fiber orientation estimated from the DT images. The in-plane projections of the first eigenvector of both vector fields describing muscle fiber orientation were extracted and compared. The directional consistency was evaluated by calculating the angle between the normalized vectors for the entire muscle and also for the right and left insertions, middle portions, and anorectal area. The values varied between 28° ± 6 (right middle portion) and 34° ± 9 (anorectal area), and were higher than the angular precision of the DT estimates, evaluated using wild bootstrapping analysis. Angular dispersion ranged from 17° ± 4 (left middle portion) to 23° ± 5 (anorectal area). Further studies are needed to examine acceptability of these differences when integrating the vectors estimated from DTI in the numerical analysis.
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Musculoskeletal (dys-)function relies for a large part on muscle architecture which can be obtained using Diffusion-Tensor MRI (DT-MRI) and fiber trac-tography. However, reconstructed tracts often continue along the tendon or aponeurosis when using conventional methods, thus overestimating fascicle lengths. In this study, we propose a new method for semiautomatic segmenta-tion of tendinous tissue using tract density (TD). We investigated the feasibility and repeatability of this method to quantify the mean fascicle length per muscle. Additionally, we examined whether the method facilitates measuring changes in fascicle length of lower leg muscles with different foot positions. Five healthy subjects underwent two DT-MRI scans of the right lower leg, with the foot in 15° dorsiflexion, neutral, and 30° plantarflexion positions. Repeatability of fasci-cle length measurements was assessed using Bland–Altman analysis. Changes in fascicle lengths between the foot positions were tested using a repeated multi-variate analysis of variance (MANOVA). Bland–Altman analysis showed good agreement between repeated measurements. The coefficients of variation in neutral position were 8.3, 16.7, 11.2, and 10.4% for soleus (SOL), fibularis longus (FL), extensor digitorum longus (EDL), and tibialis anterior (TA), respectively. The plantarflexors (SOL and FL) showed significant increase in fascicle length from plantarflexion to dorsiflexion, whereas the dorsiflexors (EDL and TA) exhibited a significant decrease. The use of a tract density for semiautomatic segmentation of tendinous structures provides more accurate estimates of the mean fascicle length than traditional fiber tractography methods. The method shows moderate to good repeatability and allows for quantification of changes in fascicle lengths due to passive stretch.
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Purpose: Recent DTI studies demonstrated the possibility of fiber geometry visualization in skeletal muscle. We tested for an association between muscle power and standard DTI parameters, e. g. fractional anisotropy. Materials and methods: Maximal muscle power (Lmax) of the soleus muscle was determined in 11 healthy subjects. Subsequently DTI was performed and standard parameters (fractional anisotropy - FA, mean diffusivity - MD, parallel diffusivity - PD, radial diffusivity - RD) were extracted in an ROI of the soleus muscle. Results: We found a signficant association of Lmax with FA (neg. correlation: r = -0.85, p = 0.0015) and RD (pos. correlation r = 0.80, p = 0.047). There was no signficant association of MD or PD. Conclusion: Maximum muscle power is an indirect measure of fiber type distribution. The correlation between muscle power and DTI parameters can be explained by differences in fiber diameter and differences in the intracellular microstructure of type-1 and type-2 fibers. DTI should be evaluated as a tool for non-invasive quantification of fiber type distribution in skeletal muscle.
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Purpose: To evaluate the performance of diffusion tensor imaging (DTI) in the evaluation of chronic exertional compartment syndrome (CECS) as compared to T2 -weighted (T2w) imaging. Materials and methods: Using an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol, spectral adiabatic inversion recovery (SPAIR) T2w imaging and stimulated echo DTI were applied to eight healthy volunteers and 14 suspected CECS patients before and after exertion. Longitudinal and transverse diffusion eigenvalues, mean diffusivity (MD), and fractional anisotropy (FA) were measured in seven calf muscle compartments, which in patients were classified by their response on T2w: normal (<20% change), and CECS (>20% change). Mixed model analysis of variance compared subject groups and compartments in terms of response factors (post/pre-exercise ratios) of DTI parameters. Results: All diffusivities significantly increased (P < 0.0001) and FA decreased (P = 0.0014) with exercise. Longitudinal diffusion responses were significantly smaller than transversal diffusion responses (P < 0.0001). Nineteen of 98 patient compartments were classified as CECS on T2w. MD increased by 3.8 ± 3.4% (volunteer), 7.4 ± 4.2% (normal), and 9.1 ± 7.0% (CECS) with exercise. Conclusion: DTI shows promise as an ancillary imaging method in the diagnosis and understanding of the pathophysiology in CECS. Future studies may explore its utility in predicting response to treatment.
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Velocity-encoded phase-contrast magnetic resonance (MR) imaging techniques and a computer-controlled MR-compatible foot pedal device were used to investigate the medial gastrocnemius muscle and aponeurosis deformations during passive and active eccentric movements of the plantarflexors. Intrafascicular strain, measured as the ratio of strain in the fascicle segment at its insertion to strain at its origin, was nonuniform along the proximodistal axis of the muscle (P < 0.01), progressively increasing from the proximal to distal direction. The high intrafascicular strain regions appeared to correlate with the muscle regions that are likely to encounter high stress concentrations, i.e., the regions where the muscle physiological cross section decreases close to the tendons. The architectural gear ratio, i.e., the mechanical amplification ratio of fascicle length displacement to that of tendon/aponeuroses in a pennate muscle, also exhibited significant regional differences, with the highest ratios in the proximal region of the muscle accompanied by a higher initial pennation angle and a larger range of fascicular rotation about the origin. Values close to unity in the distal region of the muscle suggest that the aponeurosis separation may decrease in this region. Fascicle length and pennation angle changes were significantly influenced by force generation in the muscle, probably due to a shortening of the loaded muscle fibers relative to a passive condition. Overall, our data illustrate significant proximodistal intramuscular heterogeneity as supported by a regionally variable end-to-end strain ratio of fascicles and angle changes in the medial gastrocnemius muscle during passive and active ankle movements. These observations emphasize the need to reassess current conceptual models of muscle-tendon mechanics.
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Skeletal muscles are highly organized hierarchical structures characterized by an anisotropic arrangement of muscle fibers (myocytes) in fascicles. Due to its unique non-invasive microstructure probing capabilities, diffusion-weighted Magnetic Resonance Imaging (DW-MRI) constitutes a valuable non-invasive tool in the study of such fibrous biological tissues. We have implemented a DW-MRI sequence with highly sensitive directional encoding to quantify the microarchitectural properties of human calf muscles at rest. We have specifically focused on a composite model-based analysis of diffusion tensor MRI measurements to quantify in vivo the cross-sectional asymmetry of muscle fiber geometry, which is a microstructural feature well documented in prior histological studies.
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The purpose of this work was to demonstrate the feasibility of intravoxel incoherent motion imaging (IVIM) for non-invasive quantification of perfusion and diffusion effects in skeletal muscle at rest and following exercise. After IRB approval, eight healthy volunteers underwent diffusion-weighted MRI of the forearm at 3 T and eight different b values between 0 and 500 s/mm(2) with a temporal resolution of 57 s per dataset. Dynamic images were acquired before and after a standardized handgrip exercise. Diffusion (D) and pseudodiffusion (D*) coefficients as well as the perfusion fraction (FP ) were measured in regions of interest in the flexor digitorum superficialis and profundus (FDS/FDP), brachioradialis, and extensor carpi radialis longus and brevis muscles by using a multi-step bi-exponential analysis in MATLAB. Parametrical maps were calculated voxel-wise. Differences in D, D*, and FP between muscle groups and between time points were calculated using a repeated measures analysis of variance with post hoc Bonferroni tests. Mean values and standard deviations at rest were the following: D*, 28.5 ± 11.4 × 10(-3) mm(2) /s; FP , 0.03 ± 0.01; D, 1.45 ± 0.09 × 10(-3) mm(2) /s. Changes of IVIM parameters were clearly visible on the parametrical maps. In the FDS/FDP, D* increased by 289 ± 236% (p < 0.029), FP by 138 ± 58% (p < 0.01), and D by 17 ± 9% (p < 0.01). A significant increase of IVIM parameters could also be detected in the brachioradialis muscle, which however was significantly lower than in the FDS/FDP. After 20 min, all parameters were still significantly elevated in the FDS/FDP but not in the brachioradialis muscle compared with the resting state. The IVIM approach allows simultaneous quantification of muscle perfusion and diffusion effects at rest and following exercise. It may thus provide a useful alternative to other non-invasive methods such as arterial spin labeling. Possible fields of interest for this technique include perfusion-related muscle diseases, such as peripheral arterial occlusive disease. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
Article
PurposeTo 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.ResultsThe 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. J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.
Article
The purpose of this work was to carry out diffusion tensor imaging (DTI) at multiple diffusion times Td in skeletal muscle in normal subjects and chronic exertional compartment syndrome (CECS) patients and analyze the data with the random permeable barrier model (RPBM) for biophysical specificity. Using an institutional review board approved HIPAA-compliant protocol, seven patients with clinical suspicion of CECS and eight healthy volunteers underwent DTI of the calf muscle in a Siemens MAGNETOM Verio 3 T scanner at rest and after treadmill exertion at four different Td values. Radial diffusion values λrad were computed for each of seven different muscle compartments and analyzed with RPBM to produce estimates of free diffusivity D0, fiber diameter a, and permeability κ. Fiber diameter estimates were compared with measurements from literature autopsy reference for several compartments. Response factors (post/pre-exercise ratios) were computed and compared between normal controls and CECS patients using a mixed-model two-way analysis of variance. All subjects and muscle compartments showed nearly time-independent diffusion along and strongly time-dependent diffusion transverse to the muscle fibers. RPBM estimates of fiber diameter correlated well with corresponding autopsy reference. D0 showed significant (p < 0.05) increases with exercise for volunteers, and a increased significantly (p < 0.05) in volunteers. At the group level, response factors of all three parameters showed trends differentiating controls from CECS patients, with patients showing smaller diameter changes (p = 0.07), and larger permeability increases (p = 0.07) than controls. Time-dependent diffusion measurements combined with appropriate tissue modeling can provide enhanced microstructural specificity for in vivo tissue characterization. In CECS patients, our results suggest that high-pressure interfiber edema elevates free diffusion and restricts exercise-induced fiber dilation. Such specificity may be useful in differentiating CECS from other disorders or in predicting its response to either physical therapy or fasciotomy. Copyright © 2014 John Wiley & Sons, Ltd.
Article
In the last decade, diffusion tensor imaging (DTI) has been used increasingly to investigate three-dimensional (3D) muscle architectures. So far there is no study that has proved the validity of this method to determine fascicle lengths and pennation angles within a whole muscle. To verify the DTI method, fascicle lengths of m. soleus as well as their pennation angles have been measured using two different methods. First, the 3D muscle architecture was analyzed in vivo applying the DTI method with subsequent deterministic fiber tractography. In a second step, the muscle architecture of the same muscle was analyzed using a standard manual digitization system (MicroScribe MLX). Comparing both methods, we found differences for the median pennation angles (P < 0.001) but not for the median fascicle lengths (P = 0.216). Despite the statistical results, we conclude that the DTI method is appropriate to determine the global fiber orientation. The difference in median pennation angles determined with both methods is only about 1.2° (median pennation angle of MicroScribe: 9.7°; DTI: 8.5°) and probably has no practical relevance for muscle simulation studies. Determining fascicle lengths requires additional restriction and further development of the DTI method.
Article
In this study, we have performed simulations to address the effects of diffusion encoding parameters, signal-to-noise ratio (SNR) and T2 on skeletal muscle diffusion tensor indices and fiber tracts. Where appropriate, simulations were corroborated and validated by in vivo diffusion tensor imaging (DTI) of human skeletal muscle. Specifically, we have addressed: (i) the accuracy and precision of the diffusion parameters and eigenvectors at different SNR levels; (ii) the effects of the diffusion gradient direction encoding scheme; (iii) the optimal b value for diffusion tensor estimation; (iv) the effects of changes in skeletal muscle T2 ; and, finally, the influence of SNR on fiber tractography and derived (v) fiber lengths, (vi) pennation angles and (vii) fiber curvatures. We conclude that accurate DTI of skeletal muscle requires an SNR of at least 25, a b value of between 400 and 500 s/mm(2) , and data acquired with at least 12 diffusion gradient directions homogeneously distributed on half a sphere. Furthermore, for DTI studies focusing on skeletal muscle injury or pathology, apparent changes in the diffusion parameters need to be interpreted with great care in view of the confounding effects of T2 , particularly for moderate to low SNR values. Copyright © 2013 John Wiley & Sons, Ltd.
Article
Fiber type distribution within a skeletal muscle, i.e. the quantification of the relative amount of type 1 (slow-twitching) and type 2 (fast-twitching) muscle fibers, is of great interest for the monitoring of the effects of training or the treatment of muscle diseases. The purpose of this study was to determine the feasibility of diffusion tensor imaging (DTI) as a tool for noninvasive fiber type quantification in human skeletal muscle. The right calves of 12 healthy volunteers were examined using DTI at 1.5 T. Standard DTI parameters, including fractional anisotropy (FA), and mean, radial and parallel diffusivity (MD, RD and PD, respectively), were determined in the soleus muscle. Fiber type proportion and mean fiber diameter within the soleus muscle were quantified from tissue specimens obtained via a fine needle biopsy. Linear regression analysis tested for associations between DTI and biopsy results. FA values were correlated significantly with fiber type proportion, such that higher FA values indicated a higher proportion of type 1 fibers (R(2) = 0.5, p = 0.01). This was based on lower diffusivity perpendicular to the main axis of the fiber in subjects with a higher type 1 fiber proportion (RD: R(2) = 0.52, p = 0.008). MD was also correlated with the proportion of type 1 fibers (R(2) = 0.37, p = 0.037), whereas PD showed no significant correlation. DTI is a promising method for the noninvasive estimation of fiber type proportion in skeletal muscle. This technique may be used to monitor training effects or may be further developed as a biomarker in certain muscle diseases. Copyright © 2013 John Wiley & Sons, Ltd.
Article
Purpose: We used diffusion tensor imaging (DTI) to evaluate anisotropic changes in skeletal muscle cells under external pressure. Materials and methods: In 6 healthy volunteers, we compared DTI of the tibialis anterior (TA) and soleus (SOL) muscles under pressure. We performed imaging using a 1.5-tesla magnetic resonance (MR) scanner and diffusion-weighted stimulated-echo echo-planar pulse sequences optimized for skeletal muscle. We calculated diffusion tensor eigenvalues (λ), apparent diffusion coefficients, and fractional anisotropy (FA) values in a series of axially acquired DTI and compared them between the pressurized and nonpressurized lower limbs. We also measured a cross-sectional area of skeletal muscle. Results: We observed clear differences in FA and λ₃ between pressurized muscles and the nonpressurized muscles we used as controls. The mean control FAs were 0.36±0.02 (TA) and 0.30±0.02 (SOL). The mean control λ₃s were 0.74±0.02 s/mm² (TA) and 0.85±0.03 s/mm² (SOL). FA values in the pressurized (200 mmHg) limbs increased to 0.39±0.02 (TA) and 0.35±0.04 (SOL) compared with those values in the nonpressurized controls. λ₃ values in the pressurized (200 mmHg) limbs decreased to 0.68±0.05 s/mm² (TA) and 0.77±0.06 s/mm² (SOL) compared with those in controls. Moreover, the mean value of cross-sectional area of skeletal muscle (control) was 907.3±140.1 mm² (TA) and 1522±201.0 mm² (SOL). The cross-sectional area in the pressurized (200 mmHg) limbs decreased to 590.3±68.1 mm² (TA) and 1131±112.6 mm² (SOL) compared with those in controls. One-way analysis of variance (ANOVA) and post hoc Tukey-Kramer tests showed significant differences. Conclusion: Anisotropy changed markedly on pressurizing the lower limb based on the correlation of the cross-sectional area and λ₃ suggested marked changed in anisotropy following application of pressure to the lower limb. If compression of the cross-sectional area is assumed to represent compression of the cell, change in λ₃ reflected the change in the size of muscle cells.
Article
To design a time-efficient patient-friendly clinical diffusion tensor MRI protocol and postprocessing tool to study the complex muscle architecture of the human forearm. The 15-minute examination was done using a 3 T system and consisted of: T(1) -weighted imaging, dual echo gradient echo imaging, single-shot spin-echo echo-planar imaging (EPI) diffusion tensor MRI. Postprocessing comprised of signal-to-noise improvement by a Rician noise suppression algorithm, image registration to correct for motion and eddy currents, and correction of susceptibility-induced deformations using magnetic field inhomogeneity maps. Per muscle one to five regions of interest were used for fiber tractography seeding. To validate our approach, the reconstructions of individual muscles from the in vivo scans were compared to photographs of those dissected from a human cadaver forearm. Postprocessing proved essential to allow muscle segmentation based on combined T(1) -weighted and diffusion tensor data. The protocol can be applied more generally to study human muscle architecture in other parts of the body. The proposed protocol was able to visualize the muscle architecture of the human forearm in great detail and showed excellent agreement with the dissected cadaver muscles. J. Magn. Reson. Imaging 2012. © 2012 Wiley Periodicals, Inc.
Article
To design a time-efficient patient-friendly clinical diffusion tensor MRI protocol and postprocessing tool to study the complex muscle architecture of the human forearm. The 15-minute examination was done using a 3 T system and consisted of: T(1) -weighted imaging, dual echo gradient echo imaging, single-shot spin-echo echo-planar imaging (EPI) diffusion tensor MRI. Postprocessing comprised of signal-to-noise improvement by a Rician noise suppression algorithm, image registration to correct for motion and eddy currents, and correction of susceptibility-induced deformations using magnetic field inhomogeneity maps. Per muscle one to five regions of interest were used for fiber tractography seeding. To validate our approach, the reconstructions of individual muscles from the in vivo scans were compared to photographs of those dissected from a human cadaver forearm. Postprocessing proved essential to allow muscle segmentation based on combined T(1) -weighted and diffusion tensor data. The protocol can be applied more generally to study human muscle architecture in other parts of the body. The proposed protocol was able to visualize the muscle architecture of the human forearm in great detail and showed excellent agreement with the dissected cadaver muscles.
Article
To investigate the reproducibility of diffusion tensor imaging (DTI) -derived indices and fiber architecture of calf muscles at 1.5 Tesla (T), to establish an imaging based method to confirm ankle position, and to compare fiber architecture at different ankle positions. Six subjects were imaged at 1.5T with the foot in neutral and plantarflexed positions. DTI indices were calculated in four muscle compartments (medial and lateral gastrocnemius [MG, LG], superficial and deep anterior tibialis [AT-S, AT-D]). Two subjects were scanned on 3 days to calculate the coefficient of variability (CV) and the repeatability coefficient (RC). DTI indices were close to the values obtained in earlier 3T and 1.5T studies. Fractional anisotropy decreased significantly in the MG and increased significantly in the AT-S and AT-D compartments while fiber orientation with respect to the magnet Z-axis increased significantly in the MG and decreased significantly in the AT-S compartment with plantarflexion. The CV and RC for the DTI indices and fiber orientations were comparable to 3T studies. Fiber lengths and orientation angles in the MG matched corresponding measures from ultrasound studies. DTI at 1.5T provides reproducible measures of diffusion indices and fiber architecture of calf muscle at different muscle lengths.
Article
It is widely assumed that skeletal muscle contraction is isovolumic. This assumption has been verified at the single fiber and at the myofibril level. Model development and mechanical analyses often exploit this assumption when investigating skeletal muscle and evaluating muscle mechanical properties. This communication describes a method whereby individual muscle fibers and bundles of fibers, which include their constituent extracellular matrix (ECM), were tested to define the change in volume with axial strain. The results demonstrate that fibers are isovolumic, but bundles decrease in volume with strain. The loss of volume implicates a transverse force being applied to the fibers by the ECM. The nature and importance of this transverse force warrant further investigation.
Article
Diffusion tensor imaging (DTI)-based muscle fiber tracking enables the measurement of muscle architectural parameters, such as pennation angle (theta) and fiber tract length (L(ft)), throughout the entire muscle. Little is known, however, about the repeatability of either the muscle architectural measures or the underlying diffusion measures. Therefore, the goal of this study was to investigate the repeatability of DTI fiber tracking-based measurements and theta and L(ft). Four DTI acquisitions were performed on two days that allowed for between acquisition, within day, and between day analyses. The eigenvalues and fractional anisotropy were calculated at the maximum cross-sectional area of, and fiber tracking was performed in, the tibialis anterior muscle of nine healthy subjects. The between acquisitions condition had the highest repeatability for the DTI indices and the architectural parameters. The overall inter class correlation coefficients (ICC's) were greater than 0.6 for both theta and L(ft) and the repeatability coefficients were theta < 10.2 degrees and L(ft) < 50 mm. In conclusion, under the experimental and data analysis conditions used, the repeatability of the diffusion measures is very good and repeatability of the architectural measurements is acceptable. Therefore, this study demonstrates the feasibility for longitudinal studies of alterations in muscle architecture using DTI-based fiber tracking, under similar noise conditions and with similar diffusion characteristics.
Article
Medical image registration is an important task in medical image processing. It refers to the process of aligning data sets, possibly from different modalities (e.g., magnetic resonance and computed tomography), different time points (e.g., follow-up scans), and/or different subjects (in case of population studies). A large number of methods for image registration are described in the literature. Unfortunately, there is not one method that works for all applications. We have therefore developed elastix, a publicly available computer program for intensity-based medical image registration. The software consists of a collection of algorithms that are commonly used to solve medical image registration problems. The modular design of elastix allows the user to quickly configure, test, and compare different registration methods for a specific application. The command-line interface enables automated processing of large numbers of data sets, by means of scripting. The usage of elastix for comparing different registration methods is illustrated with three example experiments, in which individual components of the registration method are varied.
Article
Due to its unique non-invasive microstructure probing capabilities, diffusion tensor imaging (DTI) constitutes a valuable tool in the study of fiber orientation in skeletal muscles. By implementing a DTI sequence with judiciously chosen directional encoding to quantify in vivo the microarchitectural properties in the calf muscles of three healthy volunteers at rest, we report that the secondary eigenvalue is significantly higher than the tertiary eigenvalue, a phenomenon corroborated by prior DTI findings. Toward a physics-based explanation of this phenomenon, we propose a composite medium model that accounts for water diffusion in the space within the muscle fiber and the extracellular space. The muscle fibers are abstracted as cylinders of infinite length with an elliptical cross section, the latter closely approximating microstructural features well documented in prior histological studies of excised muscle. The range of values of fiber ellipticity predicted by our model agrees with these studies, and the spatial orientation of the cross-sectional ellipses is consistent with local muscle strain fields and the putative direction of lateral transmission of stress between fibers in certain regions in three antigravity muscles (Tibialis Anterior, Soleus, and Gastrocnemius), as well as independent measurements of deformation in active calf muscles. As a metric, fiber cross-sectional ellipticity may be useful for quantifying morphological changes in skeletal muscle fibers with aging, hypertrophy, or sarcopenia.
Article
The influence of passive shortening and stretching of the calf muscles on diffusion characteristics was investigated. The diffusion tensor was measured in transverse slices through the lower leg of eight healthy volunteers (29 +/- 7 years) on a 3 T whole-body MR unit in three different positions of the foot (40 degrees plantarflexion, neutral ankle position (0 degrees ), and -10 degrees dorsiflexion in the ankle). Maps of the mean diffusivity, the three eigenvalues of the tensor and fractional anisotropy (FA) were calculated. Results revealed a distinct dependence of the mean diffusivity and FA on the foot position and the related shortening and stretching of the muscle groups. The tibialis anterior muscle showed a significant increase of 19% in FA with increasing dorsiflexion, while the FA of the antagonists significantly decreased ( approximately 20%). Regarding the mean diffusivity of the diffusion tensor, the muscle groups showed an opposed response to muscle elongation and shortening. Regarding the eigenvalues of the diffusion tensor, lambda(2) and lambda(3) showed significant changes in relation to muscle length. In contrast, no change in lambda(1) could be found. This work reveals significant changes in diffusional characteristics induced by passive muscle shortening and stretching.
Article
Diffusion tensor (DT)-MRI studies of skeletal muscle provide information about muscle architecture, microstructure, and damage. However, the effects of noise, the diffusion weighting (b)-value, and partial volume artifacts on the estimation of the diffusion tensor (D) are unknown. This study investigated these issues using Monte Carlo simulations of 3 x 9 voxel regions of interest (ROIs) containing muscle, adipose tissue, and intermediate degrees of muscle volume fractions (f(M)). A total of 1000 simulations were performed for each of eight b-values and 11 SNR levels. The dependencies of the eigenvalues (lambda(1-3)), mean diffusivity (lambda), and fractional anisotropy (FA), and the angular deviation of the first eigenvector from its true value (alpha) were observed. For moderate b-values (b = 435-725 s/mm(2)) and f(M) = 1, an accuracy of 5% was obtained for lambda(1-3), lambda, and FA with an SNR of 25. An accuracy of 1% was obtained for lambda(1-3), lambda, and FA with f(M) = 1 and SNR = 50. For regions with f(M) = 8/9, 5% accuracy was obtained with SNR = 40. For alpha, SNRs of >or=25 and >or=45 were required for +/-4.5 degrees uncertainty with f(M) = 1 and f(M) = 0.5, respectively; SNR >or= 60 was required for +/-9 degrees uncertainty in single muscle voxels. These findings may influence the design and interpretation of DT-MRI studies of muscle microstructure, damage, and architecture.
Article
The time- and orientational-dependence of phosphocreatine (PCr) diffusion was measured using pulsed-field gradient nuclear magnetic resonance (PFG-NMR) as a means of non-invasively probing the intracellular diffusive barriers of skeletal muscle. Red and white skeletal muscle from fish was used because fish muscle cells are very large, which facilitates the examination of diffusional barriers in the intracellular environment, and because they have regions of very homogeneous fiber type. Fish were cold-acclimated (5 degrees C) to amplify the contrast between red and white fibers. Apparent diffusion coefficients, D, were measured axially, D(axially) and radially, D(radially), in small muscle strips over a time course ranging from 12 to 700 ms. Radial diffusion was strongly time dependent in both fiber types, and D decreased with time until a steady-state value was reached at a diffusion time approximately 100 ms. Diffusion was also highly anisotropic, with D(axially) being higher than D(radially) for all time points. The time scale over which changes in D(radially) occurred indicated that the observed anisotropy was not a result of interactions with the thick and thin filament lattice of actin and myosin or restriction within the cylindrical sarcolemma, as has been previously suggested. Rather, the sarcoplasmic reticulum (SR) and mitochondria appear to be the principal intracellular structures that inhibit mobility in an orientation-dependent manner. This work is the first example of diffusional anisotropy induced by readily identifiable intracellular structures.
Article
Dynamic MR longitudinal R(1) relaxometry after administration of a gadolinium contrast bolus (Gd-DTPA) has been used for in vivo measurements of the extracellular volume fraction (v) and the capillary permeability (k min(-1)) in rabbit muscles to distinguish between red slow- and white fast-twitch muscle fiber types. For this purpose a protocol imaging sequence has been used which allows fast R(1) measurements during the contrast agent uptake. Physiological tissue parameters, k and v, were obtained by computing procedures assuming a simplified monoexponential plasma model. These were shown to be about twice as large in the slow-twitch semimembranosous proprius muscle (SP), containing 100% oxidative type-I fiber, that in the fast-twitch rectus femorus muscle (RF), containing only 6% type-I fiber type. The capillary permeability has been found to be 0.25 +/- 0.02 min(-1) for the (SP) and 0.10 +/- 0.01 min(-1) for the (RF). Similarly, the extracellular volume fractions were 0.189 +/- 0.015 and 0.082 +/- 0.006 respectively, in close agreement with literature data and experimental results obtained by invasive radionuclide measurements. For the pool of the 10 studied animals, no significant variation among animals was observed in the extracellular volume fraction and the capillary permeability for the different muscle fiber types. The dynamic relaxometry method used is easy to implement on conventional MR imagers and has potential applications in muscle diseases. The method has also potential applications for tissue characterization based on extracellular volume and capillary permeability quantification. In particular, the method can be used for the evaluation of tumors and their responses to therapies.
Article
A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate.
Article
The aim of this study was to examine the diffusive properties of adjacent muscles at rest, and to determine the relationship between diffusive and architectural properties, which are task-specific to muscles. The principle, second, and third eigenvalues, trace of the diffusion tensor, and two anisotropic parameters, ellipsoid eccentricity (e) and fractional anisotropy (FA), of various muscles in the human calf were calculated by diffusion tensor imaging (DTI). Linear correlations of the calculated parameters to the muscle physiological cross-sectional area (PCSA), which is proportional to maximum muscle force, were performed to ascertain any linear relation between muscle architecture and diffusivity. Images of the left calf were acquired from six healthy male volunteers. Seven muscles were investigated in this study. These comprised the soleus, lateral gastrocnemius, medial gastrocnemius, posterior tibialis, anterior tibialis, extensor digitorum longus, and peroneus longus. All data were presented as the mean and standard error of the mean (SEM). In general, differences in diffusive parameter values occurred primarily between functionally different muscles. A strong correlation was also found between PCSA and the third eigenvalue, e, and FA. A mathematical derivation revealed a linear relationship between PCSA and the third eigenvalue as a result of their dependence on the average radius of all fibers within a single muscle. These findings demonstrated the ability of DTI to differentiate between functionally different muscles in the same region of the body on the basis of their diffusive properties.
Article
The diffusive properties of adjacent muscles at rest were evaluated in male (n = 12) and female (n = 12) subjects using diffusion tensor imaging (DTI). The principle, second and third eigenvalues, trace of the diffusion tensor [Tr(D)], and two anisotropic parameters, ellipsoid eccentricity (e) and fractional anisotropy (FA), of various muscles in the human calf were calculated from the diffusion tensor. Seven muscles were investigated in this study from images acquired of the left calf: the soleus, lateral gastrocnemius, medial gastrocnemius, posterior tibialis, anterior tibialis, extensor digitorum longus and peroneus longus. A mathematical model was also derived that relates the eigenvalues of the diffusion tensor to the muscle fiber volume fraction, which is defined as the volume of muscle fibers within a well-defined arbitrary muscle volume. Females on average had higher eigenvalues and Tr(D) compared with males, with the majority of muscles being statistically different between the sexes. In contrast, males on average had higher e and FA than females, with the large plantar flexors--soleus, lateral gastrocnemius, and medial gastrocnemius--producing statistically different results. The behavior of the mathematical model for variations in fiber volume fraction produced similar trends to those seen when the experimental data were fit to the model. The model predicts that a larger volume fraction of skeletal muscle in males is devoted to fibers than in females, but the true underlying source of the gender discrepancy remains unclear. Although the model does not fully account for other transport processes, it does provide some insight into the limiting factors that affect the diffusion of water in skeletal muscle measured by DTI.
Article
The time dependence of the apparent diffusion tensor of ex vivo calf heart and tongue was measured for diffusion times (tau(d)) between 32 and 810 ms. The results showed evidence of restricted diffusion in the muscle tissues of both organs. In regions where the myofibers are parallel, the largest eigenvalue (lambda(1)) of the diffusion tensor remained the same for all diffusion times measured, while the other eigenvalues (lambda(2), lambda(3)) decreased by 29-36% between tau(d) = 32 ms and tau(d) = 400 ms. In regions where the fibers cross, the lambda(1) also changed, decreasing by 17% between tau(d) = 32 ms and tau(d) = 400 ms. The restricting compartment size and volume fraction were effectively estimated by fitting the time courses of the eigenvalues to a model consisting of a nonrestricted compartment and a cylindrically restricted compartment. To our knowledge, this study is the first demonstrating diffusion time dependence of measured water diffusion tensor in muscular tissue. With improvement in scanning technology, future studies may permit noninvasive, in vivo detection of changes in muscle myoarchitecture due to disease, treatment, and exercise.
Article
To prospectively evaluate quantitative diffusion magnetic resonance (MR) imaging for monitoring skeletal muscle injury and repair after femoral artery ligation in mice. All experimental procedures were approved by the local institutional animal care and use committee. Muscle degeneration and regeneration were induced in 16 mice by using unilateral ligation of the femoral artery. Diffusion-tensor and T2-weighted MR imaging examinations were performed before, immediately after, and 3, 10, and 21 days after ligation. Histologic analysis was also performed at these time points. The dynamic changes in T2 and in five diffusion-tensor imaging indexes were studied by using histogram analysis. Differences between the ligated and nonligated limbs were assessed with paired t tests, and analysis of variance was used to determine temporal evolutions. Parametric maps were clustered to depict regional differences in the responses of the different MR imaging indexes. MR indexes in the ligated limb changed over time (P < .007), and temporal evolutions in the ligated and nonligated limbs differed significantly (P < .001). When ischemia was induced, diffusivity and T2 increased, with a maximum change at 3 days, when most muscle damage was observed at histologic analysis. At 10 days, diffusion values were reduced overall, whereas T2 was still increased. At 21 days, parameter values had largely returned to normal. Changes on the diffusion-tensor and T2 maps had spatial differences, which corresponded to the different phases of tissue regeneration observed at histologic analysis. An additional finding was the transient change in direction of the principal eigenvector during the period of maximal muscle damage. After femoral artery ligation, the diffusion-tensor indexes changed dynamically in association with the severity and location of muscle damage.
Article
To determine whether passive muscle extension and contraction affect the proton diffusivity of the muscle. Five male subjects were examined. The fractional anisotropy (FA), and primary (lambda(1)), secondary (lambda(2)), and tertiary eigenvalues (lambda(3)) of the right tibialis anterior and medial gastrocnemius muscles were compared between conditions of passive plantar flexion and passive dorsiflexion of the ankle joint. In the tibialis anterior, FA, and lambda(1) at dorsiflexion decreased significantly (P < 0.01 and P < 0.01, respectively) compared to those at plantar flexion, but lambda(3) at dorsiflexion increased significantly (P = 0.02). In the gastrocnemius, FA and lambda(1) at dorsiflexion increased significantly (P < 0.01 and P < 0.01, respectively) compared to those at plantar flexion, but lambda(3) at dorsiflexion decreased significantly (P < 0.01). The lambda(2) value showed no significant change in either the tibialis anterior or medial gastrocnemius. The results indicate that passive muscle extension and contraction associated with passive joint movement would affect the proton diffusivity of the muscle. This alteration of proton diffusivity is probably associated with microscopic structural changes of the muscle.
Diffusional anisotropy is induced by subcellular barriers in skeletal muscle
  • Kinsey