Study of Human Muscle Structure and Function with Velocity Encoded Phase Contrast and Diffusion Tensor Magnetic Resonance Imaging Techniques

The disproportionate loss of muscle force with aging and disuse atrophy compared to the loss of muscle mass is not yet completely understood. In addition to well-established neural and contractile determinants of force loss, remodeling of the extracellular matrix (ECM) has been recently shown in animal models to be another important contributor. In-vivo human studies exploring the structural remodeling of the ECM and its functional consequences are lacking due to the paucity of appropriate imaging techniques. This study focuses on the development and application of advanced Magnetic Resonance Imaging (MRI) methods to elucidate the mechanisms of loss of force with aging and disuse atrophy with the focus on ECM. Functional changes are investigated by strain and strain rate tensor mapping of muscle under different contraction paradigms using Velocity Encoded Phase-Contrast MRI. Methodological advances include improvements in hardware and software control of the dynamic studies. To overcome the limitation of long scan times, compressed sensing MR acquisition and reconstruction framework to reduce scan times to under a minute were developed. A multi-step automated analysis pipeline to extract 3D strain/strain rate tensors from the velocity images was implemented to process the large dynamic volumes. Strain indices reflecting the material properties of the ECM were shown to correlate with force loss leading to a hypothesis that shear strain may serve as a surrogate marker for lateral transmission of force. Diffusion tensor imaging has been applied previously to study skeletal muscle fiber architecture. The resolution of the images precludes direct inferences to be made about the microstructure. To address this limitation, bicompartmental and Random Permeable Barrier models of diffusion were applied to the diffusion data obtained with spin-echo and custom-developed stimulated echo echo-planar-imaging sequences respectively. Model derived parameters (fiber diameter, wall permeability) obtained from fitting time-dependent diffusion data were in physiologically reasonable range, with potential for tracking age related changes in muscle microstructure. The developed imaging and modeling techniques were applied to a cohort of young/senior subjects and to longitudinal tracking of disuse atrophy induced by Unilateral Limb Suspension. These studies may potentially provide the causal link between age- and disuse-related structural remodeling and its functional consequences

Study of Human Muscle Structure and Function with Velocity Encoded Phase Contrast and Diffusion Tensor Magnetic Resonance Imaging Techniques

The disproportionate loss of muscle force with aging and disuse atrophy compared to the loss of muscle mass is not yet completely understood. In addition to well-established neural and contractile determinants of force loss, remodeling of the extracellular matrix (ECM) has been recently shown in animal models to be another important contributor. In-vivo human studies exploring the structural remodeling of the ECM and its functional consequences are lacking due to the paucity of appropriate imaging techniques. This study focuses on the development and application of advanced Magnetic Resonance Imaging (MRI) methods to elucidate the mechanisms of loss of force with aging and disuse atrophy with the focus on ECM. Functional changes are investigated by strain and strain rate tensor mapping of muscle under different contraction paradigms using Velocity Encoded Phase-Contrast MRI. Methodological advances include improvements in hardware and software control of the dynamic studies. To overcome the limitation of long scan times, compressed sensing MR acquisition and reconstruction framework to reduce scan times to under a minute were developed. A multi-step automated analysis pipeline to extract 3D strain/strain rate tensors from the velocity images was implemented to process the large dynamic volumes. Strain indices reflecting the material properties of the ECM were shown to correlate with force loss leading to a hypothesis that shear strain may serve as a surrogate marker for lateral transmission of force. Diffusion tensor imaging has been applied previously to study skeletal muscle fiber architecture. The resolution of the images precludes direct inferences to be made about the microstructure. To address this limitation, bicompartmental and Random Permeable Barrier models of diffusion were applied to the diffusion data obtained with spin-echo and custom-developed stimulated echo echo-planar-imaging sequences respectively. Model derived parameters (fiber diameter, wall permeability) obtained from fitting time-dependent diffusion data were in physiologically reasonable range, with potential for tracking age related changes in muscle microstructure. The developed imaging and modeling techniques were applied to a cohort of young/senior subjects and to longitudinal tracking of disuse atrophy induced by Unilateral Limb Suspension. These studies may potentially provide the causal link between age- and disuse-related structural remodeling and its functional consequences

3D T1rho sequences with FASE, UTE, and MAPSS acquisitions for knee evaluation

PurposeFor biochemical evaluation of soft tissues of the knee, T1rho magnetic resonance imaging (MRI) has been proposed. Purpose of this study was to compare three T1rho sequences based on fast advanced spin echo (FASE), ultrashort echo time (UTE), and magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS) acquisitions for the knee evaluation.Materials and methodsWe developed two T1rho sequences using 3D FASE or 3D radial UTE acquisitions. 3D MAPSS T1rho was provided by the manufacturer. Agarose phantoms with varying concentrations were imaged. Additionally, bilateral knees of asymptomatic subjects were imaged sagittally. T1rho values of the phantoms and 4 regions of interest (ROI) of the knees (i.e., anterior and posterior meniscus, femoral and tibial cartilage) were determined.ResultsIn phantoms, all T1rho values monotonically decreased with increasing agarose concentration. 3D MAPSS T1rho values of 51, 34, and 38 ms were found for 2, 3, and 4% agarose, respectively, similar to published values on another platform. In the knee, the raw images were detailed with good contrast. Cartilage and meniscus T1rho values varied with the pulse sequence, being the lowest in the 3D UTE T1rho sequence. Comparing different ROIs, menisci generally had lower T1rho values compared to cartilage, as expected in healthy knees.ConclusionWe have successfully developed and implemented the new T1rho sequences and validated them using agarose phantoms and volunteer knees. All sequences were optimized to be clinically feasible (~ 5 min or less) and yielded satisfactory image quality and T1rho values consistent with the literature

Magnetic resonance imaging based muscle strain rate mapping during eccentric contraction to study effects of unloading induced by unilateral limb suspension

Age- and disuse-related loss of muscle force is disproportionately larger than the loss of muscle mass. Earlier studies reported that comparing concentric and eccentric contractions, there is a significant age-related decrease in force only in concentric contractions. Magnetic Resonance Imaging enables mapping of muscle deformation and has been used to study isometric but not eccentric contractions. We report MRI based strain rate mapping of the medial gastrocnemius in subjects pre- and post-unloading induced by Unilateral Limb Suspension. In contrast to isometric contraction, no difference in strain rate indices were observed post-unloading, in conformance with preserved force during eccentric contractions

Deep-Learning-Aided Evaluation of Spondylolysis Imaged with Ultrashort Echo Time Magnetic Resonance Imaging.

Isthmic spondylolysis results in fracture of pars interarticularis of the lumbar spine, found in as many as half of adolescent athletes with persistent low back pain. While computed tomography (CT) is the gold standard for the diagnosis of spondylolysis, the use of ionizing radiation near reproductive organs in young subjects is undesirable. While magnetic resonance imaging (MRI) is preferable, it has lowered sensitivity for detecting the condition. Recently, it has been shown that ultrashort echo time (UTE) MRI can provide markedly improved bone contrast compared to conventional MRI. To take UTE MRI further, we developed supervised deep learning tools to generate (1) CT-like images and (2) saliency maps of fracture probability from UTE MRI, using ex vivo preparation of cadaveric spines. We further compared quantitative metrics of the contrast-to-noise ratio (CNR), mean squared error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) between UTE MRI (inverted to make the appearance similar to CT) and CT and between CT-like images and CT. Qualitative results demonstrated the feasibility of successfully generating CT-like images from UTE MRI to provide easier interpretability for bone fractures thanks to improved image contrast and CNR. Quantitatively, the mean CNR of bone against defect-filled tissue was 35, 97, and 146 for UTE MRI, CT-like, and CT images, respectively, being significantly higher for CT-like than UTE MRI images. For the image similarity metrics using the CT image as the reference, CT-like images provided a significantly lower mean MSE (0.038 vs. 0.0528), higher mean PSNR (28.6 vs. 16.5), and higher SSIM (0.73 vs. 0.68) compared to UTE MRI images. Additionally, the saliency maps enabled quick detection of the location with probable pars fracture by providing visual cues to the reader. This proof-of-concept study is limited to the data from ex vivo samples, and additional work in human subjects with spondylolysis would be necessary to refine the models for clinical use. Nonetheless, this study shows that the utilization of UTE MRI and deep learning tools could be highly useful for the evaluation of isthmic spondylolysis

Dynamics of Quadriceps Muscles during Isometric Contractions : Velocity-Encoded Phase Contrast MRI Study

Objective: To quantify the spatial heterogeneity of displacement during voluntary isometric contraction within and between the different compartments of the quadriceps. Methods: The thigh muscles of seven subjects were imaged on an MRI scanner while performing isometric knee extensions at 40% maximal voluntary contraction. A gated velocity-encoded phase contrast MRI sequence in axial orientations yielded tissue velocity-encoded dynamic images of the four different compartments of the thigh muscles (vastus lateralis (VL), vastus medialis (VM), vastus intermedius (VI), and rectus femoris (RF)) at three longitudinal locations of the proximal–distal length: 17.5% (proximal), 50% (middle), and 77.5% (distal). The displacement, which is the time integration of the measured velocity, was calculated along the three orthogonal axes using a tracking algorithm. Results: The displacement of the muscle tissues was clearly nonuniform within each axial section as well as between the three axial locations. The ensemble average of the magnitude of the total displacement as a synthetic vector of the X, Y, and Z displacements was significantly larger in the VM at the middle location (p < 0.01), and in the VI at the distal location than in the other three muscles. The ensemble average of Z-axis displacement, which was almost aligned with the line of action, was significantly larger in VI than in the other three muscles in all three locations. Displacements of more than 20 mm were observed around the central aponeuroses, such as those between VI and the other surrounding muscles. Conclusions: These results imply that the quadriceps muscles act as one functional unit in normal force generation through the central aponeuroses despite complex behavior in each of the muscles, each of which possesses different physiological characteristics and architectures.peerReviewe