Multiparametric exchange protons using Z-spectrum analysis proton (ZAP) and CEST on phantoms and human abdomen.

PURPOSE: This study aims to investigate a multiparametric exchange proton approach using CEST and Z-spectrum analysis protons (ZAP) in human abdominal organs, focusing on tissue differentiation for a potential early biomarker of abnormality. Prior to human studies, CEST and ZAP effects were studied in phantoms containing exchange protons. METHODS: Phantoms composed of iopamidol and iohexol solutions with varying pH levels, along with 12 human subjects, were scanned on a clinical 3T MR scanner. Subsequent ZAP analyses employed a two-Lorentzian pool model to provide free and restricted apparent T 2 f , r ex $$ {\mathrm{T}}_{2\ \mathrm{f},\mathrm{r}}^{\mathrm{ex}} $$ , and their fractions for data acquired across a wide range of offset frequencies (±100 kHz or ± 800 ppm), while a narrower range (±7 ppm or ± 900 Hz) was used for CEST analysis to estimate magnetization transfer ratio asymmetry (MTRAsym) for exchange protons like hydroxyl (OH), amine (NH2), and amide (NH), resonating ˜1, 2, and 3.5 ppm, respectively. Differences in ZAP metrics across various organs were statistically analyzed using one-way analysis of variance (ANOVA). RESULTS: The phantom study differentiated contrast agents based on resonance peaks detected from CEST analysis, while ZAP metrics showed sensitivity to pH variations. In human, ZAP metrics revealed significant differences in abdominal organs, with a subgroup study indicating changes in ZAP metrics due to the presence of gallstones. CONCLUSION: CEST and ZAP techniques demonstrated promise in specific CEST protons and wide range ZAP protons and identifying tissue-specific characteristics. The preliminary findings underscore the necessity for more extensive study involving a broader subject pool to potentially establish biomarkers for diseased states.

Non-contrast MRI of micro-vascularity of the feet and toes.

PURPOSE: This study aimed to develop novel non-contrast MR perfusion techniques for assessing micro-vascularity of the foot in human subjects. METHODS: All experiments were performed on a clinical 3 T scanner using arterial spin labeling (ASL). Seven healthy subjects (30-72 years old, 5 males and 2 females) were enrolled and bilateral feet were imaged with tag-on and tag-off alternating inversion recovery spin labeling for determining micro-vascularity. We compared an ASL technique with 1-tag against 4-tag pulses. For perfusion, we determined signal increase ratio (SIR) at varying inversion times (TI) from 0.5 to 2 s. SIR versus TI data were fit to determine perfusion metrics of peak height (PH), time to peak (TTP), full width at half maximum (FWHM), area under the curve (AUC), and apparent blood flow (aBF) in the distal foot and individual toes. Using analysis of variance (ANOVA), effects of tag pulse and region of interest (ROI) on the mean perfusion metrics were assessed. In addition, a 4-tag pulse perfusion experiment was performed on patients with peripheral artery disease (PAD) and Raynaud's disease. RESULTS: Using our MR perfusion techniques, SIR versus TI data showed well-defined leading and trailing edges, with a peak near TI of 0.75-1.0 s and subsiding quickly to near zero by TI of 2 s, particularly when 4-tag pulses were used. When imaged with 4-tag pulse, we found significantly greater values in perfusion metrics, as compared to 1-tag pulse. The patients with PAD and Raynaud's disease showed a reduced or scattered perfusion curves compared to the healthy control. CONCLUSION: MR perfusion imaging of the distal foot shows greater SIR and perfusion metrics with the 4-tag pulse compared to the 1-tag pulse technique. This will likely benefit those with low perfusion due to aging, PAD, diabetic foot, and other vascular diseases.

Physical Exercise Alters Egress Pathways for Intrinsic CSF Outflow: An Investigation Performed with Spin-labeling MR Imaging.

PURPOSE: Cerebrospinal fluid (CSF) clearance is essential for maintaining a healthy brain and cognition by removal of metabolic waste from the central nervous system. Physical exercise has been shown to improve human health; however, the effect of physical exercise on intrinsic CSF outflow in humans remains unexplored. The purpose of this study was to investigate intrinsic CSF outflow pathways and quantitative metrics of healthy individuals with active and sedentary lifestyles. In addition, the effect of exercise was investigated among the sedentary subjects before and after 3 weeks of physical activity. METHODS: This study was performed on 18 healthy adults with informed consent, using a clinical 3-Tesla MRI scanner. We classified participants into two groups based on reported time spent sitting per day (active group: < 7 hours sitting per day and sedentary group: ≥ 7 hours sitting per day). To elucidate the effect of exercise, sedentary individuals increased their activity to 3.5 hours for 3 weeks. RESULTS: We show that there are two intrinsic CSF egress pathways of the dura mater and lower parasagittal dura (PSD). The adults with an active lifestyle had greater intrinsic CSF outflow metrics than adults with a more sedentary lifestyle. However, after increased physical activity, the sedentary group showed improved CSF outflow metrics. This improvement was particularly notable at the lower PSD, where outflow metrics were highest among the active group. CONCLUSION: Our findings describe the relationship between physical activity and intrinsic CSF outflow and show a potential selective outflow pathway with increasing physical activity in the lower PSD pathway, potentially from the perivascular space or cortical venous subpial space.

Aliphatic and Olefinic Fat Suppression in the Orbit Using Polarity-altered Spectral and Spatial Selective Acquisition (PASTA) with Opposed Phase.

PURPOSE: Fatty acid composition of the orbit makes it challenging to achieve complete fat suppression during orbit MR imaging. Implementation of a fat suppression technique capable of suppressing signals from saturated (aliphatic) and unsaturated (olefinic or protons at double-bonded carbon sites) fat would improve the visualization of an optical nerve. Furthermore, the ability to semi-quantify the fractions of aliphatic and olefinic fat may potentially provide valuable information in assessing orbit pathology. METHODS: A phantom study was conducted on various oil samples on a clinical 3 Tesla scanner. The imaging protocol included three 2D fast spin echo (FSE) sequences: in-phase, polarity-altered spectral and spatial selective acquisition (PASTA), and a combination of PASTA with opposed phase in olefinic and aliphatic chemical shift. The results were validated against high-resolution 11.7T NMR and compared with images acquired with spectral attenuated inversion recovery (SPAIR) and chemical shift selective (CHESS) fat suppression techniques. In-vivo data were acquired on eight healthy subjects and were compared with the prior histological studies. RESULTS: PASTA with opposed phase achieved complete suppression of fat signals in the orbits and provided images of well-delineated optical nerves and muscles in all subjects. The olefinic fat fraction in the olive, walnut, and fish oil phantoms at 3T was found to be 5.0%, 11.2%, and 12.8%, respectively, whereas 11.7T NMR provides the following olefinic fat fractions: 6.0% for olive, 11.5% for walnut, and 12.6% for fish oils. For the in-vivo study, on average, olefinic fat accounted for 9.9% ± 3.8% of total fat while the aliphatic fat fraction was 90.1% ± 3.8%, in the normal orbits. CONCLUSION: We have introduced a new fat suppression technique using PASTA with opposed phase and applied it to human orbits. The purposed method achieves an excellent orbital fat suppression and the quantification of aliphatic and olefinic fat signals.

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.

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

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

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

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

Lung T2 * mapping using 3D ultrashort TE with tight intervals δTE.

PURPOSE: To develop 3D ultrashort-TE (UTE) sequences with tight TE intervals (δTE), allowing for accurate T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping of lungs under free breathing. METHODS: We have implemented a four-echo UTE sequence with δTE (< 0.5 ms). A Monte-Carlo simulation was performed to identify an optimal number of echoes that would result in a significant improvement in the accuracy of the T 2 * $$ {\mathrm{T}}_2^{\ast } $$ fit within an acceptable scan time. A validation study was conducted on a phantom with known short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ values (< 5 ms). The scanning protocol included a combination of a standard multi-echo UTE with six echoes (2.2-ms intervals) and a new four-echo UTE (TE < 2 ms) with tight TE intervals δTE. The human imaging was performed at 3 T on 6 adult volunteers. T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping was performed with mono-exponential and bi-exponential models. RESULTS: The simulation for the proposed 10-echo acquisition predicted over 2-fold improvement in the accuracy of estimating the short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ compared with the regular six-echo acquisition. In the phantom study, the T 2 * $$ {\mathrm{T}}_2^{\ast } $$ was measured up to three times more accurately compared with standard six-echo UTE. In human lungs, T 2 * $$ {\mathrm{T}}_2^{\ast } $$ maps were successfully obtained from 10 echoes, yielding average values T 2 * $$ {\mathrm{T}}_2^{\ast } $$ = 1.62 ± 0.48 ms for mono-exponential and T 2 s * $$ {\mathrm{T}}_{2s}^{\ast } $$ = 1.00 ± 0.53 ms for bi-exponential models. CONCLUSION: A UTE sequence using δTE was implemented and validated on short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ phantoms. The sequence was successfully applied for lung imaging; the bi-exponential signal model fit for human lung imaging may provide valuable insights into the diseased human lungs.

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

PURPOSE: For 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 METHODS: We 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. RESULTS: In 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. CONCLUSION: We 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.

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

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

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

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

Age-related Decline of Intrinsic Cerebrospinal Fluid Outflow in Healthy Humans Detected with Non-contrast Spin-labeling MR Imaging.

PURPOSE: Clearance of cerebrospinal fluid (CSF) is important for the removal of toxins from the brain, with implications for neurodegenerative diseases. Imaging evaluation of CSF outflow in humans has been limited, relying on venous or invasive intrathecal injections of contrast agents. The objective of this study was to introduce a novel spin-labeling MRI technique to detect and quantify the movement of endogenously tagged CSF, and then apply it to evaluate CSF outflow in normal humans of varying ages. METHODS: This study was performed on a clinical 3-Tesla MRI scanner in 16 healthy subjects with an age range of 19-71 years with informed consent. Our spin-labeling MRI technique applies a tag pulse on the brain hemisphere, and images the outflow of the tagged CSF into the superior sagittal sinus (SSS). We obtained 3D images in real time, which was analyzed to determine tagged-signal changes in different regions of the meninges involved in CSF outflow. Additionally, the signal changes over time were fit to a signal curve to determine quantitative flow metrics. These were correlated against subject age to determine aging effects. RESULTS: We observed the signal of the tagged CSF moving from the dura mater and parasagittal dura, and finally draining into the SSS. In addition, we observed a possibility of another pathway which is seen in some young subjects. Furthermore, quantitative CSF outflow metrics were shown to decrease significantly with age. CONCLUSION: We demonstrate a novel non-invasive MRI technique identifying two intrinsic CSF clearance pathways, and observe an age-related decline of CSF flow metrics in healthy subjects. Our work provides a new opportunity to better understand the relationships of these CSF clearance pathways during the aging process, which may ultimately provide insight into the age-related prevalence of neurodegenerative diseases.

Time-Resolved Noncontrast Magnetic Resonance Perfusion Imaging of Paraspinal Muscles.

BACKGROUND: While evaluation of blood perfusion in lumbar paraspinal muscles is of interest in low back pain, it has not been performed using noncontrast magnetic resonance (MR) techniques. PURPOSE: To introduce a novel application of a time-resolved, noncontrast MR perfusion technique for paraspinal muscles and demonstrate effect of exercise on perfusion parameters. STUDY TYPE: Longitudinal. SUBJECTS: Six healthy subjects (27-48 years old, two females) and two subjects with acute low back pain (46 and 65 years old females, one with diabetes/obesity). FIELD STRENGTH/SEQUENCE: 3-T, MR perfusion sequence. ASSESSMENT: Lumbar spines of healthy subjects were imaged axially at L3 level with a tag-on and tag-off alternating inversion recovery arterial spin labeling technique that suppresses background signal and acquires signal increase ratio (SIR) from the in-flow blood at varying inversion times (TI) from 0.12 seconds to 3.5 seconds. SIR vs. TI data were fit to determine the perfusion metrics of peak height (PH), time to peak (TTP), mean transit time, apparent muscle blood volume (MBV), and apparent muscle blood flow (MBF) in iliocostal, longissimus, and multifidus. Imaging was repeated immediately after healthy subjects performed a 20-minute walk, to determine the effect of exercise. STATISTICAL TESTS: Repeated measures analysis of variance. RESULTS: SIR vs. TI data showed well-defined leading and trailing edges, with sharply increasing SIR to TI of approximately 500 msec subsiding quickly to near zero around TI of 1500 msec. After exercise, the mean SIR at every TI increased markedly, resulting in significantly higher PH, MBV, and MBF (each P < 0.001 and F > 28.9), and a lower TTP (P < 0.05, F = 4.5), regardless of the muscle. MBF increased 2- to 2.5-fold after exercise, similar to the expected increase in cardiac output, given the intensity of the exercise. DATA CONCLUSIONS: Feasibility of an MR perfusion technique for muscle perfusion imaging was demonstrated, successfully detecting significantly increased perfusion after exercise. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

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

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

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.

3D Muscle Deformation Mapping at Submaximal Isometric Contractions: Applications to Aging Muscle.

3D strain or strain rate tensor mapping comprehensively captures regional muscle deformation. While compressive strain along the muscle fiber is a potential measure of the force generated, radial strains in the fiber cross-section may provide information on the material properties of the extracellular matrix. Additionally, shear strain may potentially inform on the shearing of the extracellular matrix; the latter has been hypothesized as the mechanism of lateral transmission of force. Here, we implement a novel fast MR method for velocity mapping to acquire multi-slice images at different % maximum voluntary contraction (MVC) for 3D strain mapping to explore deformation in the plantar-flexors under isometric contraction in a cohort of young and senior subjects. 3D strain rate and strain tensors were computed and eigenvalues and two invariants (maximum shear and volumetric strain) were extracted. Strain and strain rate indices (contractile and in-plane strain/strain rate, shear strain/strain rate) changed significantly with %MVC (30 and 60% MVC) and contractile and shear strain with age in the medial gastrocnemius. In the soleus, significant differences with age in contractile and shear strain were seen. Univariate regression revealed weak but significant correlation of in-plane and shear strain and shear strain rate indices to %MVC and correlation of contractile and shear strain indices to force. The ability to map strain tensor components provides unique insights into muscle physiology: with contractile strain providing an index of the force generated by the muscle fibers while the shear strain could potentially be a marker of lateral transmission of force.

Role of the Extracellular Matrix in Loss of Muscle Force With Age and Unloading Using Magnetic Resonance Imaging, Biochemical Analysis, and Computational Models.

The focus of this review is the application of advanced MRI to study the effect of aging and disuse related remodeling of the extracellular matrix (ECM) on force transmission in the human musculoskeletal system. Structural MRI includes (i) ultra-low echo times (UTE) maps to visualize and quantify the connective tissue, (ii) diffusion tensor imaging (DTI) modeling to estimate changes in muscle and ECM microstructure, and (iii) magnetization transfer contrast imaging to quantify the macromolecular fraction in muscle. Functional MRI includes dynamic acquisitions during contraction cycles enabling computation of the strain tensor to monitor muscle deformation. Further, shear strain extracted from the strain tensor may be a potential surrogate marker of lateral transmission of force. Biochemical and histological analysis of muscle biopsy samples can provide "gold-standard" validation of some of the MR findings. The review summarizes biochemical studies of ECM adaptations with age and with disuse. A brief summary of animal models is included as they provide experimental confirmation of longitudinal and lateral force transmission pathways. Computational muscle models enable exploration of force generation and force pathways and elucidate the link between structural adaptations and functional consequences. MR image findings integrated in a computational model can explain and predict subject specific functional changes to structural adaptations. Future work includes development and validation of MRI biomarkers using biochemical analysis of muscle tissue as a reference standard and potential translation of the imaging markers to the clinic to noninvasively monitor musculoskeletal disease conditions and changes consequent to rehabilitative interventions.

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.

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

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

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

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