Purpose

Evaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected.

Methods

The DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth.

Results

Across all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models.

Conclusion

These findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.

Background

Muscle atrophy and fatty infiltration of the lumbar extensors is associated with LBP. Exercise-based rehabilitation targets strengthening these muscles, but few studies show consistent changes in muscle quality with standard-of-care rehabilitation. The goal of this study was to assess the effect of high-intensity resistance exercise on lumbar extensor muscle size (cross sectional area) and quality (fat fraction) in individuals with low back pain (LBP).

Methods

Fourteen patients with LBP were recruited from a local rehabilitation clinic. Patients underwent MRI scanning before and after a standardized 10-week high-intensity machine-based, resistance exercise program. Patient pain, disability, anxiety/depression, satisfaction, strength, and range of motion was compared pre- and post-rehabilitation using analysis of covariance (covariates: age, gender). Exercise-induced changes in MRI, and patient functional outcome measures were correlated using Pearson's correlation test.

Results

No significant differences were found in muscle size or fatty infiltration of the lumbar extensors over the course of rehabilitation (p > 0.31). However, patients reported reduced pain (p = 0.002) and were stronger (p = 0.03) at the conclusion of the program. Improvements in muscle size and quality for both multifidus and erector spinae correlated with improvements in disability, anxiety/depression, and strength.

Conclusion

While average muscle size and fatty infiltration levels did not change with high-intensity exercise, the results suggest that a subgroup of patients who demonstrate improvements in muscle health demonstrate the largest functional improvements. Future research is needed to identify which patients are most likely to respond to this type of treatment.

Background

Magnetic Resonance Imaging (MRI) is commonly used to assess the health of the lumbar spine and supporting structures. Studies have suggested that fatty infiltration of the posterior lumbar muscles is important in predicting responses to treatment for low back pain. However, methodological differences exist in defining the region of interest (ROI) of a muscle, which limits the ability to compare data between studies. The purpose of this study was to determine reliability and systematic differences within and between two commonly utilized methodologies for ROI definitions of lumbar paraspinal muscle.

Methods

T2-weighted MRIs of the mid-L4 vertebrae from 37 patients with low back pain who were scheduled for lumbar spine surgery were included from a hospital database. Fatty infiltration for these patients ranged from low to high, based on Kjaer criteria. Two methods were used to define ROI: 1) segmentation of the multifidus and erector spinae based on fascial planes including epimuscular fat, and 2) segmentation of the multifidus and erector spinae based on visible muscle boundaries, which did not include epimuscular fat. Total cross sectional area (tCSA), fat signal fraction (FSF), muscle cross sectional area, and fat cross sectional area were measured. Degree of agreement between raters for each parameter was assessed using intra-class correlation coefficients (ICC) and area fraction of overlapping voxels.

Results

Excellent inter-rater agreement (ICC > 0.75) was observed for all measures for both methods. There was no significant difference between area fraction overlap of ROIs between methods. Method 1 demonstrated a greater tCSA for both the erector spinae (14-15%, p < 0.001) and multifidus (4%, p < 0.016) but a greater FSF only for the erector spinae (11-13%, p < 0.001).

Conclusion

The two methods of defining lumbar spine muscle ROIs demonstrated excellent inter-rater reliability, although significant differences exist as method 1 showed larger CSA and FSF values compared to method 2. The results of this study confirm the validity of using either method to measure lumbar paraspinal musculature, and that method should be selected based on the primary outcome variables of interest.

The experimental study of prions requires a model for their propagation. However, because prions lack nucleic acids, the simple techniques used to replicate bacteria and viruses are not applicable. For much of the history of prion research, time-consuming bioassays in animals were the only option for measuring infectivity. Although cell models and other in vitro tools for the propagation of prions have been developed, they all suffer limitations, and animal bioassays remain the gold standard for measuring infectivity. A wealth of recent data argues that both β-amyloid (Aβ) and tau proteins form prions that cause Alzheimer's disease, and α-synuclein forms prions that cause multiple system atrophy and Parkinson's disease. Cell and animal models that recapitulate some of the key features of cell-to-cell spreading and distinct strains of prions can now be measured.

Advancement of tissue engineering and regenerative medicine (TERM) strategies to replicate tissue structure and function has led to the need for noninvasive assessment of key outcome measures of a construct's state, biocompatibility, and function. Histology based approaches are traditionally used in pre-clinical animal experiments, but are not always feasible or practical if a TERM construct is going to be tested for human use. In order to transition these therapies from benchtop to bedside, rigorously validated imaging techniques must be utilized that are sensitive to key outcome measures that fulfill the FDA standards for TERM construct evaluation. This review discusses key outcome measures for TERM constructs and various clinical- and research-based imaging techniques that can be used to assess them. Potential applications and limitations of these techniques are discussed, as well as resources for the processing, analysis, and interpretation of biomedical images.

The ability to noninvasively assess skeletal muscle microstructure, which predicts function and disease, would be of significant clinical value. One method that holds this promise is diffusion tensor magnetic resonance imaging (DT-MRI), which is sensitive to the microscopic diffusion of water within tissues and has become ubiquitous in neuroimaging as a way of assessing neuronal structure and damage. However, its application to the assessment of changes in muscle microstructure associated with injury, pathology, or age remains poorly defined, because it is difficult to precisely control muscle microstructural features in vivo. However, recent advances in additive manufacturing technologies allow precision-engineered diffusion phantoms with histology informed skeletal muscle geometry to be manufactured. Therefore, the goal of this study was to develop skeletal muscle phantoms at relevant size scales to relate microstructural features to MRI-based diffusion measurements. A digital light projection based rapid 3D printing method was used to fabricate polyethylene glycol diacrylate based diffusion phantoms with (1) idealized muscle geometry (no geometry; fiber sizes of 30, 50, or 70 μm or fiber size of 50 μm with 40% of walls randomly deleted) or (2) histology-based geometry (normal and after 30-days of denervation) containing 20% or 50% phosphate-buffered saline (PBS). Mean absolute percent error (8%) of the printed phantoms indicated high conformity to templates when "fibers" were >50 μm. A multiple spin-echo echo planar imaging diffusion sequence, capable of acquiring diffusion weighted data at several echo times, was used in an attempt to combine relaxometry and diffusion techniques with the goal of separating intracellular and extracellular diffusion signals. When fiber size increased (30-70 μm) in the 20% PBS phantom, fractional anisotropy (FA) decreased (0.32-0.26) and mean diffusivity (MD) increased (0.44 × 10^-3 mm²/s-0.70 × 10^-3 mm²/s). Similarly, when fiber size increased from 30 to 70 μm in the 50% PBS diffusion phantoms, a small change in FA was observed (0.18-0.22), but MD increased from 0.86 × 10^-3 mm²/s to 1.79 × 10^-3 mm²/s. This study demonstrates a novel application of tissue engineering to understand complex diffusion signals in skeletal muscle. Through this work, we have also demonstrated the feasibility of 3D printing for skeletal muscle with relevant matrix geometries and physiologically relevant tissue characteristics.

Military members are required to carry heavy loads frequently during training and active duty combat. We investigated if operationally relevant axial loads affect lumbar disc kinematics in forty-one male active duty Marines with no previous clinically diagnosed pathology. Marines were imaged standing upright with and without load. From T2-weighted magnetic resonance images, IVD health and kinematic changes between loading conditions and across lumbar levels were evaluated using two-way repeated measures analysis of variance tests. IVD kinematics with loading were compared between individuals with and without signs of degeneration on imaging. Linear regression analyses were performed to determine associations between IVD position and kinematic changes with loading. Fifty-eight percent (118/205) of IVDs showed evidence of degeneration and 3% (7/205) demonstrated a disc bulge. IVD degeneration was not related to posterior annular position (p>0.205). Changes in sagittal intervertebral angle were not associated with changes in posterior annular position between baseline and loaded conditions at any lumbar level (r<0.267; p=.091-0.746). Intervertebral angles were significantly larger in the lower regions of the spine (p<0.001), indicating increased local lordosis when moving in the caudal direction Disc height at the L5/S1 level was significantly smaller (6.3mm, mean difference =1.20) than all other levels (p<0.001) and baseline posterior disc heights tended to be larger at baseline (7.43mm ± 1.46) than after loading (7.18 ±1.57, p=0.071). Individuals with a larger baseline posterior annular position demonstrated greater reduction with load at all levels (p<0.002), with the largest reductions at L5/S1 level. Overall, while this population demonstrated some signs of disc degeneration, operationally relevant loading did not significantly affect disc kinematics.

Vertebral level-dependent, angular, and linear translations of the spine have been measured in 2D and 3D using several imaging methods to quantify postural changes due to loading conditions and tasks. Here, we propose and validate a semiautomated method for measuring lumbar intervertebral angles and translations from upright MRI images using an endplate-based, joint coordinate system (JCS). This method was validated using 3D printed structures, representing intervertebral discs (IVD) at predetermined angles and heights, which were positioned between adjacent cadaveric vertebrae as a gold standard. Excellent agreement between our measurements and the gold standard was found for intervertebral angles in all anatomical planes (ICC > .997) and intervertebral distance measurements (ICC > .949). The proposed endplate-based JCS was compared with the vertebral body-based JCS proposed by the International Society of Biomechanics (ISB) using the 3D printed structures placed between 3 adjacent vertebrae from a cadaver with scoliosis. The endplate-based method was found to have better agreement with angles in the sagittal plane (ICC = 0.985) compared with the vertebral body-based method (ICC = .280). Thus, this method is accurate for measuring 3D intervertebral angles in the healthy and diseased lumbar spine.

Purpose

To establish a series of relationships defining how muscle microstructure and diffusion tensor imaging (DTI) are related.

Methods

The relationship among key microstructural features of skeletal muscle (fiber size, fibrosis, edema, and permeability) and the diffusion tensor were systematically simulated over physiologically relevant dimensions individually, and in combination, using a numerical simulation application. Stepwise multiple regression was used to identify which microstructural features of muscle significantly predict the diffusion tensor using single-echo and multi-echo DTI pulse sequences. Simulations were also performed in models with histology-informed geometry to investigate the relationship between fiber size and the diffusion tensor in models with real muscle geometry.

Results

Fiber size is the strongest predictor of λ2, λ3, mean diffusivity, and fractional anisotropy in skeletal muscle, accounting for approximately 40% of the variance in the diffusion model when calculated with single-echo DTI. This increased to approximately 70% when diffusion measures were calculated from the short T₂ component of the multi-echo DTI sequence. This nonlinear relationship begins to plateau in fibers with greater than 60-μm diameter.

Conclusions

As the normal fiber size of a human muscle fiber is 40 to 60 μm, this suggests that DTI is a sensitive tool to monitor muscle atrophy, but may be limited in measurements of muscle with larger fibers. Magn Reson Med 80:317-329, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Background The relationship between lumbar spine posture and muscle structure is not well understood. Objectives To investigate the predictive capacity of muscle structure on lumbar spine posture in active-duty Marines. Methods Forty-three Marines were scanned in this cross-sectional study, using an upright magnetic resonance imaging scanner while standing without load and standing, sitting, and prone on elbows with body armor. Cobb, horizontal, and sacral angles were measured. Marines were then scanned while unloaded in supine using a supine magnetic resonance imaging scanner. The imaging protocol consisted of T2 intervertebral disc mapping; high-resolution, anatomical, fat-water separation, and diffusion tensor imaging to quantify disc hydration and muscle volume, fat fraction, and restricted diffusion profiles in the lumbar muscles. A stepwise multiple linear regression model was used to identify physiological measures predictive of lumbar spine posture. Results The multiple regression model demonstrated that fractional anisotropy of the erector spinae was a significant predictor of lumbar posture for 7 of 18 dependent variables measured, and explained 20% to 35% of the variance in each model. Decreased fractional anisotropy of the erector spinae predicted decreased lordosis, lumbosacral extension, and anterior pelvic tilt. Conclusion Fractional anisotropy is inversely related with muscle fiber size, which is associated with the isometric force-generating capacity of a muscle fiber. This suggests that stronger erector spinae muscles predict decreased lordosis, lumbosacral extension, and anterior pelvic tilt in a highly trained population. J Orthop Sports Phys Ther 2018;48(8):613-621. Epub 17 May 2018. doi:10.2519/jospt.2018.7865.