Throughout the body, muscle structure and function can be interrogated using a variety of noninvasive magnetic resonance imaging (MRI) methods. Recently, intravoxel incoherent motion (IVIM) MRI has gained momentum as a method to evaluate components of blood flow and tissue diffusion simultaneously. Much of the prior research has focused on highly vascularized organs, including the brain, kidney, and liver. Unique aspects of skeletal muscle, including the relatively low perfusion at rest and large dynamic range of perfusion between resting and maximal hyperemic states, may influence the acquisition, postprocessing, and interpretation of IVIM data. Here, we introduce several of those unique features of skeletal muscle; review existing studies of IVIM in skeletal muscle at rest, in response to exercise, and in disease states; and consider possible confounds that should be addressed for muscle-specific evaluations. Most studies used segmented nonlinear least squares fitting with a b-value threshold of 200 sec/mm² to obtain IVIM parameters of perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D). In healthy individuals, across all muscles, the average ± standard deviation of D was 1.46 ± 0.30 × 10^-3  mm² /sec, D* was 29.7 ± 38.1 × 10^-3  mm² /sec, and f was 11.1 ± 6.7%. Comparisons of reported IVIM parameters in muscles of the back, thigh, and leg of healthy individuals showed no significant difference between anatomic locations. Throughout the body, exercise elicited a positive change of all IVIM parameters. Future directions including advanced postprocessing models and potential sequence modifications are discussed. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

The magnetism of hemoglobin - being paramagnetic in its deoxy and diamagnetic in its oxy state - offers unique opportunities to probe oxygen metabolism in blood and tissues. The magnetic susceptibility χ of blood scales linearly with blood oxygen saturation, which can be obtained by measuring the magnetic field ΔB of the intravascular MR signal relative to tissue. In contrast to χ, the induced field ΔB is non-local. Therefore, to obtain the intravascular susceptibility Δχ relative to adjoining tissue from the measured ΔB demands solution of an inverse problem. Fortunately, for ellipsoidal structures, to which a straight, cylindrically shaped blood vessel segment conforms, the solution is trivial. The article reviews the principle of MR susceptometry-based blood oximetry. It then discusses applications for quantification of whole-brain oxygen extraction - typically on the basis of a measurement in the superior sagittal sinus - and, in conjunction with total cerebral blood flow, the cerebral metabolic rate of oxygen (CMRO2 ). By simultaneously measuring flow and venous oxygen saturation (SvO2 ) a temporal resolution of a few seconds can be achieved, allowing the study of the response to non-steady-state challenges such as volitional apnea. Extensions to regional measurements in smaller cerebral veins are also possible, as well as voxelwise quantification of venous blood saturation in cerebral veins accomplished by quantitative susceptibility mapping (QSM) techniques. Applications of susceptometry-based oximetry to studies of metabolic and degenerative disorders of the brain are reviewed. Lastly, the technique is shown to be applicable to other organ systems such as the extremities using SvO2 as a dynamic tracer to monitor the kinetics of the microvascular response to induced ischemia. Copyright © 2016 John Wiley & Sons, Ltd.

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.

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.

Background

Quantification of the magnitude and spatial distribution of muscle blood flow changes following exercise may improve our understanding of the effectiveness of various exercise prescriptions. Intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) is a technique that quantifies molecular diffusion and microvascular blood flow, and has recently gained momentum as a method to evaluate a muscle's response to exercise. It has also been shown to predict responses to exercise-based physical therapy in individuals with low back pain. However, no study has evaluated the sensitivity of IVIM-MRI to exercise of varying intensity in humans. Here, we aimed to evaluate IVIM signal changes of the paraspinal muscles in response to moderate and high intensity lumbar extension exercise in healthy individuals.

Methods

IVIM data were collected in 11 healthy volunteers before and immediately after a 3-min bout of moderate and high-intensity resisted lumbar extension. IVIM data were analyzed to determine the average perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D) in the bilateral paraspinal muscles. Changes in IVIM parameters were compared between the moderate and high intensity exercise bouts.

Results

Exercise increased all IVIM parameters, regardless of intensity (p < 0.003). Moderate intensity exercise resulted in a 11.2, 19.6, and 3.5% increase in f, D* and D, respectively. High intensity exercise led to a similar increase in f (12.2%), but much greater changes in D* (48.6%) and D (7.9%).

Conclusion

IVIM parameter increases suggest that both the moderate and high-intensity exercise conditions elicited measurable changes in blood flow (increased f and D*) and extravascular molecular diffusion rates (increased D), and that there was a dose-dependence of exercise intensity on D* and D.

Magnetic resonance imaging (MRI) is a diagnostic tool that can be used to noninvasively assess lumbar muscle size and fatty infiltration, important biomarkers of muscle health. Diffusion tensor imaging (DTI) is an MRI technique that is sensitive to muscle microstructural features such as fiber size (an important biomarker of muscle health), which is typically only assessed using invasive biopsy techniques. The goal of this study was to establish normative values of level-dependent lumbar muscle size, fat signal fraction, and restricted diffusion assessed by MRI in a highly active population. Forty-two active-duty Marines were imaged using a (a) high-resolution anatomical, (b) fat-water separation, and (c) DT-MRI scan. The multifidus and erector spinae muscles were compared at each level using two-way repeated measures ANOVA. Secondary analysis included Three dimensional (3D) reconstructions to qualitatively assess lumbar muscle size, fatty infiltration, and fiber orientation via tractography. The erector spinae was found to be larger than the multifidus above L5, with lower fat signal fraction above L3, and a less restricted diffusion profile than the multifidus above L4, with this pattern reversed in the lower lumbar spine. 3D reconstructions demonstrated accumulations of epimuscular fat in the anterior and posterior regions of the lumbar musculature, with minimal intramuscular fatty infiltration. Tractography images demonstrated different orientations of adjacent lumbar musculature, which cannot be visualized with standard MRI pulse sequences. The level dependent differences found in this study provide a normative baseline, for which to better understand whole muscle and microstructural changes associated with aging, low back pain, and pathology.