In JoVE (1)

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Articles by Bruce M. Damon in JoVE

 JoVE Medicine

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

1Institute of Imaging Science, Vanderbilt University, 2Department of Radiology and Radiological Sciences, Vanderbilt University, 3Department of Biomedical Engineering, Vanderbilt University, 4Department of Molecular Physiology and Biophysics, Vanderbilt University, 5Department of Physical Medicine and Rehabilitation, Vanderbilt University, 6Department of Physics and Astronomy, Vanderbilt University


JoVE 52352

Other articles by Bruce M. Damon on PubMed

Intracellular Acidification and Volume Increases Explain R(2) Decreases in Exercising Muscle

Magnetic Resonance in Medicine. Jan, 2002  |  Pubmed ID: 11754438

Exercise-induced decreases in the (1)H transverse relaxation rate (R(2)) of muscle have been well documented, but the mechanism remains unclear. In this study, the hypothesis was tested that R(2) decreases could be explained by pH decreases and apparent intracellular volume (V(i)') increases. (31)P and (1)H spectroscopy, biexponential R(2) analysis, and imaging were performed prior to and following fatiguing exercise in iodoacetate-treated (IAA, to inhibit glycolysis), NaCN-treated (to inhibit oxidative phosphorylation), and untreated frog gastrocnemii. In all exercised muscles, the apparent intracellular R(2) (R(2i)') and pH decreased, while intracellular osmolytes and V(i)' increased. These effects were larger in NaCN-treated and untreated muscles than in IAA-treated muscles. Multiple regression analysis showed that pH and V(i)' changes explain 70% of the R(2i)' variance. Separate experiments in unexercised muscles demonstrated causal relationships between pH and R(2i)' and between V(i)' and R(2i)'. These data indicate that the R(2) change of exercise is primarily an intracellular phenomenon caused by the accumulation of the end-products of anaerobic metabolism. In the NaCN-treated and untreated muscles, the R(2i)' change increased as field strength increased, suggesting a role for pH-modulated chemical exchange.

Validation of Diffusion Tensor MRI-based Muscle Fiber Tracking

Magnetic Resonance in Medicine. Jul, 2002  |  Pubmed ID: 12111936

Diffusion-tensor (DT) MRI fiber tracking may potentially be used for in vivo structural analysis. The purpose of this study was to assess quantitatively the ability of a DT-MRI fiber-tracking algorithm to measure the fiber orientation (pennation) in skeletal muscle in vivo. In five adult Sprague-Dawley rats, the pennation angle (theta) was measured in the rat lateral gastrocnemius with DT-MRI (theta(DT-MRI)) and by direct anatomical inspection (DAI) (theta(DAI)). The mean theta(DT-MRI) was not significantly different from the mean theta(DAI). In addition, the two methods were highly correlated (r = 0.89) and the regression of theta(DT-MRI) on theta(DAI) resulted in a slope not significantly different from 1 and an intercept not significantly different from zero. These data indicate that DT-MRI-based fiber tracking as implemented here is a valid tool for in vivo structural analysis of small-animal skeletal muscle.

Early Postexercise Muscle Glycogen Recovery is Enhanced with a Carbohydrate-protein Supplement

Journal of Applied Physiology (Bethesda, Md. : 1985). Oct, 2002  |  Pubmed ID: 12235033

In the present study, we tested the hypothesis that a carbohydrate-protein (CHO-Pro) supplement would be more effective in the replenishment of muscle glycogen after exercise compared with a carbohydrate supplement of equal carbohydrate content (LCHO) or caloric equivalency (HCHO). After 2.5 +/- 0.1 h of intense cycling to deplete the muscle glycogen stores, subjects (n = 7) received, using a rank-ordered design, a CHO-Pro (80 g CHO, 28 g Pro, 6 g fat), LCHO (80 g CHO, 6 g fat), or HCHO (108 g CHO, 6 g fat) supplement immediately after exercise (10 min) and 2 h postexercise. Before exercise and during 4 h of recovery, muscle glycogen of the vastus lateralis was determined periodically by nuclear magnetic resonance spectroscopy. Exercise significantly reduced the muscle glycogen stores (final concentrations: 40.9 +/- 5.9 mmol/l CHO-Pro, 41.9 +/- 5.7 mmol/l HCHO, 40.7 +/- 5.0 mmol/l LCHO). After 240 min of recovery, muscle glycogen was significantly greater for the CHO-Pro treatment (88.8 +/- 4.4 mmol/l) when compared with the LCHO (70.0 +/- 4.0 mmol/l; P = 0.004) and HCHO (75.5 +/- 2.8 mmol/l; P = 0.013) treatments. Glycogen storage did not differ significantly between the LCHO and HCHO treatments. There were no significant differences in the plasma insulin responses among treatments, although plasma glucose was significantly lower during the CHO-Pro treatment. These results suggest that a CHO-Pro supplement is more effective for the rapid replenishment of muscle glycogen after exercise than a CHO supplement of equal CHO or caloric content.

The Carnosine C-2 Proton's Chemical Shift Reports Intracellular PH in Oxidative and Glycolytic Muscle Fibers

Magnetic Resonance in Medicine. Feb, 2003  |  Pubmed ID: 12541242

The appearance of new peaks in the 7.7-8.6 and 6.8-7.4 ppm regions of the postexercise (1)H spectrum of frog muscle is reported. These new peaks result from the splitting of single pre-exercise carnosine C-2 and C-4 peaks into two peaks, representing the intracellular pH (pH(I)) of oxidative and glycolytic fibers. The following data support this conclusion: 1) comparison of means and regression analysis indicates equivalence of the pH(I) measurements by (1)H and (31)P NMR; 2) the pre- and poststimulation concentrations of carnosine are equal; 3) in ischemic rat hindlimb muscles, the presence of a single, more acidic peak in the plantaris; a single, less acidic peak in the soleus; and two peaks (more and less acidic) in the gastrocnemius correspond to published values for the fiber-type composition of these muscles; and 4) in muscles treated with iodoacetate prior to and during stimulation, a second peak never appears. These data indicate that it is feasible to measure separately the pH(I) of oxidative and glycolytic fibers using (1)H NMR spectroscopy.

Cluster Analysis of Muscle Functional MRI Data

Journal of Applied Physiology (Bethesda, Md. : 1985). Sep, 2003  |  Pubmed ID: 12766178

Muscle functional magnetic resonance imaging (mfMRI) is frequently used to determine spatial patterns of muscle involvement in exercising humans. A frequent finding in mfMRI is that, even within synergistic muscle groups, signal intensity (SI) data from individual voxels can be quite heterogeneous. The purpose of this study was to develop a novel method for organizing heterogeneous mfMRI data into clusters whose members behave similarly to each other but distinctly from members of other clusters and apply it in studies of functional compartmentalization in the anterior compartment of the leg. An algorithm was developed that compared the SI time courses of adjacent voxels and grouped together voxels that were sufficiently similar. The algorithm's performance was verified by using simulated data sets with known regional differences in SI time courses that were then applied to experimental mfMRI data acquired from six male subjects (age 22.6 +/- 0.9 yr, mean +/- SE) who sustained isometric contractions of the dorsiflexors at 40% of maximum voluntary contraction. The experimental data were also characterized by using a traditional analysis (user-specified regions of interest from a single image), in which the relative change in SI and the contrast-to-noise ratio [CNR; 100%x(SI(RESTING) - SI(ACTIVE)/(noise standard deviation)] were measured. In general, clusters were found in areas in which the CNR exceeded 5. Cluster analysis made functional distinctions between regions of muscle that were not seen with traditional analysis. In conclusion, cluster analysis's use of the full SI time course provides more sensitivity to muscle functional compartmentation than traditional analysis.

Comparison of MRI with EMG to Study Muscle Activity Associated with Dynamic Plantar Flexion

Magnetic Resonance Imaging. Oct, 2003  |  Pubmed ID: 14599535

This study compared magnetic resonance imaging (MRI) and surface electromyography (EMG) to evaluate the effect of knee angle upon plantar flexion activity in the triceps surae muscles [medial & lateral gastrocnemius (MG, LG) and the soleus (SOL)]. Two weight & height matched groups performed identical protocols, twelve (6M, 6F) in the MRI group, twelve (8M, 4F) in the EMG group. Subjects plantar flexed dynamically for 2 min at 25% of 1-repetition maximum voluntary contraction (1-RM). Exercise was performed with the knee extended (0 degrees flexion), flexed (90 degrees ), and partially flexed (45 degrees ). In the MRI group spin-echo images were acquired before and immediately following each exercise session. T(2) times, calculated at rest and after exercise by fitting the echoes to a monoexponential decay pattern with a least-squares algorithm, were compared with EMG data. In the EMG group a bipolar electrode was used to collect samples were from the MG, LG, SOL, and anterior tibialis (TA) during exercise at each knee angle, MRI also examined the peroneus (PER). At 0 degrees flexion MRI demonstrated a significant post-exercise T(2) increase in the MG (p < or = 0.001), LG (p < or = 0.001), and PER (p < or = 0.01), with no T(2) change in the SOL or TA. At 90 degrees flexion there was a significant T(2) increase in the SOL (p < or = 0.001) with no significant T(2) change in the MG, LG, PER, or TA. At 45 degrees T(2) increased significantly in the SOL (p < or = 0.001) and LG (p < or = 0.05), but not the MG, PER, or TA. EMG produced similar results with the exception that there was significant activity in the TA during the relaxation cycle of the 90 degrees protocol. We conclude that: 1) Soleus activity is measurable by MRI; and 2) MRI and EMG produce similar results from different physiological sources, and are therefore complementary tools for evaluating muscle activity.

Biophysical Basis of Magnetic Resonance Imaging of Small Animals

Methods in Enzymology. 2004  |  Pubmed ID: 15130731

Physiological Basis of Muscle Functional MRI: Predictions Using a Computer Model

Journal of Applied Physiology (Bethesda, Md. : 1985). Jan, 2005  |  Pubmed ID: 15333610

Muscle functional MRI (mfMRI) has been proposed as a tool for noninvasively measuring the metabolic and hemodynamic responses to muscle activation, but its theoretical basis remains unclear. One challenge is that it is difficult to isolate individually those variables affecting the magnitude and temporal pattern of the mfMRI response. Therefore, the purpose of this study was to develop a computer model of how physiological factors altered during exercise affect the mfMRI signal intensity time course and then predict the contributions made by individual factors. A model muscle containing 39,204 fibers was defined. The fiber-type composition and neural activation strategies were designed to represent isometric contractions of the human anterior tibialis muscle, for which published mfMRI data exist. Sustained isometric contractions at 25 and 40% maximum voluntary contraction were modeled, as were the vascular (capillary recruitment, blood oxygen extraction) and metabolic (lactate accumulation, phosphocreatine hydrolysis, pH) responses. The effects on the transverse relaxation of MRI signal were estimated, and the mfMRI signal intensity time course was measured from simulated images. The model data agreed well qualitatively with published experimental data, and at long exercise durations the quantitative agreement was also good. The model was then used to predict that NMR relaxation effects secondary to blood volume and oxygenation changes, plus the creatine kinase reaction, dominate the mfMRI time course at short exercise durations (up to approximately 45 s) and that effects secondary to glycolysis are the main contributors at later times.

Delayed Blood Reoxygenation Following Maximum Voluntary Contraction

Medicine and Science in Sports and Exercise. Feb, 2007  |  Pubmed ID: 17277589

To characterize the total hemoglobin concentration ([THb]) and oxyhemoglobin saturation (%HbO2) time courses after brief dorsiflexion maximal voluntary contractions (MVC) and to determine whether these responses varied by gender.

Dual Gradient-echo MRI of Post-contraction Changes in Skeletal Muscle Blood Volume and Oxygenation

Magnetic Resonance in Medicine. Apr, 2007  |  Pubmed ID: 17390346

Analysis of post-contraction MRI signal intensity (SI) transients may allow noninvasive studies of microvascular reactivity and blood oxygenation recovery. The purpose of this study was to determine the physiological basis for post-contraction changes in short-echo (6 ms) and long-echo (46 ms) gradient-echo (GRE) MRI signals (S(6) and S(46), respectively). Six healthy subjects were studied with the use of dual GRE MRI and near-infrared spectroscopy (NIRS). S(6), S(46), total hemoglobin concentration ([THb]), and oxyhemoglobin saturation (%HbO(2)) were measured before, during, and after 2 and 8 s dorsiflexion maximal voluntary contractions, and 5 min of proximal arterial occlusion. The changes in S(6) and [THb] after the 2-s contractions were similar to those following 8-s contractions, but changes in %HbO(2) and S(46) were greater following 8-s contractions than after the 2-s contractions. [THb] and S(6) did not change during and following 5 min of arterial occlusion, but %HbO(2) and S(46) were both significantly depressed at similar occlusion durations. Also, distance measures indicated similarity between S(6) and [THb] and between S(46) and %HbO(2). We conclude that following brief human skeletal muscle contractions, changes in S(6) primarily reflect changes in blood volume and changes in S(46) primarily reflect changes in blood oxygenation.

Quantitative Diffusion Tensor MRI-based Fiber Tracking of Human Skeletal Muscle

Journal of Applied Physiology (Bethesda, Md. : 1985). Aug, 2007  |  Pubmed ID: 17446411

Diffusion-tensor magnetic resonance imaging (DT-MRI) offers great potential for understanding structure-function relationships in human skeletal muscles. The purposes of this study were to demonstrate the feasibility of using in vivo human DT-MRI fiber tracking data for making pennation angle measurements and to test the hypothesis that heterogeneity in the orientation of the tibialis anterior (TA) muscle's aponeurosis would lead to heterogeneity in pennation angle. Eight healthy subjects (5 male) were studied. T(1)-weighted anatomical MRI and DT-MRI data were acquired of the TA muscle. Fibers were tracked from the TA's aponeurosis by following the principal eigenvector. The orientations of the aponeurosis and muscle fiber tracts in the laboratory frame of reference and the orientation of the fiber tracts with respect to the aponeurosis [i.e., the pennation angle (theta)] were determined. The muscle fiber orientations, when expressed relative to the laboratory frame of reference, did not change as functions of superior-to-inferior position. The sagittal and coronal orientations of the aponeurosis did not change in practically significant manners either, but the aponeurosis' axial orientation changed by approximately 40 degrees . As a result, the mean value for theta decreased from 16.3 (SD 6.9) to 11.4 degrees (SD 5.0) along the muscle's superior-to-inferior direction. The mean value of theta was greater in the deep than in the superficial compartment. We conclude that pennation angle measurements of human muscle made using DT-MRI muscle fiber tracking are feasible and reveal that in the foot-head direction, there is heterogeneity in the pennation properties of the human TA muscle.

Absolute and Relative Contributions of BOLD Effects to the Muscle Functional MRI Signal Intensity Time Course: Effect of Exercise Intensity

Magnetic Resonance in Medicine. Aug, 2007  |  Pubmed ID: 17654591

The time course of exercise-induced T(2)-weighted signal intensity (SI) changes contains an initial rise, early dip, and secondary rise. The purposes of this study were to test the hypothesis that the secondary rise occurs earlier during more intense contractions, and to determine the contribution of BOLD contrast to the SI changes. Eight subjects performed 90-s isometric dorsiflexion contractions at 30% and 60% of maximum voluntary contraction (MVC) while T(2)-weighted (TR/TE = 4000 ms/35 ms) images were acquired and total hemoglobin ([THb]) and oxy-Hb saturation (%HbO(2)) were measured. At 30% MVC, [THb] remained constant and %HbO(2) decreased from 66.3% (standard error [SEM] = 2.6%) to 32.4% (SEM = 6.4%). At t = 88 s, SI increased by approximately 8% and was greater than at t = 8 and 56 s. At 60% MVC, [THb] remained constant and %HbO(2) decreased from 70.2% (SEM = 2.3%) to 40.4% (SEM = 5.4%). SI increased by approximately 17% and at t = 56 and 88 s was greater than at t = 8 and 20 s. The absolute contribution of calculated BOLD effects was -1% at 30% and 60% MVC. The relative contribution was greater at 30% than at 60% MVC (up to -26% and -10%, respectively). We conclude that the secondary rise occurs earlier at 60% MVC and that the relative contribution of BOLD effects is greater during less intense contractions.

Physiological Basis of Muscle Functional MRI

Journal of Gravitational Physiology : a Journal of the International Society for Gravitational Physiology. Jul, 2007  |  Pubmed ID: 18372712

Muscle functional magnetic resonance imaging (MRI) refers to changes in the contrast properties of certain MR images that occur in exercising muscles. In part, these changes result indirectly from increased rates of cellular energy metabolism, which alter the image contrast properties by increasing the water content and by decreasing the intracellular pH. Also, increases in blood oxygen extraction cause a rapidly evolving, small, and negative contribution to signal. Together, these changes produce a complex time course of contrast changes during exercise. Analysis of this time course may provide insight into the physiology of exercising muscles. These contrast changes also provide a non-invasive method for determining the spatial pattern of muscle activation.

Diffusion Tensor MRI Assessment of Skeletal Muscle Architecture

Current Medical Imaging Reviews. 2007  |  Pubmed ID: 26236177

Diffusion-tensor magnetic resonance imaging (DTI) offers great potential for understanding structure-function relationships in skeletal muscle. The basis for these studies is that water diffuses more readily along the long axes of muscle fibers than along their transverse axes. This diffusion anisotropy can be characterized using a tensor, with the orientation of the principal eigenvalue corresponding to the long axis of the muscle fiber. These local, voxel-based directions can be combined by a fiber tracking algorithm to reconstruct the whole-muscle architecture. The fiber tracking data can be used to characterize important muscle architectural parameters, such as pennation angle, fiber length, and physiological cross-sectional area. The second and third eigenvalues convey information about muscle structural properties along the fibers' transverse axes. A comprehensive description of the sources of transverse diffusion restriction in muscle and how their relative importance may vary with the image acquisition conditions does not yet exist, but may ultimately make DTI a useful tool in studies of skeletal muscle microstructure as well. Ultimately, DTI-based longitudinal studies of changes in muscle architecture may provide insight into the relationships between structure and function in muscle, the time frames of muscle wasting, and in studying adaptations that maintain muscle functionality.

Spatial Heterogeneity in the Muscle Functional MRI Signal Intensity Time Course: Effect of Exercise Intensity

Magnetic Resonance Imaging. Oct, 2008  |  Pubmed ID: 18508220

It has previously been observed that during isometric dorsiflexion exercise, the time course of T2-weighted signal intensity (SI) changes is spatially heterogeneous. The purpose of this study was to test the hypothesis that this spatial heterogeneity would increase at higher contraction intensities. Eight subjects performed 90-s isometric dorsiflexion contractions at 30% and 60% of maximum voluntary contraction (MVC) while T2-weighted (repetition time/echo time=4000/35 ms) images were acquired. SI was measured before, during and after the contractions in regions of interest (ROIs) in the extensor digitorum longus (EDL) muscle and the deep and superficial compartments of the tibialis anterior (D-TA and S-TA, respectively). For all ROIs at 30% MVC, SI changes were similar. The maximum postcontraction SI was greater than the SI during exercise. At 60% MVC, SI changes during contraction were greater in the S-TA than in the D-TA and EDL. For the EDL and D-TA, the maximum postcontraction SI was greater than those during exercise. For the S-TA, the maximum postcontraction change was greater than the changes at t=8, 20 and 56 s but not the end-exercise value. We conclude that spatial heterogeneity increases during more intense dorsiflexion contractions, possibly reflecting regional differences in perfusion or neural activation of the muscle.

Effects of Image Noise in Muscle Diffusion Tensor (DT)-MRI Assessed Using Numerical Simulations

Magnetic Resonance in Medicine. Oct, 2008  |  Pubmed ID: 18816814

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.

Transverse Relaxation and Magnetization Transfer in Skeletal Muscle: Effect of PH

Magnetic Resonance in Medicine. Mar, 2009  |  Pubmed ID: 19097244

Exercise increases the intracellular T(2) (T(2,i)) of contracting muscles. The mechanism(s) for the T(2,i) increase have not been fully described, and may include increased intracellular free water and acidification. These changes may alter chemical exchange processes between intracellular free water and proteins. In this study, the hypotheses were tested that (a) pH changes T(2,i) by affecting the rate of magnetization transfer (MT) between free intracellular water and intracellular proteins, and (b) the magnitude of the T(2,i) effect depends on acquisition mode (localized or nonlocalized) and echo spacing. Frog gastrocnemius muscles were excised and their intracellular pH was either kept at physiological pH (7.0) or modified to model exercising muscle (pH 6.5). The intracellular transverse relaxation rate (R(2,i) = 1/T(2,i)) always decreased in the acidic muscles, but the changes were greater when measured using more rapid refocusing rates. The MT rate from the macromolecular proton pool to the free water proton pool, its reverse rate, and the spin-lattice relaxation rate of water decreased in acidic muscles. It is concluded that intracellular acidification alters the R(2,i) of muscle water in a refocusing rate-dependent manner, and that the R(2,i) changes are correlated with changes in the MT rate between macromolecules and free intracellular water.

Quantitative Assessment of DTI-based Muscle Fiber Tracking and Optimal Tracking Parameters

Magnetic Resonance in Medicine. Feb, 2009  |  Pubmed ID: 19161166

Diffusion tensor imaging-based fiber tracking in skeletal muscle has been used to reconstruct and quantify muscle architecture. In addition, the consistent pattern of muscle fiber geometry enables a quantitative assessment of the fiber tracking. This work describes a method to determine the accuracy of individual muscle fiber tracts based on the location at which the fibers terminate, the fiber path, and similarity to the neighboring fibers. In addition, the effect of different stop criteria settings on this quantitative assessment was investigated. Fiber tracking was performed on the tibialis anterior muscle of nine healthy subjects. Complete fiber tracts covered 89.4 +/- 9.6% and 75.0 +/- 15.2% of the aponeurosis area in the superficial and deep compartments, respectively. Applications of the method include the exclusion of erroneous fiber-tracking results, quantitative assessment of data set quality, and the assessment of fiber-tracking stop criteria.

DTI-based Muscle Fiber Tracking of the Quadriceps Mechanism in Lateral Patellar Dislocation

Journal of Magnetic Resonance Imaging : JMRI. Mar, 2009  |  Pubmed ID: 19243049

To determine the feasibility of using diffusion tensor MRI (DT-MRI) -based muscle fiber tracking to create biomechanical models of the quadriceps mechanism in healthy subjects and those with chronic lateral patellar dislocation (LPD).

Frontiers of Biomedical Imaging Science 2009: Workshop Report and Research Opportunities

Cancer Research. Oct, 2009  |  Pubmed ID: 19808955

Repeatability of DTI-based Skeletal Muscle Fiber Tracking

NMR in Biomedicine. Apr, 2010  |  Pubmed ID: 20099372

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.

Absence of a Significant Extravascular Contribution to the Skeletal Muscle BOLD Effect at 3 T

Magnetic Resonance in Medicine. Aug, 2010  |  Pubmed ID: 20665796

Blood oxygenation level dependent (BOLD) contrast in skeletal may reflect the contributions of both intravascular and extravascular relaxation effects. The purpose of this study was to determine the significance of the extravascular BOLD effect in skeletal muscle at 3 T. In experiments, R(2)* was measured before and during arterial occlusion under the following conditions: (1) the leg extended and rotated (to vary the capillary orientation with respect to the amplitude of static field) and (2) with the blood's signal nulled using a multiecho vascular space occupancy experiment. In the leg rotation protocol, 3 min of arterial occlusion decreased oxyhemoglobin saturation from 67% to 45% and increased R(2)* from 34.2 to 36.6 sec(-1), but there was no difference in the R(2)* response to occlusion between the extended and rotated positions. Numerical simulations of intra- and extravascular BOLD effects corresponding to these conditions predicted that the intravascular BOLD contribution to the R(2)* change was always > 50 times larger than the extravascular BOLD contribution. Blood signal nulling eliminated the change in R(2)* caused by arterial occlusion. These data indicate that under these experimental conditions, the contribution of the extravascular BOLD effect to skeletal muscle R(2)* was too small to be practically important.

Image-based Calculation of Perfusion and Oxyhemoglobin Saturation in Skeletal Muscle During Submaximal Isometric Contractions

Magnetic Resonance in Medicine. Sep, 2010  |  Pubmed ID: 20806379

The relative oxygen saturation of hemoglobin and the rate of perfusion are important physiological quantities, particularly in organs such as skeletal muscle, in which oxygen delivery and use are tightly coupled. The purpose of this study was to demonstrate the image-based calculation of the relative oxygen saturation of hemoglobin and quantification of perfusion in skeletal muscle during isometric contractions. This was accomplished by establishing an empirical relationship between the rate of radiofrequency-reversible dephasing and near-infrared spectroscopy-observed oxyhemoglobin saturation (relative oxygen saturation of hemoglobin) under conditions of arterial occlusion and constant blood volume. A calibration curve was generated and used to calculate the relative oxygen saturation of hemoglobin from radiofrequency-reversible dephasing changes measured during contraction. Twelve young healthy subjects underwent 300 s of arterial occlusion and performed isometric contractions of the dorsiflexors at 30% of maximal contraction for 120 s. Muscle perfusion was quantified during contraction by arterial spin labeling and measures of muscle T(1). Comparisons between the relative oxygen saturation of hemoglobin values predicted from radiofrequency-reversible dephasing and that measured by near-infrared spectroscopy revealed no differences between methods (P = 0.760). Muscle perfusion reached a value of 34.7 mL 100 g(-1) min(-1) during contraction. These measurements hold future promise in measuring muscle oxygen consumption in healthy and diseased skeletal muscle.

A Method for Detecting the Temporal Sequence of Muscle Activation During Cycling Using MRI

Journal of Applied Physiology (Bethesda, Md. : 1985). Mar, 2011  |  Pubmed ID: 21164153

Surface electromyography (EMG) can assess muscle recruitment patterns during cycling, but has limited applicability to studies of deep muscle recruitment and electrically stimulated contractions. We determined whether muscle recruitment timing could be inferred from MRI-measured transverse relaxation time constant (T(2)) changes and a cycle ergometer modified to vary power as a function of pedal angle. Six subjects performed 6 min of single-leg cycling under two conditions (E0°-230° and E90°-230°), which increased the power from 0°-230° and 90-230° of the pedal cycle, respectively. The difference condition produced a virtual power output from 0-180° (V0°-180°). Recruitment was assessed by integrating EMG over the pedal cycle (IEMG) and as the (post-pre) exercise T(2) change (ΔT(2)). For E0°-230°, the mean IEMG for vastus medialis and lateralis (VM/VL; 49.3 ± 3.9 mV·s; mean ± SE) was greater (P < 0.05) than that for E90°-230° (17.9 ± 1.9 mV·s); the corresponding ΔT(2) values were 8.7 ± 1.0 and 1.4 ± 0.5 ms (P < 0.05). For E0°-230° and E90°-230°, the IEMG values for biceps femoris/long head (BF(L)) were 37.7 ± 5.4 and 27.1 ± 5.6 mV·s (P > 0.05); the corresponding ΔT(2) values were 0.9 ± 0.9 and 1.5 ± 0.9 ms (P > 0.05). MRI data indicated activation of the semitendinosus and BF/short head for E0°-230° and E90°-230°. For V0°-180°, ΔT(2) was 7.2 ± 0.9 ms for VM/VL and -0.6 ± 0.6 ms for BF(L); IEMG was 31.5 ± 3.7 mV·s for VM/VL and 10.6 ± 7.0 mV·s for BF(L). MRI and EMG data indicate VM/VL activity from 0 to 180° and selected hamstring activity from 90 to 230°. Combining ΔT(2) measurements with variable loading allows the spatial and temporal patterns of recruitment during cycling to be inferred from MRI data.

Combined Diffusion and Strain Tensor MRI Reveals a Heterogeneous, Planar Pattern of Strain Development During Isometric Muscle Contraction

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. May, 2011  |  Pubmed ID: 21270344

The purposes of this study were to create a three-dimensional representation of strain during isometric contraction in vivo and to interpret it with respect to the muscle fiber direction. Diffusion tensor MRI was used to measure the muscle fiber direction of the tibialis anterior (TA) muscle of seven healthy volunteers. Spatial-tagging MRI was used to measure linear strains in six directions during separate 50% maximal isometric contractions of the TA. The strain tensor (E) was computed in the TA's deep and superficial compartments and compared with the respective diffusion tensors. Diagonalization of E revealed a planar strain pattern, with one nonzero negative strain (ε(N)) and one nonzero positive strain (ε(P)); both strains were larger in magnitude (P < 0.05) in the deep compartment [ε(N) = -40.4 ± 4.3%, ε(P) = 35.1 ± 3.5% (means ± SE)] than in the superficial compartment (ε(N) = -24.3 ± 3.9%, ε(P) = 6.3 ± 4.9%). The principal shortening direction deviated from the fiber direction by 24.0 ± 1.3° and 39.8 ± 6.1° in the deep and superficial compartments, respectively (P < 0.05, deep vs. superficial). The deviation of the shortening direction from the fiber direction was due primarily to the lower angle of elevation of the shortening direction over the axial plane than that of the fiber direction. It is concluded that three-dimensional analyses of strain interpreted with respect to the fiber architecture are necessary to characterize skeletal muscle contraction in vivo. The deviation of the principal shortening direction from the fiber direction may relate to intramuscle variations in fiber length and pennation angle.

Postmaximal Contraction Blood Volume Responses Are Blunted in Obese and Type 2 Diabetic Subjects in a Muscle-specific Manner

American Journal of Physiology. Heart and Circulatory Physiology. Aug, 2011  |  Pubmed ID: 21572006

The purpose of this study was to determine whether there are differences in postisometric contraction blood volume and oxygenation responses among groups of type 2 diabetes mellitus (T2DM), obese, and lean individuals detectable using MRI. Eight T2DM patients were individually matched by age, sex, and race to non-T2DM individuals with similar body mass index (obese) and lean subjects. Functional MRI was performed using a dual-gradient-recalled echo, echo-planar imaging sequence with a repetition time of 1 s and at two echo times (TE = 6 and 46 ms). Data were acquired before, during, and after 10-s isometric dorsiflexion contractions performed at 50 and 100% of maximal voluntary contraction (MVC) force. MRI signal intensity (SI) changes from the tibialis anterior and extensor digitorum longus muscles were plotted as functions of time for each TE. From each time course, the difference between the minimum and the maximum postcontraction SI (ΔSI) were determined for TE = 6 ms (ΔSI(6)) and TE = 46 ms (ΔSI(46)), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI(6) values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ∼56% lower ΔSI(6) than the lean individuals. Also following MVC only, the ΔSI(46) response in the EDL was lower in T2DM subjects than in lean individuals. These data suggest that skeletal muscle small vessel impairment occurs in T2DM and body mass index-matched subjects, in muscle-specific and contraction intensity-dependent manners.

Hepatic Glucagon Action is Essential for Exercise-induced Reversal of Mouse Fatty Liver

Diabetes. Nov, 2011  |  Pubmed ID: 21885872

Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver.

Diffusion-Tensor MRI Based Skeletal Muscle Fiber Tracking

Imaging in Medicine. Nov, 2011  |  Pubmed ID: 25429308

A skeletal muscle's function is strongly influenced by the internal organization and geometric properties of its fibers, a property known as muscle architecture. Diffusion-tensor magnetic resonance imaging-based fiber tracking provides a powerful tool for non-invasive muscle architecture studies, has three-dimensional sensitivity, and uses a fixed frame of reference. Significant advances have been made in muscle fiber tracking technology, including defining seed points for fiber tracking, quantitatively characterizing muscle architecture, implementing denoising procedures, and testing validity and repeatability. Some examples exist of how these data can be integrated with those from other advanced MRI and computational methods to provide novel insights into muscle function. Perspectives are offered regarding future directions in muscle diffusion-tensor imaging, including needs to develop an improved understanding for the microstructural basis for reduced and anisotropic diffusion, establish the best practices for data acquisition and analysis, and integrate fiber tracking with other physiological data.

Polynomial Fitting of DT-MRI Fiber Tracts Allows Accurate Estimation of Muscle Architectural Parameters

Magnetic Resonance Imaging. Jun, 2012  |  Pubmed ID: 22503094

Fiber curvature is a functionally significant muscle structural property, but its estimation from diffusion-tensor magnetic resonance imaging fiber tracking data may be confounded by noise. The purpose of this study was to investigate the use of polynomial fitting of fiber tracts for improving the accuracy and precision of fiber curvature (κ) measurements. Simulated image data sets were created in order to provide data with known values for κ and pennation angle (θ). Simulations were designed to test the effects of increasing inherent fiber curvature (3.8, 7.9, 11.8 and 15.3 m(-1)), signal-to-noise ratio (50, 75, 100 and 150) and voxel geometry (13.8- and 27.0-mm(3) voxel volume with isotropic resolution; 13.5-mm(3) volume with an aspect ratio of 4.0) on κ and θ measurements. In the originally reconstructed tracts, θ was estimated accurately under most curvature and all imaging conditions studied; however, the estimates of κ were imprecise and inaccurate. Fitting the tracts to second-order polynomial functions provided accurate and precise estimates of κ for all conditions except very high curvature (κ=15.3 m(-1)), while preserving the accuracy of the θ estimates. Similarly, polynomial fitting of in vivo fiber tracking data reduced the κ values of fitted tracts from those of unfitted tracts and did not change the θ values. Polynomial fitting of fiber tracts allows accurate estimation of physiologically reasonable values of κ, while preserving the accuracy of θ estimation.

MRI Techniques: a Review and Update for the Orthopaedic Surgeon

The Journal of the American Academy of Orthopaedic Surgeons. Dec, 2012  |  Pubmed ID: 23203937

MRI plays a critical role in all orthopaedic practices. A basic working knowledge of the most commonly used pulse sequences in musculoskeletal imaging and the appearance of normal tissues on those sequences is critical to confident MRI interpretation. The orthopaedic surgeon should be familiar with appropriate use of intravenous and intra-articular contrast and its limitations. Concepts key to MRI interpretation include image contrast and resolution, signal, noise, and pulse sequence. Recent advances in anatomic and functional imaging highlight the robust potential of MRI for musculoskeletal evaluation. As MRI technology evolves, the orthopaedic surgeon must stay current on these technologic advances to use this tool to its fullest potential.

Quantitative Effects of Inclusion of Fat on Muscle Diffusion Tensor MRI Measurements

Journal of Magnetic Resonance Imaging : JMRI. Nov, 2013  |  Pubmed ID: 23418124

To determine the minimum water percentage in a muscle region of interest that would allow diffusion tensor (DT-) MRI data to reflect the diffusion properties of pure muscle accurately.

Multi-parametric MRI Characterization of Inflammation in Murine Skeletal Muscle

NMR in Biomedicine. Jun, 2014  |  Pubmed ID: 24777935

Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, non-invasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi-parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT-MRI), and dynamic contrast enhanced (DCE-MRI) parameters were calculated from data acquired in a single imaging session conducted 6-8 hours following the injection of λ-carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi-exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE-MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed for other single or complex myopathy models.

Multi-parametric MRI Characterization of Healthy Human Thigh Muscles at 3.0 T - Relaxation, Magnetization Transfer, Fat/water, and Diffusion Tensor Imaging

NMR in Biomedicine. Sep, 2014  |  Pubmed ID: 25066274

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo-pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin-echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re-imaged an average of 35 days later. Pre-testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between-day intra-class correlations were observed in all quantitative indices except for the macromolecular-to-free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two-way analysis of variance revealed no significant between-day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland-Altman plots, and low repeatability coefficients were obtained for all parameters. Among-muscle differences in the quantitative MRI indices and inter-class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1 , T2 , fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters.

Evaluation of a Multiple Spin- and Gradient-echo (SAGE) EPI Acquisition with SENSE Acceleration: Applications for Perfusion Imaging in and Outside the Brain

Magnetic Resonance Imaging. Dec, 2014  |  Pubmed ID: 25179133

Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation.

Evaluation of Post-contrast Myocardial T1 in Duchenne Muscular Dystrophy Using Cardiac Magnetic Resonance Imaging

Pediatric Cardiology. Jan, 2015  |  Pubmed ID: 25070387

The objective of the study was to perform a retrospective pilot study to evaluate the potential of myocardial T1 in assessment of Duchenne muscular dystrophy (DMD) cardiomyopathy. Early identification of DMD cardiac disease, particularly myocardial fibrosis, would allow earlier therapy, potentially improving outcomes. Shortened myocardial T1 measured by cardiac MRI (CMR) is a measure of cardiac fibrosis that may be detected before late gadolinium enhancement (LGE). We hypothesized that the post-contrast T1 obtained from the Look-Locker sequences (T1LL), an easily obtainable surrogate of myocardial T1, would be abnormally shortened in DMD compared with controls. T1LL measurement was performed on 21 DMD subjects and 11 controls; to account for individual variations in gadolinium distribution, myocardial T1LL was divided by blood pool T1LL, deriving T1LL ratios. DMD subjects had shorter mean T1LL ratio than controls (1.42 vs 1.72, p < 0.001). Subset analyses in DMD subjects with normal LVEF and without LGE also demonstrated significantly shorter T1LL ratio (-0.28, p < 0.001 and -0.25, p = 0.028). Post-contrast T1LL ratio is abnormally shortened in DMD compared with controls, even in DMD patients with otherwise normal CMRs. The application of more aggressive therapy for those with shorter T1LL may favorably alter morbidity and improve mortality associated with DMD cardiomyopathy. These data suggest that further prospective evaluation of myocardial T1 will be of benefit to patients with DMD.

A Rapid Approach for Quantitative Magnetization Transfer Imaging in Thigh Muscles Using the Pulsed Saturation Method

Magnetic Resonance Imaging. Apr, 2015  |  Pubmed ID: 25839394

Quantitative magnetization transfer (qMT) imaging in skeletal muscle may be confounded by intramuscular adipose components, low signal-to-noise ratios (SNRs), and voluntary and involuntary motion artifacts. Collectively, these issues could create bias and error in parameter fitting. In this study, technical considerations related to these factors were systematically investigated, and solutions were proposed. First, numerical simulations indicate that the presence of an additional fat component significantly underestimates the pool size ratio (F). Therefore, fat-signal suppression (or water-selective excitation) is recommended for qMT imaging of skeletal muscle. Second, to minimize the effect of motion and muscle contraction artifacts in datasets collected with a conventional 14-point sampling scheme, a rapid two-parameter model was adapted from previous studies in the brain and spinal cord. The consecutive pair of sampling points with highest accuracy and precision for estimating F was determined with numerical simulations. Its performance with respect to SNR and incorrect parameter assumptions was systematically evaluated. QMT data fitting was performed in healthy control subjects and polymyositis patients, using both the two- and five-parameter models. The experimental results were consistent with the predictions from the numerical simulations. These data support the use of the two-parameter modeling approach for qMT imaging of skeletal muscle as a means to reduce total imaging time and/or permit additional signal averaging.

Noninvasive Measurements of Glycogen in Perfused Mouse Livers Using Chemical Exchange Saturation Transfer NMR and Comparison to (13)C NMR Spectroscopy

Analytical Chemistry. Jun, 2015  |  Pubmed ID: 25946616

Liver glycogen represents an important physiological form of energy storage. It plays a key role in the regulation of blood glucose concentrations, and dysregulations in hepatic glycogen metabolism are linked to many diseases including diabetes and insulin resistance. In this work, we develop, optimize, and validate a noninvasive protocol to measure glycogen levels in isolated perfused mouse livers using chemical exchange saturation transfer (CEST) NMR spectroscopy. Model glycogen solutions were used to determine optimal saturation pulse parameters which were then applied to intact perfused mouse livers of varying glycogen content. Glycogen measurements from serially acquired CEST Z-spectra of livers were compared with measurements from interleaved natural abundance (13)C NMR spectra. Experimental data revealed that CEST-based glycogen measurements were highly correlated with (13)C NMR glycogen spectra. Monte Carlo simulations were then used to investigate the inherent (i.e., signal-to-noise-based) errors in the quantification of glycogen with each technique. This revealed that CEST was intrinsically more precise than (13)C NMR, although in practice may be prone to other errors induced by variations in experimental conditions. We also observed that the CEST signal from glycogen in liver was significantly less than that observed from identical amounts in solution. Our results demonstrate that CEST provides an accurate, precise, and readily accessible method to noninvasively measure liver glycogen levels and their changes. Furthermore, this technique can be used to map glycogen distributions via conventional proton magnetic resonance imaging, a capability universally available on clinical and preclinical magnetic resonance imaging (MRI) scanners vs (13)C detection, which is limited to a small fraction of clinical-scale MRI scanners.

Anisotropic Smoothing Improves DT-MRI-Based Muscle Fiber Tractography

PloS One. 2015  |  Pubmed ID: 26010830

To assess the effect of anisotropic smoothing on fiber tracking measures, including pennation angle, fiber tract length, and fiber tract number in the medial gastrocnemius (MG) muscle in healthy subjects using diffusion-weighted magnetic resonance imaging (DW-MRI).

Matching of Postcontraction Perfusion to Oxygen Consumption Across Submaximal Contraction Intensities in Exercising Humans

Journal of Applied Physiology (Bethesda, Md. : 1985). Aug, 2015  |  Pubmed ID: 26066829

Studying the magnitude and kinetics of blood flow, oxygen extraction, and oxygen consumption at exercise onset and during the recovery from exercise can lead to insights into both the normal control of metabolism and blood flow and the disturbances to these processes in metabolic and cardiovascular diseases. The purpose of this study was to examine the on- and off-kinetics for oxygen delivery, extraction, and consumption as functions of submaximal contraction intensity. Eight healthy subjects performed four 1-min isometric dorsiflexion contractions, with two at 20% MVC and two at 40% MVC. During one contraction at each intensity, relative perfusion changes were measured by using arterial spin labeling, and the deoxyhemoglobin percentage (%HHb) was estimated using the spin- and gradient-echo sequence and a previously published empirical calibration. For the whole group, the mean perfusion did not increase during contraction. The %HHb increased from ∼28 to 38% during contractions of each intensity, with kinetics well described by an exponential function and mean response times (MRTs) of 22.7 and 21.6 s for 20 and 40% MVC, respectively. Following contraction, perfusion increased ∼2.5-fold. The %HHb, oxygen consumption, and perfusion returned to precontraction levels with MRTs of 27.5, 46.4, and 50.0 s, respectively (20% MVC), and 29.2, 75.3, and 86.0 s, respectively (40% MVC). These data demonstrate in human subjects the varied recovery rates of perfusion and oxygen consumption, along with the similar rates of %HHb recovery, across these exercise intensities.

Comparison of Muscle BOLD Responses to Arterial Occlusion at 3 and 7 Tesla

Magnetic Resonance in Medicine. Mar, 2016  |  Pubmed ID: 25884888

The purpose of this study was to determine the feasibility of muscle BOLD (mBOLD) imaging at 7 Tesla (T) by comparing the changes in R2* of muscle at 3 and 7T in response to a brief period of tourniquet-induced ischemia.

Increased Myocardial Native T1 and Extracellular Volume in Patients with Duchenne Muscular Dystrophy

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2016  |  Pubmed ID: 26795569

Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE).

Skeletal Muscle Diffusion Tensor-MRI Fiber Tracking: Rationale, Data Acquisition and Analysis Methods, Applications and Future Directions

NMR in Biomedicine. Jun, 2016  |  Pubmed ID: 27257975

The mechanical functions of muscles involve the generation of force and the actuation of movement by shortening or lengthening under load. These functions are influenced, in part, by the internal arrangement of muscle fibers with respect to the muscle's mechanical line of action. This property is known as muscle architecture. In this review, we describe the use of diffusion tensor (DT)-MRI muscle fiber tracking for the study of muscle architecture. In the first section, the importance of skeletal muscle architecture to function is discussed. In addition, traditional and complementary methods for the assessment of muscle architecture (brightness-mode ultrasound imaging and cadaver analysis) are presented. Next, DT-MRI is introduced and the structural basis for the reduced and anisotropic diffusion of water in muscle is discussed. The third section discusses issues related to the acquisition of skeletal muscle DT-MRI data and presents recommendations for optimal strategies. The fourth section discusses methods for the pre-processing of DT-MRI data, the available approaches for the calculation of the diffusion tensor and the seeding and propagating of fiber tracts, and the analysis of the tracking results to measure structural properties pertinent to muscle biomechanics. Lastly, examples are presented of how DT-MRI fiber tracking has been used to provide new insights into how muscles function, and important future research directions are highlighted. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetic Resonance Imaging of Skeletal Muscle Disease

Handbook of Clinical Neurology. 2016  |  Pubmed ID: 27430444

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multifaceted pathology. The goals of this chapter are to describe and evaluate the use of quantitative magnetic resonance imaging (MRI) methods to characterize muscle pathology. The following criteria are used for this evaluation: objective measurement of continuously distributed variables; clear and well-understood relationship to the pathology of interest; sensitivity to improvement or worsening of clinical status; and the measurement properties of accuracy and precision. Two major classes of MRI methods meet all of these criteria: (1) MRI methods for measuring muscle contractile volume or cross-sectional area by combining structural MRI and quantitative fat-water MRI; and (2) an MRI method for characterizing the edema caused by inflammation, the measurement of the transverse relaxation time constant (T2). These methods are evaluated with respect to the four criteria listed above and examples from neuromuscular disorders are provided. Finally, these methods are summarized and synthesized and recommendations for additional quantitative MRI developments are made.

Statement of Retraction. Hepatic Glucagon Action Is Essential for Exercise-Induced Reversal of Mouse Fatty Liver. Diabetes 2011;60:2720-2729. DOI: 10.2337/db11-0455

Diabetes. Aug, 2016  |  Pubmed ID: 27456624

FloWave.US: Validated, Open-source, and Flexible Software for Ultrasound Blood Flow Analysis

Journal of Applied Physiology (Bethesda, Md. : 1985). Oct, 2016  |  Pubmed ID: 27516540

Automated software improves the accuracy and reliability of blood velocity, vessel diameter, blood flow, and shear rate ultrasound measurements, but existing software offers limited flexibility to customize and validate analyses. We developed FloWave.US-open-source software to automate ultrasound blood flow analysis-and demonstrated the validity of its blood velocity (aggregate relative error, 4.32%) and vessel diameter (0.31%) measures with a skeletal muscle ultrasound flow phantom. Compared with a commercial, manual analysis software program, FloWave.US produced equivalent in vivo cardiac cycle time-averaged mean (TAMean) velocities at rest and following a 10-s muscle contraction (mean bias <1 pixel for both conditions). Automated analysis of ultrasound blood flow data was 9.8 times faster than the manual method. Finally, a case study of a lower extremity muscle contraction experiment highlighted the ability of FloWave.US to measure small fluctuations in TAMean velocity, vessel diameter, and mean blood flow at specific time points in the cardiac cycle. In summary, the collective features of our newly designed software-accuracy, reliability, reduced processing time, cost-effectiveness, and flexibility-offer advantages over existing proprietary options. Further, public distribution of FloWave.US allows researchers to easily access and customize code to adapt ultrasound blood flow analysis to a variety of vascular physiology applications.

Post-contractile BOLD Contrast in Skeletal Muscle at 7 T Reveals Inter-individual Heterogeneity in the Physiological Responses to Muscle Contraction

NMR in Biomedicine. Dec, 2016  |  Pubmed ID: 27753155

Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (TR : 1000 and 2500 ms) to determine the potential of T1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two TR values (3.8 ± 0.9 versus 4.0 ± 0.6% for TR  = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction.

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