Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.

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.

Comparison of muscle BOLD responses to arterial occlusion at 3 and 7 Tesla.

PURPOSE: 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. METHODS: Eight subjects (three male), aged 29.5 ± 6.1 years (mean ± standard deviation, SD), 167.0 ± 10.6 cm tall with a body mass of 62.0 ± 18.0 kg, participated in the study. Subjects reported to the lab on four separate occasions including a habituation session, two MRI scans, and in a subset of subjects, a session during which changes in blood flow and blood oxygenation were quantified using Doppler ultrasound (U/S) and near-infrared spectroscopy (NIRS) respectively. For statistical comparisons between 3 and 7T, R2* rate constants were calculated as R2* = 1/T2*. RESULTS: The mean preocclusion R2* value was greater at 7T than at 3T (60.16 ± 2.95 vs. 35.17 ± 0.35 s(-1), respectively, P < 0.001). Also, the mean ΔR2 *END and ΔR2*POST values were greater for 7T than for 3T (-2.36 ± 0.25 vs. -1.24 ± 0.39 s(-1), respectively, Table 1). CONCLUSION: Muscle BOLD contrast at 7T is as much as six-fold greater than at 3T. In addition to providing greater SNR and CNR, 7T mBOLD studies may offer further advantages in the form of greater sensitivity to pathological changes in the muscle microcirculation.

Matching of postcontraction perfusion to oxygen consumption across submaximal contraction intensities in exercising humans.

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.

Anisotropic Smoothing Improves DT-MRI-Based Muscle Fiber Tractography.

PURPOSE: 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). MATERIALS AND METHODS: 3T DW-MRI data were used for muscle fiber tractography in the MG of healthy subjects. Anisotropic smoothing was applied at three levels (5%, 10%, 15%), and pennation angle, tract length, fiber tract number, fractional anisotropy, and principal eigenvector orientation were quantified for each smoothing level. RESULTS: Fiber tract length increased with pre-fiber tracking smoothing, and local heterogeneities in fiber direction were reduced. However, pennation angle was not affected by smoothing. CONCLUSION: Modest anisotropic smoothing (10%) improved fiber-tracking results, while preserving structural features.

Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.

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.

Combined diffusion and strain tensor MRI reveals a heterogeneous, planar pattern of strain development during isometric muscle contraction.

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.

A method for detecting the temporal sequence of muscle activation during cycling using MRI.

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.

Image-based calculation of perfusion and oxyhemoglobin saturation in skeletal muscle during submaximal isometric contractions.

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.

Absence of a significant extravascular contribution to the skeletal muscle BOLD effect at 3 T.

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.

Effects of electrical stimulation parameters on fatigue in skeletal muscle.

STUDY DESIGN: Experimental laboratory study. OBJECTIVES: The primary purpose was to investigate the independent effects of current amplitude, pulse duration, and current frequency on muscle fatigue during neuromuscular electrical stimulation (NMES). A second purpose was to determine if the ratio of the evoked torque to the activated area could explain muscle fatigue. BACKGROUND: Parameters of NMES have been shown to differently affect the evoked torque and the activated area. The efficacy of NMES is limited by the rapid onset of muscle fatigue. METHODS AND MEASURES: Seven healthy participants underwent 4 NMES protocols that were randomly applied to the knee extensor muscle group. The NMES protocols were as follows: standard protocol (Std), defined as 100-Hz, 450-micros pulses and amplitude set to evoke 75% of maximal voluntary isometric torque (MVIT); short pulse duration protocol (SP), defined as 100-Hz, 150-micros pulses and amplitude set to evoke 75% of MVIT; low-frequency protocol (LF), defined as 25-Hz, 450-micros pulses and amplitude set to evoke 75% of MVIT; and low-amplitude protocol (LA), defined as 100-Hz, 450-micros pulses and amplitude set to evoke 45% of MVIT. The peak torque was measured at the start and at the end of the 4 protocols, and percent fatigue was calculated. The outcomes of the 4 NMES protocols on the initial peak torque and activated cross-sectional area were recalculated from a companion study to measure torque per active area. RESULTS: Decreasing frequency from 100 to 25 Hz decreased fatigue from 76% to 39%. Decreasing the amplitude and pulse duration resulted in no change of muscle fatigue. Torque per active area accounted for 57% of the variability in percent fatigue between Std and LF protocols. CONCLUSIONS: Altering the amplitude of the current and pulse duration does not appear to influence the percent fatigue in NMES. Lowering the stimulation frequency results in less fatigue, by possibly reducing the evoked torque relative to the activated muscle area.

High specific torque is related to lengthening contraction-induced skeletal muscle injury.

Animal models implicate multiple mechanical factors in the initiation of exercise-induced muscle injury. Muscle injury has been widely studied in humans, but few data exist regarding the underlying cause of muscle injury. This study sought to examine the role of torque per active muscle volume in muscle injury. Eight subjects performed 80 electrically stimulated [via electromyostimulation (EMS)] eccentric contractions of the right and left quadriceps femoris (QF) through an 80 degrees arc at 120 degrees /s. Specific torque was varied by applying 25-Hz EMS to one thigh and 100-Hz EMS to the contralateral thigh. Transverse relaxation time (T2) magnetic resonance images of the QF were collected before and 3 days after the eccentric exercise bouts. Injury was assessed via changes in isometric force and ratings of soreness over the course of 14 days after exercise and by determining changes in T2 and muscle volume 3 days after exercise. The 100-Hz EMS induced greater force loss (P < 0. 05), soreness (P < 0.05), change in muscle volume (P = 0.03), and volume of muscle demonstrating increased T2 (P = 0.005) than the 25-Hz EMS. In addition, injury was found to be similar across the QF in all but the most proximal regions of the QF. Our findings suggest that, in humans, high torque per active volume during lengthening muscle contractions is related to muscle injury.

Oxygen cost of dynamic or isometric exercise relative to recruited muscle mass.

BACKGROUND: Oxygen cost of different muscle actions may be influenced by different recruitment and rate coding strategies. The purpose of this study was to account for these strategies by comparing the oxygen cost of dynamic and isometric muscle actions relative to the muscle mass recruited via surface electrical stimulation of the knee extensors. METHODS: Comparisons of whole body pulmonary delta VO2 were made in seven young healthy adults (1 female) during 3 minutes of dynamic or isometric knee extensions, both induced by surface electrical stimulation. Recruited mass was quantified in T2 weighted spin echo magnetic resonance images. RESULTS: The delta VO2 for dynamic muscle actions, 242 +/- 128 ml x min(-1) (mean +/- SD) was greater (p = 0.003) than that for isometric actions, 143 +/- 99 ml x min(-1). Recruited muscle mass was also greater (p = 0.004) for dynamic exercise, 0.716 +/- 282 versus 0.483 +/- 0.139 kg. The rate of oxygen consumption per unit of recruited muscle (VO2(RM)) was similar in dynamic and isometric exercise (346 +/- 162 versus 307 +/- 198 ml x kg(-1) x min(-1); p = 0.352), but the VO2(RM) calculated relative to initial knee extensor torque was significantly greater during dynamic exercise 5.1 +/- 1.5 versus 3.6 +/- 1.6 ml x kg(-1) x Nm(-1) x min(-1) (p = 0.019). CONCLUSION: These results are consistent with the view that oxygen cost of dynamic and isometric actions is determined by different circumstances of mechanical interaction between actin and myosin in the sarcomere, and that muscle recruitment has only a minor role.

Determining the extent of neural activation during maximal effort.

PURPOSE: The purpose of this study was to compare the extent of neural activation assessed by the central activation ratio (CAR) versus activation estimated from T2 magnetic resonance imaging (MRI) and neuromuscular electrical stimulation (NMES). METHODS: Seven college-age individuals volunteered for this study. CAR was determined by manually superimposing a train of NMES (50 Hz, 450-mus biphasic pulses) for 1 s during a maximal voluntary effort. The MRI-NMES method assessed activation by stimulating the knee extensors for 3 min in a 2 s on, 2 s off cycle. T2 MR images were taken at rest and after NMES was administered. Theoretical maximal torque (TMT) of the knee extensors was calculated based on the MRI-NMES activation data. The TMT was then divided by the maximal voluntary isometric contraction (MVIC) of each subject to determine the extent of neural activation during a MVIC. RESULTS: The results for CAR reveal the percent activation (mean +/- SD) of the quadriceps femoris during a MVIC was 92 +/- 7% for the right thigh and 96 +/- 4% for the left thigh. The MRI-NMES method estimated that MVIC could be achieved if 75 +/- 14% of the knee extensors on the right thigh and 74 +/- 14% on the left thigh were activated. These results are similar to findings that showed MVIC could be achieved by stimulating 71% of the knee extensors. CONCLUSIONS: We conclude that CAR overestimates the extent of neural activation during an MVIC because the 3D shape of the thigh is altered. This will change electric current flow to the axonal motor neuron branches and limit the artificially evoked torque, thereby resulting in an overestimation of CAR.