Muscle Blood Oxygen Level-dependent Research Articles

Denoising of the gradient artifact present in simultaneous studies of muscle blood oxygen level dependent (BOLD) signal and electromyography (EMG)

The MR-induced gradient artifact affects EMG recordings during simultaneous muscle BOLD/EMG acquisitions. However, no dedicated hardware can remove the gradient artifact easily, and alternative methods are expensive and time-consuming. This study aimed to develop three denoising methods requiring different processing levels and MR-compatible hardware.At two time points, surface EMG was recorded from the lower leg of 6 participants (50:50 sex ratio, age = 26.24.6 yrs., height = 173.59.2 cm, weight = 71.511.4 kg) using a plantar flexion-based block design consisting of 30s of rest followed by 30s of flexion for 5 min, under three conditions: inside the MRI bore, with and without a BOLD sequence (3 T, BOLD sequence, GRE EPI, 10 slices, 64×64 matrix, 2 mm thickness, and TE/TR/flip = 35/3000 ms/70), and outside the MRI environment. Simultaneous BOLD/EMG recordings were denoised using average artifact subtraction with three methods of artifact template creation, each having varying timing and hardware requirements. Method M1 builds the artifact template by recording the scanner triggers coming from the MRI; M2 creates the artifact template with a constant artifact period computed as TR/[number of slices]; M3 estimates the artifact template by looking at the periodicity of the gradient artifact located in the EMG recordings. Following postprocessing, SNR analysis was performed, comparing rest-to-flexion periods, to assess the efficacy of denoising methods and to compare differences between conditions.Linear mixed-effects models showed no significant differences in the mean SNR between denoising methods (p = 0.656). Furthermore, EMG SNR measurements were significantly affected by the magnetic environment (p < 0.05) but not by muscle fatigue over time (p = 0.975).EMG recordings contaminated with gradient artifacts during simultaneous BOLD/EMG can be efficiently denoised using all proposed methods, with two methods requiring no extra hardware. With minimal post-processing, EMG can easily be performed during muscle BOLD MRI studies.

Dynamic magnetic resonance measurements of calf muscle oxygenation and energy metabolism in peripheral artery disease.

BackgroundClinical assessments of peripheral artery disease (PAD) severity are insensitive to pathophysiological changes in muscle tissue oxygenation and energy metabolism distal to the affected artery.PurposeTo quantify the blood oxygenation level‐dependent (BOLD) response and phosphocreatine (PCr) recovery kinetics on a clinical MR system during a single exercise‐recovery session in PAD patients.Study TypeCase–control study.SubjectsFifteen Fontaine stage II patients, and 18 healthy control subjectsField Strength/SequenceInterleaved dynamic multiecho gradient‐echo 1H T2* mapping and adiabatic pulse‐acquire 31P‐MR spectroscopy at 3T.AssessmentBlood pressure in the arms and ankles were measured to determine the ankle‐brachial index (ABI). Subjects performed a plantar flexion exercise‐recovery protocol. The gastrocnemius and soleus muscle BOLD responses were characterized using the T2* maps. High‐energy phosphate metabolite concentrations were quantified by fitting the series of 31P‐MR spectra. The PCr recovery time constant (τPCr) was derived as a measure of in vivo mitochondrial oxidative capacity.Statistical TestsComparisons between groups were performed using two‐sided Mann–Whitney U‐tests. Relations between variables were assessed by Pearson's r correlation coefficients.ResultsThe amplitude of the functional hyperemic BOLD response in the gastrocnemius muscle was higher in PAD patients compared with healthy subjects (–3.8 ± 1.4% vs. –1.4 ± 0.3%; P < 0.001), and correlated with the ABI (r = 0.79; P < 0.001). PCr recovery was slower in PAD patients (τPCr = 52.0 ± 13.5 vs. 30.3 ± 9.7 sec; P < 0.0001), and correlated with the ABI (r = –0.64; P < 0.001). Moreover, τPCr correlated with the hyperemic BOLD response in the gastrocnemius muscle (r = –0.66; P < 0.01).Data ConclusionMR readouts of calf muscle tissue oxygenation and high‐energy phosphate metabolism were acquired essentially simultaneously during a single exercise‐recovery session. A pronounced hypoxia‐triggered vasodilation in PAD is associated with a reduced mitochondrial oxidative capacity. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:98–107.

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 2500ms) 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 2500ms, 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.

Safe MRI-Compatible electrical muscle stimulation (EMS) system.

To develop an inexpensive magnetic resonance imaging (MRI)-compatible electrical muscle stimulation (EMS) unit and test it for safety and efficacy. A simple MRI-compatible EMS device was developed using radiofrequency (RF) translucent electrodes at 3T. RF heating concerns were assessed using optical temperature measurements at electrode sites, during scanning of a phantom. EMS efficacy and consistency was investigated through in vivo (n = 5) measures of 31 P-MRS phosphocreatine (PCr) reduction, and altered blood oxygen level-dependent (BOLD) signal and the results were compared to effects from equivalent voluntary effort on the same subjects. The presence of an EMS pulse did not interfere with the T2 * signal in a phantom. However, signal-to-noise ratio (SNR) was reduced by 70% at electrode sites, but only by 10% 4 cm distally. Under RF intense conditions, the temperature at the electrode site increased by only 4.7°C over a 16-minute time span. In vivo muscle stimulation resulted in 13.5 ± 1.8% reduction in PCr, which was not significantly (P < 0.195) different from voluntary contraction. Reproducible muscle BOLD signal changes following EMS were noted, with a maximal increase of 10.0 ± 2.6% seen in the central soleus. For soleus and gastrocnemius compartments, EMS produced significantly higher BOLD signal change compared to voluntary contraction (P < 0.05). A safe and inexpensive MRI-compatible EMS unit can be easily built for evaluating muscle function and metabolism within a 3T MRI scanner. Clinical applications might include evaluating skeletal muscle function in patients with limited or absent voluntary skeletal motor function or inadequate exercise capacity. J. Magn. Reson. Imaging 2016;44:1530-1538.

Dynamic Blood Oxygen Level-dependent MR Imaging of Muscle: Comparison of Postocclusive Reactive Hyperemia in Young Smokers and Nonsmokers.

The role of early stage functional assessment of muscle blood flow response (MFR) by dynamic muscle blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is unknown. We investigated the effect of smoking on vascular function according to MFR derived from dynamic muscle BOLD MR imaging during postocclusive reactive hyperemia in young smokers and nonsmokers. Sixteen healthy male volunteers (8 smokers, 8 nonsmokers; mean age, 30.4 ± 4.6 years) underwent BOLD MR imaging of the left calf muscle. During reactive hyperemia provoked by a cuff-compression technique, we measured muscle BOLD (mB) using a 3-tesla single-shot multi-echo gradient-echo echo-planar imaging sequence. The 2 key mB variables in the reactive hyperemic phase that we studied were times to half hyperemic peak (T(1/2peak)) and peak (TTP), each measured from cuff deflation. We used the Welch test to assess differences in these between smokers and nonsmokers. T(1/2peak) and TTP were significantly longer in smokers (P < 0.05) in reactive hyperemia. T(1/2peak) was 13.8 ± 5.4 s in smokers and 7.6 ± 1.5 s in nonsmokers, and TTP was 67.5 ± 18.8 s in smokers and 45.4 ± 7.1 s in nonsmokers. Dynamic BOLD MR imaging of calf muscle during postocclusive reactive hyperemia demonstrated statistically significant differences in T(1/2peak) and TTP between young smokers and nonsmokers, indicating the presence of early stage smoking-related deterioration in MFR.

Automatic model‐based analysis of skeletal muscle BOLD‐MRI in reactive hyperemia

To propose a quantitative model for a reliable and operator independent estimation of parameters describing blood oxygen-level dependent (BOLD) MRI time course in calf muscles during reactive hyperemia. Echo planar imaging-based BOLD-MRI of the human calf were acquired during and after cuff-induced ischemia of the leg. Regions of interest were drawn in soleus, gastrocnemius and tibialis anterior muscles. A gamma-variate plus a sigmoidal function were fitted to the reactive hyperemia time courses and parameters including time to peak (TTP), hyperemic peak value (HPV), peak area, and peak width were calculated. In addition, the TTP and HPV parameters were estimated manually by two operators to validate the reliability of the fitting procedure. The model function was fitted successfully to all data with a minimum reduced R(2) around 0.9. The in vivo results were in agreement with manually determined values (r ≥ 0.69), although significant inter-operator differences were observed. The proposed method allows for rapid, operator independent and robust quantification of muscle BOLD signal during reactive hyperemia. The model worked equally well over a wide range of imaging parameters and data quality. This approach should contribute significantly to the standardization of skeletal muscle BOLD-MRI, an important step toward its clinical application.

Skeletal muscle BOLD MRI: From underlying physiological concepts to its usefulness in clinical conditions

Blood oxygenation-level dependent (BOLD) MRI has gained particular attention in functional brain imaging studies, where it can be used to localize areas of brain activation with high temporal resolution. To a higher degree than in the brain, skeletal muscles show extensive but transient alterations of blood flow between resting and activation state. Thus, there has been interest in the application of the BOLD effect in studying the physiology of skeletal muscles (healthy and diseased) and its possible application to clinical practice. This review outlines the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation of physiological and pathological alterations in the peripheral limb perfusion, such as in peripheral arterial occlusive disease. Moreover, current knowledge is summarized regarding the complex mechanisms eliciting BOLD effect in skeletal muscle. We describe technical fundaments of the procedure that should be taken into account when performing skeletal muscle BOLD MRI, including the most often applied paradigms to provoke BOLD signal changes and key parameters of the resulting time courses. Possible confounding effects in muscle BOLD imaging studies, like age, muscle fiber type, training state, and drug effects are also reviewed in detail.

Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD) MRI

Blood-oxygenation-level-dependent (BOLD) contrast in magnetic resonance (MR) imaging of skeletal muscle mainly depends on changes of oxygen saturation in the microcirculation. In recent years, an increasing number of studies have evaluated the clinical relevance of skeletal muscle BOLD MR imaging in vascular diseases, such as peripheral arterial occlusive disease, diabetes mellitus, and chronic compartment syndrome. BOLD imaging combines the advantages of MR imaging, i.e., high spatial resolution, no exposure to ionizing radiation, with functional information of local microvascular perfusion. Due to intrinsic contrast provoked via changes in hemoglobin oxygen saturation, it is a safe and easy applicable procedure on standard whole-body MR devices. Therefore, BOLD MR imaging of skeletal muscle is a potential new diagnostic tool in the clinical evaluation of vascular, inflammatory, and muscular pathologies. Our review focuses on the current evidence concerning the use of BOLD MR imaging of skeletal muscle under pathological conditions and highlights ways for future clinical and scientific applications.

Blood oxygenation level‐dependent (BOLD) MRI of human skeletal muscle at 1.5 and 3 T

To evaluate the dependence of skeletal muscle blood oxygenation level-dependent (BOLD) effect and time course characteristics on magnetic field strength in healthy volunteers using an ischemia/reactive hyperemia paradigm. Two consecutive skeletal muscle BOLD magnetic resonance imaging (MRI) measurements in eight healthy volunteers were performed on 1.5 T and 3.0 T whole-body MRI scanners. For both measurements a fat-saturated multi-shot multiecho gradient-echo EPI sequence was applied. Temporary vascular occlusion was induced by suprasystolic cuff compression of the thigh. T2 time courses were obtained from two different calf muscles and characterized by typical curve parameters. Ischemia- and hyperemia-induced changes in R2 (ΔR2) were calculated for both muscles in each volunteer at the two field strengths. Skeletal muscle BOLD changes are dependent on magnetic field strength as the ratio ΔR2(3.0 T)/ΔR2(1.5 T) was found to range between 1.6 and 2.2. Regarding time course characteristics, significantly higher relative T2 changes were found in both muscles at 3.0 T. The present study shows an approximately linear field strength dependence of ΔR2 in the skeletal muscle in response to ischemia and reactive hyperemia. Using higher magnetic fields is advisable for future BOLD imaging studies of peripheral limb pathologies.

Impaired skeletal muscle microcirculation in systemic sclerosis

IntroductionMuscle symptoms in systemic sclerosis (SSc) may originate from altered skeletal muscle microcirculation, which can be investigated by means of blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI).MethodsAfter ethics committee approval and written consent, 11 consecutive SSc patients (5 men, mean age 52.6 years, mean SSc disease duration 5.4 years) and 12 healthy volunteers (4 men, mean age 45.1 years) were included. Subjects with peripheral arterial occlusive disease were excluded. BOLD MRI was performed on calf muscles during cuff-induced ischemia and reactive hyperemia, using a 3-T whole-body scanner (Verio, Siemens, Erlangen, Germany) and fat-suppressed single-short multi-echo echo planar imaging (EPI) with four different effective echo times. Muscle BOLD signal time courses were obtained for gastrocnemius and soleus muscles: minimal hemoglobin oxygen saturation (T2*min) and maximal T2* values (T2*max), time to T2* peak (TTP), and slopes of oxygen normalization after T2* peaking.ResultsThe vast majority of SSc patients lacked skeletal muscle atrophy, weakness or serum creatine kinase elevation. Nevertheless, more intense oxygen desaturation during ischemia was observed in calf muscles of SSc patients (mean T2*min -15.0%), compared with controls (-9.1%, P = 0.02). SSc patients also had impaired oxygenation during hyperemia (median T2*max 9.2% vs. 20.1%, respectively, P = 0.007). The slope of muscle oxygen normalization was significantly less steep and prolonged (TTP) in SSc patients (P<0.001 for both). Similar differences were found at a separate analysis of gastrocnemius and soleus muscles, with most pronounced impairment in the gastrocnemius.ConclusionsBOLD MRI demonstrates a significant impairment of skeletal muscle microcirculation in SSc.

Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.

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.

Blood Oxygenation Level-Dependent MRI of the Skeletal Muscle during Ischemia in Patients with Peripheral Arterial Occlusive Disease

To compare calf muscle Blood Oxygenation Level-Dependent (BOLD) response during ischemia in patients suffering from peripheral arterial occlusive disease (PAOD) and age-matched non-PAOD subjects. PAOD patients with symptoms of intermittent calf claudication and an age-matched control group underwent T 2*-weighted single-shot multi-echo planar imaging on a whole-body MR scanner at 1.5 T. The muscle BOLD signal in the calf was acquired during 60 sec of baseline and 240 sec of ischemia induced by cuff compression. T 2* time courses in four calf muscles were evaluated. Significant differences in the mean T 2* values were noted after 150 sec of measurement (p < 0.05). Patients with PAOD revealed a significantly reduced BOLD signal decrease compared to an age-matched control group. Potential cause for this observation may be changes in the structure and/or the metabolic turnover of the muscle in PAOD patients.

Calf Muscles at Blood Oxygen Level–Dependent MR Imaging: Aging Effects at Postocclusive Reactive Hyperemia

To prospectively investigate age-related changes in muscle reperfusion by using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging of the calf in young and elderly healthy volunteers during postocclusive reactive hyperemia. Institutional review board approval and informed consent were obtained. Eleven healthy elderly (mean age, 64.0 years +/- 6.4 [standard deviation]; six men, five women) and 17 healthy young volunteers (mean age, 30.3 years +/- 6.5; seven men, 10 women) underwent muscle BOLD MR imaging of the calf. A fat-suppressed T2*-weighted single-shot multiecho echo-planar imaging sequence was used. Temporary vascular occlusion was induced with suprasystolic cuff compression of the thigh. T2* time courses of the muscle BOLD MR signal intensity were obtained from four calf muscles and were characterized by the following curve parameters: hyperemia peak value, time to peak, and T2* end value after 360 seconds of hyperemia. Differences in these parameters between the two cohorts were assessed by using a Student t test. Considerably lower T2* maxima were observed in the elderly group during hyperemia (P < .005), with a mean hyperemia peak value of 13.1% +/- 3.0 compared with 18.9% +/- 4.8 in young healthy adults. Peaking occurred earlier in the elderly group (P < .05), with a mean time to peak of 32.2 seconds +/- 10.6 compared with 43.1 seconds +/- 10.7 in young adults. Furthermore, the elderly group had a significantly slower decrease of the muscle BOLD signal after the hyperemia peak (P < .001), which led to a higher end value of 8.6% +/- 3.0 compared with 2.6% +/- 2.1 in the young group. BOLD MR imaging results of the calf demonstrated statistically significant age-dependent differences in the rate, intensity, and recovery of the postocclusive muscle BOLD signal.

Blood Oxygenation Level–Dependent Magnetic Resonance Imaging of the Skeletal Muscle in Patients With Peripheral Arterial Occlusive Disease

Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has been used to measure T2* changes in skeletal muscle tissue of healthy volunteers. The BOLD effect is assumed to primarily reflect changes in blood oxygenation at the tissue level. We compared the calf muscle BOLD response of patients with peripheral arterial occlusive disease (PAOD) to that of an age-matched non-PAOD group during postischemic reactive hyperemia. PAOD patients (n=17) with symptoms of intermittent calf claudication and an age-matched non-PAOD group (n=11) underwent T2*-weighted single-shot multiecho planar imaging on a whole-body magnetic resonance scanner at 1.5 T. Muscle BOLD MRI of the calf was performed during reactive hyperemia provoked by a cuff-compression paradigm. T2* maps were generated with an automated fitting procedure. Maximal T2* change (deltaT2*(max)) and time to peak to reach deltaT2*(max) for gastrocnemius, soleus, tibial anterior, and peroneal muscle were evaluated. Compared with the non-PAOD group, patients revealed significantly lower deltaT2*(max)-values, with a mean of 7.3+/-5.3% versus 13.1+/-5.6% (P<0.001), and significantly delayed time-to-peak values, with a mean of 109.3+/-79.3 versus 32.2+/-13.3 seconds (P<0.001). T2* time courses of the muscle BOLD MRI signal during postocclusive reactive hyperemia revealed statistically significant differences in the key parameters (deltaT2*(max); time to peak) in PAOD patients compared with age-matched non-PAOD controls.