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Introduction: Phantoms mimicking tissue motion have become a valuable tool for quality control in various fields of medical physics including lung phantoms for image-guided radiotherapy and functional imaging in nuclear medicine or magnetic resonance imaging (MRI) in the body. In MRI, precise kinematic models are more difficult to realize owing to the requirements of MRcompatibility. Pneumatic stepper motors built entirely of non-conducting materials can be safely used in an MR environment, with pressurized air supply and switching residing outside the magnet room. Methods: In this research, a torso phantom was built adopting a 3D-printed linear stepper drive for use with high-field MR scanners. It was possible to simulate respiratory motion of a 3D-printed left ventricle phantom using the stepper. Results and discussion: Precise and accurate motion for a time of 15 min over a range of 8 cm were achieved with speeds up to 5.5 mm/s when the stepper was loaded with the left ventricle phantom. It was shown that the motor is an effective tool for quality control in multi-modal medical imaging. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Muscular insulin resistance is frequently characterized by blunted increases in glucose-6-phosphate (G-6-P) reflecting impaired glucose transport/phosphorylation. These abnormalities likely relate to excessive intramyocellular lipids and mitochondrial dysfunction. We [...]

Purpose: Lactate is a key metabolite in skeletal muscle and whole‐body physiology. Its MR visibility in muscle is affected by overlapping lipid signals and fiber orientation. Double‐quantum filtered (DQF) 1H MRS selectively detects lactate at 1.3 ppm, but at ultra‐high field the efficiency of slice‐selective 3D‐localization with conventional RF pulses is limited by bandwidth. This novel 3D‐localized 1H DQF MRS sequence uses adiabatic refocusing pulses to unambiguously detect lactate in skeletal muscle at 7 T. Methods: Lactate double‐quantum coherences were 3D‐localized using slice‐selective Shinnar–Le Roux optimized excitation and adiabatic refocusing pulses (similar to semi‐LASER). DQF MR spectra were acquired at 7 T from lactate phantoms, meat specimens with injected lactate (exploring multiple TEs and fiber orientations), and human gastrocnemius in vivo during and after exercise (without cuff ischemia). Results: Lactate was readily detected, achieving the full potential of 50% signal with a DQF, in solution. The effects of fiber orientation and TE on the lactate doublet (peak splitting, amplitude, and phase) were in good agreement with theory and literature. Exercise‐induced lactate accumulation was detected with 30 s time resolution. Conclusion: This novel 3D‐localized 1H DQF MRS sequence can dynamically detect glycolytically generated lactate in muscle during exercise and recovery at 7 T. [ABSTRACT FROM AUTHOR]

Abstract Background Nuclear magnetic resonance (NMR) imaging and spectroscopy have been applied to assess skeletal muscle oxidative metabolism. Therefore, in-vivo NMR may enable the characterization of ischemia-reperfusion injury. The goal of this study was to evaluate whether NMR could detect the effects of ischemic preconditioning (IPC) in healthy subjects. Methods Twenty-three participants were included in two randomized crossover protocols in which the effects of IPC were measured by NMR and muscle force assessments. Leg ischemia was administered for 20 minutes with or without a subsequent impaired reperfusion for 5 minutes (stenosis model). IPC was administered 4 or 48 hours prior to ischemia. Changes in 31phosphate NMR spectroscopy and blood oxygen level-dependent (BOLD) signals were recorded. 3-Tesla NMR data were compared to those obtained for isometric muscular strength. Results The phosphocreatine (PCr) signal decreased robustly during ischemia and recovered rapidly during reperfusion. In contrast to PCr, the recovery of muscular strength was slow. During post-ischemic stenosis, PCr increased only slightly. The BOLD signal intensity decreased during ischemia, ischemic exercise and post-ischemic stenosis but increased during hyperemic reperfusion. IPC 4 hours prior to ischemia significantly increased the maximal PCr reperfusion signal and mitigated the peak BOLD signal during reperfusion. Conclusions Ischemic preconditioning positively influenced muscle metabolism during reperfusion; this resulted in an increase in PCr production and higher oxygen consumption, thereby mitigating the peak BOLD signal. In addition, an impairment of energy replenishment during the low-flow reperfusion was detected in this model. Thus, functional NMR is capable of characterizing changes in reperfusion and in therapeutic interventions in vivo. Trial Registration ClinicalTrials.gov: NCT00883467

Exercise studies investigating the metabolic response of calf muscles using 31PMRS are usually performed with a single knee angle. However, during natural movement, the distribution of workload between the main contributors to force, gastrocnemius and soleus is influenced by the knee angle. Hence, it is of interest to measure the respective metabolic response of these muscles to exercise as a function of knee angle using localized spectroscopy. Time-resolved multivoxel 31P MRS at 7 T was performed simultaneously in gastrocnemius medialis and soleus during rest, plantar flexion exercise and recovery in 12 healthy volunteers. This experiment was conducted with four different knee angles. PCr depletions correlated negatively with knee angle in gastrocnemius medialis, decreasing from 79±14 % (extended leg) to 35±23 % (~ 40°), and positively in soleus, increasing from 20±21 % to 36±25 %; differences were significant. Linear correlations were found between knee angle and end-exercise PCr depletions in gastrocnemius medialis (R² = 0.8) and soleus (R² = 0.53). PCr recovery times and end-exercise pH changes that correlated with PCr depletionwere consistent with the literature in gastrocnemius medialis and differences between knee angles were significant. These effects were less pronounced in soleus and not significant for comparable PCr depletions. Maximum oxidative capacity calculated for all knee angles was in excellent Agreement with the literature and showed no significant changes between different knee angles. In conclusion, these findings confirm that plantar flexion exercise with a straight leg is a suitable paradigm, when data are acquired from gastrocnemius only (using either localized MRS or small surface coils), and that activation of soleus requires the knee to be flexed. The present study comprises a systematic investigation of the effects of the knee angle on metabolic parameters, measured with dynamic multivoxel 31PMRS during muscle exercise and recovery, and the findings should be used in future study design. [ABSTRACT FROM AUTHOR]

Purpose Separate measurements are required when investigating multiple exercising muscles with singlevoxel-localized dynamic 31P-MRS. With multivoxel spectroscopy, 31P-MRS time-series spectra are acquired from multiple independent regions during one exercise-recovery experiment with the same time resolution as for singlevoxel measurements. Methods Multiple independently selected volumes were localized using temporally interleaved semi-LASER excitations at 7T. Signal loss caused by mutual saturation from shared excitation or refocusing slices was quantified at partial and full overlap, and potential contamination was investigated in phantom measurements. During an exercise-recovery experiment both gastrocnemius medialis and soleus of two healthy volunteers were measured using multivoxel acquisitions with a total TR of 6 s, while avoiding overlap of excitation slices. Results Signal reduction by shared adiabatic refocusing slices selected 1 s after the preceding voxel was between 10% (full overlap) and 20% (half overlap), in a phantom measurement. In vivo data were acquired from both muscles within the same exercise experiment, with 13-18% signal reduction. Spectra show phosphocreatine, inorganic phosphate, adenosine-triposphate, phosphomonoesters, and phosphodiesters. Conclusion Signal decrease was relatively low compared to the 2-fold increase in information. The approach could help to improve the understanding in metabolic research and is applicable to other organs and nuclei. Magn Reson Med 77:921-927, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. [ABSTRACT FROM AUTHOR]

Purpose To enhance sensitivity and coverage for calf muscle studies, a novel, form-fitted, three-channel phosphorus-31 (31P), two-channel proton (1H) transceiver coil array for 7 T MR imaging and spectroscopy is presented. Methods Electromagnetic simulations employing individually generated voxel models were performed to design a coil array for studying nonpathological muscle metabolism. Static phase combinations of the coil elements' transmit fields were optimized based on homogeneity and efficiency for several voxel models. The best-performing design was built and tested both on phantoms and in vivo. Results Simulations revealed that a shared conductor array for 31P provides more robust interelement decoupling and better homogeneity than an overlap array in this configuration. A static B1 + shim setting that suited various calf anatomies was identified and implemented. Simulations showed that the 31P array provides signal-to-noise ratio (SNR) benefits over a single loop and a birdcage coil of equal radius by factors of 3.2 and 2.6 in the gastrocnemius and by 2.5 and 2.0 in the soleus muscle. Conclusion The performance of the coil in terms of B1+ and achievable SNR allows for spatially localized dynamic 31P spectroscopy studies in the human calf. The associated higher specificity with respect to nonlocalized measurements permits distinguishing the functional responses of different muscles. Magn Reson Med 73:2376-2389, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Alternate methods to quantify mitochondrial activity or function have been extensively used for studying insulin resistance and type 2 diabetes mellitus, namely saturation transfer and phosphocreatine (PCr) recovery. As these methods are in fact determining different parameters, this study aimed to compare saturation transfer results to PCr recovery measurements within the same group. Fifteen subjects underwent saturation transfer and ischemic exercise-recovery experiments. PCr decrease during ischemia ( Q), induced by cuff inflation, served as an additional measure of resting ATP (adenosine triphosphate) production. ATP synthetic rate (fATP) measured by saturation transfer (0.234 ± 0.043 mM/s) was greater than ( Q = 0.0077 ± 0.0011 mM/s), but correlated well with Q ( r = 0.63 P = 0.013). Parameters of PCr recovery correlated well with fATP ( Qmax,lin: r = 0.71, P = 0.003, Qmax,ADP: r = 0.66, P = 0.007) and Q ( Qmax,lin: r = 0.92, P = 0.000002, Qmax,ADP: r = 0.76, P = 0.001). In conclusion, although saturation transfer yields higher ATP synthetic rates than PCr decrease during ischemia, their significant correlation indicates that fATP can be used as a marker of mitochondrial activity. The finding that both Q and fATP correlate with PCr recovery kinetics suggests that skeletal muscle with greater maximal aerobic ATP synthetic rates is also metabolically more active at rest. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Mitochondrial gene mutations lead to mitochondrial diabetes with defects of insulin secretion and sensitivity. Mitochondrial dysfunction is also involved in common insulin resistance, but secondary metabolic events may be confounding the metabolic picture in overt type 2 diabetes. Acromegaly is associated with alterations of energy expenditure and insulin action and might serve as model to investigate the role of mitochondrial function. Thus, we examined glucose metabolism, intracellular fat deposition and mitochondrial function in patients with a history of acromegaly (AM). Six AM (4f/2m, age: 49±4 years, body mass index, BMI: 27±1 kg/m²) with an at least 7-years history of successful treatment and age-/BMI-matched healthy volunteers (CON: 3 f/3m, 43±5 years, 26±2 kg/m²) were studied. Insulin sensitivity (OGIS), first-phase and adaptive insulin secretion were assessed from the frequently sampled OGTT (insulinogenic index, ISEC, adaptation index ADAP). Fasting mitochondrial function was assessed from ATP synthetic flux (fATP) using [sup 31]P magnetic resonance spectroscopy (MRS) of calf muscle. Intracellular lipid contents of tibialis anterior (IMCLt) and soleus muscles (IMCLs) as well as liver (HCL) were measured with [sup 1]H MRS. IGF-1 did not differ between groups (AM: 1774-36; CON: 145±21 ng/ml). Fasting plasma glucose was ∼16% higher in AM than in CON (99±3 vs. 85±2 mg/dl, p<0.05). OGIS was comparable (AM: 395±30, CON: 415±6 ml.min[sup -1].m[sup -2]), whereas ISEC was ∼87% (AM: 0.9±0.4, CON: 6.7±1.7 pmol/mmol, p<0.05) and ADAP was ∼84% lower in AM (0.44±0.19, CON: 2.77∼0.7 min[sup -2]/mmol.l[sup -1] p<0.05), fATP was ∼22% lower in AM (10.1±0.6 vs. 12.9±1.0 mmol.l[sup -1]min[sup -1], p<0.05) and related positively to ISEC (r=.687, p<0.01) and ADAP (r=0.744, p<0.005). IMCLt, IMCLs and HCL were not different between groups. IMCLs related negatively to insulin sensitivity (r=-0.745, p=0.005). Patients with a history of acromegaly exhibit reduced β cell and muscle mitochondrial function despite normal insulin sensitivity. Previous long-term exposure to high growth hormone and IGF concentrations and/or chronic increases in plasma glucose concentrations could lead to similar abnormalities in both tissues. [ABSTRACT FROM AUTHOR]

REL feature impaired glucose transport which relates to reduced myocellular ATP synthesis (fATP). We hypothesized that exercise stimulates fATP, decreases intramyocellular lipids (IMCL) and so improves insulin action. Glucose tolerant REL (4f/6m, age: 39±4a, BMI: 24±lkg/m²) and CON (4f/6m, 38±4a, 24±1 kg/m²) with comparable O2[sub 2] uptake at respiratory compensation (VO[sub 2]rcp; REL:25±2, CON:26±1ml.kg[sup -1].min[sup -1];ns) underwent OGTT to measure insulin sensitivity (OGIS) and ¹H/[sup 31]P MR spectroscopy to assess IMCL and ATP synthesis from P-creatine (fPCR) and inorganic phosphate (fATP). Both tests were done before and after 1-week cycling training (2x40 min, 90% VO[sub 2]rcp). OGIS (ml.min[sup -1].m[sup -2]) was 13% lower in REL (370±20 vs 424±8;P<.05) without changes alter exercise. Basal fATP was similar but exercise increased fATP by 20% in CON (P=10[sup -4]) being 21% higher than in REL (12±1 vs 15±2µmol.ml[sup -1] min[sup -1]; P<.05). Basal fATP/fPCR ratios were 23% higher in REL (30±2, 36±2;P=.02) and decreased (P<.005) being comparable after exercise as was IMCL. VO[sub 2]max and VO[sub 2]rcp correlated with fATP (R=.617, P=.004; R=.748; P=10[sup -4]) with VO[sub 2]max independently explaining 40% (P=.004) of fATP variation. Short-term exercise training increases ATP synthesis despite unchanged insulin sensitivity in CON suggesting that stimulation of mitochondrial function precedes training effects on insulin sensitivity. In REL, impaired ATP synthesis remains despite exercise-induced normalization of the equilibrium of energy generating processes supporting the concept of inherited mitochondrial dysfunction beyond reduced mitochondrial contents. [ABSTRACT FROM AUTHOR]

Purpose: Lactate is a key metabolite in skeletal muscle and whole-body physiology. Its MR visibility in muscle is affected by overlapping lipid signals and fiber orientation. Double-quantum filtered (DQF) 1 H MRS selectively detects lactate at 1.3 ppm, but at ultra-high field the efficiency of slice-selective 3D-localization with conventional RF pulses is limited by bandwidth. This novel 3D-localized 1 H DQF MRS sequence uses adiabatic refocusing pulses to unambiguously detect lactate in skeletal muscle at 7 T., Methods: Lactate double-quantum coherences were 3D-localized using slice-selective Shinnar-Le Roux optimized excitation and adiabatic refocusing pulses (similar to semi-LASER). DQF MR spectra were acquired at 7 T from lactate phantoms, meat specimens with injected lactate (exploring multiple TEs and fiber orientations), and human gastrocnemius in vivo during and after exercise (without cuff ischemia)., Results: Lactate was readily detected, achieving the full potential of 50% signal with a DQF, in solution. The effects of fiber orientation and TE on the lactate doublet (peak splitting, amplitude, and phase) were in good agreement with theory and literature. Exercise-induced lactate accumulation was detected with 30 s time resolution., Conclusion: This novel 3D-localized 1 H DQF MRS sequence can dynamically detect glycolytically generated lactate in muscle during exercise and recovery at 7 T., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Exercise studies investigating the metabolic response of calf muscles using 31 P MRS are usually performed with a single knee angle. However, during natural movement, the distribution of workload between the main contributors to force, gastrocnemius and soleus is influenced by the knee angle. Hence, it is of interest to measure the respective metabolic response of these muscles to exercise as a function of knee angle using localized spectroscopy. Time-resolved multivoxel 31 P MRS at 7 T was performed simultaneously in gastrocnemius medialis and soleus during rest, plantar flexion exercise and recovery in 12 healthy volunteers. This experiment was conducted with four different knee angles. PCr depletions correlated negatively with knee angle in gastrocnemius medialis, decreasing from 79±14 % (extended leg) to 35±23 %(∼40°), and positively in soleus, increasing from 20±21 % to 36±25 %; differences were significant. Linear correlations were found between knee angle and end-exercise PCr depletions in gastrocnemius medialis (R 2 =0.8) and soleus (R 2 =0.53). PCr recovery times and end-exercise pH changes that correlated with PCr depletion were consistent with the literature in gastrocnemius medialis and differences between knee angles were significant. These effects were less pronounced in soleus and not significant for comparable PCr depletions. Maximum oxidative capacity calculated for all knee angles was in excellent agreement with the literature and showed no significant changes between different knee angles. In conclusion, these findings confirm that plantar flexion exercise with a straight leg is a suitable paradigm, when data are acquired from gastrocnemius only (using either localized MRS or small surface coils), and that activation of soleus requires the knee to be flexed. The present study comprises a systematic investigation of the effects of the knee angle on metabolic parameters, measured with dynamic multivoxel 31 P MRS during muscle exercise and recovery, and the findings should be used in future study design., (© 2018 The Authors. NMR in Biomedicine. Published by John Wiley & Sons, Ltd.)

Purpose: Separate measurements are required when investigating multiple exercising muscles with singlevoxel-localized dynamic 31 P-MRS. With multivoxel spectroscopy, 31 P-MRS time-series spectra are acquired from multiple independent regions during one exercise-recovery experiment with the same time resolution as for singlevoxel measurements., Methods: Multiple independently selected volumes were localized using temporally interleaved semi-LASER excitations at 7T. Signal loss caused by mutual saturation from shared excitation or refocusing slices was quantified at partial and full overlap, and potential contamination was investigated in phantom measurements. During an exercise-recovery experiment both gastrocnemius medialis and soleus of two healthy volunteers were measured using multivoxel acquisitions with a total T R of 6 s, while avoiding overlap of excitation slices., Results: Signal reduction by shared adiabatic refocusing slices selected 1 s after the preceding voxel was between 10% (full overlap) and 20% (half overlap), in a phantom measurement. In vivo data were acquired from both muscles within the same exercise experiment, with 13-18% signal reduction. Spectra show phosphocreatine, inorganic phosphate, adenosine-triposphate, phosphomonoesters, and phosphodiesters., Conclusion: Signal decrease was relatively low compared to the 2-fold increase in information. The approach could help to improve the understanding in metabolic research and is applicable to other organs and nuclei. Magn Reson Med 77:921-927, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To enhance sensitivity and coverage for calf muscle studies, a novel, form-fitted, three-channel phosphorus-31 ((31) P), two-channel proton ((1) H) transceiver coil array for 7 T MR imaging and spectroscopy is presented., Methods: Electromagnetic simulations employing individually generated voxel models were performed to design a coil array for studying nonpathological muscle metabolism. Static phase combinations of the coil elements' transmit fields were optimized based on homogeneity and efficiency for several voxel models. The best-performing design was built and tested both on phantoms and in vivo., Results: Simulations revealed that a shared conductor array for (31) P provides more robust interelement decoupling and better homogeneity than an overlap array in this configuration. A static B1 (+) shim setting that suited various calf anatomies was identified and implemented. Simulations showed that the (31) P array provides signal-to-noise ratio (SNR) benefits over a single loop and a birdcage coil of equal radius by factors of 3.2 and 2.6 in the gastrocnemius and by 2.5 and 2.0 in the soleus muscle., Conclusion: The performance of the coil in terms of B1 (+) and achievable SNR allows for spatially localized dynamic (31) P spectroscopy studies in the human calf. The associated higher specificity with respect to nonlocalized measurements permits distinguishing the functional responses of different muscles., (© 2014 Wiley Periodicals, Inc.)

Alternate methods to quantify mitochondrial activity or function have been extensively used for studying insulin resistance and type 2 diabetes mellitus, namely saturation transfer and phosphocreatine (PCr) recovery. As these methods are in fact determining different parameters, this study aimed to compare saturation transfer results to PCr recovery measurements within the same group. Fifteen subjects underwent saturation transfer and ischemic exercise-recovery experiments. PCr decrease during ischemia (Q), induced by cuff inflation, served as an additional measure of resting ATP (adenosine triphosphate) production. ATP synthetic rate (fATP) measured by saturation transfer (0.234 ± 0.043 mM/s) was greater than (Q = 0.0077 ± 0.0011 mM/s), but correlated well with Q (r = 0.63 P = 0.013). Parameters of PCr recovery correlated well with fATP (Q(max,lin) : r = 0.71, P = 0.003, Q(max,ADP) : r = 0.66, P = 0.007) and Q (Q(max,lin) : r = 0.92, P = 0.000002, Q(max,ADP) : r = 0.76, P = 0.001). In conclusion, although saturation transfer yields higher ATP synthetic rates than PCr decrease during ischemia, their significant correlation indicates that fATP can be used as a marker of mitochondrial activity. The finding that both Q and fATP correlate with PCr recovery kinetics suggests that skeletal muscle with greater maximal aerobic ATP synthetic rates is also metabolically more active at rest. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc., (Copyright © 2011 Wiley-Liss, Inc.)