Single‐voxel ¹H NMR spectra from gastrocnemius and soleus muscle were acquired in healthy volunteers at 7T with the objective of measuring the concentration of intramyocellular lipid [IMCL] (note: throughout this article, square brackets indicate concentration). However, significant asymmetry in the resonance assigned to the methylene protons (‐CH₂‐)_n in extramyocellular lipids (EMCL) interfered with fitting the spectra. Since muscle fibers in these tissues are generally not parallel to B₀, the influence of variable orientation in strands of extracellular fat was examined using a mathematical model. Modest variation in orientation produced asymmetric lineshapes that were qualitatively similar to typical observations at 7T. Analysis of simulated spectra by fitting with a Voigt function overestimated [IMCL]/[EMCL] except when EMCL fibers were nearly parallel to B₀. Estimates of [IMCL]/[EMCL] were improved by including variations in fiber orientation in the lineshape analysis (fiber orientation modeling, or FOM). Calculated [IMCL] using FOM, 4.8 ± 2.2 mmol/kg wet weight, was lower compared to most previous reports in soleus. Magn Reson Med 61:16–21, 2009.

BACKGROUND: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation. METHODS: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO ₂ ) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO ₂ slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO ₂ , and muscle oxygen diffusive conductance. In a subset of participants (n=36), phosphocreatine recovery time was measured by magnetic resonance spectroscopy to determine skeletal muscle oxidative capacity. RESULTS: Peak VO ₂ during cardiopulmonary exercise testing was not different between groups (central: 13.9±5.7 versus peripheral: 12.0±3.1 mL/min per kg; P =0.135); however, the peripheral group had a lower peak arterial-to-venous oxygen content difference (central: 13.5±2.0 versus peripheral: 11.1±1.6 mLO ₂ /dL blood; P <0.001). During single leg knee extension, there was no difference in peak leg VO ₂ ( P =0.306), but the peripherally limited group had greater blood flow/VO ₂ ratio ( P =0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO ₂ /dL blood; P =0.013), and lower muscle oxygen diffusive conductance ( P =0.021). A difference in magnetic resonance spectroscopy–derived phosphocreatine recovery time was not detected ( P =0.199). CONCLUSIONS: Peripherally limited patients with heart failure with preserved ejection fraction identified by cardiopulmonary exercise testing have impairments in oxygen transport and utilization at the level of the skeletal muscle quantified by invasive knee extension exercise testing, which includes an increased blood flow/V̇O ₂ ratio and poor muscle diffusive capacity. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04068844.

Purpose: To develop a simplified method for quantitative measurement of NAD⁺/NADH (nicotinamide adenine dinucleotides) levels in human brain by ³¹P MRS without interference from the α‐ATP signal and with inclusion of multiple UDP‐sugar components.Methods: Simple pulse‐acquire ³¹P MR spectra were collected at 7T with and without a frequency‐selective inversion pulse to remove the dominant α‐ATP signal from the underlying NAD(H) signal. Careful inspection of the ³¹P signal at −9.8 ppm previously assigned to UDP‐glucose revealed multiple UDP‐sugar components that must also be considered when deconvoluting the NAD(H) signal to quantify NAD⁺ and NADH. Finally, the overlapping NAD(H) and UDP(G) resonances were deconvoluted into individual components using Voigt lineshape analysis and UDP(G) modeling.Results: The inversion‐based spectral editing method enabled clean separation of the NAD(H) signal from the otherwise dominant α‐ATP signal. In addition, the upfield signal near −9.8 ppm appears more “quartet‐like” than a simple doublet consistent with contributions from other nucleotide sugars such as UDP‐galactose, UDP‐N‐acetyl‐galactosamine, and UDP‐N‐acetyl‐glucosamine in addition to UDP‐glucose. Deconvolution of the combined NAD(H) and UDP(G) signals showed that the measured NAD⁺/NAD ratio was heavily influenced by UDP(G) modeling (7.5 ± 1.8 when the UDP(G) signal was fitted as multiple doublets versus 5.3 ± 0.6 when a simplified pseudo doublet model was used). In a test/re‐test experiments separated by 2 weeks, consistent NAD⁺/NADH ratios were measured in the brain of seven human subjects.Conclusions: The NAD⁺/NADH ratio in human brain can be measured using ³¹P MR spectra simplified by spectral editing and with inclusion of multiple UDP‐sugar components in the data analysis.

Despite its importance in energy metabolism, lactate in human skeletal muscle has been difficult to detect by noninvasive ¹H‐magnetic resonance spectroscopy mainly due to interference from large water and lipid signals. Long echo‐time acquisitions at 7 T effectively attenuates the water and lipid signals in forearm muscle allowing direct observation of both lactate resonances, the methine at 4.09 ppm and the methyl at 1.31 ppm. Using this approach, we were able to monitor lactate dynamics at a temporal resolution of 32 s. While lactate was not detectable at rest, immediately after an acute period of exercise to fatigue the forearm muscle, lactate rose to a level comparable to that of creatine (∼30 mmol/kg wet weight). In a typical ¹H‐magnetic resonance spectrum collected using a echo‐time of 140 ms, the lactate methine and methyl resonances both appear as doublets with an unusually large splitting of ∼20 Hz due to residual dipolar coupling. During muscle recovery following exercise, the lactate signals decay rapidly with a time constant of t_½ = 2.0 ± 0.6 min (n = 12 subjects). This fast and simple lactate detection method may prove valuable for monitoring lactate metabolism in cancer and in sports medicine applications. Magn Reson Med 70:610–619, 2013.