Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes

OBJECTIVE - Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective beta-cell mitochondria and secretion. RESEARCH DESIGN AND METHODS - We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using P-31/H-1 magnetic resonance spectroscopy and insulin sensitivity and endogenous glucose production (EGP) using hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female patient suffering from MELAS(myopathy,encephalopathy, lactic acidosis, and stroke-like episodes) syndrome and in six control subjects. RESULTS - The MELAS patient showed impaired insulin sensitivity (4.3 vs. 8.6 +/- 0.5 mg . kg(-1) . min(-1)) and suppression of EGP (69 vs. 94 +/- 1%), and her baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 vs. 10.6 +/- 1.0 and 12.8 +/- 1.3 mu mol . l(-1) . min(-1)) compared with those of the control subjects. HCLs and IMCLs were comparable between the MELAS patient and control subjects. CONCLUSIONS - Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in some patients with the MELAS syndrome

Simultaneous and interleaved acquisition of NMR signals from different nuclei with a clinical MRI scanner.

Modification of a clinical MRI scanner to enable simultaneous or rapid interleaved acquisition of signals from two different nuclei. A device was developed to modify the local oscillator signal fed to the receive channel(s) of an MRI console. This enables external modification of the frequency at which the receiver is sensitive and rapid switching between different frequencies. Use of the device was demonstrated with interleaved and simultaneous <sup>31</sup> P and <sup>1</sup> H spectroscopic acquisitions, and with interleaved <sup>31</sup> P and <sup>1</sup> H imaging. Signal amplitudes and signal-to-noise ratios were found to be unchanged for the modified system, compared with data acquired with the MRI system in the standard configuration. Interleaved and simultaneous <sup>1</sup> H and <sup>31</sup> P signal acquisition was successfully demonstrated with a clinical MRI scanner, with only minor modification of the RF architecture. While demonstrated with <sup>31</sup> P, the modification is applicable to any detectable nucleus without further modification, enabling a wide range of simultaneous and interleaved experiments to be performed within a clinical setting. Magn Reson Med 76:1636-1641, 2016. © 2015 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

Skeletal muscle ATP synthesis and cellular H+ handling measured by localized 31P-MRS during exercise and recovery

31P magnetic resonance spectroscopy (MRS) is widely used for non-invasive investigation of muscle metabolism dynamics. This study aims to extend knowledge on parameters derived from these measurements in detail and comprehensiveness: proton (H+) efflux, buffer capacity and the contributions of glycolytic (L) and oxidative (Q) rates to ATP synthesis were calculated from the evolutions of phosphocreatine (PCr) and pH. Data are reported for two muscles in the human calf, for each subject and over a wide range of exercise intensities. 22 subjects performed plantar flexions in a 7T MR-scanner, leading to PCr changes ranging from barely noticeable to almost complete depletion, depending on exercise protocol and muscle studied by localized MRS. Cytosolic buffer capacity was quantified for the first time non-invasively and individually, as was proton efflux evolution in early recovery. Acidification started once PCr depletion reached 60–75%. Initial and end-exercise L correlated with end-exercise levels of PCr and approximately linear with pH. Q calculated directly from PCr and pH derivatives was plausible, requiring fewer assumptions than the commonly used ADP-model. In conclusion, the evolution of parameters describing cellular energy metabolism was measured over a wide range of exercise intensities, revealing a relatively complete picture of muscle metabolism

Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy

Acknowledgements We would like to thank Dr. Nicholas Senn for conducting data auditing, Dr. Matthew Clemence (Philips Healthcare Clinical Science, UK) for clinical scientist support, Dr. Tim Smith for biologist support, Mr. Gordon Buchan for technician support, Ms Bolanle Brikinns for patient recruitment support, Ms Dawn Younie for logistic support, Prof. Andrew M. Blamire for advice on MRS. We would also like to thank Mr Roger Bourne and Ms Mairi Fuller for providing access to the patients. Data availability Data supporting this publication are stored at Institute of Medical Sciences and available upon request. Funding information This project was funded by Friends of Aberdeen and North Centre for Haematology, Oncology and Radiotherapy (ANCHOR) (RS2015 004). Sai Man Cheung’s PhD study was jointly supported by Elphinstone scholarship, Roland Sutton Academic Trust and John Mallard scholarship.Peer reviewedPublisher PD

Investigating the effect of trigger delay on cardiac 31P MRS signals

The heart’s geometry and its metabolic activity vary over the cardiac cycle. The effect of these fluctuations on phosphorus (31P) magnetic resonance spectroscopy (MRS) data quality and metabolite ratios was investigated. 12 healthy volunteers were measured using a 7 T MR scanner and a cardiac 31P-1H loop coil. 31P chemical shift imaging data were acquired untriggered and at four different times during the cardiac cycle using acoustic triggering. Signals of adenosine-triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi) and 2,3-diphosphoglycerate (2,3-DPG) and their fit quality as Cramér-Rao lower bounds (CRLB) were quantified including corrections for contamination by 31P signals from blood, flip angle, saturation and total acquisition time. The myocardial filling factor was estimated from cine short axis views. The corrected signals of PCr and γ-ATP were higher during end-systole and lower during diastasis than in untriggered acquisitions (P<0.05). Signal intensities of untriggered scans were between those with triggering to end-systole and diastasis. Fit quality of PCr and γ-ATP peaks was best during end-systole when blood contamination of ATP and Pi signals was lowest. While metabolite ratios and pH remained stable over the cardiac cycle, signal amplitudes correlated strongly with myocardial voxel filling. Triggering of cardiac 31P MRS acquisitions improves signal amplitudes and fit quality if the trigger delay is set to end-systole. We conclude that triggering to end-systole is superior to triggering to diastasis

Comparison of four 31P single-voxel MRS sequences in the human brain at 9.4 T

Purpose: In this study, different single-voxel localization sequences were implemented and systematically compared for the first time for phosphorous MRS (31 P-MRS) in the human brain at 9.4 T. Methods: Two multishot sequences, image-selected in vivo spectroscopy (ISIS) and a conventional slice-selective excitation combined with localization by adiabatic selective refocusing (semiLASER) variant of the spin-echo full intensity-acquired localized spectroscopy (SPECIAL-semiLASER), and two single-shot sequences, semiLASER and stimulated echo acquisition mode (STEAM), were implemented and optimized for 31 P-MRS in the human brain at 9.4 T. Pulses and coil setup were optimized, localization accuracy was tested in phantom experiments, and absolute SNR of the sequences was compared in vivo. The SNR per unit time (SNR/t) was derived and compared for all four sequences and verified experimentally for ISIS in two different voxel sizes (3 × 3 × 3 cm3 , 5 × 5 × 5 cm3 , 10-minute measurement time). Metabolite signals obtained with ISIS were quantified. The possible spectral quality in vivo acquired in clinically feasible time (3:30 minutes, 3 × 3 × 3 cm3 ) was explored for two different coil setups. Results: All evaluated sequences performed with good localization accuracy in phantom experiments and provided well-resolved spectra in vivo. However, ISIS has the lowest chemical shift displacement error, the best localization accuracy, the highest SNR/t for most metabolites, provides metabolite concentrations comparable to literature values, and is the only one of the sequences that allows for the detection of the whole 31 P spectrum, including β-adenosine triphosphate, with the used setup. The SNR/t of STEAM is comparable to the SNR/t of ISIS. The semiLASER and SPECIAL-semiLASER sequences provide good results for metabolites with long T2 . Conclusion: At 9.4 T, high-quality single-voxel localized 31 P-MRS can be performed in the human brain with different localization methods, each with inherent characteristics suitable for different research issues

Comparing localized and nonlocalized dynamic (31) P magnetic resonance spectroscopy in exercising muscle at 7T

Item does not contain fulltextBy improving spatial and anatomical specificity, localized spectroscopy can enhance the power and accuracy of the quantitative analysis of cellular metabolism and bioenergetics. Localized and nonlocalized dynamic (31) P magnetic resonance spectroscopy using a surface coil was compared during aerobic exercise and recovery of human calf muscle. For localization, a short echo time single-voxel magnetic resonance spectroscopy sequence with adiabatic refocusing (semi-LASER) was applied, enabling the quantification of phosphocreatine, inorganic phosphate, and pH value in a single muscle (medial gastrocnemius) in single shots (T(R) = 6 s). All measurements were performed in a 7 T whole body scanner with a nonmagnetic ergometer. From a series of equal exercise bouts we conclude that: (a) with localization, measured phosphocreatine declines in exercise to a lower value (79 � 7\% cf. 53 � 10\%, P = 0.002), (b) phosphocreatine recovery shows shorter half time (t(1/2) = 34 � 7 s cf. t(1/2) = 42 � 7 s, nonsignificant) and initial postexercise phosphocreatine resynthesis rate is significantly higher (32 � 5 mM/min cf. 17 � 4 mM/min, P = 0.001) and (c) in contrast to nonlocalized (31) P magnetic resonance spectroscopy, no splitting of the inorganic phosphate peak is observed during exercise or recovery, just an increase in line width during exercise. This confirms the absence of contaminating signals originating from weaker-exercising muscle, while an observed inorganic phosphate line broadening most probably reflects variations across fibers in a single muscle. Magn Reson Med, 2012. � 2012 Wiley Periodicals, Inc