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

PURPOSE: Modification of a clinical MRI scanner to enable simultaneous or rapid interleaved acquisition of signals from two different nuclei. METHODS: 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 31 P and 1 H spectroscopic acquisitions, and with interleaved 31 P and 1 H imaging. RESULTS: 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. CONCLUSION: Interleaved and simultaneous 1 H and 31 P signal acquisition was successfully demonstrated with a clinical MRI scanner, with only minor modification of the RF architecture. While demonstrated with 31 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

Lower Fasting Muscle Mitochondrial Activity Relates to Hepatic Steatosis in Humans

OBJECTIVE Muscle insulin resistance has been implicated in the development of steatosis and dyslipidemia by changing the partitioning of postprandial substrate fluxes. Also, insulin resistance may be due to reduced mitochondrial function. We examined the association between mitochondrial activity, insulin sensitivity, and steatosis in a larger human population. RESEARCH DESIGN AND METHODS We analyzed muscle mitochondrial activity from ATP synthase flux (fATP) and ectopic lipids by multinuclei magnetic resonance spectroscopy from 113 volunteers with and without diabetes. Insulin sensitivity was assessed from M values using euglycemic-hyperinsulinemic clamps and/or from oral glucose insulin sensitivity (OGIS) using oral glucose tolerance tests. RESULTS Muscle fATP correlated negatively with hepatic lipid content and HbA1c. After model adjustment for study effects and other confounders, fATP showed a strong negative correlation with hepatic lipid content and a positive correlation with insulin sensitivity and fasting C-peptide. The negative correlation of muscle fATP with age, HbA1c, and plasma free fatty acids was weakened after adjustment. Body mass, muscle lipid contents, plasma lipoproteins, and triglycerides did not associate with fATP. CONCLUSIONS The association of impaired muscle mitochondrial activity with hepatic steatosis supports the concept of a close link between altered muscle and liver energy metabolism as early abnormalities promoting insulin resistance

Evaluation of Acute Supplementation With the Ketone Ester ( R )-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle 31 P Magnetic Resonance Spectroscopy

In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (31P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23–70 years for cardiac 31P-MRS, and 16 aged 60–75 years for skeletal muscle 31P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle 31P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG®, was administered after the baseline scan. Administration was timed so that post-intervention 31P-MRS would take place 30 min after deltaG® ingestion. The deltaG® ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (−28.8%, p ≪ 0.001; −28.2%, p = 0.02; and −49.1%, p ≪ 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p ≪ 0.001). There were no significant changes in cardiac PCr/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in 31P-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function

Methods of multi nuclear magnetic resonance spectroscopy for metabolic research

Zsfassung in dt. SpracheDie Dissertation mit dem Titel Methods of Multi Nuclear Magnetic Resonance Spectroscopy for Metabolic Research geschrieben von DI.Albrecht Schmid, beurteilt von Prof. Badurek und Prof. Moser beschaftigt sich mit in-vivo Kernspinresonanzspektroskopie. Fur die Untersuchung des Energiestoffwechsels sind Phosphor-31- und Kohlenstoff-13-Spektroskopie von großer Bedeutung. Dabei erlaubt Phosphorspektroskopie die quantitative Bestimmung der energiereichen Phosphate, C-13-Spektroskopie hingegen ermöglicht die Anwendung isotopenangereicherter Substrate, deren Verstoffwechselung verfolgt werden kann.Nach einer Einfuhrung in die Grundlagen der Kernspinresonanz und der Radiofrequenzpulse, insbesondere B1-unabhängige, sogenannte adiabatische Pulse folgt ein Kapitel uber die Relevanz der Multikernspektroskopie fur die physiologische Forschung. Die zentralen Elemente im Verständnis unserer Energieversorgung sind die Bestimmung der Aktivität des Zitronensäurezyklus und der Rate der oxidativen Phosphorilierung. Das Experiment, welches in Kapitel 7 vorgestellt wird, ist die Implementierung des refokusierten INEPT Experiments mittels B1-unempfindlicher Radiofrequenzpulse. Glutamatbestimmung im Zuge der selektiven Isotopenanreicherung durch Verstoffwechselung von C-13-isotopenmarkierten Substraten ist der Schlussel zur Bestimmung der Zitronensäureyklusaktivität.Mittels des vorgestellten INEPT-Experiments sollte das Glutamatsignal wesentlich besser quantifiziert werden können.Ein anderer Schwerpunkt dieser Arbeit ist die Bestimmung der oxidativen Phosphorilierung in Form von ATP Synthese im Skelettmuskel. Zu diesem Zwecke ist ein robustes Messprotokoll entwickelt worden, das mittlerweile au mehr als hundert Probanden angewendet worden ist. Basierend auf diesen Experimenten wurde ein lokalisiertes Sättigungstransferexperiment speziell für die Leber entwickelt, welches den damit verbundnen hohen Anforderungen gerecht wird und die Messzeit in einem für die meisten Menschen erträglichem Ausmaß bleibt. Es ist damit weltweit erstmals gelungen, die hepatischen ATP Synthese in-vivo quantitativ zu bestimmen.Zusammenfassend bieten die vorgestellten Experimente eine solide Basis für weiterführende klinische Studien, welche das Verständnis des menschlichen Energiestoffwechsels erweitern werden. Die damit verbundenen neuen Erkenntnisse werden helfen, zukünftig die Diagnose und Therapie verbreiteter Störungen wie Insulinresistenz, Diabetes mellitus, diffuse Lebererkrankungen sowie Herzkreislauferkrankungen zu verbessern.Nuclear magnetic resonance (NMR) is an established technique for the investigation of various kinds of materials, especially organic substances and tissues. For the study of energy metabolism phosphorus (31P) and carbon (13C) spectroscopy are especially useful After an introduction and a summary of the basics of nuclear magnetic resonance and radiofrequency pulses follows a chapter about the physiological relevance of multnuclear NMR spectroscopy. Measuring the activity of the tricarboxylic acid (TCA) cycle and the rates of oxidative phosphorilation are the keys to understanding the backbone of our energy supply.The experiment presented in Chapter 7 is an implementation of the refocused INEPT experiment with B1 insensitive radiofrequency pulses. Glutamate detection after 13C enriched label incorporation is the key to TCA cycle measurements. With the presented fully adiabatic INEPT sequence the glutamate signal should be quantifiable significantly better.Another focus of this work is measuring oxidative phosphorilation in the form of ATP synthesis in human skeletal muscle. To this end a robust measurement protocol has been developed and applied to more than a hundred subjects.Based on this experience, a localised 31P saturation transfer experiment has been developed specific for the application to human liver that meets the necessary requirements on signal to noise within a tolerable measurement duration for most people. With this protocol hepatic ATP synthesis could be measured for the first time in-vivo.In conclusion, the presented experiments form a solid basis for on-going clinical research studies. These will lead to a significant gain of information accompanied by a better understanding of human metabolism. In consequence, progress in diagnosis and therapy of various metabolic disorders including insulin resistance, diabetes mellitus, diffuse liver disease or cardiovascular diseases can be expected in the future.14

A Flexible Array for Cardiac 31P MR Spectroscopy at 7 T

Purpose: The simulation optimization and implementation of a flexible 31P transmit/receive coil array, under the geometrical constraint of fitting into the housing of an already existing 12-channel proton array, to enable localized cardiac 31P MRS at 7 T is presented. Methods: The performance in terms of homogeneity, power and SAR efficiency, and receive benchmark of 32 potential array designs was compared by full wave 3D electromagnetic simulation considering the respective optimal static B+1 shims. The design with the best performance was built and compared to a commercially available single loop in simulation and measurement. Results: Simulation revealed an optimal array design comprising three overlapping elements, each sized 94 × 141 mm2. Simulation comparison with a single loop coil predicted a performance increase due to increased power efficiency and lower SAR values. This was verified by phantom measurements, where an SNR increase of 46% could be observed for localized 31P spectroscopy in a voxel positioned comparable to an in vivo cardiac measurement scenario. Conclusion: A flexible 31P/1H RF coil array with improved SNR is presented, enabling localized in vivo cardiac 31P spectroscopy at 7 T