In Vivo Creatine Kinase Kinetics in Diabetic Heart: Relationship to Cardiac Work
Adil Bashir¹, Robert J. Gropler^1
1Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States

In vivo measurements of creatine kinase kinetics provide a better measure of cardiac energy metabolism than PCr to ATP ratio. Using optimized magnetization transfer approach we have measured energy production in rat hearts at two levels of cardiac performance and found it to be closely coupled with work load in normal rat hearts. In diabetic hearts the PCr concentration was lower at rest and the energy production for cardiac work was maintained by higher CK rate constant. When cardiac work was increased the CK flux in diabetic animals did not increase in proportion to the work indicating impaired energy production.

Hyperpolarised [2-¹³C]Pyruvate Uniquely Reveals the Role of Acetylcarnitine as a Mitochondrial Substrate Buffer in the Heart
Marie Allen Schroeder¹, Helen J. Atherton¹, Philip Lee², Michael S. Dodd¹, Lowri E. Cochlin¹, Kieran E. Clarke¹, George K. Radda^1,2, Damian J. Tyler^1
1Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom; ²Biomedical Sciences Institute, Singapore Bioimaging Consortium, Singapore, Singapore

Mitochondrial acetylcarnitine may be involved in balancing the glucose-fatty acid cycle in the heart. Here, we used hyperpolarised [2-¹³C]pyruvate with magnetic resonance spectroscopy to monitor the incorporation of acetyl-CoA formed by pyruvate dehydrogenase into the acetylcarnitine pool, and the metabolites of the Krebs cycle, in real-time and in vivo. Our results demonstrated that most pyruvate-derived acetyl-CoA entering the Krebs cycle does not immediately condense with oxaloacetate, but is first converted to acetylcarnitine. Examination of acetylcarnitine production from pyruvate-derived acetyl-CoA in vivo revealed that acetylcarnitine provides a rapidly mobilised mitochondrial buffer for oxidative substrate and may be fundamental in maintaining high, constant ATP levels in the heart.

Quantification of Myocardial Triglycerides: Ex-Vivo and In-Vivo Evaluations by Two-Point Water-Fat Imaging and 1H Spectroscopy
Chia-Ying Liu¹, Alban Redheuil¹, Ronald Ouwerkerk², Charles Steenbergen³, Shenghan Lai⁴, Joao Lima¹, David Bluemke^5
1Department of Radiology, Johns Hopkins Hospital, Baltimore, MD, United States; ²The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States; ³Department of Pathology, The Johns Hopkins University, Baltimore, MD, United States; ⁴Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, United States; ⁵Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, United States

The concept of fat contained within the myocardium, has recently received attention because of its potential role in diabetic myocardial disease, obesity, and HIV infected individuals. Measurements of myocardial triglycerides in humans have been accessed using proton MR spectroscopy (1H MRS). We studied the accuracy of the dual-echo Dixon MRI in quantifying the fatty content of the myocardium in autopsies and patients. 1H MRS as an independent method was also applied for comparison.

Human Cardiac Creatine Kinase Flux Measurement at 3T Using 31P Magnetization Transfer MRS
Adil Bashir¹, Robert J. Gropler^1
1Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States

31P magnetization transfer MRS can measure energy turnover in the myocardium through the creatine kinase (CK) reaction. The in vivo application of this technique has been lagging especially for human studies. We have developed an optimized strategy to measure adenosine diphosphate (ATP) production in human heart via CK system. This is the first demonstration of the technique for human studies at 3T. The high field magnet provides reduction in total experiment time and improved spectral resolution over 1.5T magnet. Our results also demonstrate that the energy production in diabetic heart is impaired.  

Cardiac Spectroscopy in Chronic Fatigue Syndrome (CFS) Correlates with Autonomic Abnormalities on Standing and Stratifies Oxidative Function in Skeletal Muscle - not available
Kieren Grant Hollingsworth¹, David Emerys Jones², Roy Taylor¹, Julia Lindsay Newton³, Andrew Mark Blamire^1
1Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom; ²Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom; ³Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom

Studies of muscle metabolism in chronic fatigue syndrome (CFS) have often had contradictory results and suggested the presence of mixed phenotypes. Recent evidence has suggested that cardiac output is adversely affected in CFS.  12 female CFS/ME patients and 8 controls were recruited. Cardiac phosphorus spectroscopy, muscle exercise phosphorus spectroscopy and impedance cardiography were acquired. Cardiac PCr/ATP ratio was related to changes in cardiac index on standing and reduced PCr/ATP ratio was found to correlate with impaired oxidative function (half-times for PCr and ADP recovery).  Cardiac spectroscopy was found to be useful in stratifying oxidative function in CFS.

In Vivo ¹⁷O MRS Imaging for Assessing Myocardial Oxygen Metabolism in Rat Heart at 9.4T - not available
Xiao-Hong Zhu¹, Yi Zhang¹, Wei Chen^1
1Center for Magnetic Resonance Research, Department of Radiology, Minneapolis, MN, United States

Heart, similar to brain, is a highly aerobic organ which consumes a large portion of oxygen utilized by the entire body. The myocardial oxygen metabolism provides essential energy for performing myocyte contraction/relaxation and maintaining normal cardiac functions. It is, thus, important to develop an in vivo MR imaging approach capable of noninvasively imaging the myocardial oxygen metabolic rate (MVO₂). Recently, high-field in vivo ¹⁷O MRS imaging (MRSI) has been applied to imaging the rat brain oxygen metabolism. In this study, we exploit the feasibility of the ¹⁷O approach for imaging rat MVO₂ at 9.4T with a brief inhalation of ¹⁷O-labeled oxygen gas under basal and workload conditions.

Myocardial Fat Content: Single Breath-Hold ¹H-MR Spectroscopy at 3 T
Belen Rial¹, Stefan Neubauer¹, Matthew D. Robson¹, Jurgen E. Schneider^1
1Cardiovascular Medicine, Oxford University, Oxford, Oxfordshire, United Kingdom

Proton MR Spectroscopy provides a window into myocardial metabolism. Cardiac and respiratory motion still degrades the sensitivity of the method and hence metabolite detection. Some techniques for reducing this problem have recently emerged, however a compromise between feasible scan duration and easy implementation of these techniques in a clinical scanner has not been reached yet. In this study we demonstrate feasible single breath-hold ¹H-MR spectroscopy in the human heart at 3 T, obtaining one unsuppressed-water spectrum and three metabolite spectra, which allowed reliable quantification of fat as percentage of water content in the myocardium of healthy volunteers.

Myocardial Lipids and Myocardial Function in Insulin Resistant Population
Martin Krssak^1,2, Yvonne Winhofer², Christian Göbl², Martin Bischof², Gert Reiter³, Alexandra Kautzky-Willer², Anton Luger², Michael Krebs², Christian Anderwald^2
1Radiology, Medical University of Vienna, Wien, Austria; ²Internal Medicine III, Medical University of Vienna, Wien, Austria; ³Siemens Healthcare Austria, Graz, Austria

Myocardial lipid accumulation and myocardial function were measured by 1H MR spectroscopy and imaging in a group of non-diabetic insulin sensitive and metabolically matched non-diabetic insulin resistant women. No differences were found between these two groups, but hampered myocardial function and increased myocardial lipid accumulation was found in a group patients with type 2 diabetic mellitus, who served as a negative controls. Our results suggest that increased myocardial lipid content and restricted myocardial capacity are not linked to insulin resistance per se, but might develop after the manifestation of type-2 diabetes.