Experimental Myocardial Imaging & Spectroscopy
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Monday May 9th
Room 511D-F  11:00 - 13:00 Moderators: David Sosnovik and Gustav Strijkers

11:00 14.   Introduction
Frederick H. Epstein


11:12 15.   Regional Quantification of Myocardial Stiffness Using MR Elastography  
Arunark Kolipaka1, Kiaran McGee1, Shivani Aggarwal1, Qingshan Chen1, Nandan Anavekar1, Armando Manduca1, Richard Ehman1, and Philip Araoz1
1Mayo Clinic, Rochester, Minnesota, United States

The mechanical properties of the myocardium are known to be essential for normal cardiac function. Magnetic resonance elastography (MRE) is a noninvasive phase contrast technique to estimate stiffness of soft tissues. The purpose of this study was to regionally quantitate effective stiffness in infarcted and remote, non-infarcted myocardium using MRE. Post 3 weeks of induced infarction on 13 pigs, MRE and mechanical testing was performed. We found significant difference in stiffness estimates between infarcted and remote, non-infarcted myocardium both using MRE and mechanical testing.

11:24 16.   Embryonic cardiomyocytes improve contractility and viability of ischemic myocardium  
Leonie E Paulis1, Alexandra Klein2, Tessa Geelen1, Bernd Fleischmann2, Wilhelm Roell2, Klaas Nicolay1, and Gustav J Strijkers1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 2Institute for Physiology, Life and Brain Centre, University of Bonn, Bonn, Germany

Regenerative therapy after myocardial infarction by embryonic cardiomyocyte (eCM) transplantation has potential to increase infarct contractility induced by the electrical coupling of eCM with native myocardium. In this study, it was shown with in vivo (contrast enhanced) cardiac MRI that besides improved global cardiac function (ejection fraction and cardiac output) and reduced infarct volume, eCMs indeed significantly improved infarct wall thickening (WT) in a mouse model of myocardial infarction. These effects were not observed after transplantation of skeletal myoblasts (SMs) or mesenchymal stem cells (MSCs), which lack the intrinsic ability of electrical coupling and also did not differentiate into cardiomyocytes.

11:36 17.   Beyond Qualitative Tractography: A Novel and Reproducible Technique for the Quantitative Analysis of Cardiac Diffusion MR Tractography Datasets In Vivo  
Choukri Mekkaoui1, Shuning Huang1, Guangping Dai1, Timothy G Reese1, Udo Hoffmann2, Marcel P Jackowski3, and David E Sosnovik1
1Radiology, Harvard Medical School, Massachusetts General Hospital, Martinos Center For Biomedical Imaging, Charlestown, MA, United States, 2Radiology, Massachusetts General Hospital, Harvard Medical School, United States, 3Computer Science, University of São Paulo, Institute of Mathematics and Statistics, São Paulo, Brazil

Diffusion tensor MRI tractography can be used to resolve 3D myofiber architecture in the heart. The analysis of these tractograms, however, has been purely qualitative. Here we present a novel metric to quantify regional variation and measurement noise in diffusion tractography datasets in the heart. The technique is applied in human hearts ex vivo, in infarcted sheep hearts, and in mouse hearts in vivo. The use of this metric revealed that high quality diffusion tractograms of the mouse heart can be acquired in vivo, and that fibers in the remote zone of an infarct undergo a right-handed helix angle rotation.

11:48 18.   Microstructural Signatures of Ischemia and Stem Cell Therapy in the Myocardium Revealed with Serial Diffusion Tensor MRI and Tractography of the Mouse Heart In Vivo.  
Shuning Huang1, Choukri Mekkaoui1, Howard H. Chen1, Soeun Ngoy2, Michael Bauer2, Ruopeng Wang1, Van J Wedeen1, Guangping E Dai1, Ronglih Liao2, and David E Sosnovik1,3
1Martinos Center for Biomedical Imaging, Mass General Hospital, Charlestown, MA, United States, 2Cardiology, Brigham and Woman's Hospital, Boston, MA, United States,3Cardiology, Mass General Hospital, Charlestown, MA, United States

Diffusion tensor MRI (DTI) and tractography of the myocardium has been limited to ex-vivo studies. Here, we show that DTI and tractography of the mouse heart can be performed in-vivo. We report, for the first time, the serial changes in myocardial microstructure seen in acute ischemia, infarct healing, and following stem cell injection. Mean diffusivity increased in acute ischemia and returned towards baseline as the infarct healed. The injection of bone marrow derived progenitor cells produced a transient increase in myocardial microstructure. The value of this approach in guiding the development of stem cell therapy is robustly demonstrated.

12:00 19.   Quantitative Assessment of Mitochondrial Metabolic Efficiency by 17O and 31P MR Spectroscopy in Isolated Rat Hearts  
Bharath Atthe1,2, Mary Kemerer1,2, Ya Chen1,2, Ming Lu1,2, Gheorghe Mateescu2,3, Chris Flask2,3, and Xin Yu1,2
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 2Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, United States, 3Radiology, Case Western Reserve University School of Medicine, Cleveland, OH, United States

In this study, we investigated the potential of combining 17O spectroscopy (17O-MRS) and 31P magnetization transfer (31P-MT) method for evaluating metabolic efficiency in perfused hearts. ATP synthesis rate was determined from 31P-MT experiments, while mitochondrial oxidation was quantified by the rate of H217O production. 2,4-dinitrophenol (DNP) was used to induce the uncoupling of mitochondrial oxidation and phosphorylation. Our results suggest that the ratio of ATP synthesis measured by31P-MT to mitochondrial H217O production quantified by 17O-MRS can be used as an indicator of metabolic efficiency.

12:12 20.   Creatine Kinase Overexpression Increases in vivo ATP Synthesis in the Failing Mouse Heart   -permission withheld
Ashish Gupta1,2, Vadappuram P. Chacko3, Yibin Wang4, and Robert G. Weiss2,5
1Department of Medicine, Division of Cardiology, The Johns Hopkins University, School of Medicine, Baltimore, MD, United States, 2Department of Radiology, Division of Magnetic Resonance Research, The Johns Hopkins University, Baltimore, MD, United States, 3Department of Radiology,Division of Magnetic Resonance Research, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 4Department of Anesthesiology and medicine, University of California, Los Angeles, CA, United States,5Department of Medicine, Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Because it was hypothesized that failing heart is energy starved, we used a transgenic approach to augment ATP synthesis in failing hearts. The in vivo rate of ATP synthesis through cardiac creatine kinase (CK Flux) was measured using localized 31P MR triple repetition saturation transfer (TRiST) in healthy mice (n=11), others with heart failure (HF) following thoracic aortic constriction (TAC, n=10), and non-operated (n=8) and TAC (n=7) mice overexpressing the muscle isoform of creatine kinase (CK-M). CK flux was significantly increased in CK-M TAC hearts, indicating that CK-M overexpression offers a means to augment ATP delivery in HF.

12:24 21.   Hyperpolarized 13C Magnetic Resonance Imaging and Spectroscopy Uniquely Reveal Early and Late Onset Metabolic Changes in the Failing Heart  
Marie Allen Schroeder1,2, Angus Z Lau1,3, Albert Chen4, Kim Connelly1,5, Xudong Hu5, Jennifer Barry1, Damian J Tyler2, Kieran Clarke2, Graham A Wright1,3, and Chuck H Cunningham1,3
1Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 2Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom, 3Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 4GE-Healthcare, Toronto, Ontario, Canada, 5Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada

The aim of this study was to use hyperpolarized 13C MRI and MRS to monitor cardiac substrate utilization alongside structure and function, measured using standard cine-MRI, throughout HF progression. Metabolism of [2-13C]pyruvate to 13C-glutamate was reduced by 59% at an early stage in HF, with no change to PDH flux, indicating that13C-glutamate relative to H13CO3- production could be an early marker of disease. Carbohydrate oxidation via PDH was maintained until end-stage HF, at which point PDH flux was reduced by 62%. Hyperpolarised 13C MR may be useful to characterize HF progression, and to diagnose disease, in patients.

12:36 22.   Assessment of Chemical exchange saturation transfer effects in Myocardial Tissue at 7T  
Mohammad Haris1, Anup Singh1, Kejia Cai1, Walter R. T. Witschey2, James J. Pilla1, Giovanni Ferrari3, Kevin Koomalsingh3, Robin Hinmon3, Gerald Zsido1, Joseph H. Gorman III3, Robert C. Gorman3, Hari Hariharan1, and Ravinder Reddy1
1CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2University Hospital Freiburg, Germany, 3Department of Surgery, University of Pennsylvania

We observed the chemical exchange saturation transfer (CEST) effects of water signal in left ventricular infarcted swine heart tissue on 7T clinical scanner. Significantly low CEST contrast was observed in infarcted region compared to non-infarcted region. Low CEST contrast in infarcted region may be due to combined effect from decreased concentration of creatine and low pH. Further characterization of this method on in-vivo animal model of myocardial infarction is in progress.

12:48 23.   High Spatial Resolution Free Breathing 3D T2 Mapping for Edema Detection in Radio Frequency Ablation  
Haiyan Ding1,2, Di Xu1, M Muz Zviman3, Valeria Sena-Weltin3, Luciano Amado3, Saman Nazarian3, Henry Halperin3, Elliot R McVeigh1, and Daniel A Herzka1
1Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, United States, 2Department of Biomedical Engineering, Tsinghua University, Beijing, China, People's Republic of, 3Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, United States

Differentiating between viable myocardium, scar and injured tissue (edema) in both ventricles and atria can very helpful in predicting the recurrence of arrhythmias after radiofrequency ablation (RFA). We propose a 3D navigator gated imaging sequence designed for high resolution T2 mapping and edema detection. T2 maps pre- and post injection of contrast were generated from an interleaved series of T2-prepared 3D volumes acquired 2hrs post RFA the left atrium of a swine. Enhancement due to edema in pre-contrast T2map was confirmed by T2-STIR and delayed enhancement images. T2 values calculated were comparable to those previously reported.