Arunark Kolipaka¹, Kiaran McGee¹, Shivani Aggarwal¹, Qingshan Chen¹, Nandan Anavekar¹, Armando Manduca¹, Richard Ehman¹, and Philip Araoz^1
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.

Leonie E Paulis¹, Alexandra Klein², Tessa Geelen¹, Bernd Fleischmann², Wilhelm Roell², Klaas Nicolay¹, and Gustav J Strijkers^1
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.

Choukri Mekkaoui¹, Shuning Huang¹, Guangping Dai¹, Timothy G Reese¹, Udo Hoffmann², Marcel P Jackowski³, and David E Sosnovik^1
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.

Shuning Huang¹, Choukri Mekkaoui¹, Howard H. Chen¹, Soeun Ngoy², Michael Bauer², Ruopeng Wang¹, Van J Wedeen¹, Guangping E Dai¹, Ronglih Liao², and David E Sosnovik^1,3
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.

Bharath Atthe^1,2, Mary Kemerer^1,2, Ya Chen^1,2, Ming Lu^1,2, Gheorghe Mateescu^2,3, Chris Flask^2,3, and Xin Yu^1,2
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.

Ashish Gupta^1,2, Vadappuram P. Chacko³, Yibin Wang⁴, and Robert G. Weiss^2,5
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.

Marie Allen Schroeder^1,2, Angus Z Lau^1,3, Albert Chen⁴, Kim Connelly^1,5, Xudong Hu⁵, Jennifer Barry¹, Damian J Tyler², Kieran Clarke², Graham A Wright^1,3, and Chuck H Cunningham^1,3
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.

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 Reddy^1
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.

Haiyan Ding^1,2, Di Xu¹, M Muz Zviman³, Valeria Sena-Weltin³, Luciano Amado³, Saman Nazarian³, Henry Halperin³, Elliot R McVeigh¹, and Daniel A Herzka^1
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.