Multimodality Imaging of Myocardial Injury and Remodeling

Advances in cardiovascular molecular imaging have come at a rapid pace over the last several years. Multiple approaches have been taken to better understand the structural, molecular, and cellular events that underlie the progression from myocardial injury to myocardial infarction (MI) and, ultimately, to congestive heart failure. Multimodality molecular imaging including SPECT, PET, cardiac MRI, and optical approaches is offering new insights into the pathophysiology of MI and left ventricular remodeling in small-animal models. Targets that are being probed include, among others, angiotensin receptors, matrix metalloproteinases, integrins, apoptosis, macrophages, and sympathetic innervation. It is only a matter of time before these advances are applied in the clinical setting to improve post-MI prognostication and identify appropriate therapies in patients to prevent the onset of congestive heart failure.

[1]  W. Burchert,et al.  I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[2]  Insights into myocardial microstructure during infarct healing and remodeling: pathologists need not apply. , 2009, Circulation. Cardiovascular imaging.

[3]  Stephen B. Tuttle,et al.  Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue. , 2008, The Review of scientific instruments.

[4]  P. Merlet,et al.  Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  J. Thiran,et al.  Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. , 2006, Radiographics : a review publication of the Radiological Society of North America, Inc.

[6]  V. Dilsizian,et al.  Imaging left ventricular remodeling: targeting the neurohumoral axis , 2008, Nature Clinical Practice Cardiovascular Medicine.

[7]  Vasilis Ntziachristos,et al.  Free-space fluorescence molecular tomography utilizing 360 degrees geometry projections. , 2007, Optics letters.

[8]  Biplab Das,et al.  Collagen-targeted MRI contrast agent for molecular imaging of fibrosis. , 2007, Angewandte Chemie.

[9]  B. Rosen,et al.  Impact of field strength and iron oxide nanoparticle concentration on the linearity and diagnostic accuracy of off‐resonance imaging , 2008, NMR in biomedicine.

[10]  René M. Botnar,et al.  Molecular Magnetic Resonance Imaging of Myocardial Perfusion With EP-3600, a Collagen-Specific Contrast Agent: Initial Feasibility Study in a Swine Model , 2009, Circulation.

[11]  M. Fini,et al.  Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction. , 2006, American journal of physiology. Heart and circulatory physiology.

[12]  M. Akers,et al.  Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction. , 1991, The American journal of cardiology.

[13]  P. Zardini,et al.  Therapy Left Ventricular Remodeling After Myocardial Infarction : Pathophysiology and , 2000 .

[14]  Frederick H Epstein,et al.  Measurement of myocardial mechanics in mice before and after infarction using multislice displacement-encoded MRI with 3D motion encoding. , 2005, American journal of physiology. Heart and circulatory physiology.

[15]  P. Hagmann,et al.  Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging , 2005, Magnetic resonance in medicine.

[16]  C M Kramer,et al.  Integrated approach to ischemic heart disease. The one-stop shop. , 1998, Cardiology clinics.

[17]  Maythem Saeed,et al.  MR imaging of spatial extent of microvascular injury in reperfused ischemically injured rat myocardium: value of blood pool ultrasmall superparamagnetic particles of iron oxide. , 2002, Radiology.

[18]  Ralph Weissleder,et al.  Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications , 2008, Basic Research in Cardiology.

[19]  Ralph Weissleder,et al.  Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto‐optical nanoparticle , 2005, Magnetic resonance in medicine.

[20]  G. Dai,et al.  Abstract 593: Molecular MRI of Cardiomyocyte Apoptosis With Simultaneous Delayed Enhancement MRI Distinguishes Apoptotic and Necrotic Myocytes in vivo: Potential for Midmyocardial Salvage in Acute Ischemia , 2009 .

[21]  G. Schmidt,et al.  Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes. , 2000, Circulation.

[22]  Ralph Weissleder,et al.  Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. , 2003, The New England journal of medicine.

[23]  Jiqiu Chen,et al.  Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction , 2005, Circulation.

[24]  J. Ross,et al.  Fiber Orientation in the Canine Left Ventricle during Diastole and Systole , 1969, Circulation research.

[25]  M. Cima,et al.  Multiparameter magnetic relaxation switch assays. , 2007, Analytical chemistry.

[26]  R. Weissleder,et al.  Molecular Magnetic Resonance Imaging in Cardiovascular Medicine , 2007, Circulation.

[27]  Ralph Weissleder,et al.  Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates. , 2006, Radiology.

[28]  Ralph Weissleder,et al.  Nanoparticle imaging of integrins on tumor cells. , 2006, Neoplasia.

[29]  Vasilis Ntziachristos,et al.  A submillimeter resolution fluorescence molecular imaging system for small animal imaging. , 2003, Medical physics.

[30]  E. Creemers,et al.  Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice. , 2003, American journal of physiology. Heart and circulatory physiology.

[31]  Amy H Herlihy,et al.  Assessment of myocardial infarction in mice by Late Gadolinium Enhancement MR imaging using an inversion recovery pulse sequence at 9.4T , 2008, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[32]  M. Goumans,et al.  Toll-Like Receptor 4 Mediates Maladaptive Left Ventricular Remodeling and Impairs Cardiac Function After Myocardial Infarction , 2008, Circulation research.

[33]  Yi-Hwa Liu,et al.  Hotspot quantification of myocardial focal tracer uptake from molecular targeted SPECT/CT images: experimental validation , 2008, SPIE Medical Imaging.

[34]  John A Hossack,et al.  3D perfusion mapping in post-infarct mice using myocardial contrast echocardiography. , 2006, Ultrasound in medicine & biology.

[35]  N. Sharpe,et al.  Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. , 2000, Circulation.

[36]  P. Libby,et al.  The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions , 2007, The Journal of experimental medicine.

[37]  André Constantinesco,et al.  Assessment of left ventricular perfusion, volumes, and motion in mice using pinhole gated SPECT. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[38]  H. Halperin,et al.  Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction. , 2008, Journal of the American College of Cardiology.

[39]  Vasilis Ntziachristos,et al.  Free-space fluorescence molecular tomography utilizing 360° geometry projections , 2007 .

[40]  P. Jakob,et al.  Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics. , 2006, American journal of physiology. Heart and circulatory physiology.

[41]  D. D. Streeter,et al.  Engineering Mechanics for Successive States in Canine Left Ventricular Myocardium: II. Fiber Angle and Sarcomere Length , 1973, Circulation research.

[42]  C. Kramer,et al.  Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling. , 1997, Journal of the American College of Cardiology.

[43]  Patrick A Helm,et al.  Postinfarction myocardial scarring in mice: molecular MR imaging with use of a collagen-targeting contrast agent. , 2008, Radiology.

[44]  D. A. Christopher,et al.  Advances in ultrasound biomicroscopy. , 2000, Ultrasound in medicine & biology.

[45]  Saleh Saleh,et al.  Cardiac Mechanics Revisited: The Relationship of Cardiac Architecture to Ventricular Function , 2008, Circulation.

[46]  S. Cherry,et al.  Cardiac PET imaging in mice with simultaneous cardiac and respiratory gating , 2005, Physics in medicine and biology.

[47]  Elena Aikawa,et al.  Diffusion Spectrum MRI Tractography Reveals the Presence of a Complex Network of Residual Myofibers in Infarcted Myocardium , 2009, Circulation. Cardiovascular imaging.

[48]  E. Botvinick,et al.  Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction. , 1991, Journal of the American College of Cardiology.

[49]  B. K. Swann,et al.  PET/MR images acquired with a compact MR-compatible PET detector in a 7-T magnet. , 2007, Radiology.

[50]  F. Epstein,et al.  Quantification and MRI validation of regional contractile dysfunction in mice post myocardial infarction using high resolution ultrasound. , 2006, Ultrasound in medicine & biology.

[51]  Vasilis Ntziachristos,et al.  Fluorescence Tomography and Magnetic Resonance Imaging of Myocardial Macrophage Infiltration in Infarcted Myocardium In Vivo , 2007, Circulation.

[52]  Stefan Neubauer,et al.  Quantitative 3-Dimensional Echocardiography for Accurate and Rapid Cardiac Phenotype Characterization in Mice , 2004, Circulation.

[53]  G. Schmidt,et al.  Presence of sympathetically denervated but viable myocardium and its electrophysiologic correlates after early revascularised, acute myocardial infarction. , 2004, European heart journal.

[54]  Alberto Del Guerra,et al.  State-of-the-art of PET, SPECT and CT for small animal imaging , 2007 .

[55]  V. Wedeen,et al.  Diffusion MR tractography of the heart , 2009, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[56]  Paul D Acton,et al.  Noninvasive assessment of myocardial viability in a small animal model: Comparison of MRI, SPECT, and PET , 2008, Magnetic resonance in medicine.

[57]  Vasilis Ntziachristos,et al.  Born Normalization for Fluorescence Optical Projection Tomography for Whole Heart Imaging , 2009, Journal of visualized experiments : JoVE.

[58]  Stuart S Berr,et al.  Simultaneous Evaluation of Infarct Size and Cardiac Function in Intact Mice by Contrast-Enhanced Cardiac Magnetic Resonance Imaging Reveals Contractile Dysfunction in Noninfarcted Regions Early After Myocardial Infarction , 2004, Circulation.

[59]  I. Meredith,et al.  Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. , 1990, Physiological reviews.

[60]  D. D. Streeter Engineering Mechanics for Successive States in Canine Left Ventricular Myocardium: I. CAVITY AND WALL GEOMETRY , 1973, Circulation research.

[61]  Martin Paul,et al.  Physiology of local renin-angiotensin systems. , 2006, Physiological reviews.

[62]  F. Epstein,et al.  Borderzone contractile dysfunction is transiently attenuated and left ventricular structural remodeling is markedly reduced following reperfused myocardial infarction in inducible nitric oxide synthase knockout mice. , 2007, Journal of the American College of Cardiology.

[63]  S. Kaul,et al.  Noninvasive Ultrasound Imaging of Inflammation Using Microbubbles Targeted to Activated Leukocytes , 2000, Circulation.

[64]  G. Schuler,et al.  Alterations of myocardial presynaptic sympathetic innervation in patients with multi-vessel coronary artery disease but without history of myocardial infarction , 2003, Nuclear medicine communications.

[65]  H. Tamekiyo,et al.  Cardiac sympathetic dysfunction contributes to left ventricular remodelling after acute myocardial infarction , 2000, European Journal of Nuclear Medicine.

[66]  Vasilis Ntziachristos,et al.  Normalized Born ratio for fluorescence optical projection tomography. , 2009, Optics letters.

[67]  R Weissleder,et al.  Near-infrared optical imaging of protease activity for tumor detection. , 1999, Radiology.

[68]  Stuart S Berr,et al.  Reperfused myocardial infarction in mice: 3D mapping of late gadolinium enhancement and strain. , 2006, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[69]  Francis G Spinale,et al.  Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. , 2007, Physiological reviews.

[70]  Eric Tom,et al.  Myocardial Ischemic Memory Imaging With Molecular Echocardiography , 2007, Circulation.

[71]  V. Dilsizian,et al.  Early imaging in heart failure: Exploring novel molecular targets , 2007, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[72]  B. Tromberg,et al.  Noninvasive imaging of angiotensin receptors after myocardial infarction. , 2008, JACC. Cardiovascular imaging.

[73]  W. Gilson,et al.  Serial MRI evaluation of cardiac structure and function in mice after reperfused myocardial infarction , 2002, Magnetic resonance in medicine.

[74]  K. Weber,et al.  Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. , 1997, Circulation.

[75]  Vasilis Ntziachristos,et al.  Shedding light onto live molecular targets , 2003, Nature Medicine.

[76]  V. Dilsizian,et al.  Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischemic cardiomyopathy using targeted radiotracer technique. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[77]  P. Libby,et al.  Activatable Magnetic Resonance Imaging Agent Reports Myeloperoxidase Activity in Healing Infarcts and Noninvasively Detects the Antiinflammatory Effects of Atorvastatin on Ischemia-Reperfusion Injury , 2008, Circulation.

[78]  T. Guy,et al.  Region- and Type-Specific Induction of Matrix Metalloproteinases in Post–Myocardial Infarction Remodeling , 2003, Circulation.

[79]  Matthias Nahrendorf,et al.  In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging , 2005, Magnetic resonance in medicine.

[80]  R. Beyers,et al.  Noninvasive Tracking of Cardiac Embryonic Stem Cells In Vivo Using Magnetic Resonance Imaging Techniques , 2007, Stem cells.

[81]  I. Carrió Cardiac neurotransmission imaging. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[82]  Ralph Weissleder,et al.  Dual Channel Optical Tomographic Imaging of Leukocyte Recruitment and Protease Activity in the Healing Myocardial Infarct , 2007, Circulation research.

[83]  D. Dione,et al.  Noninvasive Targeted Imaging of Matrix Metalloproteinase Activation in a Murine Model of Postinfarction Remodeling , 2005, Circulation.

[84]  P. Camici,et al.  123I-mIBG Scintigraphy to predict risk for adverse cardiac outcomes in heart failure patients: Design of two prospective multicenter international trials , 2009, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[85]  Stuart S. Berr,et al.  Angiotensin II Type 2 Receptor Overexpression Preserves Left Ventricular Function After Myocardial Infarction , 2002, Circulation.

[86]  M. Schwaiger,et al.  Assessment of cardiac sympathetic neuronal function using PET imaging , 2004, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[87]  G. Dai,et al.  Molecular MRI Detects Low Levels of Cardiomyocyte Apoptosis in a Transgenic Model of Chronic Heart Failure , 2009, Circulation. Cardiovascular imaging.

[88]  Yi-Hwa Liu,et al.  A New Method for SPECT Quantification of Targeted Radiotracers Uptake in the Myocardium , 2005, MICCAI.

[89]  Leslie L. Clark,et al.  Specific Temporal Profile of Matrix Metalloproteinase Release Occurs in Patients After Myocardial Infarction: Relation to Left Ventricular Remodeling , 2006, Circulation.