Prospective Evaluation of 18F-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome

Background—The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI 18F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of 18F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. Methods and Results—We prospectively enrolled 49 patients with ST-segment–elevation myocardial infarction and performed 18F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, 99mTc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of 18F-FDG-uptake and late gadolinium enhancement showed substantial overlap (&kgr;=0.66), whereas quantitative analysis demonstrated that 18F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14high/CD16+ monocytes correlated with the infarction size and 18F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). 18F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (&Dgr; ejection fraction: P<0.04, &Dgr; end-diastolic volume: P<0.02, &Dgr; end-systolic volume: P<0.005). Conclusions—In this study, the intensity of 18F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, 18F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury.

[1]  Ahmed Tawakol,et al.  PET/MRI of inflammation in myocardial infarction. , 2012, Journal of the American College of Cardiology.

[2]  M. Nahrendorf,et al.  Leukocyte Behavior in Atherosclerosis, Myocardial Infarction, and Heart Failure , 2013, Science.

[3]  O. Prante,et al.  Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[4]  J. Piek,et al.  Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. , 2014, European heart journal.

[5]  D. Fliser,et al.  Cd14؉؉cd16؉ Monocytes Independently Predict Cardiovascular Events a Cohort Study of 951 Patients Referred for Elective Coronary Angiography , 2022 .

[6]  T. Akasaka,et al.  Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. , 2009, Journal of the American College of Cardiology.

[7]  Joshua N. Baker,et al.  Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells. , 2015, Cell stem cell.

[8]  M. Pittet,et al.  Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. , 2010, Circulation.

[9]  J. Barrio,et al.  Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model. , 1985, Journal of the American College of Cardiology.

[10]  G. Lip,et al.  Immunophenotypic characterization of human monocyte subsets: possible implications for cardiovascular disease pathophysiology , 2011, Journal of thrombosis and haemostasis : JTH.

[11]  A. Kastrati,et al.  A randomized trial comparing stenting with balloon angioplasty in small vessels in patients with symptomatic coronary artery disease. ISAR-SMART Study Investigators. Intracoronary Stenting or Angioplasty for Restenosis Reduction in Small Arteries. , 2000, Circulation.

[12]  Johan Nuyts,et al.  Completion of a truncated attenuation image from the attenuated PET emission data , 2013, IEEE Nuclear Science Symposuim & Medical Imaging Conference.

[13]  John Andersson,et al.  Adaptive immunity and atherosclerosis. , 2010, Clinical immunology.

[14]  Ahmed Tawakol,et al.  Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. , 2010, JACC. Cardiovascular imaging.

[15]  S. Nekolla,et al.  Simultaneous positron emission tomography/magnetic resonance imaging identifies sustained regional abnormalities in cardiac metabolism and function in stress-induced transient midventricular ballooning syndrome: a variant of Takotsubo cardiomyopathy. , 2012, Circulation.

[16]  J. Piek,et al.  A proinflammatory monocyte response is associated with myocardial injury and impaired functional outcome in patients with ST-segment elevation myocardial infarction: monocytes and myocardial infarction. , 2012, American heart journal.

[17]  F. Bengel,et al.  Characterizing the Inflammatory Tissue Response to Acute Myocardial Infarction by Clinical Multimodality Noninvasive Imaging , 2014, Circulation. Cardiovascular imaging.

[18]  M. Cybulsky,et al.  GM-CSF regulates intimal cell proliferation in nascent atherosclerotic lesions , 2009, The Journal of experimental medicine.

[19]  S. Nekolla,et al.  Hybrid PET/MR Imaging of the Heart: Potential, Initial Experiences, and Future Prospects , 2013, The Journal of Nuclear Medicine.

[20]  S. Schoenberg,et al.  Phase-sensitive inversion-recovery MR imaging in the detection of myocardial infarction. , 2005, Radiology.

[21]  O. Simonetti,et al.  The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. , 2000, The New England journal of medicine.

[22]  R. Gibbons,et al.  Feasibility of tomographic 99mTc-hexakis-2-methoxy-2-methylpropyl-isonitrile imaging for the assessment of myocardial area at risk and the effect of treatment in acute myocardial infarction. , 1989, Circulation.

[23]  P. Libby,et al.  Chigh Monocytes Depend on Nr 4 a 1 to Balance Both Inflammatory and Reparative Phases in the Infarcted Myocardium , 2014 .

[24]  W. Wijns,et al.  Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake. , 1988, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  T. Spinks,et al.  Increased uptake of 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina. , 1986, Circulation.

[26]  B. V. Van Tassell,et al.  Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. , 2014, Journal of the American College of Cardiology.

[27]  S. Nekolla,et al.  Quantitative assessment of glucose metabolism in the vessel wall of abdominal aortic aneurysms: correlation with histology and role of partial volume correction , 2013, The International Journal of Cardiovascular Imaging.

[28]  M. Schwaiger,et al.  Myocardial glucose transporter GLUT1: translocation induced by insulin and ischemia. , 1999, Journal of molecular and cellular cardiology.

[29]  M. Cerqueira,et al.  Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. , 2002, Circulation.

[30]  Sungeun Kim,et al.  Metabolic Activity of the Spleen and Bone Marrow in Patients With Acute Myocardial Infarction Evaluated by 18F-Fluorodeoxyglucose Positron Emission Tomograpic Imaging , 2014, Circulation. Cardiovascular imaging.

[31]  V. Roger,et al.  Heart failure after myocardial infarction: clinical presentation and survival , 2005, European journal of heart failure.

[32]  Michael J Pencina,et al.  Long-Term Trends in the Incidence of Heart Failure After Myocardial Infarction , 2008, Circulation.

[33]  Ernst J. Rummeny,et al.  Phenotyping of Tumor Biology in Patients by Multimodality Multiparametric Imaging: Relationship of Microcirculation, αvβ3 Expression, and Glucose Metabolism , 2010, The Journal of Nuclear Medicine.

[34]  P. Franken,et al.  Compared Performance of High-Sensitivity Cameras Dedicated to Myocardial Perfusion SPECT: A Comprehensive Analysis of Phantom and Human Images , 2012, The Journal of Nuclear Medicine.

[35]  J. Rudd,et al.  PET imaging of inflammation in atherosclerosis , 2014, Nature Reviews Cardiology.

[36]  石丸 伸司.  Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis , 2005 .

[37]  Nassir Navab,et al.  Tissue Classification as a Potential Approach for Attenuation Correction in Whole-Body PET/MRI: Evaluation with PET/CT Data , 2009, Journal of Nuclear Medicine.

[38]  M. Cerqueira,et al.  Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association , 2002, The international journal of cardiovascular imaging.

[39]  G. Delso,et al.  Performance Measurements of the Siemens mMR Integrated Whole-Body PET/MR Scanner , 2011, The Journal of Nuclear Medicine.

[40]  R. Wahl,et al.  From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors , 2009, Journal of Nuclear Medicine.

[41]  C. Love,et al.  FDG PET of infection and inflammation. , 2005, Radiographics : a review publication of the Radiological Society of North America, Inc.

[42]  P. Libby,et al.  Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography. , 2011, Journal of the American College of Cardiology.

[43]  G. Filippatos,et al.  Anti‐Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study , 2015, Circulation.

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

[45]  A. Drzezga,et al.  First Clinical Experience with Integrated Whole-Body PET/MR: Comparison to PET/CT in Patients with Oncologic Diagnoses , 2012, The Journal of Nuclear Medicine.

[46]  N. Frangogiannis,et al.  The inflammatory response in myocardial injury, repair, and remodelling , 2014, Nature Reviews Cardiology.

[47]  Nassir Navab,et al.  Registration of myocardial PET and SPECT for viability assessment using mutual information. , 2010, Medical physics.

[48]  A Randomized Trial Comparing Stenting With Balloon Angioplasty in Small Vessels in Patients With Symptomatic Coronary Artery Disease , 2000 .

[49]  R. Weissleder,et al.  Differential Contribution of Monocytes to Heart Macrophages in Steady-State and After Myocardial Infarction , 2014, Circulation research.

[50]  E. Piccaluga,et al.  The Role of PET with 13N-Ammonia and 18F-FDG in the Assessment of Myocardial Perfusion and Metabolism in Patients with Recent AMI and Intracoronary Stem Cell Injection , 2010, The Journal of Nuclear Medicine.

[51]  T. Hackl,et al.  Acute myocardial infarction: serial cardiac MR imaging shows a decrease in delayed enhancement of the myocardium during the 1st week after reperfusion. , 2010, Radiology.

[52]  Kyung-Han Lee,et al.  Augmented 18F-FDG uptake in activated monocytes occurs during the priming process and involves tyrosine kinases and protein kinase C. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[53]  P. Libby,et al.  Impaired infarct healing in atherosclerotic mice with Ly-6C(hi) monocytosis. , 2010, Journal of the American College of Cardiology.

[54]  M. Nishimura,et al.  Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis. , 2005, European heart journal.

[55]  R. Gibbons,et al.  Quantitative myocardial SPECT for infarct sizing: feasibility of a multicenter trial evaluated using a cardiac phantom. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[56]  V. Dilsizian,et al.  Imaging myocardial metabolism and ischemic memory , 2008, Nature Clinical Practice Cardiovascular Medicine.

[57]  M. Forsting,et al.  Standardized uptake values for [¹⁸F] FDG in normal organ tissues: comparison of whole-body PET/CT and PET/MRI. , 2013, European journal of radiology.