18F-Fluoro-2-deoxyglucose positron emission tomography in cardiac sarcoidosis

  • Hiroshi Ohira
  • Ichizo TsujinoEmail author
  • Keiichiro Yoshinaga
Review Article


Cardiac sarcoidosis (CS) is a rare and potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and most notably sudden cardiac death. Accurate diagnosis of CS is thus mandatory; however, a reliable approach that enables diagnosis of CS with high sensitivity and specificity has yet to be established. Recent studies have demonstrated the promising potential of 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) in the diagnosis and assessment of CS. Indeed, 18F-FDG PET provides a wide variety of advantages over previous imaging modalities; however, there are pitfalls and limitations that should be recognized. In this review article, (1) the rationale for 18F-FDG PET application in CS, (2) suitable pretest preparations, and (3) evaluation protocols for the 18F-FDG PET images obtained will be addressed. In particular, sufficient suppression of physiological 18F-FDG uptake in the heart is essential for accurate assessment of CS. Also, (4) recent studies addressing the diagnostic role of 18F-FDG PET and (5) the clinically important differences between 18F-FDG PET and other imaging technologies will be reviewed. For example, active sarcoid lesions and their response to steroid treatment will be better detected by 18F-FDG PET, whereas fibrotic lesions might be shown more clearly by magnetic resonance imaging or other nuclear myocardial perfusion imaging. In the last decade, 18F-FDG PET has substantially enhanced detection of CS; however, CS would be better evaluated by a combination of multiple modalities. In the future, advances in 18F-FDG PET and other emerging imaging modalities are expected to enable better management of patients with sarcoidosis.


Cardiac sarcoidosis 18F-Fluoro-2-deoxyglucose positron emission tomography Fasting Low-carbohydrate diet Heparin Magnetic resonance imaging 



The authors acknowledge Dr. Masaharu Nishimura, Professor of the first Department of Medicine of the Hokkaido University School of Medicine, and Dr. Nagara Tamaki, Professor of the Department of Nuclear Medicine of the Hokkaido University School of Medicine, for critical reading of the manuscript. We also thank Ms. Yuka Yoshida, a nutritionist at the Hokkaido University Hospital, for her cooperation in the preparation of the low-carbohydrate meals.

Conflicts of interest



  1. 1.
    Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med 1997;336:1224–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Sharma OP, Maheshwari A, Thaker K. Myocardial sarcoidosis. Chest 1993;103:253–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 1978;58:1204–11.PubMedGoogle Scholar
  4. 4.
    Matsui Y, Iwai K, Tachibana T, Fruie T, Shigematsu N, Izumi T, et al. Clinicopathological study of fatal myocardial sarcoidosis. Ann N Y Acad Sci 1976;278:455–69.PubMedCrossRefGoogle Scholar
  5. 5.
    Lorell B, Alderman EL, Mason JW. Cardiac sarcoidosis. Diagnosis with endomyocardial biopsy and treatment with corticosteroids. Am J Cardiol 1978;42:143–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Ishikawa T, Kondoh H, Nakagawa S, Koiwaya Y, Tanaka K. Steroid therapy in cardiac sarcoidosis. Increased left ventricular contractility concomitant with electrocardiographic improvement after prednisolone. Chest 1984;85:445–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Hiraga H, Hiroe M, Iwai K. Guidelines for diagnosis of cardiac sarcoidosis: study report on diffuse pulmonary diseases (in Japanese). Tokyo: The Japanese Ministry of Health and Welfare; 1993. p. 23–4.Google Scholar
  8. 8.
    Yamagishi H, Shirai N, Takagi M, Yoshiyama M, Akioka K, Takeuchi K, et al. Identification of cardiac sarcoidosis with (13)N-NH(3)/(18)F-FDG PET. J Nucl Med 2003;44:1030–6.PubMedGoogle Scholar
  9. 9.
    Okumura W, Iwasaki T, Toyama T, Iso T, Arai M, Oriuchi N, et al. Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis. J Nucl Med 2004;45:1989–98.PubMedGoogle Scholar
  10. 10.
    Ishimaru S, Tsujino I, Takei T, Tsukamoto E, Sakaue S, Kamigaki M, et al. Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis. Eur Heart J 2005;26:1538–43.PubMedCrossRefGoogle Scholar
  11. 11.
    Ohira H, Tsujino I, Ishimaru S, Oyama N, Takei T, Tsukamoto E, et al. Myocardial imaging with 18F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis. Eur J Nucl Med Mol Imaging 2008;35:933–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Langah R, Spicer K, Gebregziabher M, Gordon L. Effectiveness of prolonged fasting 18f-FDG PET-CT in the detection of cardiac sarcoidosis. J Nucl Cardiol 2009;16:801–10.PubMedCrossRefGoogle Scholar
  13. 13.
    Takeda N, Yokoyama I, Hiroi Y, Sakata M, Harada T, Nakamura F, et al. Positron emission tomography predicted recovery of complete A-V nodal dysfunction in a patient with cardiac sarcoidosis. Circulation 2002;105:1144–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Tadamura E, Yamamuro M, Kubo S, Kanao S, Hosokawa R, Kimura T, et al. Images in cardiovascular medicine. Multimodality imaging of cardiac sarcoidosis before and after steroid therapy. Circulation 2006;113:e771–3.PubMedCrossRefGoogle Scholar
  15. 15.
    Pandya C, Brunken RC, Tchou P, Schoenhagen P, Culver DA. Detecting cardiac involvement in sarcoidosis: a call for prospective studies of newer imaging techniques. Eur Respir J 2007;29:418–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Roberts WC, McAllister Jr HA, Ferrans VJ. Sarcoidosis of the heart. A clinicopathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 11). Am J Med 1977;63:86–108.PubMedCrossRefGoogle Scholar
  17. 17.
    Bleeker-Rovers CP, Vos FJ, Mudde AH, Dofferhoff AS, de Geus-Oei LF, Rijnders AJ, et al. A prospective multi-centre study of the value of FDG-PET as part of a structured diagnostic protocol in patients with fever of unknown origin. Eur J Nucl Med Mol Imaging 2007;34:694–703.PubMedCrossRefGoogle Scholar
  18. 18.
    Jaffer FA, Libby P, Weissleder R. Molecular imaging of cardiovascular disease. Circulation 2007;116:1052–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Brudin LH, Valind SO, Rhodes CG, Pantin CF, Sweatman M, Jones T, et al. Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography. Eur J Nucl Med 1994;21:297–305.PubMedCrossRefGoogle Scholar
  20. 20.
    Lewis PJ, Salama A. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med 1994;35:1647–9.PubMedGoogle Scholar
  21. 21.
    Warshauer DM, Lee JK. Imaging manifestations of abdominal sarcoidosis. AJR Am J Roentgenol 2004;182:15–28.PubMedGoogle Scholar
  22. 22.
    Ishimaru S, Tsujino I, Sakaue S, Oyama N, Takei T, Tsukamoto E, et al. Combination of 18F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in assessing cardiac sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:234–5.PubMedGoogle Scholar
  23. 23.
    Smedema JP, Reenaers V, Geukens R. Images in cardiology. Cardiac sarcoidosis in a 60 year old woman. Heart 2006;92:688.PubMedCrossRefGoogle Scholar
  24. 24.
    Wu YW, Tadamura E, Yamamuro M, Kanao S, Hosokawa R, Kimura T, et al. Complementary appearance of glucose and lipid metabolism in cardiac sarcoidosis. Int J Cardiol 2007;116:281–3.PubMedCrossRefGoogle Scholar
  25. 25.
    Nomura S, Funabashi N, Tsubura M, Uehara M, Shiina Y, Daimon M, et al. Cardiac sarcoidosis evaluated by multimodality imaging. Int J Cardiol. In press 2010.Google Scholar
  26. 26.
    Bartlett ML, Bacharach SL, Voipio-Pulkki LM, Dilsizian V. Artifactual inhomogeneities in myocardial PET and SPECT scans in normal subjects. J Nucl Med 1995;36:188–95.PubMedGoogle Scholar
  27. 27.
    Gropler RJ, Siegel BA, Lee KJ, Moerlein SM, Perry DJ, Bergmann SR, et al. Nonuniformity in myocardial accumulation of fluorine-18-fluorodeoxyglucose in normal fasted humans. J Nucl Med 1990;31:1749–56.PubMedGoogle Scholar
  28. 28.
    Lum DP, Wandell S, Ko J, Coel MN. Reduction of myocardial 2-deoxy-2-[18F]fluoro-D-glucose uptake artifacts in positron emission tomography using dietary carbohydrate restriction. Mol Imaging Biol 2002;4:232–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Williams G, Kolodny GM. Suppression of myocardial 18F-FDG uptake by preparing patients with a high-fat, low-carbohydrate diet. AJR Am J Roentgenol 2008;190:W151–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Wykrzykowska J, Lehman S, Williams G, Parker JA, Palmer MR, Varkey S, et al. Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med 2009;50:563–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Cheng VY, Slomka PJ, Ahlen M, Thomson LE, Waxman AD, Berman DS. Impact of carbohydrate restriction with and without fatty acid loading on myocardial 18F-FDG uptake during PET: a randomized controlled trial. J Nucl Cardiol 2010;17:286–91.PubMedCrossRefGoogle Scholar
  32. 32.
    Wisneski JA, Gertz EW, Neese RA, Mayr M. Myocardial metabolism of free fatty acids. Studies with 14C-labeled substrates in humans. J Clin Invest 1987;79:359–66.PubMedCrossRefGoogle Scholar
  33. 33.
    Yoshinaga K, Tamaki N. Imaging myocardial metabolism. Curr Opin Biotechnol 2007;18:52–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Choi Y, Brunken RC, Hawkins RA, Huang SC, Buxton DB, Hoh CK, et al. Factors affecting myocardial 2-[F-18]fluoro-2-deoxy-D-glucose uptake in positron emission tomography studies of normal humans. Eur J Nucl Med 1993;20:308–18.PubMedCrossRefGoogle Scholar
  35. 35.
    Lum D, Wandell S, Ko J, Coel M. 1. Positron emission tomography of thoracic malignancies. Reduction of myocardial fluorodeoxyglucose uptake artifacts with a carbohydrate restricted diet. Clin Positron Imaging 2000;3:155.PubMedCrossRefGoogle Scholar
  36. 36.
    Nuutila P, Koivisto VA, Knuuti J, Ruotsalainen U, Teräs M, Haaparanta M, et al. Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo. J Clin Invest 1992;89:1767–74.PubMedCrossRefGoogle Scholar
  37. 37.
    Persson E. Lipoprotein lipase, hepatic lipase and plasma lipolytic activity. Effects of heparin and a low molecular weight heparin fragment (Fragmin). Acta Med Scand Suppl 1988;724:1–56.PubMedCrossRefGoogle Scholar
  38. 38.
    Blockmans D. The use of (18F)fluoro-deoxyglucose positron emission tomography in the assessment of large vessel vasculitis. Clin Exp Rheumatol 2003;21:S15–22.PubMedGoogle Scholar
  39. 39.
    Nuutila P, Knuuti MJ, Raitakari M, Ruotsalainen U, Teräs M, Voipio-Pulkki LM, et al. Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans. Am J Physiol 1994;267:E941–6.PubMedGoogle Scholar
  40. 40.
    Koiwa H, Tsujino I, Ohira H, Yoshinaga K, Otsuka N, Nishimura M. Images in cardiovascular medicine: imaging of cardiac sarcoid lesions using fasting cardiac 18F-fluorodeoxyglucose positron emission tomography: an autopsy case. Circulation 2010;122:535–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Kaminaga T, Takeshita T, Yamauchi T, Kawamura H, Yasuda M. The role of iodine-123-labeled 15-(p-iodophenyl)-3R,S-methylpentadecanoic acid scintigraphy in the detection of local myocardial involvement of sarcoidosis. Int J Cardiol 2004;94:99–103.PubMedCrossRefGoogle Scholar
  42. 42.
    Ohira H, Tsujino I, Sato T, Yoshinaga K, Manabe O, Oyama N, et al. Early detection of cardiac sarcoid lesions with 18F-fluoro-2-deoxyglucose positron emission tomography. Intern Med. In press 2011.Google Scholar
  43. 43.
    Alavi A, Gupta N, Alberini JL, Hickeson M, Adam LE, Bhargava P, et al. Positron emission tomography imaging in nonmalignant thoracic disorders. Semin Nucl Med 2002;32:293–321.PubMedCrossRefGoogle Scholar
  44. 44.
    Chang JM, Lee HJ, Goo JM, Lee HY, Lee JJ, Chung JK, et al. False positive and false negative FDG-PET scans in various thoracic diseases. Korean J Radiol 2006;7:57–69.PubMedCrossRefGoogle Scholar
  45. 45.
    Matsuki M, Matsuo M. MR findings of myocardial sarcoidosis. Clin Radiol 2000;55:323–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Smedema JP, Snoep G, van Kroonenburgh MP, van Geuns RJ, Dassen WR, Gorgels AP, et al. Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis. J Am Coll Cardiol 2005;45:1683–90.PubMedCrossRefGoogle Scholar
  47. 47.
    Shimada T, Shimada K, Sakane T, Ochiai K, Tsukihashi H, Fukui M, et al. Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy by gadolinium-DTPA-enhanced magnetic resonance imaging. Am J Med 2001;110:520–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Vignaux O. Cardiac sarcoidosis: spectrum of MRI features. AJR Am J Roentgenol 2005;184:249–54.PubMedGoogle Scholar
  49. 49.
    Vignaux O, Dhote R, Duboc D, Blanche P, Dusser D, Weber S, et al. Clinical significance of myocardial magnetic resonance abnormalities in patients with sarcoidosis: a 1-year follow-up study. Chest 2002;122:1895–901.PubMedCrossRefGoogle Scholar
  50. 50.
    Serra JJ, Monte GU, Mello ES, Coral GP, Avila LF, Parga JR, et al. Images in cardiovascular medicine. Cardiac sarcoidosis evaluated by delayed-enhanced magnetic resonance imaging. Circulation 2003;107:e188–9.PubMedGoogle Scholar
  51. 51.
    Matoh F, Satoh H, Shiraki K, Odagiri K, Saitoh T, Urushida T, et al. The usefulness of delayed enhancement magnetic resonance imaging for diagnosis and evaluation of cardiac function in patients with cardiac sarcoidosis. J Cardiol 2008;51:179–88.PubMedCrossRefGoogle Scholar
  52. 52.
    Patel MR, Cawley PJ, Heitner JF, Klem I, Parker MA, Jaroudi WA, et al. Detection of myocardial damage in patients with sarcoidosis. Circulation 2009;120:1969–77.PubMedCrossRefGoogle Scholar
  53. 53.
    Mehta D, Lubitz SA, Frankel Z, Wisnivesky JP, Einstein AJ, Goldman M, et al. Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value of outpatient testing. Chest 2008;133:1426–35.PubMedCrossRefGoogle Scholar
  54. 54.
    Casset-Senon D, Philippe L, Renard JP, Cosnay P. Recurrent ventricular tachycardia in cardiac sarcoidosis: usefulness of fluorodeoxyglucose positron emission tomography for adequate management of corticoid therapy after placement of an implantable cardioverter defibrillator. J Nucl Cardiol 2008;15:282–5.PubMedCrossRefGoogle Scholar
  55. 55.
    Györik S, Ceriani L, Menafoglio A, Gallino A, Wyttenbach R. 18F-FDG PET scan as follow-up tool for sarcoidosis with symptomatic cardiac conduction disturbances requiring a pacemaker. Thorax 2007;62:560.PubMedCrossRefGoogle Scholar
  56. 56.
    Thompson RC, Cullom SJ. Issues regarding radiation dosage of cardiac nuclear and radiography procedures. J Nucl Cardiol 2006;13:19–23.PubMedCrossRefGoogle Scholar
  57. 57.
    Okayama K, Kurata C, Tawarahara K, Wakabayashi Y, Chida K, Sato A. Diagnostic and prognostic value of myocardial scintigraphy with thallium-201 and gallium-67 in cardiac sarcoidosis. Chest 1995;107:330–4.PubMedCrossRefGoogle Scholar
  58. 58.
    Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol 2003;42:1318–33.PubMedCrossRefGoogle Scholar
  59. 59.
    Nakazawa A, Ikeda K, Ito Y, Iwase M, Sato K, Ueda R, et al. Usefulness of dual 67Ga and 99mTc-sestamibi single-photon-emission CT scanning in the diagnosis of cardiac sarcoidosis. Chest 2004;126:1372–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Kiuchi S, Teraoka K, Koizumi K, Takazawa K, Yamashina A. Usefulness of late gadolinium enhancement combined with MRI and 67-Ga scintigraphy in the diagnosis of cardiac sarcoidosis and disease activity evaluation. Int J Cardiovasc Imaging 2007;23:237–41.PubMedCrossRefGoogle Scholar
  61. 61.
    Tadamura E, Yamamuro M, Kubo S, Kanao S, Saga T, Harada M, et al. Effectiveness of delayed enhanced MRI for identification of cardiac sarcoidosis: comparison with radionuclide imaging. AJR Am J Roentgenol 2005;185:110–5.PubMedGoogle Scholar
  62. 62.
    Machac J, Bacharach SL, Bateman TM, Bax JJ, Beanlands R, Bengel F, et al. Positron emission tomography myocardial perfusion and glucose metabolism imaging. J Nucl Cardiol 2006;13:e121–51.PubMedCrossRefGoogle Scholar
  63. 63.
    Yoshinaga K, Klein R, Tamaki N. Generator-produced rubidium-82 positron emission tomography myocardial perfusion imaging-from basic aspects to clinical applications. J Cardiol 2010;55:163–73.PubMedCrossRefGoogle Scholar
  64. 64.
    Yoshinaga K, Manabe O, Tamaki N. Which imaging modality is the best for evaluation of myocardial ischemia? Physiological assessment of myocardial perfusion using nuclear cardiology would enhance coronary artery disease patient care—nuclear cardiology revisited: it’s not the end of an era, just the beginning of a new era. Circ J 2011;75:713–22.PubMedCrossRefGoogle Scholar
  65. 65.
    Tellier P, Paycha F, Antony I, Nitenberg A, Valeyre D, Foult JM, et al. Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis. Am J Med 1988;85:189–93.PubMedCrossRefGoogle Scholar
  66. 66.
    Eguchi M, Tsuchihashi K, Hotta D, Hashimoto A, Sasao H, Yuda S, et al. Technetium-99m sestamibi/tetrofosmin myocardial perfusion scanning in cardiac and noncardiac sarcoidosis. Cardiology 2000;94:193–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Le Guludec D, Menad F, Faraggi M, Weinmann P, Battesti JP, Valeyre D. Myocardial sarcoidosis. Clinical value of technetium-99m sestamibi tomoscintigraphy. Chest 1994;106:1675–82.PubMedCrossRefGoogle Scholar
  68. 68.
    Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, 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. Circulation 2002;105:539–42.PubMedCrossRefGoogle Scholar
  69. 69.
    Smulders NM, Bast A, van Kroonenburgh MJ, Drent M. Improvement of cardiac sympathetic nerve function in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:140–2.PubMedGoogle Scholar
  70. 70.
    Hoitsma E, Faber CG, van Kroonenburgh MJ, Gorgels AP, Halders SG, Heidendal GA, et al. Association of small fiber neuropathy with cardiac sympathetic dysfunction in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:43–50.PubMedGoogle Scholar
  71. 71.
    Hyodo E, Hozumi T, Takemoto Y, Watanabe H, Muro T, Yamagishi H, et al. Early detection of cardiac involvement in patients with sarcoidosis by a non-invasive method with ultrasonic tissue characterisation. Heart 2004;90:1275–80.PubMedCrossRefGoogle Scholar
  72. 72.
    Smedema JP. Tissue Doppler imaging in cardiac sarcoidosis. Eur J Echocardiogr 2008;9:579–80.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hiroshi Ohira
    • 1
  • Ichizo Tsujino
    • 1
    Email author
  • Keiichiro Yoshinaga
    • 2
  1. 1.First Department of MedicineHokkaido University School of MedicineSapporoJapan
  2. 2.Department of Photobiology, Division of Molecular Cellular ImagingHokkaido University School of MedicineSapporoJapan

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