Evaluation of normal physiologic left ventricular myocardial 18F-FDG uptake at fasting state

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1 Evaluation of normal physiologic left ventricular myocardial 18F-FDG uptake at fasting state Poster No.: C-1192 Congress: ECR 2012 Type: Scientific Exhibit Authors: H. Nose, H. Otsuka, Y. Otomi, K. Terazawa, S. IWAMOTO, S. Takao, M. Harada; Tokushima/JP Keywords: DOI: Physiological studies, PET, Cardiac, Tissue characterisation /ecr2012/C-1192 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 13

2 Purpose 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) assessment of the myocardium is useful in the evaluation of the primary cardiac tumor or cardiac metastasis, viability of myocardial ischemia, and in the detection of inflammatory myocardial sarcoid lesions. However, cardiac FDG uptake shows several patterns in the fasting state, it is often difficult to distinguish between normal or abnormal uptake. SO it is recommended that glucose loading is undertaken to raise this uptake prior to estimating viability. In addition, heparin loading is carried out to suppress the physiological uptake of FDG in the myocardium before attempting the detection of inflammatory lesions. In the present study, we evaluated normal physiological cardiac accumulation of FDG in the fasting state. Methods and Materials Between 30 March and 13 May 2011 at our hospital, 209 consecutive outpatients whose clinical information we could check in detail were enrolled in the study. However, 24 patients were excluded for the following reasons: 11 had cardiac disease (ischemia, infarction, arrhythmia or congestive heart failure); seven underwent radiation therapy during which the heart was included in the irradiated field; five had no information with regard to their smoking history; and one had very poor imaging data due to obesity and hyperglycemia. None of the remaining patients had serious pulmonary hypertension. In total, we investigated 185 patients (81 men and 104 women; mean age, 64.0 years; and age range, years). FDG PET/CT All patients fasted for at least 6 h prior to PET/CT imaging. After verification of their blood glucose level patients were intravenously injected with MBq/kg of FDG. Patients were then examined using a PET/CT scanner (Auiduo: Toshiba Medical Systems Corporation, Tochigi, Japan) at 1 h after FDG injection. Image acquisition was performed from the top of the head to the middle of the thigh. The attenuation-corrected PET image, non-attenuation-corrected PET image and CT image were reviewed, and the attenuationcorrected PET and CT images were co-registered using commercial software (Aquarius NET Viewer: TeraRecon Inc, San Mateo, CA, USA). Analysis of FDG PET imaging Page 2 of 13

3 FDG uptake in the myocardium was classified into four patterns as described in two previous reports [1,2]: 'none'; 'diffuse'; 'focal'; and 'focal on diffuse' (Figure 1). The none pattern indicated no uptake of FDG in the myocardium or less uptake than in the mediastinum. The diffuse pattern indicated diffuse and homogeneous uptake of FDG in the left ventricle (LV) wall. The pattern was only classified as focal when focal uptake was observed. The focal on diffuse pattern indicated focal uptake overlying the diffuse pattern. However, if focal nodular uptake was only seen in the lateral wall of the LV, we did not classify it as a focal or focal on diffuse pattern (Figure 2), because normal papillary muscle often shows focal uptake in the lateral wall. When focal or focal on diffuse patterns were seen, we classified focal FDG uptake into three further patterns when it only occurred in the basal wall (Figure 3). These three patterns were the 'ring' pattern, 'over half' pattern and 'spot' pattern. The ring pattern showed diffuse accumulation of FDG in the basal wall, the over half pattern showed more than 50% accumulation and the spot pattern showed less than 50% accumulation. Two or three board-certified radiologists, who were blinded to all of the clinical information, performed the visual analysis and classified uptake patterns. Statistical Analysis The statistical significance of differences in maximum standardized uptake value (SUVmax), age, blood glucose level, weight and size difference between malignant and benign lesions was examined using Fisher's exact test, and values of p <0.05 were considered as being statistically significant. The optimum cutoff value of SUVmax for the differentiation of malignancy was defined as the point on the ROC curve with the minimum distance from the 100% true positive and 0% false positive rate. The sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were calculated using the SUVmax cutoff value and the final diagnosis. Images for this section: Page 3 of 13

4 Fig. 1 Page 4 of 13

5 Fig. 2 Page 5 of 13

6 Fig. 3 Page 6 of 13

7 Results The frequencies of the myocardial FDG uptake patterns were as follows: none, n = 51 (27.5%); diffuse, n = 63 (34.1%); focal on diffuse, n = 39 (21.1%); and focal, n = 32 (17.3%) (Table 1). Age, blood glucose level, weight and dose of FDG did not differ significantly (p >0.05) for each pattern (Table 2). Focal and focal on diffuse patterns were seen in 71 patients and 63 patients exhibited focal uptake of FDG in the basal wall only (ring, n = 27; over half, n = 20; and spot, n = 16) (Table 3). Patients with a focal on diffuse pattern did not have a spot pattern and only one patient had a focal pattern with a ring pattern. Eight patients had focal uptake in other lesions (apex, n = 4; lateral, n = 3; and anterior, n = 1). Conclusion The myocardium metabolizes fatty acids and glucose as energy sources. With sufficiently extended fasting, the myocardium shifts from a predominantly glycolytic metabolism to a fatty acid metabolism [3]. In oncology, FDG PET is usually performed on patients in the fasting state, so fatty acid metabolism will be more predominant than glucose metabolism. However, cardiac FDG uptake often shows several patterns in the fasting state, and even in the same patient it often shows different uptake patterns at different times. There have been some previous reports on physiologic cardiac FDG uptake [4-8]. In these reports it was stated that cardiac uptake showed various patterns but parameters such as age, blood glucose level, weight and dose of FDG did not have relationship with uptake patterns of myocardium. Myocardial metabolic rate is related to serum free fatty acid levels, but it does not only depend on the fasting period. In line with this, it was found in our study that cardiac FDG uptake showed various patterns but no parameters had a significant effect on these patterns. Patients with cardiac sarcoidosis show abnormally high accumulation of FDG, so FDG PET is often used in the detection of cardiac sarcoidosis [1,2, 9-12]. We also investigated patients who showed focal FDG uptake. Thirty-two patients (17.3%) exhibited a focal pattern and 39 (21.1%) a diffuse pattern. Indeed 71 patients (38.4%) showed focal uptake. Thus, cardiac focal uptake was frequently seen in normal patients. However, almost all of these patients (63/71, 88.7%) accumulated FDG only in the basal wall, which showed various patterns and degrees of focal uptake. Uptake in the basal wall did not always indicate an abnormal finding when examination was undertaken in the fasting state. On the other hand, if we found focal uptake of FDG in other lesions rather than in the basal wall, we suspected the presence of cardiac diseases such as sarcoidosis, pulmonary hypertension [13], hypertrophic cardiomyopathy [14-16] or damage to the myocardium caused by radiotherapy [17-21]. However, normal patients rarely show focal uptake of FDG in other lesions. In our study, 8 of 185 (4.3%) patients exhibited focal uptake in other lesions. If we decided that focal uptake of FDG in the basal wall was Page 7 of 13

8 normal and focal uptake in other lesions was abnormal, accuracy and specificity rose, but sensitivity fell and we could not determine the true level of abnormal uptake in the basal wall. Heparin increases serum free fatty acid levels, reduces saccharometabolism and possibly minimizes background myocardial uptake of FDG. Heparin also activates plasma lipoprotein lipase which has the function of separating fatty acids. It is difficult to evaluate cardiac uptake in the fasting state and we should carry out heparin loading before injecting FDG. When heparin loading is performed in patients without cardiac disease, cardiac FDG uptake shows either the none pattern or the diffuse pattern, so we can easily evaluate cardiac uptake. It is useful to use cardiac MRI or blood-flow scintigraphy in combination with this approach. Limitations of our study were that we labeled some patient as having no cardiac disease only on the basis of clinical symptoms and anamnesis, so that it could not be definitely confirmed that all enrolled patients did not have cardiac disease. Normal myocardial FDG uptake followed several patterns and frequently involved focal uptake. Focal uptake was often seen in patients with sarcoidosis and other diseases, but it did not always indicate abnormal findings when FDG accumulation only occurred in the basal wall. On the other hand, if focal FDG uptake was found in other regions, with the exception of the basal wall, cardiac disease such as cardiac sarcoidosis or cardiomyopathy should be considered. We should therefore be aware of the normal physiologic uptake pattern when PET examination is performed on patients in a fasting state. Images for this section: Page 8 of 13

9 Table 1 Page 9 of 13

10 Table 2 Page 10 of 13

11 Table 3 Page 11 of 13

12 References 1. Ishimaru S, Tsujino I, Takei T, et al. Focal uptake on 18 F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis. Eur Heart 2005;26: Ohira H, Tsujino I, Ishimaru S, et al. Myocardial imaging with 18 F-fluoro-2- deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis. Eur J Nucl Med Mol Imaging 2008;35: Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol 1974;36: Shreve PD, Anzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 1999;19: Yamanouchi M, Yoshida K, Niwayama H, Nakagawa K, Aioi S, Shikama N. Effect of the duration of fasting on myocardial fluorine-18-fluorodexyglucose positron emission tomography images in normal males. Jpn Circ J 1996;60: de Groot M, Meeuwis AP, Kok PJ, Corstens FH, Oyen WJ. Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut. Eur J Nucl Med Mol Imaging 2005;32: Kaneta T, Hakamatsuka T, Takanami K, et al. Evaluation of the relationship between physiological FDG uptake in the heart and age, blood glucose level, fasting period, and hospitalization. Ann Nucl Med. 2006;20: Gropler RJ, Siegel BA, Lee KJ, et al. Non uniformity in myocardial accumulation of fluorine-18-fluorodeoxyglucose in normal fasted humans. J Nucl Med 1990;31: Langah R, Spicer K, Gebregziabher M, Gordon L. Effectiveness of prolonged fasting 18 F-FDG PET-CT in the detection of cardiac sarcoidosis. J Nucl Cardiol 2009;16: Okumura W, Iwasaki T, Toyama T, et al. Usefulness of fasting 18 F-FDG PET in identification of cardiac sarcoidosis. J Nucl Med 2004;45: Mehta D, Lubitz SA, Frankel Z, et al. Cardiac involvement in patients with sarcoidosis : Diagnostic and prognostic value of outpatient testing. Chest 2008;133: Langah R, Spicer K, Gebregziabher M, Gordon L. Effectiveness of prolonged fasting 18 F-FDG PET-CT in the detection of cardiac sarcoidosis. J Nucl Cardiol : Page 12 of 13

13 13. Kluge R, Barthel H, Pankau H, et al. Different mechanisms for changes in glucose uptake of the right and left ventricular myocardium in pulmonary hypertension. J Nucl Med 2005;46; Ishida Y, Nagata S, Uehara T, Yasumura Y, Fukuchi K, Miyatake K. Clinical analysis of myocardial perfusion and metabolism in patients with hypertrophic cardiomyopathy by single photon emission tomography and positron emission tomography. J Cardiol 2001;37 Suppl 1: Ito Y, Hasegawa S, Yamaguchi H, Yoshioka J, Uehara T, Nishimura T. Relation between thallium-201/iodine 123-BMIPP subtraction and fluorine 18 deoxyglucose polar maps in patients with hypertrophic cardiomyopathy. J Nucl Cardiol 2000;7: Park J-S, Cho I-H, Shin D-G, Kim Y-J, Hong G-R, Shim B-S. Hypertrophic cardiomyopathy complicated by left ventricular apical necrosis and aneurysm in a young man: FDG-PET findings. Korean J Intern Med 2007;22: Jingo K, Kaneta T, Nemoto K, et al. The utility of 18 F-fluorodeoxyglucose positron emission tomography for early diagnosis of radiation induced myocardial damage. Int J Radiat Oncol Biol Phys 2006;66: Jingo K, Nemoto K, Kaneta T, et al. A case of high FDG-uptake into the myocardium after radiotherapy for esophageal cancer. Nippon Igaku Hoshasen Gakkai Zasshi 2005;65: Ishikura S, Nihei K, Ohtsu A, et al. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol 2003;21: Small GR, Nicolson M, Buchan K, et al. Pericardial malignant mesothelioma: a latent complication of radiotherapy? Eur J Cardiothorac Surg 2008;33: Mukherjee S, Aston D, Minett M, et al. The significance of cardiac doses received during chemoradiation of oesophageal and gastro-oesophageal junctional cancers. Clin Oncol 2003;15: Personal Information Page 13 of 13