Annals of Nuclear Medicine (v.27, #6)

Voxel-based analysis of 201Tl SPECT for grading and diagnostic accuracy of gliomas: comparison with ROI analysis by Tomoyuki Kuwako; Sunao Mizumura; Ryusuke Murakami; Tamiko Yoshida; Masato Shiiba; Hidetaka Sato; Yoshimitsu Fukushima; Akira Teramoto; Shin-ichiro Kumita (493-501).
The aim of this retrospective study was to assess the utility of a voxel-based analysis (VBA) method for 201Tl SPECT in glioma, compared to conventional ROI analysis.We recruited 24 patients with glioma (high-grade 15; low-grade 9), for whom pre-operative 201Tl SPECT and MRI were performed. SPECT images were coregistered with MRI. The uptake ratio (UR) images of tumor to contralateral normal tissue were measured on early and delayed images, and the 201Tl retention index (RI) map was calculated from the early and delayed uptake ratio maps. In the ROI analysis, tumors were traced on a UR map, and the mean and maximal uptake ratio values on the early images were, respectively, defined as the mean and maximal UR. The mean and maximal RI values (mean and maximal RI) were calculated by division of the mean and maximal UR, respectively, on the delayed image by the mean and maximal UR on the early image. For the RI map calculated voxel by voxel, the maximal RI value was defined as VBA-RI. We evaluated sensitivity and accuracy of differential analysis with the mean and maximal UR, RI, and VBA-RI.The high- and low-grade groups showed no significant difference in mean and maximal RI (0.98 ± 0.12 vs. 1.05 ± 0.09 and 0.98 ± 0.18 vs. 1.05 ± 0.14, respectively). The AUC and accuracy of the mean and maximal RI were 0.681 and 66.7 %, and 0.622 and 62.5 %, respectively. In contrast, VBA-RI was higher in high-grade than in low-grade glioma (1.69 ± 0.27 vs. 0.68 ± 0.66, p < 0.001). The AUC and accuracy of VBA-RI were 0.963 and 95.8 %, which are higher than those obtained for mean (p < 0.05) and maximal RI (p < 0.01). There was no significant difference in ROC between the VBA-RI and the mean UR (0.911, p = 0.456) and maximal UR (0.933, p = 0.639); however, the AUC, sensitivity, and diagnostic accuracy of VBA-RI were all higher than those of the mean and maximal UR.The voxel-based analysis method of 201Tl SPECT may improve diagnostic performance for gliomas, compared with ROI analysis.
Keywords: 201Tl SPECT; Glioma; Voxel-based analysis

Underestimation of the ejection fraction using the quantitative gated SPECT for patients with myocardial hypertrophy by Hidenori Yamaguchi; Masahiro Toba; Yasuo Amano; Keiichi Ishihara; Kyoichi Mizuno; Shin-ichiro Kumita (502-507).
The aim of the present study is to quantify the degree of the error as a function of the left ventricular (LV) wall thickness, in calculation of the ejection fraction (EF) using gated single-photon emission computed tomography (SPECT). The essential error of quantitative gated SPECT (QGS) software in patients with myocardial hypertrophy has not been quantitatively estimated.Forty-six patients with known or suspected hypertrophic cardiomyopathy underwent gated myocardial perfusion SPECT and cardiac magnetic resonance (MR) imaging. The EF value was automatically calculated from gated SPECT using the QGS software. Twelve points of regional LV wall thickness and the EF value were estimated from MR images.Only a fair correlation was found between the QGS-EF and the MR-EF values (r = 0.48, y = 0.49x + 26.80, p < 0.01), and the QGS-EF was underestimated (r = 0.25, y = 0.90x) in 30 patients with myocardial hypertrophy (mean wall thickness > 12 mm). The magnitude of the error of the EF quantification from gated SPECT showed a significant negative correlation with the mean 12-point LV wall thickness in all 46 patients (r = −0.67, y = −4.12x + 40.44, p < 0.0001). The degree of the error of the ESV and that of the EDV showed positive correlation with the mean LV wall thickness (r = 0.55, y = 5.46x − 56.13, p < 0.0001; r = 0.31, y = 4.20x − 55.28, p < 0.05, respectively).The underestimation of EF increases with the degree of myocardial hypertrophy, because of the overestimation of the LV cavity especially in the end-systolic phase.
Keywords: Quantitative gated SPECT; Cardiac magnetic resonance imaging; Hypertrophic cardiomyopathy; Ejection fraction

Imaging quality of F-18-FDG PET/CT in the inpatient versus outpatient setting by Xuexian Yan; Jian Kang; Yanli Zhou; Ramisa Ehsan; Raghuveer Halkar; Kimberly E. Applegate; David M. Schuster (508-514).
The purpose of this study is to investigate potential differences in the image quality of inpatient versus outpatient F-18-FDG PET/CT to provide evidence for appropriate policies and procedures to be promulgated on inpatient referrals.100 consecutive inpatient and 100 outpatient F-18-FDG PET/CT scans were compared from the same time period and PET/CT scanner. Each study was evaluated for a subjective overall rating (optimal vs. suboptimal), and also by objective measurements (SUVmean) in four background structures (brain, blood pool, liver, and muscle).96 outpatient scans were rated optimal and 4 suboptimal whereas corresponding numbers for inpatient scans were 77 and 23 (p < 0.001). Of the objective indices, cerebellar SUV was significantly different in inpatient versus outpatient (5.3 vs. 6.9; p < 0.001) as well as suboptimal versus optimal rated groups (4.8 vs. 6.3; p < 0.001). While mean blood glucose was higher for inpatients (108.01 vs. 101.49 mg/dl; p = 0.017), it was not significantly different between optimal and suboptimal exams. Linear regression analysis between blood glucose levels and cerebellar uptake revealed an inverse relationship (R = −0.38, p < 0.001).There was a significantly higher number of inpatient PET/CT scans rated as suboptimal in comparison to outpatient scans. Decreased cerebellar uptake was present in suboptimal rated studies and in inpatient studies. Altered biodistribution is thus a potential etiology of reduced scan quality among inpatients. These findings, if duplicated among other readers and centers, may form the basis of quality control recommendations for inpatient PET/CT ordering patterns.
Keywords: F-18-FDG; PET/CT; Quality control

Role of 2-[18F]fluoro-2-deoxyglucose positron emission tomography in preoperative management of solid-type small-sized lung cancer by Shinsuke Saisho; Koichiro Yasuda; Ai Maeda; Takuro Yukawa; Riki Okita; Yuji Hirami; Katsuhiko Shimizu; Masao Nakata (515-522).
2-[18F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is routinely used for the diagnosis of primary lung cancer. However, the role of FDG-PET in the diagnosis and staging of small-sized lung cancer has not been sufficiently evaluated. The purpose of this study was to determine the utility of FDG-PET for preoperative staging of solid-type small-sized lung cancer manifesting as solid-component predominant nodules.One-hundred and eighteen patients with solid-type small-sized (≤2 cm) lung cancer diagnosed as clinical stage IA based on thin-slice computed tomography (TS-CT) were included in this study. Before surgery, FDG-PET was performed in 78 patients (CT/PET group), and TS-CT alone was performed in 40 patients (CT group). Clinical and pathological stage and prognosis were retrospectively reviewed according to whether FDG-PET had been performed.No significant differences in clinical factors were observed when comparing the CT/PET group and the CT group. Of the 78 patients in the CT/PET group, 12 (15.4 %) were diagnosed with clinical stage IIA or IIIA disease based on FDG-PET findings, but no advanced cases with contraindications for curative surgery were seen. In the CT/PET group, the pathological stage was IA in 66 patients, IB in eight patients, IIA in one patient, and IIIA in three patients; 16 patients had incorrectly staged disease. The accurate staging rate was 79.5 % for the CT–PET group and 70.0 % for the CT group (P = 0.262). Among patients diagnosed with clinical stage IA disease, the 3-year overall survival rate was 85.5 % for the 66 patients in the CT/PET group and 76.8 % for the 40 patients in the CT group (P = 0.554). No significant difference was observed in accuracy of preoperative staging and prognosis between the two groups.FDG-PET produced no clear benefit for the preoperative management of patients with solid-type clinical T1aN0M0 lung cancer, in terms of postoperative survival and the concordance rate of clinical and pathological stage.
Keywords: Small-sized lung cancer; Preoperative staging; FDG-PET; CT

Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction by Hirofumi Aoki; Ichiro Matsunari; Yusuke Nomura; Wataru Fujita; Ryoko Komatsu; Yoshiharu Miyazaki; Stephan G. Nekolla; Kouji Kajinami (523-531).
The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction.In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by 11C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using 11C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique.The 11C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P < 0.05), and negatively with peak longitudinal strain in systole in the non-infarcted myocardium (r = −0.561, P < 0.05). Kmono, as an index of oxidative metabolism, was significantly correlated with rate pressure product (r = 0.649, P < 0.01), but not with 11C-HED retention (r = 0.188, P = 0.442). Furthermore, there was no significant correlation between Kmono and LVEF (r = 0.106, P = 0.666) or peak longitudinal strain in systole (r = −0.256, P = 0.291) in the non-infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (>41 mL) was associated with reduced 11C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups.This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.
Keywords: Sympathetic innervation; Oxidative metabolism; Myocardial infarction; Speckle tracking echocardiography; Positron emission tomography

Therapeutic efficacy of 188Re-MN-16ET lipiodol in an animal model of hepatocellular carcinoma by Ping-Wun Huang; Shih-Chung Tsai; Tsai-Yueh Luo; Chia-Hung Kao; Wan-Yu Lin (532-537).
In our recent study, we developed a new radiopharmaceutical (Re-188 MN-16ET lipiodol) with encouraging results for the treatment of liver malignancy. In this study, we further evaluated the therapeutic efficacy of this radiopharmaceutical by measuring tumor response and survival times in rats with liver tumors after intra-hepatic arterial injection of Re-188 MN-16ET lipiodol.Twelve male rats bearing hepatic tumors were divided into three groups. Group 1 received an intra-hepatic arterial injection of 18.5 MBq Re-188 MN-16ET lipiodol; Group 2 received lipiodol and Group 3 received normal saline. Tumor size was measured by liver sonography before injection, at 2, 4, and 8 weeks after injection. Survival time and response rate were calculated.All rats showed good response and survived over 60 days in Group 1 while all rats showed poor response in Group 2 and Group 3 with only 25 % of rats in Group 2 and none (0 %) in Group 3 survived over 60 days. The p value was 0.0067 between Group 1 and Group 3; 0.04 between Group 1 and Group 2; and 0.034 between Group 2 and Group 3.Re-188 MN-16ET lipiodol has good potential for the treatment of hepatoma.
Keywords: Rhenium-188; Lipiodol; Therapeutic effects; Hepatoma; Intra-hepatic arterial injection

Physiological and tumoral uptake of 68Ga-DOTATATE: standardized uptake values and challenges in interpretation by Serkan Kuyumcu; Zeynep Gözde Özkan; Yasemin Sanli; Ebru Yilmaz; Ayse Mudun; Isik Adalet; Seher Unal (538-545).
The objective of this study is to determine the range of SUVmax of 68Ga-DOTATATE in normal organs and tumoral lesions and establish uptake unrelated to NET.One hundred and twenty patients (57 men, 63 women), who underwent 68Ga-DOTATATE PET/CT imaging in our institution were analyzed. Patients were indicated for 68Ga-DOTATATE PET/CT imaging to detect primary tumor or metastasis of suspected or previously known NET, to determine SSTR positivity and to detect occult source of ectopic Cushing syndrome. Normal range of uptake was calculated for the organs that were proven to have no pathology by either conventional radiological imaging or clinical follow-up, using SUVmax as a semiquantitative measure. Uptake and tumor to background (T/B) ratios of tumoral lesions in liver, pancreas, bone, brain and lymph nodes were calculated. Uptakes due to lesions unrelated to NET were also documented.Significant uptake was found in spleen, kidneys, adrenal glands, liver and pituitary gland with mean SUVmax of 24.67, 14.30, 13.73, 9.12 and 9.74 respectively. Uptake was measured separately for the pancreatic head and body separately, however, besides a slightly heterogeneous uptake; the difference was not statistically significant. Uptake in the tumoral lesions had high (T/B) ratios with mean SUVmax of 28.72, 25.21, 18.28, 34.73 and 12.59 for liver, pancreas, bone, brain and lymph nodes, respectively. Incidental benign tumoral lesions were detected in 3 patients (2.5 %) which were meningioma and fibrous dysplasia demonstrating significant and breast fibroadenoma demonstrating mild 68Ga-DOTATATE uptake. Non-neoplastic processes were detected in 4 patients (14.1 %), including postsurgical inflammation, reactive lymph nodes, arthritis and demonstrated faint to mild 68Ga-DOTATATE uptake, with the exception of significant uptake in accessory spleen. 68Ga-DOTATATE has high T/B ratio with physiological biodistribution comparable to its counterparts. However, the presence of SSTRs in benign and malignant lesions unrelated to NET may be challenging in interpretation particularly where the physiological uptake is variable.
Keywords: 68Ga-DOTATATE; SUVmax ; PET/CT; Neuroendocrine tumors

The aim of this study was to evaluate the clinical value of 18F-fluorodeoxyglucose (FDG) uptake and the clinicopathological or immunohistochemical findings of the primary tumor to predict axillary lymph node (ALN) metastasis in breast cancer with clinically negative ALN.This study retrospectively enrolled 104 women (49.43 ± 9.9 years) having breast cancer with clinically negative ALN using all types of preoperative imaging modalities including ultrasonography, FDG positron emission tomography, and magnetic resonance imaging. All cases of breast cancer in this study were proven as invasive ductal carcinoma with ≥1 cm in size. The final diagnosis of ALN status was confirmed by permanent pathology after operation.Among 104 breast cancers with clinically negative ALN, 21 breast cancers (20.2 %) were proven to have ALN metastasis. The ROC curve analysis showed that the best cut-off value of SUVmax for identifying ALN metastasis was 9.8 with 33.3 % sensitivity and 92.8 % specificity (AUC = 0.656; p = 0.027). The multivariable analysis revealed that primary tumors with SUVmax >9.8 (p = 0.011) and D2-40 positivity (p = 0.027) were independently associated with ALN metastasis with odds ratios of 5.516 (CI 1.475–20.6333) and 3.409 (CI 1.154–10.072), respectively.Our study demonstrates that the incidence of ALN metastasis in even rigorously clinically evaluated breast cancer without suspiciously positive ALN is still not negligible, and while a high SUVmax of the primary tumor may be associated with a higher incidence of ALN metastasis in breast cancer with clinically negative ALN, a low SUVmax does not exclude ALN metastasis.
Keywords: Breast cancer; Axillary lymph node; FDG PET; SUVmax ; D2-40

The usefulness of 18F-FDG PET/MRI fusion image in diagnosing pancreatic tumor: comparison with 18F-FDG PET/CT by Shigeki Nagamachi; Ryuichi Nishii; Hideyuki Wakamatsu; Youichi Mizutani; Shogo Kiyohara; Seigo Fujita; Shigemi Futami; Tatefumi Sakae; Eiji Furukoji; Shozo Tamura; Hideo Arita; Kazuo Chijiiwa; Keiichi Kawai (554-563).
This study aimed at demonstrating the feasibility of retrospectively fused 18F FDG-PET and MRI (PET/MRI fusion image) in diagnosing pancreatic tumor, in particular differentiating malignant tumor from benign lesions. In addition, we evaluated additional findings characterizing pancreatic lesions by FDG-PET/MRI fusion image.We analyzed retrospectively 119 patients: 96 cancers and 23 benign lesions. FDG-PET/MRI fusion images (PET/T1 WI or PET/T2WI) were made by dedicated software using 1.5 Tesla (T) MRI image and FDG-PET images. These images were interpreted by two well-trained radiologists without knowledge of clinical information and compared with FDG-PET/CT images. We compared the differential diagnostic capability between PET/CT and FDG-PET/MRI fusion image. In addition, we evaluated additional findings such as tumor structure and tumor invasion.FDG-PET/MRI fusion image significantly improved accuracy compared with that of PET/CT (96.6 vs. 86.6 %). As additional finding, dilatation of main pancreatic duct was noted in 65.9 % of solid types and in 22.6 % of cystic types, on PET/MRI-T2 fusion image. Similarly, encasement of adjacent vessels was noted in 43.1 % of solid types and in 6.5 % of cystic types. Particularly in cystic types, intra-tumor structures such as mural nodule (35.4 %) or intra-cystic septum (74.2 %) were detected additionally. Besides, PET/MRI-T2 fusion image could detect extra benign cystic lesions (9.1 % in solid type and 9.7 % in cystic type) that were not noted by PET/CT.In diagnosing pancreatic lesions, FDG-PET/MRI fusion image was useful in differentiating pancreatic cancer from benign lesions. Furthermore, it was helpful in evaluating relationship between lesions and surrounding tissues as well as in detecting extra benign cysts.
Keywords: 18F FDG-PET/CT; 18F FDG-PET/MRI fusion image; Pancreatic tumor

Scintigraphic comparison of renal ischemia–reperfusion injury models in rats: correlations with biochemical and histopathological findings by Salih Sinan Gültekin; Öner Odabaş; Zeynep Giniş; Aysun Gökçe; Metin Yığman; Serkan Doğan; Başak Boztok (564-571).
This study aimed to compare the effect on renal functions of ischemia–reperfusion (I–R) injury models by renal scintigraphy and to investigate possible correlations among scintigraphic, biochemical and pathological findings.An experimental I–R injury was performed on the left kidneys of 40 Wistar rats: pedincular continuous clamping in Group 1 (n = 10), pedincular cyclic clamping in Group 2 (n = 10), arterial continuous clamping in Group 3 (n = 10) and arterial cyclic clamping in Group 4 (n = 10). A functional and morphological assessment was made by 99mTc-MAG3 scintigraphy, biochemical tests and histopathological examination in the late period of I–R injury. Data were analyzed statistically.Statistically significant differences were found in the peak counting (C max), normalized residual activity (NORA), renal retention (RR), split renal function (SRF) and the time to the C max (T max) parameters between the right and left kidneys in each group (p < 0.001). In multiple group comparisons for the left kidney statistically significant differences were determined for C max (F = 4.75, df = 3, p < 0.05), NORA (F = 4.362, df = 3, p < 0.05), RR (F = 10.49, df = 3, p < 0.001) and SRF (F = 4.17, df = 3, p < 0.05) but not T max (F = 1.13, df = 3, p > 0.05). The total scores of Groups 1, 2, 3, and 4 were, respectively, found to be 18, 30, 20 and 24 by grading of renogram curves and 22, 28, 23 and 25 by pathological scoring system. There was a significant correlation among the two score data (r = 0.867, p < 0.001). 99mTc-MAG3 scintigraphy was a reliable method to evaluate renal dysfunction in the late period of I–R injury. Cyclic clamping, especially pedincular type was compatible with higher tubular dysfunction and structural damage.
Keywords: Renal scintigraphy; 99mTc-MAG3; Ischemia–reperfusion injury; Ischemia–reperfusion scintigraphic patterns; Ischemia–reperfusion scintigraphic parameters; Rats

Incidental focal FDG uptake in heart is a lighthouse for considering cardiac screening by Ryogo Minamimoto; Miyako Morooka; Yoko Miyata; Kimiteru Ito; Momoko Okasaki; Hisao Hara; Osamu Okazaki; Masao Moroi; Kazuo Kubota (572-580).
Cardiac FDG uptake is known to show a variety of patterns under clinical fasting conditions. We hypothesized that focal FDG uptake in the heart (FUH) represents a sign of cardiac disease risk, especially in coronary artery disease (CAD).The aim of this study was to clarify the relationship between FUH and cardiac disease.Cases showing FUH were selected based on comments in diagnostic reports or identification on retrospective review. Quantitative analysis was performed using maximum standardized uptake value (SUVmax), with regions of interest drawn over focal uptake areas in the heart as confirmed by PET/CT and in lateral side of the same slice showing focal FDG uptake.For the 20 patients (11 men, 9 women) with confirmed FUH, coronary artery stenosis or history of treatment for coronary disease was present in 11 patients (55.0 %), and 2 patients showed apical hypertrophy. Mean SUVmax of FUH did not differ significantly between patients with confirmed cardiac disease and those with no evidence of cardiac disease (P = 0.78).FUH suggests a high likelihood of CAD in patients without myocardial symptoms. Cardiac screening or a check of the history of cardiac disease is thus worth considering when FUH is seen incidentally on FDG-PET/CT.
Keywords: FDG; PET/CT; Heart; Focal cardiac uptake; Apical hypertrophy