Annals of Nuclear Medicine (v.30, #10)

Analysis of the influence of 111In on 90Y-bremsstrahlung SPECT based on Monte Carlo simulation by Hiroaki Shiba; Akihiko Takahashi; Shingo Baba; Kazuhiko Himuro; Yasuo Yamashita; Masayuki Sasaki (675-681).
90Y-ibritumomab tiuxetan (Zevalin) which is used for the treatment of malignant lymphomas can be used for SPECT imaging based on bremsstrahlung from 90Y beta particles. However, gamma rays emitted by 111In, which is administered to evaluate the indication for the treatment, contaminate the 90Y bremsstrahlung images. Our objective is to investigate the influence of 111In on the 90Y SPECT images using Monte Carlo simulation.We used an in-house developed simulation code for the Monte Carlo simulation of electrons and photons (MCEP). Two hot spheres with diameters of 40 mm were put in an elliptical phantom. Both spheres (“sphere 1” and “sphere 2”) were filled with 90Y and 111In mixed solutions. The activities of 90Y in sphere 1 and sphere 2 were 241 and 394 kBq/mL, respectively, and the ones of 111In were 8.14 and 13.3 kBq/mL, respectively. The background activity of 90Y was 38.6 kBq/mL, whereas that of 111In was 1.30 kBq/mL; moreover, the acquisition time was 30 min. Two energy windows were used: one is 90–190 keV included the 111In photopeak; the other is 90–160 keV. To evaluate the quality of the SPECT images, the contrast recovery coefficient (CRC) and the constant noise ratio (CNR) of the SPECT images were derived.For the energy window between 90 and 160 keV, the 111In count was 74 % of the total. In that case, the CRC values were 30.1 and 30.7 % for “sphere 1” and “sphere 2”, respectively, whereas the CNR values were 6.8 and 12.1, respectively. For the energy window between 90 and 190 keV, the 111In count reached 85 % of the total count. The CRC and CNR values were 38.6 and 40.0 % and 10.6 and 19.4, respectively.Our simulation study revealed that the cross talk between 111In and 90Y in SPECT imaging is rather serious. Even for the energy window excluding the 111In photopeak, the count ratio of 90Y was less than 30 % of the total. However, the influence of 111In on 90Y-SPECT imaging cannot be ignored, and the count ratio because of 111In is important to estimate the density of 90Y.
Keywords: 90Y; 111In; Single photon emission computed tomography (SPECT); Monte Carlo simulation; Ibritumomab tiuxetan (Zevalin)

Automated quantification of amyloid positron emission tomography: a comparison of PMOD and MIMneuro by Woo Hee Choi; Yoo Hyun Um; Won Sang Jung; Sung Hoon Kim (682-689).
The aim of this study was to examine and compare two automated quantitative software tools (PMOD and MIMneuro) for the quantification of amyloid positron emission tomography (PET).A total of 30 subjects—15 Alzheimer’s disease (AD) patients and 15 cognitively normal age- and sex-matched controls—were enrolled. All subjects underwent structural volumetric magnetic resonance imaging (MRI) and amyloid PET scans with F-18 florbetaben. Regional standardized uptake value ratios (SUVRs) using the cerebellar cortex as a reference region were obtained using PMOD and MIMneuro.The SUVRs using both PMOD and MIMneuro showed high discriminatory power between the AD patients and cognitively normal controls. While PMOD and MIMneuro yielded significantly different SUVRs in some brain regions, the two methods had good overall agreement.MIMneuro provides comparable performance to PMOD without the need to acquire brain MRI. Therefore, MIMneuro might be suitable for clinical use to determine amyloid positivity.
Keywords: Quantification; Florbetaben; PET; β-Amyloid; Alzheimer’s disease

Validation of a simplified scatter correction method for 3D brain PET with 15O by Masanobu Ibaraki; Keisuke Matsubara; Kaoru Sato; Tetsuro Mizuta; Toshibumi Kinoshita (690-698).
Positron emission tomography (PET) enables quantitative measurements of various biological functions. Accuracy in data acquisition and processing schemes is a prerequisite for this. The correction of scatter is especially important when a 3D PET scanner is used. The aim of this study was to validate the use of a simplified calculation-based scatter correction method for 15O studies in the brain.We applied two scatter correction methods to the same 15O PET data acquired from patients with cerebrovascular disease (n = 10): a hybrid dual-energy-window scatter correction (reference method), and a deconvolution scatter correction (simplified method). The PET study included three sequential scans for 15O-CO, 15O-O2, and 15O-H2O, from which the following quantitative parameters were calculated, cerebral blood flow, cerebral blood volume, cerebral metabolic rate of oxygen, and oxygen extraction fraction.Both scatter correction methods provided similar reconstruction images with almost identical image noise, although there were slightly greater differences in white-matter regions compared with gray matter regions. These differences were also greater for 15O-CO than for 15O-H2O and 15O-O2. Region of interest analysis of the quantitative parameters demonstrated that the differences were less than 10 % (except for cerebral blood volume in white-matter regions), and the agreement between the methods was excellent, with intraclass correlation coefficients above 0.95 for all the parameters.The deconvolution scatter correction despite its simplified implementation provided similar results to the hybrid dual-energy-window scatter correction. We consider it suitable for application in a clinical 15O brain study using a 3D PET scanner.
Keywords: PET; Scatter correction; Brain; 15O

Development of a myocardial phantom and analysis system toward the standardization of myocardial SPECT image across institutions by Takayuki Shibutani; Masahisa Onoguchi; Tetsuro Katafuchi; Seigo Kinuya (699-707).
We developed a novel myocardial phantom and analysis program to standardize using a quantitative index to objectively evaluate the image quality. We aimed to reveal whether our proposed phantom and analysis program are suitable for image standardization.An evaluation system of myocardial image based on technical grounds (EMIT) phantom was developed to standardize the image quality of myocardial SPECT and was constructed with the lung and myocardium in the thorax phantom; the myocardial phantom included five normal areas and eight defective areas with four defects in size (5, 10, 15, and 20 mm) and four defects in thickness (10, 7.5, 5, and 2.5 mm). Therefore, this phantom was appropriate to simultaneously simulate eight different defects and normal myocardium. The %rate value, calculated using the region of interest method, and the %count value, calculated from the profile method, were automatically analyzed to evaluate myocardial defects. The phantom was validated using difference in count levels and filter parameters compared with those in previously reported models.The average %count of eight defects by 0.3, 0.4, 0.5, and 0.6 cycles/cm were 56.8, 47.4, 44.3, and 43.4 %, respectively, whereas the %count for 0.3 cycles/cm was significantly higher than that for 0.5 and 0.6 cycles/cm. The uniformity between full- and half-time images was 16.5 ± 4.2 and 18.7 ± 5.5 % for integral uniformity and 3.4 ± 1.2 and 3.4 ± 1.3 % for differential uniformity, respectively, revealing a significant difference in integral uniformity between the two acquisition times. Visual differences in defects were evident in full-time images between 0.30 and 0.50 cycles/cm, and defect detectability of the myocardial image at 0.30 cycles/cm was poor. Normal myocardial thickness widened in comparison with images at 0.50 cycles/cm. Compared with full-time myocardial image at the same cut-off frequency, the half-time myocardial image demonstrated inhomogeneous distribution and thickness of the normal myocardium.We developed a new phantom and program to standard image quality among multicenter for myocardial SPECT. The EMIT phantom and quantitative indices were useful for evaluating image quality. The physical characteristics of the image quality, including defects and uniformity, were properly measured by this method.
Keywords: EMIT phantom; Myocardial SPECT; Standardization; Image quality evaluation

Correlation of HIF-1α/HIF-2α expression with FDG uptake in lung adenocarcinoma by Kotaro Higashi; Toshiaki Yamagishi; Yoshimichi Ueda; Yasuhito Ishigaki; Miyako Shimasaki; Yuka Nakamura; Manabu Oguchi; Tsutomu Takegami; Motoyasu Sagawa; Hisao Tonami (708-715).
Hypoxia is a key element involved in the development and progression of tumors. HIF-1α may transiently induce and mediate the response to acute and severe hypoxia, while HIF-2α may induce a longer response and may control the response to chronic and moderate hypoxia. Hypoxia increases the cellular uptake of FDG. Therefore, HIF may play an important role in the process of the cellular uptake of FDG. The aim of this study was to compare HIF-1α/HIF-2α expression with FDG uptake, Glut-1 expression, and prognosis in the patients with lung adenocarcinoma and to investigate the role of HIF-1α/HIF-2α in the uptake of FDG in lung adenocarcinoma.In the current work, we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 44 patients with lung adenocarcinoma. The relationships between HIF-α expression and Glut-1 expression, FDG uptake, and clinicopathological factors, including prognosis, were analyzed.There was a marginal association between HIF-1α and HIF-2α expressions (P = 0.076). We found a significant correlation between HIF-2α expression and FDG uptake (P = 0.0001). HIF-1α expression showed a marginal association with FDG uptake (P = 0.066). FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression. A significant correlation was noticed between Glut-1 expression and both HIF-1α and HIF-2α expressions (P = 0.005 and P = 0.003, respectively). Univariate analysis of disease-free survival demonstrated that FDG uptake and HIF-2α expression, but not HIF-1α expression, were related to recurrence (P < 0.0001).FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression, and both FDG uptake and HIF-2α expression, but not HIF-1α expression was correlated with post-operative recurrence in the patients with lung adenocarcinoma. These results suggest that both FDG uptake and HIF-2α expression may represent a more aggressive phenotype and that HIF-2α may play a more important role than HIF-1α in the uptake of FDG in lung adenocarcinoma.
Keywords: PET; 18F-FDG; Lung adenocarcinoma; Hypoxia-inducible factor; Recurrence

Usefulness of the novel risk estimation software, Heart Risk View, for the prediction of cardiac events in patients with normal myocardial perfusion SPECT by Tomohiko Sakatani; Satoshi Shimoo; Kazuaki Takamatsu; Atsushi Kyodo; Yumika Tsuji; Kayoko Mera; Masahiro Koide; Koji Isodono; Yoshinori Tsubakimoto; Akiko Matsuo; Keiji Inoue; Hiroshi Fujita (716-721).
Myocardial perfusion single-photon emission-computed tomography (SPECT) can predict cardiac events in patients with coronary artery disease with high accuracy; however, pseudo-negative cases sometimes occur. Heart Risk View, which is based on the prospective cohort study (J-ACCESS), is a software for evaluating cardiac event probability.We examined whether Heart Risk View was useful to evaluate the cardiac risk in patients with normal myocardial perfusion SPECT (MPS).We studied 3461 consecutive patients who underwent MPS to detect myocardial ischemia and those who had normal MPS were enrolled in this study (n = 698). We calculated cardiac event probability by Heart Risk View and followed-up for 3.8 ± 2.4 years. The cardiac events were defined as cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization. During the follow-up period, 21 patients (3.0 %) had cardiac events. The event probability calculated by Heart Risk View was higher in the event group (5.5 ± 2.6 vs. 2.9 ± 2.6 %, p < 0.001). According to the receiver-operating characteristics curve, the cut-off point of the event probability for predicting cardiac events was 3.4 % (sensitivity 0.76, specificity 0.72, and AUC 0.85). Kaplan–Meier curves revealed that a higher event rate was observed in the high-event probability group by the log-rank test (p < 0.001).Although myocardial perfusion SPECT is useful for the prediction of cardiac events, risk estimation by Heart Risk View adds more prognostic information, especially in patients with normal MPS.
Keywords: 99mTc-tetrofosmin myocardial perfusion SPECT; Heart Risk View; Risk estimation

Respiratory-gated time-of-flight PET/CT during whole-body scan for lung lesions: feasibility in a routine clinical setting and quantitative analysis by Naohisa Suzawa; Yasutaka Ichikawa; Masaki Ishida; Yoya Tomita; Ryohei Nakayama; Hajime Sakuma (722-730).
To demonstrate the feasibility of respiratory gating during whole-body scan for lung lesions in routine 18F-FDG PET/CT examinations using a time-of-flight (TOF)-capable scanner to determine the effect of respiratory gating on reduction of both misregistration (between CT and PET) and image blurring, and on improvement of the maximum standardized uptake value (SUVmax).Patients with lung lesions who received FDG PET/CT were prospectively studied. Misregistration, volume of PET (Vp), and SUVmax were compared between ungated and gated images. The difference in respiratory gating effects was compared between lesions located in the upper or middle lobes (UML) and the lower lobe (LL). The correlation between three parameters (% change in misregistration, % change in Vp, and lesion size) and % change in SUVmax was analyzed.The study population consisted of 60 patients (37 males, 23 females; age 68 ± 12 years) with lung lesions (2.5 ± 1.7 cm). Fifty-eight out of sixty respiratory gating studies were successfully completed with a total scan time of 20.9 ± 1.9 min. Eight patients’ data were not suitable for analysis, while the remaining 50 patients’ data were analyzed. Respiratory gating reduced both misregistration by 21.4 % (p < 0.001) and Vp by 14.2 % (p < 0.001). The SUVmax of gated images improved by 14.8 % (p < 0.001). The % change in misregistration, Vp, and SUVmax by respiratory gating tended to be larger in LL lesions than in UML lesions. The correlation with % change in SUVmax was stronger in % change in Vp (r = 0.57) than % change in misregistration (r = 0.35). There was no statistically significant correlation between lesion size and % change in SUVmax (r = −0.20).Respiratory gating during whole-body scan in routine TOF PET/CT examinations is feasible and can reduce both misregistration and PET image blurring, and improve the SUVmax of lung lesions located primarily in the LL.
Keywords: Lung; PET/CT; TOF; Respiratory gating; Routine

Brain perfusion alterations in depressed patients with Parkinson’s disease by Young-Do Kim; Hyeonseok S. Jeong; In-Uk Song; Yong-An Chung; Eun Namgung; Yong-Duk Kim (731-737).
Although Parkinson’s disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using 99mTc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT).Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups.The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients.This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.
Keywords: Parkinson’s disease; Depression; Brain perfusion; SPECT; Regional cerebral blood flow

Assessment of radiological techniques application possibility for non-invasive diagnostics of latent inflammatory processes in myocardium in patients with atrial fibrillation by Svetlana I. Sazonova; Julia N. Ilyushenkova; Yuri B. Lishmanov; Roman E. Batalov; Alexey E. Sazonov; Ludmila A. Larionova; Evgeniy A. Nesterov; Natalia V. Varlamova; Julia V. Rogovskaya; Tatyana A. Shelkovnikova; Sergey V. Popov (738-748).
Aim was to study the performance of single-photon emission computed tomography (SPECT) with 99mTc-pyrophosphate (99mTc-PYP) in diagnostics of chronic latent inflammation in myocardium of patients with atrial fibrillation (AF).The research included 70 patients (the average age of 49.3 ± 10.2 years) with persistent form of idiopathic AF. All patients underwent myocardium SPECT with 99mTc-PYP and cardiac magnetic resonance imaging (CMR) before the ablation. During the ablation endomyocardium sampling for histological and immunohistochemical verification of myocarditis was performed.Sensitivity of SPECT with 99mTc-PYP in diagnoses of chronic latent myocarditis in patients with AF in relation to endomyocardial biopsy was 80 %, specificity—83 % and diagnostic accuracy—82 %. Sensitivity, specificity and diagnostic accuracy of myocardium perfusion scintigraphy for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 30, 50 and 50 % correspondingly. Also the close correlation between the size of the perfusion defect and the severity of myocardial fibrosis in patients with AF was revealed. Specificity of the Lake Louise criteria for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 77.6 %, sensitivity—60 % and diagnostic accuracy—74.5 %. For only LGE specificity was 16 %, sensitivity—90 % and diagnostic accuracy—28 %.The study showed the possibility of successful application of radionuclide methods for diagnoses of chronic latent myocarditis at AF. Taking into account high informative values the results of scintigraphy can be also considered as a promising additional criteria for selecting patients with AF of unexplained etiology for non-invasive endomyocardial biopsy procedure.
Keywords: Atrial fibrillation; Myocarditis; CMR; 99mTc-pyrophosphate

Assessment of 10B concentration in boron neutron capture therapy: potential of image-guided therapy using 18FBPA PET by Eku Shimosegawa; Kayako Isohashi; Sadahiro Naka; Genki Horitsugi; Jun Hatazawa (749-755).
In boron neutron capture therapy (BNCT) for cancer, the accurate estimation of 10B tissue concentrations, especially in neighboring normal organs, is important to avoid adverse effects. The 10B concentration in normal organs after loading with 10B, however, has not been established in humans. In this study, we performed 4-borono-2-[18F]-fluoro-phenylalanine (18FBPA) PET in healthy volunteers and estimated the chronological changes in the 10B concentrations of normal organs.In 6 healthy volunteers, whole-body 18FBPA PET scans were repeated 7 times during 1 h, and the mean 18FBPA distributions of 13 organs were measured. Based on the 18FBPA PET data, we then estimated the changes in the 10B concentrations of the organs when the injection of a therapeutic dose of 10BPA–fructose complex (10BPA–fr; 30 g, 500 mg/kg body weight) was assumed.The maximum mean 18FBPA concentrations were reached at 2–6 min after injection in all the organs except the brain and urinary bladder. The mean 18FBPA concentration in normal brain plateaued at 24 min after injection. When the injection of a therapeutic dose of 10BPA–fr was assumed, the estimated mean 10B concentration in the kidney increased to 126.1 ± 24.2 ppm at 3 min after injection and then rapidly decreased to 30.9 ± 7.4 ppm at 53 min. The estimated mean 10B concentration in the bladder gradually increased and reached 383.6 ± 214.7 ppm at 51 min. The mean 10B concentration in the brain was estimated to be 7.6 ± 1.5 ppm at 57 min. 18FBPA PET has a potential to estimate 10B concentration of normal organs before neutron irradiation of BNCT when several assumptions are validated in the future studies.
Keywords: PET; 18FBPA; 10BPA; BNCT; 10B

Residual FDG uptake of primary thyroid lymphoma after treatment may overestimate residual lymphoma by Hayahiko Fujii; Masashi Nakadate; Hiroaki Tanaka; Naoki Harata; Sayako Oota; Jun Isogai; Katsuya Yoshida (756-759).
To assess 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images in primary thyroid lymphoma (PTL) patients before and after treatment.We conducted a retrospective review of data for ten patients (four men, six women) of mean age 65 (range 48–88) years, with histopathologically confirmed malignant thyroid lymphoma who underwent pre-treatment and post-treatment 18F-FDG PET between January 2005 and December 2014. Thyroid uptake was assessed by the 5-point scale score based on maximum intensity projection images.Four of the ten patients were judged to have a complete metabolic response (scores 1–3) and four to have a partial metabolic response (PMR; scores 4–5). Three of the four PMR patients had a good outcome with a treatment-free interval and overall survival of at least 53.0 months, although two of these three patients showed residual FDG uptake in the thyroid for more than 2 years after completion of treatment. Two of the ten patients were considered to have progressive metabolic disease.In patients with PTL, residual FDG uptake in the thyroid after treatment that corresponds to a PMR may not always indicate a poor outcome.
Keywords: Primary thyroid lymphoma; FDG PET/CT; Lugano classification; 5-Point scale; Treatment response