Annals of Nuclear Medicine (v.29, #8)

Evaluation of a revised version of computer-assisted diagnosis system, BONENAVI version 2.1.7, for bone scintigraphy in cancer patients by Mitsuru Koizumi; Noriaki Miyaji; Taisuke Murata; Kazuki Motegi; Kenta Miwa; Masamichi Koyama; Takashi Terauchi; Kei Wagatsuma; Kazunori Kawakami; Jens Richter (659-665).
BONENAVI is a computer-assisted diagnosis system that analyzes bone scintigraphy automatically. We experienced more than a few segmentation errors with the previous BONENAVI version (2.0.5). We have since obtained a revised version (2.1.7) and evaluate it.Bone scans of patients were analyzed by BONENAVI version 2.0.5 and a revised version 2.1.7 with regard to segmentation errors, sensitivity, and specificity. Patients with skeletal metastases from prostate cancer, lung cancer, breast cancer, and other cancers were included in the study as true-positive cases. Patients with no skeletal metastasis (regardless of hot spots), and patients with abnormal bone scans but no skeletal metastasis were included as negative cases. Bone-scan patients were subjected to artificial neural network (ANN) evaluation. Values equal to or above 0.5 were regarded as positive, and those below 0.5 as negative. The patients whose clinical status did not correspond to their ANN scores were assessed for any similarities.The frequency of segmentation errors was statistically significantly reduced when using BONENAVI version 2.1.7. The differences in sensitivity and specificity for the results of version 2.0.5 versus version 2.1.7 were not different, giving a high Cohen’s kappa coefficient. In the patients who showed an increased ANN value with version 2.1.7, a few false-positive thoracic lesions were identified. Patients whose ANN value was significantly high with version 2.0.5 showed no tendencies.Revised BONENAVI version 2.1.7 for bone scintigraphy was superior with regard to segmentation errors. However, its sensitivity and specificity were similar to those of version 2.0.5. The false-positive identification of thoracic lesions in revised version 2.1.7 might be subject to remedy.
Keywords: Bone scan; Skeletal metastasis; Computer-aided diagnosis; BONENAVI version 2.1.7

Formula corrected maximal standardized uptake value in FDG-PET for partial volume effect and motion artifact is not a prognostic factor in stage I non-small cell lung cancer treated with stereotactic body radiotherapy by Takaya Yamamoto; Noriyuki Kadoya; Yuko Shirata; Tomohiro Kaneta; Masashi Koto; Rei Umezawa; Youjirou Ishikawa; Masaki Kubozono; Toshiyuki Sugawara; Haruo Matsushita; Keiko Abe; Ken Takeda; Keiichi Jingu (666-673).
It is known that the partial volume effect and respiratory motion blur affect quantitative parameters such as the maximum standardized uptake value (SUVmax) in FDG-PET, especially in small lesions. The purpose of this study was to assess the prognostic value of corrected SUVmax, which was corrected SUVmax for the partial volume effect and respiratory motion blur, in patients with stage I non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT).Fifty-one patients who were treated with SBRT between 2005 and 2011 in our institute were enrolled. The median tumor diameter was 2.2 cm (range 0.9–3.9 cm). The prescribed dose was typically 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions to the isocenter of irradiation fields. Each raw SUVmax was corrected using the recently proposed formula, and the correlations of raw SUVmax and corrected SUVmax with local control rate (LCR) were analyzed retrospectively.Median raw SUVmax before SBRT was 6.4 (range 0.6–22.8). Median corrected SUVmax was 8.0 (range 0.8–22.8), which was significantly increased (p < 0.01). The median follow-up period for survivors was 45.3 months (range 18.5–82.0 months). The 3-year LCR and overall survival rates were 81.8 and 65.2 %, respectively. In univariate analysis, raw SUVmax [per 1 increase; p = 0.02, hazard ratio (HR) 1.20, 95 % confidence interval (CI) 1.03–1.42] was significantly correlated with LCR, but corrected SUVmax did not show a significant correlation with LCR (per 1 increase; p = 0.15, HR 1.07, 95 % CI 0.96–1.19). Other factors significantly correlated with LCR were diagnosis (pathological diagnosis vs. clinical diagnosis; p = 0.04, HR 6.17, 95 % CI 1.08–116) and tumor diameter (per 1 mm increase; p < 0.01, HR 1.33, 95 % CI 1.15–1.61).Tumor diameter was the most significant predictor of LCR after SBRT. Correction for the partial volume effect and respiratory motion blur may weaken the prognostic value of SUVmax.
Keywords: Stereotactic body radiotherapy; Lung cancer; Prognosis; Corrected SUVmax

Diagnostic value of Thallium-201 scintigraphy in differentiating malignant bone tumors from benign bone lesions by Ryota Inai; Takayoshi Shinya; Akihiro Tada; Shuhei Sato; Tomohiro Fujiwara; Ken Takeda; Toshiyuki Kunisada; Hiroyuki Yanai; Toshifumi Ozaki; Susumu Kanazawa (674-681).
This retrospective study aims to evaluate the diagnostic capacity of thallium-201 (201Tl) scintigraphy for differentiating malignant bone tumors from benign bone lesions.Between January 2006 and December 2012, 279 patients with bone lesions (51 malignant and 228 benign) underwent 201Tl scintigraphy before treatment. To evaluate 201Tl uptake, we investigated tumor-to-background contrast (TBC) as well as TBC washout rate (WR). The differences of TBC on early and delayed images and WR were estimated by the Mann–Whitney U test. Receiver operating characteristic (ROC) analyses were used to determine the cut-off TBC values for differentiating malignant bone tumors from benign bone lesions.There were statistically significant differences in median TBC between malignant tumors and benign lesions. These differences occurred for early imaging (1.57 vs. 0.09, p < 0.001) as well as for delayed imaging (0.83 vs. 0.07, p < 0.001). However, there was no statistical difference in WR between malignant tumors and benign lesions (44 vs. 43 %, NS). The chosen TBC cut-off value was 0.68 for early imaging and 0.38 for delayed imaging. Using these cut-off values, the prediction of malignancy had a 77 % sensitivity, 74 % specificity, and 75 % accuracy for early imaging and an 80 % sensitivity, 76 % specificity, and 77 % accuracy for delayed imaging.201Tl scintigraphy may have the ability to distinguish malignant bone tumors from benign bone lesions.
Keywords: Thallium-201 scintigraphy; Malignant bone tumor; Benign bone tumor; Receiver operating characteristic (ROC) analysis; Tumor-to-background contrast (TBC)

High-resolution brain SPECT imaging by combination of parallel and tilted detector heads by Atsuro Suzuki; Wataru Takeuchi; Takafumi Ishitsu; Yuichi Morimoto; Keiji Kobashi; Yuichiro Ueno (682-696).
To improve the spatial resolution of brain single-photon emission computed tomography (SPECT), we propose a new brain SPECT system in which the detector heads are tilted towards the rotation axis so that they are closer to the brain. In addition, parallel detector heads are used to obtain the complete projection data set. We evaluated this parallel and tilted detector head system (PT-SPECT) in simulations.In the simulation study, the tilt angle of the detector heads relative to the axis was 45°. The distance from the collimator surface of the parallel detector heads to the axis was 130 mm. The distance from the collimator surface of the tilted detector heads to the origin on the axis was 110 mm. A CdTe semiconductor panel with a 1.4 mm detector pitch and a parallel-hole collimator were employed in both types of detector head. A line source phantom, cold-rod brain-shaped phantom, and cerebral blood flow phantom were evaluated. The projection data were generated by forward-projection of the phantom images using physics models, and Poisson noise at clinical levels was applied to the projection data. The ordered-subsets expectation maximization algorithm with physics models was used. We also evaluated conventional SPECT using four parallel detector heads for the sake of comparison.The evaluation of the line source phantom showed that the transaxial FWHM in the central slice for conventional SPECT ranged from 6.1 to 8.5 mm, while that for PT-SPECT ranged from 5.3 to 6.9 mm. The cold-rod brain-shaped phantom image showed that conventional SPECT could visualize up to 8-mm-diameter rods. By contrast, PT-SPECT could visualize up to 6-mm-diameter rods in upper slices of a cerebrum. The cerebral blood flow phantom image showed that the PT-SPECT system provided higher resolution at the thalamus and caudate nucleus as well as at the longitudinal fissure of the cerebrum compared with conventional SPECT.PT-SPECT provides improved image resolution at not only upper but also at central slices of the cerebrum.
Keywords: Brain SPECT; Cadmium telluride (CdTe) detector; Collimator

Evaluation of semi-quantitative method for quantification of dopamine transporter in human PET study with 18F-FE-PE2I by Yoko Ikoma; Takeshi Sasaki; Yasuyuki Kimura; Chie Seki; Yoshiro Okubo; Tetsuya Suhara; Hiroshi Ito (697-708).
Positron emission tomography (PET) with 18F-FE-PE2I is useful for investigating the function of dopamine transporter, and kinetics of 18F-FE-PE2I could be described by standard two-tissue compartment model (2CM) using plasma input function. In this study, we investigated the feasibility of semi-quantitative methods for estimating binding potential (BPND) and transporter occupancy to shorten the scan period and to reduce the effect of statistical noise on quantitative outcomes using computer simulation and human PET studies with 18F-FE-PE2I.In the simulations, time-activity curves (TACs) for the putamen with a wide range of BPND were generated. In these TACs, BPNDs were estimated by standardized uptake value ratio (SUVR) using various integration intervals and the simplified reference tissue model (SRTM) with the cerebellum as reference region, and reduction of BPND assuming transporter occupancy by antipsychotics was calculated from BPND obtained from TACs with various BPND values. These estimates were evaluated by comparison with those of 2CM. In human studies with normal volunteers, BPNDs were estimated in the caudate and putamen using SUVR and SRTM with the cerebellar reference region, and compared with BPND by standard 2CM.In the simulations, BPND estimated by SUVR with late time frames and SRTM showed linear correlation with those by 2CM, although the estimates by SUVR were overestimated and affected by the cerebral blood flow as BPND became higher. As for transporter occupancy, SRTM showed higher linearity with 2CM and less effect of statistical noise than the SUVR method. In human studies, BPND by SRTM and SUVR with late time frames showed good correlation with BPND by 2CM.Although SRTM is more reliable than the SUVR method for BPND and occupancy estimation, SUVR using late time frames has the potential to provide practical indices of BPND and occupancy with a shorter scan period.
Keywords: Positron emission tomography; 18F-FE-PE2I; Binding potential; Standardized uptake value ratio (SUVR); Occupancy

Development of a 99mTc-labeled lactam bridge-cyclized alpha-MSH derivative peptide as a possible single photon imaging agent for melanoma tumors by Danial Shamshirian; Mostafa Erfani; Davood Beiki; Babak Fallahi; Mohammad Shafiei (709-720).
Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge α-MSH analog was labeled with 99mTc via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated.HYNIC-GABA-Nle-CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 °C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor.Labeling yield of >98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 ± 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 ± 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 ± 0.68 % ID/g at 2 h after injection).The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.
Keywords: α-MSH; 99mTc; B16/F10 cells; Tumor imaging

High metabolic tumor volume and total lesion glycolysis are associated with lateral lymph node metastasis in patients with incidentally detected thyroid carcinoma by Bo Hyun Kim; Seong-Jang Kim; Keunyoung Kim; Heeyoung Kim; So Jung Kim; Won Jin Kim; Yun Kyung Jeon; Sang Soo Kim; Yong Ki Kim; In Joo Kim (721-729).
The objective of this study was to investigate whether total lesion glycolysis (TLG) and metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) could predict the aggressiveness and lymph node metastasis (LNM) in patients with incidentally detected differentiated thyroid carcinoma.A total 358 patients with focal FDG-avid thyroid incidentaloma during cancer evaluation were enrolled. Among 235 patients in whom fine-needle aspiration biopsy was performed, 51 patients underwent total thyroidectomy with LN dissection. We analyzed the relationship between volume-based parameters and clinicopathologic characteristics.The mean age and tumor size were 57.1 ± 11.3 years and 1.15 ± 0.81 cm, respectively. The prevalence of malignancy was 21.7 % (51/235). When SUVmax > 5.91, MTV2.5 > 2.05 cm3, and TLG2.5 > 9.09 were used as cutoff points, sensitivity, specificity, and area under curve (AUC) for prediction of lateral LNM were 77.9, 69.1 %, 0.716 (P = 0.047), 77.8, 88.1 %, 0.839 (P < 0.001), 77.8, 85.1 %, and 0.815 (P = 0.002), respectively. However, MTV and TLG had no value in prediction of central LNM, extrathyroidal extension, and multifocality. On comparison ROC curve analysis, the MTV and TLG showed the statistical differences for the prediction of lateral LNM compared with SUVmax (all P’s < 0.05).This study has shown for the first time that volume-based PET functional parameters had a significant value for the prediction of lateral LNM in incidentally detected PTC. These results suggest that higher MTV and TLG can be potential new risk factors for preoperative risk stratification. The usefulness of TLG and MTV in preoperative risk stratification in patients with PTC needs to be confirmed in further large studies.
Keywords: Metabolic tumor volume; Total lesion glycolysis; Papillary thyroid carcinoma; Lymphatic metastasis

Application of the newly developed Japanese adenosine normal database for adenosine stress myocardial scintigraphy by Shingo Harata; Satoshi Isobe; Itsuro Morishima; Susumu Suzuki; Hideyuki Tsuboi; Takahito Sone; Hideki Ishii; Toyoaki Murohara (730-739).
The currently available Japanese normal database (NDB) in stress myocardial perfusion scintigraphy recommended by the Japanese Society of Nuclear Medicine (JSNM-NDB) is created based on the data from exercise tests. The newly developed adenosine normal database (ADS-NDB) remains to be validated for patients undergoing adenosine stress test. We tested whether the diagnostic accuracy of adenosine stress test is improved by the use of ADS-NDB (Kanazawa University).Of 233 consecutive patients undergoing 99mTc-MIBI adenosine stress test, 112 patients were tested. The stress/rest myocardial 99mTc-MIBI single-photon emission computed tomography (SPECT) images were analyzed by AutoQUANT 7.2 with both ADS-NDB and JSNM-NDB. The summed stress score (SSS) and summed difference score (SDS) were calculated. The agreements of the post-stress defect severity between ADS-NDB and JSNM-NDB were assessed using a weighted kappa statistic.In all patients, mean SSSs of all, right coronary artery (RCA), left anterior descending (LAD), and left circumflex (LCx) territories were significantly lower with ADS-NDB than those with JSNM-NDB. Mean SDSs in all, RCA, and LAD territories were significantly lower with ADS-NDB than those with JSNM-NDB. In 28 patients with significant coronary stenosis, the mean SSS in the RCA territory was significantly lower with ADS-NDB than that with JSNM-NDB. In 84 patients without ischemia, both mean SSSs and SDSs in all, RCA, LAD, and LCx territories were significantly lower with ADS-NDB than those with JSNM-NDB. Weighted kappa values of all patients, patients with significant stenosis, and patients without ischemia were 0.89, 0.83, and 0.92, respectively.Differences were observed between results from ADS-NDB and JSNM-NDB. The diagnostic accuracy of adenosine stress myocardial perfusion scintigraphy may be improved by reducing false-positive results.
Keywords: Adenosine normal database; Japanese Society of Nuclear Medicine normal database; 99mTc-MIBI

Folate therapy improves the stress-to-rest mean LV volume ratio in myocardial perfusion imaging in patients with diabetes by Alireza Emami-Ardekani; Alireza Esteghamati; Saeed Farzanefar; Mohammadtaghi Abousaidi; Mehrshad Abbasi; Soraya Abdollahi; Babak Fallahi; Davood Beiki; Armaghan Fard-Esfahani; Manouchehr Nakhjavani; Mohamad Eftekhari (740-744).
Patients with diabetes have higher stress-to-rest mean left ventricular volume (SRLVV) ratio in myocardial perfusion imaging (MPI) and hyperhomocysteinemia. We studied the effect of folate therapy on SRLVV ratio and plasma homocysteine levels in patients with diabetes.Forty patients were enrolled and thirty-two completed the study. The patients underwent a 2-day pharmacological stress test and rest MPI before and 2 months after treatment with either 5 mg folic acid or placebo. SRLVV ratios were calculated, and plasma homocysteine levels were measured, before and after treatment.Among the 32 patients who completed the study, 15 received folic acid and 17 received placebo. The age of subjects (folate 51.5 ± 6.1 years; placebo 50.6 ± 8.1 years), male/female ratio (folate 6/11; placebo 9/6),or MPI findings (proportion of normal results: folate 80.0 %; placebo 94.1 %) were similar between the two groups. The baseline SRLVV ratio was similar between groups (folate: 1.00 ± 0.09 vs. placebo: 0.97 ± 0.13); however, the post-treatment SRLVV ratio was significantly lower (P < 0.001) in the folate group than in the placebo group (folate: 0.93 ± 0.10 vs. placebo: 1.04 ± 0.17). A general linear repeated-measures model showed a significant difference in the change in SRLVV ratio between participants receiving folate and those receiving placebo. Post-treatment homocysteine level was lower after folate treatment (from 14.5 ± 4.6 to 11.5 ± 5.3 µmol/L), as compared to placebo (from 13.7 ± 5.0 to 17.9 ± 4.5 µmol/L) (P = 0.01). The changes in SRLVV ratio and homocysteine level were correlated (r = 0.45; P = 0.016).Short-term folate therapy reduced SRLVV ratio and plasma homocysteine level.
Keywords: Diabetes; Endothelial dysfunction; Stress-to-rest mean left ventricular volume; Myocardial perfusion imaging; Folate; Homocysteinemia

Comparison of estimated human dose of 68Ga-MAA with 99mTc-MAA based on rat data by Saeed Shanehsazzadeh; Afsaneh Lahooti; Hassan Yousefnia; Parham Geramifar; Amir Reza Jalilian (745-753).
99mTc macroaggregated albumin (99mTc-MAA) that had been used as a perfusion agent has been evaluated. In this study, we tried to estimate human absorbed dose of 68Ga-MAA via commercially available kit from Pars-Isotopes, based on biodistribution data in wild-type rats, and compare our estimation with the available absorbed dose data from 99mTc-MAA.For biodistribution of 68Ga-MAA, three rats were sacrificed at each selected times after injection (15, 30, 45, 60, and 120 min) and the percentage of injected dose per gram of each organ was measured by direct counting from rats data from 11 harvested organs. The medical internal radiation dose formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans.The biodistribution data for 68Ga-MAA showed that the most of the activity was taken up by the lung (more than 97 %) in no time. Our dose prediction shows that a 185-MBq injection of 68Ga-MAA into humans might result in an estimated absorbed dose of 4.31 mGy in the whole body. The highest absorbed doses are observed in the adrenals, spleen, pancreas, and red marrow with 0.36, 0.34, 0.26, and 0.19 mGy, respectively.Since the 99mTc-MAA remains longer than 68Ga-MAA in the lung and 68Ga-MAA has good image qualities and results in lower amounts of dose delivery to the critical organs such as gonads, red marrow, and adrenals, the use of 68Ga-MAA is recommended.
Keywords: Biodistribution; Effective absorbed dose; Gallium 68; Macroaggregated albumin (MAA)