Annals of Nuclear Medicine (v.33, #1)

Techniques for generating attenuation map using cardiac SPECT emission data only: a systematic review by Getu Ferenji Tadesse; Parham Geramifar; Eyachew Misganew Tegaw; Mohammad Reza Ay (1-13).
To reliably interpret and perform quantitative analysis, attenuation correction for cardiac single-photon emission computed tomography (SPECT) is fundamental. Thus, knowledge of the patient-specific attenuation map for accurate correction is required in SPECT quantitative imaging. The aim of this systematic review is to present general principles of attenuation correction and provide a structured summary of the approaches that have been proposed for generating the attenuation map for cardiac SPECT. We identified relevant articles published in English pertaining to the attenuation map (AM) determination using SPECT emission data only by searching PubMed, EMBASE, Scopus, and Web of Science databases. Moreover, other articles were hand searched. The protocol of this systematic review was registered in PROSPERO and the code given is CRD42017060512. Transmissionless techniques of determining attenuation map including calculated methods, statistical modeling for simultaneous estimation of attenuation and emission, consistency conditions criteria, using scattered data and other methods were reviewed. Methods for performing attenuation map for cardiac SPECT are developing and the progresses made are promising. However, much work is needed to assess the efficacy of the correction schemes in the clinical routine.
Keywords: Attenuation correction; Attenuation map; Cardiac; SPECT; Emission data

Count-based method for specific binding ratio calculation in [I-123]FP-CIT SPECT analysis by Mahmudur G. M. Rahman; Muhammad M. Islam; Tetsuya Tsujikawa; Yasushi Kiyono; Hidehiko Okazawa (14-21).
To calculate the specific binding ratio (SBR) appropriately in dopamine transporter (DAT) imaging, a method for extracting the striatal volume of interest (VOI) was developed.This study included 200 patients (72 ± 10 years) who were suspected of parkinsonian syndromes (PS) or dementia with Lewy body (DLB). The patients were divided into three groups of PS with dopaminergic degeneration, DLB and non-PS after [123I]ioflupane (FP-CIT) SPECT and clinical follow-up. The image data were reconstructed with CT attenuation correction and scatter correction, and with only CT attenuation correction (CTAC). The new method extracted striatal VOI according to the high-level counts and the average striatum volume, and calculated SBR using the reference occipital counts. The SBR values for each patient were obtained using the Tossici-Bolt method (SBRBolt) and our method. Reproducibility of SBR calculation using our method was compared by two operators.The mean SBR values for the PS and DLB groups were significantly different from that of the non-PS group with both methods. The coefficients of variation of the SBR were significantly smaller with the proposed method compared with those of SBRBolt (p < 0.001), except for the CTAC images. There were no differences in SBR between the two operators using our method. The diagnostic accuracies with our method for the PS and DLB groups were 98.4 and 96.0%, respectively.Our new method for SBR calculation in the FP-CIT SPECT showed less coefficients of variation with high reproducibility, which would be useful for clinical diagnosis and in assessing the severity of diseases in follow-up studies.
Keywords: [I-123]ioflupane (FP-CIT) SPECT; DAT; SBR; ACSC; CTAC

Volume-based parameters on FDG PET may predict the proliferative potential of soft-tissue sarcomas by Tomoka Kitao; Tohru Shiga; Kenji Hirata; Mitsunori Sekizawa; Toshiki Takei; Katsushige Yamashiro; Nagara Tamaki (22-31).
Soft-tissue sarcomas (STS) are rare types of tumors that have variable levels of tumor differentiation. F-18 fluorodeoxyglucose positron emission tomography (FDG PET) has been established as an useful tool for STS patients, and the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are reported to be useful in various cancers. We compared the diagnostic value of four PET parameters (maximum standardized uptake value [SUVmax], SUVmean, MTV, and TLG) from two acquisition timings for predicting the expression of the pathological marker of cell proliferation Ki-67, based on pathological investigation.In this retrospective study, we investigated 20 patients (59 ± 19 years old, 18–87 years old) with pathologically confirmed STS who underwent FDG PET before surgical intervention. The patients fasted ≥ 6 h before the intravenous injection of FDG. The whole body was scanned twice; at an early phase (61.5 ± 2.6 min) and at a delayed phase (118.0 ± 2.1 min) post-injection. The SUVmax, SUVmean, MTV, and TLG of the primary lesion were measured with a tumor boundary determined by SUV ≥ 2.0. Ki-67 was measured using MIB-1 immunohistochemistry. We used Pearson’s correlation coefficient to analyze the relationships between the PET parameters and Ki-67 expressions. The Kaplan–Meier analysis with the log-rank test was performed to compare overall survival between high-group and low-group at each of the four PET parameters and Ki-67 expression.All four PET parameters at each phase showed significant correlations with Ki-67. Among them, the Pearson’s correlation coefficient (r) was largest for TLG (r = 0.76 and 0.77 at the early and delayed phases, respectively), followed by MTV (0.70 and 0.72), SUVmax (r = 0.65 and 0.66), and SUVmean (r = 0.62 and r = 0.64). From early to delayed phases, the SUVmax and SUVmean both increased in all 20 patients, whereas the MTV and TLG increased in 13/20 (65%) and 16/20 (80%) patients, respectively. None of the %increases of the PET parameters were significantly correlated with Ki-67. The overall survival was shorter for high-SUVmax, high-SUVmean, high-TLG, and high-Ki-67 groups than the other groups, although the difference did not reach statistical significance.The SUVmax, SUVmean, MTV, and TLG acquired at both 1 and 2 h after injection showed significant correlations with Ki-67. Among them, correlation coefficient with Ki-67 expression was highest for TLG, although the best parameter should be determined in a larger population. The delayed-phase FDG PET was equally useful as that of early-phase to predict tumor aggressiveness in STS.
Keywords: Soft tissue sarcoma; MTV; TLG; FDG; Ki-67; PET

The purpose was to evaluate the correlation of the pre-treatment hematological parameters with metabolic parameters of primary tumor in baseline 18F-FDG PET/CT in patients with colorectal cancer (CRC) and estimate the prognostic value of both.We retrospectively investigated 231 patients with CRC who underwent baseline 18F-FDG PET/CT. Routine blood sampling was tested in the same term. PET parameters in term of hematological parameters and pathological characteristics of primary tumor were compared. Kaplan–Meier survival analysis was performed in the patients without distant metastasis. The differences of disease-free survival between groups were compared by log-rank tests.Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were significantly correlated with all the metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG). The patients with NLR > 3 had higher MTV (24.82 ± 18.16 vs 19.06 ± 13.30, P = 0.039) and TLG (219.04 ± 186.94 vs 166.45 ± 146.39, P = 0.047) than those whose NLR ≤ 3. NLR in those patients with distant metastasis was significantly higher than those without distant metastasis (P = 0.018) while LMR in those patients with distant metastasis was significantly lower than those without distant metastasis (P = 0.032). Survival analysis showed that those patients with low MTV (P = 0.015), low NLR (P = 0.008) and high LMR (P = 0.027) revealed significant survival benefit.There was a significant association between the pre-treatment hematological parameters and metabolic parameters of baseline 18F-FDG PET/CT in the patients with CRC. It might be helpful in those patients with high NLR and low LMR to undergo 18F-FDG PET/CT to detect distant metastasis and predict prognosis.
Keywords: Colorectal cancer; PET; NLR; LMR; Prognosis

Our study was designed to compare the diagnostic efficacies of integrated 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single-photon emission computed tomography (SPECT) images and computed tomography (CT) images in lymph node metastasis in the patients with esophageal cancer.From September 2015 and May 2018, 32 patients with histologically proven primary esophageal carcinoma underwent both 99mTc-3PRGD2 SPECT and CT scans followed by esophagectomy with lymph node dissection. The results of reviewing 99mTc-3PRGD2 SPECT and CT images for the lymph node metastasis were compared in relation with pathologic findings.During surgery, a total of 168 lymph nodes were dissected in 32 patients, of which 42 node groups in 18 patients were malignant on histologic examination. Preoperative nodal staging was compared with postoperative histopathological staging, The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 99mTc-3PRGD2 SPECT for lymph nodes were 80.95%, 86.51%, 85.12%, 66.67%, and 93.16% on per-node basis, respectively; compared with 59.52%, 73.02%, 69.64%, 42.37%, and 84.40% for CT (p = 0.034, 0.008, 0.005, 0.011, and 0.038, respectively). 70.59% (12/17) false-negative interpretations and 50% (17/34) false-positive interpretations on CT were corrected by 99mTc-3PRGD2 SPECT. 37.5% false-negative interpretations on 99mTc-3PRGD2 SPECT were corrected by CT. 11.90% (5/42) positive lymph nodes and 13.49% (17/126) negative nodes at pathology were incorrectly diagnosed both by 99mTc-3PRGD2 SPECT and CT. The accuracy of 99mTc-3PRGD2 SPECT (87.50%, 28/32) was significantly higher than that of CT (62.50, 20/32; p = 0.022) on per-patient basis. 99mTc-3PRGD2 SPECT showed significantly higher sensitivity and accuracy in the neck and upper thoracic regions than CT. For nodal staging, 99mTc-3PRGD2 SPECT was correct in 78.12% (25/32) of the patients, whereas CT was correct in 53.12% (17/32), p = 0.037. 99mTc-3PRGD2 SPECT is more accurate than CT for preoperative assessment of lymph node metastasis in esophageal cancer and may be helpful in determining the therapeutic plan.
Keywords: 99mTc-3PRGD2 ; Esophageal cancer; SPECT; CT; Lymph node

Comparison of 18F-Choline PET/CT and MRI functional parameters in prostate cancer by Xavier Palard-Novello; Luc Beuzit; Giulio Gambarota; Florence Le Jeune; Etienne Garin; Pierre-Yves Salaün; Anne Devillers; Solène Querellou; Patrick Bourguet; Hervé Saint-Jalmes (47-54).
18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI.Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (K trans and V e using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman’s correlation coefficients were calculated to compare parameters.The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K 1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K 1 (from FCH PET/CT imaging) was moderately correlated with K trans (from perfusion MR imaging) (r = 0.55, p = 0.041).No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.
Keywords: 18F-Choline; Positron emission tomography; Prostate cancer; Kinetic analysis; Multiparametric MRI

Clinical feasibility of early scanning after administration of 68Ga-DOTATOC by Yuji Nakamoto; Takayoshi Ishimori; Kohei Sano; Yoichi Shimizu; Kaori Togashi (55-60).
Positron emission tomography (PET)/computed tomography (CT) using 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe1-Tyr3-octreotide (DOTATOC) is usually performed about 1-h post-injection; however, because of rapid blood clearance, the waiting time for scanning could possibly be shortened without affecting diagnostic performance. The purpose of this study was to investigate the feasibility of early scanning at 30 min post-injection.Thirty-eight patients who underwent DOTATOC-PET/CT were analyzed. After administration of 68Ga-DOTATOC, data acquisition was performed twice, at 30-min and 60-min post-injection. The number of known or suspected pathological lesions, and quantitative values of those lesions and physiological uptake were compared. SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion uptake (TLU) were calculated as quantitative values of the pathological lesions.A total of 125 known or suspected pathological lesions were found at both timepoints, with no differences between the two datasets. The SUVmax, SUVpeak, MTV, and TLU were highly reproducible, with Spearman’s ρ of 0.983, 0.986, 0.918, and 0.981, respectively. The average percent differences (%DIFFave) defined as the differences of the values divided by the value at 1-h post-injection were 11.1% for SUVmax, 8.5% for SUVpeak, 15.1% for MTV, and 20.6% for TLU. Physiological uptake in the two datasets was closely comparable in the pituitary gland (Spearman’s ρ = 0.954, %DIFFave = 11.0%), liver (0.989, 3.9%), spleen (0.970, 6.3%), adrenal glands (0.879, 13.0%), and pancreatic uncus (0.946, 12.7%).The diagnostic performance of visual interpretation should be comparable between DOTATOC-PET/CT images obtained at 30-min and 60-min post-injection. Some differences between quantitative values may exist; however, they appear to be minimal.
Keywords: PET; DOTATOC; Waiting time

The role of 13 N-ammonia in the differential diagnosis of gliomas and brain inflammatory lesions by Chang Yi; Xinchong Shi; Xuezhen Zhang; Ganhua Luo; Bing Zhang; Xiangsong Zhang (61-67).
To investigate the utility of 13 N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations. 13 N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13 N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13 N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA.29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13 N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively. 13 N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.
Keywords: Glioma; Brain inflammation; 13 N-ammonia; PET-CT