Annals of Nuclear Medicine (v.31, #10)

Bone metastases from breast cancer: associations between morphologic CT patterns and glycolytic activity on PET and bone scintigraphy as well as explorative search for influential factors by Tsutomu Sugihara; Mitsuru Koizumi; Masamichi Koyama; Takashi Terauchi; Naoya Gomi; Yoshinori Ito; Kiyohiko Hatake; Naohiro Sata (719-725).
This study aimed to compare the detection of bone metastases from breast cancer on F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scintigraphy (BS). An explorative search for factors influencing the sensitivity or uptake of BS and FDG-PET was also performed.Eighty-eight patients with bone metastases from breast cancer were eligible for this study. Histological confirmation of bone metastases was obtained in 31 patients. The bone metastases were visually classified into four types based on their computed tomography (CT) appearance: osteoblastic, osteolytic, mixed, and negative. The sensitivity of BS and FDG-PET were obtained regarding CT type, adjuvant therapy, and the primary tumor characteristics. The FDG maximum standardized uptake value (SUVmax) was analyzed.The sensitivities of the three modalities (CT, BS, and FDG-PET) were 77, 89, and 94%, respectively. The sensitivity of FDG-PET for the osteoblastic type (69%) was significantly lower than that for the other types (P < 0.001), and the sensitivity of BS for the negative type (70%) was significantly lower than that for the others. Regarding tumor characteristics, the sensitivity of FDG-PET significantly differed between nuclear grade (NG)1 and NG2–3 (P = 0.032). The SUVmax of the osteoblastic type was significantly lower than that of the other types (P = 0.009). The SUVmax of NG1 was also significantly lower than that of NG2–3 (P = 0.011). No significant difference in FDG uptake (SUVmax) was detected between different histological types.Although FDG-PET is superior to BS for the detection of bone metastases from breast cancer, this technique has limitations in depicting osteoblastic bone metastases and NG1.
Keywords: Bone metastases; FDG-PET; Bone scintigraphy; Breast cancer

Textural features and SUV-based variables assessed by dual time point 18F-FDG PET/CT in locally advanced breast cancer by Ana María Garcia-Vicente; David Molina; Julián Pérez-Beteta; Mariano Amo-Salas; Alicia Martínez-González; Gloria Bueno; María Jesús Tello-Galán; Ángel Soriano-Castrejón (726-735).
To study the influence of dual time point 18F-FDG PET/CT in textural features and SUV-based variables and their relation among them.Fifty-six patients with locally advanced breast cancer (LABC) were prospectively included. All of them underwent a standard 18F-FDG PET/CT (PET-1) and a delayed acquisition (PET-2). After segmentation, SUV variables (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained. Eighteen three-dimensional (3D) textural measures were computed including: run-length matrices (RLM) features, co-occurrence matrices (CM) features, and energies. Differences between all PET-derived variables obtained in PET-1 and PET-2 were studied.Significant differences were found between the SUV-based parameters and MTV obtained in the dual time point PET/CT, with higher values of SUV-based variables and lower MTV in the PET-2 with respect to the PET-1. In relation with the textural parameters obtained in dual time point acquisition, significant differences were found for the short run emphasis, low gray-level run emphasis, short run high gray-level emphasis, run percentage, long run emphasis, gray-level non-uniformity, homogeneity, and dissimilarity. Textural variables showed relations with MTV and TLG.Significant differences of textural features were found in dual time point 18F-FDG PET/CT. Thus, a dynamic behavior of metabolic characteristics should be expected, with higher heterogeneity in delayed PET acquisition compared with the standard PET. A greater heterogeneity was found in bigger tumors.
Keywords: Dual time point 18F-FDG PET/CT; Breast cancer; Tumor heterogeneity; Textural features

Uptake of AV-1451 in meningiomas by Tyler J. Bruinsma; Derek R. Johnson; Ping Fang; Matthew Senjem; Keith A. Josephs; Jennifer L. Whitwell; Bradley F. Boeve; Mukesh K. Pandey; Kejal Kantarci; David T. Jones; Prashanthi Vemuri; Melissa Murray; Jonathan Graff-Radford; Christopher G. Schwarz; David S. Knopman; Ronald C. Petersen; Clifford R. Jack Jr.; Val J. Lowe (736-743).
AV-1451 is an imaging agent labeled with the positron-emitting radiolabel Fluorine-18. 18F-AV-1451 binds paired helical filament tau (PHF-tau), a pathology related to Alzheimer’s disease. In our study of AV-1451 uptake in the brains of cognitively normal subjects, we noted a case of a meningioma with visually significant uptake of AV-1451.We initiated the present retrospective study to further examine cases of meningioma that underwent AV-1451 imaging.We searched the patient records of 650 patients who had undergone AV-1451 at our institution for the keyword “meningioma” to identify potential cases. PET/CT and MRI results were visually reviewed and semi-quantitative analysis of PET was performed. A paired student’s t test was run between background and tumor standard uptake values. Fisher’s exact test was used to examine the association between AV-1451 uptake and presence of calcifications on CT.We identified 12 cases of meningioma, 58% (7/12) of which demonstrated uptake greater than background using both visual analysis and tumor-to-normal cortex ratios (T/N + 1.90 ± 0.83). The paired student’s t test revealed no statistically significant difference between background and tumor standard uptake values (p = 0.09); however, cases with a T/N ratio greater than one showed statistically higher uptake in tumor tissue (p = 0.01). A significant association was noted between AV-1451 uptake and presence of calcifications (p = 0.01).AV-1451 PET imaging should be reviewed concurrently with anatomic imaging to prevent misleading interpretations of PHF-tau distribution due to meningiomas.
Keywords: Meningioma; AV-1451; Imaging

The effect of short-term treatment with lithium carbonate on the outcome of radioiodine therapy in patients with long-lasting Graves’ hyperthyroidism by Vladan Sekulić; Milena Rajić; Marina Vlajković; Slobodan Ilić; Miloš Stević; Marko Kojić (744-751).
The outcome of radioiodine therapy (RIT) in Graves’ hyperthyroidism (GH) mainly depends on radioiodine (131I) uptake and the effective half-life of 131I in the gland. Studies have shown that lithium carbonate (LiCO3) enhances the 131I half-life and increases the applied thyroid radiation dose without affecting the thyroid 131I uptake. We investigated the effect of short-term treatment with LiCO3 on the outcome of RIT in patients with long-lasting GH, its influence on the thyroid hormones levels 7 days after RIT, and possible side effects.Study prospectively included 30 patients treated with LiCO3 and 131I (RI-Li group) and 30 patients only with 131I (RI group). Treatment with LiCO3 (900 mg/day) started 1 day before RIT and continued 6 days after. Anti-thyroid drugs withdrawal was 7 days before RIT. Patients were followed up for 12 months. We defined a success of RIT as euthyroidism or hypothyroidism, and a failure as persistent hyperthyroidism.In RI-Li group, a serum level of Li was 0.571 ± 0.156 mmol/l before RIT. Serum levels of TT4 and FT4 increased while TSH decreased only in RI group 7 days after RIT. No toxic effects were noticed during LiCO3 treatment. After 12 months, a success of RIT was 73.3% in RI and 90.0% in RI-Li group (P < 0.01). Hypothyroidism was achieved faster in RI-Li (1st month) than in RI group (3rd month). Euthyroidism slowly decreased in RI-Li group, and not all patients became hypothyroid for 12 months. In contrast, euthyroidism rapidly declined in RI group, and all cured patients became hypothyroid after 6 months.The short-term treatment with LiCO3 as an adjunct to 131I improves efficacy of RIT in patients with long-lasting GH. A success of RIT achieves faster in lithium-treated than in RI group. Treatment with LiCO3 for 7 days prevents transient worsening of hyperthyroidism after RIT. Short-term use of LiCO3 shows no toxic side effects.
Keywords: Graves’ hyperthyroidism; 131I therapy; Lithium carbonate; Thyroid

Assessment of intratumor heterogeneity in mesenchymal uterine tumor by an 18F-FDG PET/CT texture analysis by Tetsuya Tsujikawa; Makoto Yamamoto; Kunihiro Shono; Shizuka Yamada; Hideaki Tsuyoshi; Yasushi Kiyono; Hirohiko Kimura; Hidehiko Okazawa; Yoshio Yoshida (752-757).
The aim of this study was to retrospectively evaluate the clinical significance of 18F-FDG PET/CT textural features for discriminating uterine sarcoma from leiomyoma.Fifty-five patients with suspected uterine sarcoma based on ultrasound and MRI findings who underwent pretreatment 18F-FDG PET/CT were included. Fifteen patients were histopathologically proven to have uterine sarcoma, 14 patients by surgical operation and one by biopsy, and 40 patients were diagnosed with leiomyoma by surgical operation or in a follow-up for at least 2 years. A texture analysis was performed on PET/CT images from which second- and higher order textural features were extracted in addition to standardized uptake values (SUVs) and other first-order features. The accuracy of PET features for differentiating between uterine sarcoma and leiomyoma was evaluated using a receiver-operating-characteristic (ROC) analysis.The intratumor distribution of 18F-FDG was more heterogeneous in uterine sarcoma than in leiomyoma. Entropy, correlation, and uniformity calculated from normalized gray-level co-occurrence matrices and SUV standard deviation derived from histogram statistics showed greater area under the ROC curves (AUCs) than did maximum SUV for differentiating between sarcoma and leiomyoma. Entropy, as a single feature, yielded the greatest AUC of 0.974 and the optimal cut-off value of 2.85 for entropy provided 93% sensitivity, 90% specificity, and 92% accuracy. When combining conventional features with textural ones, maximum SUV (cutoff: 6.0) combined with entropy (2.85) and correlation (0.73) provided the best diagnostic performance (100% sensitivity, 94% specificity, and 95% accuracy).In combination with the conventional histogram statistics and/or volumetric parameters, 18F-FDG PET/CT textural features reflecting intratumor metabolic heterogeneity are useful for differentiating between uterine sarcoma and leiomyoma.
Keywords: Mesenchymal uterine tumor; PET; Texture analysis; Differentiation

Inter- and intra-observer reproducibility of quantitative analysis for FP-CIT SPECT in patients with DLB by Atsutaka Okizaki; Michihiro Nakayama; Kaori Nakajima; Takayuki Katayama; Takahiro Uno; Fumiyoshi Morikawa; Juichiro Naoe; Koji Takahashi (758-763).
Dopamine transporter single photon emission CT (DAT-SPECT) is useful in the evaluation of dementia with Lewy bodies (DLB). The specific binding ratio (SBR) is an index to measure DAT density. However, poorly reproducible cases are occasionally experienced in clinical practice. We hypothesized that distance-weighted histogram (DWH) may be useful to improve the reproducibility of SBR. The purpose of this study was to investigate inter- and intra-observer reproducibility of SBR with conventional and DWH methods, and to visually evaluate the precision in reference voxel of interest (VOI) definition using these methods.This study included 50 adult patients with probable DLB. They underwent brain MRI, DAT-SPECT, and cerebral blood flow SPECT with N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP). SBR of the striatum was calculated using conventional and DWH method. For inter-observer reproducibility validation, conventional and DWH SBR were independently evaluated by experienced nuclear medicine physicians; these measurements were repeated by the nuclear medicine physician to investigate intra-observer reproducibility.Proper reference VOI definition was achieved in 60.0% using conventional SBR and in 98.0% with DWH SBR. Both conventional and DWH SBR demonstrated good inter- and intra-observer reproducibility, however, there were statistically significant inter- and intra-observer variations with conventional SBR measurements. Average inter- and intra-observer errors of conventional SBR were 7.9 and 6.1%, respectively. Conversely, DWH SBR errors were not observed in all patients. Moreover, average inter- and intra-observer errors were significantly higher in conventional SBR with improper reference VOI definition than in that with proper reference VOI definition.Although the reproducibility of conventional and DWH SBR was good, inter- and intra-observer bias could not be ignored in conventional SBR, particularly with improper reference VOI definition. Thus, DWH may be useful to improve inter- and intra-observer reproducibility of SBR.
Keywords: FP-CIT SPECT; DAT density; SBR; Histogram; DLB

CT-based SPECT attenuation correction and assessment of infarct size: results from a cardiac phantom study by Alexander Stephan Kroiss; Stephan Gerhard Nekolla; Georg Dobrozemsky; Thomas Grubinger; Barry Lynn Shulkin; Markus Schwaiger (764-772).
Myocardial perfusion SPECT is a commonly performed, well established, clinically useful procedure for the management of patients with coronary artery disease. However, the attenuation of photons from myocardium impacts the quantification of infarct sizes. CT-Attenuation Correction (AC) potentially resolves this problem. This contention was investigated by analyzing various parameters for infarct size delineation in a cardiac phantom model.A thorax phantom with a left ventricle (LV), fillable defects, lungs, spine and liver was used. The defects were combined to simulate 6 infarct sizes (5–20% LV). The LV walls were filled with 100120 kBq/ml 99mTc and the liver with 10–12 kBq/ml 99mTc. The defects were filled with water of 50% LV activity to simulate transmural and non-transmural infarction, respectively. Imaging of the phantom was repeated for each configuration in a SPECT/CT system. The defects were positioned in the anterior as well as in the inferior wall. Data were acquired in two modes: 32 views, 30 s/view, 180° and 64 views, 15 s/view, 360° orbit. Images were reconstructed iteratively with scatter correction and resolution recovery. Polar maps were generated and defect sizes were calculated with variable thresholds (40–60%, in 5% steps). The threshold yielding the best correlation and the lowest mean deviation from the true extents was considered optimal.AC data showed accurate estimation of transmural defect extents with an optimal threshold of 50% [non attenuation correction (NAC): 40%]. For the simulation of non-transmural defects, a threshold of 55% for AC was found to yield the best results (NAC: 45%). The variability in defect size due to the location (anterior versus inferior) of the defect was reduced by 50% when using AC data indicating the benefit from using AC. No difference in the optimal threshold was observed between the different orbits.Cardiac SPECT/CT shows an improved capability for quantitative defect size assessment in phantom studies due to the positive effects of attenuation correction.
Keywords: Attenuation correction; Cardiac SPECT; Infarct size; SPECT/CT