Annals of Nuclear Medicine (v.28, #2)

Lung uptake on I-131 therapy and short-term outcome in patients with lung metastasis from differentiated thyroid cancer by Shozo Okamoto; Tohru Shiga; Yuko Uchiyama; Osamu Manabe; Kentaro Kobayashi; Keiichiro Yoshinaga; Nagara Tamaki (81-87).
It is sometimes difficult to assess I-131 lung uptake at the initial I-131 therapy because of strong artifacts from I-131 uptake in the thyroid bed. The aim of this study was to analyze the lung uptake at the second I-131 therapy for lung metastasis in patients who did not have lung uptake at the initial therapy from differentiated thyroid carcinoma (DTC). Then, we also analyzed the relationship between the initial lung uptake and short-term outcome after I-131 therapies.This study included 62 DTC patients with lung metastasis. The patients were classified into 2 groups according to the lung uptake at the initial I-131 therapy such as patients with lung uptake (positive uptake group n = 31) and those without lung uptake (negative uptake group n = 31). The lung uptake was analyzed at the second therapy in both groups. The short-term outcome was also analyzed based on the CT findings of lung metastasis size and serum thyroglobulin level between the two groups.The positive uptake group showed positive lung uptake at the second therapy in 23 patients (74 %), whereas none of negative uptake group showed any lung uptake at the second therapy (P < 0.01). The positive uptake group significantly decreased in the size of lung metastasis from the initial therapy to the second therapy (20.0 ± 11.7 to 16.6 ± 9.6 mm, P < 0.01) with further decrease after the second therapy (P < 0.05). The serum thyroglobulin level was also significantly decreased from the initial therapy to the second therapy (4348 ± 7011 to 2931 ± 4484 ng/ml, P < 0.05). In contrast, the negative uptake group significantly increased in the size of lung metastasis from the initial therapy to the second therapy (17.3 ± 12.2 to 19.9 ± 14.3 mm, P < 0.01) with further increase after the second therapy (P < 0.01).No patients without lung uptake at the initial I-131 therapy showed lung uptake at the second therapy, or showed treatment effect. Therefore, second I-131 therapy for these patients with initially negative lung uptake should be considered cautiously.
Keywords: Thyroid cancer; Lung metastasis; I-131 therapy; Radioiodine therapy

Combination of both morphological and functional information has gained more and more appreciation with the concept of “functionally relevant coronary artery lesion (FRCAL)” and “functional revascularization”. This has paved the way for non-invasive single-photon emission computed tomography (SPECT)/computed tomography angiography (CTA) hybrid imaging. We aimed at assessing the value of cardiac hybrid imaging on the detection of FRCAL and its potential as a gatekeeper for invasive examination and treatment.In Two hundred and thirty-eight patients with known or suspected coronary artery disease (CAD) underwent CTA and myocardial perfusion imaging (MPI) using SPECT on a dual system scanner in one session before treatment. 78 patients underwent invasive coronary angiography (CAG) within 1 month. Detection of FRCAL by the combination of SPECT/CTA was compared with SPECT/CAG, which served as a standard of reference. According to the both combination results, treatment decision (revascularization or medical treatment) was chosen in the catheterization laboratory.Sensitivity, specificity, accuracy, positive and negative prediction rate by SPECT/CTA vs. SPECT/CAG for the detection of flow-limiting coronary stenosis on patient- and vessel-based analysis were 94.33, 72.00, 87.18, 87.71, 85.71 % and 88.71, 92.44, 91.45, 80.89, 95.78 %, respectively. No revascularization procedures were performed in patients without flow-limiting stenosis. However, more than one-third (25/67, 37 %) of revascularized vessels were not associated with ischemia on MPI.The cardiac SPECT/CTA hybrid imaging can accurately detect FRCAL and thereby it may be used as a gatekeeper for CAG and revascularization procedures.
Keywords: Coronary artery disease; Coronary CT angiography; Myocardial perfusion imaging; Conventional coronary angiography

Clinical use of 11C-methionine and 18F-FDG-PET for germinoma in central nervous system by Yoshiyuki Okochi; Takashi Nihashi; Masazumi Fujii; Katsuhiko Kato; Yumiko Okada; Yoshio Ando; Satoshi Maesawa; Shigenori Takebayashi; Toshihiko Wakabayashi; Shinji Naganawa (94-102).
The purpose of this study was to examine the 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) findings of central nervous system (CNS) germinoma and the diagnostic utility of these findings.We retrospectively evaluated the cases of 10 patients who were diagnosed with CNS germinoma according to their histopathological or clinical findings. All the patients underwent pretreatment MET and/or FDG-PET scans, and the resultant images were assessed qualitatively and quantitatively. In the qualitative assessments, we used 3- and 5-grade visual scoring systems for the MET- and FDG-PET images, respectively. In the quantitative assessments, the maximal standardized uptake value (SUVmax) and the ratio of the SUVmax of the tumor (T) divided by the mean SUV for the normal white or gray matter [T/N (WM), T/N (GM)], was calculated.The mean and SD values of SUVmax, T/N (WM), and T/N (GM) were 1.9 ± 1.4, 2.5 ± 1.3, and 1.7 ± 0.9 on MET-PET and 5.8 ± 2.2, 1.6 ± 0.5, and 0.8 ± 0.2 on FDG-PET, respectively. On MET-PET, only one lesion was not detected. On the other hand, on FDG-PET all of the lesions exhibited uptake values that were intermediate between those of the normal white matter and gray matter.In terms of its tumor-contouring ability, MET is a good tracer for diagnosing CNS germinomas; therefore, MET-PET is considered to be useful for planning biopsies or surgery. Although FDG-PET is capable of detecting CNS germinomas, it produced insufficient image contrast in the present study. Further studies are needed before FDG-PET can be used in clinical examinations of CNS germinoma.
Keywords: Germinoma; Positron emission tomography; 11C-methionine; 18F-FDG

Radius dependence of FP-CIT quantification: a Monte Carlo-based simulation study by Walter Koch; Peter Bartenstein; Christian la Fougère (103-111).
Dopamine transporter imaging with SPECT is a valuable tool for both clinical routine and research studies. Semi-quantitative analysis plays a key role in interpreting the scans, but is dependent on numerous factors, rotational radius being one of them. This study systematically evaluates the potential influence of radius of rotation on apparent tracer binding and describes methods for correction.Monte Carlo simulation scans of a digital brain phantom with various disease states and various radii of rotation ranging from 13 to 30 cm were analyzed using 4 different methods of semi-quantification. Different volumes of interest as well as a method with partial volume correction were applied.For conventional 3D semi-quantification methods the decrease of measured striatal binding per cm additional radius rotation lied in the range between 2.5 and 3.1 %, whereas effects were negligible when applying recovery-corrected quantification. Effects were independent of disease state.Partial volume effects with increasing radius of rotation can lead to considerable decrease of measured binding ratios, particularly when applying dopamine transporter imaging in a research setting. Standardization of acquisition radius can avoid the effect; correction seems feasible, but the correction factors depend on the quantification approach applied.
Keywords: Iterative reconstruction; FP-CIT; Radius of rotation; Monte Carlo simulation; Dopamine transporter

89Sr bremsstrahlung single photon emission computed tomography using a gamma camera for bone metastases by Seiichiro Ota; Masaki Uno; Masaki Kato; Masanobu Ishiguro; Takahiro Natsume; Kaoru Kikukawa; Masanori Tadokoro; Takashi Ichihara; Hiroshi Toyama (112-119).
Strontium-89 chloride (89Sr) bremsstrahlung single photon emission computed tomography (SPECT) imaging was evaluated for detecting more detailed whole body 89Sr distribution. 89Sr bremsstrahlung whole body planar and merged SPECT images were acquired using two-detector SPECT system. Energy window A (100 keV ± 50 %) for planar imaging and energy window A plus adjacent energy window B (300 keV ± 50 %) for SPECT imaging were set on the continuous spectrum. Thirteen patients with multiple bone metastases were evaluated. Bone metastases can be detected with 99mTc-HMDP whole body planar and merged SPECT images and compared with 89Sr bremsstrahlung whole body planar and merged SPECT images. Based on the location of metastatic lesions seen as hot spots on 99mTc-HMDP images as a reference, the hot spots on 89Sr bremsstrahlung images were divided into the same bone parts as 99mTc-HMDP images (a total of 35 parts in the whole body), and the number of hot spots were counted. We also evaluated the incidence of extra-osseous uptakes in the intestine on 89Sr bremsstrahlung whole body planar images.A total of 195 bone metastatic lesions were detected in both 99mTc-HMDP whole body planar and merged SPECT images. Detection of hot spot lesions in 89Sr merged SPECT images (127 of 195; 66 %) was more frequent than in 89Sr whole body planar images (108 of 195; 56 %), based on metastatic bone lesions in 99mTc-HMDP whole body planar and merged SPECT images. A large intestinal 89Sr accumulation was detected in 5 of the 13 patients (38 %). 89Sr bremsstrahlung-merged SPECT imaging could be more useful for detailed detection of whole body 89Sr distribution than planar imaging. Intestinal 89Sr accumulation due to 89Sr physiologic excretion was detected in feces for 4 days after tracer injection.
Keywords: Strontium-89 chloride; Bremsstrahlung; SPECT; Gamma camera; Bone metastasis

Influence of left ventricular geometry on thallium-201 gated single-photon emission tomographic findings in patients with known or suspected coronary artery disease by Satoshi Kurisu; Toshitaka Iwasaki; Hiroki Ikenaga; Noriaki Watanabe; Tadanao Higaki; Takashi Shimonaga; Ken Ishibashi; Naoya Mitsuba; Yoshihiro Dohi; Yasuki Kihara (120-127).
Recent studies have shown good correlations between echocardiography and Tl-201 gated single-photon emission computed tomography (SPECT) for the assessment of left ventricular volumes and ejection fraction. We assessed how left ventricular geometry affected correlations between these values measured by the 2 methods in patients with known or suspected coronary artery disease.There were 109 patients with normal left ventricular geometry, 20 patients with concentric remodeling, 32 patients with eccentric hypertrophy and 28 patients with concentric hypertrophy. In all 4 groups, there were good correlations between end-diastolic volume (EDV) and end-systolic volume (ESV) values measured by echocardiography and quantitative gated SPECT (QGS). EDV and ESV values measured by QGS were significantly underestimated than those measured by echocardiography except for ESV in eccentric hypertrophy. In all 4 groups, ejection fraction (EF) value measured by echocardiography significantly correlated with that measured by QGS, but Bland–Altman plot showed a proportional error. EF value measured by QGS was likely to be overestimated when EF value increased from the median value, and to be underestimated when EF value decreased from the median value especially in concentric remodeling.Tl-201 gated SPECT is a useful tool for the assessment of left ventricular volumes and function, but it requires methodological considerations according to left ventricular geometry.
Keywords: Ventricular function; Ventricular volume; Ejection fraction

Metabolic information on staging FDG-PET–CT as a prognostic tool in the evaluation of 97 patients with gastric cancer by Nicholas A. Coupe; Deme Karikios; Shanley Chong; June Yap; Weng Ng; Neil Merrett; Michael Lin (128-135).
Gastric cancer remains a leading cause of malignancy-related mortality. Many patients with locally advanced disease succumb despite peri-operative chemotherapy and the survival benefit of chemotherapy for advanced disease is modest, suggesting that current staging is imperfect. The role of fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the staging of gastric cancer remains to be determined. This study aimed to determine, and compare with computerized tomography (CT), the association between FDG-PET uptake in the primary tumour and regional lymph nodes, and overall survival in patients with all stage gastric cancer.Patients with histologically confirmed gastric cancer (any stage) who, at diagnosis, had received a staging FDG-PET–CT at our institution between 2006 and 2011 were included. Records were retrospectively analysed. Patients with >50 % of tumour above the gastro-oesophageal junction or an active second malignancy were excluded.97 patients were included in the analysis. Surgery with curative intent was performed in 68 patients. In univariate analysis, an association with overall survival was seen in patients who had FDG-PET-positive primary tumours (hazard ratio (HR) for death 3.33, 95 % confidence interval (95 % CI) 1.63–6.80, p = 0.001). FDG-PET lymph node positive (vs node negativity) was associated with inferior overall survival (HR 8.66, 95 % CI 4.59–16.37, p < 0.0001), and remained an independent predictor in the multivariate analysis. In contrast, positive lymphadenopathy identified on CT was not associated with overall survival (HR 1.34, 95 % CI 0.79–2.29, p = 0.82).FDG-PET-positive tumours are associated with an inferior overall survival. In contrast to CT, FDG-PET-positive lymphadenopathy is associated with a decreased overall survival.
Keywords: PET; Gastric cancer; Prognosis; Computerized tomography

The purpose of our study was to demonstrate metabolic patterns on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with adhesive capsulitis (AC).We retrospectively reviewed 18F-FDG PET/CT performed on 22 shoulders of 21 patients diagnosed with AC: 2 shoulders with stage I, 14 with stage II, and 6 with stage III. A clinical diagnosis of AC was retrospectively made based on clinical examination, clinical course, and imaging. The pattern of radiotracer uptake was analyzed. Standardized uptake values in rotator interval (RI), anterior joint capsule (AJC), axillary recess (AR), and greater tuberosity were measured and compared to those of the contralateral side and the control group consisting of 40 shoulders in 20 subjects without shoulder pain.Four patterns of uptake were noted: (1) glenoid type I (n = 16), with uptake in RI, AJC, and AR; (2) glenoid type II (n = 2),with uptake in AJC and AR; (3) glenoid type III (n = 2), with uptake in RI and AJC; (4) focal type (n = 2), with uptake in RI or AR. Affected side SUVmax for RI, AJC, and AR was significantly higher compared with the unaffected side and the control group. Two shoulders with stage I AC had patterns similar to the ones with stage II or III.Specific patterns of 18F-FDG uptake with dominant uptake in RI, AJC, or AR may be related to AC.
Keywords: Shoulder pain; Adhesive capsulitis; 18F-Fluorodeoxyglucose positron emission tomography/computed tomography

Characterization of lipid-rich adrenal tumors by FDG PET/CT: Are they hormone-secreting or not? by Kentaro Takanami; Tomohiro Kaneta; Ryo Morimoto; Fumitoshi Satoh; Yasuhiro Nakamura; Kei Takase; Shoki Takahashi (145-153).
The purpose of this study was to evaluate the diagnostic ability of FDG PET/CT to predict the hormone-secretion status of lipid-rich adrenal tumors.This study included 29 lipid-rich (CT number <10 HU) adrenal tumors 2 cm or larger in diameter in 28 patients who underwent FDG PET/CT. The diagnoses were based on endocrine examinations, including adrenal venous sampling and subsequent surgical resection, or on the endocrinological and morphological imaging follow-up during a period of at least 6 months. The FDG uptake of the adrenal tumors was evaluated semi-quantitatively using maximum standardized uptake values (SUVmax) and a ratio of the adrenal SUVmax compared to the liver SUVmax (SUVratio) was used for comparison. The statistical significance of differences was assessed using the Mann–Whitney U test, and a p value <0.05 was considered to be statistically significant.The lipid-rich adrenal tumors were proved to be 16 non-hormone-secreting tumors (15 adenomas and one myelolipoma) and 13 hormone-secreting tumors (five subclinical cortisol-producing adenomas, six aldosterone-producing adenomas and two adenomas that produced both cortisol and aldosterone). None of the patients had pheochromocytoma or a malignant adrenal tumor. The SUVmax (median, range) of the hormone-secreting tumors (3.2, 2.0–8.3) was higher than that of the non-hormone-secreting tumors (2.4, 1.8–3.3) (p < 0.05). Similarly, the SUVratio of the hormone-secreting tumors (0.95, 0.70–3.10) was higher than that of the non-hormone-secreting tumors (0.72, 0.54–0.95) (p < 0.01). There was no significant difference in the tumor diameter between the two groups (p = 0.8). The sensitivity, specificity and accuracy of FDG PET/CT for differentiating hormone-secreting tumors from non-hormone-secreting tumors were 0.69, 0.81 and 0.76 for cutoff SUVratio of 0.8, and were 0.46, 1 and 0.76 for the cutoff SUVratio of 1.0, respectively.A lipid-rich adrenal tumor presenting increased FDG uptake compared with that of the liver is likely to be a hormone-secreting adenoma. Therefore, additional endocrinological investigations are strongly recommended when an FDG-avid lipid-rich incidentaloma is detected on FDG PET/CT.
Keywords: FDG; PET; CT; Adrenal; Lipid

O-(2-[18F]fluoroethyl)-l-tyrosine uptake is an independent prognostic determinant in patients with glioma referred for radiation therapy by Reinhart Sweeney; Bülent Polat; Samuel Samnick; Christoph Reiners; Michael Flentje; Frederik A. Verburg (154-162).
To evaluate the prognostic value of O-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II–IV gliomas.We studied 28 patients with WHO tumor grade II–IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax.Tumor volumes were a median (range) of 88.6 (2.6–467.4) ml (MRI alone), 84.2 (2.8–474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0–512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46–4.08); TBR-SUVmax was 1.71 (0.97–2.85). During a follow-up of 18.7 (2.5–36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p = 0.005) and progression-free survival (p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p = 0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean.In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval.
Keywords: Glioma; FET-PET; Radiotherapy; Therapy planning; Prognosis

Differential diagnosis of trampoline fracture from osteomyelitis by bone scan with pinhole collimator by Mathieu Gauthé; Danielle Mestas; Federico Canavese; Antoine Samba; Florent Cachin (163-166).
A 2-year-old girl with recent history of trampoline fall presented to the A&E Department for complete functional impairment of the left lower extremity and fever. Blood examination revealed an inflammatory syndrome, while plain radiographs were normal. As magnetic resonance imaging was unavailable, a bone scintigraphy was performed. While standard acquisition found an intense uptake focused on the left proximal tibial metaphysis whose appearance was suggestive of acute hematogenous osteomyelitis, complementary acquisition with the pinhole collimator demonstrated that this abnormal uptake was clearly distinct from the cartilage growth plate. One month follow-up radiographs showed a fracture that confirmed the diagnosis of trampoline fracture.
Keywords: Acute hematogenous osteomyelitis; Bone scintigraphy; Gait disorders; Trampoline fracture

Disseminated osteomyelitis or bone metastases of breast cancer: 18F-FDG-PET/CT helps unravel an unusual presentation by Ramin Mandegaran; Alexa Debard; Muriel Alvarez; Bruno Marchou; Patrice Massip; Thomas Wagner (167-171).
We present a case wherein striking 18F-FDG-PET/CT findings initially considered consistent with recurrent disseminated skeletal metastases of breast cancer were later identified as an unusual presentation of disseminated chronic pyogenic osteomyelitis with Staphylococcus aureus and warneri identified on microbiological culture. A 76-year-old female with previous history of breast cancer presented with a 6-month history of pyrexia, myalgia and weight loss. Besides neutrophilia and elevated C-reactive protein, other blood indices, cultures and conventional imaging failed to identify the cause of pyrexia of unknown origin (PUO). 18F-FDG-PET/CT demonstrated multiple widespread foci of intense FDG uptake in lytic lesions throughout the skeleton. Coupled with previous history of malignancy, findings were strongly suggestive of disseminated metastases of breast cancer. Through targeting an FDG avid lesion, 18F-FDG-PET/CT aided CT-guided biopsy, which instead identified the lesions as chronic pyogenic osteomyelitis. Following prolonged antibiotic therapy, repeat 18F-FDG-PET/CT demonstrated significant resolution of lesions. This case demonstrated an unusual presentation of disseminated osteomyelitis on 18F-FDG-PET/CT and highlighted the use of 18F-FDG-PET/CT as a trouble shooter in PUO but demonstrated that unusual presentations of benign or malignant pathologies cannot always reliably be differentiated on imaging alone without aid of tissue sampling. Furthermore, this case highlights the potential role 18F-FDG-PET/CT could provide in assessing response to antibiotic therapy.
Keywords: 18F-FDG-PET/CT; Osteomyelitis; Bone metastases; PUO; Antibiotic response

Bootstrap methods for estimating PET image noise: experimental validation and an application to evaluation of image reconstruction algorithms by Masanobu Ibaraki; Keisuke Matsubara; Kazuhiro Nakamura; Hiroshi Yamaguchi; Toshibumi Kinoshita (172-182).
Accurate and validated methods for estimating regional PET image noise are helpful for optimizing image processing. The bootstrap is a data-based simulation method for statistical inference, which can be used to estimate the PET image noise without repeated measurements. The aim of this study was to experimentally validate bootstrap-based methods as a tool for estimating PET image noise and demonstrate its usefulness for evaluating image reconstruction algorithms.Two bootstrap-based method, the list-mode data bootstrap (LMBS) and the sinogram bootstrap (SNBS), were implemented on a clinical PET scanner. A uniform cylindrical phantom filled with 18F solution was scanned using list-mode acquisition. A reference standard deviation (SD) map was calculated from 60 statistically independent measured list-mode data. Using one of the 60 list-mode data, 60 bootstrap replicates were generated and used to calculate bootstrap SD maps. Brain 18F-FDG data from a healthy volunteer were also processed as an example of the bootstrap application. Three reconstruction algorithms, FBP 2D and both 2D and 3D versions of dynamic row-action maximum likelihood algorithm (DRAMA), were assessed.For all the reconstruction algorithms used, the bootstrap SD maps agreed well with the reference SD map, confirming the validity of the bootstrap methods for assessing image noise. The two bootstrap methods were equivalent with respect to the performance of image noise estimation. The bootstrap analysis of the FDG data showed the better contrast–noise relation curve for DRAMA 3D compared to DRAMA 2D and FBP 2D.The bootstrap methods provide the estimates of image noise for various reconstruction algorithms with reasonable accuracy, require only a single measurement, not repeated measures, and are, therefore, applicable for a human PET study.
Keywords: PET; Image reconstruction; Image noise; Bootstrap