Extrastriatal binding of [¹²³I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls.

PURPOSE: Apart from binding to the dopamine transporter (DAT), [(123)I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. METHODS: SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. RESULTS: Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. CONCLUSION: The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [(123)I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [(123)I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors.

Automatic semi-quantification of [123I]FP-CIT SPECT scans in healthy volunteers using BasGan version 2: results from the ENC-DAT database.

PURPOSE: The aim of this study was to assess striatal dopamine transporter (DAT) availability in a large group of normal subjects. METHODS: The study included 122 healthy subjects, aged 18-83 years, recruited in the multicentre 'ENC-DAT' study (promoted by the European Association of Nuclear Medicine). Brain single photon emission computed tomography (SPECT) was acquired by means of dual-head cameras 3 h after [(123)I]FP-CIT administration. Specific to nondisplaceable binding ratios (SBRs) in the basal ganglia were computed using the 'BasGan' software, allowing automatic value extraction with partial volume effect correction. Multicentre camera inhomogeneity was taken into account by calibrating values on basal ganglia phantom data. SBR in each caudate nucleus (C) and putamen (P) were the dependent variables in a repeated measures general linear model analysis; age, gender, handedness and body mass index (BMI) were the independent variables. RESULTS: SBR values in C and P were significantly associated with age (mean rate decrease with age: 0.0306 per year, or 0.57 % of the general mean; p < 0.0001) and gender (women had higher values; p = 0.015), while no significant effect was found for handedness and BMI. A significant interaction was found between age and region (p < 0.0001) as the age-related decline was 0.028 for left C, 0.026 for right C and 0.034 for both P. P/C ratio analysis confirmed that age-related SBR decrease was stronger in P than in C (p < 0.0001). No significant effect was found for season or time of the day when the scan was acquired by analysing the residual of SBR values in C and P, after subtraction of age and gender effects. CONCLUSION: This study confirms the dependency of DAT on ageing and highlights the gender differences in a large sample of healthy subjects, while it does not support the dependency of DAT on BMI, handedness, circadian rhythm or season.

European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis.

PURPOSE: Dopamine transporter (DAT) imaging with [(123)I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [(123)I]FP-CIT SPECT scans in healthy controls. METHODS: SPECT data from 139 healthy controls (74 men, 65 women; age range 20-83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR). RESULTS: A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade. CONCLUSION: This study provides a large database of [(123)I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for nuclear medicine centres and for clinical trials using [(123)I]FP-CIT SPECT as the imaging marker.

Calibration of gamma camera systems for a multicentre European ¹²³I-FP-CIT SPECT normal database.

PURPOSE: A joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [(123)I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization and harmonization of the imaging equipment of the institutions involved. METHODS: (123)I SPECT images of a striatal phantom filled with striatal to background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute ratios measured from aliquots. The images were reconstructed by a core lab using ordered subset expectation maximization (OSEM) without corrections (NC), with attenuation correction only (AC) and additional scatter and septal penetration correction (ACSC) using the triple energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR), was measured using the "Southampton" methodology that accounts for the partial volume effect and compared against the actual values obtained from the aliquots. Camera-specific recovery coefficients were derived from linear regression and the error of the measurements was evaluated using the coefficient of variation (COV). RESULTS: The relationship between measured and actual sSBRs was linear across all systems. Variability was observed between different manufacturers and, to a lesser extent, between cameras of the same type. The NC and AC measurements were found to underestimate systematically the actual sSBRs, while the ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range 69-89%, ACSC range 87-116%). The COV improved from 46% (NC) to 32% (AC) and to 14% (ACSC) (p < 0.001). CONCLUSION: A satisfactory linear response was observed across all cameras. Quantitative measurements depend upon the characteristics of the SPECT systems and their calibration is a necessary prerequisite for data pooling. Together with accounting for partial volume, the correction for scatter and septal penetration is essential for accurate quantification.

Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival.

The aim of the present study was to investigate the prognostic role of pre- and/or early post-autologous stem cell transplantation (ASCT) (18)F-flourodeoxyglucose (FDG) positron emission tomography (PET) in patients with relapsed/refractory Hodgkin lymphoma. Forty-three consecutive patients were enrolled in this study. FDG-PET/CT was performed following salvage chemotherapy within 6 weeks of undergoing ASCT and at the first month after ASCT. FDG-PET positivity was found in 26 patients before ASCT and in 13 patients after ASCT. The patients who had negative PET scan before or after ASCT had significantly better outcomes in terms of overall survival (OS) and progression-free survival (PFS). Pre- and post-ASCT FDG-PET positivity was found to be independently associated with PFS while post-ASCT FDG-PET was an independent factor with an impact on OS in multivariate analysis. (18)F-flourodeoxyglucose positron emission tomography imaging may be useful in predicting prognosis after ASCT. Furthermore, effective treatment options including allogeneic stem cell transplantation might be considered in patients with positive FDG-PET scan after salvage chemotherapy and ASCT.

EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2.

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using (123)I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [1] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a consensus statement of the imaging centres included in the "Kompetenznetz-Parkinson" sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3]. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2.

The guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2 receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, which will increase the impact of this technique in neurological practice.The present document is an update of the first guidelines for SPECT using D2 receptor ligands labelled with (123)I [1] and was guided by the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines intend to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

EANM procedure guideline for brain perfusion SPECT using 99mTc-labelled radiopharmaceuticals, version 2.

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of brain perfusion single photon emission computed tomography (SPECT) studies using (99m)Tc-labelled radiopharmaceuticals. The aim is to achieve a high quality standard for brain perfusion SPECT imaging, which will increase the diagnostic impact of this technique in clinical practice. The present document replaces a former version of the guideline published in 2001 which was inspired by the Society of Nuclear Medicine Procedure Guideline for Brain Perfusion SPECT [1], the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

EANM procedure guidelines for PET brain imaging using [18F]FDG, version 2.

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose ([(18)F]FDG) PET imaging of the brain. The aim is to help achieve a high standard of FDG imaging, which will increase the diagnostic impact of this technique in neurological and psychiatric practice. The present document replaces a former version of the guidelines that were published in 2002 [1] and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging. These guidelines are intended to present information specifically adapted for European practice. The information provided should be taken in the context of local conditions and regulations.

Crossed Wernicke's aphasia after aneurysmal subarachnoid hemorrhage: a case report.

Crossed aphasia (CA) refers to aphasia occurring after right brain damage in right handers. In the literature, numerous CA cases following cerebral ischemia have been reported, but few met the criteria for a prompt diagnosis. The authors present the case of a 52-year-old woman with SAH caused by a right middle cerebral artery (MCA) saccular aneurysm who developed non-fluent aphasia characterized by reduced verbal output, word-finding disturbances and phonemic paraphasias in both oral and written language. 99mTc-HMPAO SPECT was also consistent with right parieto-temporal and frontoparietal ischemia with crossed cerebellar diaschisis on the right cerebellum. A diagnosis of CA was made. One year follow-up showed improvement in communication skills but persistent right fronto-temporo-parietal ischemia. Cerebral vasospasm after aneurysmal SAH symptomatology may vary from motor and sensory disturbances to cognitive disabilities. Aphasia developing after cerebral ischemia of the right hemisphere in a right-hand dominant patient following vasospasm may be a misleading symptom for the localization of the insult. Keeping a high index of suspicion may help in making the correct diagnosis. The changes in the perfusion patterns of cerebellum as assessed by SPECT study during the acute and recovery phases suggests the involvement of cerebellum in language functions.

The impact of reconstruction and scanner characterisation on the diagnostic capability of a normal database for [123I]FP-CIT SPECT imaging.

BACKGROUND: The use of a normal database for [123I]FP-CIT SPECT imaging has been found to be helpful for cases which are difficult to interpret by visual assessment alone, and to improve reproducibility in scan interpretation. The aim of this study was to assess whether the use of different tomographic reconstructions affects the performance of a normal [123I]FP-CIT SPECT database and also whether systems benefit from a system characterisation before a database is used. Seventy-seven [123I]FP-CIT SPECT studies from two sites and with 3-year clinical follow-up were assessed quantitatively for scan normality using the ENC-DAT normal database obtained in well-documented healthy subjects. Patient and normal data were reconstructed with iterative reconstruction with correction for attenuation, scatter and septal penetration (ACSC), the same reconstruction without corrections (IRNC), and filtered back-projection (FBP) with data quantified using small volume-of-interest (VOI) (BRASS) and large VOI (Southampton) analysis methods. Test performance was assessed with and without system characterisation, using receiver operating characteristics (ROC) analysis for age-independent data and using sensitivity/specificity analysis with age-matched normal values. The clinical diagnosis at follow-up was used as the standard of truth. RESULTS: There were no significant differences in the age-independent quantitative assessment of scan normality across reconstructions, system characterisation and quantitative methods (ROC AUC 0.866-0.924). With BRASS quantification, there were no significant differences between the values of sensitivity (67.4-83.7%) or specificity (79.4-91.2%) across all reconstruction and calibration strategies. However, the Southampton method showed significant differences in sensitivity between ACSC (90.7%) vs IRNC (76.7%) and FBP (67.4%) reconstructions with calibration. Sensitivity using ACSC reconstruction with this method was also significantly better with calibration than without calibration (65.1%). Specificity using the Southampton method was unchanged across reconstruction and calibration choices (82.4-88.2%). CONCLUSIONS: The ability of a normal [123I]FP-CIT SPECT database to assess clinical scan normality is equivalent across all reconstruction, system characterisation, and quantification strategies using BRASS quantification. However, when using the Southampton quantification method, performance is sensitive to the reconstruction and calibration strategy used.

Primary renal lymphoma and xanthogranulomatous pyelonephritis in childhood.

Primary renal non-Hodgkin's lymphoma is very rare in childhood. A six-year-old boy presented with bilateral non-obstructive multinodular nephromegaly and renal failure. Percutaneous needle biopsy showed large-cell lymphoma. The patient was started on chemotherapy. A right nephrectomy was done when systemic hypertension developed in the presence of a non-functional right kidney. Histopathologic examination revealed focal lymphomatous infiltration and xanthogranulomatous pyelonephritis which is an atypical form of chronic renal infection. The case is discussed in relation to previons reports.

Association between survival and maximum standardized uptake value of liver metastases detected by 18-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography in patients with adenocarcinoma of unknown primary origin.

OBJECTIVE: The objective of this retrospective study is to investigate the association between survival and maximum standardized uptake values (SUVmax) of liver metastases detected by pre-treatment positron emission tomography-computed tomography (PET-CT) in patients with adenocarcinoma of unknown primary origin (ACUP). METHODS: A total of 58 patients with ACUP and liver metastases confirmed histopathologically by liver biopsy and pre-treatment PET-CT were included in this study. SUVmax values of the liver lesions were measured and their association with survival was investigated. RESULTS: The median age was 62 years; 63.8 % of the patients were males and 36.2 % were females. The median overall survival was calculated as 10.7 months (OS). The median SUVmax of the liver metastases was 8.6. Accordingly, two groups were established: one with values <8.6 and the other with ones ≥8.6. No differences were detected between the two groups with respect to general characteristics. Median OS was 13.2 months in the group with SUVmax <8.6 compared to 7.4 months in the group with SUVmax ≥8.6. This difference was statistically significant (p = 0.033). SUVmax (HR 1.104, 95 % CI 1.013-1.204, p = 0.025), age (HR 1.033, 95 % CI 1.002-1.064, p = 0.034), presence of chemotherapy (HR 2.296, 95 % CI 1.136-4.641, p = 0.021) and LDH level (HR 1.002, 95 % CI 1.001-1.003, p = 0.007) were identified as independent prognostic factors affecting survival in the multivariable analysis. This is the first report evaluating the impact of SUVmax for liver metastases on ACUP patient survival. CONCLUSION: The SUVmax of liver metastases evaluated by PET-CT is a prognostic factor influencing survival of patients with ACUP.

No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [123I]FP-CIT (DaTSCAN) and SPECT.

BACKGROUND: Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D2-like receptors. Molecular imaging studies of the relationship between DAT availability/dopamine synthesis capacity and active cigarette smoking have shown conflicting results. Through the collaboration between 13 SPECT centres located in 10 different European countries, a database of FP-CIT-binding in healthy controls was established. We used the database to test the hypothesis that striatal DAT availability is changed in active smokers compared to non-smokers and ex-smokers. METHODS: A total of 129 healthy volunteers were included. Subjects were divided into three categories according to past and present tobacco smoking: (1) non-smokers (n = 64), (2) ex-smokers (n = 39) and (3) active smokers (n = 26). For imaging of the DAT availability, we used [123I]FP-CIT (DaTSCAN) and single photon emission computed tomography (SPECT). Data were collected in collaboration between 13 SPECT centres located in 10 different European countries. The striatal measure of DAT availability was analyzed in a multiple regression model with age, SPECT centre and smoking as predictor. RESULTS: There was no statistically significant difference in DAT availability between the groups of active smokers, ex-smokers and non-smokers (p = 0.34). Further, we could not demonstrate a significant association between striatal DAT and the number of cigarettes per day or total lifetime cigarette packages in smokers and ex-smokers. CONCLUSION: Our results do not support the hypothesis that large differences in striatal DAT availability are present in smokers compared to ex-smokers and healthy volunteers with no history of smoking.

The nodal standard uptake value (SUV) as a prognostic factor in head and neck squamous cell cancer.

BACKGROUND/AIMS: The aim of present study is to evaluate the predictive and prognostic role of high [18F] fluoro-D-glucose (FDG) uptake of primary tumor and nodal metastasis in squamous cell carcinoma of head and neck (HNSCC). METHODOLOGY AND PATIENTS: Between February 2006 and July 2010, we retrospectively evaluated 64 patients with primary HNSCC in an institutional imaging trial. All patients who underwent evaluation pretreatment FDG-positron emission tomography/computarized tomography (FDG-PET/CT) imaging and 33 (51%) had pre- and after treatment FDG-PET/CT imaging. All treatments were performed with curative intent. Abnormal FDG uptakes were analyzed using maximum standardized uptake values (SUVm). The disease-free survival (DFS) and overall survival (OS) were evaluated with several prognostic factors such as pre-treatment SUVm and %change in SUVm. RESULTS: Tumor sites are nasopharynx (n=29, 45.3%), larynx (n=16, 25%), oropharynx (n=13, 20.4%) and hypopharynx (n=6, 9.4%). Median age was 58 (range: 16-87) and most patients (84.4%) had stage III/IV lesions. Objective response rate was 78.2%. The median primary tumor SUVm was 13.4 (range, 4.8-33.1), median nodal SUVm was 4.45 (range, 0-25.6) and median % change in SUVm was 74.1 (range, -61-100). On multivariate analysis, nodal SUVm and surgery remained significant predictors of DFS. There was no statistical significance found between survival and other factors. CONCLUSIONS: We have found that while nodal SUVm is prognostic for DFS, primary tumor SUVm and % change in SUVm are not.

A comparison of radionuclide thyroid angiography, (99m)Tc-MIBI scintigraphy and power Doppler ultrasonography in the differential diagnosis of solitary cold thyroid nodules.

We prospectively studied 43 patients with solitary cold thyroid nodules greater than 1.5 cm in diameter to determine the comparative diagnostic value of radionuclide thyroid angiography (RTA), technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy and power Doppler ultrasonography (PDUS) in the differentiation of benign and malignant thyroid nodules. Perfusion of the nodules in RTA was compared with the perfusion in the surrounding normal thyroid tissue and classified as follows: 0, avascular; 1, hypovascular; 2, isovascular; 3, hypervascular. (99m)Tc-MIBI uptake in the nodules compared with that in surrounding thyroid tissue was scored for both early and delayed images as follows: 0, cold; 1, decreased; 2, equal; 3, increased. PDUS patterns were classified as nodule vascularisation patterns. The malignancy criteria were set as follows: hypervascular nodule with rapid washout in RTA; complex ring sign with anarchic structure or delta sign in PDUS, and positive retention and increased uptake in the nodule in the early and delayed (99m)Tc-MIBI images. These data were compared with the histopathological results. Histology revealed thyroid carcinoma in nine patients (five cases of papillary carcinoma, three of follicular carcinoma and one of medullary carcinoma) and benign conditions in 34 patients (30 cases of nodular goitre, three of lymphocytic thyroiditis and one of follicular adenoma). Sensitivity, specificity and accuracy were, respectively, 0.89, 1.00 and 0.97 for RTA, 1.00, 0.76 and 0.81 for PDUS, and 0.67, 0.91 and 0.86 for (99m)Tc-MIBI scintigraphy (when nodules with increased uptake in both the early and the delayed images and a positive retention index were considered as malignant). RTA, (99m)Tc-MIBI scintigraphy and PDUS could be helpful in the preoperative assessment of solitary cold thyroid nodules. In this study, RTA was found to be the most accurate and specific method for differentiation of malignant from benign thyroid nodules.