Histopathological changes resulting from selective internal radiotherapy (SIRT).

BACKGROUND: Selective internal radiotherapy (SIRT) has emerged as an effective therapy for patients with liver malignancies. Here, we report our analysis of histopathological changes in tumors and healthy liver tissue after SIRT and liver resection. Our main intent was to determine if specific histopathological changes occur in tumor and normal liver tissues. METHODS: We identified 17 patients in whom SIRT was applied to achieve liver resectability. Samples were taken from the resected liver tissue. The tumor, tumor peripheries, and tumor-free tissue were examined microscopically. RESULTS: Microspheres were identified in the vascular tumor bed, tumor-free liver, and portal tract. More microspheres were detected in the tumor than in the healthy liver tissue. When the effects of SIRT were analyzed, most patients showed a partial pathological response. Specific histopathological changes could not be described. We did not find any typical signs of radiation-induced hepatitis in healthy liver tissue. CONCLUSIONS: Our findings support the clinical experience of effective tumor control after SIRT together with minimal impairment of healthy liver tissue. The observed histopathological changes suggest that SIRT might play a role in preoperative downsizing of liver malignancies.

Reduction in camera-specific variability in [(123)I]FP-CIT SPECT outcome measures by image reconstruction optimized for multisite settings: impact on age-dependence of the specific binding ratio in the ENC-DAT database of healthy controls.

PURPOSE: Quantitative estimates of dopamine transporter availability, determined with [(123)I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [(123)I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. METHODS: Of 73 healthy subjects from the European Normal Control Database of [(123)I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera-specific "to kBq/ml" calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [(123)I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. RESULTS: The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. CONCLUSION: QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [(123)I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding.

Implementation of the European multicentre database of healthy controls for [(123)I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes.

PURPOSE: Even though [(123)I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden). METHODS: We identified 101 patients with inconclusive findings who underwent an [(123)I]FP-CIT SPECT between 2003 and 2010 as part of the diagnostic process of suspected PS at the University of Munich, and re-evaluated these scans using iterative reconstruction algorithms and the new corrected EARL-BRASS. Clinical follow-up was obtained in 62 out of the 101 patients and constituted the gold standard for the re-evaluation to assess the possible improvement in diagnostic accuracy. RESULTS: Clinical follow-up confirmed the diagnosis of PS in 11 of the 62 patients. In patients in whom both visual and semiquantitative analysis showed concordant findings (48 patients), a high negative predictive value (93 %), positive predictive value (100 %) and accuracy (94 %) were found, and thus a correct diagnosis was obtained in 45 of the 48 patients. Among the 14 patients with discordant findings, the additional semiquantitative analysis correctly identified all five of nine patients patients without PS by nonpathological semiquantitative findings in visually pathological or inconclusive scans. In contrast, four of the remaining five patients with decreased semiquantitative values but visually normal scans did not show a PS during follow-up. CONCLUSION: The age-corrected and camera-corrected mode of evaluation using EARL-BRASS provided a notable improvement in the diagnostic accuracy of [(123)I]FP-CIT SPECT in PS patients with previously inconclusive findings. The gain in accuracy might be achieved by better discrimination between physiological low striatal [(123)I]FP-CIT binding due to age-related loss of the dopamine transporter or pathological loss of binding.

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0.

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard-of-care for intermediate-stage unresectable, hepatocellular carcinoma (HCC), as first-line treatment. METHODS: SIRTACE was an open-label multicenter randomized-controlled pilot study, which prospectively compared primarily safety and health-related quality of life (HRQoL) changes following TACE and SIRT. Patients with unresectable HCC, Child-Pugh ≤B7, ECOG performance status ≤2 and ≤5 liver lesions (≤20 cm total maximum diameter) without extrahepatic spread were randomized to receive either TACE (at 6-weekly intervals until tumour enhancement was not observed on MRI or disease progression) or single-session SIRT (yttrium-90 resin microspheres). RESULTS: Twenty-eight patients with BCLC stage A (32.1%), B (46.4%) or C (21.4%) received either a mean of 3.4 (median 2) TACE interventions (N = 15) or single SIRT (N = 13). Both treatments were well tolerated. Despite SIRT patients having significantly worse physical functioning at baseline, at week-12, neither treatment had a significantly different impact on HRQoL as measured by Functional Assessment of Cancer Therapy-Hepatobiliary total or its subscales. Both TACE and SIRT were effective for the local control of liver tumours. Best overall response-rate (RECIST 1.0) of target lesions were 13.3% and 30.8%, disease control rates were 73.3% and 76.9% for TACE and SIRT, respectively. Two patients in each group were down-staged for liver transplantation (N = 3) or radiofrequency ablation (N = 1). CONCLUSIONS: Single-session SIRT appeared to be as safe and had a similar impact on HRQoL as multiple sessions of TACE, suggesting that SIRT might be an alternative option for patients eligible for TACE.

Liver resection after selective internal radiotherapy (SIRT): Proof of concept, initial survival, and safety.

BACKGROUND AND OBJECTIVES: Extent of liver resections are restricted by the volume of the future liver remnant. Different strategies have been developed to increase the frequency of curative resections. Selective internal radiation therapy (SIRT) has emerged as an effective therapy for patients with primary non-resectable malignancies of the liver. Here, we report the first clinical series of patients with curative liver resection following SIRT. METHODS: Starting 2010, patients with marginally resectable liver metastases treated by SIRT followed by liver resection were identified and prospectively documented in a database for subsequent retrospective analysis. RESULTS: Thirteen patients (five female, eight male; age 70 years [32-77 years]) with marginally resectable liver metastases were selected for liver resection after SIRT. After performing SIRT, 12 patients had potentially curative hepatic resection. In two patients, liver resection after SIRT could not be performed due to the appearance of new extrahepatic metastases. Analyzing the effect of SIRT, we observed a decrease in tumor size with central scaring. None of the patients developed liver necrosis after SIRT. Liver resection was performed safely in all patients. CONCLUSIONS: The combination of SIRT with state-of-the-art liver surgery opens up new therapeutic options in patients with liver metastases.

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.

No association between striatal dopamine transporter binding and body mass index: a multi-center European study in healthy volunteers.

INTRODUCTION: Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated. METHODS: The study included 123 healthy individuals from a large European multi-center database. They had a BMI range of 18.2-41.1 kg/m(2) and were scanned using [(123)I]FP-CIT SPECT imaging. Scans were analyzed with both region-of-interest and voxel-based analysis to determine the binding potential for DAT availability in the caudate nucleus and putamen. A direct relation between BMI and DAT availability was assessed and groups with high and low BMI were compared for DAT availability. RESULTS: No association between BMI and striatal DAT availability was found. CONCLUSION: The lack of an association between BMI and striatal DAT availability suggests that the regulation of striatal synaptic dopamine levels by DAT plays no or a limited role in the pathophysiology of overweight and obesity.

Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients.

Radioembolization therapy (RE) is an efficient locoregional treatment for liver metastases from colorectal cancer. Serum biomarkers involved in immunogenic cell death are potentially valuable for early predicting therapy response and estimating prognosis. In a prospective observation study, blood samples were taken from 49 consecutive colorectal cancer patients with extensive hepatic metastases before, 24 and 48 hr after RE. Serum levels of high mobility group box 1 (HMGB1), receptor of glycation end products (RAGE) and activity of desoxyribonuclease were compared with response to therapy regularly determined radiologically 3 months after therapy and with overall survival. Serum levels of HMGB1 were increased already 24 hr after RE, while RAGE levels were decreased and DNAse remained unchanged. In radiological staging, 35 patients demonstrated disease progression while 14 patients had stable disease or remission. Serum HMGB1 levels 24 hr after RE were significantly higher in progressive than in nonprogressive patients while for RAGE and DNAse no difference was observed between the response groups. Concerning overall survival, high pretherapeutic (0 hr) and 24 hr levels of HMGB1 were associated with poor outcome. Multivariate analysis including HMGB1, tumor, liver and inflammation markers revealed HMGB1 and CRP as independent prognostic parameters. HMGB1 is a valuable serum biomarker for early estimation of therapy response and prognosis in colorectal cancer patients with liver metastases undergoing RE therapy.

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.

Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database.

PURPOSE: Multi-centre trials are an important part of proving the efficacy of procedures, drugs and interventions. Imaging components in such trials are becoming increasingly common; however, without sufficient control measures the usefulness of these data can be compromised. This paper describes a framework for performing high-quality multi-centre trials with single photon emission computed tomography (SPECT), using a pan-European initiative to acquire a normal control dopamine transporter brain scan database as an example. METHODS: A framework to produce high-quality and consistent SPECT imaging data was based on three key areas: quality assurance, the imaging protocol and system characterisation. Quality assurance was important to ensure that the quality of the equipment and local techniques was good and consistently high; system characterisation helped understand and where possible match the performance of the systems involved, whereas the imaging protocol was designed to allow a degree of flexibility to best match the characteristics of each imaging device. RESULTS: A total of 24 cameras on 15 sites from 8 different manufacturers were evaluated for inclusion in our multi-centre initiative. All results matched the required level of specification and each had their performance characterised. Differences in performance were found between different system types and cameras of the same type. Imaging protocols for each site were modified to match their individual characteristics to produce comparable high-quality SPECT images. CONCLUSION: A framework has been designed to produce high-quality data for multi-centre SPECT studies. This framework has been successfully applied to a pan-European initiative to acquire a healthy control dopamine transporter image database.

Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy.

BACKGROUND: Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. METHODS: Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. RESULTS: Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. CONCLUSION: Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy.

Compensation for cranial spill-in into the cerebellum improves quantitation of striatal dopamine D2/3 receptors in rats with prolonged [¹8F]-DMFP infusions.

The condition of steady-state receptor binding in positron emission tomography (PET) studies is best obtained through the use of a bolus plus steady-infusion paradigm. This is a particularly important consideration in the context of in vivo competition studies, where a pharmacological challenge can be administered during the interval of steady-state ligand binding, as in the case of [¹¹C]-raclopride studies with amphetamine challenge. However, the short half-life of ¹¹C imposes limits on the practical duration of constant infusions. Therefore, we chose to test [¹8F]-DMFP as a tracer for dopamine D2/3 receptors in rat striatum in the paradigm. Using a conventional bolus injection, the [¹8F]-DMFP BP(ND) was 3.8 in striatum of anesthetized rats. When followed by a constant infusion, we obtained quasi-stable BP(ND) estimates of 4.5 within an interval of 45 min. During infusions lasting up to 4 h, BP(ND) declined progressively. This seemed due to the progressive spill-in of radioactivity from the cranium to the cerebellum reference region, despite optimized iterative reconstruction of the images. Therefore, we propose a new concept of compensation for this spill-in effect using pharmacokinetic considerations, without requiring high-resolution anatomical images. Challenge with amphetamine (1 and 4 mg/kg) evoked an ∼25% reduction in BP(ND) . There was no clear evidence of dose-dependence in the striatal-binding changes, despite the considerably greater physiological effect, as documented by ECG. Thus, the general applicability of the bolus plus infusion method with [¹8F]-DMFP for small animal studies is impeded by the substantial labeling of the cranium. The cranial uptake was linear, indicating first-order kinetics for the enzymatic defluorination of the tracer. Based on this phenomenon, we developed an analytic method compensating for the effects of progressive cranial labeling on the estimation of specific binding in striatum.

Iterative reconstruction or filtered backprojection for semi-quantitative assessment of dopamine D2 receptor SPECT studies?

PURPOSE: In routine clinical practice striatal dopamine D(2) receptor binding is generally assessed using data reconstructed by filtered backprojection (FBP). The aim of this study was to investigate the use of an iterative reconstruction algorithm (ordered subset expectation maximization, OSEM) and to assess whether it may provide comparable or even better results than those obtained by standard FBP. METHODS: In 56 patients with parkinsonian syndromes, single photon emission computed tomography (SPECT) scans were acquired 2 h after i.v. application of 185 MBq [(123)I]iodobenzamide (IBZM) using a triple-head gamma camera (Siemens MS 3). The scans were reconstructed both by FBP and OSEM (3 iterations, 8 subsets) and filtered using a Butterworth filter. After attenuation correction the studies were automatically fitted to a mean template with a corresponding 3-D volume of interest (VOI) map covering striatum (S), caudate (C), putamen (P) and several reference VOIs using BRASS software. RESULTS: Visual assessment of the fitted studies suggests a better separation between C and P in studies reconstructed by OSEM than FBP. Unspecific background activity appears more homogeneous after iterative reconstruction. The correlation shows a good accordance of dopamine receptor binding using FBP and OSEM (intra-class correlation coefficients S: 0.87; C: 0.88; P: 0.84). Receiver-operating characteristic (ROC) analyses show comparable diagnostic power of OSEM and FBP in the differentiation between idiopathic parkinsonian syndrome (IPS) and non-IPS. CONCLUSION: Iterative reconstruction of IBZM SPECT studies for assessment of the D(2) receptors is feasible in routine clinical practice. Close correlations between FBP and OSEM data suggest that iteratively reconstructed IBZM studies allow reliable quantification of dopamine receptor binding even though a gain in diagnostic power could not be demonstrated.

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.

Dopaminergic mechanisms of target detection - P300 event related potential and striatal dopamine.

The P300 is a cortically generated event related potential (ERP) widely used in neurophysiological research since it is related to cognitive functions and central information processing. Intracerebral recordings and functional neuroimaging studies have demonstrated that this potential is generated by various brain regions including frontal, temporal and parietal cortices. Regarding the neurochemical background, clinical and genetic investigations suggest that dopaminergic neurons could be involved in the generation of the P300. However, there is no direct evidence in vivo that P300 amplitudes and latencies are related to dopaminergic parameters. The aim of this study was to further elucidate dopaminergic aspects of the P300 ERP by combining neurophysiological and nuclear medicine assessments in vivo. Patients with a major depressive episode underwent both P300 recordings and dynamic [¹²³I] IBZM SPECT for the evaluation of striatal dopamine D2/D3-receptor availability. There were statistically significant positive correlations of the striatal dopamine D2/D3-receptor status with P300 amplitudes and significant negative correlations with P300 latencies. Using this combined approach, the study presents direct evidence in vivo that the central dopaminergic system might play an important role in the generation of the P300 and that central dopaminergic activity could be involved in the modulation of P300 parameters. This association might be of relevance for the interpretation of P300 studies in psychiatric disorders.

The impact of reconstruction method on the quantification of DaTSCAN images.

PURPOSE: Reconstruction of DaTSCAN brain studies using OS-EM iterative reconstruction offers better image quality and more accurate quantification than filtered back-projection. However, reconstruction must proceed for a sufficient number of iterations to achieve stable and accurate data. This study assessed the impact of the number of iterations on the image quantification, comparing the results of the iterative reconstruction with filtered back-projection data. METHODS: A striatal phantom filled with (123)I using striatal to background ratios between 2:1 and 10:1 was imaged on five different gamma camera systems. Data from each system were reconstructed using OS-EM (which included depth-independent resolution recovery) with various combinations of iterations and subsets to achieve up to 200 EM-equivalent iterations and with filtered back-projection. Using volume of interest analysis, the relationships between image reconstruction strategy and quantification of striatal uptake were assessed. RESULTS: For phantom filling ratios of 5:1 or less, significant convergence of measured ratios occurred close to 100 EM-equivalent iterations, whereas for higher filling ratios, measured uptake ratios did not display a convergence pattern. Assessment of the count concentrations used to derive the measured uptake ratio showed that nonconvergence of low background count concentrations caused peaking in higher measured uptake ratios. Compared to filtered back-projection, OS-EM displayed larger uptake ratios because of the resolution recovery applied in the iterative algorithm. CONCLUSION: The number of EM-equivalent iterations used in OS-EM reconstruction influences the quantification of DaTSCAN studies because of incomplete convergence and possible bias in areas of low activity due to the nonnegativity constraint in OS-EM reconstruction. Nevertheless, OS-EM using 100 EM-equivalent iterations provides the best linear discriminatory measure to quantify the uptake in DaTSCAN studies.

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.