Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence.

Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [18F]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction. CLINICAL TRIAL REGISTRATION: NCT01679145.

Prospective comparison of diffusion-weighted MRI and dynamic Gd-EOB-DTPA-enhanced MRI for detection and staging of hepatic fibrosis in primary sclerosing cholangitis.

PURPOSE: To assess the diagnostic value of multiparametric magnetic resonance imaging (MRI) including dynamic Gd-EOB-DTPA-enhanced (DCE) and diffusion-weighted (DW) imaging for diagnosis and staging of hepatic fibrosis in primary sclerosing cholangitis (PSC) using transient elastography as a standard reference. MATERIAL AND METHODS: Multiparametric MRI was prospectively performed on a 3.0-Tesla scanner in 47 patients (age 43.9±14.3 years). Transient elastography derived liver stiffness measurements (LSM), DCE-MRI derived parameters (hepatocellular uptake rate (Ki), arterial (Fa), portal venous (Fv) and total (Ft) blood flow, mean transit time (MTT), and extracellular volume (Ve)) and the apparent diffusion coefficient (ADC) were calculated. Correlation and univariate analysis of variance with post hoc pairwise comparison were applied to test for differences between LSM derived fibrosis stages (F0/F1, F2/3, F4). ROC curve analysis was used as a performance measure. RESULTS: Both ADC and Ki correlated significantly with LSM (r= -0.614; p<0.001 and r= -0.368; p=0.01). The ADC significantly discriminated fibrosis stages F0/1 from F2/3 and F4 (p<0.001). Discrimination of F0/1 from F2/3 and F4 reached a sensitivity/specificity of 0.917/0.821 and 0.8/0.929, respectively. Despite significant inter-subject effect for classification of fibrosis stages, post hoc pairwise comparison was not significant for Ki (p>0.096 for F0/1 from F2/3 and F4). LSM, ADC and Ki were significantly associated with serum-based liver functional tests, disease duration and spleen volume. CONCLUSION: DW-MRI provides a higher diagnostic performance for detection of hepatic fibrosis and cirrhosis in PSC patients in comparison to Gd-EOB-DTPA-enhanced DCE-MRI. KEY POINTS: • Both ADC and hepatocellular uptake rate (Ki) correlate significantly with liver stiffness (r= -0.614; p<0.001 and r= -0.368; p=0.01). • The DCE-imaging derived quantitative parameter hepatocellular uptake rate (Ki) fails to discriminate pairwise intergroup differences of hepatic fibrosis (p>0.09). • DWI is preferable to DCE-imaging for discrimination of fibrosis stages F0/1 to F2/3 (p<0.001) and F4 (p<0.001).

Altered cerebral glucose metabolism normalized in a patient with a pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS)-like condition following treatment with plasmapheresis: a case report.

BACKGROUND: Pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS) is a specific autoimmune response to group-A streptococcal infections in children and adolescents with a sudden onset of obsessive-compulsive disorders or tic-like symptoms. Cerebral metabolic changes of patients have not yet been observed. CASE PRESENTATION: We present a case of an 18-year old male with a PANDAS-like condition after developing tic-like symptoms and involuntary movements three weeks after cardiac surgery. The patient had suffered from pharyngotonsillitis before the symptoms started. The anti-streptolysin O (ASO) titer was elevated (805 kU/l). Antibiotic therapy did not improve his condition. Intravenous immunoglobulins and high-dose cortisone therapy had minor beneficial effects on his involuntary movements. 18F-Fluorodeoxyglucose positron emission tomography/ computer tomography (18F-FDG PET/CT) demonstrated pronounced hypermetabolism of the basal ganglia and cortical hypometabolism. The patient was treated with five cycles of plasmapheresis. A marked clinical improvement was observed after four months. Cerebral metabolic alterations had completely normalized. CONCLUSIONS: This is the first report of cerebral metabolic changes observed on FDG-PET/CT in a patient with a PANDAS-like condition with a normalization following immunomodulatory treatment. Cerebral FDG-PET/CT might be a promising tool in the diagnosis of PANDAS.

Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose.

BACKGROUND AND PURPOSE: The aim of this pilot study was (1) to evaluate the combination of [(18)F]fluorodeoxyglucose (FDG) and [(15)O]water for detection of flow-metabolism mismatch in advanced cervical carcinomas, i.e., increased glycolysis at low blood flow, as a possible parameter for prediction of response to treatment, and (2) to propose a method for automated quantification of its spatial extent. PATIENTS AND METHODS: The study retrospectively included 10 women with advanced cervical carcinoma in whom PET with both FDG and [(15)O]water had been performed prior to therapy. The metabolically active tumor volume was delineated automatically in the FDG images. For computation of the regional blood flow in the tumor, a recovery corrected image-derived arterial input function was used. A tumor voxel was classified as mismatched when the voxel SUV of FDG was larger than the median tumor SUV and the voxel perfusion (K1) was smaller than the median perfusion. The absolute mismatch volume (aMMV) was defined as the volume of all mismatched voxels in ml, and the relative mismatch volume (rMMV) as the ratio of the aMMV to the metabolic tumor volume in percent. RESULTS: The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV clustered into 2 groups: "large aMMV" ≥ 10 ml in 40 % of patients and "small aMMV" ≤ 5 ml in 60 % of patients. The rMMV ranged from 12.7-24.9 %. There was no correlation between rMMV and metabolic tumor volume. There was a tendency (p = 0.126) for an association between rMMV and histological grading, rMMV being about 20 % higher in G3 than in G2 tumors. rMMV did not correlate with SUV or perfusion. CONCLUSION: These results suggest that combined PET with FDG and [(15)O]water allows detection and quantitative characterization of flow-metabolism mismatch in advanced cervical carcinomas.

Transcranial sonography and [18F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison.

BACKGROUND AND PURPOSE: Brain imaging with positron emission tomography using [(18) F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared. METHODS: Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). RESULTS: After a median follow-up period of 9 months, the final clinical diagnoses (reference standard) were Parkinson's disease, n = 15; MSA, n = 9; PSP, n = 7; and CBD, n = 5 (n = 21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P = 0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P = 1.00). CONCLUSIONS: FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

FDG PET/CT in cancer therapy monitoring: computer-assisted analysis of baseline together with up to two follow-ups.

OBJECTIVES: We developed and tested a software tool for computer-assisted analysis of FDG-PET/CT in cancer therapy monitoring. The tool provides automatic semi-quantitative analysis of a baseline scan together with up to two follow-up scans (standardized uptake values, glycolytic volume). The tool also supports visual analysis by local spatial registration which allows display of tumor lesions with the same orientation in all scans. The tool's stability and accuracy was tested at typical everyday image quality. PATIENTS, METHODS: Ten unselected cancer patients in whom three FDG PET/CT scans had been performed were included. A total of 18 lesions were analyzed. RESULTS: Automatic lesion tracking worked properly in all lesions but one. In this lesion local coregistration had to be adjusted manually which, however, is easily performed with the tool. Semi-automatic lesion segmentation and fully automatic semi-quantitative analysis worked properly in all cases. Computer-assisted analysis was significantly less time consuming than manual analysis. CONCLUSIONS: The novel software tool appears useful for analysis of FDG-PET/CT in cancer therapy monitoring in clinical routine patient care.

IBZM SPECT and FDG PET in the differential diagnosis of Parkinsonian syndromes: comparison with respect to inter-rater agreement.

AIM: Both IBZM SPECT and FDG PET may be used for differentiation between Parkinson's disease (PD) and atypical neurodegenerative parkinsonian syndromes (APS). However, there are only very limited data of both modalities in the same subjects. The present study compared both modalities with respect to inter-rater agreement in 30 patients with neurodegenerative parkinsonian syndromes (PS) confirmed by FP-CIT SPECT. METHODS: IBZM SPECT and FDG PET were categorized as PD or APS by visual inspection of standardized report pages and statistical parametric maps (SPMs). Categorization was performed independently by five readers. Inter-rater agreement was quantified using Cohen's kappa kappa. RESULTS: IBZM SPECT resulted in PD and APS in 11 and 19 cases, respectively (majoritarian categorization). Inter-rater agreement was kappa=0.64+/-0.10. FDG PET resulted in PD and APS in 12 and 18 cases, respectively (majoritarian categorization). Inter-rater agreement was kappa=0.68+/-0.07. Majoritarian diagnosis disagreed between IBZM SPECT and FDG PET in 13 cases (43%). Semi-quantitative analysis of IBZM SPECT using the striatum-to-reference distribution volume ratio was in good agreement with visual categorization (area under ROC curve 0.92). CONCLUSION: In neurodegenerative PS, inter-rater agreement of visual analysis is substantial in both IBZM SPECT and FDG PET. Furthermore, (I) visual analysis of IBZM SPECT is reliable if adequate standardized image display is used, (II) visual analysis of FDG SPMs allows unique categorization as either PD or APS in most subjects, and (III) IBZM SPECT and FDG PET are discordant in a significant fraction of cases.

GlyT1 encephalopathy: Characterization of presumably disease causing GlyT1 mutations.

Glycine constitutes a major inhibitory neurotransmitter predominantly in caudal regions of the CNS. The extracellular glycine concentration is regulated synergistically by two high affinity, large capacity transporters GlyT1 and GlyT2. Both proteins are encoded by single genes SLC6A9 and SLC6A5, respectively. Mutations within the SLC6A5 gene encoding for GlyT2 have been demonstrated to be causative for hyperekplexia (OMIM #614618), a complex neuromuscular disease, in humans. In contrast, mutations within the SLC6A9 gene encoding for GlyT1 have been associated with GlyT1 encephalopathy (OMIM #601019), a disease causing severe postnatal respiratory deficiency, muscular hypotonia and arthrogryposis. The consequences of the respective GlyT1 mutations on the function of the transporter protein, however, have not yet been analysed. In this study we present the functional characterisation of three previously published GlyT1 mutations, two mutations predicted to cause truncation of GlyT1 (GlyT1Q573* and GlyT1K310F+fs*31) and one predicted to cause an amino acid exchange within transmembrane domain 7 of the transporter (GlyT1S407G), that are associated with GlyT1 encephalopathy. Additionally, the characterization of a novel mutation predicted to cause an amino acid exchange within transmembrane domain 1 (GlyT1V118M) identified in two fetuses showing increased nuchal translucency and arthrogryposis in routine ultrasound scans is demonstrated. We show that in recombinant systems the two presumably truncating mutations resulted in an intracellular retained GlyT1 protein lacking the intracellular C-terminal domain. In both cases this truncated protein did not show any residual transport activity. The point mutations, hGlyT1S407G and hGlyT1V118M, were processed correctly, but showed severely diminished activity, thus constituting a functional knock-out in-vivo. Taken together our data demonstrate that all analysed mutations of GlyT1 that have been identified in GlyT1 encephalopathy patients cause severe impairment of transporter function. This is consistent with the idea that loss of GlyT1 function is indeed causal for the disease phenotype.

Performance evaluation of a novel multi-pinhole collimator for dopamine transporter SPECT.

There is a tradeoff between spatial resolution and count sensitivity in SPECT with conventional collimators. Multi-pinhole (MPH) collimator technology has potential for concurrent improvement of resolution and sensitivity in clinical SPECT of 'small' organs. This study evaluated a novel MPH collimator specifically designed for dopamine transporter (DAT) SPECT with a triple-head SPECT camera. Count sensitivity was measured with a 99mTc point source placed on the lattice points of a 1 cm grid covering the whole field-of-view (FOV). Spatial resolution was assessed with a Derenzo type hot rod phantom. An anthropomorphic striatum phantom was scanned with total activity representative of a typical patient scan and different striatum-to-background activity concentration ratios. Recovery of striatum-to-background contrast was assessed by the contrast-recovery-coefficient. Measurements were repeated with double-head SPECT with fan-beam or low-energy-high-resolution-high-sensitivity (LEHRHS) collimators. A patient referred to DAT SPECT because of suspicion of Parkinson's disease was scanned with both LEHRHS and MPH collimators after a single tracer injection. The axial MPH sensitivity profile was approximately symmetrical around its peak, although it was shifted 7 cm towards the patient to simplify positioning. Peak sensitivity of the triple-head MPH system in the center of the FOV was 620 cps MBq-1 compared to 225 cps MBq-1 for the double-head fan-beam system. Sensitivity of the MPH system decreased towards the edges of the FOV. The full width of the sensitivity profile at 200 cps MBq-1 was 21 cm transaxially and 11 cm axially. In MPH SPECT of the Derenzo phantom all rods with ≥ 5 mm diameter were clearly visible. MPH SPECT improved striatal contrast recovery by ≥ 20% compared to fan-beam SPECT. The patient scan demonstrated good image quality of MPH SPECT with almost PET-like delineation of putamen and caudate nucleus. SPECT with dedicated MPH collimators provides considerable improvement of the resolution-sensitivity tradeoff in DAT SPECT compared to SPECT with fan-beam or LEHRHS collimators.

Computer simulations suggest that acute correction of hyperglycaemia with an insulin bolus protocol might be useful in brain FDG PET.

AIM: FDG PET in hyperglycaemic subjects often suffers from limited statistical image quality, which may hamper visual and quantitative evaluation. In our study the following insulin bolus protocol is proposed for acute correction of hyperglycaemia (>7.0 mmol/l) in brain FDG PET. (i) Intravenous bolus injection of short-acting insulin, one I.E. for each 0.6 mmol/l blood glucose above 7.0. (ii) If 20 min after insulin administration plasma glucose is

The simplified reference tissue model for SPECT/PET brain receptor studies. Interpretation of its parameters.

AIM: The SRTM (simplified reference tissue model) of brain receptor imaging assumes that the time activity curve in the receptor-rich region of interest can be fitted satisfactorily by the 1-tissue compartment model. This assumption has been formulated by a rather restrictive constraint on the rate constants. Empirically, the SRTM might well describe also tracers which do not fulfil this constraint, such as [(11)C]raclopride, for example. However, this has not been justified rigorously. METHODS: The requirements for the SRTM to be applicable are analyzed in detail. RESULTS: The SRTM is applicable under a less restrictive constraint than described previously. The interpretation of the SRTM parameters R(1) and k(2) in physiological terms depends on the constraint, while the interpretation of BP(ND) does not. CONCLUSION: Correct interpretation of the results of the SRTM is tracer specific. In particular, the parameter R(1), which in case of compliance with the original constraint might be used to detect perfusion and/or extraction effects, might not be appropriate for this purpose in case of raclopride-like tracers.

Hypermetabolism in the hippocampal formation of cognitively impaired patients indicates detrimental maladaptation.

Structural deterioration and volume loss of the hippocampal formation is observed in many diseases associated with memory decline. Paradoxically, glucose metabolism of the hippocampal formation can be increased at the same time. This might be a consequence of compensatory (beneficial) or maladaptive (detrimental) mechanisms. Aim of this study was to differentiate between compensation and maladaptation by analyzing the association between glucose metabolism in the hippocampal formation measured by positron emission tomography with the glucose analogue 18F-fluorodeoxyglucose and cognitive performance as characterized by the extended Consortium to Establish a Registry for Alzheimer's Disease test battery in a sample of 87 patients (81.8 ± 5.4 years) with mild cognitive impairment or mild dementia and varying etiological diagnoses. Glucose metabolism in the hippocampal formation was negatively correlated with the performance in several cognitive subdomains, most pronounced for verbal semantic fluency, independent of overall neuronal dysfunction, presence of clinical Alzheimer's disease, and overall cognitive performance. This finding provides evidence that increased glucose metabolism in the hippocampal formation of cognitively impaired patients indicates detrimental maladaptation rather than a beneficial compensatory reaction. Excess glucose metabolism in the hippocampal formation might be a useful therapeutic target in these patients.

[Image quality of thickened slabs in multislice CT chest examinations: postprocessing vs. direct reconstruction]. / Bildqualität aufaddierter Schichten bei MSCT-Untersuchungen des Thorax: Bildnachverarbeitung versus Direktrekonstruktion.

PURPOSE: Postprocessing offers the possibility of real-time creation of thickened slabs from a set of thin slices. This allows the interactive change from thick to thin slices for better evaluation of unclear lesions. As a result the clinical workflow of MSCT evaluation can be improved. However, to be able to apply this postprocessing software in the clinical routine, degradations in the image quality (compared to standard original reconstructed images) have to be avoided. The purpose of this study was to compare the image quality of thickened slabs from MSCT chest examinations that have either been directly reconstructed from the raw data or have been retrospectively generated via postprocessing. MATERIALS AND METHODS: Chest MSCT examinations of 20 patients (mean age: 56 years) were performed on a 16-slice MSCT scanner (Mx8000IDT16, Philips, Best, Netherlands) using the following scan parameters: 120 kV, 94 effective mAs, 16 x 1.5 mm collimation, 512 x 512 matrix, field of view 371 x 371 mm, CTDIvol = 6.3 mGy, DLP = 210 mGyxcm). Slices with a thickness of 3 and 5 mm were generated for each examination both directly from the raw data and via postprocessing. Corresponding images from postprocessing and direct reconstruction (lung/soft tissue window) were evaluated by two radiologists with respect to 5 criteria on the basis of a five-point scale: organ structure, contour of small objects, contrast, image noise and artifacts. Differences between both data sets regarding image quality were assessed for each of the 5 criteria using a Wilcoxon test with Bonferroni correction. In addition, image noise was analyzed quantitatively in a region of interest in the aorta. RESULTS: For the lung and soft tissue window, both reviewers and all criteria, no differences in image quality were detected between the thickened slices obtained via direct reconstruction and the postprocessing method. In 96 % and 95 % of the cases images of the two reconstruction methods were graded identically for 3 mm and 5 mm slices. In the remaining 4 % and 5 %, the evaluations differed only by one point on the five-point scale. The median grade of the first reviewer was 1 and that of the second reviewer was 2. There were no differences in the quantitative analysis of image noise between both methods. CONCLUSION: The interactive creation of thickened slices is an effective tool for the evaluation of MSCT examinations. For the defined scan parameters in this study there were no differences in image quality between postprocessing methods (e. g. slab viewer) and direct image reconstruction.

Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective.

Although 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a known serotonergic neurotoxin in different animal species, there is to date no conclusive evidence of its neurotoxicity in humans. MDMA use was associated with impairments of psychological well-being, verbal memory and altered serotonergic functioning in a number of cross-sectional studies. Due to inherent methodological limitations, such as the notorious polydrug use of ecstasy users and lack of control of possible pre-existing differences between ecstasy users and control participants, researchers have called for well-controlled, prospective longitudinal studies to shed more light on the issue of MDMA neurotoxicity to the human brain. This longitudinal study investigated whether mood, cognition and central serotonin transporters (SERT) would deteriorate with continued MDMA use and whether or not they would recover over increasing periods of MDMA abstinence. In a repeated-measures design, 11 current and ten ex-ecstasy users, and 11 polydrug (but not MDMA) and 15 drug-naive controls participated three times within approximately two years. Both ecstasy user groups reported a polydrug use pattern besides heavy ecstasy use. Subjective reports of ecstasy use or abstinence were verified by toxicological analyses. On each trial, the participants underwent a cognitive test battery and filled in the Symptom Check List. The availability of central SERT was assessed with positron emission tomography using the McN5652 ligand for all groups at t1, and only for the ecstasy user groups on follow-ups. The factor Group yielded significant results in the SCL-90 scales Global Severity Index, Anxiety, Obsessive/compulsive and Interpersonal sensitivity, with the ex-ecstasy users reporting the highest symptom scores. There were significant Group effects in all measures of verbal memory, with the lowest performance in the group of ex-ecstasy users. The repeated-measures analyses yielded no significant Group x Time interactions in any SCL-90 scales or measures of memory performance, with the exception of AVLT 1 immediate recall. Thus the ex-ecstasy users' psychopathological symptoms and memory performance failed to improve, and the current ecstasy users' failed to deteriorate, over time relative to the other groups. While there was a significant effect of Group in all brain regions examined (except the control region white matter), the current users' SERT availability seems to have recovered in the mesencephalon, as indicated by a significant Group x Time interaction. Reduced SERT availability might be a transient effect of heavy ecstasy use, since it partially recovered as the current users reduced their MDMA use. However, this measure may not necessarily be a valid indicator of the number or integrity of serotonergic neurons. Ex-ecstasy users' verbal memory showed no sign of improvement even after over 2.5 years of abstinence and thus may represent persistent functional consequences of MDMA neurotoxicity. However, alternative causes such as pre-existing group differences cannot be completely ruled out in spite of the longitudinal design.

Myocardial viability assessed by positron emission tomography in infants and children after the arterial switch operation and suspected infarction.

OBJECTIVES: The aim of the study was to assess regional glucose metabolism and contractile function by gated positron emission tomography using fluoro-18-deoxyglucose (FDG-PET) in pediatric patients after the arterial switch operation and suspected myocardial infarction. BACKGROUND: Morbidity and mortality after the arterial switch operation for transposition of the great arteries are often related to impaired coronary function. Justification of high-risk revascularization procedure in infancy requires thorough evaluation of myocardial viability. Although PET is state-of-the-art for evaluation of myocardial viability in adults there are no reports on its impact and feasibility in infants and children. METHODS: We applied electrocardiogram-triggered FDG-PET for assessment of metabolic and functional status of the myocardium in seven infants and seven children. Glucose metabolism, wall motion and wall thickening were evaluated visually and quantitatively on the basis of parametric 3-D images. Additionally, single-photon emission computed tomography perfusion scan was performed in six children. RESULTS: In two of seven infants, FDG-PET demonstrated viable myocardium in akinetic or hypokinetic regions corresponding to a coronary artery stenosis or occlusion. Therefore, indication for revascularization was derived from this finding. In six of the seven children, impaired glucose uptake reflecting myocardial scarring was present. Two patients had pathological findings on coronary angiography and signs of ischemia but were not suitable for revascularization. CONCLUSIONS: Myocardial viability and contractile function can be assessed simultaneously by gated FDG-PET even in infant hearts. This method contributes pertinent information to guide further therapy after the arterial switch operation and suspected myocardial infarction.

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing.

UNLABELLED: The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. PATIENTS, MATERIAL AND METHODS: 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. RESULTS: Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. CONCLUSIONS: SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

Quality assurance in PET: evaluation of the clinical relevance of detector defects.

UNLABELLED: Defective detector blocks in PET may cause serious image artifacts. To estimate the influence of malfunctioning detectors on image quality, a method is described for transferring the actual detector defect onto previously acquired scans. METHODS: Consequences of detector defects of varying types and extensions were simulated in phantom studies as well as in clinical 18F-fluorodeoxyglucose investigations. First, a condition frame was obtained by dividing the sinogram of a blank measurement, obtained with rod sources on the defective PET camera, by the sinogram of a reference blank acquired before the appearance of the defect. Second, the sinogram of a previously acquired typical patient study was multiplied by the condition frame and reconstructed. Thereafter, images from corrupted sinograms were compared visually with their originals. For repairing defective sinograms, linear interpolation and the constrained Fourier space method were tested. RESULTS: The effects of detector defects can be simulated accurately in patient studies. The correction methods applied are especially helpful in cases of (a) several neighboring defective detectors and small study objects, (b) small hot artifacts and (c) several nonadjacent defective detectors. Linear interpolation is faster than the constrained Fourier space method; it is more widely applicable and provides similar results. CONCLUSION: The proposed approach allows specific evaluation of clinical consequences of detector defects. This technique simplifies the decision as to whether a planned patient study can be performed or must be postponed. Even in cases of serious detector problems, sinogram repair may help eliminate image artifacts and minimize the loss of image quality.

Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan.

UNLABELLED: FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false-positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L.

In vitro and in vivo tracer characteristics of an established multidrug-resistant human colon cancer cell line.

UNLABELLED: 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) has been suggested as a tracer for the scintigraphic detection of multidrug resistance (MDR). The aim of this study was to compare MDR characteristics in vitro and in vivo by immunohistochemic and functional uptake assays in established tumor cell lines cultured and grown in severe combined immunodeficient (SCID) mice. METHODS: The presence of MDR was assessed in vitro in drug-resistant HT-29(mdr1) colon carcinoma cells and in nonresistant HT-29(par) cells by JSB-1 immunohistochemistry, uptake of the fluorescent dye Rhodamine 123, and quantitative measurement of 99mTc-MIBI accumulation. For in vivo imaging, SCID mice bearing subcutaneous xenografts of these cell lines were injected with 99mTc-MIBI and 18F-FDG for scintigraphic and PET examination. After imaging, tumors were analyzed by immunohistochemistry and electron microscopy. RESULTS: All HT-29(mdr1) cells cultured in vitro exhibited distinct JSB-1 immunoreactivity, although to a variable degree, whereas HT-29(par) cells were completely devoid of JSB-1 staining. Rhodamine 123 accumulated poorly in HT-29(mdr1) cells but strongly in HT-29(par) cells. Accumulation of 99mTc-MIBI was 0.05% +/- 0.01% of the activity of the external medium in HT-29(mdr1) cells, but about eight times higher in HT-29(par) cells (0.40% +/- 0.09%), a very low percentage compared with other tumor cell lines. No difference in 201TlCl accumulation was observed between both cell lines. In vivo, neither HT-29(par) nor HT-29(mdr1) tumors grown in SCID mice could be detected by 99mTc-MIBI scintigraphy. In FDG PET, both HT-29(mdr1) and HT-29(par) tumors were clearly visible. FDG uptake was, however, markedly higher in HT-29(par) than in HT-29(mdr1) tumors. Both tumor types were poorly vascularized, as shown histologically. JSB-1 immunoreactivity was absent in all HT-29(par) tumors examined, whereas the majority of HT-29(par) tumor cells were stained. Electron microscopy showed that HT-29(par) tumors contained significantly less mitochondria than hepatocytes of the SCID mouse liver, which displayed high 99mTc-MIBI uptake in our scintigraphy studies. CONCLUSION: Sufficient 99mTc-MIBI uptake is the major prerequisite for distinguishing successfully between drug-resistant and sensitive cells. Negative 99mTc-MIBI scintigrams are not necessarily associated with MDR expression. In some tumors, FDG may be an in vivo marker for MDR as suggested by PET.

FDG PET detection of unknown primary tumors.

UNLABELLED: The management of patients presenting with metastases of unknown primary origin remains a clinical challenge despite a large variety of imaging modalities. The aim of this study was to evaluate FDG PET in detecting the sites of primary cancer in these patients. METHODS: Fifty-three patients with metastatic cervical adenopathy (n = 44) or extracervical metastases (n = 9) of unknown primary origin were included after extensive but inconclusive conventional diagnostic work-up. Patients received 370 MBq FDG (10 mCi) intravenously, and whole-body images were acquired at 60 min after injection. Clinical, surgical, and histopathologic findings and complete correlative imaging were used to assess the results. RESULTS: In 27 of 53 patients FDG PET showed focal tracer accumulations corresponding to potential primary tumor sites located in the lungs (n = 12), the palatine tonsil (n = 5), the salivary glands (n = 2), the nasopharynx (n = 1), the oropharynx (n = 3), the maxillary sinus (n = 1), and the larynx (n = 1). Moreover, in 2 patients FDG PET revealed lesions suspected to be tumors in the breast and the ileocolonic area. In 20 (37.8%) of these 53 patients FDG PET was true-positive, identifying the primary tumor in the lungs (n = 10), the head and neck region (n = 8), the breast (n = 1), and the ileocolonic area (n = 1). In 6 of 27 patients FDG PET was false-positive, predominantly identifying suspicious areas in the palatine tonsil (n = 3). One patient denied further diagnostic work-up after PET; thus, positive PET could not be evaluated. In 26 of 53 patients PET did not reveal lesions suspected to be the primary. However, primary tumors were not found in these patients at clinical follow-up. CONCLUSION: FDG PET is a valuable diagnostic tool in patients with cancer of unknown primary because it imaged unknown primary tumors in about one third of all patients investigated. In addition, FDG PET assists in both guiding biopsies for histologic evaluation and selecting the appropriate treatment protocols for these patients.