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.

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.

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.

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.

Global scaling for semi-quantitative analysis in FP-CIT SPECT.

UNLABELLED: Semi-quantitative characterization of dopamine transporter availability from single photon emission computed tomography (SPECT) with 123I-ioflupane (FP-CIT) is based on uptake ratios relative to a reference region. The aim of this study was to evaluate the whole brain as reference region for semi-quantitative analysis of FP-CIT SPECT. The rationale was that this might reduce statistical noise associated with the estimation of non-displaceable FP-CIT uptake. PATIENTS, METHODS: 150 FP-CIT SPECTs were categorized as neurodegenerative or non-neurodegenerative by an expert. Semi-quantitative analysis of specific binding ratios (SBR) was performed with a custom-made tool based on the Statistical Parametric Mapping software package using predefined regions of interest (ROIs) in the anatomical space of the Montreal Neurological Institute. The following reference regions were compared: predefined ROIs for frontal and occipital lobe and whole brain (without striata, thalamus and brainstem). Tracer uptake in the reference region was characterized by the mean, median or 75th percentile of its voxel intensities. The area (AUC) under the receiver operating characteristic curve was used as performance measure. RESULTS: The highest AUC of 0.973 was achieved by the SBR of the putamen with the 75th percentile in the whole brain as reference. The lowest AUC for the putamen SBR of 0.937 was obtained with the mean in the frontal lobe as reference. CONCLUSION: We recommend the 75th percentile in the whole brain as reference for semi-quantitative analysis in FP-CIT SPECT. This combination provided the best agreement of the semi-quantitative analysis with visual evaluation of the SPECT images by an expert and, therefore, is appropriate to support less experienced physicians.

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.

Evaluation of PET quantification accuracy in vivo. Comparison of measured FDG concentration in the bladder with urine samples.

UNLABELLED: Quantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans. AIM: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. PATIENTS, METHODS: We determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: n = 19). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined. RESULTS: Activity concentration in the bladder (PET) was systematically lower than in the urine samples (well counter). The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively. CONCLUSIONS: The investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.

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.

IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment.

OBJECTIVE: To report that antibodies to synaptic proteins may occur in association with slow, progressive cognitive decline. METHODS: A total of 24 patients with progressive cognitive dysfunction of unclear etiology were examined for onconeuronal and synaptic receptor antibodies. The effect of serum was examined in cultures of dissociated mouse hippocampal neurons. RESULTS: Seven patients had immunoglobulin A (IgA), but no immunoglobulin G (IgG), antibodies against NMDA receptor (NMDAR). Anti-NMDAR IgA positive patients' serum, but not serum from control individuals, caused dramatic decrease of the levels of NMDAR and other synaptic proteins in neurons, along with prominent changes in NMDAR-mediated currents. These effects correlated with the titer of IgA NMDAR antibodies and were reversed after removing patients' serum from the culture media. When available, comprehensive clinical assessment and brain metabolic imaging showed neurologic improvement after immunotherapy. CONCLUSIONS: A subset of patients with slowly progressive cognitive impairment has an underlying synaptic autoimmunity that decreases the density of NMDAR and other synaptic proteins, and alters synaptic currents. This autoimmunity can be demonstrated examining patients' serum and CSF for NMDAR IgA antibodies, identifying possible candidates for immunotherapy.

MR Imaging of Prostate Cancer: Diffusion Weighted Imaging and (3D) Hydrogen 1 (H) MR Spectroscopy in Comparison with Histology.

UNLABELLED: Purpose. To evaluate retrospectively the impact of diffusion weighted imaging (DWI) and (3D) hydrogen 1 ((1)H) MR-spectroscopy (MRS) on the detection of prostatic cancer in comparison to histological examinations. MATERIALS AND METHODS: 50 patients with suspicion of prostate cancer underwent a MRI examination at a 1.5T scanner. The prostate was divided into sextants. Regions of interest were placed in each sextant to evaluate the apparent diffusion coefficient (ADC)-values. The results of the DWI as well as MRS were compared retrospectively with the findings of the histological examination. Sensitivity and specificity of ADC and metabolic ratio (MET)-both separately and in combination-for identification of tumor tissue was computed for variable discrimination thresholds to evaluate its receiver operator characteristic (ROC). An association between ADC, MET and Gleason score was tested by the non-parametric Spearman ρ-test. Results. The average ADC-value was 1.65 ± 0.32mm(2)/s × 10(-3) in normal tissue and 0.96±0.24 mm(2)/s × 10(-3) in tumor tissue (mean ± 1 SD). MET was 0.418 ± 0.431 in normal tissue and 2.010 ± 1.649 in tumor tissue. The area under the ROC curve was 0.966 (95%-confidence interval 0.941-0.991) and 0.943 (0.918-0.968) for DWI and MRS, respectively. There was a highly significant negative correlation between ADC-value and the Gleason score in the tumor-positive tissue probes (n = 62, ρ = -0.405, P = .001). MRS did not show a significant correlation with the Gleason score (ρ = 0.117, P = .366). By using both the DWI and MRS, the regression model provided sensitivity and specificity for detection of tumor of 91.9% and 98.3%, respectively. Conclusion. The results of our study showed that both DWI and MRS should be considered as an additional and complementary tool to the T2-weighted MRI for detecting prostate cancer.

[MR imaging of the Achilles tendon: evaluation of criteria for the differentiation of asymptomatic and symptomatic tendons]. / MR-Tomografie der Achillessehne: Evaluation von Kriterien zur Differenzierung von asymptomatischen und symptomatischen Sehnen.

PURPOSE: The purpose of this study was to develop quantitative and qualitative MRI criteria to differentiate between healthy and pathological Achilles tendons. MATERIALS AND METHODS: 364 Achilles tendons were examined on a 1.5 T MRI scanner. 264 patients had Achilles tendon complaints, 100 asymptomatic Achilles tendons served as a control. T 1-weighted, T 2-weighted and a STIR sequence were performed in sagittal and axial orientation. Images were evaluated in consensus by two radiologists. Quantitative and qualitative criteria were assessed. A Mann-Whitney-U-Test and a regression analysis were used for statistical analysis. RESULTS: There were statistically significant differences between the patients with disorders and the control group concerning the depth (12.0 mm and 6.3 mm, p < 0.001) and length (83.2 mm and 45.9 mm, p < 0.001) of the tendon, the area of the tendon cross section (1.60 mm (2) and 061 mm (2), p < 0.001), as well as the length of the bursa retrocalcanea (8.3 mm and 5.3 mm, p < 0.001). There was a sensitivity of 97 % and a specificity of 91 % using a formula including the 3 criteria: tendon depth (A4), length of bursa (A5) and area of tendon (F). CONCLUSION: The measurement of the Achilles tendon and the binary-logistic regression analysis allow differentiation between normal and pathological Achilles tendons.

Screening for atherosclerotic plaques in the abdominal aorta in high-risk patients with multicontrast-weighted MRI: a prospective study at 3.0 and 1.5 tesla.

OBJECTIVE: This prospective study compares MRI of atherosclerotic plaque in the abdominal aorta at 3 T with that at 1.5 T in patients suffering from hereditary hyperlipidaemia, a major risk factor for atherosclerosis. METHODS: MRI of the abdominal aorta at 1.5 and 3 T was performed in 21 patients (mean age 58 years). The study protocol consisted of proton density (PD), T(1), T(2) and fat-saturated T(2) weighted black blood images of the abdominal aorta in corresponding orientation. Two independent radiologists performed image rating. First, image quality was rated on a five-point scale. Second, atherosclerotic plaques were scored according to the modified American Heart Association (AHA) classification and analysed for field strength-related differences. Weighted κ statistics were calculated to assess interobserver agreement. RESULTS: Interobserver agreement was substantial for nearly all categories. MRI at 3 T offered superior image quality in all contrast weightings, most significantly in T(1) and T(2) weighted techniques. Plaque burden in the study collective was unexpectedly moderate. The majority of plaques were classified as AHA III lesions; no lesions were classified above AHA V. There was no significant influence of the field strength regarding the AHA classification. CONCLUSION: Abdominal aortal plaque screening is basically feasible at both field strengths, whereas the image quality is rated superior at 3 T. However, the role of the method in clinical practice remains uncertain, since substantial findings in the high-risk collective were scarce.

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.

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

Dementia and leukoencephalopathy due to lymphomatosis cerebri.

Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL). Clinically, the disease typically presents with a rapidly progressive dementia and unsteadiness of gait. Its presentation on cerebral MRI, which is characterised by diffuse leukoencephalopathy without contrast enhancement, often causes diagnostic confusion1 with suspected diagnoses ranging from Binswanger's disease to leukoencephalopathy or encephalomyelitis. Here we report a patient with subacute dementia and diffuse bilateral white matter changes in the cerebral hemispheres and additional involvement of the brainstem, basal ganglia and thalamus on MRI. Initially, she was considered to suffer from an autoimmune encephalitis, transiently responded to immunosuppression but then developed multiple solid appearing cerebral lymphomas.