123I] ADAM brainstem binding correlates with the loudness dependence of auditory evoked potentials

The in vivo assessment of brain serotonergic function might be of clinical relevance in neuropsychiatry. The loudness dependence of auditory evoked potentials (LD) has been proposed as an indirect indicator of cortical serotonergic activity, whereas single photon emission computed tomography (SPECT) and [123I]ADAM allow the selective assessment of brain serotonin transporters (SERT). The aim of this study was to investigate LD and SERT availability as independent variables of the brain serotonergic system in healthy volunteers. Fifteen (six male, nine female) subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analyzed using dipole source analysis. SPECT was performed four hours after injection of 137 +/- 11.4 MBq [123I]ADAM. As a measure of SERT availability specific ADAM brainstem binding was used. LD correlated significantly with SERT availability (Pearson's correlations: rho = -0.57, p < 0.05). The correlations remained significant after controlling for the effects of age or gender (partial correlations: rho = -0.60, p < 0.05) but were pronounced in the female group (rho = -0.83, p < 0.01). Associations between LD and SERT availability contribute to the understanding of the central serotonergic system and further validate the use of neurophysiological approaches as indirect measures of neurochemical brain activity.     

Growth hormone response in low-dose apomorphine test correlates with nigrostriatal dopamine transporter binding in patients with Parkinson’s disease

Summary. Challenge with low-dose apomorphine causes a rise in growth hormone (GH) in patients with Parkinson’s disease (PD). We studied 18 patients with early PD, who showed an increase of GH in the low-dose apomorphine test, by means of [¹²³I] FP-CIT-SPECT. The mean specific dopamine transporter binding of the 18 patients was 1.50 ± 0.56 in the striatum, 1.20 ± 0.59 in the putamen, and 1.76 ± 0.59 in the caudate nucleus. The increase of GH (1.05 ± 1.01 ng/ml at baseline to 9.46 ± 6.36 ng/ml 45 min after apomorphine injection; p < 0.001) was significant. There was a significant negative correlation of the increase of GH with the mean specific dopamine transporter binding in all three regions (r between −0.490 and −0.587; p between 0.04 and 0.01). Challenge with low-dose apomorphine may therefore be used as an indirect tool to measure the extent of nigrostriatal neurodegeneration in early PD.     

Prevalence of cognitive and functional impairment in a community sample in Ribeirão Preto, Brazil

OBJECTIVE: This study aimed at estimating the prevalence of cognitive and functional impairment (CFI) in a community sample in Ribeir?o Preto, Brazil, evaluating its distribution in relation to various socio-demographic and clinical factors. METHODS: The population was a representative sample aged 60 and older, from three different socio-economic classes. Cluster sampling was applied. Instruments used to select CFI (a syndromic category that does not exclude dementia): 'Mini Mental State Examination' (MMSE), 'Fuld Object Memory Evaluation' (FOME), 'Informant Questionnaire on Cognitive Decline in the Elderly' (IQCODE), 'Bayer Activities of Daily Living Scale' (B-ADL) and clinical interviews. The data obtained were submitted to bivariate and logistic regression analysis. RESULTS: A sample of 1.145 elderly persons was evaluated, with a mean age of 70.9 years (60-100; DP: 7.7); 63.4% were female, and 52.8% had up to 4 years of schooling. CFI prevalence was 18.9% (n = 217). Following logistic regression analysis, higher age, low education, stroke, epilepsy and depression were associated with CFI. Female sex, widowhood, low social class and head trauma were associated with CFI only on bivariate analysis. CONCLUSION: CFI prevalence results were similar to those found by studies in Brazil, Puerto Rico and Malaysia. Cognitive and functional impairment is a rather heterogeneous condition which may be associated with various clinical conditions found in the elderly population. Due to its high prevalence and association with higher mortality and disability rates, this clinical syndrome should receive more attention on public health intervention planning.     

FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading

Purpose Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [¹⁸F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients. Methods Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II–III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV_max and the ratio to background (SUV_max/BG) were calculated (sum image: 20–40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies. Results Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV_max/BG: 2.16 ± 0.98) and HG (n = 34; SUV_max/BG: 3.29 ± 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10–20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967). Conclusions Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method.     

Optimization of automated quantification of 123I-IBZM uptake in the striatum applied to parkinsonism.

Evaluation of therapies for parkinsonism by dopamine receptor SPECT requires a reproducible, optimized quantitation technique. This study presents a new, objective, automated technique for semiquantitative analysis of dopamine receptor density, as applied to the differential diagnosis of parkinsonism. METHODS: Dopamine receptor density measured by 123I-iodobenzamide (IBZM) SPECT was retrospectively analyzed in nonidiopathic parkinsonism (NIPS), in Parkinson's disease (PD), and in healthy volunteers (n = 19, 38, and 13, respectively). A mean template was created from coregistered control studies. Registration errors were assessed using studies with simulated binding deficits. Patient studies were registered to the mean template, and striatal binding was calculated from a corresponding map of 3-dimensional regions of interest (ROIs). The striatal binding ratio and deficits determined by voxelwise comparison with the normal template were investigated and tested with various 3-dimensional ROI sizes and positions. Separation of patient groups was determined by tscore after automatically processing all studies. Results were compared with manual ROI analyses. RESULTS: The automatic method was completely reproducible in 64 of 70 cases. The best diagnostic discriminator was the minimum binding ratio of the 2 striatal nuclei, with the following values: NIPS, 1.33+/-0.13; PD, 1.50+/-0.12; healthy volunteers, 1.49+/-0.08 (+/-SD). The deficit size from voxelwise analysis was: NIPS, 20.5+/-8.2 mL; PD, 9.5+/-8.3; healthy volunteers, 8.9+/-6.0 (+/-SD). The accuracy, measured by receiver operating characteristic areas, was 0.85+/-0.05, 0.77+/-0.06, and 0.80+/-0.06 (+/-SE) for the optimal predictor (automated) and 2 blinded observers (manual), respectively. CONCLUSION: A new 3-dimensional, automated technique has been developed to semiquantitate receptor density that dramatically improves reproducibility. The optimal diagnostic discriminator of parkinsonism determined by the automatic technique has good accuracy compared with the manual technique.     

Role of positron emission tomography (PET) and single photon emission tomography (SPECT) in so-called "multiple chemical sensitivity"

Functional imaging with SPECT and PET is increasingly used to prove evidence for the existence of a syndrome "Multiple Chemical Sensitivity" (MCS) and plays a major role in legal trials to justify compensation for the exposure to solvents. This paper critically reviews the literature on the use of SPECT and PET for the determination of MCS. The authors come to the conclusion that the current data are not sufficient to justify the claim of the existence of such a syndrome. The low specificity of the observed PET and especially SPECT-findings makes it very difficult to establish a cause-result relationship and therefore makes the use of these methods in legal trials on this issue doubtful.     

Nichtinvasives Protokoll für die epilepsiechirurgische Behandlung fokaler Epilepsien

We present a non-invasive epilepsy surgery protocol, which includes EEG-video-monitoring, magnetic resonance imaging (MRI), interictal positron emission tomography (PET) and ictal single photon emission computerized tomography (SPECT). According to this non-invasive protocol 50 of 173 patients with medically intractable focal epilepsy underwent resective surgery. The localization of the epileptogenic zone was based on the congruence of the localizing results of EEG-video-monitoring, MRI, interictal PET and ictal SPECT. 46 (92%) of the patients had temporal and 4 (8%) had extratemporal epilepsies. 78% (n = 39) of all patients operated according to our non-invasive protocol were postoperatively completely or almost seizure free. Extramesiotemporal resections could be carried out without invasive EEG-recording if the epileptogenic zone was not adjacent to the eloquent cortex. We conclude from our results that in a considerable number of patients with medically intractable particularly temporal focal epilepsies, resective epilepsy surgery can be based on non-invasive EEG-evaluations and the risk of invasive recordings can be avoided.     

Selective internal radiation therapy with SIR-Spheres in patients with nonresectable liver tumors

AIM: Transarterial embolization of branches of the hepatic artery with biocompatible 90Y-labeled microspheres (SIR-Spheres) is a local treatment modality for patients with liver tumors, which, most recently, has become available in Europe. The aim of this study was to evaluate the feasibility and efficacy of this selective internal radiation therapy (SIRT). METHODS: Twenty-three patients with nonresectable hepatic metastases or hepatocellular carcinoma nonresponding to polychemotherapy and/or other local treatment were treated with SIRT. SIR-Spheres (mean activity, 2270 MBq) were administered by gentle intra-arterial infusion in the hepatic artery. A follow-up was documented by fluorodeoxyglucose-positron emission tomography (FDG-PET), course of tumor markers, and computed tomography (CT). RESULTS: Common minor side-effects were abdominal pain, nausea, and fever. Mild pancreatitis and peptic ulceration were observed once each. Currently, all patients are still alive, with survival times ranging from 11 to 518 days from SIRT up to the present. Three-month follow-up investigations are available in 13 of 23 patients, which, so far, are showing a marked decrease of FDG uptake, a drop of tumor markers, and unchanged or slightly decreasing lesion size (CT) in 10 of 13 patients. Two patients showed stable findings, while another patient showed progressive disease. Long-term follow-up investigations are available in 2 of 23 patients, showing hepatic and extrahepatic progression 6 and 9 months after SIRT. CONCLUSIONS: Our initial experience confirms that SIRT is a promising local therapeutic approach in patients with nonresectable liver tumors which is feasible and has an acceptable toxicity profile. Prospective data on comparing this treatment alone or in combination with other modalities are needed to answer whether long-term survival in this unfavorable stage of disease can be markedly improved.     

Is a low-dose Tc-99m-MIBI protocol suitable for first-pass RNV?

Tc-99m-labelled radiopharmaceuticals, such as Tc-99m-sestamibi (Tc-99m-MIBI), offer the opportunity to measure myocardial perfusion and function with one injection only. The aim of this study was to evaluate whether first-pass (FP) radionuclide ventriculography (RNV) consecutively followed by myocardial perfusion single photon emission computed tomography (SPECT) may be performed according to a low-dose MIBI 1-day protocol using a multi-crystal gamma camera. Two hundred and seventy consecutive, predominantly obese [61% with a body mass index (BMI) of >25 kg x m(-2)] patients (169 male, 101 female), referred for myocardial perfusion SPECT with Tc-99m-MIBI [4 MBq x kg(-1) (>300 MBq) at stress; 9 MBq x kg(-1) (> 650 MBq) at rest], were studied with FP RNV prior to SPECT. Bicycle ergometry (29%), dobutamine (6%) or dipyridamole stress (65%) was performed. Adequate count (ct) statistics for FP RNV were defined as follows: (1) > 2000 cts within the background-corrected, end-diastolic (ED), left ventricular (LV) region of interest (ROI) of the representative cycle; and (2) >4 heart beats with > 1000 cts within the ED LV ROI (> 50% of maximal cts). A net mean dose of 318+/-64 MBq (4.3+/-1.1 MBq x kg(-1)) was injected during stress and 674+/-55 MBq (9.1+/-1.7 MBq x kg(-1)) during rest. There was no statistical difference among the three stress modalities concerning the net dose. Two hundred and fifty-six out of 270 (95%) stress and a basis for reliable all 270 (100%) rest FP RNV studies showed adequate count statistics as functional analysis. The 14 patients with insufficient count statistics were all obese and had received less than the planned dose. For the vast majority of patients, even a low-dose 1-day protocol with Tc-99m-MIBI is suitable for the assessment of FP RNV prior to SPECT. A minimum of 300 MBq and 4 MBq x (kg body weight)(-1) should be administered in order to obtain technically adequate results even in obese patients.