Myocardial sympathetic innervation in the course of Guillain-Barré syndrome.
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Biomedical subjects
Publications and source records attributed to O Schober.
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BACKGROUND: The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by (123)I-MIBG-single-photon emission computed tomography. METHODS AND RESULTS: This study investigated neuronal reuptake of norepinephrine (uptake-1) and beta-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V(d)) of [(11)C]hydroxyephedrine ((11)C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B(max)) of [(11)C]CGP-12177 ((11)C-CGP-12177) to assess postsynaptic beta-adrenergic receptor density, and [(15)O]H(2)O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic beta-adrenergic receptor density compared with that in control subjects (B(max) of (11)C-CGP-12177: 5.9+/-1.3 vs 10.2+/-2.9 pmol/g tissue, P<0.0007), whereas the presynaptic uptake-1 tended toward reduction only (V(d) of (11)C-HED: 59.1+/-25.2 vs 71.0+/-18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects. CONCLUSIONS: The findings demonstrate a significant reduction of myocardial beta-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.
BACKGROUND: Single photon emission computed tomography (SPECT) with 201Tl and 123I-alpha-methyl tyrosine (123I-IMT) are routine methods for the evaluation of brain tumors. 123I-IMT transport across the blood brain barrier is mediated by an amino acid carrier, 201Tl accumulation is analogous to cerebral potassium uptake. PATIENTS AND METHODS: To determine the differences in glioma extension as shown by the 2 methods, 17 patients with malignant gliomas were included in this comparative imaging study: astrocytoma III: n = 6, ependymoma III: n = 1, oligodendroglioma III: n = 1, glioblastoma IV: n = 9. The tomographic image sets were matched anatomically and the slices showing maximal tumor extension were identified in both image sets respectively. Tumor spread was compared visually and the tumor extension was quantified. RESULTS: In gliomas WHO III tumor extension was delineated significantly larger by 123I-IMT-SPECT than by 201Tl-SPECT (mean +/- SD: 816 +/- 281 pixels vs 600 +/- 220 pixels, n = 8, p < 0.05). The size of glioblastomas was shown in a comparable manner by the 2 methods (977 +/- 571 vs 1.051 +/- 588, n = 9, ns, p = 0.57), but there were considerable regional differences between the area of 201Tl uptake and amino acid retention. In the whole group a weak but significant negative correlation between intensity of 201Tl uptake on the one hand and a ratio of the area as depicted by 123I-IMT vs area as depicted by 201Tl on the other hand, was found (n = 17, r = 0.49, p < 0.05). Thus the differences in the delineation of areas became smaller with increasing 201Tl uptake. CONCLUSIONS: These preliminary data indicate that the extension of gliomas is depicted differently by the 2 methods. 123I-IMT-SPECT shows a larger tumor extension especially in gliomas WHO III. Since 201Tl uptake has previously been shown to correlate with disruption of the blood brain barrier, 123I-IMT-SPECT may delineate tumor parts without endothelial leakage. This additional information may be helpful in planning surgical or radiation therapy. The advantages of 123I-IMT in this respect decrease with increasing 201Tl uptake and with increasing malignancy.
Four types of radionuclide investigations are described here: 99mTc-labeled red blood cell scintigraphy, colloid liver scintigraphy, hepatobiliary scintigraphy, and positron emission tomography with [18F]fluorodeoxyglucose. The role of nuclear imaging techniques in the diagnosis of liver diseases has changed in recent years and now compliments morphological imaging modalities by offering the unique ability to visualize function and metabolism. The studies described here are therefore rarely performed now by themselves for the delineation of secondary liver tumors. These radionuclide investigations are used principally to narrow the differential diagnosis of focal liver disease.
The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewing's sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.
In clinical and research studies, images obtained using carrier-added meta-[123I]iodobenzylguanidine (c.a. [123I]MIBG) have shown quite variable quality, with varying levels of uptake in lung, liver and mediastinum; this is a significant problem for quantification of the myocardial uptake by means of region ratios. First experimental and preliminary human data in respect of no-carrier-added (n.c.a.) [123I]MIBG are indicative of improved imaging quality. The aim of the present study was to evaluate the clinical value of myocardial scintigraphy with n.c.a. [123I]MIBG in patients with tachyarrhythmias. The study population comprised 24 patients with tachyarrhythmogenic diseases routinely studied by cardiac single-photon emission tomography (SPET) with [123I]MIBG. Twelve of the 24 patients were studied with c.a. [123I]MIBG (seven females and five males; mean age 42+/-13 years, range 20-60 years), whereas the other 12 were studied with n.c.a. [123I]MIBG (ten females, two males; mean age 41+/-11 years, range 18-60 years, P=NS). For quantification of the specific uptake in the different organs, count ratios were calculated on SPET images acquired 4 h p.i. Visual analysis of all [123I]MIBG scans showed improved image quality (improved contrast between heart and neighbouring organs) in n.c.a. studies as compared with c.a. studies. A significantly higher heart/left atrial blood ratio was found in the n.c.a. studies as compared with the c.a. studies (10.3+/-3.2 vs 5.3+/-1.3, P=0.0003); furthermore, significantly higher heart/lung and heart/liver ratios (2.5+/-0.6 vs 1.5+/-0.3, P=0.0002, and 0.8+/-0.2 vs 0.6+/-0.1, P=0.0006, respectively) were obtained in the c.a. studies, whereas lung/left atrial blood and liver/left atrial blood ratios showed no significant differences (4.2+/-1.3 vs 3.6+/-1.1, P=0.39, and 13.7+/-5.2 vs 9.6+/-2.2, P=0.21, respectively). In conclusion, the use of n.c.a. [123I]MIBG yields a significantly higher myocardial uptake associated with improvement in contrast between the heart and neighbouring organs and is therefore superior to the commercially available c.a. [123I]MIBG for use in clinical and research studies of the myocardial presynaptic sympathetic nervous system. Furthermore, our data indicate that for quantification the use of a left atrial blood reference region of interest, which is only available on SPET studies, is to be recommended.
Both thallium-201 and iodine-123 alpha-methyltyrosine (123I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of 201Tl and 123I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. 201Tl SPET and 123I-IMT SPET were performed [start of 201Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of 123I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked 201Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant 201Tl accumulation [Tl(15')>2.0]; 123I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs. 2.1 vs. 1.8), with metastases showing a high variability in 123I-IMT uptake (range: 0.8-3.6). Using 201Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of 201Tl and 123I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial 201Tl SPET study and an additional 123I-IMT SPET study in the event of positive 201Tl uptake.
In 1991, our group started to develop a catheter interventional therapy for hypertrophic obstructive cardiomyopathy (HOCM). The new concept was proposed in 1994. It is based on the conventional PTCA technique with the aim of inducing an artificial myocardial infarction by instillation of 96% ethanol into the most proximally situated septal branch of the left anterior descending coronary artery. This leads to a subaortic contraction disorder with subsequent decrease of the intraventricular pressure gradient, shrinkage of the hypertrophied septal bulge and widening of the outflow tract ("therapeutic remodeling"). The subaortic defect is small and well demarcated as assessed by left ventricular angiography, transesophageal echocardiography and 18 F-glucose positron emission tomography. The term transcoronary ablation of septum hypertrophy (TASH) was suggested. Our patient cohort that now comprises 215 therapeutic procedures in 187 patients underwent a large variety of prospective studies (maximum follow-up 4.5 years) including invasive controls at regular intervals, investigation of hemodynamics at rest and at exercise, transesophageal and transthoracic echocardiography, Doppler echocardiography during bicycle exercise, electrophysiologic testing, Holter monitoring and measurement of myocardial metabolism and perfusion, assessment of microembolic events by transcranial Doppler sonography and histological examinations. This article gives an overview and reports our increasing experience in applying TASH. The following post-TASH findings were obtained: significant hemodynamic and clinical improvement at rest and at exercise, decrease of septum thickness, increase of outflow tract area and decrease of induced ventricular tachycardia. There were well-demarcated, histologically atypical subaortic myocardial defects, no microembolic events, abnormal early peak of infarct related enzymes, and no change of baroreflex sensitivity. Pre-/post-TASH evaluations of the patients should be based in particular on clinical symptoms correlated to the intraventricular gradient measured by bicycle exercise Doppler echocardiography and to outflow tract area as assessed by transesophageal echocardiography. Since 1994, as a roughly estimate, worldwide 1000 patients in 20 countries have been treated. According to published articles, abstract presentations and workshops, TASH consistently leads to a pronounced clinical and hemodynamic benefit for patients with HOCM. TASH has become an established technique. At least in centers with a high level of expertise, it is no longer experimental but a routinely performed alternative to surgical treatment for HOCM, i.e., the previous gold standard of therapy. Of course, patient outcome needs further careful clinical and prognostic evaluation. With respect to complications, TASH appears to be superior to surgery (transaortic septal myectomy) for HOCM. Like surgical treatment, TASH is currently indicated in critically ill patients with typical HOCM (subaortic form), who exhibit with drug refractory symptoms, including patients, who preferred DDD pacemaker therapy as a first therapeutic step but in whom this produced no subsequent clinical benefit.
BACKGROUND: The proportion of patients with left-ventricular dysfunction (LVD) undergoing high risk revascularization is increasing. In this patient group, the perioperative risk is elevated because of the pre-existing pathophysiology. Detailed evaluation and interdisciplinary differential therapeutic considerations on the basis of the comparative benefit rationale, with cardiac transplantation alternative, is mandatory. METHODS: Among 7275 patients who underwent coronary artery bypass grafting between 1990 and 1998 in our institution, we found 51 patients who had had an ejection fraction <20%, and thus were candidates for transplantation (group CABG); these were compared with 163 patients who were listed for cardiac transplantation because of ischemic cardiomyopathy (group HTX). The survival analysis was performed on the basis of the intention-to-treat principle independent of subsequent transplantation. RESULTS: Both groups were comparable with regard to left-ventricular ejection fraction; pulmonary capillary wedge pressure and serum creatinine, but patients in the CAGB group were older (63+/-11 vs 56+/-8; p = 0.001) and included a higher percentage of women (m/f: 42/9 vs 152/11; p = 0.03). Nevertheless, there was a similar 1-year survival in both groups (group BP 71.9% vs group HTX 66.3%; p = ns). Looking at the CABG group, the internal thoracic artery was used in 36/51 patients, an intra-aortic balloon pump was used preoperatively in 26 patients, and intraoperatively in 6. Left-ventricular assist devices had to be inserted in three patients, extracorporeal membrane oxygenation once. Perioperative (30 day) survival was 88.2 %. An elevated preoperative serum creatinine and the nonusage of the internal thoracic artery predicted an adverse outcome. In the long-term course, the NYHA functional class improved in most cases from III preoperatively to I after 26 (2-66) months. CONCLUSION: We conclude that patients with ischemic cardiomyopathy, viable myocardium, and graftable vessels can be revascularized with acceptable risk. Since for these patients a standby of mechanical circulatory support must be anticipated perioperatively, this infrastructure should be established within the center.
PURPOSE: The purpose of this study was to evaluate the potential of positron emission tomography using F-18-fluoro-2-deoxy-D-glucose (FDG PET) to assess the chemotherapy response of primary osseous tumors compared with the degree of necrosis determined histologically. PATIENTS AND METHODS: Seventeen patients with primary bone tumors (11 osteosarcomas, 6 Ewing's sarcomas) were examined using FDG PET and planar bone scintigraphy before neoadjuvant chemotherapy and before surgery. Tumor response was classified histologically according to Salzer-Kuntschik (grades I-II: good response; grades IV-VI: poor response). In both imaging methods, quantification was performed using tumor to nontumor ratios (T:NT). RESULTS: Histologically, 15 patients were classified as having good responses (grade I, n = 1; grade II, n = 6; grade III, n = 8) and two as having poor responses (grades IV and V). FDG PET showed more than a 30% decrease in T:NT ratios in all patients who had good responses. However, three of these patients had increasing bone scintigraphy T:NT ratios, and another five had decreasing ratios of less than 30%. The patients with poor responses had increasing T:NT ratios and decreasing ratios of less than 30%, respectively, using both imaging methods. CONCLUSIONS: FDG PET seems to be a promising tool for evaluating the response of primary osseous tumors to chemotherapy. In this preliminary study, FDG PET was superior to planar bone scintigraphy.
PURPOSE: Positron emission tomography (PET) using 18F-radiolabeled deoxyglucose (18F-FDG) is a sensitive procedure for detection of epileptogenic foci. Although alterations in glucose consumption are not restricted to the area of seizure generation itself, the magnitude and extent of cerebral metabolic disturbances induced by epileptic discharges can be detected. Despite two decades of epilepsy research using 18F-FDG-PET, little is known about the metabolic changes during therapy of focal epilepsy. We report on a child with frontal epilepsy with severe glucose hypometabolism that was nearly completely normalized during drug therapy. METHODS: Interictal 18F-FDG-PET was performed at the onset of epilepsy and after optimized drug therapy in a 5-year-old boy with behavioral abnormalities and repetitive seizures of frontal origin with bifrontal interictal EEG slowing for 8 weeks. Both scans were anatomically matched; initial and intratherapeutic glucose metabolism were compared. RESULTS: In accordance with the epileptogenic focus as identified by EEG and ictal/interictal perfusion single-photon emission tomography (SPECT), bifrontal hypometabolism was depicted by 18F-FDG-PET. Magnetic resonance imaging (MRI) was unremarkable. After dual-drug therapy (valproate, carbamazepine), the boy became seizure free, and his initial behavioral deficits disappeared. A control PET study after 3 months of therapy showed restored glucose consumption; the frontal EEG slowing was normalized. CONCLUSIONS: This case demonstrates that reduction of glucose metabolism in epileptogenic foci may be a result of reversible neuronal dysfunction that correlates with the electroclinical follow-up.
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AIM: In an earlier study (study I) we had calculated the costs for FDG-PET investigations with our satellite concept (19). 433 patients were included in the study. Compared to the general indications for PET examinations the proportions of investigations were somewhat untypical: Both parameters have changed actually. Therefore we carried out a renewed data analysis (study II). METHODS: All economic parameters were kept, in order to ensure the comparability of both studies. Only an adjustment of the costs to actual conditions was performed. RESULTS: Proportions of investigations: Oncology 63%, Neurology 28%, Cardiology 9%; 3.5 investigations per working day. According to the increased number of investigations the structure of the total costs (DM 1601831) shows a small rise of the percentage costs for the FDG (41% to 42%) and a percentage decrease of the fixed overheads (48% to 43%). The percentage of personnel costs has increased (11% to 15%), the average cost per investigation has diminished: They amounted to DM 2783 in the earlier study (ranging from DM 2458 to 3463). The new data analysis results in the average cost of DM 2366 (-15%) per investigation (ranging from DM 2114 to 2840). Exemplary calculations show that a minimum of the costs will be achieved, if four investigations per day are performed. Retaining all parameters, which do not refer to the costs of the FDG, the average amount for one investigation would vary from DM 2000 (no delivery time) to DM 3300 (4 hours of delivery time). CONCLUSIONS: The results are in good agreement to the general laws of economic science, according to which an increase of the "number of units" with the same fixed overheads will result in a relative reduction of the costs of the "products". A further increase in the frequency of investigations will lead to a rise of the average costs per investigation, because of the physical decay of the FDG delivered once a day.
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3-[(123)I]Iodo-l-alpha-methyltyrosine ((123)I-IMT) is used for the diagnosis and monitoring of brain tumours by means of single-photon emission tomography (SPET). To date, little has been known about the system for the transport of (123)I-IMT into brain tumour cells. It is assumed that (123)I-IMT is transported by a specific carrier for large, neutral amino acids (L-system). In this study, rat C6 glioma cells were used to characterize the uptake system of (123)I-IMT and to investigate its precise kinetics. The time course of (123)I-IMT uptake into the cells was examined for a range of 1-60 min. (123)I-IMT uptake rates with varying concentrations of (123)I-IMT (2. 5-50 microM) in the medium were quantified to assess the kinetic parameters of (123)I-IMT transport. Furthermore, competition of (123)I-IMT with other amino acids was investigated to identify the distinct transport systems involved in (123)I-IMT uptake. (123)I-IMT uptake into C6 glioma cells was linear for approximately 10 min and reached a steady-state level within 30 min. The analysis of the rate of uptake of (123)I-IMT at different concentrations was concordant with the predominance of a single uptake system. The apparent Michaelis constant (K(m)) of (123)I-IMT was 26.2+/-1.9 microM, and the maximum transport velocity (V(max)) was 35.4+/-1.7 nmol/mg protein per 10 min. 77%+/-10% of (123)I-IMT transport was sodium independent and 23%+/-3% was sodium dependent. Competitive inhibition of (123)I-IMT uptake by 2-aminobicyclo[2.2. 1]heptane-2-carboxylic acid, alpha-(methylamino)isobutyric acid and naturally occurring amino acids revealed a major (123)I-IMT transport via the sodium-independent system L (72%) and a minor uptake via the sodium-dependent system B(0,+) (17%). Our results show that (123)I-IMT transport into C6 glioma cells is principally mediated by the L-system and to a minor extent by the B(0,+)-system. The kinetic parameters of (123)I-IMT uptake are in the range of those of naturally occurring amino acids.
Since the human heart has a complex anatomy, the two-dimensional analysis of myocardial scintigrams obviously is not satisfactory. Three-dimensional display can be more easily read by clinicians and depicts more accurately tracer accumulation defects. In this study we propose a three-dimensional myocardial contour detection approach using elastic surfaces. After manual reorientation into short-axis slices and transformation into heart coordinates, the myocardial mid-wall surface passing through the radial activity mass points is calculated using a second-order partial differential equation as a mathematical model. Special considerations are implemented to demarcate organs close to the heart. In a total of 1102 myocardial scintigrams the three-dimensional contour detection calculated a reasonable shape of the left ventricular myocardium in all cases. Even in areas with severe myocardial infarction, this approach was able to bridge tracer accumulation defects. Inter- and intra-observer variability tests confirmed a high reproducibility and user independence. In conclusion, in this study the proposed three-dimensional contour detection of left ventricular myocardium using elastic surfaces was found to be fast, user-independent and reliable, leading to realistic three-dimensional parametric images of myocardial scintigrams that even clinicians not experienced in nuclear cardiology can easily read.