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Biomedical subjects

Otmar Schober

Publications and source records attributed to Otmar Schober.

At least 19 recordsLinked to original sources
PubMed2007

Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: validation of an elastic surface model approach in comparison to cardiac magnetic resonance imaging, 4D-MSPECT and QGS.

PURPOSE: The segmentation algorithm ESM based on an elastic surface model was validated for the assessment of left ventricular volumes and ejection fraction from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was used as the reference method. METHODS: SPECT and MRI were performed on 70 consecutive patients with suspected or proven coronary artery disease. End-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were derived from SPECT studies by using the segmentation algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI. RESULTS: ESM-derived values for EDV and ESV correlated well with those from cardiac MRI (correlation coefficients R=0.90 and R=0.95, respectively), as did the measurements for LVEF (R=0.86). Both EDV and ESV were slightly overestimated for larger ventricles but not for smaller ventricles; LVEF was slightly overestimated irrespective of ventricle size. The above correlation coefficients are comparable to those for the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the three segmentation algorithms are not interchangeable. CONCLUSION: The ESM algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT images. Overall, the performance was similar to that of 4D-MSPECT and QGS when compared with cardiac MRI. Results obtained with the three tested segmentation methods are not interchangeable, so that the same algorithm should be used for follow-up studies and control subjects.

Adult↗
PubMed2007

Molecular cardiovascular imaging using scintigraphic methods.

Molecular cardiovascular imaging plays an increasingly important role both in basic research and in clinical diagnosis. Scintigraphic methods have long been used to study pathophysiological changes on a cellular and molecular level, and they are likely to remain important molecular imaging modalities in the foreseeable future. This article provides an overview over current developments in cardiovascular molecular imaging using scintigraphic methods. The focus lies on imaging of cardiac innervation, plaque instability, hypoxia and angiogenesis, gene expression and stem and progenitor cell migration and proliferation.

Animals↗
PubMed2006

5-pyrrolidinylsulfonyl isatins as a potential tool for the molecular imaging of caspases in apoptosis.

Caspases are the unique enzymes responsible for the execution of the cell death program and may represent an exclusive target for the specific molecular imaging of apoptosis in vivo. 5-Pyrrolidinylsulfonyl isatins represent potent nonpeptidyl caspase inhibitors that may be suitable for the development of caspase binding radioligands (CBRs). (S)-5-[1-(2-Methoxymethylpyrrolidinyl)sulfonyl]isatin (7) served as a lead compound for modification of its N-1-position. Corresponding pairs of N-1-substituted 2-methoxymethyl- and 2-phenoxymethylpyrrolidinyl derivatives were examined in vitro by biochemical caspase inhibition assays. All target compounds possess high in vitro caspase inhibition potencies in the nanomolar to subnanomolar range for caspase-3 (Ki=0.2-56.1 nM). As shown for compound (S)-1-(4-(2-fluoroethoxy)benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (35), the class of N-1-substituted 5-pyrrolidinylsulfonyl isatins competitively inhibits caspase-3. All caspase inhibitors show selectivity for the effector caspases-3 and -7 in vitro. The 2-methoxymethylpyrrolidinyl versions of the isatins appear to possess superior caspase inhibition potencies in cellular apoptosis inhibition assays compared with the 2-phenoxymethylpyrrolidinyl inhibitors.

Apoptosis↗
PubMed2006

High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor.

BACKGROUND: All treatments of acute myocardial infarction are aimed at rapid revascularization of the occluded vessel; however, no clinical strategies are currently available to protect the heart from ischemia/reperfusion injury after restitution of blood flow. We hypothesized that some of the cholesterol transport-independent biological properties of high-density lipoprotein (HDL) implied in atheroprotection may also be beneficial in settings of acute myocardial reperfusion injury. METHODS AND RESULTS: In an in vivo mouse model of myocardial ischemia/reperfusion, we observed that HDL and its sphingolipid component, sphingosine-1-phosphate (S1P), dramatically attenuated infarction size by approximately 20% and 40%, respectively. The underlying mechanism was an inhibition of inflammatory neutrophil recruitment and cardiomyocyte apoptosis in the infarcted area. In vitro, HDL and S1P potently suppressed leukocyte adhesion to activated endothelium under flow and protected rat neonatal cardiomyocytes against apoptosis. In vivo, HDL- and S1P-mediated cardioprotection was dependent on nitric oxide (NO) and the S1P3 lysophospholipid receptor, because it was abolished by pharmacological NO synthase inhibition and was completely absent in S1P3-deficient mice. CONCLUSIONS: Our data demonstrate that HDL and its constituent, S1P, acutely protect the heart against ischemia/reperfusion injury in vivo via an S1P3-mediated and NO-dependent pathway. A rapid therapeutic elevation of S1P-containing HDL plasma levels may be beneficial in patients at high risk of acute myocardial ischemia.

Animals↗
PubMed2006

Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model.

PURPOSE: As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model. METHODS: Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2-7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) or 9.4 MBq (mean) [(18)F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions. RESULTS: Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [(18)F]fluoride PET by virtue of decreased [(18)F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically. CONCLUSION: Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.

Animals↗
PubMed2006

Impact of sympathetic innervation on recurrent life-threatening arrhythmias in the follow-up of patients with idiopathic ventricular fibrillation.

PURPOSE: Idiopathic ventricular fibrillation (IVF) is defined as VF in the absence of any identifiable structural or functional cardiac disease. The underlying pathophysiological mechanisms are unknown. This study was performed to investigate the potential impact of sympathetic dysfunction, assessed by (123)I-meta-iodo-benzylguanidine scintigraphy ((123)I-MIBG SPECT), on the long-term prognosis of patients with IVF. METHODS: (123)I-MIBG SPECT was performed in 20 patients (mean age 37+/-13 years) with IVF. Mean follow-up of patients after study entry was 7.2+/-1.5 years (range 4.9-10.5 years). Ten patients (five men, five women; mean age 43+/-12 years; p=NS versus study group) with medullary carcinoma of the thyroid gland served as an age-matched control group. RESULTS: Abnormal (123)I-MIBG uptake was observed in 13 patients (65%). During follow-up, 18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF patients with abnormal (123)I-MIBG uptake whereas only two episodes of monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient with normal (123)I-MIBG uptake. CONCLUSION: Impairment of sympathetic innervation may indicate a higher risk of future recurrent episodes of life-threatening ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are required to validate the significance of (123)I-MIBG SPECT during the long-term follow-up of these patients.

3-Iodobenzylguanidine↗
PubMed2006

Gated listmode acquisition with the quadHIDAC animal PET to image mouse hearts.

PURPOSE: The aim of this study was to develop ECG and respiratory gating in combination with listmode acquisition for the quadHIDAC small-animal PET scanner. METHODS: ECG and respiratory gating was realized with the help of an external trigger device (BioVET) synchronized with the listmode acquisition. Listmode data of a mouse acquisition (injected with 6.5 MBq of 18F-FDG) were sorted according to three different gating definitions: 12 cardiac gates, 8 respiratory gates and a combination of 8 cardiac and 8 respiratory gates. Images were reconstructed with filtered back-projection (ramp filter), and parameters like left ventricular wall thickness (WT), wall-to-wall separation (WS) and blood to myocardium activity ratios (BMR) were calculated. RESULTS: Cardiac gated images show improvement of all parameters (WT 2.6 mm, WS 4.1 mm, BRM 2.3) in diastole compared to ungated images (WT 3.0 mm, WS 3.4 mm, BMR 1.3). Respiratory gating had little effect on calculated parameters. CONCLUSION: ECG gating with the quadHIDAC can improve myocardial image quality in mice. This could have a major impact on the calculation of an image-derived input function for kinetic modelling.

Animals↗
PubMed2006

Organ movement reduction in PET/CT using dual-gated list-mode acquisition.

PURPOSE: Imaging of moving organs using the PET leads to blurred images due to long acquisition times. Simultaneous cardiac and respiratory gating of list-mode PET/CT is evaluated with the aim to improve image quality and assess the organ movement. METHODS: We performed a N-13 ammonia PET/CT scan with a human volunteer, using the Siemens Biograph Sensation 16 scanner with list-mode acquisition. For ECG gating we used the scanner's integrated ECG device. Respiratory gating was done with the BioVet pneumatic sensor system. RESULTS: The sorting of the list-mode data post acquisition produced the desired matrix of eight cardiac times eight respiratory images. Organ movement could be measured in the series of gated PET images. The quantitation of tracer uptake in the myocardium showed artifacts due to the CT-based attenuation correction. CONCLUSION: Double gating is feasible in human PET/CT scans using a list-mode-based scan protocol. The image quality can be enhanced using double gated list-mode acquisition in PET/CT Attenuation correction protocols in PET using a single not gated fast CT introduces artifacts in moving organs.

Electrocardiography↗
PubMed2006

Idiopathic left ventricular aneurysm and sudden cardiac death in young adults.

AIMS: We report three young patients presenting with life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) and/or survived sudden cardiac arrest, who were admitted to our institution for further diagnostic evaluation. METHODS AND RESULTS: In all patients, idiopathic left ventricular (LV) aneurysms were identified after a detailed non-invasive and invasive evaluation. Sustained VT/VF was inducible during programmed ventricular stimulation in two of the three patients. Left ventricular aneurysms were depicted and characterized by various imaging modalities (echocardiography, magnetic resonance imaging, LV angiography). To elucidate the pathogenesis further, both myocardial viability and regional sympathetic innervation were assessed by radionuclide imaging techniques. Defects of innervation and metabolism were documented in the area of the aneurysm but distal to the aneurysm there were no signs of downstream denervation. CONCLUSION: Life-threatening arrhythmias may be the first manifestation of an idiopathic LV aneurysm, which can be reliably diagnosed with modern imaging techniques. Radionuclide imaging may yield additional information as to the involvement of the autonomic nervous system potentially associated with arrhythmogenesis. Management strategies in patients with an idiopathic LV aneurysm range from antiarrhythmic drug treatment, implantation of an automatic cardioverter-defibrillator to surgical aneurysmectomy.

Adult↗
PubMed2006

Whole-body PET/CT with 11C-meta-hydroxyephedrine in tumors of the sympathetic nervous system: feasibility study and comparison with 123I-MIBG SPECT/CT.

UNLABELLED: The 11C-labeled tracer meta-hydroxyephedrine (11C-HED) is a noradrenaline analog that was developed to visualize the sympathetic nervous system with PET. Initial clinical studies show a rapid uptake of 11C-HED in localized tumors of this system. Whole-body imaging with 11C-HED PET is now possible as PET/CT scanners allow a rather short examination time. The aim of this study was to evaluate the feasibility of whole-body 11C-HED PET/CT for examination of tumors of the sympathetic nervous system and to directly compare the results with 123I-labeled meta-iodobenzylguanidine (123I-MIBG) scintigraphy, including SPECT/CT. METHODS: In 19 consecutive patients, 9 mo to 68 y old (median, 32 y), 24 whole-body 11C-HED PET/CT (low-dose CT) examinations were performed. Scans were compared with attenuation-corrected 123I-MIBG SPECT/CT scans (24-h scan, low-dose CT). The intensity of tracer accumulation above background was visually analyzed in both scans, PET and SPECT, using a 4-value scale. In 11C-HED PET, mean and maximum standardized uptake values were determined for all lesions. RESULTS: In 14 patients with 19 pairs of examinations, the following tumors were confirmed histologically: 6 neuroblastomas, 5 pheochromocytomas, 1 ganglioneuroblastoma, and 2 paragangliomas. In 5 patients, each having 1 pair of examinations, clinical follow-up and/or histologic examination did not reveal any tumor deriving from the sympathetic nervous system. 11C-HED PET/CT detected 80 of 81 totally depicted tumor lesions (sensitivity, 0.99; soft tissue, 61; bone, 19). 123I-MIBG SPECT/CT detected 75 of 81 lesions (sensitivity, 0.93; soft tissue, 56; bone, 19). With both methods, there were no false-positive lesions. The tumor-to-background contrast of 11C-HED uptake was higher in comparison with 123I-MIBG uptake in 26 lesions (0.32; soft tissue, 18; bone, 8), equal in 39 lesions (0.48; soft tissue, 30; bone, 9), and lower than 123I-MIBG uptake in 16 lesions (0.20; soft tissue, 14; bone, 2). CONCLUSION: Whole-body imaging using 11C-HED PET/CT is feasible in the clinical setting of patients with tumors of the sympathetic nervous system. 11C-HED PET/CT detected more tumor lesions than 123I-MIBG SPECT/CT. However, tumor-to-background contrast of 11C-HED in lesions can be higher, equal, or lower compared with 123I-MIBG.

3-Iodobenzylguanidine↗
PubMed2006

Accurate noninvasive measurement of infarct size in mice with high-resolution PET.

UNLABELLED: Reliable, repeatable, and time-efficient noninvasive measurement of infarct size in mice with PET would benefit studies aimed at the exploration of biochemical and functional changes associated with acute myocardial infarction (MI). PET with the radioactively labeled glucose derivative (18)F-FDG is used in humans to distinguish between viable but dysfunctional and nonviable myocardium. In this study, the feasibility, accuracy, and time efficiency of (18)F-FDG PET for quantification of infarct size in mice using a high-resolution animal PET device was evaluated in comparison with histomorphometry. METHODS: Mice were subjected to surgery with permanent ligation of the left anterior descending artery. PET was performed before and 7 d after surgery. The infarct size was determined from the PET studies using both manual and automated delineation. The second PET scan was followed by histomorphometric analysis. RESULTS: An excellent correlation between PET and histomorphometry was found for both manual (R = 0.98) and automated (R = 0.98) delineation, with linear regression curves close to unity (manual: y = 1.10x - 0.01; automated: y = 1.12x - 0.02). Automated analysis required <1 min per study. CONCLUSION: The measurement of infarct size in mice with (18)F-FDG PET is feasible and highly accurate. This noninvasive methodology permits unique longitudinal studies of biochemical parameters in mice and facilitates studies that aim to assess the effect of surgical and pharmacologic intervention after acute MI.

Algorithms↗
PubMed2005

Synthesis, in vitro pharmacology and biodistribution studies of new PD 156707-derived ET(A) receptor radioligands.

It is assumed that the regulation of cardiac endothelin (ET) receptor density is abnormal in heart diseases. From that perspective, an ET receptor radioligand is needed to assess ET receptor density in vivo. The nonpeptidyl ET(A) receptor antagonist PD 169390 was labelled with radioiodine to give a putative radioligand for SPECT. Labelling with [125I]iodide and [123I]iodide was accomplished with good to excellent radiochemical yields. The affinities of the nonradioactive reference and those of selected precursor compounds for ET(A) receptors were determined, using [125I]iodine labelled endothelin-1 with mouse ventricular membranes. All employed substances exhibited potent in vitro pharmacological characteristics with Ki values comparable to that of the lead compound PD 156707. Biodistribution studies and scintigraphic imaging experiments in mice, however, showed no significant uptake of the [123I] derivative in the heart.

Animals↗
PubMed2005

C-5-disubstituted barbiturates as potential molecular probes for noninvasive matrix metalloproteinase imaging.

Studies have demonstrated a positive correlation between inflammation, metastasis, or atherosclerosis and the unbalanced or culminated expression of matrix metalloproteinases (MMPs). The molecular imaging of locally upregulated MMP activity in vivo is a clinical challenge. Actually, radioligands based on nonpeptidyl MMP inhibitors (MMPIs) are currently in development as putative radiopharmaceutical agents for the noninvasive in vivo assessment of activated MMPs. Nonpeptidyl MMPIs bind to the zinc active site of the activated enzyme via mono- (e.g. carboxylate) or bidentate (e.g. hydroxamate) complexation thereby exhibiting a broad-spectrum MMP binding potency. Thus, these mentioned endopeptidase inhibitors should be useable lead compounds for the redevelopment as diagnostic MMPI radiotracers. Recently, the non-hydroxamate C-5-disubstituted pyrimidine-2,4,6-triones were disclosed as subgroup-selective MMP inhibitors. We here describe a set of fine-tuned barbiturates as a new class of MMPI radiotracers for the noninvasive in vivo visualization of activated MMPs using scintigraphic techniques such as SPECT or PET.

Barbiturates↗
PubMed2005

[Scintigraphic molecular imaging].

Modern medicine is currently focusing its basic and clinical research towards "molecular medicine". This trend, together with the decoding of the human genome and the resulting design and use of transgenic mouse models of human diseases, demands that innovative imaging approaches are developed for man and mice. Non-invasive imaging modalities capable of quantifying molecular processes in vivo (collectively defined as "molecular imaging" techniques) are extremely interesting in this respect. This review focuses on the clinical and experimental scintigraphic molecular-imaging modalities SPECT and PET, and summarizes their actual and future impact in medicine.

Animals↗