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Biomedical subjects

Stefan Eberl

Publications and source records attributed to Stefan Eberl.

10 recordsLinked to original sources
PubMed2006

Quantitative mapping of basal and vasareactive cerebral blood flow using split-dose 123I-iodoamphetamine and single photon emission computed tomography.

A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min)=1.07x(ml/100 g/min)-1.14, r=0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest-rest study was 1.5+/-5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease.

Aged↗
PubMed2006

Lung deposition of mannitol powder aerosol in healthy subjects.

Mannitol as a dry powder aerosol is used for bronchoprovocation testing and to enhance mucus clearance in people with excessive airway secretions. The dose and distribution of the deposited aerosol in the lung was investigated using fast single photon emission tomography (SPECT) imaging. Mannitol powder (3 microm particle size) was produced by spray drying and radiolabeled with (99m)Tc-DTPA. Approximately 60 mg of radiolabeled mannitol (containing 52-68 MBq of (99m)Tc-DTPA) was administered to 10 healthy subjects using the Inhalator dry powder inhaler (DPI), and SPECT images (1 min each) were collected. Thirteen percent to 31% of the dose of mannitol loaded in the inhaler deposited in the lungs and the deposited dose correlated positively with the peak inhalation air flow. The regional aerosol lung distribution, as expressed by the penetration index (i.e., ratio of peripheral to central deposition in the lung) varied from 0.31 to 0.88, which however showed no dependency on any flow parameters. The variation in response to the same dose of mannitol within the asthmatic population may in part be explained by these findings.

Adult↗
PubMed2006

SPECT Imaging for Radioaerosol Deposition and Clearance Studies.

Planar gamma camera scintigraphy is well established for measuring the deposition and clearance of radioaerosols. Single photon emission computed tomography (SPECT) provides threedimensional (3D) reconstructions of the radioactivity distribution, thus avoiding the compression of 3D data into two-dimensional (2D) images and potentially offering superior assessment of aerosol deposition patterns. However, SPECT has traditionally been associated with long imaging times, making it unsuitable for measuring deposition and clearance of radioaerosols with fast clearance. Multi-detector SPECT systems can collect complete SPECT studies in <1 min, allowing both initial deposition and clearance over time to be assessed by dynamic SPECT. Simultaneous transmission measurement with an external source provides attenuation correction for absolute activity quantification as well as aiding in the definition of the lung volume of interest. A dynamic SPECT imaging protocol has been developed to allow fast imaging from the oropharynx to the abdomen using gamma cameras with limited axial field of views. This allows activity quantification not only in the lungs, but also in areas outside the thorax. However, fast dynamic SPECT imaging is technically and computationally more demanding and provides less scope for reducing the radioactivity administered to the subjects. It has been shown that dynamic SPECT, compared to planar imaging, is more sensitive in detecting changes in deposition as measured by the Penetration Index (PI). Thus, SPECT can better differentiate between large and small airways, which is important for lung regional analysis.

Administration, Inhalation↗
PubMed2006

Segmentation of VOI from multidimensional dynamic PET images by integrating spatial and temporal features.

Segmentation of multidimensional dynamic positron emission tomography (PET) images into volumes of interest (VOIs) exhibiting similar temporal behavior and spatial features is a challenging task due to inherently poor signal-to-noise ratio and spatial resolution. In this study, we propose VOI segmentation of dynamic PET images by utilizing both the three-dimensional (3-D) spatial and temporal domain information in a hybrid technique that integrates two independent segmentation techniques of cluster analysis and region growing. The proposed technique starts with a cluster analysis that partitions the image based on temporal similarities. The resulting temporal partitions, together with the 3-D spatial information are utilized in the region growing segmentation. The technique was evaluated with dynamic 2-[18F] fluoro-2-deoxy-D-glucose PET simulations and clinical studies of the human brain and compared with the k-means and fuzzy c-means cluster analysis segmentation methods. The quantitative evaluation with simulated images demonstrated that the proposed technique can segment the dynamic PET images into VOIs of different kinetic structures and outperforms the cluster analysis approaches with notable improvements in the smoothness of the segmented VOIs with fewer disconnected or spurious segmentation clusters. In clinical studies, the hybrid technique was only superior to the other techniques in segmenting the white matter. In the gray matter segmentation, the other technique tended to perform slightly better than the hybrid technique, but the differences did not reach significance. The hybrid technique generally formed smoother VOIs with better separation of the background. Overall, the proposed technique demonstrated potential usefulness in the diagnosis and evaluation of dynamic PET neurological imaging studies.

Algorithms↗
PubMed2005

Synthesis and in vivo evaluation of a novel peripheral benzodiazepine receptor PET radioligand.

The novel pyrazolopyrimidine ligand, N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-acetamide 1 (DPA-713), has been reported as a potent ligand for the peripheral benzodiazepine receptor (PBR) displaying an affinity of K(i)=4.7 nM. In this study, 1 was successfully synthesised and demethylated to form the phenolic derivative 6 as precursor for labelling with carbon-11 (t(1/2) = 20.4 min). [11C]1 was prepared by O-alkylation of 6 with [11C]methyl iodide. The radiochemical yield of [(11)C]1 was 9% (non-decay corrected) with a specific activity of 36 GBq/micromol at the end of synthesis. The average time of synthesis including formulation was 13.2 min with a radiochemical purity >98%. In vivo assessment of [11C]1 was performed in a healthy Papio hamadryas baboon using positron emission tomography (PET). Following iv administration of [11C]1, significant accumulation was observed in the baboon brain and peripheral organs. In the brain, the radioactivity peaked at 20 min and remained constant for the duration of the imaging experiment. Pre-treatment with the PBR-specific ligand, PK 11195 (5 mg/kg), effectively reduced the binding of [11C]1 at 60 min by 70% in the whole brain, whereas pre-treatment with the central benzodiazepine receptor ligand, flumazenil (1mg/kg), had no inhibitory effect on [11C]1 uptake. These results indicate that accumulation of [11C]1 in the baboon represents selective binding to the PBR. These exceptional in vivo binding properties suggest that [11C]1 may be useful for imaging the PBR in disease states. Furthermore, [11C]1 represents the first ligand of its pharmacological class to be labelled for PET studies and therefore has the potential to generate new information on the pathological role of the PBR in vivo.

Acetamides↗
PubMed2005

Mucociliary clearance in patients with chronic asthma: effects of beta agonists.

OBJECTIVE: Chronic asthma is characterized by airway inflammation, mucus hypersecretion and impaired mucociliary clearance (MCC). We investigated baseline MCC and the acute effect of terbutaline in chronic asthmatics with sputum production while on long-term treatment with salmeterol in combination with inhaled corticosteroids (ICS). METHODOLOGY: MCC was measured at baseline and in response to 1 mg terbutaline (or placebo) on three visits over 80 min in 16 asthmatics (52+/-13 years of age). Subjects who had greater than 10% absolute increase in MCC above baseline and placebo, after terbutaline, were categorized in group A and subjects who had less than 10% in group B. RESULTS: In group A subjects (n=6), MCC increased from 23.7+/-4.0% at baseline to 43.7+/-4.9% with terbutaline (P<0.0001) and to 34.4+/-5.7% with placebo (P<0.01). In group B subjects (n=10), MCC remained similar: 11.3+/-3.2% at initial baseline, 12.0+/-3.2% with terbutaline and 7.3+/-3.0% with placebo (P>0.05). Group B subjects withdrew from all beta(2) agonists for a week and MCC was remeasured. After withdrawal, baseline MCC (7.0+/-1.8%) was similar to the initial baseline value (P>0.1) and MCC with terbutaline (15.8+/-4.9%) was greater than baseline (P<0.005) but remained abnormal in most subjects. Baseline percentage predicted FEV(1) and FEF(25--75%) were 77.3+/-7.2 and 41.7+/-5.6 in group A and 59.9+/-8.1 and 29.5+/-8.4 in group B subjects, respectively. CONCLUSION: MCC was impaired in most of these asthmatics with persistent airway obstruction and sputum production, despite regular treatment with ICS and salmeterol. In addition, there was little or no stimulation of MCC acutely after terbutaline in most of these asthmatics.

Administration, Inhalation↗
PubMed2005

Optimizing injected dose in clinical PET by accurately modeling the counting-rate response functions specific to individual patient scans.

UNLABELLED: To optimize the injected dose of radiopharmaceutical in PET, one needs to know its relationship to some metric of data quality for individual patient scans, such as noise-equivalent counting rate (NECR). In this paper, we show how one may accurately model the clinical NECR response corresponding to specific patient scans much as if a counting-rate test had been performed on each patient. We apply this technique to patient data and show how it can lead to improved clinical scanning protocols. METHODS: True and random coincidence rates expressed as functions of an appropriate measurable system parameter such as the detector single-event rate have functional forms that are largely independent of the object being scanned. Thus, reference true and random response functions may be scaled directly to the specific counting rates measured on a clinical scan, thereby yielding a curve of NECR versus injected dose. We have applied this technique to 2 groups of 163 clinical (18)F-FDG scans each. One of the groups was obtained on a lutetium oxyorthosilicate PET/CT scanner with conventional front-end electronics, and the other was obtained on a lutetium oxyorthosilicate PET/CT scanner with a new digital data processing system (Pico-3D). RESULTS: At 90%-95% of maximum signal-to-noise ratio (SNR), the mean optimal dose for a 60-min uptake period ranged from 366 to 717 MBq depending on the electronics and randoms processing method. There was only a slight (1 MBq/kg) dependence of optimal dose on patient weight but a larger dependence on position in the body. Pico-3D electronics improved optimal data SNR by 35% for a 70-kg person, but in both cases NECR fell rapidly with increasing weight (1.4%/kg). For an equivalent data SNR, a 120-kg person would have to be scanned 2.3 times longer than a 60-kg person. Over this range of weight, the mean scatter fraction increased by 12% whereas the ratio of mean randoms to trues increased by 48%. CONCLUSION: The methodology developed here allows one to directly estimate the optimal dose to inject for specific clinical scans and permits a detailed analysis of the sources of noise in PET data and of their variation with parameters such as patient weight.

Computer Simulation↗
PubMed2004

Sequential 123I-iododexetimide scans in temporal lobe epilepsy: comparison with neuroimaging scans (MR imaging and 18F-FDG PET imaging).

PURPOSE: Muscarinic acetylcholine receptors (mAChRs) play an important role in the generation of seizures. Single-photon emission computed tomography (SPECT) with 12I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to: (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine the accuracy of IDEX scans in the localisation of seizure foci when compared with video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c) characterise the distribution of IDEX binding in the temporal lobes and (d) compare IDEX SPECT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in identifying seizure foci. METHODS: We performed sequential scans using IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory TLE undergoing assessment for epilepsy surgery. Visual and region of interest analyses of the mesial, lateral and polar regions of the temporal lobes were used to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation. RESULTS: The 6-h IDEX scan (92%; kappa=0.83, p=0.003) was superior to the 0-h (36%; kappa=0.01, p>0.05), 3-h (55%; kappa=0.13, p>0.05) and 24-h IDEX scans in identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly predicted the temporal lobe of seizure origin in two patients who required intracranial EEG recordings to define the seizure onset. Reduced ligand binding was most marked at the temporal pole and mesial temporal structures. IDEX SPECT was superior to interictal FDG PET (75%; kappa=0.66, p=0.023) in seizure onset localisation. MR imaging was non-localising in two patients in whom it was normal and in another patient in whom there was bilateral symmetrical hippocampal atrophy. CONCLUSION: The 6-h IDEX SPECT scan is a viable alternative to FDG PET imaging in seizure onset localisation in TLE.

Adult↗
PubMed2002

Changes in lung deposition of aerosols due to hygroscopic growth: a fast SPECT study.

Our objective was to use rapid dynamic SPECT to study the effect of hygroscopic growth on aerosol deposition in the lung. Six healthy volunteers inhaled radiolabeled ((99m)Tc-DTPA) saline aerosols of two different droplet sizes (MMAD Small 3.2 +/- 0.2 and Large 6.5 +/- 0.2 microm, span 1.8 and 1.7, respectively) and tonicities (normal saline, NS, 0.9% and hypertonic saline 'HS' 7.0% NaCl) reproducibly on 4 occasions. Simultaneous emission-transmission scanning with a triple detector gamma camera was used to collect the lung images. Regional lung deposition was quantified by the penetration index or PI. The results revealed significant differences of aerosol deposition in the lung, which follows precisely the expectation from particle size and hygroscopicity. The difference in the PI values between the aerosols increases in the order of: Large NS-Large HS < Small NS-Small HS < Small HS-Large NS < Small HS-Large HS < Small NS-Large NS < Small NS-Large HS.

Aerosols↗