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S P Müller

Publications and source records attributed to S P Müller.

17 recordsLinked to original sources
PubMed1998

A method for approximating the density of maximum-likelihood and maximum a posteriori estimates under a Gaussian noise model.

The performance of maximum-likelihood (ML) and maximum a posteriori (MAP) estimates in non-linear problems at low data SNR is not well predicted by the Cramér-Rao or other lower bounds on variance. In order to better characterize the distribution of ML and MAP estimates under these conditions, we derive a point approximation to density values of the conditional distribution of such estimates. In an example problem, this approximate distribution captures the essential features of the distribution of ML estimates in the presence of Gaussian-distributed noise.

Algorithms↗
PubMed1998

Involvement of the human cerebellum during habituation of the acoustic startle response: a PET study.

The present study investigated the involvement of the human cerebellum in the habituation of the acoustic startle response using PET. The startle response was elicited in seven young, healthy subjects by a tone presented via headphones. Startle responses were recorded from the right sternocleidomastoid muscle. Regional cerebral blood flow (rCBF) was assessed in nine scans and one startle stimulus was applied during each scan. The reduction of size of the sternocleidomastoid muscle response was correlated with changes in rCBF during the ongoing process of startle response habituation. A significant decrease of rCBF was found in the medial cerebellum. These data are consistent with an involvement of the medial parts of the human cerebellum in non-associative learning as proposed by previous animal studies.

Acoustic Stimulation↗
PubMed1998

Technetium-99m-furifosmin in the follow-up of differentiated thyroid carcinoma.

UNLABELLED: Tumor scintigraphy with flow tracers, such as 201TI-chloride, has an established role in the follow-up of differentiated thyroid cancer. We investigated a new tracer, 99mTc-furifosmin (Technescan Q12, Mallinckrodt Diagnostika, Hennef, Germany), in patients with elevated thyroglobulin levels or sonographic suspicion of lymph node metastases or recurrent disease. METHODS: In a prospective study, we examined 20 patients with 99mTc-furifosmin. All patients underwent a 18F-fluorodeoxyglucose (FDG) PET scan of the neck and chest. Positive 99mTc-furifosmin findings were validated by biopsy, (131)I scan, CT or 18F-FDG PET examinations. RESULTS: In three patients with cervical lymph node metastases detected on a planar 99mTc-furifosmin scan, we found a rapid tracer accumulation in the tumor (maximum < 2 min) and a significant washout in 2 of 3 patients after 4 hr. The visual contrast and the tumor-to-nontumor ratio was rather poor (average 1.2:1). In 3 additional patients, 3 pulmonary and 2 mediastinal lymph node metastases were detected by the 99mTc-furifosmin SPECT scan. Two patients were true-negative, and in 13 of 18 patients, the tumor could be localized by 18F-FDG PET (10 cervical, 6 mediastinal, 4 pulmonary metastases, 1 bone metastasis); 5 patients were false-negative. In 3 of these false-negative cases we could not localize the tumor with other diagnostic methods. Two patients had a true-negative PET examination. CONCLUSION: The statistical analysis of our data on 99mTc-furifosmin reveals that the sensitivity and 95% confidence interval of 33% (11%-56%) on a patient-by-patient basis and of 34% (17%-57%) for the lesion-by-lesion analysis is significantly lower than the sensitivity and 95% confidence interval of 72% (50%-89%) on a patient-by-patient basis and of 91% (78%-100%) on lesion-by-lesion basis for 18F-FDG. The sensitivity of 99mTc-furifosmin appears to be poor, even for cervical and mediastinal tumor manifestations where the value of 201TI-chloride is established.

Carcinoma, Papillary↗
PubMed1997

The relevance of sensory input for the cerebellar control of movements.

The performance of a motor task not only requires subjects to plan, prepare, and initiate but also to monitor how a movement is performed. We used positron emission tomography to examine to what extent the human cerebellum is involved in controlling motor output or sensory input from movements in normal subjects. In the first study, we compared the active performance of a motor task (flexion and extension of the right elbow) to the passive execution of the same movements. Passive movements were driven by a motor with the arm fixed in a guide hinge. Active movements (compared to rest) elicited increases of rCBF mainly in the ipsilateral neocerebellar hemisphere and vermis of the posterior lobe. During passive movements, almost identical parts of the cerebellar hemispheres and vermis were activated (compared to the rest condition). The direct comparison of active and passive movement conditions revealed a small activation of the neocerebellar hemisphere of the posterior lobe and cerebellar nuclei ipsilateral to the movement. Approximately 90% of cerebellar neuronal activity was related to sensory input. In the second study, we compared the execution of a free selection joystick movement task to a condition in which subjects simply imagined the movements. The execution of movements (compared to rest) was associated with increases of rCBF in the ipsilateral neocerebellar hemisphere and vermis of the posterior lobe. During movement imagination, a small part of the ipsilateral cerebellar hemisphere and vermis of the posterior lobe was activated (compared to rest). The increase of rCBF during movement imagination accounted for only 20% of the signal seen during movement execution. Our results indicate that the neocerebellum may be much more concerned with sensory information processing than has been considered previously.

Adult↗
PubMed1997

Cardiotoxicity of chlorodibromomethane and trichloromethane in rats and isolated rat cardiac myocytes.

The cardiovascular effects were investigated after acute and subacute treatment with chlorodibromomethane (CDBM; 0.4 to 3.2 mmol/kg p.o.), trichloromethane (TCM; 0.31 and 1.25 mmol/kg p.o.) and mixtures of CDBM and TCM (acute, 0.8 mmol CDBM/kg + 1.25 mmol TCM/kg p.o.; subacute, 0.4 mmol CDBM/kg + 0.31 mmol TCM/kg p.o.) in conscious and urethane anaesthetized male Wistar rats (n = 6-10 per treatment). Furthermore it was observed whether cardiovascular responses were modified in CDBM or TCM treated rats after administration of exogenous catecholamines (epinephrine, 1 microg/kg; norepinephrine, 2 microg/kg) and underpinned with in vitro alterations of Ca2+ dynamics in cardiac myocytes. The present findings demonstrated that single and subacute oral administration of CDBM or TCM and mixtures of CDBM and TCM resulted in arrhythmogenic and negative chronotropic and dromotropic effects in conscious and urethane anaesthetized rats. The atrioventricular conduction time and the intraventricular extension time were extended. A slight shortening of the repolarization velocity was observed. The myocardial contractility was depressed and the heart was sensitized to the arrhythmogenic effects of epinephrine. After catecholamine injection the adrenergic cardiovascular responses in urethane anesthetized rats were modified: increased hypertensive epinephrine and norepinephrine action as well as augmentation of negative chronotropic and negative dromotropic cardiac effects of catecholamines were observed. The positive inotropic adrenergic response was diminished. The present in vivo findings, myocardial depression after acute CDBM treatment, as determined by different indices of contractility, correlate well with the observed inhibitory actions of CDBM on Ca2+ dynamics in isolated cardiac myocytes. All cardiovascular alterations found after CDBM or TCM treatment were not intensified after treatment with mixtures of CDBM and TCM. The effects observed were distinctly stronger after TCM (1.25 and 0.31 mmol/kg) treatment compared to CDBM (0.8 and 0.4 mmol/kg) treatment.

Animals↗
PubMed1997

Nonuniform collimator sensitivity: improved precision for quantitative SPECT.

UNLABELLED: Attenuation of photons degrades both the accuracy and the precision of SPECT images; attenuation correction algorithms correct the bias but cannot improve precision. Increased noise due to photon attenuation is most pronounced in regions deep in solid body sections, such as the brain and abdomen. We have quantified the degradation in performance in several estimation tasks that can be attributed to photon attenuation and determined the degree to which performance might be improved by a collimator with a nonuniform sensitivity profile. METHODS: The analysis used ideal-observer models of performance in tasks involving estimation of the activity and size of a focal lesion. The models were based on the Cramer-Rao lower bound on the variance with which lesion activity and size can be estimated by an unbiased procedure. To quantify the effects of attenuation, values of the Cramer-Rao bound were calculated for each estimation task as a function of location of the lesion in circularly-shaped attenuators of 10- and 20-cm radii, with and without attenuation. Values of the bound were also determined for two nonuniform sensitivity profiles, one of which was designed to equalize (or nearly equalize) task performance throughout the image. RESULTS: For 99mTc, photon attenuation increased the variance of the estimates by factors of up to 4.5 for the 10-cm radius attenuator and up to 20.0 for the 20-cm radius attenuator. A collimator with a nonuniform sensitivity function reduced variance by factors of up to 1.8 for the 10-cm radius attenuator and up to 2.8 for the 20-cm radius attenuator. These gains in estimation performance were insensitive to the imaging task and to deviations from the assumed attenuator size and shape. CONCLUSION: Performance in estimation tasks using images from SPECT systems with uniform sensitivity collimators is considerably lower than the theoretical optimum. We have derived a sensitivity function, realizable using existing technology, that improves performance substantially.

Calibration↗
PubMed1996

Cerebellar activation during classical conditioning of the human flexion reflex: a PET study.

The present study investigated the involvement of the cerebellum in classical conditioning of the cutaneomuscular flexion reflex in four normal volunteers using positron emission tomography (PET). The flexion reflex was elicited by electrical pulses applied to the medial plantar nerve (unconditioned stimulus, US). A tone was presented as the conditioning stimulus, which co-terminated with the US. The incidence of conditioned responses was correlated with changes in rCBI during the acquisition process of flexion reflex conditioning. Blood flow was significantly increased in an area extending from the ipsilateral cerebellum and hippocampus to bilateral frontal regions (p = 0.009). These data provide support for an involvement of the cerebellum as well as hippocampus among other neural systems in classical flexion reflex conditioning.

Adult↗
PubMed1996

Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (stage pT4).

BACKGROUND: The role of adjuvant external radiotherapy in the survival of patients with differentiated thyroid cancer (DTC) is controversial. To our knowledge, no attempt has been undertaken thus far to assess the impact of this therapy with respect to the papillary and follicular types of thyroid cancer as separate entities. METHODS: Between 1979 and 1992, 238 patients with differentiated papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) with Stage pT4 have been treated and followed in our clinic. One hundred sixty-nine patients free of metastases at the final staging, which was performed after the second radioiodine therapy, were included in this study. The standard treatment comprised total thyroidectomy, ablative radioiodine therapy, and thyroid-stimulating hormone-suppressive therapy with levothyroxin. Ninety-nine patients free of disease after the final staging received additional external radiotherapy to the neck (with a dose of 50-60 Gy), whereas the remaining 70 patients were treated with the standard treatment protocol only. Distributions of age, sex, and follow-up time were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence of age, sex, histologic subtype, and lymph node status as well as of external radiotherapy on the time to first locoregional and distant failure (LDF), and the time to locoregional recurrence (LR), was accomplished using Cox's proportional hazard model. RESULTS: In patients with DTC, external radiotherapy was a predictive factor for improvement of both LR (P = 0.004) and locoregional and distant failure (P = 0.0003). When the time to first locoregional and distant failure was calculated separately for patients with PTC and FTC, there was a significant difference in the PTC group in favor of irradiated patients (P = 0.0001), whereas there was no effect of external radiotherapy in the FTC group (P = 0.38). Further analyses disclosed that this effect was significantly present only in patients with PTC and lymph node involvement (P = 0.002), whereas those without lymph node involvement did not benefit from an additional adjuvant radiotherapy (P = 0.27). Because none of the patients younger than age 40 years died due to the disease nor had progressive disease during follow-up, we reassessed our results in patients older than age 40 years. The effect of external radiotherapy could be confirmed in this subgroup of patients (P = 0.0009) and in the subgroup of lymph node positive patients older than age 40 years with invasive PTC (P = 0.01). CONCLUSIONS: In addition to total thyroidectomy, treatment with radioiodine, and TSH-suppressive therapy with thyroid hormone, adjuvant external radiotherapy improves the recurrence-free survival in patients older than age 40 years with invasive PTC and lymph node involvement.

Adenocarcinoma, Follicular↗
PubMed1996

Calcium dynamics in cardiac myocytes as a target of dichloromethane cardiotoxicity.

The purpose of the present study was to determine if cardiac actions of dichloromethane (DCM) in vivo correlate with in vitro alterations of Ca2+ dynamics in cardiac myocytes. Neonatal rat ventricular myocytes were obtained from 2- to 4-day-old rats, and electrically induced fluctuations of cytosolic free Ca2+ concentration ([Ca2+]i) in single cardiomyocytes were investigated using spectrofluorometric analysis of fura-2-[Ca2+]i binding. In cultured myocytes, cumulative exposure to 0.64-40.96 mM DCM resulted in a concentration-dependent and reversible decrease in the magnitude of [Ca2+]i transients with IC10 and IC50 values of 7.98 and 18.82 mM, respectively. Total inhibition of [Ca2+]i transients and cessation of beating were observed at 40.96 mM DCM. Suffusion with DCM for 40 min did not cause morphological alterations of the myocytes. In a urethane-anesthetized rat model, left ventricular pressure was measured by introducing a tip catheter via the carotid artery into the left ventricle, the ECG was recorded by two needle electrodes applied subcutaneously to the chest wall, and arterial pressure was measured via the femoral artery. Oral administration of 3.1-12.4 mmol DCM/kg resulted in DCM blood concentrations between 1.0 and 1.6 mM, accompanied by a dose-dependent decrease in contractile force and heart rate without influencing blood pressure and ECG tracings. Moreover, DCM treatment provided significant protection against arrhythmia development due to CaCl2-infusion. In spite of the slight discrepancy between DCM blood concentrations and in vitro concentrations of DCM for [Ca2+]i transient inhibition, present data are consistent with the view that cardiac effects after DCM exposure are mediated by alterations of Ca2+ dynamics during excitation-contraction coupling.

Anesthesia↗
PubMed1995

[Studies and recommendations on the design ov ROC analyses in nuclear medicine].

ROC analysis is the method of choice for an objective assessment of diagnostic tests; however, it requires large sample sizes. We investigated the influence of study design and data analysis on sampling requirements. A sample size of 123 for the patient as well as the control group, is required to prove a difference in sensitivity of 75% vs 90% (specificity 90%, statistical power 0.8). Analysis with the binormal bivariate ROC model allows > 35% reduction in sample size. If the patient group is increased the control group can be smaller, and vice versa; here the correlated ROC model also allows substantial decreases in sample size. If both diagnostic tests are performed in the same patient and control group and evaluated with the correlated ROC model, an objective, statistically sound assessment of diagnostic performance is possible with relatively small samples.

Analysis of Variance↗
PubMed1994

Comparison of magnetic and metabolic brain activity during a verb generation task.

The magnetic and metabolic activational patterns of the brain during the perception, generation and silent articulation of words overlap to some extent, yet also measure concrete activational patterns. In the present study, auditory evoked magnetic fields (MEG) and changes in regional cerebral blood flow (PET) were examined in healthy subjects during a verb generation task. The aim of the study was to determine whether the advantages of both recording techniques can be combined so as to identify distributed sources of brain activity during particular tasks such as language processing. Given the currently observed disparity of the results from the two types of brain imaging we conclude that PET data will most likely not provide physiologically meaningful constraints for the distributed source analysis of MEG data, and may not necessarily validate results of distributed source analyses.

Brain↗
PubMed1994

[ROC analysis of tumor identification using 201Tl-(I)-chloride and 99mTc-(I)-hexakis (2-methoxy-2-isobutylisonitrile].

We investigated tumor detectability of bronchial carcinoma using 201Tl and 99mTc-MIBI with planar scintigraphy and SPECT. We studied 30 tumor patients and 7 patients with coronary artery disease in a clinical phase III trial. The lung was partitioned into 6 areas, which were read independently, to provide a sufficiently large sample of tumor-free reference regions. We calculated the statistical power for the comparison of sensitivities at a given specificity of 95% (TPF-test) to demonstrate that the subdivision of the lung and the application of the bivariate bi-normal ROC model allows an objective assessment of diagnostic performance even for the small sample size of our study. There were no significant differences between 201Tl and 99mTc-MIBI for both observers; therefore, no advantage of 99mTc-MIBI over 201Tl for tumor scintigraphy could be demonstrated. SPECT was significantly superior to planar scintigraphy and should be preferred for tumor detection in the thorax.

Adenocarcinoma↗
PubMed1992

Clinical and cerebral blood flow studies in patients with intracranial hemorrhage and amyloid angiopathy typical of Alzheimer's disease.

Spontaneous intracerebral hemorrhages can occur in patients with severe amyloid angiopathy and other morphological signs of Alzheimer's disease (AD). We observed 15 patients in whom histological examination of brain tissue specimens obtained at surgery revealed characteristic congophilic amyloid deposits in subcortical arteries and/or nerve cells. Clinical follow-up examinations were carried out up to 9 years after diagnosis. In addition, three survivors from the operated group were investigated by neuropsychological testing and single photon emission computer tomography (SPECT) using Tc-99m-HMPAO for determination of regional cerebral blood flow (rCBF). SPECT could not differentiate between the "typical Alzheimer disease pattern" of bilateral temporo-parietal rCBF reduction and flow deficits resulting from previous hemorrhage. Intellectual functioning was found to be impaired to various degrees ranging from normal function to severe dementia (MMS test scores varied between 15 and 26 points); again, it was difficult to differentiate clinically between the nosologic entities mentioned above. On the basis of our present experience we cannot distinguish between brain dysfunction due to Alzheimer's disease and intracranial hemorrhage from amyloid angiopathy. This supports the idea that intracranial hemorrhage may only be one clinical manifestation of amyloid deposits, another one being "Alzheimer's disease" with varying preponderance.

Activities of Daily Living↗
PubMed1990

Maximum-likelihood estimation: a mathematical model for quantitation in nuclear medicine.

In a stimulation study, we investigated the limitations of quantitation in nuclear medicine using a maximum-likelihood (ML) estimation model. We estimated activity, size, and position of a disk-shaped object on a circular, uniform background of unknown activity. The parameter estimates were unbiased, and their standard error was proportional to the square root of the total image counts. The estimates of object activity and size were strongly (negatively) correlated; the position estimates, however, were not correlated with estimates of any other parameters. This implies that a priori knowledge of object location does not improve precision. The minimal model of quantitation tasks should incorporate unknown object activity and size as well as unknown background activity. The ML estimation procedure was used to investigate the trade-off between resolution and sensitivity in gamma camera collimator design. The results implied that for complex tasks such as the multiparameter estimation task investigated here, optimum performance is achieved at a better resolution than that previously found optimal for detection of a well-specified object in a known background.

Humans↗
PubMed1988

SPECT image noise power: effects of nonstationary projection noise and attenuation compensation.

The effects of nonstationary projection noise and attenuation compensation are included in a theoretic calculation of the radial noise power spectrum (NPS) of single photon emission computed tomographic (SPECT) images. The nonstationary projection noise is shown to cause a relatively large d.c. component in the NPS, especially for small objects; whereas, attenuation compensation increases the total noise variance while only changing the d.c. component slightly. The theoretic calculation agrees well with a radial NPS estimated from 1,250 SPECT images simulated from projections of random Gaussian noise, even though the effects of discrete data collection and reconstruction were not included in the theoretical model.

Computer Simulation↗