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Hans-Wilhelm Müller

Publications and source records attributed to Hans-Wilhelm Müller.

13 recordsLinked to original sources

Learning related interactions among neuronal systems involved in memory processes.

Functional neuroimaging techniques using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have provided new insights in our understanding of brain function from the molecular to the systems level. While subtraction strategy based data analyses have revealed the involvement of distributed brain regions in memory processes, covariance analysis based data analysis strategies allow functional interactions between brain regions of a neuronal network to be assessed. The focus of this chapter is to (1) establish the functional topography of episodic and working memory processes in young and old normal volunteers, (2) to assess functional interactions between modules of networks of brain regions by means of covariance based analyses and systems level modelling and (3) to relate neuroimaging data to the underpinning neural networks. Male normal young and old volunteers without neurological or psychiatric illness participated in neuroimaging studies (PET, fMRI) on working and episodic memory. Distributed brain areas are involved in memory processes (episodic and working memory) in young volunteers and show much of an overlap with respect to the network components. Systems level modelling analyses support the hypothesis of bihemispheric, asymmetric networks subserving memory processes and revealed both similarities in general and differences in the interactions between brain regions during episodic encoding and retrieval as well as working memory. Changes in memory function with ageing are evident from studies in old volunteers activating more brain regions compared to young volunteers and revealing more and stronger influences of prefrontal regions. We finally discuss the way in which the systems level models based on PET and fMRI results have implications for the understanding of the underlying neural network functioning of the brain.

Animals↗

Striatal dopamine transporter density in drug naive patients with attention-deficit/hyperactivity disorder.

BACKGROUND AND AIM: Dopamine transporters are the target of psychostimulants used for treatment of attention-deficit/hyperactivity disorder (ADHD). Therefore, the present study aimed to evaluate striatal dopamine transporter density in adult patients with ADHD. METHODS: Twenty patients (11 female, nine male; mean age 35+/-7 years) and 20 control subjects (11 female, nine male, mean age 32 +/- 8 years) were examined with SPECT using the specific radiotracer 123I-FP-CIT. The ratio of striatal to cortical radioactivity concentration was used for semiquantitative evaluation of dopamine transporter binding potential (V3''). There was a significant influence of age (P < 0.001) and a trend towards an influence of gender (P = 0.053) on V3''. An ANCOVA with these covariates showed a slightly higher V3'' in the patients than in the control subjects (4.24 +/- 0.48 vs. 4.03 +/- 0.56; P = 0.02). CONCLUSION: This study provides further in-vivo evidence for an involvement of the dopamine transporter in ADHD. However, compared to previous studies, the increase of dopamine transporter density in the patient group is less pronounced here.

Adolescent↗

Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study.

OBJECTIVES: Stem cell therapy may be useful in chronic myocardial infarction (MI); this is conceivable, but not yet demonstrated in humans. BACKGROUND: After acute MI, bone marrow-derived cells improve cardiac function. METHODS: We treated 18 consecutive patients with chronic MI (5 months to 8.5 years old) by the intracoronary transplantation of autologous bone marrow mononuclear cells and compared them with a representative control group without cell therapy. RESULTS: After three months, in the transplantation group, infarct size was reduced by 30% and global left ventricular ejection fraction (+15%) and infarction wall movement velocity (+57%) increased significantly, whereas in the control group no significant changes were observed in infarct size, left ventricular ejection fraction, or wall movement velocity of infarcted area. Percutaneous transluminal coronary angioplasty alone had no effect on left ventricular function. After bone marrow cell transplantation, there was an improvement of maximum oxygen uptake (VO2max, +11%) and of regional 18F-fluor-desoxy-glucose uptake into infarct tissue (+15%). CONCLUSIONS: These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be realized in humans by bone marrow mononuclear cell transplantation.

Adult↗

[123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine--an in vivo imaging study with a dedicated small animal SPECT.

PURPOSE: This study assessed [123I]iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT. METHODS: Subsequent to baseline quantifications of D2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D2 receptors and dopamine transporters, respectively. RESULTS: Striatal baseline equilibrium ratios (V3'') of [123I]iodobenzamide binding were 1.42+/-0.31 (mean+/-SD). After pre-treatment with haloperidol and methylphenidate, V3'' values decreased to 0.54+/-0.46 (p<0.0001) and 0.98+/-0.48 (p=0.009), respectively. CONCLUSION: The decrease in [123I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [123I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [123I]iodobenzamide binding to D2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine.

Animals↗

O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas.

MRI is commonly used to determine the location and extent of cerebral gliomas. We investigated whether the diagnostic accuracy of MRI could be improved by the additional use of PET with the amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (FET). In a prospective study, PET with FET and MRI was performed in 31 patients with suspected cerebral gliomas. PET and MRIs were co-registered and 52 neuronavigated tissue biopsies were taken from lesions with both abnormal MRI signal and increased FET uptake (match), as well as from areas with abnormal MR signal but normal FET uptake or vice versa (mismatch). Biopsy sites were labelled by intracerebral titanium pellets. The diagnostic performance for the identification of cellular tumour tissue was analysed for either MRI alone or MRI combined with FET PET using alternative free response receiver operating characteristic curves (ROCs). Histologically, 26 biopsy samples corresponded to cellular glioma tissue and 26 to peritumoral brain tissue. The diagnostic performance, as determined by the area under the ROC curve (Az), was Az = 0.80 for MRI alone and Az = 0.98 for the combined MRI and FET PET approach (P < 0.001). MRI yielded a sensitivity of 96% for the detection of tumour tissue but a specificity of only 53%, and combined use of MRI and FET PET yielded a sensitivity of 93% and a specificity of 94%. Combined use of MRI and FET PET in patients with cerebral gliomas significantly improves the identification of cellular glioma tissue and allows definite histological tumour diagnosis. Thus, our findings may have considerable impact on target selection for diagnostic biopsies as well as therapy planning.

Adolescent↗

[TierSPECT: performance of a dedicated small-animal-SPECT camera and first in vivo measurements].

This paper presents the performance of a new small-animal camera (TierSPECT) devised for the in vivo measurements of radiolabeled substances in small laboratory animals such as mice and rats. In a scatter medium, the camera has a tomographic spatial resolution of 2.87 mm and a sensitivity of 22 cps/MBq in a usable Field-of-View (FOV) with a diameter of 82 mm. The planar homogeneity amounts to 3.3%, the tomographic homogeneity lies between 3.2% and 3.5%. The deviation between filled and measured concentration of activity in a cylindrical 4-chamber-phantom was smaller than 2.6%. Using a novel rat head phantom with chamber volumes in the order of magnitude of the spatial resolution (between 0.065 ml and 0.19 ml) it could be demonstrated that studies of the rat neostriatal dopaminergic system are feasible under observance of physiological conditions. In vivo studies using [99mTc]diphosphonato-1,2-propandicarbonic acid (99mTc-DPD) and [123I]N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)-nortropane (123I-FP-CIT) proved that bone metabolism and dopamine transporter binding can be visualized with the TierSPECT. The fusion of 99mTc-DPD and 123I-FP-CIT images allowed the differentiation between intra- and extracerebral structures. Pretreatment with methylphenidate resulted in blockade of striatal dopamine transporter binding.

Animals↗

Multimodal metabolic imaging of cerebral gliomas: positron emission tomography with [18F]fluoroethyl-L-tyrosine and magnetic resonance spectroscopy.

OBJECT: The purpose of this study was to determine the predictive value of [18F]fluoroethyl-L-tyrosine (FET)-positron emission tomography (PET) and magnetic resonance (MR) spectroscopy for tumor diagnosis in patients with suspected gliomas. METHODS: Both FET-PET and MR spectroscopy analyses were performed in 50 consecutive patients with newly diagnosed intracerebral lesions supposed to be diffuse gliomas on contrast-enhanced MR imaging. Lesion/brain ratios of FET uptake greater than 1.6 were considered positive, that is, indicative of tumor. Results of MR spectroscopy were considered positive when N-acetylaspartate (NAA) was decreased in conjunction with an absolute increase of choline (Cho) and an NAA/Cho ratio of 0.7 or less. An FET lesion/brain ratio, an NAA/Cho ratio, and signal abnormalities on MR images were compared with histological findings in neuronavigated biopsy specimens. The FET lesion/brain ratio and the NAA/Cho ratio were identified as significant independent predictors for the histological identification of tumor tissue. The accuracy in distinguishing neoplastic from nonneoplastic tissue could be increased from 68% with the use of MR imaging alone to 97% with MR imaging in conjunction with FET-PET and MR spectroscopy. Sensitivity and specificity for tumor detection were 100 and 81% for MR spectroscopy and 88 and 88% for FET-PET, respectively. Results of histological studies did not reveal tumor tissue in any of the lesions that were negative on FET-PET and MR spectroscopy. In contrast, a tumor diagnosis was made in 97% of the lesions that were positive with both methods. CONCLUSIONS: In patients with intracerebral lesions supposed to be diffuse gliomas on MR imaging, FET-PET and MR spectroscopy analyses markedly improved the diagnostic efficacy of targeted biopsies.

Adolescent↗

Fluorine-18-labeled fluorodeoxyglucose-positron emission tomography studies of acute brainstem Lyme neuroborreliosis [corrected] Case report.

The authors report on a patient suffering from acute Lyme borreliosis who underwent two consecutive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) studies demonstrating the course of the disease. The first FDG-PET study revealed markedly increased glucose metabolism in the brainstem, matching exactly the signal abnormalities exhibited on magnetic resonance images and indicating a brainstem tumor. A second PET scan demonstrated no abnormality in this region, thus reflecting clinical remission following antibiotic therapy. Data in the present case indicate that hypermetabolic findings on FDG-PET studies in the brainstem region should be regarded with caution and that neuroborreliosis must be considered as a possible differential diagnosis.

Acute Disease↗

Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT.

PURPOSE: The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [123I]FP-CIT. METHODS: [123I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [123I]FP-CIT scans with bone metabolism and perfusion scans obtained with 99mTc-DPD and 99mTc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [123I]FP-CIT scans with images of brain perfusion obtained with 99mTc-HMPAO. RESULTS: Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''3) of 0.24+/-0.26 (mean +/- SD) and 1.09+/-0.42, respectively (t test, two-tailed, p<0.0001). Cortical V''3 values amounted to 0.05+/-0.28 (methylphenidate) and 0.3+/-0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [123I]FP-CIT accumulation. CONCLUSION: The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [123I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and small animal imaging systems.

Animals↗

Can the apparent diffusion coefficient be used as a noninvasive parameter to distinguish tumor tissue from peritumoral tissue in cerebral gliomas?

PURPOSE: To determine whether the apparent diffusion coefficient (ADC) can be used to distinguish between tumor tissue and peritumoral brain tissue in cerebral gliomas. MATERIALS AND METHODS: Twenty-two patients with 44 biopsies were enrolled in this study. ADC maps calculated from a diffusion-weighted (DW) multislice EPI sequence were coregistered with conventional MR images. Neuronavigated biopsies and intraoperative markers were used for correlation with the histologic specimens. ADC values and lesion-to-brain ratios of the different sequences were calculated and compared for tumor tissue and peritumoral brain tissue. A logistic regression analysis was performed to determine the diagnostic value of the ADC maps. RESULTS: The ADC values and ratios demonstrated a large overlap between tumor tissue and peritumoral tissue. Group comparisons revealed a significantly (P=0.03) lower ADC ratio in tumor tissue (mean=1.28 +/- 0.39) compared to peritumoral tissue (mean=1.48 +/- 0.30), whereas the absolute ADC values did not differ significantly. In the logistic regression analysis, the lesion-to-brain ratio of the gadolinium (Gd)-enhanced T1-weighted sequence was the most valuable predictor of the presence of tumor tissue. The ADC value and ratio were not identified as significant predictors. CONCLUSION: The ADC is not helpful for distinguishing tumor tissue from peritumoral brain tissue in gliomas.

Adolescent↗

The contribution of small animal positron emission tomography to the neurosciences--a critical evaluation.

This article presents an overview of those animal studies which so far have been performed with dedicated small animal positron emission tomographs in the field of the neurosciences. In vivo investigations focus on energy metabolism, perfusion and receptor/transporter binding in rat models of reinforcement, learning and memory, traumatic brain injury, epilepsy, depression, cardiovascular diseases--such as ischemia and focal stroke--and neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. In the majority of studies, important novel aspects arise from the fact that the investigators made use of an option inherent to in vivo studies, namely to conduct longitudinal investigations on the same animals. Relevant findings pertain to the relationship of brain metabolism/perfusion and the cholinergic system, the regulation state of dopamine receptors upon cocaine administration and withdrawal, the regulation state of dopamine receptors and transporters in animal models of Parkinson's and Huntington's disease, and potential treatments of progressive dopaminergic depletion with adenoviral vectors, embryonic grafts, stem cells and nerve growth factors.

Animals↗

In vivo measurement of D2 receptor density and affinity for 18F-(3-N-methyl)benperidol in the rat striatum with a PET system for small laboratory animals.

UNLABELLED: A recent investigation showed that intracerebral radioactivity concentrations can reliably be quantified in vivo with a small-animal PET device. The purpose of the current study was to investigate the binding characteristics of the D(2) receptor radioligand (18)F-(3-N-methyl)benperidol ((18)FMB) in rat striatum by determining receptor density (B(max)) and affinity (K(d)) in vivo. For validation, K(d) and B(max) additionally were determined in vitro using storage phosphor autoradiography. METHODS: Striatal radioactivity was measured with PET in 8 Sprague-Dawley rats after injection of (18)FMB in increasing specific activities. Free radioligand concentrations were estimated from cortical radioactivity concentrations and were subtracted from striatal radioactivity concentrations to obtain specific binding. In vitro saturation experiments were performed on 7 further rats according to the isotopic dilution method. Specific binding was determined by both subtraction of (18)FMB binding in the presence of raclopride and subtraction of cortical radioactivity concentrations from total radioligand binding. Saturation binding curves were obtained by plotting specifically bound radioligand concentrations against free radioligand concentrations and were evaluated with regression analysis. RESULTS: PET yielded a K(d) of 6.2 nmol/L and a B(max) of 16 fmol/mg for the striatal D(2) receptor. In vitro, K(d) and B(max) amounted to 4.4 nmol/L and 84.1 fmol/mg (subtraction of (18)FMB binding in the presence of raclopride), respectively, and 7.9 nmol/L and 70.1 fmol/mg (subtraction of cortical radioactivity concentrations), respectively. CONCLUSION: K(d) values measured with PET and autoradiography agreed and corresponded to inhibition constants obtained in previous in vitro studies. B(max) values lay within the same order of magnitude. The results of in vitro saturation binding analyses also agreed, irrespective of the mode of determination of free radioligand concentrations. Thus, B(max) and K(d) may be determined with PET in analogy to the evaluation of in vitro binding data by regression analysis of bound-versus-free ligand concentrations. Our results show that small-animal tomographs are valuable tools for the in vivo characterization of receptor radioligands as an alternative to autoradiography.

Animals↗