Dieter Meier

Bio: Dieter Meier is an academic researcher from ETH Zurich. The author has contributed to research in topics: Blood flow & Imaging phantom. The author has an hindex of 26, co-authored 59 publications receiving 2722 citations. Previous affiliations of Dieter Meier include École Polytechnique Fédérale de Lausanne & University of Zurich.

Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease

Abstract: Summary We used PET scans with the tracers []SF]fluorodeoxyglucose (FDG) and [uC]raclopride (RACLO) to study glucose metabolism and dopamine D2 receptor binding in the caudate nucleus and putamen of 18 carriers of the Huntington's disease gene mutation (10 asymptomatic subjects and eight untreated symptomatic Huntington's disease patients in an early disease stage). We also performed MRI scans and measured the bicaudate ratio (BCR) in the same subjects. Data were compared with those from nine mutation-negative members of Huntington's disease families and separate groups of age matched controls. The PET scans were repeated 1.5-3 years later in six of the asymptomatic gene carriers. Symptomatic Huntington 's disease patients showed a marked reduction of FDG and RACLO uptake in the caudate nucleus and putamen and a significant increase of BCR. Asymptomatic mutation carriers revealed significant hypometabolism in the caudate nucleus and putamen. The RACLO binding was significantly decreased in the putamen. Decrements of caudate nucleus tracer uptake, particularly RACLO, correlated significantly with BCR increases in both symptomatic and asymptomatic gene carriers. In asymptomatic carriers, metabolic and receptor binding decreases were also significantly associated with the CAG repeat number but not with the individual's age. Discriminant function analysis correctly classified clinical and genetic status in 24 of 27 subjects on the basis of their striatal PET values (83% sensitivity and 100% specificity). Three asymptomatic mutation carriers were classified/grouped together with mutation-negative subjects, indicating that these individuals had normal striatal RACLO and FDG uptake. Follow-up PET data from gene-positive subjects showed a significant reduction in the mean striatal RACLO binding of 6.3% per year. Striatal glucose metabolism revealed an overall non significant 2.3% decrease per year. These data indicate that asymptomatic Huntington's disease mutation carriers may show normal neuronal function for a long period of life. These findings also suggest that it may be possible to predict when an asymptomatic gene carrier will develop clinical symptoms from serial PET measurements of striatal function.

A new correlation-based fuzzy logic clustering algorithm for fMRI

Abstract: Fuzzy logic clustering algorithms are a new class of processing strategies for functional MRI (fMRI). In this study, the ability of such methods to detect brain activation on application of a stimulus task is demonstrated. An optimization of the selected algorithm with regard to different parameters is proposed. These parameters include (a) those defining the pre-processing procedure of the data set; (b) the definition of the distance between two time courses, considered as p-dimensional vectors, where p is the number of sequential images in the fMRI data set; and (c) the number of clusters to be considered. Based on the assumption that such a clustering algorithm should cluster the pixel time courses according to their similarity and not their proximity (in terms of distance), cross-correlation-based distances are defined. A clear mathematical description of the algorithm is proposed, and its convergence is proven when similarity measures are used instead of conventional Euclidean distance. The differences between the membership function given by the algorithm and the probability are clearly exposed. The algorithm was tested on artificial data sets, as well as on data sets from six volunteers undergoing stimulation of the primary visual cortex. The fMRI maps provided by the fuzzy logic algorithm are compared to those achieved by the well established cross-correlation technique.

T2 relaxation time in patients with Parkinson's disease

Abstract: Postmortem studies of patients with Parkinson's disease (PD) reveal an increase in iron concentration in the substantia nigra. Iron content in the brain is associated with decreased signal intensity on T2-weighted MRI. We measured in vivo the T2 relaxation time in 30 PD patients and 33 healthy volunteer subjects, using a 1.5-T whole-body MRI system. In comparison with healthy controls, T2 values in PD patients were reduced in the following brain regions: substantia nigra, caudate nucleus, and putamen. Due to the overlap between patients and control subjects, we could not differentiate, in a given patient, healthy from diseased state on the basis of T2 relaxation time. Our findings support the notion of increased iron deposition in the substantia nigra of patients with PD. However, the shortening of T2 values in the substantia nigra did not correlate with disease duration nor with clinical severity.

Sensitivity-encoded spectroscopic imaging.

Abstract: Sensitivity encoding (SENSE) offers a new, highly effective approach to reducing the acquisition time in spectroscopic imaging (SI). In contrast to conventional fast SI techniques, which accelerate k-space sampling, this method permits reducing the number of phase encoding steps in each phase encoding dimension of conventional SI. Using a coil array for data acquisition, the missing encoding information is recovered exploiting knowledge of the distinct spatial sensitivities of the individual coil elements. In this work, SENSE is applied to 2D spectroscopic imaging. Fourfold reduction of scan time is achieved at preserved spectral and spatial resolution, maintaining a reasonable SNR. The basic properties of the proposed method are demonstrated by phantom experiments. The in vivo feasibility of SENSE-SI is verified by metabolic imaging of N-acetylaspartate, creatine, and choline in the human brain. These results are compared to conventional SI, with special attention to the spatial response and the SNR.

True myocardial motion tracking.

Abstract: Myocardial tagging is a powerful tool for the assessment of in-plane cardiac motion. However, for previous myocardial tagging techniques, the imaged slice is fixed with respect to the magnet coordinate system. Thus, images acquired at different heart phases do not always represent the same slice of the myocardium. A new myocardial tagging technique is presented, which takes the through-plane motion into consideration. It involves tagging of the desired myocardial slice and applying a subtraction imaging technique to image just that part of the myocardium. The examination time can be reduced considerably by the acquisition of two one-dimensionally tagged images. To increase the signal-to-noise ratio especially at later heart phases, variable imaging RF excitation flip angles are applied. To reduce motion artifacts a repetitive breathhold scheme was applied. in vivo results demonstrate that the tags can be accurately tracked within the entire heart period with a temporal resolution of 35 ms, even at a top basal level of the heart and right ventricle.

Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging

Abstract: The brain is a singular organ of unique biological complexity that serves as the command center for cognitive and motor function. As such, this specialized system also possesses a unique chemical composition and reactivity at the molecular level. In this regard, two vital distinguishing features of the brain are its requirements for the highest concentrations of metal ions in the body and the highest per-weight consumption of body oxygen. In humans, the brain accounts for only 2% of total body mass but consumes 20% of the oxygen that is taken in through respiration. As a consequence of high oxygen demand and cell complexity, distinctly high metal levels pervade all regions of the brain and central nervous system. Structural roles for metal ions in the brain and the body include the stabilization of biomolecules in static (e.g., Mg2+ for nucleic acid folds, Zn2+ in zinc-finger transcription factors) or dynamic (e.g., Na+ and K+ in ion channels, Ca2+ in neuronal cell signaling) modes, and catalytic roles for brain metal ions are also numerous and often of special demand.

Genetic Dissection of Complex Traits

Abstract: Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Geneticists have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits—describing the methods, limitations, and recent applications to biological problems.

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

Abstract: Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.