Junior Research Group Bioimaging
| Call for proposals: | 2006 |
| Funding period: | 2007 - 2012 |
| Funding volume: | 20 Mio. EUR |
| Number of projects: | 11 |
1. Objectives of funding
Imaging techniques have become a key technology in modern biomedicine. Increasingly efficient large-scale research equipment and the continuous further and new development of imaging examination methods, inter alia magnetic resonance tomography (MRT) and positron emission tomography (PET), have made a particular contribution to this rapid development.
New clinical areas of application are evolving not only due to improved methods for displaying human organs but also due to the scientific use of functional imaging in the neurosciences. Additionally, imaging techniques are being used increasingly to examine animal models of human diseases and therefore allow a better understanding of fundamental pathophysiological mechanisms and the definition of new therapeutic approaches.
This development has led to a greater need for qualified scientific staff in leading positions. The funding measure “Junior Research Group Bioimaging” is designed to provide support for outstanding young scientists in their scientific careers. By allowing them to conduct independent research at an early stage in their careers the impending shortage of qualified researchers in this area is counteracted and at the same time young scientists are enabled to develop an independent profile as researchers in the field of non-invasive imaging to improve their career prospects.
2. State of the funding measure
In response to the public call 66 proposals were submitted applying for a total volume of about 88 mio €.
The majority of proposals were focused on the area of Neuroscience and the cardiovascular system, and equally covered methodological as well as clinical aspects. In the course of the evaluation of projects by an international and interdisciplinary review board 11 proposals were recommended for funding. Successful projects have been funded since midyear 2007 with a total volume of 11.3 mio € for a five year funding period. Particularly well qualified groups will be given the opportunity to apply for funding for an additional sixth year, and if appropriate, for a further Ph.D. student position.
3. Funded projects
a) Short description of current projects
High field Cholinergic MRI of Cognition in the Primate Brain
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Max-Planck-Institut für biologische Kybernetik |
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The goal of the junior research group is to describe the effects of cholinergic neuromodulation in the primate brain. The spatial distribution of these effects in the brain will be determined using functional magnetic resonance imaging (fMRI). The project consists of three thematic areas: (1) Registration of the BOLD (blood-oxygenation-level-dependent) signal under cholinergic manipulations. (2) Simultaneous EEG-fMRI to reveal neural basis of metabolic activations. (3) Determination of metabolites in the blood during cholinergic manipulations to gain insights into associated biochemical processes. Experiments will employ non-invasive methods, allowing translation to clinical setting. The combination of neurophysiological, metabolic and neurochemical signals acquired non-invasively may refine clinically employed methods for the diagnosis of neurodegenerative cholinergic disorders such as Alzheimer’s disease. In particular, this might allow early diagnosis of such disorders, permitting more effective therapeutic intervention with available medications.
Physiological MR imaging during Thrombolysis
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Ruprecht-Karls-Universität Heidelberg |
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Main goal of the project is to provide new insights to the pathophysiology of stroke during the hyperacute phase. Better understanding of these dynamic processes following embolic occlusion of a cerebral artery may have important implications regarding selection of patients for therapy. Furthermore, monitoring of therapy may have the potential to better estimate dosage and duration of therapy and may help to prevent secondary parenchymal hemorrhage. A second major goal is to better understand focal and global bioeffects of ultrasound in brain tissue and to investigate the potential benefit of ultrasound for thrombolysis. Existing Magnetic-Resonance-Imaging techniques to assess physiological parameters like perfusion, diffusion and oxygen saturation will be improved to achieve a temporally resolved measurement. Markerless optical tracking will be developed to correct for patient motion. Clinical ultrasound imaging will be used simultaneously during the MR examination. This project is an important step towards optimized patient-specific therapy. Long-term goals are, among others, the opening of the blood-brain-barrier using ultrasound under direct control by MRI. This would allow localized drug delivery and gene therapy. Commercialization appears reasonable.
EEG/fMRI signatures of spontaneous brain activity in physiological and pathological conditions
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Johann Wolfgang Goethe-Universität Frankfurt am Main |
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Dynamics of brain activity depend on the brain state and transitions between states, prototypically perturbed by epilepsy and narcolepsy. Close links exist between epileptic and physiological brain activity across different states of vigilance and consciousness evidenced at the neuronal level: e.g. electroencephalogram (EEG) sleep phenomena, like K-complexes and slow oscillations, share common principles in their generation with that of epileptic spike and slow wave activity. The aim of this project is to determin signatures of haemodynamic and electric neuronal activity during different brain states and their transition by EEG recording combined with simultaneous functional magnetic resonance imaging. The interaction of sleep- and seizure-modulating brain regions will be investigated. The project shall lead to a better understanding of epilepsy and sleep disorders and subsequently guide treatment developments. A next step should be the extension to patients with severely impaired consciousness (e.g. coma), their prognosis and related management.
Cardiovascular MRI in Congenital Heart Disease
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Deutsches Herzzentrum Berlin |
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The research project mainly focusses on the development of an MRI technique to determine myocardial contractility; the examination of cardiac structures on a microscopic level to represent cardiac myofibrils and the conduction system, and the implementation of a teleradiologic network for the central analysis of data from clinical and/or scientific MRI examinations. The work plan includes the assessment of the predictive value of pressure-volume relations in a clinical pilot-study; the visualisation of cardiac myofibrils and the conduction system in animal experiments by using high resolution MRI (3.0 Tesla) and the internet based connection of leading national and international institutions in the field of MRI in congenital heart disease to a “competence laboratory” for central MRI data analysis. The utilisation of results derived from the studies includes the determination of the optimal timing for heart-valve replacement; the simplification of electrophysiological examinations and noninvasive early detection of cardiomyopathies and the improvement of quality of quantitative MRI examinations by reduced variability.
Cardiovascular 7D MRI
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Albert-Ludwigs-Universität Freiburg |
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The purpose of this research project is the development of a novel and interdisciplinary strategy for the diagnosis of cardiovascular disease which has the potential to considerably enhance the understanding of the interrelationship of cardiovascular pathologies and associated functional and hemodynamic consequences. A multi-modular Magnetic Resonance Imaging (MRI) approach is proposed offering the opportunity to merge different functional aspects of each anatomical region into a single more complete model of local and global anatomy and function of the left ventricle, aortic valve and thoracic aorta. To achieve these goals, the project focuses on the development of flow and motion sensitive MR imaging strategies with true 3D spatial encoding. Further insights into the effect of specific pathologies or progression of disease such as aortic stenoses are expected from the development of realistic cardiovascular in-vitro model systems suitable for MR compatible simulations of consequences of cardiovascular pathologies or surgical intervention in a controlled environment. The individual assessment of the interrelationship between cardiac, valvular and vascular function has the potential to change patient management with respect to therapeutic interventions, treatment planning and monitoring. Specific emphasis is given to the interrelationship between in-vivo results and realistic in-vitro model systems. The research project will explore new experimental tools to determine the link between derived functional and blood flow parameters and cardiovascular disease.
Neurocomputation und Neuroimaging - Modelling of somatensory information processing
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Charité - Universitätsmedizin Berlin |
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The aim of the project is to develop a neurobiologically informed computational network model for connectivity and function in the human somatosensory system. Initially, a series of fMRI and MEG experiments with an identical tactile stimulus setup but varying cognitive contexts will be performed. Based on these fMRI and MEG data, a neuronal network model grounded in dynamic causal modelling will be developed for the somatosensory system. In a first step, parameters indicating, for example, coupling between different brain areas are determined for each experiment. In a second and entirely novel step, a unified neurobiologically informed computational network model will then be constructed, based on the parameters obtained in the individual experiments, using Bayesian networks on the meta-experimental-level to integrate all data in a formal multiple -constraint manner. The architecture of this network will be extended and confirmed by fMRI and MEG data obtained in patients with specific lesions in the somatosensory system as well as in normal subjects using simultaneous fMRI and repetitive transcranial magnetic stimulation. This network model will allow describing physiological and pathophysiological information processing in the human somatosensory system in a novel hierarchical Bayesian framework.
Coronary Artery Imaging with Computed Tomography
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Friedrich-Alexander-Universität Erlangen-Nürnberg |
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Aims of the project are the development, improvement, and validation of methods for non-invasive visualization of the coronary arteries by computed tomography. The two major areas of work will be (A) “non-invasive coronary angiography” by computed tomography for the detection and quantification of coronary artery stenoses and (B) the detection and analysis of non-stenotic, early coronary atherosclerotic plaque. In both areas of work, the project will incorporate technical development, clinical evaluation and prospective validation. Technical developments include methods for image reconstruction and -analysis, as well as mechanisms and protocols for reduction of radiation exposure. Based on this work, clinical assessment of CT acquisition, reconstruction and evaluation protocols will be performed in defined clinical patient populations. Final prospective work will analyze the prognostic implications of CT coronary visualization in the context of coronary artery disease. Increasing robustness and accuracy of coronary artery visualization, stenosis detection, and plaque analysis by computed tomography will firmly establish CT imaging as a diagnostic tool in the workup of patients with suspected coronary artery disease. It can be expected that CT imaging will be used for less invasive diagnosis as well as early detection and treatment of patients with coronary artery disease and asymptomatic individuals at risk for myocardial infarction.
Patient classification using computational morphometry
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Friedrich-Schiller-Universität Jena |
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Aim of this project is to develop new classification methods of neurological disorders to aid diagnosis using computational morphometry. The idea is to use the distribution of anatomical alterations of the brain in a large training database to classify (and diagnose) a given new subject. Dementia and schizophrenia are two examples for potential applications. People with mild cognitive impairment, a presumed early stage of dementia, often show little or subtle structural changes that would predict clinical progression. Using classification methods would therefore form a basis for estimating the risk of further disease progression or classification into different stages of a continuing neurological condition. Similarly, in schizophrenia structural changes detected are often very subtle. Classification methods could take into account a pattern of structural changes to give a probability for the diagnosis (e.g. in early / prodromal disease stages), or serve to classify these patterns into subgroups to delineate syndromes within a heterogeneous clinical phenotype. This project comprises the development of new MR image processing methods and their clinical application in psychiatric and neurological conditions.
How spontaneous is the brain? Functional connectivity of the brain in rest paves the way for clinical MRI
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Klinikum rechts der Isar |
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Functional magnetic resonance imaging (fMRI) is an essential tool for the characterisation of brain function. Here the investigation of the resting state, meaning the brain at rest but not asleep, is of special interest. Alterations of the resting state under psychiatric pathologies have been described. The analysis of functional connectivity of the resting brain offers for the first time clinical application of fMRI to psychiatric disorders. An essential premise of the clinical introduction of rest-fMRI is the realization of a two-part methodological project. First, the development of a well interacting set of methods for measuring functional connectivity. And second, an integration of other imaging techniques (MRI, PET) to increase sensitivity of pathology detection. Methods will be developed and specified for Alzheimer’s disease, and extended for affective disorders and pain disorders. The long-term goal consists in the introduction of the optimised methods into clinics for early diagnosis.
Influence of drug consumption on the maturation of the adolescent brain
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Technische Universität Dresden |
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Adolescence is a period of growth, exploration and cognitive-affective maturation. During this critical phase of development most adolescents initiate use of alcohol, nicotine or cannabis and a substantial portion of them develops a substance use disorder. The project aims to investigates the consequences of drug use on brain maturation and the course of cognitive affective development in adolescents as well as the neuro-cognitive and genetic risk factors determining the liability to substance use disorders. To address these objectives a longitudinal study in 200 adolescents will be conducted. They will be examined at the age of 14, 16 and 18 using multimodal magnetic resonance imaging (i.e. fMRI, sMRI and DTI) to assess sensitivity to reward and punishment, emotional reactivity, impulse control and conflict-monitoring as well as the maturation of the underlying brain circuits. Drug use has an enormous impact on health and socio-economics. A better understanding of these neuro-developmental processes and the role of genes and drugs are essential for developing improved etiological models for substance use disorders and ultimately to improve therapeutic approaches.
Multimodal functional imaging of auditory awareness and its disorders following focal brain lesions
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Ruprecht-Karls-Universität Heidelberg |
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As there is a limit for information to reach conscious processing, it is often impossible to be aware of and follow multiple auditory streams in ecological environments. This project aims at understanding the neuronal underpinnings of auditory perceptual awareness and its disorders after focal lesions of auditory and supramodal cortex. Normal listeners and patients with focal cerebral lesions will be studied using functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and electroencephalgoraphy (EEG). In a subproject, the interrelations of signals measured in fMRI and MEG will be evaluated, to advance the use of multimodal imaging as a standard tool for cognitive sciences. A long-term goal of the clinical studies, beyond the gain of scientific knowledge, is to establish clinical tests for auditory processing disorders, which could e.g. be used to evaluate new rehabilitation strategies.
b) Neuroimaging: Expired projects