Programme leader: Prof. dr. M.A. van Buchem
In our research program we study specific diseases of the central nervous system using state-of-the-art imaging technology, with an emphasis on MRI. We have organized our research in themes that are primarily based on diseases and themes with primarily a methodological focus. For each theme a principal investigator is responsible. Due to the interdisciplinary nature of modern neuroimaging research, our group hosts experts with various backgrounds, such as medicine, physics, chemistry, biology, biomedical sciences, and neuropsychology. Within the department of Radiology, there are close interactions with researchers from the Cardiovascular Imaging Research Group in order to exploit the interactions between the heart and systemic vasculature on the one hand, and the brain on the other.
Aim and focus Biomedical themes
The aging brain and neurodegenerative disorders (Van Buchem, Van der Grond, Van Osch, Rombouts, Van der Weerd)
Focus-1: the brain in old age and dementia. The first aim is to increase our understanding of the processes that are responsible for age-related decline and dementia. For this aim, characterization of the structural and functional changes that occur in the aging brain serves as a starting point for disentangling the causes and functional consequences of these changes. We are particularly interested in the contribution of diseases of the heart and blood vessels to age-related brain changes. Focus-2: specific neurodegenerative diseases: Alzheimer’s disease, cerebral amyloid angiopathy, Parkinson’s disease and Huntington’s disease. The second aim is to develop imaging markers that allow for early and specific diagnosis of diseases underlying decline in neuropsychiatric function in the elderly.
Neuroimaging in metabolic disorders. (Van der Grond)
This theme is centered around the common denominator obesity. It includes studies on functional and structural brain changes in persons with the metabolic syndrome, type II diabetes or severe overweight. General theme is to unravel the metabolic pathway between fat storage, eating behavior and functional and structural brain changes. Studies include measures of metabolic function and organ cirrhosis and its association to brain changes.
The brain in systemic inflammatory diseases (Van Buchem, Ronen)
The aim of this theme is to assess the presence, causes, and consequences of brain changes in systemic inflammatory disorders. Initially, we focus on brain involvement in patients with systemic lupus erythematosus (SLE), but we have also explored brain involvement in other autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, and inflammatory bowel diseases. The methodological focus of this theme is MRI, with an emphasis on quantitative MRI.
Neuroimaging of primary headaches (Kruit)
The aim is to increase our knowledge of the mechanisms behind important headache disorders, such as migraine and cluster headache. Focus is on changes in the human brain that may be considered as consequences of headache attacks. Also, we study brain changes before, during and after headache attacks that reveal how, why and when headache attacks occur. For both directions of research, we evaluate changes in function, perfusion, biochemical composition and anatomical structure of the brains of headache
Stroke (Van Walderveen)
Focus: ischemic and hemorrhagic stroke. The aim in ischemic stroke is to identify radiological parameters that have predictive value for clinical outcome and thus improve patient selection for recanalization therapies, within and outside currently used time-windows, based on imaging criteria. For this aim we use whole brain CT perfusion, dynamic CTA, and permeability measurements. For hemorrhagic stroke, the aim is to increase our knowledge on the pathophysiological mechanisms behind primary intracerebral hemorrhage and to characterize underlying vessel disease. We apply MRI (3T, 7T) and CTA.
Imaging in neuromuscular disease (Kan)
Focus: imaging the brain and skeletal muscle in neuromuscular disorders (e.g. Duchenne and Becker muscular dystrophy). Imaging of the brain in Duchenne aims to understand more of the pathophysiology of the cognitive impairment and behavioral problems that occur in addition to the skeletal muscle problems in this disease. In skeletal muscle, we aim to assess disease progression and response to therapy using quantitative MRI and MRS.
Aim and focus Methodological themes
Ultra-high field MRI (Webb, Ronen, Kan, Van Osch)
Aim: to exploit the advantages of the 7T whole-body MRI system for brain imaging. We have a special focus on high-resolution imaging (cerebral cortex, eye, auditory labyrinth) and on the detection of cerebral iron deposition in neurodegenerative diseases.
Cerebrovascular imaging (Van Osch)
Focus: development, implementation, validation and application of MRI and CT perfusion imaging methodology, as well as advanced hemodynamic measures, such as oxygen extraction fraction, cerebrovascular reactivity and arteriolar vessel wall condition. Emphasis is on the clinical acceptance and technical advancement of arterial spin labeling MRI, which is the only truly non-invasive perfusion imaging method.
Functional brain imaging (Rombouts)
Focus: development and application of FMRI to study brain function, in patient groups and controls. Most research involves the so-called ‘resting state’ FMRI technique, used to study large-scale interactions between brain regions without the application of an externally controlled task. These interactions in the brain are organized in resting state networks (RSNs). In our group, RSNs are usually studied in combination with MRI techniques measuring brain anatomy (gray matter volumes), anatomical connectivity, and perfusion. With so-called machine learning techniques, we aim to predict early neurodegeneration in individuals by combining these modalities. In collaboration with the Center for Human Drug Research (CHDR) and the Department of Anesthesiology of the LUMC, we perform pharmacological FMRI techniques to study pharmacologically induced changes in brain function.
Brain tissue characterization (Ronen)
Focus-1: develop a set of robust MR-based tools for compartment-specific investigation of neural tissue using diffusion-weighted MRS. The aim is to provide sensitive and specific biomarkers for tissue damage in neurological disorders such as multiple sclerosis, schizophrenia, stroke, ALS and others. Diffusion MRS specifically probes the motility properties of brain metabolites. Focus-2: develop a set of sensitive and specific quantitative MRI methods for the characterization and quantification of brain tissue damage in neuropsychiatric systemic lupus erythematosus (NPSLE), where the main challenges are to provide a better MRI-based diagnosis for NPSLE, including the distinction between neuroinflammation and ischemia. Focus-3: develop MR methods that directly visualize myelin content. We aim to achieve this using Ultra Short Echo Time (UTE) MRI, a method that can visualize the distribution of hydrogen-containing macromolecules. Focus-4: devise a multimodal-microstructural diagnostic tool for dementia.
Molecular and pre-clinical imaging (Van der Weerd)
Aim: to develop and validate new molecular and conventional imaging techniques to study neurodegenerative and cardiovascular diseases. Our research consists of two lines. Firstly, we focus on the development and validation of targeted contrast agents for detection of (early) biomarkers of pathology using MRI, PET/SPECT or optical imaging. Specific examples of such methods are camelid heavy chain antibody fragments for diagnostic and therapeutic targeting of amyloid, and native susceptibility-weighted MRI contrast to detect iron and myelin alteration during neurodegeneration. Secondly, we study animal models for pathologies such as Alzheimer's disease, migraine and atherosclerosis to improve our understanding of the disease process.
Imaging genetics (Lelieveldt)
Focus: develop methods to integrate and analyze high-dimensional genetic, proteomic and imaging data across different levels and scales to produce new insights about structural and functional organization of the brain. Our aim is to discover associations between neuroanatomical and neurophysiological observations and the underlying molecular mechanisms in healthy and diseased brains. We use a computational approach to cross-link heterogeneous multimodal neuroimaging data and high-throughput "omics" data.
Position in international context
Based on the acquisition of major research grants, the Neuroimaging Research Group has grown steadily over the past few years. Currently, the group is thriving, hosting an international group of highly qualified, well connected, and proliferative researchers. This group comprises on the one hand clinical researchers and on the other hand researchers with primarily a technological focus. The close interaction between these two breeds of researchers is unique and gives rise to a proliferative research program that is internationally acknowledged. Our group is internationally known for its research on aging/dementia, cerebral lupus (NPSLE), Duchenne and Becker muscular dystrophy, and migraine on the one hand, and it is recognized as a center of expertise on advanced neuro-MRI in general and ultra-high field MRI in particular, as well as on the topic of imaging genetics. As such, our group attracts talent on a national and international level and it has proven to have a strong earning power, both for national as well as for international grants. Our group is involved in multiple national and international collaborations.
Local and national embedding
- Our program fits in several of the research themes of the LUMC: “Ageing”, “Translational Neuroscience”, “Vascular Medicine”, and “Biomedical Imaging”.
- Our program fits in several of the 11 research profile areas of Leiden University: “Brain function and dysfunction over the lifespan” (Rombouts and (until recently) van Buchem are leaders of this theme), “Bioscience”, “Vascular and Regenerative Medicine”, “Health, prevention and the human life cycle”, the Neurological Motor Disorders (NMD 30703) program of the LUMC, which is integrated in the Leiden Centre for Translational Neuroscience (LCTN), the Neurological Motor Disorders (NMD 30703) program of the LUMC, which is integrated in the Leiden Centre for Translational Neuroscience (LCTN).
- The Neuroimaging Research Group is a vital component of the Leiden Institute for Brain and Cognition (LIBC), a collaboration between the LUMC and the faculties of Social Sciences, Science, and Humanities of Leiden University. Rombouts is director of the LIBC, and van Buchem was until recently chairman of the board of the LIBC.
- Our group is actively involved in the Medical Delta, an alliance between the universities of Leiden, Delft, and Rotterdam aimed on developing novel techniques for healthcare. Van Buchem is clinical director of the Medical Delta Imaging Institute.
- High-field MRI research is performed in close collaboration with researchers in Utrecht, Nijmegen, and Essen (Germany) in the Virtual Institute for Seven Tesla Applications (VISTA). Close ties also exist with the newly formed UHF-MRI group of the Spinoza Center (Amsterdam).
- On a technological level, our group closely collaborates with Philips Healthcare as a Philips luminary site for development, application, and validation of new techniques and clinical paradigms for diseases of the nervous system.
- Our group is member of the Duchenne Centrum Nederland and we are NFU expertise center for Duchenne, Becker, and facioscapulohumeral muscular dystrophy.