Brain Imaging
Program Committee
Adriaan Lammertsma (program leader)
Dick Veltman (program leader)
Frederik Barkhof
Eco de Geus
Kees Stam
Ruud Verdaasdonk
Rationale
Modern neuroscience increasingly depends on advanced, state-of-the-art brain imaging techniques to characterize brain function and morphology in healthy subjects and in patients with neurological and psychiatric disorders. In addition, brain imaging is increasingly being used in animal models of disease. The VU/VUmc is unique in that it is the only academic centre in the Netherlands that houses all major imaging technologies, i.e. (a) positron/single photon emission tomography (PET/SPECT, (b) magnetic resonance imaging (MRI), including a 3 Testla functional MRI (fMRI) and MR spectroscopy (MRS), (c) magneto-encephalography (MEG) and EEG, including MRI-compatible EEG, (d) repetitive transcranial magnetic stimulation (rTMS), (e) optical imaging. Since state of the art applied research requires similarly advanced methodological expertise, the Brain Imaging program encompasses all methodological developments needed for pursuing advanced research goals in applied (clinical and preclinical) projects.
Functional Connectivity and Structural Imaging
Connectivity in the brain exists at several levels: neuroanatomical, functional, and effective connectivity. Functional connectivity has been defined as the temporal relation between spatially remote neural events, whereas effective connectivity refers to the causal influence one neural system exerts – directly or indirectly – over another. Connectivity has become one of the most influential concepts in modern neuroscience, in view of the shift from functional segregation to functional integration. In particular, it has become clear that connectivity analyses from both activation paradigms and resting state studies may provide important insights into neural dysfunction in various neuropsychiatric disorders, such as Alzheimer’s disease. The boundary between neuroanatomical and functional connectivity is considered to be fuzzy as formation and elimination of connections is to a considerable extent driven by functional demands. Characterizing brain morphology, for example for endophenotyping purposes, can be performed using shape analysis or tissue typing with the help of quantitative MR techniques. For example, shape analysis may consist of gray matter density mapping in standard space (e.g. voxel-based morphometry or cortical thickness mapping), or be determined from serial imaging, e.g. to determine the rate of atrophy using registration/subtraction or deformation field mapping. Tissue typing using quantitative MR techniques can employ a variety of techniques, such as T1-relaxation time mapping, magnetization transfer imaging or diffusion tensor imaging (DTI). Quantitative MR maps can be analyzed voxel-wise, or subjected to data-reduction steps such as histogram analysis. As part of the validation of MR techniques we collaborate with the Dutch brain-bank using post-mortem imaging to establish imaging-pathology relationships.
Molecular Imaging
Molecular imaging refers to imaging and measuring molecular pathways and interactions in vivo. Historically, molecular imaging is the domain of nuclear techniques, although more recently MRI-techniques, such as MRS and pharmacological MRI, and optical imaging, the latter primarily in animal models of disease, are emerging. Within the field of medical technology, molecular imaging is the fastest growing technique, with great opportunities for basic (pathophysiological) research, drug development, developing new non-invasive diagnostic procedures, and individualised treatment. At the VU/VUmc, at present molecular imaging is performed using both PET and MRI. PET has superior selectivity and sensitivity (pico- to nanomolar range), whilst MRI has unrivalled spatial resolution. Apart from its use in various clinical (research) applications, there is a strong methodological component to molecular imaging, which is related to developing procedures for an ever-increasing number of molecular targets and for developing analytical methods with improved quantitative accuracy. An important aspect of molecular imaging is that it has the potential to be more than just an imaging technique. As mentioned above, it is primarily a non-invasive in vivo method for performing regional tissue measurements on a variety of molecular targets, pathways and interactions.
Imaging Analysis
under construction
Executive Summary
The aims of the Brain Imaging methodology program are twofold. First, to make optimal use of the extensive imaging facilities present at the VU, including integrating these techniques with each other, the program instigates and performs methodological imaging research, in particular with regard to functional and structural connectivity, and molecular imaging. Second, the program aims to function as a centre of expertise, to provide advice and if necessary assistance for scientists from other programmes. The expertise in the field of imaging analysis is a stronghold of the VUmc, and will receive more attention in the near future.
Future Perspectives
Brain imaging methodology is a rapidly evolving field, and imaging technology at the VU campus provides clinicians and neuroscientists with a unique set of tools for non-invasive, in vivo investigations of the brain, both in humans and in animal models. Neuro-imaging is likely to be employed not only for characterizing the neural substrate of various neuropsychiatric disorders, but also for assessment of psychopathological traits cutting across diagnostic categories, and identification of endophenotypes which may aid in understanding the genetic basis of these disorders.
