Non-invasive functional neuroimaging methods such as functional magnetic resonance imaging (fMRI) have become indispensable tools for the neurosciences. The underlying principle of the most frequently used methods is the brain’s local, dynamic regulation of blood flow. The correct interpretation of the neuroimaging results requires an in-depth understanding of the structural and functional neurovascular coupling underlying this regulation. Our group combines ex-vivo and in-vivo experiments in the rodent somatosensory cortex to close the gap between structural and functional aspects of the haemodynamic response.
Structural part: Immunohistochemical methods as well as synchrotron-based X-ray computed tomography is applied to study the cerebral microvasculature in the rat and monkey tissue. The aim is to elucidate the relationship between the vascular density and the metabolic demands and to provide exact 3d structural basis for the modeling part. Functional part: State-of-the-art optical methods are used to study the 2d and 3d haemodynamic response topography. Modeling part: In this completely new approach, the structural information will be used as a basis for simulating the cerebral blood flow topology using appropriate models. In an iterative process in which the modeling parameters will be optimized, the simulation results will be compared with the 3d in-vivo response patterns.
Optical imaging of the hemodynamic response in the a-chloralose anesthetized rat. Concurrent multiwavelength spectroscopy, laser speckle imaging and extracellular electrophysiological recording shows the events following a 2 Hz stimulation of a single vibrissa during 4 seconds. A. The tactile stimuli elicit brief increases in spiking activity (multi unit activity, MUA) and synaptic activity (local field potentials, LFP) in the corresponding area of the contralateral somatosensory cortex. B. Absorption spectra of oxyhemoglobin and deoxyhemoglobin. Multiwavelength spectroscopy was performed using 6 wavelengths as indicated with the vertical gray lines (Dunn et al., 2005). C. Spatiotemporal evolution of the cerebral blood flow response as measured with laser speckle imaging. First frame shows vascular pattern of the cortical surface. Maximum of signal change is located over a circumscribed cortical region representing the stimulated vibrissa. D.-F. Same as C but for oxyhemoglobin, deoxyhemoglobin and total hemoglobin concentration. G. Time courses of the relative changes as observed in the center of activation averaged over 10 stimulations (shaded areas show error of the mean).
Calcinaghi, N, Jolivet R, Wyss MT, Gasparini F, Ametamey S, Buck A and Weber B. Metabotropic glutamate receptor mGluR5 is not involved in the early hemodynamic response. Journal of Cerebral Blood Flow and Metabolism 31(9):e1-10, 2011.
Weber B, Spath N, Wyss M, Wild D, Burger C, Stanley R, Buck A. Quantitative cerebral blood flow measurements in the rat using a beta-probe and H2 15O. J Cereb Blood Flow Metab 23(12):1455-60. (2003)
Weber B, Burger C, Wyss MT, von Schulthess GK, Scheffold F, Buck A. Optical imaging of the spatiotemporal dynamics of cerebral blood flow and oxidative metabolism in the rat barrel cortex. Eur J Neurosci 20(10):2664-70. (2004)
Swiss National Science Foundation