Development of concurrent MRI and Optical Spectroscopy for measurement of neuronal cell biophysical/microstructural changes
Lead Research Organisation:
University of York
Department Name: Chemistry
Abstract
Current models of, and imaging strategies for, neuronal activation are based on the transient electrical and biochemical events associated with the excitation process. However, there is a growing base of evidence supporting, often ignored but extremely important, supplementary biophysical microstructural changes in excited neuronal tissue. Development of imaging techniques to observe these changes in-vivo is of great importance because it would allow a more direct measure of neuronal events, such as membrane expansion. Such imaging strategies offer a more reliable measure of activity with less physiological confounds than methods such as the widely used Blood Oxygenation Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) signal.
One method showing great promise is Diffusion based Magnetic Resonance Imaging (DW-MRI) - an imaging technique sensitive to such microstructural changes in cell structure; with cell membranes and macromolecules acting as microscopic obstacles that hinder the free diffusion of water protons. Observed decreases in the water diffusion coefficient during neuronal activation are presumed to reflect the transient swelling of cortical cells and reduction of the extracellular space, increasing its tortuosity for diffusing molecules. However, the exact origin of the DW-MRI response still remains unsupported and unclear.
This Ph.D project involves the development and implementation of concurrent high field (7 Tesla) DW-MRI and spatial frequency domain optical imaging (SFDI) to investigate the underpinnings of this potentially important MR biomarker of neuronal activity. SFDI is a complementary optical imaging technique which is sensitive to changes in light scattering and absorption coefficients that are induced when the micro-structure of the cell changes (e.g. during neuronal cell swelling). The developed concurrent imaging method will be applied in-vivo on rodents and in models where neurovascular coupling is impaired. We will examine the degree of concordance between the two imaging methods; allowing separation of signal sources due to both the vascular and cell microstructure components. Furthermore, the project will involve the development of tissue models in the analysis of intrinsic optical imaging signals during neuronal activity, based on the 3D functional MRI data; with a view to extracting changes in cytochrome oxidase and relating that to mitochondrial function in health and disease. Data will be used to refine the current biophysical models of cortical layer based neuronal activation and ultimately expedite the use of DW-MRI in clinical measures of brain activity.
One method showing great promise is Diffusion based Magnetic Resonance Imaging (DW-MRI) - an imaging technique sensitive to such microstructural changes in cell structure; with cell membranes and macromolecules acting as microscopic obstacles that hinder the free diffusion of water protons. Observed decreases in the water diffusion coefficient during neuronal activation are presumed to reflect the transient swelling of cortical cells and reduction of the extracellular space, increasing its tortuosity for diffusing molecules. However, the exact origin of the DW-MRI response still remains unsupported and unclear.
This Ph.D project involves the development and implementation of concurrent high field (7 Tesla) DW-MRI and spatial frequency domain optical imaging (SFDI) to investigate the underpinnings of this potentially important MR biomarker of neuronal activity. SFDI is a complementary optical imaging technique which is sensitive to changes in light scattering and absorption coefficients that are induced when the micro-structure of the cell changes (e.g. during neuronal cell swelling). The developed concurrent imaging method will be applied in-vivo on rodents and in models where neurovascular coupling is impaired. We will examine the degree of concordance between the two imaging methods; allowing separation of signal sources due to both the vascular and cell microstructure components. Furthermore, the project will involve the development of tissue models in the analysis of intrinsic optical imaging signals during neuronal activity, based on the 3D functional MRI data; with a view to extracting changes in cytochrome oxidase and relating that to mitochondrial function in health and disease. Data will be used to refine the current biophysical models of cortical layer based neuronal activation and ultimately expedite the use of DW-MRI in clinical measures of brain activity.