A viable isolated tissue system : a tool for detailed MR measurements and controlled perturbations in physiologically stable tissue

The research presented in this thesis revolves around developing, testing and applications of a tool for the development and assessment of diffusion weighted MRI and methods. The tool is a viable isolated tissue (VIT) maintenance chamber. The chamber was designed to maintain a section of rat optic n...

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Bibliographic Details
Main Author: Richardson, Simon
Other Authors: Alexander, Daniel ; Lythgoe, Mark ; Siow, Bernard
Published: University College London (University of London) 2014
Subjects:
610
Online Access:https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.626554
Description
Summary:The research presented in this thesis revolves around developing, testing and applications of a tool for the development and assessment of diffusion weighted MRI and methods. The tool is a viable isolated tissue (VIT) maintenance chamber. The chamber was designed to maintain a section of rat optic nerve white matter in a stable state, as close to in vivo conditions as possible, while removing all of the confounding problems of imaging such tissue in a live animal. The chamber was designed to fit into a small volume coil in a high field horizontal bore MRI scanner and to enable extended periods of in depth, detailed experimentation. Additive layer manufacturing was used to construct the chamber. A series of validation experiments were conducted to demonstrate the performance of the chamber and the stability of optic nerves maintained within it. Fixed samples have been used extensively in diffusion MRI (dMRI) studies. However, fixation causes significant structural changes in tissue. The chamber was used to evaluate fixed white matter as a surrogate for viable white matter during development and validation of dMRI methods. Diffusion tensors and multi-compartment white matter signal models were fit to the data. The data demonstrated that fixed tissue, while maintaining the broad water environment of viable tissue, differs significantly in diffusion parameters. The chamber was further developed to enable in MRI electrophysiological stimulation and recording from the rat optic nerve. This EP-MRI chamber was designed to enable investigation of the existence of a dMRI measurable structural change in the tissue upon electrical activation. The functional diffusion MRI (dfMRI) signal could be more specific to in vivo functional activation that the gold-standard fMRI method which measures blood oxygenation levels to produce contrast. Preliminary data suggests that a purely structural dfMRI effect, though marginal, may be present in this simplified system.