Use this URL to cite or link to this record in EThOS:
Title: Functional MRI studies of cerebral physiology and pharmacology in the rat
Author: Houston, G. C.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
The purpose of the work described in this thesis was to investigate the potential of MRI for the longitudinal study of pharmacological activity within the central nervous system. For these investigations a robust physiological rat preparation, together with optimised imaging hardware, was developed for preclinical functional MRI studies at clinical field strengths of 2 Tesla. Graded asymmetric spin-echo echo planar imaging (ASE-EPI) was used to investigate changes in cerebral blood oxygenation induced by transient hypoxia in the anaesthetised rat. Increments of spin-echo asymmetry produced a linear increase in the sensitivity of data acquisition to the blood oxygenation level changes and revealed a heterogeneous response across four brain regions (the outer and inner neocortex, hippocampus and medial geniculate nucleus). In addition, the graded ASE-EPI protocol provided data pertaining to the vascular components that contributed to the observed signal. Having established optimal ASE-EPI imaging methods, the protocols were adapted to determine if pharmacologically induced metabolic changes were detectable in the anaesthetised rodent. To this end, the effects of two well characterised psychotropic compounds (MK-801 and mCPP) were studied. Time resolved statistical maps of significant signal change (p < 0.001) were produced for each brain slice using a rolling t-test to identify regions of interest for further analysis. The functional MRI signal closely mirrored the spatial pattern of both localised cerebral blood flow and glucose uptake, previously established by empirical autoradiographic methods. This work demonstrates that multiple time points of pharmacological activity can be mapped in a single subject using MR techniques.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available