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Title: Non-invasive cytometry of tumours using diffusion MRI, measuring water exchange across the cell membrane with Diffusion Exchange Spectroscopy (DEXSY)
Author: Breen-Norris, James Olav
ISNI:       0000 0004 7965 0806
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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The aim of this thesis was to develop a technique to carry out non- invasive cytometry in tumours using diffusion MRI, by measuring water exchange across the cell membrane. My thesis is built on previous work done to charac- terise tumour micro-structure in-vivo, using Vascular Extracellular and Restricted Diffusion for Cytometry in Tumours (VERDICT) MRI by E. Pangiotaki and S. Walker-Samuel et al. [81], and work on Diffusion Exchange Spectroscopy (DEXSY) by Dr Bernard Siow [93] and P. T. Callaghan who first developed DEXSY as a technique for studying porous media [18]. In particular I aimed to develop DEXSY to measure cell membrane permeability. These advanced diffusion MRI techniques could reduce the need for invasive tissue biopsies, enable earlier di- agnosis and better monitoring of disease progression in cancer, through in-vivo characterisation of tissue micro-structure. These advanced diffusion techniques could also be used to gain a better understanding of barriers to drug delivery in mouse models of cancer. I have developed a biological phantom for validating dif- fusion MRI techniques, and used physical phantoms to demonstrate the accuracy of diffusion measurements made with DEXSY. My computational simulations sug- gest that DEXSY can be used to provide a quantitative indicator of cell membrane permeability, as I observe a monotonic relationship between Diffusion Exchange Index (DEI) and permeability in-silico, for a range of permeabilities greater than the physiological range. The DEXSY data acquired from yeast phantoms con- firm that we can observe diffusion exchange in-vitro with this technique. Further work to evaluate the technique in-vivo suggests that DEXSY is sensitive to dif- fusion exchange and tissue micro-structure in tumours. The work in this thesis demonstrates that DEI could be used as a quantitative indicator of cell membrane permeability, and as a potential imaging biomarker in cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available