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Non-invasive cytometry of tumours using diffusion MRI, measuring water exchange across the cell membrane with Diffusion Exchange Spectroscopy (DEXSY)

Breen-Norris, James Olav; (2019) Non-invasive cytometry of tumours using diffusion MRI, measuring water exchange across the cell membrane with Diffusion Exchange Spectroscopy (DEXSY). Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

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.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Non-invasive cytometry of tumours using diffusion MRI, measuring water exchange across the cell membrane with Diffusion Exchange Spectroscopy (DEXSY)
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10072922
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