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Title: Developing a spectroscopic technique for assessing liver health
Author: Ember, Katherine Joanna Irene
ISNI:       0000 0004 8509 3743
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2020
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As our largest internal organ, the liver is responsible for the breakdown of toxic compounds, synthesis of multiple hormones and also plays a vital role in metabolism. However, liver disease is the only major cause of death in the UK that is increasing annually, and it remains a worldwide problem. It is clear that novel methods of diagnosis are required; symptoms are fairly generic, whilst blood tests may show liver function to be normal even after significant damage has occurred. The bile duct cancer cholangiocarcinoma has a dismal survival rate - only 5% of individuals survive 5 years post-diagnosis. This partly due to the lack of spatial resolution and chemical specificity in conventional imaging techniques leading to a late stage of diagnosis. Moreover, in 2013, approximately 25,000 liver transplants were carried out worldwide and yet surgeons lack a quantitative means of determining whether a liver is suitable for transplantation or not. Here, I present my work towards a non-invasive, label-free method for assessing liver health with molecular specificity. To establish whether spectroscopy can be used to detect liver damage, I investigated a porcine model of donation after circulatory death. After the heart ceases contracting, the liver is subject to a period of warm ischemia, when there is no circulation and oxygen delivery to the organs. The liver can be reperfused at body temperature using a machine through normothermic regional perfusion (NRP). In this thesis, I obtained in vivo spectral data using a 785 nm handheld Raman spectrometer prior to death, after 45 mins of warm ischemia and after 2 hours of NRP. I observed significant spectral changes over the time course. Furthermore, I took liver and bile duct biopsies before and after ischemia for analysis using Raman microspectroscopy, stimulated Raman scattering (SRS), nuclear magnetic resonance spectroscopy (NMR) and immunostaining. By applying these techniques to serial tissue sections, I have been able to detect morphological and biomolecular variations in samples. These results strongly suggest that removing 10% of the circulating volume of blood reduces liver congestion. Moreover, my experimental findings using a multiphoton microscope suggest that there are differences in the autofluorescence properties of non-tumour and tumour tissue in biopsies obtained from patients with the bile duct cancer cholangiocarcinoma. Initial results suggest there are also differences between the Raman profiles of the tumour and non-tumour tissue. In summary, the results in this thesis could inform the development of a device incorporating autofluorescence and Raman spectroscopy for assessment of liver health. Such a technique could be used to detect liver damage including congestion and cholangiocarcinoma.
Supervisor: Forbes, Stuart ; Campbell, Colin ; Faulds, Karen Sponsor: Engineering and Physical Sciences Research Council (EPSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Raman spectroscopy ; spectroscopy ; liver ; transplantation ; NMR ; biomedical imaging ; DCD ; ischemia