[Thesis]. Manchester, UK: The University of Manchester; 2017.
It is well established that lipids play an important role in diseases such as non-alcoholic
fatty liver disease and cardiovascular diseases. However, in the past decade, it has
come to light that lipids may be important in other diseases; particularly in cancer
and neurological disorders. Here, lipid metabolism has been investigated using pre-clinical
cancer models for melanoma, glioma, non-small-cell lung cancer and colorectal cancer.
The role of lipids in the recovery post-stroke has also been studied. Mass spectrometry
imaging offers an ideal tool to study lipids in tissue ex-vivo. Lipids ionise well
in a number of mass spectrometry modalities, and hundreds of lipids can be imaged
in one mass spectrometry imaging experiment. Furthermore, mass spectrometry imaging
offers excellent spatial resolution. In this work, both MALDI-MS and DESI-MS have
been used for mass spectrometry imaging.Tumour lipid heterogeneity has been a particular
focus of this this project. Heterogeneity exists within tumours, as well as between
tumours in the same patient; and this causes major problems for therapy. Owing to
the untargeted nature, and high spatial resolution of mass spectrometry imaging, it
is an excellent technique to study lipid heterogeneity. Adjacent sections (or in some
cases the same section used for mass spectrometry imaging), were used for immunofluorescence
and H&E staining. By comparing mass spectrometry images with staining techniques,
biological reasons for lipid heterogeneity can be established. Here, a particular
focus has been on hypoxia (low oxygen tensions), which is a key contributor to tumour
heterogeneity, and is associated with aggressive cancers. Additionally, hypoxia is
a feature of ischaemic stroke, and lipids in ischaemic stroke have also been investigated.
PET is a non-invasive imaging technique which is able to image a radiolabelled molecule
(tracer) in the body. Here, PET has been used as a complementary in-vivo technique
to mass spectrometry imaging. The tracers [11C] acetate and [18F]-FTHA have been used
to image fatty acid synthase and fatty acid uptake in tumours; both of which are hypothesised
to be key in cancer progression. REIMS is a newly established mass spectrometry technique.
It is ideal for analysing lipids in cells, as sample preparation is minimal. Here,
approaches for cell pellet analysis have been tested, and used to detect lipids in
cancer cell lines.