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Title: Lactate and lipid composition in breast cancer via specialist magnetic resonance spectroscopy
Author: Cheung, Sai Man
ISNI:       0000 0004 9353 7199
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2018
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Breast cancer is the most frequent female malignancy in the world and the leading cause of death for women 30 – 59 years of age in the UK. With the advancement of targeted therapies, the prognosis for breast cancer is improving. Personalised medicine, with proactive monitoring of treatment efficacy and preventive measures, is crucial to further enhancement of patient care. Aerobic glycolysis (AG) and deregulated lipid metabolism are the central tumour metabolic processes in breast cancer. Lactate concentration and lipid composition, as biomarkers of AG and lipid metabolism respectively, are altered as a result of tumour initiation and progression. We aim to examine and validate the potential of novel magnetic resonance spectroscopy (MRS) biomarkers with histological markers in whole human breast tumour for personalised medicine. We conducted a cross sectional study in 30 female patients with invasive ductal carcinoma. Specialist MRS methods were performed on freshly excised whole breast tumour to derive lactate, lipid composition and polyunsaturated fatty acids (PUFA). Double quantum filtered (DQF) MRS retained lactate and PUFA while effectively removing non-targeted lipids. DQF-correlation spectroscopy (COSY) collected detailed 2D spectral lipid composition map with focused peak pattern free from water contamination. DQF MRS provided lactate concentration measurement sensitive to tumour grades, providing the first sensitive lactate assessment approaches feasible for non-invasive patient application. DQF-COSY was sensitive to deregulated lipid composition induced by lymphovascular invasion, a major prognostic indicator difficult to confirm at biopsy stage, supporting objective prognosis evaluation in chemotherapy before surgery and for recurrence surveillance. DQF MRS for PUFA illustrated the relationship between PUFA and serotonin critical in inflammation and linked to poor prognostic outcomes. This PhD work identified and validated biomarkers central in breast cancer metabolism, providing a pivotal cornerstone for clinical translation of specialist MRS methods to facilitate future personalised patient care.
Supervisor: He, Jiabao ; Lurie, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Breast ; Magnetic Resonance Spectroscopy ; Lactates ; Lipids