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E-Thesis 640 views 81 downloads

Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine / Cerys A. Jenkins

DOI (Published version): 10.23889/Suthesis.50585

Abstract

The development of healthcare technologies to streamline patient referral systems and diagnose the early onset of disease is of great importance for improving cancer survival and is the basis of this work. This thesis details the development of Ra-man spectroscopy as a triage tool for urgent suspect...

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Published: 2019
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa50585
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first_indexed 2019-06-05T11:07:53Z
last_indexed 2023-01-11T14:27:04Z
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spelling 2022-09-27T16:27:24.0372150 v2 50585 2019-05-31 Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine 2019-05-31 The development of healthcare technologies to streamline patient referral systems and diagnose the early onset of disease is of great importance for improving cancer survival and is the basis of this work. This thesis details the development of Ra-man spectroscopy as a triage tool for urgent suspected colorectal cancer referrals. In this work the development of high-throughput, cost effective standardised plat-forms for the analysis of biofluids with Raman spectroscopy has been shown. The platforms developed allow the analysis of both dry and liquid biofluid samples.The optimal liquid biopsy for colorectal cancer applications was found to be serum due to its ability to be stored and transported without the formation of pre-cipitates within the samples. Serum samples were then used to optimise dry and liquid HT-platforms for reproducible spectral collection. Principal component analysis (PCA) was used to investigate and optimise inter-user measurements to ensure a robust measurement platform. PCA analysis showed that patient fast-ing status and sex could have potential effects on spectral reproducibility and diagnostic capability.The liquid HT platform developed had less sensitivity for colorectal cancer detection than a dry platform. However, it showed lower inter-user spectral vari-ations and the overall analysis time for each sample was faster. It was also less susceptible to freeze-thaw sampling effects in terms of diagnostic capability. This made it the method of choice when considering a translatable technology. The limits of the liquid HT platform were investigated with random forest based ma-chine learning to develop diagnostic models for serum spectra. It was established that the technique could be used for the detection of precursor cancer lesions when tested against healthy control patients with a positive predictive value (PPV) of 40.00% and a negative predictive value (NPV) of 88.89%. The technique could also detect CRC in a large cohort of test patients against healthy controls with a NPV of 94.44%. This approaches the NPV of approximately 98% for the gold standard diagnostic test (colonoscopy) for colorectal cancer. The thesis concludes by discussing the clinical translation of the technique as an effective diagnostic based upon the results presented. E-Thesis Raman spectroscopy, early diagnosis, colorectal cancer 31 12 2019 2019-12-31 10.23889/Suthesis.50585 A selection of third party content is redacted or is partially redacted from this thesis. COLLEGE NANME COLLEGE CODE Swansea University Doctoral Ph.D Cancer Research Wales (CRW) 2022-09-27T16:27:24.0372150 2019-05-31T10:58:48.3545708 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Cerys A. Jenkins 1 0050585-31052019120758.pdf Jenkins_Cerys_A_PhD_Thesis_Final_Redacted.pdf 2019-05-31T12:07:58.8630000 Output 106279390 application/pdf Redacted version - open access true 2022-05-22T00:00:00.0000000 true
title Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine
spellingShingle Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine
,
title_short Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine
title_full Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine
title_fullStr Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine
title_full_unstemmed Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine
title_sort Raman Spectroscopy and Colorectal Cancer: Towards early diagnosis and personalised medicine
author ,
author2 Cerys A. Jenkins
format E-Thesis
publishDate 2019
institution Swansea University
doi_str_mv 10.23889/Suthesis.50585
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description The development of healthcare technologies to streamline patient referral systems and diagnose the early onset of disease is of great importance for improving cancer survival and is the basis of this work. This thesis details the development of Ra-man spectroscopy as a triage tool for urgent suspected colorectal cancer referrals. In this work the development of high-throughput, cost effective standardised plat-forms for the analysis of biofluids with Raman spectroscopy has been shown. The platforms developed allow the analysis of both dry and liquid biofluid samples.The optimal liquid biopsy for colorectal cancer applications was found to be serum due to its ability to be stored and transported without the formation of pre-cipitates within the samples. Serum samples were then used to optimise dry and liquid HT-platforms for reproducible spectral collection. Principal component analysis (PCA) was used to investigate and optimise inter-user measurements to ensure a robust measurement platform. PCA analysis showed that patient fast-ing status and sex could have potential effects on spectral reproducibility and diagnostic capability.The liquid HT platform developed had less sensitivity for colorectal cancer detection than a dry platform. However, it showed lower inter-user spectral vari-ations and the overall analysis time for each sample was faster. It was also less susceptible to freeze-thaw sampling effects in terms of diagnostic capability. This made it the method of choice when considering a translatable technology. The limits of the liquid HT platform were investigated with random forest based ma-chine learning to develop diagnostic models for serum spectra. It was established that the technique could be used for the detection of precursor cancer lesions when tested against healthy control patients with a positive predictive value (PPV) of 40.00% and a negative predictive value (NPV) of 88.89%. The technique could also detect CRC in a large cohort of test patients against healthy controls with a NPV of 94.44%. This approaches the NPV of approximately 98% for the gold standard diagnostic test (colonoscopy) for colorectal cancer. The thesis concludes by discussing the clinical translation of the technique as an effective diagnostic based upon the results presented.
published_date 2019-12-31T04:02:05Z
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score 11.013148

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