The use of fluorophores for intraoperative tumour detection in breast cancer
File(s)
Author(s)
Kedrzycki, Martha
Type
Thesis
Abstract
Breast conserving surgery (BCS) is the crux of treatment for early-stage breast cancer. In BCS, the tumour is resected with a rim of healthy tissue. However, this operation comes with the risk of positive margins, necessitating re-operation to prevent recurrence. Many technologies have been developed to address this issue including localisation, margin assessment, as well as imaging techniques. However, although these decrease the positive margin rate, they do not eliminate it. This thesis explores fluorescence guided surgery as a solution.
In fluorescence guided surgery, the fluorescent properties- often mediated by contrast agents- are used to highlight the tissue of interest. Typically, this uses specific wavelengths of light to activate fluorescent agents, acquiring images in the near-infrared spectrum alongside colour images, followed by software processing, and display of the cancer/healthy tissue border using an overlay on the colour image. It provides a macroscopic view of where the tumour is, its size, and its invasiveness without impeding the view of the surgical field.
The focus of this thesis is to identify breast cancer using fluorescent guidance. Two pilot trials of the GLOW camera system were performed (in-vitro and in-vivo) to iteratively develop the prototype to incorporate it into surgical workflow. Afterwards, two feasibility trials were performed. The first used indocyanine green (ICG) administered at different timings to assess the vascular structure and permeability of the tumour. The second used aminolevulinic acid (ALA), which targets breast cancer cells via metabolic derangements.
The novelty of this work is that the trial with ICG compares the two different timings. ALA had not been assessed in-vivo previously, and thus the efficacy of a novel fluorescent agent in BCS was explored. Both trials included intraoperative and histopathological imaging, processed in a novel manner using pixel-based processing and texture metrics.
In fluorescence guided surgery, the fluorescent properties- often mediated by contrast agents- are used to highlight the tissue of interest. Typically, this uses specific wavelengths of light to activate fluorescent agents, acquiring images in the near-infrared spectrum alongside colour images, followed by software processing, and display of the cancer/healthy tissue border using an overlay on the colour image. It provides a macroscopic view of where the tumour is, its size, and its invasiveness without impeding the view of the surgical field.
The focus of this thesis is to identify breast cancer using fluorescent guidance. Two pilot trials of the GLOW camera system were performed (in-vitro and in-vivo) to iteratively develop the prototype to incorporate it into surgical workflow. Afterwards, two feasibility trials were performed. The first used indocyanine green (ICG) administered at different timings to assess the vascular structure and permeability of the tumour. The second used aminolevulinic acid (ALA), which targets breast cancer cells via metabolic derangements.
The novelty of this work is that the trial with ICG compares the two different timings. ALA had not been assessed in-vivo previously, and thus the efficacy of a novel fluorescent agent in BCS was explored. Both trials included intraoperative and histopathological imaging, processed in a novel manner using pixel-based processing and texture metrics.
Version
Open Access
Date Issued
2023-08-13
Date Awarded
01/07/2024
License URL
Advisor
Elson, Leff, Daniel Daniel
Sponsor
Imperial College London
Grant Number
PS3495_WSSS
PSH150_WSSS
PSZ087NQHAM
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)