AbstractProstate cancer (PCa), the most common cancer in men across the UK, is a multifocal disease with characteristic heterogeneity and foci that can range from low-grade indolent to aggressive disease. In current clinical care, the well-established diagnosis for PCa is trans-rectal ultrasound (TRUS) guided biopsies. The TRUS procedure follows by the Gleason scoring that usually requires the expertise of a trained histopathologist. However, an inter-observer variation exists between two histopathologists besides a large discrepancy existing on initial biopsy and after the final radical prostatectomy. Therefore, a reliable diagnosis is of high demand to make an optimal decision for PCa treatment. This research work aims to apply two emerging optical imaging modalities to quantitatively evaluate the degree of malignancy.
This research thesis presents the vibration optical coherence elastography (OCE) to quantify the tissue stiffness on a microscopic scale. A feasibility study of ten patients suspected with PCa was designed to scan TRUS guided biopsies with the vibration OCE. Meanwhile, the effect of fixatives on the tissue stiffness was studied with five different tissues preserved in the fixatives along a controlled timeline. A subsequent clinical study involving 60 more patients was conducted to follow the feasibility study, which leads to a large clinical study containing a total of 840 core biopsies. Additionally, the second harmonic generation (SHG) microscopy focused on the cells and surrounding matrix within the prostate tissue. The SHG study with 42 core biopsies was intended to investigate the reason of stiffness increase of the cancerous tissue in the prostate.
The experimental results indicates that the vibration OCE is capable to provide 2D and 3D high-resolution elastogram of biopsies with different malignancies. Moreover, a high diagnostic accuracy of differentiating malignant biopsies from benign ones is confirmed, as well as a significant difference in Young’s modulus of biopsies of different Gleason scores. For SHG, distinct patterns of collagen distribution are shown for PCa of different Gleason scores, along with a ratio of anisotropic to isotropic (A: I ratio) that correlates with the disease aggressiveness. To sum up, the two techniques described in this research thesis are complementary, where one depicts the stiffness of prostate tissues and the other illustrates the orientation of collagen structure around the cancerous lesion. With further development, these approaches may help in vivo diagnosis of PCa quantitatively and characterise grade of cancer as well.
|Date of Award||2018|
|Supervisor||Zhihong Huang (Supervisor), David McGloin (Supervisor) & Ghulam Nabi (Supervisor)|