Joint estimation of relaxation and diffusion tissue parameters for prostate cancer with relaxation-VERDICT MRI

This work presents a biophysical model of diffusion and relaxation MRI for prostate called relaxation vascular, extracellular and restricted diffusion for cytometry in tumours (rVERDICT). The model includes compartment-specific relaxation effects providing T1/T2 estimates and microstructural parameters unbiased by relaxation properties of the tissue. 44 men with suspected prostate cancer (PCa) underwent multiparametric MRI (mp-MRI) and VERDICT-MRI followed by targeted biopsy. We estimate joint diffusion and relaxation prostate tissue parameters with rVERDICT using deep neural networks for fast fitting. We tested the feasibility of rVERDICT estimates for Gleason grade discrimination and compared with classic VERDICT and the apparent diffusion coefficient (ADC) from mp-MRI. The rVERDICT intracellular volume fraction fic discriminated between Gleason 3 + 3 and 3 + 4 (p = 0.003) and Gleason 3 + 4 and ≥ 4 + 3 (p = 0.040), outperforming classic VERDICT and the ADC from mp-MRI. To evaluate the relaxation estimates we compare against independent multi-TE acquisitions, showing that the rVERDICT T2 values are not significantly different from those estimated with the independent multi-TE acquisition (p > 0.05). Also, rVERDICT parameters exhibited high repeatability when rescanning five patients (R2 = 0.79–0.98; CV = 1–7%; ICC = 92–98%). The rVERDICT model allows for accurate, fast and repeatable estimation of diffusion and relaxation properties of PCa sensitive enough to discriminate Gleason grades 3 + 3, 3 + 4 and ≥ 4 + 3

Joint estimation of relaxation and diffusion tissue parameters for prostate cancer with relaxation-VERDICT MRI

This work presents a biophysical model of diffusion and relaxation MRI for prostate called relaxation vascular, extracellular and restricted diffusion for cytometry in tumours (rVERDICT). The model includes compartment-specific relaxation effects providing T1/T2 estimates and microstructural parameters unbiased by relaxation properties of the tissue. 44 men with suspected prostate cancer (PCa) underwent multiparametric MRI (mp-MRI) and VERDICT-MRI followed by targeted biopsy. We estimate joint diffusion and relaxation prostate tissue parameters with rVERDICT using deep neural networks for fast fitting. We tested the feasibility of rVERDICT estimates for Gleason grade discrimination and compared with classic VERDICT and the apparent diffusion coefficient (ADC) from mp-MRI. The rVERDICT intracellular volume fraction fic discriminated between Gleason 3 + 3 and 3 + 4 (p = 0.003) and Gleason 3 + 4 and ≥ 4 + 3 (p = 0.040), outperforming classic VERDICT and the ADC from mp-MRI. To evaluate the relaxation estimates we compare against independent multi-TE acquisitions, showing that the rVERDICT T2 values are not significantly different from those estimated with the independent multi-TE acquisition (p > 0.05). Also, rVERDICT parameters exhibited high repeatability when rescanning five patients (R2 = 0.79–0.98; CV = 1–7%; ICC = 92–98%). The rVERDICT model allows for accurate, fast and repeatable estimation of diffusion and relaxation properties of PCa sensitive enough to discriminate Gleason grades 3 + 3, 3 + 4 and ≥ 4 + 3

A survey on computational intelligence approaches for predictive modeling in prostate cancer

Predictive modeling in medicine involves the development of computational models which are capable of analysing large amounts of data in order to predict healthcare outcomes for individual patients. Computational intelligence approaches are suitable when the data to be modelled are too complex forconventional statistical techniques to process quickly and eciently. These advanced approaches are based on mathematical models that have been especially developed for dealing with the uncertainty and imprecision which is typically found in clinical and biological datasets. This paper provides a survey of recent work on computational intelligence approaches that have been applied to prostate cancer predictive modeling, and considers the challenges which need to be addressed. In particular, the paper considers a broad definition of computational intelligence which includes evolutionary algorithms (also known asmetaheuristic optimisation, nature inspired optimisation algorithms), Artificial Neural Networks, Deep Learning, Fuzzy based approaches, and hybrids of these,as well as Bayesian based approaches, and Markov models. Metaheuristic optimisation approaches, such as the Ant Colony Optimisation, Particle Swarm Optimisation, and Artificial Immune Network have been utilised for optimising the performance of prostate cancer predictive models, and the suitability of these approaches are discussed

CAD system for early diagnosis of diabetic retinopathy based on 3D extracted imaging markers.

This dissertation makes significant contributions to the field of ophthalmology, addressing the segmentation of retinal layers and the diagnosis of diabetic retinopathy (DR). The first contribution is a novel 3D segmentation approach that leverages the patientspecific anatomy of retinal layers. This approach demonstrates superior accuracy in segmenting all retinal layers from a 3D retinal image compared to current state-of-the-art methods. It also offers enhanced speed, enabling potential clinical applications. The proposed segmentation approach holds great potential for supporting surgical planning and guidance in retinal procedures such as retinal detachment repair or macular hole closure. Surgeons can benefit from the accurate delineation of retinal layers, enabling better understanding of the anatomical structure and more effective surgical interventions. Moreover, real-time guidance systems can be developed to assist surgeons during procedures, improving overall patient outcomes. The second contribution of this dissertation is the introduction of a novel computeraided diagnosis (CAD) system for precise identification of diabetic retinopathy. The CAD system utilizes 3D-OCT imaging and employs an innovative approach that extracts two distinct features: first-order reflectivity and 3D thickness. These features are then fused and used to train and test a neural network classifier. The proposed CAD system exhibits promising results, surpassing other machine learning and deep learning algorithms commonly employed in DR detection. This demonstrates the effectiveness of the comprehensive analysis approach employed by the CAD system, which considers both low-level and high-level data from the 3D retinal layers. The CAD system presents a groundbreaking contribution to the field, as it goes beyond conventional methods, optimizing backpropagated neural networks to integrate multiple levels of information effectively. By achieving superior performance, the proposed CAD system showcases its potential in accurately diagnosing DR and aiding in the prevention of vision loss. In conclusion, this dissertation presents novel approaches for the segmentation of retinal layers and the diagnosis of diabetic retinopathy. The proposed methods exhibit significant improvements in accuracy, speed, and performance compared to existing techniques, opening new avenues for clinical applications and advancements in the field of ophthalmology. By addressing future research directions, such as testing on larger datasets, exploring alternative algorithms, and incorporating user feedback, the proposed methods can be further refined and developed into robust, accurate, and clinically valuable tools for diagnosing and monitoring retinal diseases

Developing multiparametric and novel magnetic resonance imaging biomarkers for prostate cancer

Whilst biomarker research is gaining momentum within the cancer sciences, disappointingly few biomarkers are successfully translated into clinical practice, which is partly due to lack of rigorous methodology. In this thesis, I aim to systematically study several quantitative magnetic resonance imaging (MRI) biomarkers (QIBs), at various stages of biomarker development for use as tools in the assessment of local and metastatic prostate cancer according to clinical need. I initially focus on QIBs derived from conventional multiparametric (mp) prostate MRI sequences, namely T2 weighted (T2W), apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE). Firstly, by optimising analytical methods used throughout the thesis, deciding which approach is more reliable between single-slice region-of-interest vs. contouring the whole tumour volume using two different software packages. I then consider whether metric reproducibility can be improved by normalisation to different anatomical structures, and assess whether it is preferable to use statistics derived from imaging histograms rather than the current convention of using mean values. I combine multiple QIBs in a logistic regression model to predict a Gleason 4 component in known prostate cancer, which represents an unmet clinical need, as noninvasive tools to distinguish these more aggressive tumours do not currently exist. I subsequently ‘technically validate’ a novel microstructural diffusion-weighted MRI technique called VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumours) to detect aggressive prostate cancer as part of a prospective cohort study. I assess the image quality, contrast-to-noise ratio, repeatability and performance of quantitative parametric VERDICT maps to discriminate between Gleason grades vs. the current best performing, but still imperfect tool of ADC. In the final two results chapters, motivated by the limited diagnostic accuracy of the prostate cancer staging modalities in current clinical use, I investigate the ability of mp whole-body (WB) MRI to stage aggressive cancer outside the prostate in patients with a high risk of metastases at primary diagnosis, and in biochemical failure following prostatectomy

Differentiating false positive lesions from clinically significant cancer and normal prostate tissue using VERDICT MRI and other diffusion models

False positives on multiparametric MRIs (mp-MRIs) result in many unnecessary invasive biopsies in men with clinically insignificant diseases. This study investigated whether quantitative diffusion MRI could differentiate between false positives, true positives and normal tissue non-invasively. Thirty-eight patients underwent mp-MRI and Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT) MRI, followed by transperineal biopsy. The patients were categorized into two groups following biopsy: (1) significant cancer—true positive, 19 patients; (2) atrophy/inflammation/high-grade prostatic intraepithelial neoplasia (PIN)—false positive, 19 patients. The clinical apparent diffusion coefficient (ADC) values were obtained, and the intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) and VERDICT models were fitted via deep learning. Significant differences (p < 0.05) between true positive and false positive lesions were found in ADC, IVIM perfusion fraction (f) and diffusivity (D), DKI diffusivity (DK) (p < 0.0001) and kurtosis (K) and VERDICT intracellular volume fraction (fIC), extracellular–extravascular volume fraction (fEES) and diffusivity (dEES) values. Significant differences between false positives and normal tissue were found for the VERDICT fIC (p = 0.004) and IVIM D. These results demonstrate that model-based diffusion MRI could reduce unnecessary biopsies occurring due to false positive prostate lesions and shows promising sensitivity to benign diseases

Domain Adaptation for Novel Imaging Modalities with Application to Prostate MRI

The need for training data can impede the adoption of novel imaging modalities for deep learning-based medical image analysis. Domain adaptation can mitigate this problem by exploiting training samples from an existing, densely-annotated source domain within a novel, sparsely-annotated target domain, by bridging the differences between the two domains. In this thesis we present methods for adapting between diffusion-weighed (DW)-MRI data from multiparametric (mp)-MRI acquisitions and VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors) MRI, a richer DW-MRI technique involving an optimized acquisition protocol for cancer characterization. We also show that the proposed methods are general and their applicability extends beyond medical imaging. First, we propose a semi-supervised domain adaptation method for prostate lesion segmentation on VERDICT MRI. Our approach relies on stochastic generative modelling to translate across two heterogeneous domains at pixel-space and exploits the inherent uncertainty in the cross-domain mapping to generate multiple outputs conditioned on a single input. We further extend this approach to the unsupervised scenario where there is no labeled data for the target domain. We rely on stochastic generative modelling to translate across the two domains at pixel space and introduce two loss functions that promote semantic consistency. Finally we demonstrate that the proposed approaches extend beyond medical image analysis and focus on unsupervised domain adaptation for semantic segmentation of urban scenes. We show that relying on stochastic generative modelling allows us to train more accurate target networks and achieve state-of-the-art performance on two challenging semantic segmentation benchmarks

Investigating Tissue Heterogeneity using MRI in Prostate Cancer

Multi-parametric MRI, a promising new technique for grading prostate cancer using MRI, classifies a high number of regions as indeterminate. This is a symptom of the wider problem that clinical usage of MRI in prostate cancer only includes basic techniques and does not directly categorise tissue microstructure. This work provides insight into the microstructure of the prostate using a combination of new tissue models and acquisition schemes. Each is tested with the aim of producing a method that is better at detecting and grading prostate cancer. The first section utilises microstructural diffusion models to better quantify tissue heterogeneity in the prostate. The two models investigated provided more information about the heterogeneous nature of the prostate that ADC and showed significant difference between lesions and normal tissue. The next section looks into combining multi-echo T2 (ME-T2) sequences with quantitative tissue modelling called Luminal Water Imaging (LWI). This work produced an optimal LWI fitting technique and acquisition. Then the ability of LWI to detect the PI-RADS v2.0 score of regions of interest was examined, showing that it was able to differentiate between scores better than ADC. This work also showed that LWI can differentiate between tumour and normal tissue with an AUC of 0.81 (p<0.05) when compared to ADC with an AUC of 0.75 (p<0.05) in this dataset. The next section further improves the acquisitions using larger datasets. It showed that correcting for imperfect pulse refocusing could improve on the performance of LWI in detecting PCa. This work also showed that fewer echoes could be used in the acquisition. Neural networks were then used to detect and grade prostate cancer using the data points from both multiple b-value diffusion and ME-T2 decay curves. The neural network’s ability to distinguish between different PIRADS scores was shown to have an AUC of 0.87 (p<0.05) using 32-echo data