Deep learning applications in the prostate cancer diagnostic pathway

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide and the fifth leading cause of cancer death in men, with an estimated 1.4 million new cases in 2020 and 375,000 deaths. The risk factors most strongly associated to PCa are advancing age, family history, race, and mutations of the BRCA genes. Since the aforementioned risk factors are not preventable, early and accurate diagnoses are a key objective of the PCa diagnostic pathway. In the UK, clinical guidelines recommend multiparametric magnetic resonance imaging (mpMRI) of the prostate for use by radiologists to detect, score, and stage lesions that may correspond to clinically significant PCa (CSPCa), prior to confirmatory biopsy and histopathological grading. Computer-aided diagnosis (CAD) of PCa using artificial intelligence algorithms holds a currently unrealized potential to improve upon the diagnostic accuracy achievable by radiologist assessment of mpMRI, improve the reporting consistency between radiologists, and reduce reporting time. In this thesis, we build and evaluate deep learning-based CAD systems for the PCa diagnostic pathway, which address gaps identified in the literature. First, we introduce a novel patient-level classification framework, PCF, which uses a stacked ensemble of convolutional neural networks (CNNs) and support vector machines (SVMs) to assign a probability of having CSPCa to patients, using mpMRI and clinical features. Second, we introduce AutoProstate, a deep-learning powered framework for automated PCa assessment and reporting; AutoProstate utilizes biparametric MRI and clinical data to populate an automatic diagnostic report containing segmentations of the whole prostate, prostatic zones, and candidate CSPCa lesions, as well as several derived characteristics that are clinically valuable. Finally, as automatic segmentation algorithms have not yet reached the desired robustness for clinical use, we introduce interactive click-based segmentation applications for the whole prostate and prostatic lesions, with potential uses in diagnosis, active surveillance progression monitoring, and treatment planning

Nephroblastoma in MRI Data

The main objective of this work is the mathematical analysis of nephroblastoma in MRI sequences. At the beginning we provide two different datasets for segmentation and classification. Based on the first dataset, we analyze the current clinical practice regarding therapy planning on the basis of annotations of a single radiologist. We can show with our benchmark that this approach is not optimal and that there may be significant differences between human annotators and even radiologists. In addition, we demonstrate that the approximation of the tumor shape currently used is too coarse granular and thus prone to errors. We address this problem and develop a method for interactive segmentation that allows an intuitive and accurate annotation of the tumor. While the first part of this thesis is mainly concerned with the segmentation of Wilms’ tumors, the second part deals with the reliability of diagnosis and the planning of the course of therapy. The second data set we compiled allows us to develop a method that dramatically improves the differential diagnosis between nephroblastoma and its precursor lesion nephroblastomatosis. Finally, we can show that even the standard MRI modality for Wilms’ tumors is sufficient to estimate the developmental tendencies of nephroblastoma under chemotherapy

Measurement Variability in Treatment Response Determination for Non-Small Cell Lung Cancer: Improvements using Radiomics

Multimodality imaging measurements of treatment response are critical for clinical practice, oncology trials, and the evaluation of new treatment modalities. The current standard for determining treatment response in non-small cell lung cancer (NSCLC) is based on tumor size using the RECIST criteria. Molecular targeted agents and immunotherapies often cause morphological change without reduction of tumor size. Therefore, it is difficult to evaluate therapeutic response by conventional methods. Radiomics is the study of cancer imaging features that are extracted using machine learning and other semantic features. This method can provide comprehensive information on tumor phenotypes and can be used to assess therapeutic response in this new age of immunotherapy. Delta radiomics, which evaluates the longitudinal changes in radiomics features, shows potential in gauging treatment response in NSCLC. It is well known that quantitative measurement methods may be subject to substantial variability due to differences in technical factors and require standardization. In this review, we describe measurement variability in the evaluation of NSCLC and the emerging role of radiomics. © 2019 Wolters Kluwer Health, Inc. All rights reserved

Deep learning assisted MRI guided attenuation correction in PET

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University LondonPositron emission tomography (PET) is a unique imaging modality that provides physiological and functional details of the tissue at the molecular level. However, the acquired PET images have some limitations such as the attenuation. PET attenuation correction is an essential step to obtain the full potential of PET quantification. With the wide use of hybrid PET/MR scanners, magnetic resonance (MR) images are used to address the problem of PET attenuation correction. The MR images segmentation is one simple and robust approach to create pseudo computed tomography (CT) images, which are used to generate attenuation coefficient maps to correct the PET attenuation. Recently, deep learning has been proposed and used as a promising technique to efficiently perform MR and various medical images segmentation. In this research work, deep learning guided segmentation approaches have been proposed to enhance the bone class segmentation of MR brain images in order to generate accurate pseudo-CT images. The first approach has introduced the combination of handcrafted features with deep learning features to enrich the set of features. Multiresolution analysis techniques, which generate multiscale and multidirectional coefficients of an image such as contourlet and shearlet transforms, are applied and combined with deep convolutional neural network (CNN) features. Different experiments have been conducted to investigate the number of selected coefficients and the insertion location of the handcrafted features. The second approach aims at reducing the segmentation algorithm’s complexity while maintaining the segmentation performance. An attention based convolutional encode-decoder network has been proposed to adaptively recalibrate the deep network features. This attention based network consists of two different squeeze and excitation blocks that excite the features spatially and channel wise. The two blocks are combined sequentially to decrease the number of network’s parameters and reduces the model complexity. The third approach has been focuses on the application of transfer learning from different MR sequences such as T1 weighted (T1-w) and T2 weighted (T2-w) images. A pretrained model with T1-w MR sequences is fine tuned to perform the segmentation of T2-w images. Multiple fine tuning approaches and experiments have been conducted to study the best fine tuning mechanism that is able to build an efficient segmentation model for both T1-w and T2-w segmentation. Clinical datasets of fifty patients with different conditions and diagnosis have been used to carry an objective evaluation to measure the segmentation performance of the results obtained by the three proposed methods. The first and second approaches have been validated with other studies in the literature that applied deep network based segmentation technique to perform MR based attenuation correction for PET images. The proposed methods have shown an enhancement in the bone segmentation with an increase of dice similarity coefficient (DSC) from 0.6179 to 0.6567 using an ensemble of CNNs with an improvement percentage of 6.3%. The proposed excitation-based CNN has decreased the model complexity by decreasing the number of trainable parameters by more than 46% where less computing resources are required to train the model. The proposed hybrid transfer learning method has shown its superiority to build a multi-sequences (T1-w and T2-w) segmentation approach compared to other applied transfer learning methods especially with the bone class where the DSC is increased from 0.3841 to 0.5393. Moreover, the hybrid transfer learning approach requires less computing time than transfer learning using open and conservative fine tuning

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

Multiple Sclerosis Detection in Multispectral Magnetic Resonance Images with Principal Components Analysis

This paper presents a local feature vector based method for automated Multiple Sclerosis (MS) lesion segmentation of multi spectral MRI data. Twenty datasets from MS patients with FLAIR, T1,T2, MD and FA data with expert annotations are available as training set from the MICCAI 2008 challenge on MS, and 24 test datasets. Our local feature vector method contains neighbourhood voxel intensities, histogram and MS probability atlas information. Principal Component Analysis(PCA) with log-likelihood ratio is used to classify each voxel. MRI suffers from intensity inhomogenities. We try to correct this 'bias field' with 3 methods: a genetic algorithm, edge preserving filtering and atlas based correction. A large observer variability exist between expert classifications, but the similarity scores between model and expert classifications are often lower. Our model gives the best classification results with raw data, because bias correction gives artifacts at the edges and flatten large MS lesions

Radiomic data mining and machine learning on preoperative pituitary adenoma MRI

Pituitary adenomas are among the most frequent intracranial tumors, accounting for the majority of sellar/suprasellar masses in adults. MRI is the preferred imaging modality for detecting pituitary adenomas. Radiomics represents the conversion of digital medical images into mineable high-dimensional data. This process is motivated by the concept that biomedical images contain information that reflects underlying pathophysiology and that these relationships can be revealed via quantitative image analyses. The aim of this thesis is to apply machine learning algorithms on parameters obtained by texture analysis on MRI images in order to distinguish functional from non-functional pituitary macroadenomas, to predict their ki-67 proliferation index class, and to predict pituitary macroadenoma surgical consistency prior to an endoscopic endonasal procedure