Pattern classification approaches for breast cancer identification via MRI: state‐of‐the‐art and vision for the future

Mining algorithms for Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCEMRI) of breast tissue are discussed. The algorithms are based on recent advances in multidimensional signal processing and aim to advance current state‐of‐the‐art computer‐aided detection and analysis of breast tumours when these are observed at various states of development. The topics discussed include image feature extraction, information fusion using radiomics, multi‐parametric computer‐aided classification and diagnosis using information fusion of tensorial datasets as well as Clifford algebra based classification approaches and convolutional neural network deep learning methodologies. The discussion also extends to semi‐supervised deep learning and self‐supervised strategies as well as generative adversarial networks and algorithms using generated confrontational learning approaches. In order to address the problem of weakly labelled tumour images, generative adversarial deep learning strategies are considered for the classification of different tumour types. The proposed data fusion approaches provide a novel Artificial Intelligence (AI) based framework for more robust image registration that can potentially advance the early identification of heterogeneous tumour types, even when the associated imaged organs are registered as separate entities embedded in more complex geometric spaces. Finally, the general structure of a high‐dimensional medical imaging analysis platform that is based on multi‐task detection and learning is proposed as a way forward. The proposed algorithm makes use of novel loss functions that form the building blocks for a generated confrontation learning methodology that can be used for tensorial DCE‐MRI. Since some of the approaches discussed are also based on time‐lapse imaging, conclusions on the rate of proliferation of the disease can be made possible. The proposed framework can potentially reduce the costs associated with the interpretation of medical images by providing automated, faster and more consistent diagnosis

Radiomic analysis reveals DCE-MRI features for prediction of molecular subtypes of breast cancer

This work was supported in part by financial support from the National Natural Science Foundation of China (61271063 and 61401131), the National Basic Research Program of China (973 Program) (2013CB329502), and the Natural Science Foundation of Zhejiang Province of China (LZ15F010001 and LQ14F010011).The purpose of this study was to investigate the role of features derived from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to incorporated clinical information to predict the molecular subtypes of breast cancer. In particular, 60 breast cancers with the following four molecular subtypes were analyzed: luminal A, luminal B, human epidermal growth factor receptor-2 (HER2)-over-expressing and basal-like. The breast region was segmented and the suspicious tumor was depicted on sequentially scanned MR images from each case. In total, 90 features were obtained, including 88 imaging features related to morphology and texture as well as dynamic features from tumor and background parenchymal enhancement (BPE) and 2 clinical information-based parameters, namely, age and menopausal status. An evolutionary algorithm was used to select an optimal subset of features for classification. Using these features, we trained a multi-class logistic regression classifier that calculated the area under the receiver operating characteristic curve (AUC). The results of a prediction model using 24 selected features showed high overall classification performance, with an AUC value of 0.869. The predictive model discriminated among the luminal A, luminal B, HER2 and basal-like subtypes, with AUC values of 0.867, 0.786, 0.888 and 0.923, respectively. An additional independent dataset with 36 patients was utilized to validate the results. A similar classification analysis of the validation dataset showed an AUC of 0.872 using 15 image features, 10 of which were identical to those from the first cohort. We identified clinical information and 3D imaging features from DCE-MRI as candidate biomarkers for discriminating among four molecular subtypes of breast cancer.Yeshttp://www.plosone.org/static/editorial#pee

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Advanced Computational Methods for Oncological Image Analysis

[Cancer is the second most common cause of death worldwide and encompasses highly variable clinical and biological scenarios. Some of the current clinical challenges are (i) early diagnosis of the disease and (ii) precision medicine, which allows for treatments targeted to specific clinical cases. The ultimate goal is to optimize the clinical workflow by combining accurate diagnosis with the most suitable therapies. Toward this, large-scale machine learning research can define associations among clinical, imaging, and multi-omics studies, making it possible to provide reliable diagnostic and prognostic biomarkers for precision oncology. Such reliable computer-assisted methods (i.e., artificial intelligence) together with clinicians’ unique knowledge can be used to properly handle typical issues in evaluation/quantification procedures (i.e., operator dependence and time-consuming tasks). These technical advances can significantly improve result repeatability in disease diagnosis and guide toward appropriate cancer care. Indeed, the need to apply machine learning and computational intelligence techniques has steadily increased to effectively perform image processing operations—such as segmentation, co-registration, classification, and dimensionality reduction—and multi-omics data integration.

Automatic correspondence between 2D and 3D images of the breast

Radiologists often need to localise corresponding findings in different images of the breast, such as Magnetic Resonance Images and X-ray mammograms. However, this is a difficult task, as one is a volume and the other a projection image. In addition, the appearance of breast tissue structure can vary significantly between them. Some breast regions are often obscured in an X-ray, due to its projective nature and the superimposition of normal glandular tissue. Automatically determining correspondences between the two modalities could assist radiologists in the detection, diagnosis and surgical planning of breast cancer. This thesis addresses the problems associated with the automatic alignment of 3D and 2D breast images and presents a generic framework for registration that uses the structures within the breast for alignment, rather than surrogates based on the breast outline or nipple position. The proposed algorithm can adapt to incorporate different types of transformation models, in order to capture the breast deformation between modalities. The framework was validated on clinical MRI and X-ray mammography cases using both simple geometrical models, such as the affine, and also more complex ones that are based on biomechanical simulations. The results showed that the proposed framework with the affine transformation model can provide clinically useful accuracy (13.1mm when tested on 113 registration tasks). The biomechanical transformation models provided further improvement when applied on a smaller dataset. Our technique was also tested on determining corresponding findings in multiple X-ray images (i.e. temporal or CC to MLO) for a given subject using the 3D information provided by the MRI. Quantitative results showed that this approach outperforms 2D transformation models that are typically used for this task. The results indicate that this pipeline has the potential to provide a clinically useful tool for radiologists

Mathematical approaches for the clinical translation of hyperpolarised 13C imaging in oncology

Dissolution dynamic nuclear polarisation is an emerging clinical technique which enables the metabolism of hyperpolarised 13C-labelled molecules to be dynamically and non- invasively imaged in tissue. The first molecule to gain clinical approval is [1-13C]pyruvate, the conversion of which to [1-13C]lactate has been shown to detect early treatment re- sponse in cancers and correlate with tumour grade. As the technique has recently been translated into humans, accurate and reliable quantitative methods are required in order to detect, analyse and compare regions of altered metabolism in patients. Furthermore, there is a requirement to understand the biological processes which govern lactate pro- duction in tumours in order to draw reliable conclusions from this data. This work begins with a comprehensive analysis of the quantitative methods which have previously been applied to hyperpolarised 13C data and compares these to some novel approaches. The most appropriate kinetic model to apply to hyperpolarised data is determined and some simple, robust quantitative metrics are identified which are suitable for clinical use. A means of automatically segmenting 5D hyperpolarised imaging data using a fuzzy Markov random field approach is presented in order to reliably identify regions of abnormal metabolic activity. The utility of the algorithm is demonstrated on both in silico and animal data. To gain insight into the processes driving lactate metabolism, a mathematical model is developed which is capable of simulating tumour growth and treatment response under a range of metabolic and tissue conditions, focusing on the interaction between tumour and stroma. Finally, hyperpolarised 13C-pyruvate imaging data from the first human subjects to be imaged in Cambridge is analysed. The ability to detect and quantify lactate production in patients is demonstrated through application of the methods derived in earlier chapters. The mathematical approaches presented in this work have the potential to inform both the analysis and interpretation of clinical hyperpolarised 13C imaging data and to aid in the clinical translation of this technique.Joint funded by GlaxoSmithKline and the Cambridge Biomedical Research Centre

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

IMAGE UNDERSTANDING OF MOLAR PREGNANCY BASED ON ANOMALIES DETECTION

Cancer occurs when normal cells grow and multiply without normal control. As the cells multiply, they form an area of abnormal cells, known as a tumour. Many tumours exhibit abnormal chromosomal segregation at cell division. These anomalies play an important role in detecting molar pregnancy cancer. Molar pregnancy, also known as hydatidiform mole, can be categorised into partial (PHM) and complete (CHM) mole, persistent gestational trophoblastic and choriocarcinoma. Hydatidiform moles are most commonly found in women under the age of 17 or over the age of 35. Hydatidiform moles can be detected by morphological and histopathological examination. Even experienced pathologists cannot easily classify between complete and partial hydatidiform moles. However, the distinction between complete and partial hydatidiform moles is important in order to recommend the appropriate treatment method. Therefore, research into molar pregnancy image analysis and understanding is critical. The hypothesis of this research project is that an anomaly detection approach to analyse molar pregnancy images can improve image analysis and classification of normal PHM and CHM villi. The primary aim of this research project is to develop a novel method, based on anomaly detection, to identify and classify anomalous villi in molar pregnancy stained images. The novel method is developed to simulate expert pathologists’ approach in diagnosis of anomalous villi. The knowledge and heuristics elicited from two expert pathologists are combined with the morphological domain knowledge of molar pregnancy, to develop a heuristic multi-neural network architecture designed to classify the villi into their appropriated anomalous types. This study confirmed that a single feature cannot give enough discriminative power for villi classification. Whereas expert pathologists consider the size and shape before textural features, this thesis demonstrated that the textural feature has a higher discriminative power than size and shape. The first heuristic-based multi-neural network, which was based on 15 elicited features, achieved an improved average accuracy of 81.2%, compared to the traditional multi-layer perceptron (80.5%); however, the recall of CHM villi class was still low (64.3%). Two further textural features, which were elicited and added to the second heuristic-based multi-neural network, have improved the average accuracy from 81.2% to 86.1% and the recall of CHM villi class from 64.3% to 73.5%. The precision of the multi-neural network II has also increased from 82.7% to 89.5% for normal villi class, from 81.3% to 84.7% for PHM villi class and from 80.8% to 86% for CHM villi class. To support pathologists to visualise the results of the segmentation, a software tool, Hydatidiform Mole Analysis Tool (HYMAT), was developed compiling the morphological and pathological data for each villus analysis