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

Atlas-Based Methods in Radiotherapy Treatment of Head and Neck Cancer

Radiotherapy is one of the principal methods for treating head and neck cancer (HNC). It plays an important role in the curative and palliative treatment of HNC. It uses high-energy radiation beams to kill cancer cells by damaging their DNA. Radiotherapy planning depends upon complex algorithms to determine the best trajectories and intensities of those beams by simulating their effects passing through designated areas. This requires accurate segmentation of anatomical structures and knowledge of the relative electron density within a patient body. Computed tomography (CT) has been the modality of choice in radiotherapy planning. It offers a wealth of anatomical information and is critical in providing information about the relative electron density of tissues required to calculate radiation deposited at any one site. Manual segmentation is time-consuming and is becoming impractical with the increasing demand in image acquisition for planning. Recently, planning solely based on magnetic resonance (MR) imaging has gained popularity as it provides superior soft tissue contrast compared to CT imaging and can better facilitate the process of segmentation. However, MR imaging does not provide electron density information for dose calculation. With the growing volumes of data and data repositories, algorithms based on atlases have gained popularity as they provide prior information for structure segmentation and tissue classification. In this PhD thesis, I demonstrate that atlas-based methods can be used for segmenting head and neck structures giving results as comparable as manual segmentation. In addition, I demonstrate that those methods can be used to support radiotherapy treatment solely based on MR imaging by generating synthetic CT images. The radiation doses calculated from a synthetic and real CT image agreed well, showing the clinical feasibility of methods based on atlases. In conclusion, I show that atlas-based methods are clinically relevant in radiotherapy treatment

Segmentation of pelvic structures from preoperative images for surgical planning and guidance

Prostate cancer is one of the most frequently diagnosed malignancies globally and the second leading cause of cancer-related mortality in males in the developed world. In recent decades, many techniques have been proposed for prostate cancer diagnosis and treatment. With the development of imaging technologies such as CT and MRI, image-guided procedures have become increasingly important as a means to improve clinical outcomes. Analysis of the preoperative images and construction of 3D models prior to treatment would help doctors to better localize and visualize the structures of interest, plan the procedure, diagnose disease and guide the surgery or therapy. This requires efficient and robust medical image analysis and segmentation technologies to be developed. The thesis mainly focuses on the development of segmentation techniques in pelvic MRI for image-guided robotic-assisted laparoscopic radical prostatectomy and external-beam radiation therapy. A fully automated multi-atlas framework is proposed for bony pelvis segmentation in MRI, using the guidance of MRI AE-SDM. With the guidance of the AE-SDM, a multi-atlas segmentation algorithm is used to delineate the bony pelvis in a new \ac{MRI} where there is no CT available. The proposed technique outperforms state-of-the-art algorithms for MRI bony pelvis segmentation. With the SDM of pelvis and its segmented surface, an accurate 3D pelvimetry system is designed and implemented to measure a comprehensive set of pelvic geometric parameters for the examination of the relationship between these parameters and the difficulty of robotic-assisted laparoscopic radical prostatectomy. This system can be used in both manual and automated manner with a user-friendly interface. A fully automated and robust multi-atlas based segmentation has also been developed to delineate the prostate in diagnostic MR scans, which have large variation in both intensity and shape of prostate. Two image analysis techniques are proposed, including patch-based label fusion with local appearance-specific atlases and multi-atlas propagation via a manifold graph on a database of both labeled and unlabeled images when limited labeled atlases are available. The proposed techniques can achieve more robust and accurate segmentation results than other multi-atlas based methods. The seminal vesicles are also an interesting structure for therapy planning, particularly for external-beam radiation therapy. As existing methods fail for the very onerous task of segmenting the seminal vesicles, a multi-atlas learning framework via random decision forests with graph cuts refinement has further been proposed to solve this difficult problem. Motivated by the performance of this technique, I further extend the multi-atlas learning to segment the prostate fully automatically using multispectral (T1 and T2-weighted) MR images via hybrid \ac{RF} classifiers and a multi-image graph cuts technique. The proposed method compares favorably to the previously proposed multi-atlas based prostate segmentation. The work in this thesis covers different techniques for pelvic image segmentation in MRI. These techniques have been continually developed and refined, and their application to different specific problems shows ever more promising results.Open Acces

Pulmonary Image Segmentation and Registration Algorithms: Towards Regional Evaluation of Obstructive Lung Disease

Pulmonary imaging, including pulmonary magnetic resonance imaging (MRI) and computed tomography (CT), provides a way to sensitively and regionally measure spatially heterogeneous lung structural-functional abnormalities. These unique imaging biomarkers offer the potential for better understanding pulmonary disease mechanisms, monitoring disease progression and response to therapy, and developing novel treatments for improved patient care. To generate these regional lung structure-function measurements and enable broad clinical applications of quantitative pulmonary MRI and CT biomarkers, as a first step, accurate, reproducible and rapid lung segmentation and registration methods are required. In this regard, we first developed a 1H MRI lung segmentation algorithm that employs complementary hyperpolarized 3He MRI functional information for improved lung segmentation. The 1H-3He MRI joint segmentation algorithm was formulated as a coupled continuous min-cut model and solved through convex relaxation, for which a dual coupled continuous max-flow model was proposed and a max-flow-based efficient numerical solver was developed. Experimental results on a clinical dataset of 25 chronic obstructive pulmonary disease (COPD) patients ranging in disease severity demonstrated that the algorithm provided rapid lung segmentation with high accuracy, reproducibility and diminished user interaction. We then developed a general 1H MRI left-right lung segmentation approach by exploring the left-to-right lung volume proportion prior. The challenging volume proportion-constrained multi-region segmentation problem was approximated through convex relaxation and equivalently represented by a max-flow model with bounded flow conservation conditions. This gave rise to a multiplier-based high performance numerical implementation based on convex optimization theories. In 20 patients with mild- to-moderate and severe asthma, the approach demonstrated high agreement with manual segmentation, excellent reproducibility and computational efficiency. Finally, we developed a CT-3He MRI deformable registration approach that coupled the complementary CT-1H MRI registration. The joint registration problem was solved by exploring optical-flow techniques, primal-dual analyses and convex optimization theories. In a diverse group of patients with asthma and COPD, the registration approach demonstrated lower target registration error than single registration and provided fast regional lung structure-function measurements that were strongly correlated with a reference method. Collectively, these lung segmentation and registration algorithms demonstrated accuracy, reproducibility and workflow efficiency that all may be clinically-acceptable. All of this is consistent with the need for broad and large-scale clinical applications of pulmonary MRI and CT

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

On the Real-Time Performance, Robustness and Accuracy of Medical Image Non-Rigid Registration

Three critical issues about medical image non-rigid registration are performance, robustness and accuracy. A registration method, which is capable of responding timely with an accurate alignment, robust against the variation of the image intensity and the missing data, is desirable for its clinical use. This work addresses all three of these issues. Unacceptable execution time of Non-rigid registration (NRR) often presents a major obstacle to its routine clinical use. We present a hybrid data partitioning method to parallelize a NRR method on a cooperative architecture, which enables us to get closer to the goal: accelerating using architecture rather than designing a parallel algorithm from scratch. to further accelerate the performance for the GPU part, a GPU optimization tool is provided to automatically optimize GPU execution configuration.;Missing data and variation of the intensity are two severe challenges for the robustness of the registration method. A novel point-based NRR method is presented to resolve mapping function (deformation field) with the point correspondence missing. The novelty of this method lies in incorporating a finite element biomechanical model into an Expectation and Maximization (EM) framework to resolve the correspondence and mapping function simultaneously. This method is extended to deal with the deformation induced by tumor resection, which imposes another challenge, i.e. incomplete intra-operative MRI. The registration is formulated as a three variable (Correspondence, Deformation Field, and Resection Region) functional minimization problem and resolved by a Nested Expectation and Maximization framework. The experimental results show the effectiveness of this method in correcting the deformation in the vicinity of the tumor. to deal with the variation of the intensity, two different methods are developed depending on the specific application. For the mono-modality registration on delayed enhanced cardiac MRI and cine MRI, a hybrid registration method is designed by unifying both intensity- and feature point-based metrics into one cost function. The experiment on the moving propagation of suspicious myocardial infarction shows effectiveness of this hybrid method. For the multi-modality registration on MRI and CT, a Mutual Information (MI)-based NRR is developed by modeling the underlying deformation as a Free-Form Deformation (FFD). MI is sensitive to the variation of the intensity due to equidistant bins. We overcome this disadvantage by designing a Top-to-Down K-means clustering method to naturally group similar intensities into one bin. The experiment shows this method can increase the accuracy of the MI-based registration.;In image registration, a finite element biomechanical model is usually employed to simulate the underlying movement of the soft tissue. We develop a multi-tissue mesh generation method to build a heterogeneous biomechanical model to realistically simulate the underlying movement of the brain. We focus on the following four critical mesh properties: tissue-dependent resolution, fidelity to tissue boundaries, smoothness of mesh surfaces, and element quality. Each mesh property can be controlled on a tissue level. The experiments on comparing the homogeneous model with the heterogeneous model demonstrate the effectiveness of the heterogeneous model in improving the registration accuracy

Image Processing and Analysis for Preclinical and Clinical Applications

Radiomics is one of the most successful branches of research in the field of image processing and analysis, as it provides valuable quantitative information for the personalized medicine. It has the potential to discover features of the disease that cannot be appreciated with the naked eye in both preclinical and clinical studies. In general, all quantitative approaches based on biomedical images, such as positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI), have a positive clinical impact in the detection of biological processes and diseases as well as in predicting response to treatment. This Special Issue, “Image Processing and Analysis for Preclinical and Clinical Applications”, addresses some gaps in this field to improve the quality of research in the clinical and preclinical environment. It consists of fourteen peer-reviewed papers covering a range of topics and applications related to biomedical image processing and analysis