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

Tumour grading and discrimination based on class assignment and quantitative texture analysis techniques

Medical imaging represents the utilisation of technology in biology for the purpose of noninvasively revealing the internal structure of the organs of the human body. It is a way to improve the quality of the patient's life through a more precise and rapid diagnosis, and with limited side-effects, leading to an effective overall treatment procedure. The main objective of this thesis is to propose novel tumour discrimination techniques that cover both micro and macro-scale textures encountered in computed tomography (CI') and digital microscopy (DM) modalities, respectively. Image texture can provide significant information on the (ab)normality of tissue, and this thesis expands this idea to tumour texture grading and classification. The fractal dimension (FO) as a texture measure was applied to contrast enhanced CT lung tumour images in an aim to improve tumour grading accuracy from conventional CI' modality, and quantitative performance analysis showed an accuracy of 83.30% in distinguishing between advanced (aggressive) and early stage (non-aggressive) malignant tumours. A different approach was adopted for subtype discrimination of brain tumour OM images via a set of statistical and model-based texture analysis algorithms. The combined Gaussian Markov random field and run-length matrix texture measures outperformed all other combinations, achieving an overall class assignment classification accuracy of 92.50%. Also two new histopathological multi resolution approaches based on applying the FO as the best bases selection for discrete wavelet packet transform, and when fused with the Gabor filters' energy output improved the accuracy to 91.25% and 95.00%, respectively. While noise is quite common in all medical imaging modalities, the impact of noise on the applied texture measures was assessed as well. The developed lung and brain texture analysis techniques can improve the physician's ability to detect and analyse pathologies leading for a more reliable diagnosis and treatment of disease

Recent Advances in Machine Learning Applied to Ultrasound Imaging

Machine learning (ML) methods are pervading an increasing number of fields of application because of their capacity to effectively solve a wide variety of challenging problems. The employment of ML techniques in ultrasound imaging applications started several years ago but the scientific interest in this issue has increased exponentially in the last few years. The present work reviews the most recent (2019 onwards) implementations of machine learning techniques for two of the most popular ultrasound imaging fields, medical diagnostics and non-destructive evaluation. The former, which covers the major part of the review, was analyzed by classifying studies according to the human organ investigated and the methodology (e.g., detection, segmentation, and/or classification) adopted, while for the latter, some solutions to the detection/classification of material defects or particular patterns are reported. Finally, the main merits of machine learning that emerged from the study analysis are summarized and discussed. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

A biomechanical approach for real-time tracking of lung tumors during External Beam Radiation Therapy (EBRT)

Lung cancer is the most common cause of cancer related death in both men and women. Radiation therapy is widely used for lung cancer treatment. However, this method can be challenging due to respiratory motion. Motion modeling is a popular method for respiratory motion compensation, while biomechanics-based motion models are believed to be more robust and accurate as they are based on the physics of motion. In this study, we aim to develop a biomechanics-based lung tumor tracking algorithm which can be used during External Beam Radiation Therapy (EBRT). An accelerated lung biomechanical model can be used during EBRT only if its boundary conditions (BCs) are defined in a way that they can be updated in real-time. As such, we have developed a lung finite element (FE) model in conjunction with a Neural Networks (NNs) based method for predicting the BCs of the lung model from chest surface motion data. To develop the lung FE model for tumor motion prediction, thoracic 4D CT images of lung cancer patients were processed to capture the lung and diaphragm geometry, trans-pulmonary pressure, and diaphragm motion. Next, the chest surface motion was obtained through tracking the motion of the ribcage in 4D CT images. This was performed to simulate surface motion data that can be acquired using optical tracking systems. Finally, two feedforward NNs were developed, one for estimating the trans-pulmonary pressure and another for estimating the diaphragm motion from chest surface motion data. The algorithm development consists of four steps of: 1) Automatic segmentation of the lungs and diaphragm, 2) diaphragm motion modelling using Principal Component Analysis (PCA), 3) Developing the lung FE model, and 4) Using two NNs to estimate the trans-pulmonary pressure values and diaphragm motion from chest surface motion data. The results indicate that the Dice similarity coefficient between actual and simulated tumor volumes ranges from 0.76±0.04 to 0.91±0.01, which is favorable. As such, real-time lung tumor tracking during EBRT using the proposed algorithm is feasible. Hence, further clinical studies involving lung cancer patients to assess the algorithm performance are justified

Application of Energy Dispersive X-Ray Diffraction (EDXRD) in the detection of fat nodules in liver disease and plaques in the blood vessels of the heart

Fat deposits in tissue or organs are a major health problem. Assessment of fat nodules in the liver (particularly prior to a liver transplant) or plaques in coronary arteries are important investigations that are undertaken in hospitals throughout the world. Many of the current techniques for investigation, e.g., computed tomography coronary angiography (CTCA), lead to high radiation doses or carry significant risks (catheter angiography) and hence new, quantitative tests are required. This thesis looks at using localised X-ray diffraction measurements as an alternative approach to quantifying the fat content of blood vessels or liver tissue. Energy dispersive X-ray diffraction (EDXRD) has been used to study the diffraction profiles of specially designed tissue phantoms. Phantoms have been built to represent a fatty-liver and a diseased heart where the size of the fatty inclusion can be varied. Combinations of tissue equivalent materials and real tissues have been used in each phantom. Diffraction profiles have been measured on these phantoms for a range of fat inclusions. All measurements were made on a fixed geometry diffractometer using a nominal scattering angle of 60 , a High Purity Germanium (HPGe) detector system and a tungsten target X-ray source. The diffraction data has been subjected to different analysis procedures. The results on the phantoms have shown that the minimum detectable levels of fat inclusions are clinically relevant. These results have then been used to scale up the measured diffraction data to patient-sized objects. Although these estimates demonstrate that doses need to be increased they also indicate that useful clinical data could be obtained at acceptable dose levels

Automated Strategies in Multimodal and Multidimensional Ultrasound Image-based Diagnosis

Medical ultrasonography is an effective technique in traditional anatomical and functional diagnosis. However, it requires the visual examination by experienced clinicians, which is a laborious, time consuming and highly subjective procedure. Computer-aided diagnosis (CADx) have been extensively used in clinical practice to support the interpretation of images; nevertheless, current ultrasound CADx still entails a substantial user-dependency and are unable to extract image data for prediction modelling. The aim of this thesis is to propose a set of fully automated strategies to overcome the limitations of ultrasound CADx. These strategies are addressed to multiple modalities (B-Mode, Contrast-Enhanced Ultrasound-CEUS, Power Doppler-PDUS and Acoustic Angiography-AA) and dimensions (2-D and 3-D imaging). The enabling techniques presented in this work are designed, developed and quantitively validated to efficiently improve the overall patients’ diagnosis. This work is subdivided in 2 macro-sections: in the first part, two fully automated algorithms for the reliable quantification of 2-D B-Mode ultrasound skeletal muscle architecture and morphology are proposed. In the second part, two fully automated algorithms for the objective assessment and characterization of tumors’ vasculature in 3-D CEUS and PDUS thyroid tumors and preclinical AA cancer growth are presented. In the first part, the MUSA (Muscle UltraSound Analysis) algorithm is designed to measure the muscle thickness, the fascicles length and the pennation angle; the TRAMA (TRAnsversal Muscle Analysis) algorithm is proposed to extract and analyze the Visible Cross-Sectional Area (VCSA). MUSA and TRAMA algorithms have been validated on two datasets of 200 images; automatic measurements have been compared with expert operators’ manual measurements. A preliminary statistical analysis was performed to prove the ability of texture analysis on automatic VCSA in the distinction between healthy and pathological muscles. In the second part, quantitative assessment on tumor vasculature is proposed in two automated algorithms for the objective characterization of 3-D CEUS/Power Doppler thyroid nodules and the evolution study of fibrosarcoma invasion in preclinical 3-D AA imaging. Vasculature analysis relies on the quantification of architecture and vessels tortuosity. Vascular features obtained from CEUS and PDUS images of 20 thyroid nodules (10 benign, 10 malignant) have been used in a multivariate statistical analysis supported by histopathological results. Vasculature parametric maps of implanted fibrosarcoma are extracted from 8 rats investigated with 3-D AA along four time points (TPs), in control and tumors areas; results have been compared with manual previous findings in a longitudinal tumor growth study. Performance of MUSA and TRAMA algorithms results in 100% segmentation success rate. Absolute difference between manual and automatic measurements is below 2% for the muscle thickness and 4% for the VCSA (values between 5-10% are acceptable in clinical practice), suggesting that automatic and manual measurements can be used interchangeably. The texture features extraction on the automatic VCSAs reveals that texture descriptors can distinguish healthy from pathological muscles with a 100% success rate for all the four muscles. Vascular features extracted of 20 thyroid nodules in 3-D CEUS and PDUS volumes can be used to distinguish benign from malignant tumors with 100% success rate for both ultrasound techniques. Malignant tumors present higher values of architecture and tortuosity descriptors; 3-D CEUS and PDUS imaging present the same accuracy in the differentiation between benign and malignant nodules. Vascular parametric maps extracted from the 8 rats along the 4 TPs in 3-D AA imaging show that parameters extracted from the control area are statistically different compared to the ones within the tumor volume. Tumor angiogenetic vessels present a smaller diameter and higher tortuosity. Tumor evolution is characterized by the significant vascular trees growth and a constant value of vessel diameter along the four TPs, confirming the previous findings. In conclusion, the proposed automated strategies are highly performant in segmentation, features extraction, muscle disease detection and tumor vascular characterization. These techniques can be extended in the investigation of other organs, diseases and embedded in ultrasound CADx, providing a user-independent reliable diagnosis