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

Development, Implementation and Pre-clinical Evaluation of Medical Image Computing Tools in Support of Computer-aided Diagnosis: Respiratory, Orthopedic and Cardiac Applications

Over the last decade, image processing tools have become crucial components of all clinical and research efforts involving medical imaging and associated applications. The imaging data available to the radiologists continue to increase their workload, raising the need for efficient identification and visualization of the required image data necessary for clinical assessment. Computer-aided diagnosis (CAD) in medical imaging has evolved in response to the need for techniques that can assist the radiologists to increase throughput while reducing human error and bias without compromising the outcome of the screening, diagnosis or disease assessment. More intelligent, but simple, consistent and less time-consuming methods will become more widespread, reducing user variability, while also revealing information in a more clear, visual way. Several routine image processing approaches, including localization, segmentation, registration, and fusion, are critical for enhancing and enabling the development of CAD techniques. However, changes in clinical workflow require significant adjustments and re-training and, despite the efforts of the academic research community to develop state-of-the-art algorithms and high-performance techniques, their footprint often hampers their clinical use. Currently, the main challenge seems to not be the lack of tools and techniques for medical image processing, analysis, and computing, but rather the lack of clinically feasible solutions that leverage the already developed and existing tools and techniques, as well as a demonstration of the potential clinical impact of such tools. Recently, more and more efforts have been dedicated to devising new algorithms for localization, segmentation or registration, while their potential and much intended clinical use and their actual utility is dwarfed by the scientific, algorithmic and developmental novelty that only result in incremental improvements over already algorithms. In this thesis, we propose and demonstrate the implementation and evaluation of several different methodological guidelines that ensure the development of image processing tools --- localization, segmentation and registration --- and illustrate their use across several medical imaging modalities --- X-ray, computed tomography, ultrasound and magnetic resonance imaging --- and several clinical applications: Lung CT image registration in support for assessment of pulmonary nodule growth rate and disease progression from thoracic CT images. Automated reconstruction of standing X-ray panoramas from multi-sector X-ray images for assessment of long limb mechanical axis and knee misalignment. Left and right ventricle localization, segmentation, reconstruction, ejection fraction measurement from cine cardiac MRI or multi-plane trans-esophageal ultrasound images for cardiac function assessment. When devising and evaluating our developed tools, we use clinical patient data to illustrate the inherent clinical challenges associated with highly variable imaging data that need to be addressed before potential pre-clinical validation and implementation. In an effort to provide plausible solutions to the selected applications, the proposed methodological guidelines ensure the development of image processing tools that help achieve sufficiently reliable solutions that not only have the potential to address the clinical needs, but are sufficiently streamlined to be potentially translated into eventual clinical tools provided proper implementation. G1: Reducing the number of degrees of freedom (DOF) of the designed tool, with a plausible example being avoiding the use of inefficient non-rigid image registration methods. This guideline addresses the risk of artificial deformation during registration and it clearly aims at reducing complexity and the number of degrees of freedom. G2: The use of shape-based features to most efficiently represent the image content, either by using edges instead of or in addition to intensities and motion, where useful. Edges capture the most useful information in the image and can be used to identify the most important image features. As a result, this guideline ensures a more robust performance when key image information is missing. G3: Efficient method of implementation. This guideline focuses on efficiency in terms of the minimum number of steps required and avoiding the recalculation of terms that only need to be calculated once in an iterative process. An efficient implementation leads to reduced computational effort and improved performance. G4: Commence the workflow by establishing an optimized initialization and gradually converge toward the final acceptable result. This guideline aims to ensure reasonable outcomes in consistent ways and it avoids convergence to local minima, while gradually ensuring convergence to the global minimum solution. These guidelines lead to the development of interactive, semi-automated or fully-automated approaches that still enable the clinicians to perform final refinements, while they reduce the overall inter- and intra-observer variability, reduce ambiguity, increase accuracy and precision, and have the potential to yield mechanisms that will aid with providing an overall more consistent diagnosis in a timely fashion

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

CAD system for lung nodule analysis.

Lung cancer is the deadliest type of known cancer in the United States, claiming hundreds of thousands of lives each year. However, despite the high mortality rate, the 5-year survival rate after resection of Stage 1A non–small cell lung cancer is currently in the range of 62%– 82% and in recent studies even 90%. Patient survival is highly correlated with early detection. Computed Tomography (CT) technology services the early detection of lung cancer tremendously by offering a minimally invasive medical diagnostic tool. Some early types of lung cancer begin with a small mass of tissue within the lung, less than 3 cm in diameter, called a nodule. Most nodules found in a lung are benign, but a small population of them becomes malignant over time. Expert analysis of CT scans is the first step in determining whether a nodule presents a possibility for malignancy but, due to such low spatial support, many potentially harmful nodules go undetected until other symptoms motivate a more thorough search. Computer Vision and Pattern Recognition techniques can play a significant role in aiding the process of detecting and diagnosing lung nodules. This thesis outlines the development of a CAD system which, given an input CT scan, provides a functional and fast, second-opinion diagnosis to physicians. The entire process of lung nodule screening has been cast as a system, which can be enhanced by modern computing technology, with the hopes of providing a feasible diagnostic tool for clinical use. It should be noted that the proposed CAD system is presented as a tool for experts—not a replacement for them. The primary motivation of this thesis is the design of a system that could act as a catalyst for reducing the mortality rate associated with lung cancer

Spatio-Temporal Hybrid Fusion of CAE and SWIn Transformers for Lung Cancer Malignancy Prediction

The paper proposes a novel hybrid discovery Radiomics framework that simultaneously integrates temporal and spatial features extracted from non-thin chest Computed Tomography (CT) slices to predict Lung Adenocarcinoma (LUAC) malignancy with minimum expert involvement. Lung cancer is the leading cause of mortality from cancer worldwide and has various histologic types, among which LUAC has recently been the most prevalent. LUACs are classified as pre-invasive, minimally invasive, and invasive adenocarcinomas. Timely and accurate knowledge of the lung nodules malignancy leads to a proper treatment plan and reduces the risk of unnecessary or late surgeries. Currently, chest CT scan is the primary imaging modality to assess and predict the invasiveness of LUACs. However, the radiologists' analysis based on CT images is subjective and suffers from a low accuracy compared to the ground truth pathological reviews provided after surgical resections. The proposed hybrid framework, referred to as the CAET-SWin, consists of two parallel paths: (i) The Convolutional Auto-Encoder (CAE) Transformer path that extracts and captures informative features related to inter-slice relations via a modified Transformer architecture, and; (ii) The Shifted Window (SWin) Transformer path, which is a hierarchical vision transformer that extracts nodules' related spatial features from a volumetric CT scan. Extracted temporal (from the CAET-path) and spatial (from the Swin path) are then fused through a fusion path to classify LUACs. Experimental results on our in-house dataset of 114 pathologically proven Sub-Solid Nodules (SSNs) demonstrate that the CAET-SWin significantly improves reliability of the invasiveness prediction task while achieving an accuracy of 82.65%, sensitivity of 83.66%, and specificity of 81.66% using 10-fold cross-validation.Comment: arXiv admin note: substantial text overlap with arXiv:2110.0872

Cancer diagnosis using deep learning: A bibliographic review

In this paper, we first describe the basics of the field of cancer diagnosis, which includes steps of cancer diagnosis followed by the typical classification methods used by doctors, providing a historical idea of cancer classification techniques to the readers. These methods include Asymmetry, Border, Color and Diameter (ABCD) method, seven-point detection method, Menzies method, and pattern analysis. They are used regularly by doctors for cancer diagnosis, although they are not considered very efficient for obtaining better performance. Moreover, considering all types of audience, the basic evaluation criteria are also discussed. The criteria include the receiver operating characteristic curve (ROC curve), Area under the ROC curve (AUC), F1 score, accuracy, specificity, sensitivity, precision, dice-coefficient, average accuracy, and Jaccard index. Previously used methods are considered inefficient, asking for better and smarter methods for cancer diagnosis. Artificial intelligence and cancer diagnosis are gaining attention as a way to define better diagnostic tools. In particular, deep neural networks can be successfully used for intelligent image analysis. The basic framework of how this machine learning works on medical imaging is provided in this study, i.e., pre-processing, image segmentation and post-processing. The second part of this manuscript describes the different deep learning techniques, such as convolutional neural networks (CNNs), generative adversarial models (GANs), deep autoencoders (DANs), restricted Boltzmann’s machine (RBM), stacked autoencoders (SAE), convolutional autoencoders (CAE), recurrent neural networks (RNNs), long short-term memory (LTSM), multi-scale convolutional neural network (M-CNN), multi-instance learning convolutional neural network (MIL-CNN). For each technique, we provide Python codes, to allow interested readers to experiment with the cited algorithms on their own diagnostic problems. The third part of this manuscript compiles the successfully applied deep learning models for different types of cancers. Considering the length of the manuscript, we restrict ourselves to the discussion of breast cancer, lung cancer, brain cancer, and skin cancer. The purpose of this bibliographic review is to provide researchers opting to work in implementing deep learning and artificial neural networks for cancer diagnosis a knowledge from scratch of the state-of-the-art achievements

Radiomics in Lung Cancer from Basic to Advanced: Current Status and Future Directions

Copyright © 2020 The Korean Society of Radiology.Ideally, radiomics features and radiomics signatures can be used as imaging biomarkers for diagnosis, staging, prognosis, and prediction of tumor response. Thus, the number of published radiomics studies is increasing exponentially, leading to a myriad of new radiomics-based evidence for lung cancer. Consequently, it is challenging for radiologists to keep up with the development of radiomics features and their clinical applications. In this article, we review the basics to advanced radiomics in lung cancer to guide young researchers who are eager to start exploring radiomics investigations. In addition, we also include technical issues of radiomics, because knowledge of the technical aspects of radiomics supports a well-informed interpretation of the use of radiomics in lung cancer11Nsciescopuskc

Automatic 3D pulmonary nodule detection in CT images: a survey

This work presents a systematic review of techniques for the 3D automatic detection of pulmonary nodules in computerized-tomography (CT) images. Its main goals are to analyze the latest technology being used for the development of computational diagnostic tools to assist in the acquisition, storage and, mainly, processing and analysis of the biomedical data. Also, this work identifies the progress made, so far, evaluates the challenges to be overcome and provides an analysis of future prospects. As far as the authors know, this is the first time that a review is devoted exclusively to automated 3D techniques for the detection of pulmonary nodules from lung CT images, which makes this work of noteworthy value. The research covered the published works in the Web of Science, PubMed, Science Direct and IEEEXplore up to December 2014. Each work found that referred to automated 3D segmentation of the lungs was individually analyzed to identify its objective, methodology and results. Based on the analysis of the selected works, several studies were seen to be useful for the construction of medical diagnostic aid tools. However, there are certain aspects that still require attention such as increasing algorithm sensitivity, reducing the number of false positives, improving and optimizing the algorithm detection of different kinds of nodules with different sizes and shapes and, finally, the ability to integrate with the Electronic Medical Record Systems and Picture Archiving and Communication Systems. Based on this analysis, we can say that further research is needed to develop current techniques and that new algorithms are needed to overcome the identified drawbacks

BRONCO: Automated modelling of the bronchovascular bundle using the Computed Tomography Images

Segmentation of the bronchovascular bundle within the lung parenchyma is a key step for the proper analysis and planning of many pulmonary diseases. It might also be considered the preprocessing step when the goal is to segment the nodules from the lung parenchyma. We propose a segmentation pipeline for the bronchovascular bundle based on the Computed Tomography images, returning either binary or labelled masks of vessels and bronchi situated in the lung parenchyma. The method consists of two modules, modeling of the bronchial tree and vessels. The core revolves around a similar pipeline, the determination of the initial perimeter by the GMM method, skeletonization, and hierarchical analysis of the created graph. We tested our method on both low-dose CT and standard-dose CT, with various pathologies, reconstructed with various slice thicknesses, and acquired from various machines. We conclude that the method is invariant with respect to the origin and parameters of the CT series. Our pipeline is best suited for studies with healthy patients, patients with lung nodules, and patients with emphysema