An Intelligent Radiomic Approach for Lung Cancer Screening

Funding: This project is supported by the Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER), RTI2018-095209-B-C21 (MCI/AEI/FEDER, UE), Generalitat de Catalunya, 2017-SGR-1624 and CERCA-Programme. Debora Gil is supported by Serra Hunter Fellow.This project is supported by the Ministerio de Ciencia e Innovaci?n (MCI), Agencia Estatal de Investigaci?n (AEI) and Fondo Europeo de Desarrollo Regional (FEDER), RTI2018-095209-B-C21 (MCI/AEI/FEDER, UE), Generalitat de Catalunya, 2017-SGR-1624 and CERCA-Programme. Debora Gil is supported by Serra Hunter Fellow. Barcelona Respiratory Network (BRN), Acad?mia de Ci?ncies M?diques de Catalunya i Balears, i Fundaci? Ramon Pla i Armengol.The efficiency of lung cancer screening for reducing mortality is hindered by the high rate of false positives. Artificial intelligence applied to radiomics could help to early discard benign cases from the analysis of CT scans. The available amount of data and the fact that benign cases are a minority, constitutes a main challenge for the successful use of state of the art methods (like deep learning), which can be biased, over-fitted and lack of clinical reproducibility. We present an hybrid approach combining the potential of radiomic features to characterize nodules in CT scans and the generalization of the feed forward networks. In order to obtain maximal reproducibility with minimal training data, we propose an embedding of nodules based on the statistical significance of radiomic features for malignancy detection. This representation space of lesions is the input to a feed forward network, which architecture and hyperparameters are optimized using own-defined metrics of the diagnostic power of the whole system. Results of the best model on an independent set of patients achieve 100% of sensitivity and 83% of specificity (AUC = 0.94) for malignancy detection

Lung nodules identification in CT scans using multiple instance learning.

Computer Aided Diagnosis (CAD) systems for lung nodules diagnosis aim to classify nodules into benign or malignant based on images obtained from diverse imaging modalities such as Computer Tomography (CT). Automated CAD systems are important in medical domain applications as they assist radiologists in the time-consuming and labor-intensive diagnosis process. However, most available methods require a large collection of nodules that are segmented and annotated by radiologists. This process is labor-intensive and hard to scale to very large datasets. More recently, some CAD systems that are based on deep learning have emerged. These algorithms do not require the nodules to be segmented, and radiologists need to only provide the center of mass of each nodule. The training image patches are then extracted from volumes of fixed-sized centered at the provided nodule\u27s center. However, since the size of nodules can vary significantly, one fixed size volume may not represent all nodules effectively. This thesis proposes a Multiple Instance Learning (MIL) approach to address the above limitations. In MIL, each nodule is represented by a nested sequence of volumes centered at the identified center of the nodule. We extract one feature vector from each volume. The set of features for each nodule are combined and represented by a bag. Next, we investigate and adapt some existing algorithms and develop new ones for this application. We start by applying benchmark MIL algorithms to traditional Gray Level Co-occurrence Matrix (GLCM) engineered features. Then, we design and train simple Convolutional Neural Networks (CNNs) to learn and extract features that characterize lung nodules. These extracted features are then fed to a benchmark MIL algorithm to learn a classification model. Finally, we develop new algorithms (MIL-CNN) that combine feature learning and multiple instance classification in a single network. These algorithms generalize the CNN architecture to multiple instance data. We design and report the results of three experiments applied on both generative (GLCM) and learned (CNN) features using two datasets (The Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) \cite{armato2011lung} and the National Lung Screening Trial (NLST) \cite{national2011reduced}). Two of these experiments perform five-fold cross-validations on the same dataset (NLST or LIDC). The third experiment trains the algorithms on one collection (NLST dataset) and tests it on the other (LIDC dataset). We designed our experiments to compare the different features, compare MIL versus Single Instance Learning (SIL) where a single feature vector represents a nodule, and compare our proposed end-to-end MIL approaches to existing benchmark MIL methods. We demonstrate that our proposed MIL-CNN frameworks are more accurate for the lung nodules diagnosis task. We also show that MIL representation achieves better results than SIL applied on the ground truth region of each nodule

Machine learning approaches for lung cancer diagnosis.

The enormity of changes and development in the field of medical imaging technology is hard to fathom, as it does not just represent the technique and process of constructing visual representations of the body from inside for medical analysis and to reveal the internal structure of different organs under the skin, but also it provides a noninvasive way for diagnosis of various disease and suggest an efficient ways to treat them. While data surrounding all of our lives are stored and collected to be ready for analysis by data scientists, medical images are considered a rich source that could provide us with a huge amount of data, that could not be read easily by physicians and radiologists, with valuable information that could be used in smart ways to discover new knowledge from these vast quantities of data. Therefore, the design of computer-aided diagnostic (CAD) system, that can be approved for use in clinical practice that aid radiologists in diagnosis and detecting potential abnormalities, is of a great importance. This dissertation deals with the development of a CAD system for lung cancer diagnosis, which is the second most common cancer in men after prostate cancer and in women after breast cancer. Moreover, lung cancer is considered the leading cause of cancer death among both genders in USA. Recently, the number of lung cancer patients has increased dramatically worldwide and its early detection doubles a patient’s chance of survival. Histological examination through biopsies is considered the gold standard for final diagnosis of pulmonary nodules. Even though resection of pulmonary nodules is the ideal and most reliable way for diagnosis, there is still a lot of different methods often used just to eliminate the risks associated with the surgical procedure. Lung nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. A pulmonary nodule is the first indication to start diagnosing lung cancer. Lung nodules can be benign (normal subjects) or malignant (cancerous subjects). Large (generally defined as greater than 2 cm in diameter) malignant nodules can be easily detected with traditional CT scanning techniques. However, the diagnostic options for small indeterminate nodules are limited due to problems associated with accessing small tumors. Therefore, additional diagnostic and imaging techniques which depends on the nodules’ shape and appearance are needed. The ultimate goal of this dissertation is to develop a fast noninvasive diagnostic system that can enhance the accuracy measures of early lung cancer diagnosis based on the well-known hypotheses that malignant nodules have different shape and appearance than benign nodules, because of the high growth rate of the malignant nodules. The proposed methodologies introduces new shape and appearance features which can distinguish between benign and malignant nodules. To achieve this goal a CAD system is implemented and validated using different datasets. This CAD system uses two different types of features integrated together to be able to give a full description to the pulmonary nodule. These two types are appearance features and shape features. For the appearance features different texture appearance descriptors are developed, namely the 3D histogram of oriented gradient, 3D spherical sector isosurface histogram of oriented gradient, 3D adjusted local binary pattern, 3D resolved ambiguity local binary pattern, multi-view analytical local binary pattern, and Markov Gibbs random field. Each one of these descriptors gives a good description for the nodule texture and the level of its signal homogeneity which is a distinguishable feature between benign and malignant nodules. For the shape features multi-view peripheral sum curvature scale space, spherical harmonics expansions, and different group of fundamental geometric features are utilized to describe the nodule shape complexity. Finally, the fusion of different combinations of these features, which is based on two stages is introduced. The first stage generates a primary estimation for every descriptor. Followed by the second stage that consists of an autoencoder with a single layer augmented with a softmax classifier to provide us with the ultimate classification of the nodule. These different combinations of descriptors are combined into different frameworks that are evaluated using different datasets. The first dataset is the Lung Image Database Consortium which is a benchmark publicly available dataset for lung nodule detection and diagnosis. The second dataset is our local acquired computed tomography imaging data that has been collected from the University of Louisville hospital and the research protocol was approved by the Institutional Review Board at the University of Louisville (IRB number 10.0642). These frameworks accuracy was about 94%, which make the proposed frameworks demonstrate promise to be valuable tool for the detection of lung cancer

Meningioma segmentation in T1-weighted MRI leveraging global context and attention mechanisms

Meningiomas are the most common type of primary brain tumor, accounting for approximately 30% of all brain tumors. A substantial number of these tumors are never surgically removed but rather monitored over time. Automatic and precise meningioma segmentation is therefore beneficial to enable reliable growth estimation and patient-specific treatment planning. In this study, we propose the inclusion of attention mechanisms over a U-Net architecture: (i) Attention-gated U-Net (AGUNet) and (ii) Dual Attention U-Net (DAUNet), using a 3D MRI volume as input. Attention has the potential to leverage the global context and identify features' relationships across the entire volume. To limit spatial resolution degradation and loss of detail inherent to encoder-decoder architectures, we studied the impact of multi-scale input and deep supervision components. The proposed architectures are trainable end-to-end and each concept can be seamlessly disabled for ablation studies. The validation studies were performed using a 5-fold cross validation over 600 T1-weighted MRI volumes from St. Olavs University Hospital, Trondheim, Norway. For the best performing architecture, an average Dice score of 81.6% was reached for an F1-score of 95.6%. With an almost perfect precision of 98%, meningiomas smaller than 3ml were occasionally missed hence reaching an overall recall of 93%. Leveraging global context from a 3D MRI volume provided the best performances, even if the native volume resolution could not be processed directly. Overall, near-perfect detection was achieved for meningiomas larger than 3ml which is relevant for clinical use. In the future, the use of multi-scale designs and refinement networks should be further investigated to improve the performance. A larger number of cases with meningiomas below 3ml might also be needed to improve the performance for the smallest tumors.Comment: 16 pages, 5 figures, 3 tables. Submitted to Artificial Intelligence in Medicin