Bilateral analysis based false positive reduction for computerâ aided mass detection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134848/1/mp6612.pd

Developing Novel Computer Aided Diagnosis Schemes for Improved Classification of Mammography Detected Masses

Mammography imaging is a population-based breast cancer screening tool that has greatly aided in the decrease in breast cancer mortality over time. Although mammography is the most frequently employed breast imaging modality, its performance is often unsatisfactory with low sensitivity and high false positive rates. This is due to the fact that reading and interpreting mammography images remains difficult due to the heterogeneity of breast tumors and dense overlapping fibroglandular tissue. To help overcome these clinical challenges, researchers have made great efforts to develop computer-aided detection and/or diagnosis (CAD) schemes to provide radiologists with decision-making support tools. In this dissertation, I investigate several novel methods for improving the performance of a CAD system in distinguishing between malignant and benign masses. The first study, we test the hypothesis that handcrafted radiomics features and deep learning features contain complementary information, therefore the fusion of these two types of features will increase the feature representation of each mass and improve the performance of CAD system in distinguishing malignant and benign masses. Regions of interest (ROI) surrounding suspicious masses are extracted and two types of features are computed. The first set consists of 40 radiomic features and the second set includes deep learning (DL) features computed from a pretrained VGG16 network. DL features are extracted from two pseudo color image sets, producing a total of three feature vectors after feature extraction, namely: handcrafted, DL-stacked, DL-pseudo. Linear support vector machines (SVM) are trained using each feature set alone and in combinations. Results show that the fusion CAD system significantly outperforms the systems using either feature type alone (AUC=0.756±0.042 p<0.05). This study demonstrates that both handcrafted and DL futures contain useful complementary information and that fusion of these two types of features increases the CAD classification performance. In the second study, we expand upon our first study and develop a novel CAD framework that fuses information extracted from ipsilateral views of bilateral mammograms using both DL and radiomics feature extraction methods. Each case in this study is represented by four images which includes the craniocaudal (CC) and mediolateral oblique (MLO) view of left and right breast. First, we extract matching ROIs from each of the four views using an ipsilateral matching and bilateral registration scheme to ensure masses are appropriately matched. Next, the handcrafted radiomics features and VGG16 model-generated features are extracted from each ROI resulting in eight feature vectors. Then, after reducing feature dimensionality and quantifying the bilateral asymmetry, we test four fusion methods. Results show that multi-view CAD systems significantly outperform single-view systems (AUC = 0.876±0.031 vs AUC = 0.817±0.026 for CC view and 0.792±0.026 for MLO view, p<0.001). The study demonstrates that the shift from single-view CAD to four-view CAD and the inclusion of both deep transfer learning and radiomics features increases the feature representation of the mass thus improves CAD performance in distinguishing between malignant and benign breast lesions. In the third study, we build upon the first and second studies and investigate the effects of pseudo color image generation in classifying suspicious mammography detected breast lesions as malignant or benign using deep transfer learning in a multi-view CAD scheme. Seven pseudo color image sets are created through a combination of the original grayscale image, a histogram equalized image, a bilaterally filtered image, and a segmented mass image. Using the multi-view CAD framework developed in the previous study, we observe that the two pseudo-color sets created using a segmented mass in one of the three image channels performed significantly better than all other pseudo-color sets (AUC=0.882, p<0.05 for all comparisons and AUC=0.889, p<0.05 for all comparisons). The results of this study support our hypothesis that pseudo color images generated with a segmented mass optimize the mammogram image feature representation by providing increased complementary information to the CADx scheme which results in an increase in the performance in classifying suspicious mammography detected breast lesions as malignant or benign. In summary, each of the studies presented in this dissertation aim to increase the accuracy of a CAD system in classifying suspicious mammography detected masses. Each of these studies takes a novel approach to increase the feature representation of the mass that needs to be classified. The results of each study demonstrate the potential utility of these CAD schemes as an aid to radiologists in the clinical workflow

Applying novel machine learning technology to optimize computer-aided detection and diagnosis of medical images

The purpose of developing Computer-Aided Detection (CAD) schemes is to assist physicians (i.e., radiologists) in interpreting medical imaging findings and reducing inter-reader variability more accurately. In developing CAD schemes, Machine Learning (ML) plays an essential role because it is widely used to identify effective image features from complex datasets and optimally integrate them with the classifiers, which aims to assist the clinicians to more accurately detect early disease, classify disease types and predict disease treatment outcome. In my dissertation, in different studies, I assess the feasibility of developing several novel CAD systems in the area of medical imaging for different purposes. The first study aims to develop and evaluate a new computer-aided diagnosis (CADx) scheme based on analysis of global mammographic image features to predict the likelihood of cases being malignant. CADx scheme is applied to pre-process mammograms, generate two image maps in the frequency domain using discrete cosine transform and fast Fourier transform, compute bilateral image feature differences from left and right breasts, and apply a support vector machine (SVM) method to predict the likelihood of the case being malignant. This study demonstrates the feasibility of developing a new global image feature analysis based CADx scheme of mammograms with high performance. This new CADx approach is more efficient in development and potentially more robust in future applications by avoiding difficulty and possible errors in breast lesion segmentation. In the second study, to automatically identify a set of effective mammographic image features and build an optimal breast cancer risk stratification model, I investigate advantages of applying a machine learning approach embedded with a locally preserving projection (LPP) based feature combination and regeneration algorithm to predict short-term breast cancer risk. To this purpose, a computer-aided image processing scheme is applied to segment fibro-glandular tissue depicted on mammograms and initially compute 44 features related to the bilateral asymmetry of mammographic tissue density distribution between left and right breasts. Next, an embedded LLP algorithm optimizes the feature space and regenerates a new operational vector with 4 features using a maximal variance approach. This study demonstrates that applying the LPP algorithm effectively reduces feature dimensionality, and yields higher and potentially more robust performance in predicting short-term breast cancer risk. In the third study, to more precisely classify malignant lesions, I investigate the feasibility of applying a random projection algorithm to build an optimal feature vector from the initially CAD-generated large feature pool and improve the performance of the machine learning model. In this process, a CAD scheme is first applied to segment mass regions and initially compute 181 features. An SVM model embedded with the feature dimensionality reduction method is then built to predict the likelihood of lesions being malignant. This study demonstrates that the random project algorithm is a promising method to generate optimal feature vectors to improve the performance of machine learning models of medical images. The last study aims to develop and test a new CAD scheme of chest X-ray images to detect coronavirus (COVID-19) infected pneumonia. To this purpose, the CAD scheme first applies two image preprocessing steps to remove the majority of diaphragm regions, process the original image using a histogram equalization algorithm, and a bilateral low-pass filter. Then, the original image and two filtered images are used to form a pseudo color image. This image is fed into three input channels of a transfer learning-based convolutional neural network (CNN) model to classify chest X-ray images into 3 classes of COVID-19 infected pneumonia, other community-acquired no-COVID-19 infected pneumonia, and normal (non-pneumonia) cases. This study demonstrates that adding two image preprocessing steps and generating a pseudo color image plays an essential role in developing a deep learning CAD scheme of chest X-ray images to improve accuracy in detecting COVID-19 infected pneumonia. In summary, I developed and presented several image pre-processing algorithms, feature extraction methods, and data optimization techniques to present innovative approaches for quantitative imaging markers based on machine learning systems in all these studies. The studies' simulation and results show the discriminative performance of the proposed CAD schemes on different application fields helpful to assist radiologists on their assessments in diagnosing disease and improve their overall performance

DEVELOPING NOVEL COMPUTER-AIDED DETECTION AND DIAGNOSIS SYSTEMS OF MEDICAL IMAGES

Reading medical images to detect and diagnose diseases is often difficult and has large inter-reader variability. To address this issue, developing computer-aided detection and diagnosis (CAD) schemes or systems of medical images has attracted broad research interest in the last several decades. Despite great effort and significant progress in previous studies, only limited CAD schemes have been used in clinical practice. Thus, developing new CAD schemes is still a hot research topic in medical imaging informatics field. In this dissertation, I investigate the feasibility of developing several new innovative CAD schemes for different application purposes. First, to predict breast tumor response to neoadjuvant chemotherapy and reduce unnecessary aggressive surgery, I developed two CAD schemes of breast magnetic resonance imaging (MRI) to generate quantitative image markers based on quantitative analysis of global kinetic features. Using the image marker computed from breast MRI acquired pre-chemotherapy, CAD scheme enables to predict radiographic complete response (CR) of breast tumors to neoadjuvant chemotherapy, while using the imaging marker based on the fusion of kinetic and texture features extracted from breast MRI performed after neoadjuvant chemotherapy, CAD scheme can better predict the pathologic complete response (pCR) of the patients. Second, to more accurately predict prognosis of stroke patients, quantifying brain hemorrhage and ventricular cerebrospinal fluid depicting on brain CT images can play an important role. For this purpose, I developed a new interactive CAD tool to segment hemorrhage regions and extract radiological imaging marker to quantitatively determine the severity of aneurysmal subarachnoid hemorrhage at presentation and correlate the estimation with various homeostatic/metabolic derangements and predict clinical outcome. Third, to improve the efficiency of primary antibody screening processes in new cancer drug development, I developed a CAD scheme to automatically identify the non-negative tissue slides, which indicate reactive antibodies in digital pathology images. Last, to improve operation efficiency and reliability of storing digital pathology image data, I developed a CAD scheme using optical character recognition algorithm to automatically extract metadata from tissue slide label images and reduce manual entry for slide tracking and archiving in the tissue pathology laboratories. In summary, in these studies, we developed and tested several innovative approaches to identify quantitative imaging markers with high discriminatory power. In all CAD schemes, the graphic user interface-based visual aid tools were also developed and implemented. Study results demonstrated feasibility of applying CAD technology to several new application fields, which has potential to assist radiologists, oncologists and pathologists improving accuracy and consistency in disease diagnosis and prognosis assessment of using medical image

Mammography

In this volume, the topics are constructed from a variety of contents: the bases of mammography systems, optimization of screening mammography with reference to evidence-based research, new technologies of image acquisition and its surrounding systems, and case reports with reference to up-to-date multimodality images of breast cancer. Mammography has been lagged in the transition to digital imaging systems because of the necessity of high resolution for diagnosis. However, in the past ten years, technical improvement has resolved the difficulties and boosted new diagnostic systems. We hope that the reader will learn the essentials of mammography and will be forward-looking for the new technologies. We want to express our sincere gratitude and appreciation?to all the co-authors who have contributed their work to this volume

Developing novel quantitative imaging analysis schemes based machine learning for cancer research

The computer-aided detection (CAD) scheme is a developing technology in the medical imaging field, and it attracted extensive research interest in recent years. In this dissertation, I investigated the feasibility of developing several new novel CAD schemes for different cancer research purposes. First, I investigated the feasibility of identifying a new quantitative imaging marker based on false-positives generated by a computer-aided detection (CAD) scheme to predict short-term breast cancer risk. For this study, an existing CAD scheme was applied “as is” to process each image. From CAD-generated results, some detection features were computed from each image. Two logistic regression models were then trained and tested using a leave-one-case-out cross-validation method to predict each testing case's likelihood of being positive in the next subsequent screening. This study demonstrated that CAD-generated false-positives contain valuable information to predict short-term breast cancer risk. Second, I identified and applied quantitative imaging features computed from ultrasound images of athymic nude mice to predict tumor response to treatment at an early stage. For this study, a CAD scheme was developed to perform tumor segmentation and image feature analysis. The study demonstrated the feasibility of extracting quantitative image features from the ultrasound images taken at an early treatment stage to predict tumor response to therapies. Last, I optimized a machine learning model for predicting peritoneal metastasis in gastric cancer. For this purpose, I have developed a CAD scheme to segment the tumor volume and extract quantitative image features automatically. Then, I reduced the dimensionality of features with a new method named random projection to optimize the model's performance. Finally, the gradient boosting machine model was applied along with a synthetic minority oversampling technique to predict peritoneal metastasis risk. Results suggested that the random projection method yielded promising results in improving the accuracy performance in peritoneal metastasis prediction. In summary, in my Ph.D. studies, I have investigated and tested several innovative approaches to develop different CAD schemes and identify quantitative imaging markers with high discriminatory power in various cancer research applications. Study results demonstrated the feasibility of applying CAD technology to several new application fields, which can help radiologists and gynecologists improve accuracy and consistency in disease diagnosis and prognosis assessment of using the medical image

Digital breast tomosynthesis: A state of the art review

Digital Breast Tomosynthesis (DBT) is an X-ray mammography technique where multiple low-dose projection images of the breast are reconstructed in multiple tomographic images creating a semi-3D mammogram. This enables the visualization of a sequential set of thin sections of the breast, overcoming the masking effect of overlying fibroglandular breast tissue, then improving carcinoma detection and reducing false-positive cases. This review aims at describing current DBT technique, analyzing DBT in clinical practice and providing an overview of published studies on clinical experience with DBT in the screening and diagnostic settings

Computer aided diagnosis system for breast cancer using deep learning.

The recent rise of big data technology surrounding the electronic systems and developed toolkits gave birth to new promises for Artificial Intelligence (AI). With the continuous use of data-centric systems and machines in our lives, such as social media, surveys, emails, reports, etc., there is no doubt that data has gained the center of attention by scientists and motivated them to provide more decision-making and operational support systems across multiple domains. With the recent breakthroughs in artificial intelligence, the use of machine learning and deep learning models have achieved remarkable advances in computer vision, ecommerce, cybersecurity, and healthcare. Particularly, numerous applications provided efficient solutions to assist radiologists and doctors for medical imaging analysis, which has remained the essence of the visual representation that is used to construct the final observation and diagnosis. Medical research in cancerology and oncology has been recently blended with the knowledge gained from computer engineering and data science experts. In this context, an automatic assistance or commonly known as Computer-aided Diagnosis (CAD) system has become a popular area of research and development in the last decades. As a result, the CAD systems have been developed using multidisciplinary knowledge and expertise and they have been used to analyze the patient information to assist clinicians and practitioners in their decision-making process. Treating and preventing cancer remains a crucial task that radiologists and oncologists face every day to detect and investigate abnormal tumors. Therefore, a CAD system could be developed to provide decision support for many applications in the cancer patient care processes, such as lesion detection, characterization, cancer staging, tumors assessment, recurrence, and prognosis prediction. Breast cancer has been considered one of the common types of cancers in females across the world. It was also considered the leading cause of mortality among women, and it has been increased drastically every year. Early detection and diagnosis of abnormalities in screened breasts has been acknowledged as the optimal solution to examine the risk of developing breast cancer and thus reduce the increasing mortality rate. Accordingly, this dissertation proposes a new state-of-the-art CAD system for breast cancer diagnosis that is based on deep learning technology and cutting-edge computer vision techniques. Mammography screening has been recognized as the most effective tool to early detect breast lesions for reducing the mortality rate. It helps reveal abnormalities in the breast such as Mass lesion, Architectural Distortion, Microcalcification. With the number of daily patients that were screened is continuously increasing, having a second reading tool or assistance system could leverage the process of breast cancer diagnosis. Mammograms could be obtained using different modalities such as X-ray scanner and Full-Field Digital mammography (FFDM) system. The quality of the mammograms, the characteristics of the breast (i.e., density, size) or/and the tumors (i.e., location, size, shape) could affect the final diagnosis. Therefore, radiologists could miss the lesions and consequently they could generate false detection and diagnosis. Therefore, this work was motivated to improve the reading of mammograms in order to increase the accuracy of the challenging tasks. The efforts presented in this work consists of new design and implementation of neural network models for a fully integrated CAD system dedicated to breast cancer diagnosis. The approach is designed to automatically detect and identify breast lesions from the entire mammograms at a first step using fusion models’ methodology. Then, the second step only focuses on the Mass lesions and thus the proposed system should segment the detected bounding boxes of the Mass lesions to mask their background. A new neural network architecture for mass segmentation was suggested that was integrated with a new data enhancement and augmentation technique. Finally, a third stage was conducted using a stacked ensemble of neural networks for classifying and diagnosing the pathology (i.e., malignant, or benign), the Breast Imaging Reporting and Data System (BI-RADS) assessment score (i.e., from 2 to 6), or/and the shape (i.e., round, oval, lobulated, irregular) of the segmented breast lesions. Another contribution was achieved by applying the first stage of the CAD system for a retrospective analysis and comparison of the model on Prior mammograms of a private dataset. The work was conducted by joining the learning of the detection and classification model with the image-to-image mapping between Prior and Current screening views. Each step presented in the CAD system was evaluated and tested on public and private datasets and consequently the results have been fairly compared with benchmark mammography datasets. The integrated framework for the CAD system was also tested for deployment and showcase. The performance of the CAD system for the detection and identification of breast masses reached an overall accuracy of 97%. The segmentation of breast masses was evaluated together with the previous stage and the approach achieved an overall performance of 92%. Finally, the classification and diagnosis step that defines the outcome of the CAD system reached an overall pathology classification accuracy of 96%, a BIRADS categorization accuracy of 93%, and a shape classification accuracy of 90%. Results given in this dissertation indicate that our suggested integrated framework might surpass the current deep learning approaches by using all the proposed automated steps. Limitations of the proposed work could occur on the long training time of the different methods which is due to the high computation of the developed neural networks that have a huge number of the trainable parameters. Future works can include new orientations of the methodologies by combining different mammography datasets and improving the long training of deep learning models. Moreover, motivations could upgrade the CAD system by using annotated datasets to integrate more breast cancer lesions such as Calcification and Architectural distortion. The proposed framework was first developed to help detect and identify suspicious breast lesions in X-ray mammograms. Next, the work focused only on Mass lesions and segment the detected ROIs to remove the tumor’s background and highlight the contours, the texture, and the shape of the lesions. Finally, the diagnostic decision was predicted to classify the pathology of the lesions and investigate other characteristics such as the tumors’ grading assessment and type of the shape. The dissertation presented a CAD system to assist doctors and experts to identify the risk of breast cancer presence. Overall, the proposed CAD method incorporates the advances of image processing, deep learning, and image-to-image translation for a biomedical application