A Decision Support System (DSS) for Breast Cancer Detection Based on Invariant Feature Extraction, Classification, and Retrieval of Masses of Mammographic Images

This paper presents an integrated system for the breast cancer detection from mammograms based on automated mass detection, classification, and retrieval with a goal to support decision-making by retrieving and displaying the relevant past cases as well as predicting the images as benign or malignant. It is hypothesized that the proposed diagnostic aid would refresh the radiologist’s mental memory to guide them to a precise diagnosis with concrete visualizations instead of only suggesting a second diagnosis like many other CAD systems. Towards achieving this goal, a Graph-Based Visual Saliency (GBVS) method is used for automatic mass detection, invariant features are extracted based on using Non-Subsampled Contourlet transform (NSCT) and eigenvalues of the Hessian matrix in a histogram of oriented gradients (HOG), and finally classification and retrieval are performed based on using Support Vector Machines (SVM) and Extreme Learning Machines (ELM), and a linear combination-based similarity fusion approach. The image retrieval and classification performances are evaluated and compared in the benchmark Digital Database for Screening Mammography (DDSM) of 2604 cases by using both the precision-recall and classification accuracies. Experimental results demonstrate the effectiveness of the proposed system and show the viability of a real-time clinical application

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

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

Developing and Applying CAD-generated Image Markers to Assist Disease Diagnosis and Prognosis Prediction

Developing computer-aided detection and/or diagnosis (CAD) schemes has been an active research topic in medical imaging informatics (MII) with promising results in assisting clinicians in making better diagnostic and/or clinical decisions in the last two decades. To build robust CAD schemes, we need to develop state-of-the-art image processing and machine learning (ML) algorithms to optimize each step in the CAD pipeline, including detection and segmentation of the region of interest, optimal feature generation, followed by integration to ML classifiers. In my dissertation, I conducted multiple studies investigating the feasibility of developing several novel CAD schemes in the field of medicine concerning different purposes. The first study aims to investigate how to optimally develop a CAD scheme of contrast-enhanced digital mammography (CEDM) images to classify breast masses. CEDM includes both low energy (LE) and dual-energy subtracted (DES) images. A CAD scheme was applied to segment mass regions depicting LE and DES images separately. Optimal segmentation results generated from DES images were also mapped to LE images or vice versa. After computing image features, multilayer perceptron-based ML classifiers integrated with a correlation-based feature subset evaluator and leave-one-case-out cross-validation method were built to classify mass regions. The study demonstrated that DES images eliminated the overlapping effect of dense breast tissue, which helps improve mass segmentation accuracy. By mapping mass regions segmented from DES images to LE images, CAD yields significantly improved performance. The second study aims to develop a new quantitative image marker computed from the pre-intervention computed tomography perfusion (CTP) images and evaluate its feasibility to predict clinical outcome among acute ischemic stroke (AIS) patients undergoing endovascular mechanical thrombectomy after diagnosis of large vessel occlusion. A CAD scheme is first developed to pre-process CTP images of different scanning series for each study case, perform image segmentation, quantify contrast-enhanced blood volumes in bilateral cerebral hemispheres, and compute image features related to asymmetrical cerebral blood flow patterns based on the cumulative cerebral blood flow curves of two hemispheres. Next, image markers based on a single optimal feature and ML models fused with multi-features are developed and tested to classify AIS cases into two classes of good and poor prognosis based on the Modified Rankin Scale. The study results show that ML model trained using multiple features yields significantly higher classification performance than the image marker using the best single feature (p<0.01). This study demonstrates the feasibility of developing a new CAD scheme to predict the prognosis of AIS patients in the hyperacute stage, which has the potential to assist clinicians in optimally treating and managing AIS patients. The third study aims to develop and test a new CAD scheme to predict prognosis in aneurysmal subarachnoid hemorrhage (aSAH) patients using brain CT images. Each patient had two sets of CT images acquired at admission and prior to discharge. CAD scheme was applied to segment intracranial brain regions into four subregions, namely, cerebrospinal fluid (CSF), white matter (WM), gray matter (GM), and extraparenchymal blood (EPB), respectively. CAD then computed nine image features related to 5 volumes of the segmented sulci, EPB, CSF, WM, GM, and four volumetrical ratios to sulci. Subsequently, 16 ML models were built using multiple features computed either from CT images acquired at admission or prior to discharge to predict eight prognosis related parameters. The results show that ML models trained using CT images acquired at admission yielded higher accuracy to predict short-term clinical outcomes, while ML models trained using CT images acquired prior to discharge had higher accuracy in predicting long-term clinical outcomes. Thus, this study demonstrated the feasibility of predicting the prognosis of aSAH patients using new ML model-generated quantitative image markers. The fourth study aims to develop and test a new interactive computer-aided detection (ICAD) tool to quantitatively assess hemorrhage volumes. After loading each case, the ICAD tool first segments intracranial brain volume, performs CT labeling of each voxel. Next, contour-guided image-thresholding techniques based on CT Hounsfield Unit are used to estimate and segment hemorrhage-associated voxels (ICH). Next, two experienced neurology residents examine and correct the markings of ICH categorized into either intraparenchymal hemorrhage (IPH) or intraventricular hemorrhage (IVH) to obtain the true markings. Additionally, volumes and maximum two-dimensional diameter of each sub-type of hemorrhage are also computed for understanding ICH prognosis. The performance to segment hemorrhage regions between semi-automated ICAD and the verified neurology residents’ true markings is evaluated using dice similarity coefficient (DSC). The data analysis results in the study demonstrate that the new ICAD tool enables to segment and quantify ICH and other hemorrhage volumes with higher DSC. Finally, the fifth study aims to bridge the gap between traditional radiomics and deep learning systems by comparing and assessing these two technologies in classifying breast lesions. First, one CAD scheme is applied to segment lesions and compute radiomics features. In contrast, another scheme applies a pre-trained residual net architecture (ResNet50) as a transfer learning model to extract automated features. Next, the principal component algorithm processes both initially computed radiomics and automated features to create optimal feature vectors. Then, several support vector machine (SVM) classifiers are built using the optimized radiomics or automated features. This study indicates that (1) CAD built using only deep transfer learning yields higher classification performance than the traditional radiomic-based model, (2) SVM trained using the fused radiomics and automated features does not yield significantly higher AUC, and (3) radiomics and automated features contain highly correlated information in lesion classification. In summary, in all these studies, I developed and investigated several key concepts of CAD pipeline, including (i) pre-processing algorithms, (ii) automatic detection and segmentation schemes, (iii) feature extraction and optimization methods, and (iv) ML and data analysis models. All developed CAD models are embedded with interactive and visually aided graphical user interfaces (GUIs) to provide user functionality. These techniques present innovative approaches for building quantitative image markers to build optimal ML models. The study results indicate the underlying CAD scheme's potential application to assist radiologists in clinical settings for their assessments in diagnosing disease and improving their overall performance

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

DEVELOPING MEDICAL IMAGE SEGMENTATION AND COMPUTER-AIDED DIAGNOSIS SYSTEMS USING DEEP NEURAL NETWORKS

Diagnostic medical imaging is an important non-invasive tool in medicine. It provides doctors (i.e., radiologists) with rich diagnostic information in clinical practice. Computer-aided diagnosis (CAD) schemes aim to provide a tool to assist the doctors for reading and interpreting medical images. Traditional CAD schemes are based on hand-crafted features and shallow supervised learning algorithms. They are greatly limited by the difficulties of accurate region segmentation and effective feature extraction. In this dissertation, our motivation is to apply deep learning techniques to address these challenges. We comprehensively investigated the feasibilities of applying deep learning technique to develop medical image segmentation and computer-aided diagnosis schemes for different imaging modalities and different tasks. First, we applied a two-step convolutional neural network architecture for selection of abdomen part and segmentation of subtypes of adipose tissue from abdominal CT images. We demonstrated high agreement between the segmentation generated by human and by our proposed deep learning models. Second, we explored to combine transfer learning technique with traditional hand-crafted features to improve the accuracy of breast mass classification from digital mammograms. Our results show that the ensemble of hand-crafted features and transferred features yields improvement of prediction performances. Third, we proposed a 3D fully convolutional network architecture with a novel coarse-to-fine residual module for prostate segmentation from MRI. State-of-art segmentation accuracy was obtained by using this model. We also investigated the feasibilities of applying fully convolutional network for prostate cancer detection based on multi-parametric MRI and obtained promising detection accuracy. Last, we proposed a novel cascaded neural network architecture with post-processing steps for nuclear segmentation from histology images. Superiority of the model was demonstrated by experiments. In summary, these study results demonstrated that deep learning is a very promising technology to help significantly improve efficacy of developing computer-aided diagnosis schemes of medical images and achieve higher performance

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 192

This bibliography lists 247 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1979