Preoperative Systems for Computer Aided Diagnosis based on Image Registration: Applications to Breast Cancer and Atherosclerosis

Computer Aided Diagnosis (CAD) systems assist clinicians including radiologists and cardiologists to detect abnormalities and highlight conspicuous possible disease. Implementing a pre-operative CAD system contains a framework that accepts related technical as well as clinical parameters as input by analyzing the predefined method and demonstrates the prospective output. In this work we developed the Computer Aided Diagnostic System for biomedical imaging analysis of two applications on Breast Cancer and Atherosclerosis. The aim of the first CAD application is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user-independent. Base on the fact that automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time-temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. We implemented and evaluated 3 different 3D time-series registration methods: 1. Linear affine, 2. Non-linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70±0.03, 0.74±0.03 and 0.81±0.09 (out of 1) for Affine, BSpline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons registration method outperforms also with the best breast alignment and non-negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons registration as an effective technique for time-series dynamic infrared registration, to stabilize the local temperature oscillation. The aim of the second implemented CAD application is to assess contribution of calcification in plaque vulnerability and wall rupture and to find its maximum resistance before break in image-based models of carotid artery stenting. The role of calcification inside fibroatheroma during carotid artery stenting operation is controversial in which cardiologists face two major problems during the placement: (i) “plaque protrusion” (i.e. elastic fibrous caps containing early calcifications that penetrate inside the stent); (ii) “plaque vulnerability” (i.e. stiff plaques with advanced calcifications that break the arterial wall or stent). Finite Element Analysis was used to simulate the balloon and stent expansion as a preoperative patient-specific virtual framework. A nonlinear static structural analysis was performed on 20 patients acquired using in vivo MDCT angiography. The Agatston Calcium score was obtained for each patient and subject-specific local Elastic Modulus (EM) was calculated. The in silico results showed that by imposing average ultimate external load of 1.1MPa and 2.3MPa on balloon and stent respectively, average ultimate stress of 55.7±41.2kPa and 171±41.2kPa are obtained on calcifications. The study reveals that a significant positive correlation (R=0.85, p<0.0001) exists on stent expansion between EM of calcification and ultimate stress as well as Plaque Wall Stress (PWS) (R=0.92, p<0.0001), comparing to Ca score that showed insignificant associations with ultimate stress (R=0.44, p=0.057) and PWS (R=0.38, p=0.103), suggesting minor impact of Ca score in plaque rupture. These average data are in good agreement with results obtained by other research groups and we believe this approach enriches the arsenal of tools available for pre-operative prediction of carotid artery stenting procedure in the presence of calcified plaques

COMPUTER AIDED SYSTEM FOR BREAST CANCER DIAGNOSIS USING CURVELET TRANSFORM

Breast cancer is a leading cause of death among women worldwide. Early detection is the key for improving breast cancer prognosis. Digital mammography remains one of the most suitable tools for early detection of breast cancer. Hence, there are strong needs for the development of computer aided diagnosis (CAD) systems which have the capability to help radiologists in decision making. The main goal is to increase the diagnostic accuracy rate. In this thesis we developed a computer aided system for the diagnosis and detection of breast cancer using curvelet transform. Curvelet is a multiscale transform which possess directionality and anisotropy, and it breaks some inherent limitations of wavelet in representing edges in images. We started this study by developing a diagnosis system. Five feature extraction methods were developed with curvelet and wavelet coefficients to differentiate between different breast cancer classes. The results with curvelet and wavelet were compared. The experimental results show a high performance of the proposed methods and classification accuracy rate achieved 97.30%. The thesis then provides an automatic system for breast cancer detection. An automatic thresholding algorithm was used to separate the area composed of the breast and the pectoral muscle from the background of the image. Subsequently, a region growing algorithm was used to locate the pectoral muscle and suppress it from the breast. Then, the work concentrates on the segmentation of region of interest (ROI). Two methods are suggested to accomplish the segmentation stage: an adaptive thresholding method and a pattern matching method. Once the ROI has been identified, an automatic cropping is performed to extract it from the original mammogram. Subsequently, the suggested feature extraction methods were applied to the segmented ROIs. Finally, the K-Nearest Neighbor (KNN) and Support Vector Machine (SVM) classifiers were used to determine whether the region is abnormal or normal. At this level, the study focuses on two abnormality types (mammographic masses and architectural distortion). Experimental results show that the introduced methods have very high detection accuracies. The effectiveness of the proposed methods has been tested with Mammographic Image Analysis Society (MIAS) dataset. Throughout the thesis all proposed methods and algorithms have been applied with both curvelet and wavelet for comparison and statistical tests were also performed. The overall results show that curvelet transform performs better than wavelet and the difference is statistically significant

Noise-Enhanced and Human Visual System-Driven Image Processing: Algorithms and Performance Limits

This dissertation investigates the problem of image processing based on stochastic resonance (SR) noise and human visual system (HVS) properties, where several novel frameworks and algorithms for object detection in images, image enhancement and image segmentation as well as the method to estimate the performance limit of image segmentation algorithms are developed. Object detection in images is a fundamental problem whose goal is to make a decision if the object of interest is present or absent in a given image. We develop a framework and algorithm to enhance the detection performance of suboptimal detectors using SR noise, where we add a suitable dose of noise into the original image data and obtain the performance improvement. Micro-calcification detection is employed in this dissertation as an illustrative example. The comparative experiments with a large number of images verify the efficiency of the presented approach. Image enhancement plays an important role and is widely used in various vision tasks. We develop two image enhancement approaches. One is based on SR noise, HVS-driven image quality evaluation metrics and the constrained multi-objective optimization (MOO) technique, which aims at refining the existing suboptimal image enhancement methods. Another is based on the selective enhancement framework, under which we develop several image enhancement algorithms. The two approaches are applied to many low quality images, and they outperform many existing enhancement algorithms. Image segmentation is critical to image analysis. We present two segmentation algorithms driven by HVS properties, where we incorporate the human visual perception factors into the segmentation procedure and encode the prior expectation on the segmentation results into the objective functions through Markov random fields (MRF). Our experimental results show that the presented algorithms achieve higher segmentation accuracy than many representative segmentation and clustering algorithms available in the literature. Performance limit, or performance bound, is very useful to evaluate different image segmentation algorithms and to analyze the segmentability of the given image content. We formulate image segmentation as a parameter estimation problem and derive a lower bound on the segmentation error, i.e., the mean square error (MSE) of the pixel labels considered in our work, using a modified Cramér-Rao bound (CRB). The derivation is based on the biased estimator assumption, whose reasonability is verified in this dissertation. Experimental results demonstrate the validity of the derived bound

Detecting microcalcification clusters in digital mammograms: Study for inclusion into computer aided diagnostic prompting system

Among signs of breast cancer encountered in digital mammograms radiologists point to microcalcification clusters (MCCs). Their detection is a challenging problem from both medical and image processing point of views. This work presents two concurrent methods for MCC detection, and studies their possible inclusion to a computer aided diagnostic prompting system. One considers Wavelet Domain Hidden Markov Tree (WHMT) for modeling microcalcification edges. The model is used for differentiation between MC and non-MC edges based on the weighted maximum likelihood (WML) values. The classification of objects is carried out using spatial filters. The second method employs SUSAN edge detector in the spatial domain for mammogram segmentation. Classification of objects as calcifications is carried out using another set of spatial filters and Feedforward Neural Network (NN). A same distance filter is employed in both methods to find true clusters. The analysis of two methods is performed on 54 image regions from the mammograms selected randomly from DDSM database, including benign and cancerous cases as well as cases which can be classified as hard cases from both radiologists and the computer perspectives. WHMT/WML is able to detect 98.15% true positive (TP) MCCs under 1.85% of false positives (FP), whereas the SUSAN/NN method achieves 94.44% of TP at the cost of 1.85% for FP. The comparison of these two methods suggests WHMT/WML for the computer aided diagnostic prompting. It also certifies the low false positive rates for both methods, meaning less biopsy tests per patient

COMPUTER AIDED SYSTEM FOR BREAST CANCER DIAGNOSIS USING CURVELET TRANSFORM

Breast cancer is a leading cause of death among women worldwide. Early detection is the key for improving breast cancer prognosis. Digital mammography remains one of the most suitable tools for early detection of breast cancer. Hence, there are strong needs for the development of computer aided diagnosis (CAD) systems which have the capability to help radiologists in decision making. The main goal is to increase the diagnostic accuracy rate. In this thesis we developed a computer aided system for the diagnosis and detection of breast cancer using curvelet transform. Curvelet is a multiscale transform which possess directionality and anisotropy, and it breaks some inherent limitations of wavelet in representing edges in images. We started this study by developing a diagnosis system. Five feature extraction methods were developed with curvelet and wavelet coefficients to differentiate between different breast cancer classes. The results with curvelet and wavelet were compared. The experimental results show a high performance of the proposed methods and classification accuracy rate achieved 97.30%. The thesis then provides an automatic system for breast cancer detection. An automatic thresholding algorithm was used to separate the area composed of the breast and the pectoral muscle from the background of the image. Subsequently, a region growing algorithm was used to locate the pectoral muscle and suppress it from the breast. Then, the work concentrates on the segmentation of region of interest (ROI). Two methods are suggested to accomplish the segmentation stage: an adaptive thresholding method and a pattern matching method. Once the ROI has been identified, an automatic cropping is performed to extract it from the original mammogram. Subsequently, the suggested feature extraction methods were applied to the segmented ROIs. Finally, the K-Nearest Neighbor (KNN) and Support Vector Machine (SVM) classifiers were used to determine whether the region is abnormal or normal. At this level, the study focuses on two abnormality types (mammographic masses and architectural distortion). Experimental results show that the introduced methods have very high detection accuracies. The effectiveness of the proposed methods has been tested with Mammographic Image Analysis Society (MIAS) dataset. Throughout the thesis all proposed methods and algorithms have been applied with both curvelet and wavelet for comparison and statistical tests were also performed. The overall results show that curvelet transform performs better than wavelet and the difference is statistically significant

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

Coupled Theoretical and Experimental Methods to Understand Growth and Remodeling of In Situ Engineered Vascular Grafts in Young and Aged Hosts

In 1975, Rodbard introduced the concept of mechanical homeostasis; that arteries have an inherent capacity to maintain homeostatic stress states by altering their morphology through a negative feedback mechanism in response to mechanical loads. More recently, this capacity has been leveraged to develop acellular, in situ tissue-engineered vascular grafts (iTEVGs) which promote host growth and remodeling (G&R) to develop new arteries (neoarteries) in the tissue's functional site (in situ). These grafts offer a much-needed option to address the lack of viable autologous conduits, difficulties in scaling traditional tissue engineered grafts, and the rising demand for bypass grafting in an aging population. One such acellular, poly (glycerol sebacate) (PGS) iTEVG developed by Wang et al. has demonstrated in situ mature elastin and collagen formation in young hosts. However, the trial and error nature of graft design, coupled with the lack of knowledge of fundamental mechanisms guiding neoarterial G&R impedes efforts to translate these successes across age and species. In this work, we take a coupled theoretical and experimental approach to understanding salient mechanisms guiding neoartery formation in young and aged hosts. We developed a mathematical model of graft degradation based on in vitro assessment of enzymatic degradation. Next, we translated successful neoartery development from a rat aorta to the substantially smaller, rat carotid artery. We determined that after three-months of remodeling, the neoartery has similar mechanical properties to those of the clinical gold standard, vein graft. We then successfully translated the iTEVG to an aged murine carotid model and assessed differences in mechanical, microstructural, and biological stages of neoarterial G&R in young versus aged hosts over the course of six months. Subsequently, a constrained mixture model-based G&R tool was developed, informed with these experimental data, and used to predict long-term neoarterial G&R response in both age groups. Finally, we identified a common mode of adverse remodeling in neoarteries - rupture and calcification. Motivated by these results, we developed new techniques to analyze calcification in a parallel, model system exhibiting similar modes of adverse remodeling - cerebral aneurysms. These results provide insights for future work developing strategies necessary to optimally design iTEVGs

Enhanced algorithms for lesion detection and recognition in ultrasound breast images

Mammography is the gold standard for breast cancer detection. However, it has very high false positive rates and is based on ionizing radiation. This has led to interest in using multi-modal approaches. One modality is diagnostic ultrasound, which is based on non-ionizing radiation and picks up many of the cancers that are generally missed by mammography. However, the presence of speckle noise in ultrasound images has a negative effect on image interpretation. Noise reduction, inconsistencies in capture and segmentation of lesions still remain challenging open research problems in ultrasound images. The target of the proposed research is to enhance the state-of-art computer vision algorithms used in ultrasound imaging and to investigate the role of computer processed images in human diagnostic performance. [Continues.

Novel Ultrasound Elastography Imaging System for Breast Cancer Assessment

Abstract Most conventional methods of breast cancer screening such as X-ray, Ultrasound (US) and MRI have some issues ranging from weaknesses associated with tumour detection or classification to high cost or excessive time of image acquisition and reconstruction. Elastography is a non- invasive technique to visualize suspicious areas in soft tissues such as the breast, prostate and myocardium using tissue stiffness as image contrast mechanism. In this study, a breast Elastography system based on US imaging is proposed. This technique is fast, expected to be cost effective and more sensitive and specific compared to conventional US imaging. Unlike current Elastography techniques that image relative elastic modulus, this technique is capable of imaging absolute Young\u27s modulus (YM). In this technique, tissue displacements and surface forces used to mechanically stimulate the tissue are acquired and used as input to reconstruct the tissue YM distribution. For displacements acquisition, two techniques were used in this research: 1) a modified optical flow technique, which estimates the displacement of each node from US pre- and post-compression images and 2) Radio Frequency (RF) signal cross-correlation technique. In the former, displacements are calculated in 2 dimensions whereas in the latter, displacements are calculated in the US axial direction only. For improving the quality of elastography images, surface force data was used to calculate the stress distribution throughout the organ of interest by using an analytical model and a statistical numerical model. For force data acquisition, a system was developed in which load cells are used to measure forces on the surface of the breast. These forces are input into the stress distribution models to estimate the tissue stress distribution. By combining the stress field with the strain field calculated from the acquired displacements using Hooke\u27s law, the YM can be reconstructed efficiently. To validate the proposed technique, numerical and tissue mimicking phantom studies were conducted. For the numerical phantom study, a 3D breast-shape phantom was created with synthetic US pre- and post-compression images where the results showed the feasibility of reconstructing the absolute value of YM of tumour and background. In the tissue mimicking study, a block shape gelatine- agar phantom was constructed with a cylindrical inclusion. Results obtained from this study also indicated reasonably accurate reconstruction of the YM. The quality of the obtained elasticity images shows that image quality is improved by incorporating the adapted stress calculation techniques. Furthermore, the proposed elastography system is reasonably fast and can be potentially used in real-time clinical applications