A Non Invasive Image Based System For Early Diagnosis Of Prostate Cancer

Prostate cancer is the second most fatal cancer experienced by American males. The average American male has a 16.15% chance of developing prostate cancer, which is 8.38% higher than lung cancer, the second most likely cancer. The current in-vitro techniques that are based on analyzing a patients blood and urine have several limitations concerning their accuracy. In addition, the prostate Specific Antigen (PSA) blood-based test, has a high chance of false positive diagnosis, ranging from 28%-58%. Yet, biopsy remains the gold standard for the assessment of prostate cancer, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The major limitation of the relatively small needle biopsy samples is the higher possibility of producing false positive diagnosis. Moreover, the visual inspection system (e.g., Gleason grading system) is not quantitative technique and different observers may classify a sample differently, leading to discrepancies in the diagnosis. As reported in the literature that the early detection of prostate cancer is a crucial step for decreasing prostate cancer related deaths. Thus, there is an urgent need for developing objective, non-invasive image based technology for early detection of prostate cancer. The objective of this dissertation is to develop a computer vision methodology, later translated into a clinically usable software tool, which can improve sensitivity and specificity of early prostate cancer diagnosis based on the well-known hypothesis that malignant tumors are will connected with the blood vessels than the benign tumors. Therefore, using either Diffusion Weighted Magnetic Resonance imaging (DW-MRI) or Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), we will be able to interrelate the amount of blood in the detected prostate tumors by estimating either the Apparent Diffusion Coefficient (ADC) in the prostate with the malignancy of the prostate tumor or perfusion parameters. We intend to validate this hypothesis by demonstrating that automatic segmentation of the prostate from either DW-MRI or DCE-MRI after handling its local motion, provides discriminatory features for early prostate cancer diagnosis. The proposed CAD system consists of three majors components, the first two of which constitute new research contributions to a challenging computer vision problem. The three main components are: (1) A novel Shape-based segmentation approach to segment the prostate from either low contrast DW-MRI or DCE-MRI data; (2) A novel iso-contours-based non-rigid registration approach to ensure that we have voxel-on-voxel matches of all data which may be more difficult due to gross patient motion, transmitted respiratory effects, and intrinsic and transmitted pulsatile effects; and (3) Probabilistic models for the estimated diffusion and perfusion features for both malignant and benign tumors. Our results showed a 98% classification accuracy using Leave-One-Subject-Out (LOSO) approach based on the estimated ADC for 30 patients (12 patients diagnosed as malignant; 18 diagnosed as benign). These results show the promise of the proposed image-based diagnostic technique as a supplement to current technologies for diagnosing prostate cancer.

This book covers novel strategies and state of the art approaches for automated non-invasive systems for early prostate cancer diagnosis. Prostate cancer is the most frequently diagnosed malignancy after skin cancer and the second leading cause of cancer related male deaths in the USA after lung cancer. However, early detection of prostate cancer increases chances of patients’ survival. Generally, The CAD systems analyze the prostate images in three steps: (i) prostate segmentation; (ii) Prostate description or feature extraction; and (iii) classification of the prostate status. Explores all of the latest research and developments in state-of-the art imaging of the prostate from world class experts. Contains a comprehensive overview of 2D/3D Shape Modeling for MRI data. Presents a detailed examination of automated segmentation of the prostate in 3D imaging. Examines Computer-Aided-Diagnosis through automated techniques. There will be extensive references at the end of each chapter to enhance further study.

This text encompass an up-to-date, comprehensive review of the state-of-the-art for gland preserving therapies. Fully updated and revised, this text evaluates the scientific evidence for the evolving trend to treat intermediate risk, clinically localized prostate cancer in a focally ablative manner with novel gland-preserving, focal therapy methods. Various ablative devices such as high intensity focused ultrasound, irreversible electroporation, photodynamic therapy, cryotherapy and laser ablation, among others, is discussed in regard to their strengths and limitations as a therapeutic modality. Emphasis is placed on patient selection and outcomes utilizing both advanced imaging techniques and pathologic evaluation. Current and new approaches to image cancer foci within the prostate (multiparametric ultrasonography, multiparametric magnetic resonance image, etc) are presented along with various biopsy techniques, including robotics to map prostate cancer. Patient selection based on imaging and genomic classification, adjuvants to enhance therapy, treatment strategy, outcomes and patient centered concerns is discussed, providing an acceptable balance between cancer control and improved quality of life for patients. Written by experts in the field and lavishly illustrated with detailed line-art and photographs, Imaging and Focal Therapy of Early Prostate Cancer, Second Edition is designed as a comprehensive resource for urologists, radiation oncologists, medical oncologists, radiologists, uropathologists, molecular biologists, biomedical engineers, other clinicians –- residents, fellows, nurses and allied professionals -- and researchers with an interest in the diagnosis and novel treatment of prostate cancer. It will provide insight into the latest research and clinical applications of image-guided diagnosis and minimally invasive focal, gland-preserving treatment for prostate cancer.

This conference brought together leaders of philanthropic and advocacy communities, government, industry and academia to discuss the state-of-the-art and to create the future vision for prostate cancer care. The goal of this conference is two-fold: 1) To expedite development and implementation of advanced imaging technologies for improved screening and early diagnosis; assessment of staging and aggressiveness; and 2) To advance integration between imaging and treatment modalities for facilitated drug development, treatment planning, guidance and monitoring.

Prominent physicians review past, current, and future applications of the many powerful imaging techniques now used in the diagnosis, staging, treatment, and outcomes assessment of cancers of the prostate, central nervous system (CNS), and breast. Topics range from the use of screening mammography and approaches to breast cancer detection using MRI to improved visualization of the prostate gland from transrectal ultrasound and MRI, to MRI-guided resection of neoplasms.

Prostate cancer is the most diagnosed form of cancer and one of the leading causes of cancer death in men, but survival rates are relatively high with sufficiently early diagnosis. The current clinical model for initial prostate cancer screening is invasive and subject to overdiagnosis. As such, the use of magnetic resonance imaging (MRI) has recently grown in popularity as a non-invasive imaging-based prostate cancer screening method. In particular, the use of high volume quantitative radiomic features extracted from multi-parametric MRI is gaining attraction for the auto-detection of prostate tumours since it provides a plethora of mineable data which can be used for both detection and prognosis of prostate cancer. Current image-based cancer detection methods, however, face notable challenges that include noise in MR images, variability between different MRI modalities, weak contrast, and non-homogeneous texture patterns, making it difficult for diagnosticians to identify tumour candidates. In this thesis, a comprehensive framework for computer-aided prostate cancer detection using multi-parametric MRI was introduced. The framework consists of two parts: i) a saliency-based method for identifying suspicious regions in multi-parametric MR prostate images based on statistical texture distinctiveness, and ii) automatic prostate tumour candidate detection using a radiomics-driven conditional random field (RD-CRF). The framework was evaluated using real clinical prostate multi-parametric MRI data from 20 patients, and both parts were compared against state-of-the-art approaches. The suspicious region detection method achieved a 1.5% increase in sensitivity, and a 10% increase in specificity and accuracy over the state-of-the-art method, indicating its potential for more visually meaningful identification of suspicious tumour regions. The RD-CRF method was shown to improve the detection of tumour candidates by mitigating sparsely distributed tumour candidates and improving the detected tumour candidates via spatial consistency and radiomic feature relationships. Thus, the developed framework shows potential for aiding medical professionals with performing more efficient and accurate computer-aided prostate cancer detection.

The Facts of Prostate Cancer 2/3 of men over age 50 have low grade tumors or potential cancer cells in their prostate. Only 10% will develop clinically aggressive prostate cancer. These non-invasive exams tell if a tumor is aggressive or not with an accuracy exceeding traditional biopsy results and correlate well with prognosis according to the latest international cancer conferences. The PSA test has a poor correlation with cancer detection. The digital rectal exam is more accurate in detecting high grade tumors than the PSA level. Biopsies are random, invasive and may spread tumor cells. New non-invasive treatments are guided by advanced radiologic imaging technologies. The therapeutic effect is serially studied by MRI and 3-D sonography. While generally successful, interval exams may document an unsatisfactory response, allowing "standard" treatments to be started, if necessary, in a timely manner.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection-the immunological response of the human immune system to a foreign kidney-is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient's chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today's CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images.

This cross-disciplinary book documents the key research challenges in the mathematical sciences and physics that could enable the economical development of novel biomedical imaging devices. It is hoped that the infusion of new insights from mathematical scientists and physicists will accelerate progress in imaging. Incorporating input from dozens of biomedical researchers who described what they perceived as key open problems of imaging that are amenable to attack by mathematical scientists and physicists, this book introduces the frontiers of biomedical imaging, especially the imaging of dynamic physiological functions, to the educated nonspecialist. Ten imaging modalities are covered, from the well-established (e.g., CAT scanning, MRI) to the more speculative (e.g., electrical and magnetic source imaging). For each modality, mathematics and physics research challenges are identified and a short list of suggested reading offered. Two additional chapters offer visions of the next generation of surgical and interventional techniques and of image processing. A final chapter provides an overview of mathematical issues that cut across the various modalities.