Convolutional neural networks (CNNs) have become increasingly popular in recent years because of their ability to tackle complex learning problems such as object detection, and object localization. They are being used for a variety of tasks, such as tissue abnormalities detection and localization, with an accuracy that comes close to the level of human predictive performance in medical imaging. The success is First and foremost, I would like to express my sincere gratitude to my advisor Professor Dr. Navalgund Rao for his guidance, patience, and intellectual support throughout my Ph.D. research. I feel very fortunate to get a chance to work with him who offered invaluable research advice and always provided me opportunities to participate in collaborative research projects and conferences that allowed me to grow academically and intellectually. I am also very grateful to my Committee, Dr. Vikram Dogra, Dr. Guoyu Lu, and Dr. Pengcheng Shi for their time for providing helpful suggestions and feedbacks during my Ph.D. thesis preparation, without whom this accomplishment would not even have been possible. I am very thankful to the Center for Imaging Science for all the support throughout the Ph.D. study. I would like to thank Center for Imaging Science, and the director of the center for imaging science Dr. David Messinger for providing me with a travel grant which allowed me to attend and present my works at Medical Imaging, SPIE, Defense + Commercial Sensing, SPIE, and International Conference on Semantic Computing, IEEE conferences. I would also like to extend my thanks to Elizabeth Lockwood for her countless assistance in my study arrangement during my Ph.D. study.