PURPOSE: Thermal ablation therapy is an emerging local cancer treatment to destroy cancer tissue using heat. However variations in blood flow and energy absorption rates make it extremely challenging to monitor thermal changes. Insufficient ablation may lead to recurrence of the cancer while excessive ablation may damage adjacent healthy tissues. Ultrasound could be a convenient and inexpensive imaging modality for real-time monitoring of the ablation. For the development and optimization of these methods, it is essential to have ground truth data and a reliable and quantitative validation technique before beginning clinical trials on humans. In this dissertation, my primary focus was to solve the image-to-physical space registration problem using stereotactic fiducials that provide accurate correlation of ultrasound and pathology (ground truth) images. METHOD: A previously developed validation test-bed prototype was evaluated using phantom experiments to identify the shortcomings and limitations. In order to develop an improved validation platform, a simulator was implemented for evaluating registration methods as well as different line fiducial structures. New fiducial line structures were proposed, and new methods were implemented to overcome the limitations of the old system. The new methods were then tested using simulation results and phantom studies. Phantom experiments were conducted to improve the visibility of fiducials, as well as the quality of acquired ultrasound and pathology image datasets. RESULTS: The new system outperforms the previous one in terms of accuracy, robustness, and simplicity. The new registration method is robust to missing fiducials. I also achieved complete fiducial visibility in all images. Enhancing the tissue fixation medium improved the ultrasound data quality. The quality of pathology images were improved by a new imaging method. Simulation results show improvement in pose recovery accuracy using my proposed fiducial structure. This was validated by phantom studies reducing spatial misalignment between the US and pathology image sets. CONCLUSION: A new generation of test-bed was developed that provides a reliable and quantitative validation technique for evaluating and optimizing ablation monitoring methods. / Thesis (Master, Computing) -- Queen's University, 2011-09-29 20:31:55.159