The goal of this project is to develop a novel cyber-physical system (CPS) for performing multimodal image-guided robot-assisted minimally invasive surgeries (MIS). The approach is based on: (1) novel quantitative analysis of multi-contrast data, (2) control that uses this information to maneuver conformable robotic manipulators, while adjusting on-the-fly scanning parameters to acquire additional information, and (3) human-information/machine-interfacing for comprehensive appreciation of the physical environment. The intellectual merit arises from the development of: (1) a CPS that relies on "real" and "real-time" data, minimizing parametric and abstracted assumptions, extracts and matures information from a dynamic physical system (patient and robot) by combining management of data collection (at the physical sensor site) and data analysis (at the cyber site), (2) "smart sensing", to control data acquisition based on disruptive or situation altering events, (3) control coordination by interlacing sensing, control and perception, and the incorporation of steerable tools. The societal impact arises from contributions to a leap in MIS: from "keyhole" visualization (i.e., laparoscopy) to in-situ real-time image guidance, thereby enabling a wider range of MIS. This will directly benefit patients and their families (faster recovery/reduced trauma). Economic impact arises from the cost-effectiveness of MIS to the health care system, faster patient return to the workplace, and technology commercialization. The project will integrate research and education, diversity and outreach, by enhancing current and introducing new research-intensive courses in Cyber-physical Systems, Medical Imaging and Medical Robotics, and dissemination via trans-institutional collaborations, a comprehensive web site, multimedia web-seminars, and distribution to high schools.