Project Summary/Abstract Cervical cancer causes significant impact on society, as it is a high cause of female mortality, with over 600,000 women diagnosed each year. Locally advanced disease is best treated with a combination of external beam radiation (EBRT) followed by brachytherapy. Brachytherapy delivers a focused, high dose into the tumor that is best directed by the use of MR imaging at the time of brachytherapy to ensure that the entire tumor can be treated with radiation. The placement of brachytherapy catheters, is typically done without any guidance, and complications due to inadvertent insertion into normal tissues (blood vessels, rectum, bladder), rather than into residual tumor, may result. Magnetic resonance-guided brachytherapy (MRBT) has significantly improved survival and reduced complications caused by inadvertently radiating neighboring tissues. Identifying normal tissues as residual tumor before MRBT may result in inadvertent treatment with radiation of healthy tissues, which increases complications. MRI multi-parametric identification of post-EBRT residual tumor, combined with actively-tracked catheter placement into the disease as seen on MR scanning, can result in a more precise treatment volume, and faster and more accurate MRBT catheter placement, leading to better outcomes and reduced complications. This should increase the use of MRBT in treating cervical cancer, as well as recurrent endometrial, vaginal, prostate, and other cancers. The proposed procedure utilizes several novel tools: (a) MRI sequences that map the tissue parameters perfusion, diffusion, fibrosis and oxygenation in the post-EBRT pelvis, which are analyzed by expert clinicians, and used to develop a method for providing refined remnant tumor maps; and, (b) instantaneous intraoperative dose mapping, where catheter locations at any time during placement are used to predict and guide what the clinician’s best next move should be, such as changing current catheter locations or adding more catheters. Together, these methods will culminate in dose-optimized catheter placements that will lower tumor recurrence and limit radiation side effects. This project is a collaboration between Johns Hopkins University and Elekta Inc. JHU radiation oncologists, radiologists, medical physicists and MRI physicists, along with a panel of experts in identifying remnant tumor, will work jointly with Elekta engineers to develop an innovative platform with broad applications in radiation oncology.