This thesis focused on the development of a fundamentally new way to validate the precision and accuracy of radiation therapy treatment sessions for breast cancer, by optically imaging the Cherenkov light emitted during the delivery. Specifically, the utility of Cherenkov imaging has been explored in the largest patient cohort known, and a thorough feasibility assessment was completed to determine what steps are necessary for Cherenkov light to become a viable reporter for both the consistency of the beam shape and delivered surface dose on the patient. The techniques involved applying whole-image and point-by-point correction factors to account for optical attenuation and distortion of the Cherenkov intensities due to patient-specific and treatment-specific differences, which usually arise from light absorption due to interior blood volumes and skin pigmentations. These differences skew the light intensity to-dose linearity misreport the delivered surface dose. This work determined the level of accuracy that can be achieved by correcting for patient tissue differences, beam energy, and beam-to-patient geometries within these fields. With continued development, Cherenkov images may become direct, video-rate maps of the delivered surface dose with sufficient positional and dosimetric accuracy to be used in clinical monitoring. Specific studies also examined correction methods which utilize SFDI, optical reflectance, and x-ray CT tissue composition estimation to correct for tissue optical properties. One of the more promising approaches showed through a series of controlled phantom imaging and analysis of patient imaging studies, that systematic calibrations can be introduced to correct for many of these dominant parameters, based upon the tissue radiodensity, or CT number. Further refinement can correct for inter-patient and inter-fraction superficial skin changes.Beam shape imaging serves as an additional important aspect of this work, which allowed for the quantification of patient position accuracy within the beams for multi-field irradiation of axillary nodes using a singular or dual isocenter(s). The resulting field junction accuracy, or match lines, in these treatments could be verified by Cherenkov images. The patient data collection was carried out directly in imaging sessions at both Dartmouth-Hitchcock Healthâs Lebanon and Cheshire medical centers. In summary, this work was able to demonstrate quantitative evidence that Cherenkov imaging can (i) estimate field edges to clinical accuracy, and (2) determine how to use this imaging for quantitative remote dose Imaging in whole breast radiotherapy.