Raman spectroscopy monitors adverse bone sequelae of cancer radiotherapy

Abstract

Raman spectroscopy provides information on bone chemical composition and structure via widely used metrics including mineral to matrix ratio, mineral crystallinity and carbonate content, collagen cross-linking ratio and depolarization ratios. These metrics are correlated with bone material properties, such as hardness, plasticity and Young's modulus. We review application of Raman spectroscopy to two important irradiated animal models: the mouse tibia, a model for damage to cortical bone sites including the rib (breast cancer) and to healthy tissue adjacent to extremity sarcomas, and the rat mandible, a model for radiation damage in head and neck cancer radiotherapy. Longitudinal studies of irradiated mouse tibia demonstrate that radiation-induced matrix abnormalities can persist even 26 weeks post-radiation. Polarized Raman spectroscopy shows formation of more ordered orientation of both mineral and collagen. At 8 weeks post-radiation, irradiated rat hemimandible exhibits transient hypermineralization, increased collagen cross-linking and decreased depolarization ratios of mineral and collagen. A standard radioprotectant, amifostine, mitigates rat mandible radiation damage, with none remaining detectable 18 weeks post-radiation. Already a powerful tool to monitor radiation damage, Raman spectroscopy may be important in development of new radiotherapy protocols and radioprotective agents. Further in vivo studies of radiation effects on the rodent models are underway, as are development of methodologies for eventual use in human subjects.