Abstract
OBJECTIVE: Perhaps the most vexing and exigent problem confronting head and neck cancer reconstruction is overcoming the impediments of collateral damage imposed by radiation therapy (XRT) on normal surrounding tissue. Radiation therapy is detrimental to bone and soft tissue repair resulting in an unacceptably high incidence of devastating wound healing complications as well as the associated morbidity of late pathologic fractures, reduced bone healing, and osteoradionecrosis. The consequences of XRT on bone vasculature, long known to be affected by radiation, have been poorly understood. The purpose of this study was to analyze the degree by which irradiation degrades existing bone vascularity using a powerful micro-computed tomography technique to attain highly precise quantitative metrics of the vascular tree. METHODS: Fourteen 400-g male Sprague-Dawley rats underwent 35 Gy of fractionated XRT at 7 Gy/d. The animals were euthanized after 28 days, and the left ventricle was fixed and injected with Microfil (MV-122; Flow Tech, Carver, Mass) contrast. Left hemimandibles were dissected and scanned using high-resolution micro-computed tomography (18-μm voxels). The vessel number, thickness, separation, connectivity, and vessel volume fraction were analyzed for the region of interest, defined to be the volume behind the third molar spanning a total distance of 5.1 mm. RESULTS: Stereologic analysis and subsequent analysis of variance test demonstrated a significant and quantifiable diminution in the irradiated vasculature when compared with control animals. The vessel volume fraction (0.016 vs 0.032, P ≤ 0.003) and vessel thickness (0.042 vs 0.067 mm, P ≤ 0.001) were markedly reduced. Interestingly, further analysis demonstrated no significant differences between vessel separation and vessel number. CONCLUSIONS: The results of our study specifically quantify the corrosive affects of XRT on the vasculature of the mandible. The data from this novel technique go even further and imply retention of blood vessels but a degradation of their quality and size. Further experiments can now be directed at therapeutic interventions to reverse this process and better understand the underlying mechanism of XRT-induced bone injury.