A Preliminary Investigation into the Effects of X-Ray Radiation on Superficial Cranial Vascularization

Abstract

Radiation therapy (RT) is an established treatment modality for malignant neoplasms. RT induces tissue damage that may lead to osteoradionecrosis in more severe cases. Suitable animal models to study RT-induced changes in membranous craniofacial bone are currently not available. The aim of this study was therefore to quantify RT-induced changes in cranial microcirculation using a newly developed calvaria chamber model and to relate these changes to RT-induced histological damage. New Zealand white rabbits received a total radiation dose of 18.75 Gy through the calvaria chamber, and the number of vessels, the vessel length density (VLD), and angiogenic sprouting were quantified on a weekly basis during a 12-week period. At the end of 12 weeks, the RT-treated (n = 5) or control (n = 5) calvarias were biopsied for histopathological analysis. RT resulted in a steep reduction in the number of vessels and the VLD during the first 3 weeks, particularly in larger-diameter vessels, followed by a flat stabilization/remodeling phase in the subsequent 9 weeks that never restored to baseline values. Histomorphometric analysis revealed a high degree of osteocytic depletion, prominent hypocellularity in the lacunae and intraosseous vasculature, enlarged and nonconcentric Haversian systems, and a severely disorganized bone matrix in the RT-treated calvarias. Despite the prevalence of some angiogenic potential, the RT-induced effects in the early phase persisted in the intermediate to late phase, which may have contributed to the poor recovery of the RT-treated bone.

Glucocorticoids, osteocytes, and skeletal fragility: The role of bone vascularity

“…The osteonecrosis has been attributed to fat emboli, microvascular tamponade of the blood vessels of the femoral head by marrow fat or fluid retention, and poorly mending fatigue fractures [5]. Occlusion of small bone blood vessels and a decrease in their number was observed weeks after calvarial radiation in rabbits, leading to radiation-induced osteonecrosis or osteoradionecrosis [46]. In osteoradionecrosis, loss of osteocyte viability, decreased intraosseous vasculature, and defective bone repair are pathogenetic features [46].…”

“…Occlusion of small bone blood vessels and a decrease in their number was observed weeks after calvarial radiation in rabbits, leading to radiation-induced osteonecrosis or osteoradionecrosis [46]. In osteoradionecrosis, loss of osteocyte viability, decreased intraosseous vasculature, and defective bone repair are pathogenetic features [46]. Similarly, loss of osteocyte viability was documented in patients with glucocorticoid-induced osteonecrosis [47,48].…”

Laser preconditioning on cranial bone site: Analysis of morphological vascular parameters

“…As the bone chamber was screwed on the calvarium and the digital camera was modified to secure it on the bone chamber, the images obtained were reproducible. Our first study highlighted a maximal vascular depletion induced by X‐ray radiation after 4 weeks and then a stabilization of the vascular density until the end of the 12‐week follow‐up 8. Consequently, we decided to study vascular parameters (vessel length, number of nodes, and vessels according to their diameter) at week 0 (W0) as reference data, week 4 (W4), and week 8 (W8).…”

“…Preconditioning, defined as the application of a supraphysiological stress prior to injury, has been demonstrated to be an adequate method for the promotion of soft tissue healing 6, 7. Applying the same concept to calcified tissue laser irradiation was performed as the thermal preconditioning on X‐ray irradiated bone 8. At the same time, we developed an optical bone chamber to observe the evolution of the superficial bone vascular network for a 12‐week follow‐up 9.…”

Effects of high dose of zoledronic acid on superficial vascular network of membranous bone sites: an intravital study on rat calvarium

“…The images are analysed using Aphelion 3.2® (Adsis, Herouville saint Clair France) software which was calibrated to interpret one pixel as 3 mµ. Based on the software functions, a fully automatic image processing routine was developed to measure the blood vessel parameters of perfused network [20] The main steps of the segmentation procedure consist as follow:…”