A preliminary investigation into the effects of X-ray radiation on superficial cranial vascularization (original) (raw)
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Microvascular Research, 2014
a b s t r a c t 1 2 Please cite this article as: Deshpande, S.S., et al., Vascular analysis as a proxy for mechanostransduction response in an isogenic, irradiated murine model of mandibular distraction osteogenesis, Microvasc. Res. (2014), http://dx.doi.org/10.1016/j.mvr.2014.08.005 radiotherapy is osteradionecrosis, a condition that includes ex-69 posed, devitalized bone through damaged surrounding mucosa 70 (Marx and DDS, 1983). Pathologic fracture, another associated 71 morbidity, can often be difficult to treat, affecting the quality of 72 daily life for patients. Reduced vascularity in the bone accompanies 73 the aformentioned consequences of adjuvant radiation therapy. 74 This devascularization impedes the vigor of bone cells and hampers 75 the likelihood of successful wound healing (Würzler et al., 1998). 76 Most clinical treatment practice dictates that bone defects and as-77 sociated complications of poor bone healing secondary to irradiation 78 are reconstructed utilizing rigid fixation in concert with free tissue 79 transfer. Due to the deleterious consequences of radiation, however, 80 these procedures have high failure rates and can generate additional 81 devastating complications, such as regional or distal donor site mor-82 bidity. Distraction osteogenesis (DO) is a reliable treatment ap-83 proach for reconstruction of craniofacial anomalies, which avoids 84 the issue of donor site morbidity, and furthermore simultaneously 85 generates both bone and soft tissue. In DO, mechanotransduction at 86 131 of the neovasculature due to radiation, thereby providing critical 132 information about the effect of radiation on the vascular mechanical re-133 sponse central to bone regeneration in distraction osteogenesis. 134 Materials and methods 135 Animals 136 Male Lewis rats, 400 g, were obtained through the University of 137 Michigan's Unit Laboratory Animal Medicine (ULAM) department in 138 compliance with their subdivision of the University of Michigan's Uni-139 versity Committee on Use and Care of Animals (UCUCA). Rats were 140 weighed and provided water bottles and regular chow ad libitum upon 141 arrival to the laboratory. They were acclimated for 7 days before radia-142 tion. Animals were randomly assigned to 2 groups. (1) DO (distraction 143 osteogenesis only, n = 5), (2) XRT/DO (radiation therapy + distraction 144 osteogenesis, n = 7). 145 Radiation 146 Rat hemi-mandibles were irradiated using a Philips RT250 147 orthovoltage unit (250 kV, 15 mA) (Kimtron Medical), fractionating 148 321 mation (DO: 1.893 ± 0.641, XRT/DO: 0.471 ± 0.188, p = 0.022). Vessel 322 volume fraction (VVF), defined as the fraction of the ROI composed of 323 vasculature, was also significantly lower in the XRT/DO group, suggest-324 ing a negative effect on perfusion of the surrounding tissue (DO: 325 0.048 ± 0.011, XRT/DO: 0.016 ± 0.006, p = 0.004). The XRT/DO 326 group displayed a smaller vessel thickness (VT), defined as mean 327 intraluminal diameter of each blood vessel (DO: 0.047 ± 0.003, XRT/ 328 DO: 0.027 ± 0.005, p = 0.023). 329 Another metric that was examined and quantified was the degree of 330 anisotropy (DA). Defined as the quantification of the extent of direction-331 ality and orientation of the blood vessels, the degree of anisotropy in the 332 XRT/DO group was significantly lower than the vasculature of the DO 333 group (DO: 0.413 ± 0.120, XRT/DO: 0.196 ± 0.056, p = 0.004). The 334 more randomized formation of blood vessels in the XRT/DO group sug-335
Radiation-Induced Craniofacial Bone Growth Inhibition: Development of an Animal Model
Journal of Craniofacial Surgery, 2001
Background: The authors previously established an animal model of radiationinduced craniofacial bone growth inhibition and demonstrated the effectiveness of cytoprotection in preserving growth using amifostine, but the mechanism is unclear. The objective of this study was to investigate the acute and long-term histopathologic effects of single-dose orthovoltage irradiation on craniofacial bone with and without cytoprotection. Methods: Sixty infant New Zealand White rabbits (7-week-old) were randomized into three groups (n ϭ 20 per group): group 1, 0-Gy, sham irradiation; group 2, 35-Gy single-dose orthovoltage irradiation; and group 3, cytoprotection with amifostine before irradiation. Orbitozygomatic complex bone was harvested from animals 12 hours after irradiation and at skeletal maturity (21 weeks of age). Histologic parameters measured included native bone cell (osteoblast, osteoclast, and osteocyte) populations, periosteal proliferation indices (MIB-1 stains), bone turnover rates [triple fluorochromes: tetracycline administered at 7 weeks of age (before irradiation), alizarin complexone at 12 weeks, and calcein at 16 weeks of age], and endosteal space fibrosis levels. Results: Orthovoltage irradiation significantly (p Ͻ 0.05) reduced osteoblast and osteoclast counts 12 hours after irradiation (age, 7 weeks) with or without pretreatment with amifostine but had no effect on osteocyte populations. Long-term analysis at age 21 weeks demonstrated significantly (p Ͻ 0.05) increased osteoblast counts, reduced endosteal space fibrosis, reduced periosteal proliferation indices, and improved bone turnover (fluorochrome stains) in amifostine-treated animals. Conclusion: This study suggests that amifostine cytoprotection is mediated through a combination of reduced cellular injury with enhanced promotion of cellular bone rebuilding potential.
Plastic and Reconstructive Surgery, 2005
Background: The authors previously established an animal model of radiationinduced craniofacial bone growth inhibition and demonstrated the effectiveness of cytoprotection in preserving growth using amifostine, but the mechanism is unclear. The objective of this study was to investigate the acute and long-term histopathologic effects of single-dose orthovoltage irradiation on craniofacial bone with and without cytoprotection. Methods: Sixty infant New Zealand White rabbits (7-week-old) were randomized into three groups (n ϭ 20 per group): group 1, 0-Gy, sham irradiation; group 2, 35-Gy single-dose orthovoltage irradiation; and group 3, cytoprotection with amifostine before irradiation. Orbitozygomatic complex bone was harvested from animals 12 hours after irradiation and at skeletal maturity (21 weeks of age). Histologic parameters measured included native bone cell (osteoblast, osteoclast, and osteocyte) populations, periosteal proliferation indices (MIB-1 stains), bone turnover rates [triple fluorochromes: tetracycline administered at 7 weeks of age (before irradiation), alizarin complexone at 12 weeks, and calcein at 16 weeks of age], and endosteal space fibrosis levels. Results: Orthovoltage irradiation significantly (p Ͻ 0.05) reduced osteoblast and osteoclast counts 12 hours after irradiation (age, 7 weeks) with or without pretreatment with amifostine but had no effect on osteocyte populations. Long-term analysis at age 21 weeks demonstrated significantly (p Ͻ 0.05) increased osteoblast counts, reduced endosteal space fibrosis, reduced periosteal proliferation indices, and improved bone turnover (fluorochrome stains) in amifostine-treated animals. Conclusion: This study suggests that amifostine cytoprotection is mediated through a combination of reduced cellular injury with enhanced promotion of cellular bone rebuilding potential.
Validation of a rabbit model of irradiated bone healing: preliminary report
Journal of Oral Medicine and Oral Surgery, 2020
Introduction: External radiotherapy can lead to severe bone alteration. The aim of this pilot study was to validate a model for assessment of postextractional bone healing in the irradiated rabbit mandible. Material and method: The radiation protocol consisted of 5 sessions delivering 8.5 Gy each. Surgery was performed immediately after completion of radiotherapy. Sacrifices were performed from Day 0 to Day 42. Results: The bone mineral density and the trabecular number were decreased after radiotherapy whereas trabecular separation increased. The main differences between irradiated and non-irradiated rabbits were observed at Day 28 and 42. Discussion: Radiation seems to cause a delay in bone healing. It decreases bone quality and bone mineral density. Five sessions seem to be a valuable compromise between tissues effect and feasibility of the experiment. Conclusion: This model seems to be valuable for evaluating postextractional bone healing in the irradiated rabbit mandible.
HDR brachytherapy irradiation of the jaw – as a new experimental model of radiogenic bone damage
Journal of Cranio-Maxillofacial Surgery, 2008
Hitherto, no suitable experimental model exists to test new treatments for radiogenic bone damage, such as new step from knowledge about bone growth factors or angiogenesis factors. The goal of this investigation was to establish such a standardised experimental model. Twenty-four rats were used in this study. In 12 rats a plastic tube was implanted along the right half of the mandible and treated with a single dose of 20 Gy at a high-dose-rate (HDR) using an afterloading machine, the remainder served as control (n=12). One hundred days after irradiation both sides of the mandible were examined using paraffin embedding and non-decalcified histology. All HDR irradiated rats developed localised alopecia within 2 weeks of radiotherapy. In the irradiated group, a clear growth reduction of the ipsilateral incisor was observed. Paraffin histology revealed minimal damage of the bone structure with slightly increased signs of regeneration. The bone apposition rate was significantly reduced on the irradiated right side, compared with the left side (p=0.028). The average diameter of the mandibular condyles on the irradiated right sides was significantly reduced when compared with the left sides (p=0.023). It is possible to induce radiogenic damage of the mandible by using HDR brachytherapy with a single dose of 20 Gy comparable to 45 x 2 Gy of conventional irradiation. This new model is easy and predictable and appears to be suitable for the testing of new treatment modalities. It is advantageous for the testing of bone growth and angiogenesis factors that the contralateral side exhibits completely normal bone apposition characteristics enabling a split-mouth design for future experiments.
Laboratory Animal Research, 2013
Bone changes are common sequela of radiation therapy for cancer. The purpose of this study was to establish an experimental model of radiation-induced bone loss in adult mice using micro-computed tomography (µCT). The extent of changes following 2 Gy gamma irradiation (2 Gy/min) was studied at 4, 8, 12 or 16 weeks after exposure. Adult mice that received 1, 2, 4 or 6 Gy of gamma-rays were examined 12 weeks after irradiation. Tibiae were analyzed using µCT. Serum markers and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 12 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%)= −0.071D 2 −1.799D+18.835 (r 2 =0.968, D=dose in Gy) and BMD (mg/cm 3) = −3.547D 2 −14.8D+359.07 (r 2 =0.986, D=dose in Gy). Grip strength and body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum biochemical markers and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.
Medical Journal of Indonesia, 2014
Latar belakang: Autograft tulang digunakan pada operasi rekonstruksi kasus tumor tulang. Extracorporeal irradiation (ECI) pada tulang digunakan untuk membunuh sel tumor. Namun radiasi juga menimbulkan efek negatif terhadap osteoinduksi dan osteogenensis untuk inkorporasi autograft tulang. Penelitian ini bertujuan mempelajari pengaruh iradiasi dengan dosis 50-300 Gy terhadap kemampuan inkorporasi graft tulang. Metode: Pada 24 ekor tikus Sprague-Dawley dilakukan reseksi en bloc 7 mm pada diafisis tibia. Tikus dibagi menjadi 4 kelompok: kelompok 1 tidak mendapat radiasi; kelompok 2, 3 dan 4 berturut-turut mendapat iradiasi 50, 150 dan 300 Gy pada tulang yang direseksi, selanjutnya diimplantasi kembali. Inkorporasi tulang dievaluasi pada minggu ke-6 dan -8 secara radiologi dan pada minggu ke-8 dilakukan evaluasi histopatologis, hitung osteoblas dan pengukuran ekspresi BMP-2. Data dianalisis menggunakan uji Anova dan Kruskal-Wallis. Hasil: Pada minggu ke-6, skor radiologis kelompok iradiasi 150 dan 300 Gy lebih rendah dibandingkan kontrol (4 vs 6 dan 4 vs 6; p = 0,01). Demikian juga pada minggu ke-8 (5,40 vs 7,14; p = 0,009 pada kelompok 150 Gy dan 5,60 vs 7,14; p = 0,018 pada kelompok 300 Gy). Pemeriksaan histopatologis memperlihatkan bahwa median skor histologis kelompok iradiasi 50, 150 dan 300 Gy lebih rendah secara bermakna dibanding kontrol (6 vs 7 , p = 0,017; 4 vs 7, p = 0,005; 6 vs 7, p = 0,013). Hitung osteoblas dan ekspresi BMP-2 tidak menunjukkan perbedaan bermakna pada tiap kelompok. Kesimpulan: ECI dengan dosis 50 sampai 300 Gy terhadap autograft tulang menyebabkan keterlambatan dalam inkorporasi autograft tulang, namun autograft tersebut masih memperlihatkan kemampuan osteoinduktif dan osteogenesis. Abstract Background: Bone graft has been widely used in bone tumor reconstructive surgery. Extracorporeal irradiation (ECI) is commonly used to eliminate malignant cells before bone autograft. However, it may have negative effects on autograft incorporation. This study aimed to evaluate the ability of bone autograft incorporation after extra corporeal irradiation.
Dynamics of Irradiation Injury to Bone Tissue
Acta Oncologica, 1985
The dynamic changes after a single dose of 15,25 or 40 Gy 6oCo were followed in a titanium vital microscopic bone chamber which permitted observation of the same tissue compartment for over 2 years. The chamber consists of a hollow screw containing 2 glass rods 100 pm apart. The device was inserted into the cortex of the proximal tibia1 metaphysis of a rabbit. During a healing period of 4 to 6 weeks the space between the glass rods became filled with bone and vessels and in some cases fat. Once a steady state in bone remodelling had been achieved, the animals were irradiated. Vital microscopy was then performed at' regular intervals. Mature bone was relatively radioresistant since remodelling continued at a normal rate. In contrast, immature woven bone remained unlamellarized and in some animals tended to increase in amount. The vascular architecture was largely unaltered, even after 40 Gy. Thrombosis or hemorrhage clearly attributable to irradiation was not noted. Initially, the number of fat cells was reduced but repopulation was later seen in several cases.
The irradiated human mandible: A quantitative study on bone vascularity
Oral Oncology
Hypovascularisation is thought to play an important role in the pathogenesis of osteoradionecrosis. The objective of this study was to assess the microvascular system in the irradiated mandibular bone marrow. Materials and methods: Mandibular bone biopsies were taken from 20 irradiated patients and 24 controls. Blood vessels were visualized using CD34 antibody stain to detect endothelial cells. The vascular density (VD) and vascular area fraction (VAF) were measured. Mean vessel lumen area, perimeter and diameter of the vessels were calculated for each vessel. A distinction was made between large and small vessels (cut-off point < 400 µm 2). Results: Vascular density and vascular area fraction were lower in the irradiated group. The mean vascular perimeter and mean vascular diameter were higher in samples with a local radiation dose of ≥50 Gy, whereas the percentage of small vessels was lower. Larger vessel perimeter is associated with higher radiation dose. A longer interval between biopsy and radiotherapy is associated with a larger mean vessel perimeter and a lower percentage of small vessels. Conclusions: Radiation dosages higher than 50 Gy mainly affect the smaller vessels. With increased time after irradiation, the share of smaller vessels in the mandibular bone marrow seems to decrease. In search of the exact mechanisms of irradiation damage and osteoradionecrosis of the mandible, the role of the microvascular system in the mandibular bone marrow should be further explored.