Evaluation of rib microstructure in Wistar rats using SR-mCT after radiation therapy simulation for breast cancer Liebert P. Nogueira b , Andre ´ P. de Almeida a,b,n , Delson Braz a , Cherley B. Andrade c , Camila Salata c , Giuliana Tromba d , Carlos E. de Almeida c , Regina C. Barroso b a Nuclear Instrumentation Laboratory/COPPE/UFRJ, P.O. Box 68509, 21945-970 Rio de Janeiro, Brazil b Physics Institute/State University of Rio de Janeiro, 20550-900 Rio de Janeiro, Brazil c Laboratory of Radiological Sciences/State University of Rio de Janeiro, Rio de Janeiro, Brazil d Sincrotrone Trieste SCpA, Strada Statale S.S. 14-km 163.5, 34012 Basovizza, Trieste, Italy article info Available online 5 March 2012 Keywords: Synchrotron radiation Computed microtomography Histomorphometry Bones abstract A better understanding of biological interactions that occur after exposure to photon radiation is needed in order to optimize therapeutic regimens and facilitate development and strategies that decrease radiation-induced side effects in humans. In this work, ribs of Wistar rat submitted to radiotherapy simulation were imaged using synchrotron radiation computed microtomography at Elettra Synchrotron Laboratory in Trieste, Italy. Histomorphometric parameters were calculated directly from the 3D microtomographic images and showed significant differences between irradiated and non-irradiated groups. & 2012 Elsevier Ltd. All rights reserved. 1. Introduction Although radiation therapy is known to bring deleterious consequences to bone health, it is still the golden technique to increase the survival rate of cancer patients. Radiotherapy pro- duces a milieu of hypoxia, hypovascularity, and hypocellularity in local tissues. Apoptosis of osteoblasts, osteocytes, osteoprogenitor cells, and endothelial cells occurs after radiotherapy, which leads to progressive hyalinization and fibrosis of medullary spaces and, subsequently, reduction of osseous vascularization (Blanco and Chao, 2006). In aggregate, these alterations in the normal bone microenvironment result in decreased blood flow, bone atrophy (measured by a decrease in relative dry bone weight), and a decrease in the relative amounts of calcium and phosphorus, which is suggestive of bone mineral loss (Hopewell, 2003). These risks have not been well studied, particularly the risks with standard course fractionation (Baxter et al., 2005). Bone is metabolically active throughout life. The remodeling of bone requires the sequential and coordinated actions of the osteoclasts, to remove bone (also called bone resorption), and the osteblasts to replace it. After skeletal growth is complete, remodeling of bone continues and results in an annual turnover of about 10% of the adult skeleton. A change in the balance between bone resorption and bone formation ultimately results in a net loss or gain of bone tissue. High bone turnover, with increased bone resorption—which can occur soon after irradiation and last for years—can compromise bone strength, leading to a thinning of the bone structure, resulting in abnormal bone microarchitecture and reduced bone mineralization. This, in turn, leads to a greater propensity to fracture. Because the first step in the remodeling process is bone resorption, each remodeling event is associated with the formation of a temporary cavity. The total volume of bone occupied by all remodeling cavities and unmineralized bone tissue (osteoid) is known collectively as the remodeling space (Hernandez, 2008). Increases in bone turnover result in an increase in the volume occupied by the remodeling space and cause a corresponding reduction in mineralized bone volume and alterations in trabecular microarchitecture. Radiation induced rib fracture has been recognized as a normal tissue complication after conventional radiotherapy when the radiation field is in the thoracic region, like radiotherapy for breast or lung cancer (Pettersson et al., 2009). Rib fractures occur in approximately 1.8% of patients with breast cancer (Pierce et al., 1992). Such fractures are associated with a higher radiation dose per fraction, with a higher dose ( 450 Gy) to the whole breast, and with combination of radiation therapy and chemotherapy. X-ray microtomography (mCT) is a non-destructive technique, which enables investigation of the three-dimensional structure of an object at the micron scale. Experimentally, a series of digital radiographies at different angular positions of the sample are recorded and the reconstruction of the slice, which represents a Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/apradiso Applied Radiation and Isotopes 0969-8043/$ - see front matter & 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.apradiso.2012.02.032 n Corresponding author at: Nuclear Instrumentation Laboratory/COPPE/UFRJ, P.O. Box 68509, 21945-970 Rio de Janeiro, Brazil. Tel.: þ55 21 23340699. E-mail address: apalmeid@gmail.com (A.P. de Almeida). Applied Radiation and Isotopes 70 (2012) 1296–1299