Spectral K-edge subtraction imaging of experimental non-radioactive barium uptake in bone.

PURPOSE: To evaluate the feasibility of using non-radioactive barium as a bone tracer for detection with synchrotron spectral K-edge subtraction (SKES) technique. METHODS: Male rats of 1-month old (i.e., developing skeleton) and 8-month old (i.e., skeletally mature) were orally dosed with low dose of barium chloride (33mg/kg/day Ba2+) for 4weeks. The fore and hind limbs were dissected for imaging in projection and computed tomography modes at 100µm and 52µm pixel sizes. The SKES method utilizes a single bent Laue monochromator to prepare a 550eV energy spectrum to encompass the K-edge of barium (37.441keV), for collecting both 'above' and 'below' the K-edge data sets in a single scan. RESULTS: The SKES has a very good focal size, thus limits the 'crossover' and motion artifacts. In juvenile rats, barium was mostly incorporated in the areas of high bone turnover such as at the growth plate and the trabecular surfaces, but also in the cortical bone as the animals were growing at the time of tracer administration. However, the adults incorporated approximately half the concentration and mainly in the areas where bone remodeling was predominant and occasionally in the periosteal and endosteal layers of the diaphyseal cortical bone. CONCLUSIONS: The presented methodology is simple to implement and provides both structural and functional information, after labeling with barium, on bone micro-architecture and thus has great potential for in vivo imaging of pre-clinical animal models of musculoskeletal diseases to better understand their mechanisms and to evaluate the efficacy of pharmaceuticals.

Three-dimensional labeling of newly formed bone using synchrotron radiation barium K-edge subtraction imaging.

Bone is a dynamic tissue which exhibits complex patterns of growth as well as continuous internal turnover (i.e. remodeling). Tracking such changes can be challenging and thus a high resolution imaging-based tracer would provide a powerful new perspective on bone tissue dynamics. This is, particularly so if such a tracer can be detected in 3D. Previously, strontium has been demonstrated to be an effective tracer which can be detected by synchrotron-based dual energy K-edge subtraction (KES) imaging in either 2D or 3D. The use of strontium is, however, limited to very small sample thicknesses due to its low K-edge energy (16.105 keV) and thus is not suitable for in vivo application. Here we establish proof-of-principle for the use of barium as an alternative tracer with a higher K-edge energy (37.441 keV), albeit for ex vivo imaging at the moment, which enables application in larger specimens and has the potential to be developed for in vivo imaging of preclinical animal models. New bone formation within growing rats in 2D and 3D was demonstrated at the Biomedical Imaging and Therapy bending magnet (BMIT-BM) beamline of the Canadian Light Source synchrotron. Comparative x-ray fluorescence imaging confirmed those patterns of uptake detected by KES. This initial work provides a platform for the further development of this tracer and its exploration of applications for in vivo development.