Use of small animal PET-CT imaging for in vivo assessment of tendon-to-bone healing: A pilot study

Background The availability of non-invasive means to evaluate and monitor tendon-bone healing processes in-vivo is limited. Micro Positron-Emission-Tomography (mu PET) using F-18-Fluoride is a minimally invasive imaging modality, with which osteoblast activity and bone turnover can be assessed. The aim of this study was to investigate the use of serial in-vivo mu PET/CT scans to evaluate bone turnover along the graft-tunnel interface in a rat ACL (anterior cruciate ligament) reconstruction model. Methods Unilateral autograft ACL reconstruction was performed in six rats. mu PET/CT-scans using F-18-Fluoride were performed 7, 14, 21, and 28 days postoperatively. Standard uptake values (SUV) were calculated for three tunnel regions (intraarticular aperture (IAA), mid-tunnel, and extraarticular aperture (EAA)) of the proximal tibia. Animals were sacrificed at 28 days and evaluated with mu CT and histological analysis. Results SUVs in both bone tunnels showed an increased F-18-Fluoride uptake at 7 days when compared to 14, 21, and 28 days. SUVs showed a gradient on the tibial side, with most bone turnover in the IAA and least in the EAA. At 7, 14, 21, and 28 days, there were significantly higher SUV values in the IAA compared to the EAA (p = .01, < .01, < .01, < .01). SUVs positively correlated with new bone volumetric density obtained with mu CT (r = 0.449, p = .013). Volumetric density of newly formed bone detected on mu CT correlated with osteoblast numbers observed along the tunnels in histological sections (r = 0.452, p < .016). Conclusions Serial in-vivo mu PET/CT-scanning has the potential to provide insight into bone turnover and therefore osteoblastic activity during the healing process. As a result, it allows us to directly measure the effect of interventional strategies in tendon-bone healing.