No abstract

Objectives Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. Materials and methods Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology. Results The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT (r =−0.101, 95% CI [−0.445; 0.268]) or histology (r = 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed. Conclusions These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

Background: Histology and μ-CT, the current gold standard tools for assessing angio-and osteogenesis, are invasive and/or destructive, rendering repeated measurements or further examinations by other methods virtually impossible. On the other hand, DCE-MRI, a more conservative tool, without such limitations, has shown potential in assessing the microvasculature in clinical and research studies. NOetheless, its foray into bone tissue engineering remains limited. Aim/Hypothesis: This study aimed to assess the accuracy and reproducibility of DCE-MRI in monitoring angiogenesis during bone regeneration and to evaluate whether the initial area under curve, a DCE-MRI pharmacokinetic parameter of blood perfusion, is a reliable surrogate of the efficacy of osteoplastic materials. Materials and Methods: This research was developed in an exploratory experimental design, with randomized sampling, a control group, and blINDIAd evaluators. Sixteen skeletally mature New Zealand white female rabbits were divided into four groups of four, according to the time of euthanasia. Under general anesthesia, the animals were submitted to two 8 mm craniotomies that were filled either with blood or autogenous bone. Two, 3, 4 and 6 weeks after surgery, animals were submitted to DCE-MRI, according to group assignment, and subsequently euthanized. Then, surgical specimens were harvested and submitted to μ-CT and histomorphometry. Angiogenesis was evaluated using a surrogate marker, the initial area under the curve at 140s (IAUC140), a DCE-MRI pharmacokinetic parameter of blood perfusion. Bone formation was assessed using μ-CT and histomorphometry. The outcomes evaluated were bone volume fraction (BVF) and new bone formation (NBF). Finally, correlations among findings of the three tools were calculated. Results: DCE-MRI: the mean IAUC140 of blood clot was statistically higher than of autogenous bone (P = 0.006). As for time of euthanasia, there was no statistically significant difference among groups (P = 0.132). μ-CT: the mean BVF of autogenous bone was statistically higher than of blood clot (P = 0.0001). Regarding time of euthanasia, the mean BVF at 6 weeks was statistically higher than that at 3 (P = 0.025) and 4 weeks (P = 0.0003). Histomorphometry: there was no statistically significant difference between autogenous bone and blood clot (P = 0.379). Regarding time of euthanasia, the mean NBF at 2 weeks was statistically higher than that at 3 (P = 0.012) and 4 weeks (P = 0.043). Correlations: There was a statistically significant, negative correlation between μ-CT and DCE-MRI (rho = −0.334). Between μ-CT and Histology, there was a significant, positive correlation (rho = −0.442). Between DCE-MRI and Histology, there was no statistically significant difference (rho = 0.025). Conclusions and Clinical Implications: These results further support the hypothesis that DCE-MRI can be used to monitor angiogenesis in bone tissue engineering, but contradict our premise that it could be used to predict bone formation. A reasonable extrapolation to cli...