The longitudinal assessment of osteomyelitis development by mlecular imaging in a rabbit model

\u3cp\u3eIntroduction. Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis. Methods. An intramedullary tibial infection with S. aureus was established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using \u3csup\u3e18\u3c/sup\u3eF-FDG as an infection tracer. Results. The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study. Conclusions. This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of \u3csup\u3e18\u3c/sup\u3eF-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model.\u3c/p\u3

UHMWPE sublaminar wires in posterior spinal instrumentation

\u3cp\u3eStudy Design: An animal study. Objective: To explore ultra-high molecular weight polyethylene (UHMWPE) sublaminar wires in spinal surgery and to assess stability and biocompatibility of the UHMWPE instrumentation in an ovine model. Summary of Background Data: Sublaminar wiring is a well-established technique in segmental scoliosis surgery. However, during introduction and/or removal of the metal sublaminar wires, neurological problems can occur. Abrasion after cutting metal wires for removal can lead to damage to the dural sac. Sublaminar wires have to withhold large forces and breakage of the wires can occur. Different types of sublaminar wires have been developed to address these problems. UHMWPE sublaminar wires can potentially substitute currently used metal sublaminar metal wires. In vivo testing and biocompatibility analysis of UHMWPE wires are recommended before clinical use in spinal surgery. Materials and Methods: In 6 immature sheep, pedicle screws were instrumented at lumbar level L4 and attached with titanium rods to 4 thoracolumbar vertebrae using 3- and 5-mm-wide UHMWPE sublaminar wiring constructions in 5 animals. Titanium sublaminar wires were applied in 1 animal to function as a control subject. After a follow-up period of 16 weeks, the animals were sacrificed and the spines were isolated. Radiographs and computed tomography (CT) scans were made to assess stability of the instrumentation. The vertebrae were dissected for macroscopic and histologic evaluation. Results: None of the wires had loosened and the instrumentation remained stable. CT scans and radiographs showed no signs of failure of the instrumentation and no neurological complications occurred. Although several bony bridges were seen on CT, growth was observed at the operated levels. Biocompatibility was assessed by macroscopical and histologic analysis, showing no signs of dural or epidural inflammation. Conclusions: This pilot animal study shows that UHMWPE sublaminar wiring is a safe technique. The UHMWPE wires are biocompatible and provide sufficient stability in spinal instrumentation. Heterotopic ossification because of periost reactions in the ovine spine led to some restrictions in this study.\u3c/p\u3

The Longitudinal Assessment of Osteomyelitis Development by Molecular Imaging in a Rabbit Model

Introduction. Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis. Methods. An intramedullary tibial infection with S. aureus was established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using 18F-FDG as an infection tracer. Results. The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study. Conclusions. This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of  18F-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model

Monitoring Response to Antiangiogenic Therapy in Non-Small Cell Lung Cancer Using Imaging Markers Derived from PET and Dynamic Contrast-Enhanced MRI

With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non-small cell lung cancer. Methods: Patients were evaluated using an imaging protocol including CT, F-18-FDG PET, H-2 O-15 PET, and dynamic contrast-enhanced MRI to derive measurements on tumor size, glucose metabolism, perfusion, and microvascular permeability. The percentage change in imaging parameters after 3 wk of treatment as compared with baseline was calculated and correlated with progression-free survival (PFS). Results: Forty-four patients were included, and 40 underwent CT and F-18-FDG PET at both time points. Complete datasets, containing all imaging modalities, were available for 14 patients. Bevacizumab and erlotinib treatment resulted in decreased metabolism, perfusion, and tumor size. A decrease in standardized uptake value or tumor perfusion of more than 20% at week 3 was associated with longer PFS (9.7 vs. 2.8 mo, P = 0.01, and 12.5 vs. 2.9 mo, P = 0.009, respectively). Whole-tumor K-trans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor K-trans values-that is, an increase in regions with low or high K-trans values-after 3 wk had shorter PFS (2.3 vs. 7.0 mo, P = 0.008). A partial response, according to the response evaluation criteria in solid tumors (RECIST), at week 3 was also associated with prolonged PFS (4.6 vs. 2.9 mo, P = 0.017). However, 40% of patients with a partial response as their best RECIST response still had stable disease at week 3. In these cases tumor perfusion was already decreased and K-trans heterogeneity showed no increase, indicating that the latter parameters seem to be more discriminative than RECIST at the 3-wk time point. Conclusion: PET and dynamic contrast-enhanced MRI were able to identify patients who benefit from bevacizumab and erlotinib treatment. Molecular imaging seems to allow earlier response evaluation than CT

Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response

<div><p>Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects.</p></div