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Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 43 - 43
1 Nov 2018
Aaron R
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OA pathophysiology has a vascular component consisting of venous stasis resulting in intraosseous hypertension and hypoxia. In response, osteoblasts change their cytokine expression, accelerating bone remodelling and cartilage breakdown consistent with OA. We have characterized circulatory kinetics in OA bone in animal models with dynamic contrast enhanced MRI (DCE-MRI) and . 18. F PET and have demonstrated venous stasis and reduced perfusion that temporally precede and spatially coincide with OA lesions. Osteoblast uptake of . 18. F is consistent with abnormal perfusion, bone remodelling, and severity of OA. Circulatory kinetics with DCE-MRI in humans with OA of the knee exhibit similar venous outflow obstruction. Venous stasis is associated with hypoxia in subchondral bone. As an example of the effects of hypoxia on OA osteoblasts, we have described upregulation of fibrinolytic peptides, but a deficiency in the upregulation of PAI-1, leading to the generation of plasmin by human OA osteoblasts exposed to hypoxia in vitro. Plasmin is a serine protease that has been shown to degrade cartilage in OA. Abnormal circulatory kinetics by DCE-MRI may be an imaging biomarker of OA. Pharmacologic modulation of venous stasis would have a salutary effect on the physicochemical microcirculation of subchondral osteoblasts and the pathophysiology of OA


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 39 - 39
1 Nov 2016
Vallières M Freeman C Zaki A Turcotte R Hickeson M Skamene S Jeyaseelan K Hathout L Serban M Xing S Powell T Goulding K Seuntjens J Levesque I El Naqa I
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This is quite an innovative study that should lead to a multicentre validation trial. We have developed an FDG-PET/MRI texture-based model for the prediction of lung metastases (LM) in newly diagnosed patients with soft-tissue sarcomas (STSs) using retrospective analysis. In this work, we assess the model performance using a new prospective STS cohort. We also investigate whether incorporating hypoxia and perfusion biomarkers derived from FMISO-PET and DCE-MRI scans can further enhance the predictive power of the model. A total of 66 patients with histologically confirmed STSs were used in this study and divided into two groups: a retrospective cohort of 51 patients (19 LM) used for training the model, and a prospective cohort of 15 patients (two patients with LM, one patient with bone metastases and suspicious lung nodules) for testing the model. In the training phase, a model of four texture features characterising tumour sub-region size and intensity heterogeneities was developed for LM prediction from pre-treatment FDG-PET and MRI scans (T1-weighted, T2-weighted with fat saturation) of the retrospective cohort, using imbalance-adjusted bootstrap statistical resampling and logistic regression multivariable modeling. In the testing phase, this multivariable model was applied to predict the distant metastasis status of the prospective cohort. The predictive power of the obtained model response was assessed using the area under the receiver-operating characteristic curve (AUC). In the exploratory phase of the study, we extracted two heterogeneity metrics from the prospective cohort: the area under the intensity-volume histogram of pre-treatment DCE-MRI volume transfer constant parametric maps and FMISO-PET hypoxia maps (AU-IVH-Ktrans, AU-IVH-FMISO). The impact of the addition of these two individual metrics to the texture-based model response obtained in the testing phase was first investigated using Spearman's correlation (rs), and lastly using logistic regression and leave-one-out cross-validation (LOO-CV) to account for overfitting bias. First, the texture-based model reached an AUC of 0.94, a sensitivity of 1, a specificity of 0.83 and an accuracy of 0.87 when tested in the prospective cohort. In the exploratory phase, the addition of AU-IVH-FMISO did not improve predictive power, yielding a correlation of rs = −0.42 (p = 0.12) with lung metastases, and a relative change in validation AUC of 0% in comparison with the texture-based model response alone in LOO-CV experiments. In contrast, the addition of AU-IVH-Ktrans improved predictive power, yielding a correlation of rs = −0.54 (p = 0.04) with lung metastases, and a change in validation AUC of +10%. Our results demonstrate that texture-based models extracted from pre-treatment FDG-PET and MRI anatomical scans could be successfully used to predict distant metastases in STS cancer. Our results also suggest that the addition of perfusion heterogeneity metrics may contribute to improving model prediction performance


Bone & Joint Research
Vol. 5, Issue 3 | Pages 73 - 79
1 Mar 2016
Anwander H Cron GO Rakhra K Beaule PE

Objectives. Hips with metal-on-metal total hip arthroplasty (MoM THA) have a high rate of adverse local tissue reactions (ALTR), often associated with hypersensitivity reactions. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures tissue perfusion with the parameter Ktrans (volume transfer constant of contrast agent). Our purpose was 1) to evaluate the feasibility of DCE-MRI in patients with THA and 2) to compare DCE-MRI in patients with MoM bearings with metal-on-polyethylene (MoP) bearings, hypothesising that the perfusion index Ktrans in hips with MoM THA is higher than in hips with MoP THA. Methods. In this pilot study, 16 patients with primary THA were recruited (eight MoM, eight MoP). DCE-MRI of the hip was performed at 1.5 Tesla (T). For each patient, Ktrans was computed voxel-by-voxel in all tissue lateral to the bladder. The mean Ktrans for all voxels was then calculated. These values were compared with respect to implant type and gender, and further correlated with clinical parameters. Results. There was no significant difference between the two bearing types with both genders combined. However, dividing patients by THA bearing and gender, women with MoM bearings had the highest Ktrans values, exceeding those of women with MoP bearings (0.067 min. −1. versus 0.053 min. −1. ; p-value < 0.05) and men with MoM bearings (0.067 min. −1. versus 0.034 min. −1. ; p-value < 0.001). Considering only the men, patients with MoM bearings had lower Ktrans than those with MoP bearings (0.034 min. −1. versus 0.046 min. −1. ; p < 0.05). Conclusion. DCE-MRI is feasible to perform in tissues surrounding THA. Females with MoM THA show high Ktrans values in DCE-MRI, suggesting altered tissue perfusion kinematics which may reflect relatively greater inflammation. Cite this article: Dr P. E. Beaule. Perfusion MRI in hips with metal-on-metal and metal-on-polyethylene total hip arthroplasty: A pilot stud. Bone Joint Res 2016;5:73–79. DOI: 10.1302/2046-3758.53.2000572


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IX | Pages 17 - 17
1 Mar 2012
Verdonk P Huysse W Verdonk R
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Purposes of the study. To assess the performance of an acellular synthetic scaffold in the treatment of painful partial meniscal tissue loss. Methods. Subjects recruited (n=52) had irreparable medial or lateral meniscus partial meniscus loss, intact rim, presence of both horns and a stable well aligned knee. Diagnostic imaging was used to assess tissue ingrowth at 3 months post-implantation by evidence of vascularisation in the scaffold using DCE-MRI with intravenous gadolinium contrast material (n=42). All DCE-MRI scans were assessed centrally for neovascularisation in the peripheral half of the scaffold meniscus and integration of the implanted device. Stability of tissue ingrowth and cartilage scores in the index compartment were assessed at 12 and 24 months post-implantation using anatomic MRI scans. Results. The 52 patients recruited (75% males) had a mean age of 30.8 ± 9.4 years and mean longitudinally measured lesions of 47.1 ± 10.0 mm, involving 34 medial and 18 lateral indications. At 3 months post-implantation tissue ingrowth was demonstrated in the peripheral half of the scaffold, in 36/42 (85.7%) subjects. To date stable or improved cartilage scores were seen in the index compartment at 12 months (n= 47) and 24 months (n=9). No signs of an inflammatory reaction to the scaffold or its degradation products were observed. The tissue observed on MRI at 12 months (n=47) remained stable at 24 months (n=9). No safety issues related to the scaffold were reported. Conclusions. These preliminary results indicate that this novel scaffold induces ingrowth of stable tissue