A. D. Gait

A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions

Objective Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs). Methods Eligible subjects had painful PF OA. Subjects were randomly allocated to brace or no brace for 6 weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images. The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity, and the primary structural outcome was BML volume change in the PF joint. Analyses used multiple linear regression. Results We randomised 126 subjects aged 40–70 years (mean age 55.5  years; 72 females (57.1%)). Mean nominated visual analogue scale (0–10 cm) pain score at baseline was 6.5 cm. 94 knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4 h/day. 6 subjects withdrew during the trial. After accounting for baseline values, the brace group had lower knee pain than the control group at 6 weeks (difference between groups −1.3 cm, 95% CI −2.0 to −0.7; p<0.001) and reduced PF BML volume (difference −490.6 mm3, 95% CI −929.5 to −51.7; p=0.03) but not tibiofemoral volume (difference −53.9 mm3, 95% CI −625.9 to 518.2; p=0.85). Conclusions A PF brace reduces BML volume in the targeted compartment of the knee, and relieves knee pain. Trial registration number UK. ISRCTN50380458.

Bone marrow lesions in knee osteoarthritis change in 6-12 weeks

Summary Objectives Knee osteoarthritis (OA) is thought to be a slowly evolving disease with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1–2 years with evidence that over 6 months change in cartilage is not detectable. In contrast to cartilage, bone has the capacity to adapt rapidly, such as after fracture. We tested whether bone marrow lesions (BMLs) change in volume in 6 and 12 weeks, suggesting they may provide evidence of short term fluctuations of joint damage. Methods In 62 patients with patellofemoral knee OA (mean age 55.7 years, 59.7% women, mean BMI 31.0), we obtained baseline, 6 and 12 week knee MRIs with contrast enhancement. Of those with BMLs at baseline, we assessed BML volume on the axial proton density fat saturated (FS) images and postcontrast sagittal T1 weighted FS images. We manually segmented BML volumes, testing repeatability of BML volumes in knees remeasured. Using the standard deviation of the difference between repeated measurements to calculate Bland–Altman Limits of Agreement, we determined how much BML volume change represented a change greater than due to chance. Results Fifty-two patients had BMLs at baseline. Test–retest reliability for BML volume was high (ICC 0.89, 95% CI 0.80–0.97). All knees showed at least some change in BML volume by 6 and 12 weeks. On the axial view at 6 weeks, 20/49 (40.8%) knees showed BML volume changes greater than the limits of agreement with similar results at 12 weeks. BML changes were evenly divided among knees with enlarging and shrinking BMLs. 63.3% of the knees had more than 50% change in BML volume at either 6 or 12 weeks on the axial view and 48.7% on the sagittal view. Conclusions Knee BML volumes change in several weeks in many persons with knee OA. To the extent that they could be regarded as treatment targets, trials testing BML effects could avoid the usual prolonged structure modification trials.

Synovial tissue volume: a treatment target in knee osteoarthritis (OA).

Background Synovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention. Methods Persons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association. Results 120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7–14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=−1071 mm3; 95% CI −1839 mm3 to −303 mm3, p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm3; 95% CI 25 mm3 to 2414 mm3, p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=−202 mm3; 95% CI −2008 mm3 to 1604 mm3, p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient—change in KOOS pain score per 1000 mm3 change in STV=−1.13; 95% CI −1.87 to −0.39, p=0.003), although STV accounted for only a small proportion of the variance in change in pain. Conclusions Synovial tissue volume in knee OA shrinks following steroid therapy, and rebounds in those whose pain relapses. It can be considered a treatment target in symptomatic knee OA. Trial registration number ISRCTN07329370.

Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis

Summary Objective Synovium is increasingly a target of osteoarthritis (OA) treatment, yet its optimal measurement is unclear. Using dynamic contrast enhanced (DCE) MRI in knee OA patients before and after intraarticular steroid injection, we compared the responsiveness of static synovial volume measures to measures of dynamic changes in synovial enhancement, changes that are strongly related to synovial vascularity. Methods Ninety three patients underwent DCE-MRI before and 1–2 weeks after intra-articular injection of 80 mg methylprednisolone. Synovium was segmented and volume, relative enhancement rate (RER), maximum relative enhancement (REmax), late relative enhancement (RElate) and pharmacokinetic parameters (Ktrans, ve) were calculated. KOOS (knee injury and osteoarthritis outcome score) pain score was recorded before and after injection. Standardized change scores were calculated for each parameter. Linear regression and Pearsons correlations were used to investigate the relationship between change in MRI parameters and change in pain. Results The change in standardized score for the measures of synovial enhancement, RElate and REmax were −0.58 (95% CI −0.79 to −0.37) and −0.62 (95% CI −0.83 to −0.41) respectively, whereas the score for synovial volume was −0.30 (−0.52 to −0.09). Further, change in knee pain correlated more strongly with changes in enhancement (for both REmax and RElate, r = −0.27 (95% CI −0.45 to −0.07)) than with changes in synovial volume −0.15 (−0.35 to 0.05). Conclusion This study suggests DCE-MRI derived measures of synovial enhancement may be more sensitive to the response to treatment and more strongly associated with changes in pain than synovial volume and may be better outcomes for assessment of structural effects of treatment in OA.

A parts-and-geometry initialiser for 3D non-rigid registration using features derived from spin images

Abstract Non-rigid registration is an important precursor to statistical analysis and machine learning in medical image analysis. It is commonly used to find correspondences between images which is a necessary first step for further processing. However, registering images which have large pose differences and/or are composed of substructures of similar appearance requires that registration be initialised carefully for the results to be valid. This work addresses both problems in the context of 3D volumetric images. We use parts-and-geometry models to automatically align images before registration proceeds. An important component of the parts are orientation-invariant descriptors computed using spin images. In the following we describe the construction of the parts-and-geometry models and how they can be incorporated into non-rigid registration. We use 3D CT images of the wrist and knee to demonstrate the effectiveness of the models at locating substructures with similar appearance, and show both qualitatively and quantitatively that initialisation with parts-and-geometry models improve the accuracy of registration.

Corrigendum to “Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis” [Osteoarthritis Cartilage 24 (2016) 1392–1398]

y Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK z Centre for Imaging Sciences, Institute of Population Health, The University of Manchester, Manchester, UK x Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK k NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK ¶ Warwick Medical School, The University of Warwick, Coventry, UK # Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK yy Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, UK zz Clinical Epidemiology Unit, Boston University School of Medicine, Boston, MA, USA

Response to: 'The effect of synovial tissue volume shrinking on pain relief for knee osteoarthritis was overestimated or not?' by Wei et al.

We thank Wei et al for their interest in our work and positive comments about our trial results.1 ,2 Wei et al highlight a number of issues that we address in turn. Analysis of data from our trial of patients with symptomatic knee osteoarthritis (OA) showed an association between change in the level of knee pain and change in synovial tissue volume (STV) following an intra-articular steroid injection. We agree with Wei et al that synovial shrinkage is not the only mechanism by which steroids might result in a reduction in pain; this is underscored, as we highlight …