Faculty Bibliography

Background/Purpose: Osteoarthritis (OA) etiopathogenesis includes an inflammatory component. Published reports indicate that synovial fluid urate levels, even in patients without gout, associate with OA prevalence/severity. Whether serum urate (sUA), the precursor for gout and a biomarker for cardiovascular and kidney disease, may serve as a biomarker to convey or predict OA risk is not known. We investigated whether sUA levels associate with knee OA radiographic severity and contrast MRI-measured quantitative synovial volume (SV), and whether sUA levels predict radiographic progression, in a gout-free knee OA cohort. Methods: We assessed sUA in 88 gout-free subjects who completed a 24-month prospective, natural history knee OA study. Subjects had symptomatic medial knee OA, met ACR knee OA criteria and had BMI <33 at study entry. sUA was measured (enzyme-colorimetry) in serum frozen and banked at baseline. At baseline and 24 months, patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs (SynaFlexerTM). Twenty-seven subjects additionally had a dynamic gadolinium-enhanced 3.0T knee MRI that was read for quantitative synovial volume (SV). A musculoskeletal radiologist, blinded to subject data, determined joint space width (JSW) and Kellgren-Lawrence (KL) grades at each time point. Joint space narrowing (JSN) was determined as JSW change from baseline to 24 months. Pearson's correlations, student's t-tests, one-way ANOVA with post hoc Tukey-Kramer tests, ROC and AUC curves were used in statistical analyses, as appropriate. Results: sUA correlated with JSN in both univariate (r=0.40, p<0.01) and multivariate analyses (adjusting for age, gender and BMI, r=0.28, p=0.010). There was a significant difference in mean JSN after dichotomization of sUA at 6.8mg/dL, the solubility point for serum urate, even after adjustment for age, gender and BMI (JSN [+/-SEM] of 0.90mm+/-0.20mm for sUA>6.8; JSN [+/-SEM] of 0.31mm+/-0.09mm for sUA<6.8, p<0.01). Baseline sUA distinguished progressors (JSN>0.2mm), and fast progressors (JSN>0.5mm), from non-progressors (JSN<0.0mm) in multivariate analyses (area under the receiver operating characteristic curve [AUC] 0.626, p=0.027; AUC 0.620, p=0.045, respectively). sUA also correlated with SV (r=0.44, p=0.0040), a possible marker of JSN, though this correlation did not persist after controlling for age, gender and BMI (r=0.13, p=0.562). Conclusion: In non-gout patients with knee OA, sUA levels predict JSN and may serve as a biomarker for OA progression. (Figure presented)

OBJECTIVE: Inflammatory mediators, such as PGE2 and IL-1beta, are produced by osteoarthritic joint tissues, where they may contribute to disease pathogenesis. We examined whether inflammation, reflected in plasma and peripheral blood leukocytes (PBLs) reflected presence of osteoarthritis (OA), progression or symptoms in patients with symptomatic knee osteoarthritis (SKOA). METHODS: SKOA patients were enrolled in a 24-month prospective study of radiographic progression. Standardized knee radiographs were obtained at baseline and 24 months. Biomarkers assessed at baseline included plasma lipids PGE2 and 15-HETE, and transcriptome analysis of PBLs by microarray and qPCR. RESULTS: Baseline PGE synthases (PGES) by PBL microarray gene expression, and plasma PGE2 distinguished SKOA patients from non-OA controls (AUCs 0.87 and 0.89 respectively, p<0.0001). Baseline plasma 15-HETE was significantly elevated in SKOA versus non-OA controls (p<0.019). In the 146 patients who completed the 24-month study, elevated baseline expression of IL-1beta, TNFalpha and COX-2 mRNA in PBLs predicted higher risk for radiographic progression by joint space narrowing (JSN). In a multivariate model, AUC point estimates of models containing COX-2 in combination with demographic traits overlap the confidence interval of the base model in two out of the three JSN outcome measures (JSN >0.0mm, >0.2mm and >0.5mm, AUC=0.62-0.67). CONCLUSION: Inflammatory plasma lipid biomarkers PGE2 and 15-HETE identify patients with SKOA. PBL inflammatory transcriptome identifies a subset of SKOA patients at higher risk for radiographic progression. These findings may reflect low-grade inflammation in OA and may be useful as diagnostic and prognostic biomarkers in clinical development of disease-modifying OA drugs

OBJECTIVE: Pro- and anti-inflammatory mediators, such as IL-1beta and IL1Ra, are produced by joint tissues in osteoarthritis (OA), where they may contribute to pathogenesis. We examined whether inflammatory events occurring within joints are reflected in plasma of patients with symptomatic knee osteoarthritis (SKOA). DESIGN: 111 SKOA subjects with medial disease completed a 24-month prospective study of clinical and radiographic progression, with clinical assessment and specimen collection at 6-month intervals. The plasma biochemical marker IL1Ra was assessed at baseline and 18 months; other plasma biochemical markers were assessed only at 18 months, including IL-1beta, TNFalpha, VEGF, IL-6, IL-6Ralpha, IL-17A, IL-17A/F, IL-17F, CRP, sTNF-RII, and MMP-2. RESULTS: In cross-sectional studies, WOMAC (total, pain, function) and plasma IL1Ra were modestly associated with radiographic severity after adjustment for age, gender and body mass index (BMI). In addition, elevation of plasma IL1Ra predicted joint space narrowing (JSN) at 24 months. BMI did associate with progression in some but not all analyses. Causal graph analysis indicated a positive association of IL1Ra with JSN; an interaction between IL1Ra and BMI suggested either that BMI influences IL1Ra or that a hidden confounder influences both BMI and IL1Ra. Other protein biomarkers examined in this study did not associate with radiographic progression or severity. CONCLUSIONS: Plasma levels of IL1Ra were modestly associated with the severity and progression of SKOA in a causal fashion, independent of other risk factors. The findings may be useful in the search for prognostic biomarkers and development of disease-modifying OA drugs.

Purpose: To compare the accuracy of an optimized 3D TSE (SPACE) sequence using SPARSE-SENSE (SS) acceleration with 2D TSE sequences for the detection of internal derangement of the knee. Materials and Methods: An optimized accelerated SPACE sequence prototype was developed using avariable-density poisson-disc undersampling pattern of the two phase-encoding dimensions. Optimized parameters were: TR1100, TE22, TF28, variable flip angle evolution for PD weighting, SS undersampling factor of 9, fat suppression, presence of an optimized MT module, and 0.5 x 0.5 x 0.6 mm3 voxel size. This sequence (TA 4:57) was added to our conventional knee examination (sagittal PD and FS T2, coronal PD and FS PD, axial FS T2 2D TSE sequences (TA 10:56)) for 579 patients undergoing knee MR examinations imaged on a 3T scanner (Magnetom Skyra, Siemens Healthcare). An iterative SS reconstruction [2] was performed by enforcing sparsity in the wavelet representation of the knee images. Images were then reformatted in all 3 orthogonal planes at 1.5mmthickness. 50 of the 579 patients underwent arthroscopy of the knee and two experienced MSK radiologists blindly reviewed the SS SPACE sequence and the conventional 2D TSE sequences of these 50 patients at separate sittings to evaluate for the presence of meniscal or ligamentous tears. Results: 38 patients hadmedialmeniscal tears, 23 had lateral meniscal tears, and 16 had ACL tears. There was only 1 MCLand PCL tear and there were no LCL tears. The sensitivity, specificity, and accuracy for medial meniscal, lateral meniscal, and ACL tears on the 2D TSE images and SS Space images for each reader are presented below. Sensitivity Specificity Accuracy Sensitivity Specificity Accuracy Conclusion: An optimized and accelerated 3D TSE sequence has the potential to replace 2D TSE sequences for evaluation of internal derangement of the knee. If substantiated in larger clinical studies, this could lead to significant shortening of exam time, potentially enlarging the indication and utilization of knee MR as well as decreasing its cost

OBJECTIVE: Assess the diagnostic accuracy of 3-T indirect magnetic resonance arthrography (iMRA) for hip cartilage and labral pathology detection using arthroscopy as the reference standard and compare it to the published performance of direct magnetic resonance arthrography (dMRA). MATERIALS AND METHODS: Between 2009 and 2011, 290 patients suspected of having femoroacetabular impingement underwent iMRA. Our study group consisted of 41 of these patients (17 males, mean age 35 years; 24 females, mean age 33 years) who did not have a prior history of hip surgery and who subsequently underwent arthroscopy. Two experienced musculoskeletal radiologists separately evaluated the randomized and anonymized studies for the presence and quadrant location of labral and cartilage pathology. These recorded data were compared to arthroscopic reports. RESULTS: Forty-one patients had labral pathology, 34 patients had acetabular and 5 patients had femoral cartilage pathology at arthroscopy. Sensitivity, specificity, accuracy, negative- and positive-predictive values for labral lesion detection were respectively 98, 99, 99, 99 and 98 %; for acetabular cartilage lesion detection they were 69, 98, 89, 87 and 95 %; for femoral cartilage lesion detection they were 69, 95, 93 and 39 %. Sensitivities of iMRA by quadrant (anteroinferior, anterosuperior, posteroinferior, posterosuperior) for the labrum were 100.0, 95.0, NA and 85.7 %, for acetabular cartilage were NA, 58.8, NA and 39.5 % and for femoral cartilage were 50.0, 33.3, 75.0 and 75.0 %). NA indicates results not available because of the absence of findings in those quadrants. Specificities of iMRA by quadrant (anteroinferior, anterosuperior, posteroinferior, posterosuperior) for the labrum (95.0, 100.0, 95.1, 67.5 %), acetabular (100.0, 85.7, 92.6, 79.5 %) and femoral cartilage (100.0, 94.7, 96.2, 85.9 %). CONCLUSION: iMRA at 3 T is accurate in detecting labral pathology suggesting that it is a viable alternative to dMRA.

Three cases of PIN palsy following biceps repair are presented with clinical and imaging correlation. The imaging findings in these cases will be discussed and the orthopedic literature, as regards possible surgical approaches and technical factors believed to predispose to or prevent this complication, will be reviewed. It is important for radiologists to serve as consultants in these uncommon but sometimes devastating complications, helping to quickly and accurately recognize the imaging findings corresponding to the clinical symptoms and aiding the surgeon in diagnosis and treatment by identifying the possible causes and sites of nerve compression.

OBJECTIVE: To assess the relationship between knee alignment and subregional T1rho values of the femorotibial cartilage and menisci in patients with mild (Kellgren-Lawrence grade 1) to moderate (KL3) osteoarthritis (OA) at 3T. MATERIALS AND METHODS: 26 subjects with a clinical diagnosis of KL1-3 OA were included and subdivided into three subgroups: varus, valgus, and neutral. All subjects were evaluated on a 3T MR scanner. Mann-Whitney and Wilcoxon signed rank tests were performed to determine any statistically significant differences in subregional T1rho values of femorotibial cartilage and menisci among the three subgroups of KL1-3 OA patients. RESULTS: Medial femoral anterior cartilage subregion in varus group had significantly higher (p<0.05) T1rho values than all cartilage subregions in valgus group. Medial tibial central cartilage subregion had significantly higher T1rho values (p<0.05) than lateral tibial central cartilage subregion in varus group. The posterior horn of the medial meniscus in neutral group had significantly higher T1rho values (p<0.0029) than all meniscus subregions in valgus group. CONCLUSION: There exists some degree of association between knee alignment and subregional T1rho values of femorotibial cartilage and menisci in patients with clinical OA.

We compared standard and specialized plain radiographs with computed tomography (CT) for their ability to detect screw penetration of the articular surface of the distal radius in volar plating. Eight human cadaveric specimens were implanted with a fixed angle volar plate and 5 screws. Two groups were evaluated: (1) no articular screw penetration or (2) intra-articular screw penetration. Radiographs were obtained of each specimen. CT using 0.4 mm thickness slices were obtained and images were reconstructed in the sagittal and coronal planes. The radiographs and CTs were evaluated based on whether or not articular penetration occurred. The sensitivity, specificity, and accuracy of each radiographic modality were evaluated. CT was found to be much more sensitive and specific in detecting screw penetration than plain radiographs. The kappa (kappa) statistic demonstrated "almost perfect interobserver agreement" based on CT readings, but only "substantial interobserver agreement based on plain radiographs." CT is more sensitive and specific and achieves a higher kappa statistic than plain radiographs in detecting radiocarpal screw penetration after volar plating. CT should be used in detecting screw penetration when there is suspicion for radiocarpal joint penetration.