Professor of Radiology and Medicine
Vice Chair, Academic Affairs
Assistant Dean of Diversity
Director, Quantitative Imaging Center (QIC)
Boston University School of Medicine, Boston, MA
1. Ali Guermazi, MD, PhD
Professor of Radiology and Medicine
Vice Chair, Academic Affairs
Assistant Dean of Diversity
Director, Quantitative Imaging Center (QIC)
Boston University School of Medicine, Boston, MA
Imaging of Synovitis in OA
2. • Shareholder of BICL, LLC
• Consultant to MerckSerono, AstraZeneca, Pfizer,
Roche, Galapagos, and TissueGene
Disclosure
3. Outline
Technical aspects – non CE vs CE
MRI vs Histology
Synovitis and structure
– Cross-sectional and longitudinal study
Synovitis and symptoms
– Cross-sectional and longitudinal study
Clinical trials of synovitis in OA
New techniques
Other modalities
Conclusion
4. MRI Sequences to Assess Synovitis
T1-weighted: increased volume / thickening of
the synovial membrane
T2-weighted fat-suppressed (FS) / STIR:
increased water content
Contrast-enhanced T1-weighted (FS):
vascularity and permeability of the membrane
– Differentiate effusion from true synovial thickening
Novel non-enhanced MRI sequences to asses
synovitis
5. Assessment of Synovitis using
NCEMRI in OA
Signal changes in Hoffa’s fat pad
(“Hoffa-synovitis”)
Roemer FW et al. AJR 2009
To date, synovitis in large epidemiological OA studies is assessed
using non contrast-enhanced MRI
Joint effusion
(“Effusion-synovitis”)
6. Roemer et al. AJR 2009
Compare Hoffa signal on NCEMRI with CEMRI in knee OA
Comparison of sagittal FS PD-w and CE FS T1-w MRI
50 knee OA patients
Agreement between unenhanced and CE MRI was fair
to moderate (weighted κ=0.35 and 0.45)
Hoffa fat pad signal alteration:
– LOW Specificity=10-38%
Signal in Hoffa's fat pad on NCEMRI do not always
represent synovitis but are a nonspecific albeit
sensitive
SQ scoring of synovitis in OA ideally should be
performed with T1-weighted CEMRI
7. Guermazi et al.
Ann Rheum Dis 2011
SQ scoring system for synovitis
Sagittal and axial CE FS T1-w MRI
Grades: 0-2 at each of 11 locations:
– medial and lateral parapatellar recess
– suprapatellar, infrapatellar, intercondylar,
medial and lateral perimeniscus
– adjacent to PCL, ACL, loose bodies, Baker cyst
Moderate to severe synovitis showed
significant association with maximum
WOMAC pain score item compared to
knees with no or equivocal synovitis
8. Literature evidence:
NCEMRI vs. CEMRI
Is NCEMRI sufficient for imaging assessment
of synovitis in OA trials?
NO!
NCEMRI is limited:
Non-specific
Cannot differentiate between synovium
and effusion
Inconsistent association with pain by
different studies
9. Why Gado Is Not Used in OA Studies?
Time consuming
– Add 5 min to usually 20-30 min exam
Expensive
– Add $50 to $100 per exam
Not without risk to the participant
– Very low risk of nephrogenic systemic
fibrosis (NSF)
Exclude patients with renal insufficiency (GFR)
– Unknown safety issue from Gado deposit
10. Crema et al. OAC 2013
Diagnostic performance of signal changes in HFP
assessed on NCEMRI in detecting synovitis
393 participants from the MOST
Hoffa-synovitis scored 0-3 using NCEMRI
Synovial thickness scored 0-2 on CEMRI in five
parapatellar regions (= reference)
NCEMRI:
– Sensitivity 71% (infrapatellar) & 88% (intercondylar)
– Specificity 55% (infrapatellar) & 30% (intercondylar)
– No significant association with pain
CEMRI identifies associations with pain better than
NCEMRI
12. Crema et al. Osteoarthritis Cartilage 2017
Compare SQ and Q methods for knee synovitis on
NCEMRI and CEMRI
104 end stage knee OA patients
NCEMRI used to evaluate effusion-synovitis
and Hoffa-synovitis
CEMRI used for synovitis assessment
reference standard
Effusion-synovitis showed superior correlations
and sensitivity than Hoffa-synovitis
– Correlations of effusion-synovitis with synovial
thickness and volume: r = 0.41 and r = 0.43 (P <
.001) r = 0.32 and r = 0.39 (P < .0001)
13. MRI vs. Histology
Loeuille et al. OAC 2011
30 patients with knee OA
SQ synovitis assessment using NCEMRI and
CEMRI
– Gold standard = histology of synovial membrane
biopsy
– CEMRI-detected synovitis was correlated with
histologically proven inflammation
– NCEMRI was not associated with histology
15. Atukorala et al. Ann Rheum Dis 2014
If synovitis precedes the development of ROA?
133 knees with ROA, 133 control knees, 4-year
observation
Persons w/o ROA at baseline
ORs for occurrence of incidental ROA
associated with the presence of BL effusion-
synovitis: 1.56 – 4.7
ORs for the occurrence of incidental ROA
associated with the presence of BL Hoffa-
synovitis: 1.80 – 2.47
Effusion-synovitis and Hoffa-synovitis strongly
predicted the development of incidental ROA
16. Roemer et al. OAC 2010
Anatomical distribution of synovitis and its association
with joint effusion on NCEMRI and CEMRI
111 patients with knee pain (VIDEO study)
Anatomical distribution of synovitis and its
association with joint effusion on NCEMRI and
CEMRI
In a population of mixed ROA severity, the
large majority of knees exhibited definite
synovitis at least in 1 subregion
– Commonest site = posterior to PCL (71.2%)
– Joint effusion as measured on PD FS images does not
only represent effusion but also synovial thickening
18. MacFarlane et al. Arthritis Rheum 2019
Association of changes in effusion-synovitis with
progression of cartilage damage
221 subjects from the MeTeOR study (knee OA +
meniscal tear)
SQ assessment of effusion synovitis and cartilage
damage
Patients with extensive effusion-synovitis at baseline had
a relative risk (RR) of progression of cartilage damage
depth of 1.7 (95% CI 1.0-2.7)
Compared to those with persistently minimal effusion-
synovitis, those with persistently extensive effusion-
synovitis had a significantly increased risk of progression
of cartilage damage depth (RR 2.0 [95% CI 1.1-3.4])
19. Synovitis vs Symptoms
De Lange-Brokaar et al. A&R 2015
86 subjects with symptomatic knee OA
SQ assessment of synovitis using CEMRI
Synovitis at 3 sites was associated with
radiographic severity
Different patterns of synovitis in knee OA were
observed
The pattern that included several patellar sites
was associated with pain, whereas other patterns
showed no association, suggesting that pain
perception in patients with knee OA is a localized
response
20. Wallace et al. Arthritis Care Res 2017
Associations between clinical evidence of inflammation
and synovitis in symptomatic knee osteoarthritis
107 subjects with symptomatic knee OA
SQ assessment of synovitis using CEMRI
Significant associations were found between
the number of regions affected by synovitis and
WOMAC pain, effusion, and joint line
tenderness
21. O’Neill et al. Ann Rhem Dis 2016
Synovial tissue volume: a treatment target in knee OA
120 subjects with painful knee OA, before and
after intra-articular steroid injection
Synovial tissue volume (STV) measured on post-
contrast MRI
Synovial tissue volume in knee OA shrinks
following steroid therapy, and rebounds in those
whose pain relapses
=> Synovitis potential treatment target in symptomatic
knee OA
22. Novel Techniques Using NCE-MRI
Yoo et al. (Radiology, 2017)
FLAIR-FS sequence with 3T scanner, for peripatellar synovitis
CE-MRI as gold standard
23. Yoo et al. Continued
33 patients
Strong correlations between FLAIR FS and CE
T1W FS in the assessment of peripatellar
synovitis by both readers (correlation coefficient,
0.675–0.973)
With CE T1W FS as the reference, FLAIR FS
showed relatively good diagnostic performance
for detection of synovitis of any severity (>90%
accuracy)
25. 7T MRI now has regulatory clearance to be used
clinically
Advantages: higher resolution, faster scan time,
specific metabolic imaging (Na+, CEST)
May have role in further advancing non-enhanced
synovitis assessment
We could show that CE MRI of synovitis is feasible
Common assessment approaches feasible at 7T
including SQ, Q, DCE
Roemer et al. Br J radiol, submitted
Multiparametric Synovitis Assessment
at 7T Ultra-High Field MRI
26. Comparison CE vs non CE MRI at 7T DCE at 7T is feasible
Multiparametric Synovitis Assessment
at 7T Ultra-High Field MRI
27. Ultrasound Imaging of Synovitis
Mostly used in hand OA
Synovial hypertrophy and
hyperemia (=active synovitis)
Erosion
Effusion
US-detected grey scale synovitis
and Power Doppler signals are
associated with radiographic hand
OA progression after 5 years
Mathiessen A, et al. Ann Rheum Dis 2016
Figure: Hayashi D, et al. Sem Arthritis Rheum 2011
28. PET Imaging of Synovitis
18FDG PET
Increased metabolism = active synovitis
PET-detected synovitis associated with knee pain in OA
Hybrid PET/CT or PET/MRI for accurate localization
Parsons MA, et al. Nucl Med Commun 2015
Figure: Hayashi D, et al.
PET Clin 2019
29. Summary of synovitis imaging
Synovitis can be evaluated using NCEMRI
– Hoffa-synovitis and effusion-synovitis (surrogate)
– Novel technical developments promising (e.g. FLAIR-
FS, Diffusion tensor)
CEMRI enables
– Accurate assessment of synovitis
– Differentiation between synovium and effusion
CEMRI-detected synovitis is associated with
pain in OA
– Consistent evidence from multiple studies
30. However, so far, very few high-quality clinical
trials have used synovial inflammation as an
outcome measure and most of them found
no clinical benefits
Therefore, well-designed trials of the
disease-modifying therapies should consider
synovial inflammation as an important
treatment target in patients with
inflammatory OA phenotypes
Perspective
Wang et al OAC 2018
31. Conclusions (1)
CEMRI
– Should be recommended if we aim to assess
synovitis accurately in OA (especially in clinical
trials)
– Is a reliable measure of synovitis
– Could be useful in
clinical trials as a marker of therapeutic response
clinical practice as a guide to treatment
monitoring
32. Conclusions (2)
Novel imaging techniques without contrast
administration are promising in showing
synovial inflammation
– Better than Hoffa fat pad surrogate
Targeting the inflammatory synovium has
great potential to delay or prevent structural
alterations and treat symptoms, especially in
early OA
34. What's happening at IWOAI 2019?
• Clinical & Imaging Parameters for DMOAD Trials & Update on DMOAD
Developments
• Pre-workshop on Machine Learning Segmentation Challenge
• Novel Analytics and Computational Approaches
• Linking Imaging with Tissue and Joint Function
• Imaging Early Osteoarthritis
• Phenotypes/Subgroups of Osteoarthritis
• Updates & Insight from APPROACH / OAI / MOST
• Pre-Congress Boat Trip (June 25th) & Post-Congress Bike/Beach Trip (June 29th)
June 26-28, 2019
Charlottetown, Prince Edward Island, Canada
Visit: www.ISOAI.org or www.IWOAI.org
Editor's Notes
Compare synovitis-like signal changes in Hoffa's fat pad on unenhanced proton density-weighted fat-suppressed sequences with signal alterations in Hoffa's fat pad and peripatellar synovial thickening on T1-weighted fat-suppressed contrast-enhanced sequences in patients with osteoarthritis
OBJECTIVES:
To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI.
METHODS:
Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (<2 mm), grade 1 (2-4 mm) and grade 2 (>4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter- and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed.
RESULTS:
400 subjects were included (mean age 58.8±7.0 years, body mass index 29.5±4.9 kg/m(2), 46% women). For individual sites, intrareader reliability (weighted κ) was 0.67-1.00 for reader 1 and 0.60-1.00 for reader 2. Inter-reader agreement (κ) was 0.67-0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient ( ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively).
CONCLUSIONS:
A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.
FWR=add another slide of "why use Gd in OA studies...." give lookout on novel non-enhanced MRI techniques see Edwin Oei...
PURPOSE:
To assess the diagnostic performance of signal changes in Hoffa's fat pad (HFP) assessed on non-contrast-enhanced (CE) magnetic resonance imaging (MRI) in detecting synovitis, and the association of pain with signal changes in HFP on non-CE MRI and peripatellar synovial thickness on CE MRI.
METHODS:
The Multicenter Osteoarthritis (MOST) Study is an observational study of individuals who have or are at high risk for knee OA. All subjects with available non-CE and CE MRIs were included. Signal changes in HFP were scored from 0 to 3 in two regions using non-CE MRI. Synovial thickness was scored from 0 to 2 on CE MRI in five peripatellar regions. Sensitivity, specificity and accuracy of HFP signal changes were calculated considering synovial thickness on CE MRI as the reference standard. We used logistic regression to assess the associations of HFP changes (non-CE MRI) and synovial thickness (CE MRI) with pain from walking up or down stairs, after adjusting for potential confounders.
RESULTS:
A total of 393 subjects were included. Sensitivity of infrapatellar and intercondylar signal changes in HFP was high (71% and 88%), but specificity was low (55% and 30%). No significant associations were found between HFP changes on non-CE MRI and pain. Grade 2 synovial thickness assessed on CE MRI was significantly associated with pain after adjustments for potential confounders.
CONCLUSION:
Signal changes in HFP detected on non-CE MRI are a sensitive but non-specific surrogate for the assessment of synovitis. CE MRI identifies associations with pain better than non-CE MRI.
TOP: Sagittal FS PDw (non-CE MRI) shows signal changes in HFP depicted at the intercondylar (arrows, a) and the infrapatellar (arrows, b) regions.
BOTTOM: Sagittal (a) and axial (b) FS T1w MRIs afer i.v. Gd injection demonstrate pathological synovial enhancement and thickening (synovitis) detected at the suprapatellar (SP), infrapatelar (IP), intercondylar (IC), medial parapetellar (PM), and lateral parapatellar (PL) regions.
RESULTS:
A total of 104 subjects (one knee per subject) were included. Correlations of effusion-synovitis with synovial thickness and volume were r = 0.41 and r = 0.43 (P < .001) r = 0.32 and r = 0.39 (P < .0001).
CONCLUSION:
Using synovial thickness assessed on gadolinium-enhanced sequences as the reference, effusion-synovitis showed superior correlations and sensitivity. Effusion-synovitis should be preferred over Hoffa-synovitis as a surrogate marker for synovial thickening, in studies of knee OA for which gadolinium-enhanced sequences are not available.
Osteoarthritis Cartilage. 2017 Feb;25(2):267-271. doi: 10.1016/j.joca.2016.09.016. Epub 2016 Sep 30.
Comparison between semiquantitative and quantitative methods for the assessment of knee synovitis in osteoarthritis using non-enhanced and gadolinium-enhanced MRI.
Crema MD1, Roemer FW2, Li L3, Alexander RC4, Chessell IP5, Dudley AD5, Karlsten R6, Rosen LB7, Guermazi A8.
FWR=non CE MRI was not associated with histology!
OBJECTIVE:
The purpose of this study was to evaluate synovial membrane (SM) inflammation and joint effusion scores by semiquantitative magnetic resonance imaging (MRI) assessment with and without enhanced sequences. Gold standards used for comparison were microscopic examination of SM biopsies for SM inflammation and joint volume measurement (JVM) after arthrocentesis for effusion.
METHODS:
Patients (n = 30) fulfilling ACR criteria for knee osteoarthritis (OA) and requiring joint lavage, were evaluated with MRI: (1) SM inflammation was assessed by Whole-Organ Magnetic Resonance Imaging Score (WORMS) on T2 weighted sequences (T2w) a composite score assessing together synovitis and effusion, and the MRI-synovitis score (based on synovitis thickening in five regions of interest) on a T1-weighted fat sat sequence after contrast agent injection (T1wCE). (2) Joint effusion was evaluated by MRI-effusion score (T1wCE) and the WORMS (T2w). JVM was measured after arthrocentesis, and microscopic SM inflammation was determined in SM samples (n = 86). Correlations between MRI scores and clinical, biologic and histologic parameters were studied.
RESULTS:
Both scores for effusion were well correlated [r = 0.82 (0.65-0.91); P < 0.001] and presented excellent intraclass correlation coefficient (ICC) for intra- and inter-observer reproducibility. MRI scores for effusion were well correlated with JVM (r = 0.60 for WORMS and r = 0.59 for MRI-effusion score). Synovitis scores were highly reproducible but moderately correlated (r = 0.63; P < 0.001). Only MRI-synovitis total score (T1wCE) was correlated with SM microscopic inflammation (r = 0.46; P = 0.01) and most strongly infiltration (r = 0.45; P < 0.005).
CONCLUSIONS:
T2w sequences are adequate in assessing effusion volume in compare to joint volume by arthrocentesis but only T1wCE sequences are able to detect synovitis according to the reference of synovial biopsy.
Fig. 3. Distinguishing effusion from synovitis is possible only on injected sequence. A: large effusion in the medial and lateral recesses on axial T2 image. Synovitis appeared in high signal and is undistinguishable from joint effusion also in high signal intensity; B: same location on the injected sequence, only the inflamed SM is enhanced by the contrast agent and scored according to the degree of thickening. The microscopic features of the osteoarthritic (OA) SM are presented on C, “normal” SM composed of 2e3 layers of synovial lining cells (hematoxylineeosinesafran staining). Beneath them are localized capillaries (arrow) and fat tissue of the subintima. Note that infiltration is moderate; D: severe infiltration associated with an increase of vascularization (congestion) of the subintima without increase in the number of lining cells. (original magnification 200).
OBJECTIVES:
It is unknown whether joint inflammation precedes other articular tissue damage in osteoarthritis. Therefore, this study aims to determine if synovitis precedes the development of radiographic knee osteoarthritis (ROA).
METHODS:
The participants in this nested case-control study were selected from persons in the Osteoarthritis Initiative with knees that had a Kellgren Lawrence grading (KLG)=0 at baseline (BL). These knees were evaluated annually with radiography and non-contrast-enhanced MRI over 4 years. MRIs were assessed for effusion-synovitis and Hoffa-synovitis. Case knees were defined by ROA (KLG≥2) on the postero-anterior knee radiographs at any assessment after BL. Radiographs were assessed at P0 (time of onset of ROA), 1 year prior to P0 (P-1) and at BL. Controls were participants who did not develop incident ROA (iROA) from BL to 48 months).
RESULTS:
133 knees of 120 persons with ROA (83 women) were matched to 133 control knees (83 women). ORs for occurrence of iROA associated with the presence of effusion-synovitis at BL, P-1 and P0 were 1.56 (95% CI 0.86 to 2.81), 3.23 (1.72 to 6.06) and 4.7 (1.10 to 2.95), respectively. The ORs for the occurrence of iROA associated with the presence of Hoffa-synovitis at BL, P-1 and P0 were 1.80 (1.1 to 2.95), 2.47 (1.45 to 4.23) and 2.40 (1.43 to 4.04), respectively.
CONCLUSIONS:
Effusion-synovitis and Hoffa-synovitis strongly predicted the development of iROA.
PURPOSE:
To describe the anatomical distribution of synovitis and its association with joint effusion on non-enhanced and contrast-enhanced (CE) MRI in patients with knee osteoarthritis (OA).
METHODS:
Baseline MRI was performed at 1.5T using axial proton density (PD)-weighted (w) fat suppressed (fs) and axial and sagittal T1-w fs CE sequences. Synovial enhancement was scored in nine articular subregions. Maximum synovial enhancement was grouped as absent (0), equivocal (1) and definite (2 and 3). Effusion was scored from 0 to 3 on the axial sequences. We described the anatomical distribution of synovitis, its association with effusion and compared assessment of effusion on T1-w fs CE and PD fs sequences.
RESULTS:
111 subjects were included and examined by MRI. 89.2% of knees exhibited at least one subregion with a minimum grade 2 and 39.6% at the maximum of a grade 3. The commonest sites for definite synovitis were posterior to the posterior cruciate ligament (PCL) in 71.2% and in the suprapatellar region in 59.5% of all knees. On T1-w fs CE, 73.0% of knees showed any effusion. Definite synovitis in at least one location was present in 96.3% knees with an effusion and in 70.0% without an effusion. Higher grades of effusion were scored on the PD fs sequence.
CONCLUSION:
Definite synovitis was present in the majority of knees with or without effusion with the commonest sites being posterior to the PCL and in the suprapatellar recess. Joint effusion as measured on PD fs images does not only represent effusion but also synovial thickening.
LEFT: Localized synovitis. Sagittal T1-w fs CE image shows marked synovial thickening (grade 3) posterior to the PCL (arrows). Distal PCL depicted as hypointense linear structure (arrowheads).
RIGHT: Joint effusion. (A) Axial PD fs image. Marked bright signal intensity within the joint and convexity of the joint capsule suggestive of a large joint effusion are depicted (arrowheads). (B) Axial T1 fs CE image of the same knee at the same slice position. The CE image shows marked synovial thickening depicted as hyperintense tissue lining along the joint capsule. Only a small amount of effusion is observed (arrowheads).
Arthritis Rheumatol. 2019 Jan;71(1):73-81. doi: 10.1002/art.40660. Epub 2018 Nov 29.
Association of Changes in Effusion-Synovitis With Progression of Cartilage Damage Over Eighteen Months in Patients With Osteoarthritis and Meniscal Tear.
MacFarlane LA1, Yang H2, Collins JE1, Jarraya M3, Guermazi A3, Mandl LA4, Martin SD5, Wright J6, Losina E1, Katz JN1; MeTeOR Investigator Group.
Collaborators (9)
Author information
Abstract
OBJECTIVE:
Synovitis is a feature of knee osteoarthritis (OA) and meniscal tear and has been associated with articular cartilage damage. This study was undertaken to examine the associations of baseline effusion-synovitis and changes in effusion-synovitis with changes in cartilage damage in a cohort with OA and meniscal tear.
METHODS:
We analyzed data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of surgery versus physical therapy for treatment of meniscal tear. We performed semiquantitative grading of effusion-synovitis and cartilage damage on magnetic resonance imaging, and dichotomized effusion-synovitis as none/small (minimal) and medium/large (extensive). We assessed the association of baseline effusion-synovitis and changes in effusion-synovitis with changes in cartilage damage size and depth over 18 months, using Poisson regression models. Analyses were adjusted for patient demographic characteristics, treatment, and baseline cartilage damage.
RESULTS:
We analyzed 221 participants. Over 18 months, effusion-synovitis was persistently minimal in 45.3% and persistently extensive in 21.3% of the patients. The remaining 33.5% of the patients had minimal synovitis on one occasion and extensive synovitis on the other. In adjusted analyses, patients with extensive effusion-synovitis at baseline had a relative risk (RR) of progression of cartilage damage depth of 1.7 (95% confidence interval [95% CI] 1.0-2.7). Compared to those with persistently minimal effusion-synovitis, those with persistently extensive effusion-synovitis had a significantly increased risk of progression of cartilage damage depth (RR 2.0 [95% CI 1.1-3.4]).
CONCLUSION:
Our findings indicate that the presence of extensive effusion-synovitis is associated with subsequent progression of cartilage damage over 18 months. The persistence of extensive effusion-synovitis over time is associated with the greatest risk of concurrent cartilage damage progression.
Arthritis Care Res (Hoboken). 2017 Sep;69(9):1340-1348. doi: 10.1002/acr.23162. Epub 2017 Aug 14.
Associations Between Clinical Evidence of Inflammation and Synovitis in Symptomatic Knee Osteoarthritis: A Cross-Sectional Substudy.
Wallace G1, Cro S2, Doré C2, King L3, Kluzek S1, Price A1, Roemer F4, Guermazi A5, Keen R6, Arden N7.
Author information
Abstract
OBJECTIVE:
Painful knee osteoarthritis (KOA) has been associated with joint inflammation. There is, however, little literature correlating signs of localized inflammation with contrast-enhanced (CE) magnetic resonance imaging (MRI) of synovium. This study examined the relationship between clinical and functional markers of localized knee inflammation and CE MRI-based synovial scores.
METHODS:
Patients with symptomatic KOA were enrolled into the randomized, double-blind, Vitamin D Evaluation in Osteoarthritis (VIDEO) trial. In this cross-sectional substudy, associations between validated MRI-based semiquantitative synovial scores of the knee and the following markers of inflammation were investigated: self-reported pain and stiffness, effusion, warmth, joint line tenderness, erythrocyte sedimentation rate, radiographic severity, and functional ability tests.
RESULTS:
A total of 107 patients satisfied the inclusion criteria of complete data and were included in the analysis. Significant associations were found between the number of regions affected by synovitis and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, effusion, and joint line tenderness. Each additional region affected by synovitis was associated with an increase in WOMAC pain (1.82 [95% confidence interval (95% CI) 0.05, 3.58], P = 0.04), and the association with extent of medial synovitis was particularly strong (3.21 [95% CI 0.43, 5.99], P = 0.02). Extent of synovitis was positively associated with effusion (odds ratio 1.69 [95% CI 1.37, 2.08], P < 0.01) and negatively associated with joint line tenderness (relative risk 0.87 [95% CI 0.84, 0.90], P < 0.01).
CONCLUSION:
There is a strong positive association between synovitis and self-reported patient pain and clinically detectable effusion. Nonoperative treatments directed at management of inflammation and future trials targeting the synovial tissue for treating KOA should consider these 2 factors as potential inclusion criteria.
Ann Rheum Dis. 2016 Jan;75(1):84-90. doi: 10.1136/annrheumdis-2014-206927. Epub 2015 Jun 26.
Synovial tissue volume: a treatment target in knee osteoarthritis (OA).
O'Neill TW1, Parkes MJ2, Maricar N2, Marjanovic EJ2, Hodgson R3, Gait AD3, Cootes TF3, Hutchinson CE4, Felson DT5.
Author information
Abstract
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 mm(3); 95% CI -1839 mm(3) to -303 mm(3), 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 mm(3); 95% CI 25 mm(3) to 2414 mm(3), p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=-202 mm(3); 95% CI -2008 mm(3) to 1604 mm(3), 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 mm(3) 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.
Figure 3: Axial CE knee MR images obtained in a 56-year-old woman with osteoarthritis. (a) FS T1-weighted image obtained after intravenous gadolinium-based contrast material injection demonstrates enhancing synovium with excellent tissue contrast. Note the thick enhancing synovium in the medial and lateral femoral gutters (arrowheads). (b) FLAIR FS image shows the synovium separated into two layers (arrowheads). In addition, the most superficial layer of articular cartilage of the patella is hyperintense on FLAIR FS images (arrows) and consequently appears as if the synovial lining is continuous over the articular cartilage of the patella.
Good agreement between the two readers for the synovial visibility (weighted k = 0.81–0.88) and synovitis assessments (intraclass correlation coefficient = 0.95, weighted k = 0.72–0.79) on FLAIR FS and CE T1-weighted images.
This preliminary study of FLAIR-FS sequence showed the new technique can potentially enable evaluation of inflamed synovium with high sensitivity and specificity, without the injection of a contrast agent.
Figure 3 Dorsal longitudinal power Doppler ultrasonographic
images of the osteoarthritic proximal interphalangeal joint. (A) Image taken before intramuscular corticosteroid therapy demonstrates the proximal phalanx (pp), middle phalanx (mp), and associated synovial hypertrophy (arrows). The flash of color within the region of synovial hypertrophy indicates vascularity. (B) Image taken 4 weeks after intramuscular corticosteroid therapy demonstrates a reduction in the vascularity within synovium, as indicated by a lack of the flash of color seen in (A). (Image courtesy of Dr. Helen Keen, The University of Western Australia, Australia.) (Color version of figure is available online.)
Fig. 6. PET-CT. (A) Axial fusion image of CT and FDG-PET shows marked intra-articular FDG accumulation in the
peripatellar region (short arrows) and posterior to the posterior cruciate ligament (PCL) consistent with synovitis
(long arrow). The region posterior to the PCL is the most common location affected by synovitis in OA. (B) Corresponding
fusion image in the coronal plane also shows perimeniscal synovitis in the same knee (arrows). The
contralateral knee has a total knee replacement with an inflammatory focus at the medial femoral condyle
(arrowhead).
Could be applied in large epidemiological OA studies using CE MRI