Imaging Biomarkers of Osteoarthritis

Abstract Currently no disease-modifying osteoarthritis drug has been approved for the treatment of osteoarthritis (OA) that can reverse, hold, or slow the progression of structural damage of OA-affected joints. The reasons for failure are manifold and include the heterogeneity of structural disease of the OA joint at trial inclusion, and the sensitivity of biomarkers used to measure a potential treatment effect. This article discusses the role and potential of different imaging biomarkers in OA research. We review the current role of radiography, as well as advances in quantitative three-dimensional morphological cartilage assessment and semiquantitative whole-organ assessment of OA. Although magnetic resonance imaging has evolved as the leading imaging method in OA research, recent developments in computed tomography are also discussed briefly. Finally, we address the experience from the Foundation for the National Institutes of Health Biomarker Consortium biomarker qualification study and the future role of artificial intelligence.

[1]  A. Guermazi,et al.  A call for screening MRI as a tool for osteoarthritis clinical trials , 2023, Skeletal Radiology.

[2]  L. Sharma,et al.  Which risk factors determine cartilage thickness and composition change in radiographically normal knees? – Data from the Osteoarthritis Initiative , 2023, Osteoarthritis and cartilage open.

[3]  F. Eckstein,et al.  ASSOCIATION OF QUANTITATIVE MEASURES OF MEDIALMENISCALEXTRUSION WITH STRUCTURAL AND SYMPTOMATIC KNEE OSTEOARTHRITIS PROGRESSION- DATA FROM THE OAI FNIH BIOMARKER STUDY. , 2023, Osteoarthritis and cartilage.

[4]  J. Laredo,et al.  MRI underestimates presence and size of knee osteophytes using CT as a reference standard. , 2023, Osteoarthritis and cartilage.

[5]  J. Collins,et al.  Biomarkers in osteoarthritis: current status and outlook — the FNIH Biomarkers Consortium PROGRESS OA study , 2023, Skeletal Radiology.

[6]  F. Eckstein,et al.  Worsening of Articular Tissue Damage as Defined by Semi-Quantitative MRI Is Associated With Concurrent Quantitative Cartilage Loss Over 24 Months , 2023, Cartilage.

[7]  J. Jaremko,et al.  Comparative validation of the knee inflammation MRI scoring system and the MRI osteoarthritis knee score for semi-quantitative assessment of bone marrow lesions and synovitis-effusion in osteoarthritis: an international multi-reader exercise , 2023, Therapeutic advances in musculoskeletal disease.

[8]  N. Segal,et al.  WBCT and its evolving role in OA research and clinical practice , 2022, Osteoarthritis Imaging.

[9]  L. Sharma,et al.  Comparison of Evaluation Metrics of Deep Learning for Imbalanced Imaging Data in Osteoarthritis Studies , 2022, medRxiv.

[10]  J. Laredo,et al.  MRI UNDERESTIMATES PRESENCE AND SIZE OF KNEE OSTEOPHYTES USING CT AS A REFERENCE STANDARD , 2022, Osteoarthritis and Cartilage.

[11]  M. Nevitt,et al.  Cross-sectional and longitudinal reliability of semiquantitative osteoarthritis assessment at 1.0T extremity MRI: Multi-reader data from the MOST study , 2021, Osteoarthritis and cartilage open.

[12]  F. Eckstein,et al.  The design of a randomized, placebo-controlled, dose-ranging trial to investigate the efficacy and safety of the ADAMTS-5 inhibitor S201086/GLPG1972 in knee osteoarthritis , 2021, Osteoarthritis and cartilage open.

[13]  Win Min Oo,et al.  The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date , 2021, Drug design, development and therapy.

[14]  F. Eckstein,et al.  Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study , 2021, Annals of the Rheumatic Diseases.

[15]  F. Eckstein,et al.  The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial. , 2021, Seminars in arthritis and rheumatism.

[16]  F. Eckstein,et al.  Multivariable Modeling of Biomarker Data From the Phase I Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium , 2021, Arthritis care & research.

[17]  Christian F. Baumgartner,et al.  Detection of Differences in Longitudinal Cartilage Thickness Loss Using a Deep‐Learning Automated Segmentation Algorithm: Data From the Foundation for the National Institutes of Health Biomarkers Study of the Osteoarthritis Initiative , 2020, Arthritis care & research.

[18]  B. Dube,et al.  Machine-learning, MRI bone shape and important clinical outcomes in osteoarthritis: data from the Osteoarthritis Initiative , 2020, Annals of the Rheumatic Diseases.

[19]  Christian F. Baumgartner,et al.  Accuracy and longitudinal reproducibility of quantitative femorotibial cartilage measures derived from automated U-Net-based segmentation of two different MRI contrasts: data from the osteoarthritis initiative healthy reference cohort , 2020, Magnetic Resonance Materials in Physics, Biology and Medicine.

[20]  A. Guermazi,et al.  Association of knee OA structural phenotypes to risk for progression: a secondary analysis from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study (FNIH). , 2020, Osteoarthritis and cartilage.

[21]  G. Downing.  Biomarkers , 2020, Biomarkers in Drug Discovery and Development.

[22]  F. Eckstein,et al.  Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial , 2020, Annals of the rheumatic diseases.

[23]  Vojtech Franc,et al.  On Model Evaluation Under Non-constant Class Imbalance , 2020, ICCS.

[24]  C. Kwoh,et al.  MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES). , 2020, Osteoarthritis and cartilage.

[25]  S. Kingsbury,et al.  Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis , 2019, Annals of Internal Medicine.

[26]  M. Karsdal,et al.  Recent advances in understanding the phenotypes of osteoarthritis , 2019, F1000Research.

[27]  Felix Eckstein,et al.  Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial. , 2019, JAMA.

[28]  S. Röhrich,et al.  The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas , 2019, Cartilage.

[29]  B. Jolles,et al.  Relationships between cartilage thickness and subchondral bone mineral density in non-osteoarthritic and severely osteoarthritic knees: In vivo concomitant 3D analysis using CT arthrography. , 2019, Osteoarthritis and cartilage.

[30]  Peter D Chang,et al.  Deep Learning for Detection of Complete Anterior Cruciate Ligament Tear , 2019, Journal of Digital Imaging.

[31]  W. Wirth,et al.  Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative. , 2019, Osteoarthritis and cartilage.

[32]  Stefan Zachow,et al.  Automated segmentation of knee bone and cartilage combining statistical shape knowledge and convolutional neural networks: Data from the Osteoarthritis Initiative , 2019, Medical Image Anal..

[33]  Sharmila Majumdar,et al.  3D convolutional neural networks for detection and severity staging of meniscus and PFJ cartilage morphological degenerative changes in osteoarthritis and anterior cruciate ligament subjects , 2018, Journal of magnetic resonance imaging : JMRI.

[34]  F. Liu,et al.  Deep Learning Approach for Evaluating Knee MR Images: Achieving High Diagnostic Performance for Cartilage Lesion Detection. , 2018, Radiology.

[35]  S. Majumdar,et al.  Use of 2D U-Net Convolutional Neural Networks for Automated Cartilage and Meniscus Segmentation of Knee MR Imaging Data to Determine Relaxometry and Morphometry. , 2018, Radiology.

[36]  D. Hunter,et al.  Knee osteoarthritis phenotypes and their relevance for outcomes: a systematic review. , 2017, Osteoarthritis and cartilage.

[37]  Simo Saarakkala,et al.  Automatic Knee Osteoarthritis Diagnosis from Plain Radiographs: A Deep Learning-Based Approach , 2017, Scientific Reports.

[38]  M. Nevitt,et al.  Predictive Validity of Radiographic Trabecular Bone Texture in Knee Osteoarthritis , 2017, Arthritis & rheumatology.

[39]  B. Song,et al.  Meta-analysis of dual-energy computed tomography virtual non-calcium imaging to detect bone marrow edema. , 2017, European journal of radiology.

[40]  M. Nevitt,et al.  Comparison of tibiofemoral joint space width measurements from standing CT and fixed flexion radiography , 2017, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[41]  F. Eckstein,et al.  Location-independent analysis of structural progression of osteoarthritis-Taking it all apart, and putting the puzzle back together makes the difference. , 2017, Seminars in arthritis and rheumatism.

[42]  Andrew M. Kern,et al.  Test–retest reliability of tibiofemoral joint space width measurements made using a low-dose standing CT scanner , 2017, Skeletal Radiology.

[43]  M. Nevitt,et al.  Semi-quantitative MRI biomarkers of knee osteoarthritis progression in the FNIH biomarkers consortium cohort − Methodologic aspects and definition of change , 2016, BMC Musculoskeletal Disorders.

[44]  M. Nevitt,et al.  Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium , 2016, Annals of the rheumatic diseases.

[45]  Ali Guermazi,et al.  Semi‐Quantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data from the FNIH OA Biomarkers Consortium , 2016 .

[46]  W. Wirth,et al.  Brief Report: Cartilage Thickness Change as an Imaging Biomarker of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium , 2015, Arthritis & rheumatology.

[47]  F. Eckstein,et al.  Relationship Between Medial Meniscal Extrusion and Cartilage Loss in Specific Femorotibial Subregions: Data From the Osteoarthritis Initiative , 2015, Arthritis care & research.

[48]  L. Laslett,et al.  Association Between Infrapatellar Fat Pad Volume and Knee Structural Changes in Patients with Knee Osteoarthritis , 2015, The Journal of Rheumatology.

[49]  M. Nevitt,et al.  Diagnostic performance of 3D standing CT imaging for detection of knee osteoarthritis features , 2015, The Physician and sportsmedicine.

[50]  M. Nevitt,et al.  Progression of cartilage damage and meniscal pathology over 30 months is associated with an increase in radiographic tibiofemoral joint space narrowing in persons with knee OA--the MOST study. , 2014, Osteoarthritis and cartilage.

[51]  A. Guermazi,et al.  Whole joint MRI assessment of surgical cartilage repair of the knee: cartilage repair osteoarthritis knee score (CROAKS). , 2014, Osteoarthritis and cartilage.

[52]  Ali Guermazi,et al.  Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS): Longitudinal MRI-based whole joint assessment of anterior cruciate ligament injury. , 2014, Osteoarthritis and cartilage.

[53]  Juha Töyräs,et al.  In vivo diagnostics of human knee cartilage lesions using delayed CBCT arthrography , 2014, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[54]  Christian Igel,et al.  Deep Feature Learning for Knee Cartilage Segmentation Using a Triplanar Convolutional Neural Network , 2013, MICCAI.

[55]  M. Nevitt,et al.  Predictive validity of within-grade scoring of longitudinal changes of MRI-based cartilage morphology and bone marrow lesion assessment in the tibio-femoral joint--the MOST study. , 2012, Osteoarthritis and cartilage.

[56]  Felix Eckstein,et al.  Recent advances in osteoarthritis imaging—the Osteoarthritis Initiative , 2012, Nature Reviews Rheumatology.

[57]  D. Felson,et al.  Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study) , 2012, BMJ : British Medical Journal.

[58]  Felix Eckstein,et al.  Quantitative MRI measures of cartilage predict knee replacement: a case–control study from the Osteoarthritis Initiative , 2012, Annals of the rheumatic diseases.

[59]  R. Boudreau,et al.  Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). , 2011, Osteoarthritis and cartilage.

[60]  F. Berenbaum,et al.  Osteoarthritis: an update with relevance for clinical practice , 2011, The Lancet.

[61]  H C Charles,et al.  Clinical, radiographic, molecular and MRI-based predictors of cartilage loss in knee osteoarthritis , 2011, Annals of the rheumatic diseases.

[62]  E. Losina,et al.  Responsiveness and reliability of MRI in knee osteoarthritis: a meta-analysis of published evidence. , 2011, Osteoarthritis and cartilage.

[63]  T. Mosher,et al.  Articular cartilage in the knee: current MR imaging techniques and applications in clinical practice and research. , 2011, Radiographics : a review publication of the Radiological Society of North America, Inc.

[64]  M. Nevitt,et al.  Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study , 2010, Annals of the rheumatic diseases.

[65]  M. Nevitt,et al.  Summary of the OA biomarkers workshop 2009--biochemical biomarkers: biology, validation, and clinical studies. , 2010, Osteoarthritis and cartilage.

[66]  J. Buckwalter,et al.  Relation of synovitis to knee pain using contrast-enhanced MRIs , 2010, Annals of the rheumatic diseases.

[67]  D. Burstein,et al.  A pathway and approach to biomarker validation and qualification for osteoarthritis clinical trials. , 2010, Current drug targets.

[68]  F. Eckstein,et al.  Osteoarthritis may not be a one-way-road of cartilage loss--comparison of spatial patterns of cartilage change between osteoarthritic and healthy knees. , 2010, Osteoarthritis and cartilage.

[69]  Felix Eckstein,et al.  Does the use of ordered values of subregional change in cartilage thickness improve the detection of disease progression in longitudinal studies of osteoarthritis? , 2009, Arthritis and rheumatism.

[70]  D. J. Hunter,et al.  "Why aren't we there yet?" Re-examining standard paradigms in imaging of OA: summary of the 2nd annual workshop on imaging based measures of osteoarthritis. , 2009, Osteoarthritis and cartilage.

[71]  M. Nevitt,et al.  Blinding images to sequence in osteoarthritis: evidence from other diseases. , 2009, Osteoarthritis and cartilage.

[72]  M. Nevitt,et al.  Change in MRI-detected subchondral bone marrow lesions is associated with cartilage loss: the MOST Study. A longitudinal multicentre study of knee osteoarthritis , 2008, Annals of the rheumatic diseases.

[73]  David T Felson,et al.  A new approach yields high rates of radiographic progression in knee osteoarthritis. , 2008, The Journal of rheumatology.

[74]  M. Reiser,et al.  Material differentiation by dual energy CT: initial experience , 2007, European Radiology.

[75]  A. Guermazi,et al.  The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston–Leeds Osteoarthritis Knee Score) , 2007, Annals of the rheumatic diseases.

[76]  Felix Eckstein,et al.  Quantitative MRI of cartilage and bone: degenerative changes in osteoarthritis , 2006, NMR in biomedicine.

[77]  R Burgkart,et al.  Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis. , 2006, Osteoarthritis and cartilage.

[78]  P. Emery,et al.  The validation of simple scoring methods for evaluating compartment-specific synovitis detected by MRI in knee osteoarthritis. , 2005, Rheumatology.

[79]  J. Bloem,et al.  MRI assessment of knee osteoarthritis: Knee Osteoarthritis Scoring System (KOSS)—inter-observer and intra-observer reproducibility of a compartment-based scoring system , 2005, Skeletal Radiology.

[80]  H. Genant,et al.  Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. , 2004, Osteoarthritis and cartilage.

[81]  J. Reginster,et al.  Impact of the joint space width measurement method on the design of knee osteoarthritis studies , 2003, Aging clinical and experimental research.

[82]  J. Lynch,et al.  Comparison of fixed-flexion positioning with fluoroscopic semi-flexed positioning for quantifying radiographic joint-space width in the knee: test-retest reproducibility , 2003, Skeletal Radiology.

[83]  H. Genant,et al.  New radiographic-based surrogate outcome measures for osteoarthritis of the knee. , 2003, Osteoarthritis and cartilage.

[84]  S. van der Linden,et al.  Detecting radiological changes in rheumatoid arthritis that are considered important by clinical experts: influence of reading with or without known sequence. , 2002, The Journal of rheumatology.

[85]  Baudouin Maldague,et al.  Anterior cruciate ligament tears and associated meniscal lesions: assessment at dual-detector spiral CT arthrography. , 2002, Radiology.

[86]  Baudouin Maldague,et al.  Assessment of knee cartilage in cadavers with dual-detector spiral CT arthrography and MR imaging. , 2002, Radiology.

[87]  C. Hayne,et al.  Substantial superiority of semiflexed (MTP) views in knee osteoarthritis: a comparative radiographic study, without fluoroscopy, of standing extended, semiflexed (MTP), and schuss views. , 1999, The Journal of rheumatology.

[88]  J C Buckland-Wright,et al.  Field test of the reproducibility of automated measurements of medial tibiofemoral joint space width derived from standardized knee radiographs. , 1999, The Journal of rheumatology.

[89]  K. Brandt,et al.  Is conventional radiography suitable for evaluation of a disease-modifying drug in patients with knee osteoarthritis? , 1997, Osteoarthritis and cartilage.

[90]  P. Ross,et al.  Blinded reading of radiographs increases the frequency of errors in vertebral fracture detection , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[91]  M. Dougados,et al.  Assessment of joint space width in patients with osteoarthritis of the knee: a comparison of 4 measuring instruments. , 1996, The Journal of rheumatology.

[92]  M. Hochberg,et al.  Reliability of grading scales for individual radiographic features of osteoarthritis of the knee. The Baltimore longitudinal study of aging atlas of knee osteoarthritis. , 1993, Investigative radiology.

[93]  H K Genant,et al.  Osteoarthritis of the knee: comparison of radiography, CT, and MR imaging to assess extent and severity. , 1991, AJR. American journal of roentgenology.

[94]  R. Moskowitz,et al.  Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. , 1986, Arthritis and rheumatism.

[95]  R. Leach,et al.  Weight-bearing radiography in osteoarthritis of the knee. , 1970, Radiology.

[96]  J. Kellgren,et al.  Radiological Assessment of Osteo-Arthrosis , 1957, Annals of the rheumatic diseases.

[97]  T. Mosher,et al.  OARSI Clinical Trials Recommendations: Knee imaging in clinical trials in osteoarthritis. , 2015, Osteoarthritis and cartilage.

[98]  F. Eckstein,et al.  Lateral and medial joint space narrowing predict subsequent cartilage loss in the narrowed, but not in the non-narrowed femorotibial compartment--data from the Osteoarthritis Initiative. , 2014, Osteoarthritis and cartilage.

[99]  F. Eckstein,et al.  Frequency and spatial distribution of cartilage thickness change in knee osteoarthritis and its relation to clinical and radiographic covariates - data from the osteoarthritis initiative. , 2013, Osteoarthritis and cartilage.

[100]  M. Daudon,et al.  Articular cartilage calcification in osteoarthritis: insights into crystal-induced stress. , 2011, Arthritis and rheumatism.

[101]  G. Gold,et al.  Atlas of individual radiographic features in osteoarthritis, revised. , 2007, Osteoarthritis and cartilage.

[102]  Jörg Haller,et al.  Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years. , 2006, European journal of radiology.

[103]  F Eckstein,et al.  A non-invasive technique for 3-dimensional assessment of articular cartilage thickness based on MRI. Part 2: Validation using CT arthrography. , 1997, Magnetic resonance imaging.

[104]  M Lequesne,et al.  Atlas of individual radiographic features in osteoarthritis. , 1995, Osteoarthritis and cartilage.