Raman spectroscopy of synovial fluid as a tool for diagnosing osteoarthritis.

For many years, viscosity has been the primary method used by researchers in rheumatology to assess the physiochemical properties of synovial fluid in both normal and osteoarthritic patients. However, progress has been limited by the lack of methods that provide multiple layers of information, use small sample volumes, and are rapid. Raman spectroscopy was used to assess the biochemical composition of synovial fluid collected from 40 patients with clinical evidence of knee osteoarthritis (OA) at the time of elective surgical treatment. Severity of knee osteoarthritis was assessed by a radiologist using Kellgren/Lawrence (K/L) scores from knee joint x rays, while light microscopy and Raman spectroscopy were used to examine synovial fluid (SF) aspirates (2 to 10 microL), deposited on fused silica slides. We show that Raman bands used to describe protein secondary structure and content can be used to detect changes in synovial fluid from osteoarthritic patients. Several Raman band intensity ratios increased significantly in spectra collected from synovial fluid in patients with radiological evidence of moderate-to-severe osteoarthritis damage. These ratios can be used to provide a "yes/no" damage assessment. These studies provide evidence that Raman spectroscopy would be a suitable candidate in the evaluation of joint damage in knee osteoarthritis patients.

[1]  Xiaohong Bi,et al.  Fourier transform infrared imaging spectroscopy investigations in the pathogenesis and repair of cartilage. , 2006, Biochimica et biophysica acta.

[2]  Jie Cui,et al.  Automated search for arthritic patterns in infrared spectra of synovial fluid using adaptive wavelets and fuzzy C-Means analysis , 2006, IEEE Transactions on Biomedical Engineering.

[3]  Ali Guermazi,et al.  Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee Study , 2007, Arthritis research & therapy.

[4]  Gillian McMahon,et al.  Detection of calcium phosphate crystals in the joint fluid of patients with osteoarthritis – analytical approaches and challenges , 2008, The Analyst.

[5]  T. Yakhno,et al.  On the existence of regular structures in liquid human blood serum (plasma) and phase transitions in the course of its drying , 2003 .

[6]  T.A. Yakhno,et al.  The informative-capacity phenomenon of drying drops , 2005, IEEE Engineering in Medicine and Biology Magazine.

[7]  H. Edwards,et al.  Fourier transform Raman spectroscopic study of fungi , 1995 .

[8]  Jh. Kellgren.  Radiological assessment of osteoarthrosis , 1957 .

[9]  Michael D. Morris,et al.  Raman spectroscopy of dried synovial fluid droplets as a rapid diagnostic for knee joint damage , 2008, SPIE BiOS.

[10]  H. Greiling,et al.  Assay of synovial fluid parameters: hyaluronan concentration as a potential marker for joint diseases. , 1997, Clinica chimica acta; international journal of clinical chemistry.

[11]  Vladimír Baumruk,et al.  Structure of the ring in drop coating deposited proteins and its implication for Raman spectroscopy of biomolecules , 2006 .

[12]  Ende,et al.  Comparison of manual therapy and exercise therapy in osteoarthritis of the hip: a randomized clinical trial. , 2004, Arthritis and rheumatism.

[13]  Peter J Millett,et al.  High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis , 2007, Arthritis research & therapy.

[14]  Dor Ben-Amotz,et al.  Validation of the drop coating deposition Raman method for protein analysis. , 2006, Analytical biochemistry.

[15]  S. Abramson,et al.  Biomarkers in osteoarthritis. , 2006, Bulletin of the NYU hospital for joint diseases.

[16]  J. Pelton,et al.  Spectroscopic methods for analysis of protein secondary structure. , 2000, Analytical biochemistry.

[17]  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.

[18]  S. Clarke,et al.  Serum cartilage oligomeric matrix protein and other biomarker profiles in tibiofemoral and patellofemoral osteoarthritis of the knee. , 2006, Rheumatology.

[19]  P. Riederer,et al.  High molecular weight hyaluronic acid inhibits advanced glycation endproduct‐induced NF‐κB activation and cytokine expression , 1999 .

[20]  Khaled Elsaid,et al.  Association between friction and wear in diarthrodial joints lacking lubricin , 2007, Arthritis and rheumatism.

[21]  H. Mantsch,et al.  Pathology by Infrared and Raman Spectroscopy , 2006 .

[22]  L H Kidder,et al.  Imaging of collagen and proteoglycan in cartilage sections using Fourier transform infrared spectral imaging. , 2001, Arthritis and rheumatism.

[23]  Henry H. Mantsch,et al.  A novel diagnostic test for arthritis: Multivariate analysis of infrared spectra of synovial fluid , 1997 .

[24]  S. Kotowich,et al.  Arthritis diagnosis based upon the near-infrared spectrum of synovial fluid , 2004, Rheumatology International.

[25]  H. Schumacher,et al.  Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies. , 2003, Osteoarthritis and cartilage.

[26]  Stefan Hassfeld,et al.  Analysis of temporomandibular joint synovial fluid using Fourier transform/infrared spectroscopy. , 2002, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

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

[28]  T. Dupont,et al.  Capillary flow as the cause of ring stains from dried liquid drops , 1997, Nature.

[29]  J G Larkin,et al.  The correlation of clinical assessment of synovial fluid with its measured viscosity. , 1984, British journal of rheumatology.

[30]  P. Rolfe,et al.  In vivo near-infrared spectroscopy. , 2000, Annual review of biomedical engineering.

[31]  B. Schmidt-Rohlfing,et al.  Correlation of bone and cartilage markers in the synovial fluid with the degree of osteoarthritis , 2002, Rheumatology International.

[32]  J. Koenig,et al.  Raman studies of bovine serum albumin , 1976, Biopolymers.

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

[34]  Masaaki Takahashi,et al.  Relationship between radiographic grading of osteoarthritis and the biochemical markers for arthritis in knee osteoarthritis , 2004, Arthritis research & therapy.

[35]  T. Aigner,et al.  Increase in degraded collagen type II in synovial fluid early in the rabbit meniscectomy model of osteoarthritis. , 2005, Osteoarthritis and cartilage.

[36]  P. Dieppe,et al.  Pathogenesis and management of pain in osteoarthritis , 2005, The Lancet.

[37]  V. Jovaní,et al.  Synovial fluid analysis. , 2005, Best practice & research. Clinical rheumatology.

[38]  M. Chance,et al.  A method for examining the chemical basis for bone disease: synchrotron infrared microspectroscopy. , 1998, Cellular and molecular biology.

[39]  E H JEBENS,et al.  On the viscosity and pH of synovial fluid and the pH of blood. , 1959, The Journal of bone and joint surgery. British volume.

[40]  M. Morris,et al.  Effect of Conformation and Drop Properties on Surface-Enhanced Raman Spectroscopy of Dried Biopolymer Drops , 2008, Applied spectroscopy.

[41]  B. Chiang,et al.  High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis. , 2006, Osteoarthritis and cartilage.

[42]  S. Cramer,et al.  A holistic approach to protein secondary structure characterization using amide I band Raman spectroscopy. , 1999, Analytical Biochemistry.

[43]  R. Bank,et al.  Molecular markers for osteoarthritis: the road ahead , 2002, Current opinion in rheumatology.

[44]  N. Stone,et al.  Drop coating deposition Raman spectroscopy of protein mixtures. , 2007, The Analyst.

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

[46]  Nicole J. Crane,et al.  Identifying Chemical Changes in Subchondral Bone Taken from Murine Knee Joints Using Raman Spectroscopy , 2006, Applied spectroscopy.

[47]  Dor Ben-Amotz,et al.  Chemical Segregation and Reduction of Raman Background Interference Using Drop Coating Deposition , 2004, Applied spectroscopy.

[48]  Anne E Carpenter.  Image-based chemical screening. , 2007, Nature chemical biology.

[49]  D. Felson,et al.  Osteoarthritis: is it a disease of cartilage or of bone? , 2004, Arthritis and rheumatism.

[50]  S. Marini,et al.  A correlation between knee cartilage degradation observed by arthroscopy and synovial proteinases activities. , 2003, Clinical biochemistry.

[51]  Nicholas Stone,et al.  Raman point mapping of tear ferning patterns , 2008, SPIE BiOS.

[52]  J. Bateman,et al.  Cartilage proteomics: Challenges, solutions and recent advances , 2008, Proteomics. Clinical applications.

[53]  M. Cowman,et al.  Experimental approaches to hyaluronan structure. , 2005, Carbohydrate research.

[54]  F. Boury,et al.  Conformational modifications of alpha gliadin and globulin proteins upon complex coacervates formation with gum Arabic as studied by Raman microspectroscopy. , 2006, Biomacromolecules.

[55]  D J Hunter,et al.  Classification of osteoarthritis biomarkers: a proposed approach. , 2006, Osteoarthritis and cartilage.

[56]  Dor Ben-Amotz,et al.  Raman detection of proteomic analytes. , 2003, Analytical chemistry.