Fig 1.
Study design flow diagram illustrating enrollment, data collection, treatment and analysis.
TPLO—tibial plateau leveling osteotomy for treatment of stifle instability from CR.
Fig 2.
Clinical and pathological features of partial cruciate rupture (CR) in the dog.
(A,B) Radiographic features from dogs with severe and mild disease in partial CR stifles. Synovial effusion (white arrows), and osteophyte formation (white arrow heads) is more evident in the stifle with more severe inflammatory synovitis pathology (A) (Radiographic effusion score = 1; Radiographic osteoarthritis (OA) score = 2) than the stifle with more mild disease (B) (Radiographic effusion score = 0; Radiographic OA score = 0). The radiographic scores for the mildly affected stifle were given a score of 0 by the radiographic grader (PM), but the attending clinician evaluating the case for study inclusion considered the radiographs abnormal at diagnosis. (C,D) Sagittal plane 3D FSE Cube MR images of the cranial cruciate ligament (CrCL) (white asterisk) shows that the CrCL from the partial CR stifle with more severe disease (C) is thickened compared to the partial CR stifle with more mild disease (D). (E,F) Arthroscopic images obtained from the intercondylar notch highlight the more prominent vascularity, hypertrophy and synovitis in the stifle with more severe disease (E) (Total Arthroscopic Score = 23) than the stifle with more mild disease (F) (Total Arthroscopic Score = 19). (G,H) Torn CrCL fibers are evident in both images (black asterisk). Biopsies of stifle synovial lining obtained from the medial joint compartment show the stifle with more severe disease (G) (Total Histologic Grade = 2; Histologic VAS score = 96) has greater inflammatory infiltrate, synovial cell hypertrophy and synovial intima thickness when compared to the partial CR stifle with mild disease (H) (Total Histologic Score = 1; Histologic VAS score = 6). Scale bar = 0.5mm.
Table 1.
Radiographic, magnetic resonance imaging and arthroscopic findings.
Table 2.
Inflammation in stifle synovium and stifle synovial fluid.
Table 3.
Correlation between radiographic measures, Histologic Synovitis Grade and cranial cruciate ligament fiber damage.
Table 4.
Correlation between histologic synovitis and arthroscopic assessment of synovitis and cranial cruciate ligament fiber damage.
Table 5.
Correlation between MR imaging quantification of cranial cruciate ligament properties and arthroscopic and histologic assessment.
Table 6.
Correlation between histologic assessment of synovial inflammatory cell populations and arthroscopic assessment of cranial cruciate ligament fiber damage.
Table 7.
Correlation between serum and synovial markers of inflammation, Histologic Synovitis Grade and cranial cruciate ligament fiber damage.
Fig 3.
Relationships between diagnostic variables in complete and partial cruciate rupture stifles to evaluate patterns of correlation between markers.
(A) In the complete CR stifle, correlations formed three clusters. Several inflammation markers were positively correlated with Synovial and Serum CRP concentrations, suggesting that inflammation promotes collagen degradation within affected stifles. Serum CRP was also positively correlated with histologic inflammation. In a second cluster, Radiographic effusion and OA were positively correlated with arthroscopic synovitis variables. In a third cluster, numbers of CD3+ lymphocytes were positively correlated with numbers of TRAP+ macrophages and neutrophils. (B) In the partial CR stifle, a larger number of positive correlations were identified that formed four clusters. Suppurative inflammation was positively correlated with CrCL ligament volume, assessed by MR imaging, and functional length of the ligament, suggesting that acute inflammation is related to ligament edema and loss of mechanical properties. In a second cluster, synovial and serum CRP concentrations were correlated with stifle TNCC, indicating that biochemical markers of inflammation correlate with inflammatory cell counts. In a third cluster, the synovial to serum CRP ratio was positively correlated several histologic markers of inflammation, suggesting that the synovial to serum CRP ratio is likely a clinically useful marker of stifle synovitis. In a fourth cluster, arthroscopic variables of inflammation were correlated with MR imaging measures of ligament fluid content, as measured by grayscale value, suggesting that early in the CR condition, synovitis may result in increased ligament fluid content. Abbreviations: TAS, Total Arthroscopic Score; ACVAS, Arthroscopic CrCL Fiber Damage Visual Analog Scale (VAS) score; AVAS, Arthroscopic Synovitis VAS score; CD3, CD3+ T Lymphocyte Grade; CrCLD, Radiographic length of CrCL normalized to patellar length; CRPR, C-reactive Protein (CRP) serum to synovial fluid ratio; FSEG, MR imaging CrCL FSE Grayscale; FSEV, MR imaging CrCL FSE Volume; FVIII, Synovial Factor VIII+ Vessel Grade; FVIIIVAS, Synovial Factor VIII+ Vessel VAS; Hgrade, Histologic Synovitis Grade; HVAS, Histologic Synovitis VAS Score; ICTPR, pyridinoline cross-lined carboxy-terminal telopeptide of type I collagen (ICTP) serum to synovial fluid ratio; JCRP, Synovial fluid CRP; JICTP, Synovial fluid ICTP; RADE, Radiographic Effusion score; RADOA, Radiographic OA score; SCRP, Serum C-Reactive Protein; SICTP, Serum ICTP; Supp, Suppurative Inflammation Grade; T1, MR imaging CrCL T1 Enhancement; TNCC, Synovial fluid total nucleated cell count; TPA, Tibial Plateau Angle; TRAP, TRAP+ Macrophage Grade; VIPRV, MR imaging CrCL VIPR Volume; VIPRG, MR imaging CrCL VIPR Grayscale.
Fig 4.
Relationship between partial cruciate rupture (CR) comparators and select variables.
(A) Histologic Synovitis Grade was significantly correlated with cranial cruciate ligament (CrCL) fluid content, as reflected by CrCL FSE Grayscale value (P = 0.007, SR = 0.50). (B) Histologic Synovitis Grade in the partial CR stifles was significantly associated with Synovial:Serum C-reactive protein (CRP) ratio (P = 0.03, SR = 0.42), suggesting that CRP may be a biochemical marker for synovial inflammation. (C) Radiographic osteoarthritis (OA) Score was significantly correlated with Arthroscopic Fiber Damage visual analog scale (VAS) score (P = 0.0005, SR = 0.61), supporting the use of radiography as a diagnostic test that reflects CR disease progression. The median values are indicated with a horizontal line.