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1.  Knee X-ray image analysis method for automated detection of Osteoarthritis 
We describe a method for automated detection of radiographic Osteoarthritis (OA) in knee X-ray images. The detection is based on the Kellgren-Lawrence classification grades, which correspond to the different stages of OA severity. The classifier was built using manually classified X-rays, representing the first four KL grades (normal, doubtful, minimal and moderate). Image analysis is performed by first identifying a set of image content descriptors and image transforms that are informative for the detection of OA in the X-rays, and assigning weights to these image features using Fisher scores. Then, a simple weighted nearest neighbor rule is used in order to predict the KL grade to which a given test X-ray sample belongs. The dataset used in the experiment contained 350 X-ray images classified manually by their KL grades. Experimental results show that moderate OA (KL grade 3) and minimal OA (KL grade 2) can be differentiated from normal cases with accuracy of 91.5% and 80.4%, respectively. Doubtful OA (KL grade 1) was detected automatically with a much lower accuracy of 57%. The source code developed and used in this study is available for free download at www.openmicroscopy.org.
doi:10.1109/TBME.2008.2006025
PMCID: PMC2665928  PMID: 19342330
Osteoarthritis; image classification; automated detection; X; ray; Kellgren-Lawrence classification
2.  Association of Autoimmunity to Peptidyl Arginine Deiminase Type 4 With Genotype and Disease Severity in Rheumatoid Arthritis 
Arthritis and rheumatism  2008;58(7):1958-1967.
Objective
Protein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA)–specific autoantibodies. One of the citrullinating enzymes, peptidyl arginine deiminase type 4 (PAD-4), is genetically associated with development of RA in some populations, although the mechanism(s) mediating this effect are not yet clear. There have been descriptions of anti–PAD-4 autoantibodies in different rheumatic diseases. This study was undertaken to investigate whether anti–PAD-4 antibodies are specific to RA, are associated with disease phenotype or severity, and whether PAD-4 polymorphisms influence the anti–PAD-4 autoantibody response.
Methods
Sera from patients with established RA, patients with other rheumatic diseases, and healthy adults were assayed for anti–PAD-4 autoantibodies by immunoprecipitation of in vitro–translated PAD-4. The epitope(s) recognized by PAD-4 autoantibodies were mapped using various PAD-4 truncations. PAD-4 genotyping was performed on RA patients with the TaqMan assay. Joint erosions were scored from hand and foot radiographs using the Sharp/van der Heijde method.
Results
PAD-4 autoantibodies were found in 36–42% of RA patients, and were very infrequent in controls. Recognition by anti–PAD-4 autoantibodies required the 119 N-terminal amino acids, which encompass the 3 nonsynonymous polymorphisms associated with disease susceptibility. Strikingly, the anti–PAD-4 immune response was associated with the RA susceptibility haplotype of PADI4. Anti–PAD-4 antibodies were associated with more severe joint destruction in RA.
Conclusion
Our findings indicate that anti–PAD-4 antibodies are specific markers of RA, independently associated with more severe disease, suggesting that an anti–PAD-4 immune response may be involved in pathways of joint damage in this disease. Polymorphisms in the PADI4 gene influence the immune response to the PAD-4 protein, potentially contributing to disease propagation.
doi:10.1002/art.23596
PMCID: PMC2692635  PMID: 18576335
3.  Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis 
Introduction
Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.
Methods
Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.
Results
The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.
Conclusions
Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.
doi:10.1186/ar2641
PMCID: PMC2688181  PMID: 19284547
4.  Establishing the level of digitization for wrist and hand radiographs for the third National Health and Nutrition Examination Survey 
Journal of Digital Imaging  1998;11(3):116-120.
In the third National Health and Nutrition Examination Survey (NHANES III) conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention, radiographs of the hands and knees were taken of participants 60 years and older as part of the study of arthritis and musculoskeletal conditions. The purpose of the study was to decide the digitizing resolution to be used for these radiographs. A set of wrist and hand radiographs (N=49) was graded by two radiologists for degree of bone erosions and served as a “gold standard.” The radiographs were then digitized at three resolution levels; low-resolution 150μm (2001×1634×12 bit matrix); intermediate-resolution 100 μm (3000×2400×12 bit matrix); and high-resolution 50 μm (4900×3000×12 bit matrix). A comparison of the digital images versus the gold standard reading was made at the three resolutions by two radiologists. Kappa statistics suggested fair (K>.4) to excellent (K>.75) agreement between the gold standard and the images at all levels. Intraclass correlation coefficient suggested high agreement between readers (ICC>.5), with minimal individual reader effect. Variance component estimates showed that the major contribution (78–83%) to scoring came from variability in the images themselves, not from the readers. The 100μm resolution was selected over the 150 and 50 μm on the basis of practical considerations such as storage requirements, display time, and easier manipulation of the digital images by the readers.
doi:10.1007/BF03168734
PMCID: PMC3453200  PMID: 9718501
NHANES III; radiograph; hand; digital resolution

Results 1-4 (4)