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      Refinement and validation of infrared thermal imaging (IRT): a non-invasive technique to measure disease activity in a mouse model of rheumatoid arthritis

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          Abstract

          Background

          The discovery and development of new medicines requires high-throughput screening of possible therapeutics in a specific model of the disease. Infrared thermal imaging (IRT) is a modern assessment method with extensive clinical and preclinical applications. Employing IRT in longitudinal preclinical setting to monitor arthritis onset, disease activity and therapeutic efficacies requires a standardized framework to provide reproducible quantitative data as a precondition for clinical studies.

          Methods

          Here, we established the accuracy and reliability of an inexpensive smartphone connected infrared (IR) camera against known temperature objects as well as certified blackbody calibration equipment. An easy to use protocol incorporating contactless image acquisition and computer-assisted data analysis was developed to detect disease-related temperature changes in a collagen-induced arthritis (CIA) mouse model and validated by comparison with two conventional methods, clinical arthritis scoring and paw thickness measurement. We implemented IRT to demonstrate the beneficial therapeutic effect of nanoparticle drug delivery versus free methotrexate (MTX) in vivo.

          Results

          The calibrations revealed high accuracy and reliability of the IR camera for detecting temperature changes in the rheumatoid arthritis animal model. Significant positive correlation was found between temperature changes and paw thickness measurements as the disease progressed. IRT was found to be superior over the conventional techniques specially at early arthritis onset, when it is difficult to observe subclinical signs and measure structural changes.

          Conclusion

          IRT proved to be a valid and unbiased method to detect temperature changes and quantify the degree of inflammation in a rapid and reproducible manner in longitudinal preclinical drug efficacy studies.

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          Most cited references46

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          Collagen-induced arthritis.

          The collagen-induced arthritis (CIA) mouse model is the most commonly studied autoimmune model of rheumatoid arthritis. Autoimmune arthritis is induced in this model by immunization with an emulsion of complete Freund's adjuvant and type II collagen (CII). This protocol describes the steps necessary for acquisition, handling and preparation of CII, as well as selection of mouse strains, proper immunization technique and evaluation of the arthritis incidence and severity. Typically, the first signs of arthritis appear in this model 21-28 days after immunization, and identification of the arthritic limbs is not difficult. Using the protocol described, the investigator should be able to reproducibly induce a high incidence of CIA in various strains of genetically susceptible mice as well as learn how to critically evaluate the pathology of the disease. The total time for the preparation of reagents and the immunization of ten mice is about 1.5 h.
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            Autoimmunity to type II collagen an experimental model of arthritis

            We have found that intradermal injection of native type II collagen extracted from human, chick or rat cartilage induces an inflammatory arthritis in approximately 40% of rats of several strains whether complete Freund's adjuvant or incomplete Freund's adjuvant is used. Type I or III collagen extracted from skin, cartilage proteoglycans and alpha1(II) chains were incapable of eliciting arthritis, as was type II collagen injected without adjuvant. The disease is a chronic proliferative synovitis, resembling adjuvant arthritis in rats and rheumatoid arthritis in humans. Native type II co-lagen modified by limited pepsin digestion still produces arthritis, suggesting that type- specific determinants residing in the helical region of the molecule are responsible for the induction of disease. Since homologous type II collagen emulsified in oil without bacterial preparations regularly causes the disease, this new animal model of arthritis represents a unique example of experimentally-inducible autoimmunity to a tissue component.
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              Animal models of rheumatoid arthritis.

              Animal models have been used extensively in studies of rheumatoid arthritis pathogenesis. Despite the inherent limitations of all animal models, several rodent models have significantly progressed our understanding of the fundamental mechanisms underpinning rheumatoid arthritis and contributed to several current major advances in treatment. These models include the induced arthritis models such as collagen-induced arthritis, collagen-antibody-induced arthritis, zymosan-induced arthritis, and the methylated BSA model, and the genetically manipulated or spontaneous arthritis models such as the TNF-alpha-transgenic mouse, K/BxN mouse, and the Skg mouse. Here, we describe these animal models and discuss their advantages and limitations.
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                Author and article information

                Contributors
                kathy.saatchi@ubc.ca
                urs.hafeli@ubc.ca
                Journal
                Arthritis Res Ther
                Arthritis Res Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                30 November 2020
                30 November 2020
                2020
                : 22
                : 281
                Affiliations
                [1 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, Faculty of Pharmaceutical Sciences, , University of British Columbia, ; 2405 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3 Canada
                [2 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, Department of Physics and Astronomy, , University of British Columbia, ; 6224 Agricultural Road, Vancouver, British Columbia V6T 1Z1 Canada
                [3 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Department of Pharmacy, Faculty of Health and Medical Sciences, , University of Copenhagen, ; Universitetsparken 2, 2100 Copenhagen, Denmark
                Author information
                http://orcid.org/0000-0003-0671-4509
                Article
                2367
                10.1186/s13075-020-02367-w
                7708919
                33256854
                01382018-bd8b-421e-93fa-4b760094f5a3
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 19 September 2020
                : 3 November 2020
                Funding
                Funded by: Lundbeckfonden (DK)
                Award ID: 2014-4176
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Orthopedics
                infrared thermal imaging,animal model,rheumatoid arthritis,image processing,preclinical study,arthritis assessment

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