Abstract
BackgroundThe 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.MethodsHere, 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.ResultsThe 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.ConclusionIRT 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.
Highlights
Using animals as disease models in arthritis research Animals have been used extensively in arthritis research, to examine the nature of the disease, develop new medicines, improve diagnostic procedures, and study drug toxicity
IR thermal imager: performance evaluation To validate the performance of the IR thermal imager prior to the animal study, a common functionality check was implemented, and the captured temperature profiles analyzed
We further introduced a “total temperature index” as a simple indicator of overall temperature changes within inflamed paws to be used in longitudinal studies
Summary
Using animals as disease models in arthritis research Animals have been used extensively in arthritis research, to examine the nature of the disease, develop new medicines, improve diagnostic procedures, and study drug toxicity. Animal research provides crucial data in order to assess whether a potential medicine will be effective and safe for use in humans [1]. In rheumatoid arthritis (RA) research, animal models are commonly used to screen the drug bioavailability at target inflamed joints, as well as to investigate drug disposition and therapeutic efficacy, providing information on the potential of new therapies. In preclinical drug efficacy studies, it is essential that the RA model shows similar arthritis onset, joint involvement pattern, as well as disease severity to humans, in order to accelerate drug screening and provide reliable data for subsequent testing in clinical trials. 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
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