The online version of this article (doi:10.1186/1476-9255-9-24) contains supplementary material, which is available to authorized users.
The authors, except ETA, are employees of Celsense, Inc. and receive salary and stock options. ETA serves as a paid consultant to Celsense and is a stock holder.
AB contributed to the design of the studies, production of the contrast agent, and contributed to analysis of the MRI data, including rendering 3D images, and quantification. AB was involved in the interpretation of data and revision of manuscript. BMH contributed to the design and analysis of the studies, assessment of the contrast agent and also was involved in drafting and revising the manuscript. ETA assisted with design and aided in preparation of the manuscript. AKW and CFO were responsible for the conception and planning of the experiments, and CFO helped to revise the manuscript. AKW directed the study, designed the experiments, contributed to the analysis and interpretation of the data, and drafted the manuscript. All authors have read and approved the final version of this manuscript.
Non-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA), and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC) contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by 19F MRI. With no 19F background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present.
Collagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using 19F MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and 19F MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of the PFC contrast agent and 19F MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28.
Quantification of 19F signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in 19F signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in 19F signal was observed in animals receiving treatment which resulted in clinical resolution of disease.
These results indicate that 19F MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of 19F MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory component.
Additional file 1:Table S1. Longitudinal analysis of 19F signal in CIA rats. (PDF 336 KB)12950_2011_248_MOESM1_ESM.pdf
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- Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI)
Brooke M Helfer
Eric T Ahrens
Charles F O’Hanlon III
Amy K Wesa
- BioMed Central
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