Abstract
BackgroundNon-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.MethodsCollagen-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.ResultsQuantification 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.ConclusionThese 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.
Highlights
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
To determine whether 19F Magnetic resonance imaging (MRI) could be used to monitor the effect of drug therapy on established inflammation, collagen induced arthritis (CIA) animals were randomized upon disease onset into cohorts of vehicle control or drug treatment for monitoring by serial imaging
While all CIA rats had a strong 19F signal surrounding the bones in the ankles on day 15, consistent with the presence of inflammation at those sites, naïve rats did not have any detectable 19F in the hind limbs (Figure 2B), consistent with an absence of inflammation
Summary
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. In the case of RA, imaging for clinical diagnosis is limited to anatomical imaging of bone erosion (MRI, CT), inflammation of the synovial membrane (ultrasound, MRI), and joint effusion and tissue swelling (x-ray) [9,10] These techniques, though useful, often only elucidate the disease after permanent damage is done, limiting the applicability of early intervention therapies [11]. Biofunctional imaging of arthritis focuses on metabolic activity, cellular infiltrates, and cytokine production [10], which often occur prior to the onset of permanent anatomical damage due to the disease It may serve as an indicator of the presence of disease and severity, enabling earlier diagnosis and treatment [3]. Methodologies for non-invasive detection and localization of inflammation in RA include PET/CT [13], ultrasound [14], optical (fluorescence) imaging [15], and MRI
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