Tissue-Specific Contrast Agents for Optical Fluorescence to Evaluate Rheumatoid Arthritis
Key findings
- Researchers at Massachusetts General Hospital have bioengineered fluorescent chemical compounds, called targeted fluorophores, that have different tissue specificities driven by their inherent chemical structures for specific tissue targeting
- Optical fluorescence imaging provides new opportunities for diagnosis and prognostic evaluation of rheumatoid arthritis (RA), but it is limited by a lack of tissue-specific optical contrast agents
- Using a mouse model, researchers demonstrate that by using the targeted fluorophores they could distinguish specific tissue changes at each of three inflammatory stages of RA
- The team has developed a simple scoring index that may prove useful for RA diagnosis and monitoring of disease progression
Imaging for evaluating patients with rheumatoid arthritis (RA) has improved substantially over the past decade. Today, the shape of the articular cartilage can be differentiated by ultrasonography or MRI. In addition, optical fluorescence imaging—a fast, inexpensive and non-ionizing modality—has proved useful in the diagnosis and prognostic evaluation of RA because it assesses molecular distortion (articular tissues that exhibit different pathophysiological patterns in different stages of the disease).
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The main limitation of optical fluorescence imaging in RA has been the lack of tissue-specific optical contrast agents. In previous work published in Nature Medicine, Hak Soo Choi, PhD, director of the Bioengineering and Nanomedicine Program in the Gordon Center for Medical Imaging at Massachusetts General Hospital, and colleagues developed novel near-infrared fluorescent chemical compounds, called targeted fluorophores, that have different tissue specificities driven by their inherent chemical structures, i.e., structure-inherent targeting.
Now, Dr. Choi and his team have demonstrated in a mouse model that it's possible to distinguish specific tissue changes at each of three inflammatory stages of RA by using the fluorophores. Their report appears in Advanced Science.
The researchers induced RA in mice, then studied groups of animals for up to 180 days. They made use of a dual-channel optical imaging system and four different fluorophore contrast agents: two for assessing synovitis severity and two for monitoring the destruction of cartilage and bone.
Results
When the researchers injected the mice with the targeted contrast agents, they were able to obtain tissue-specific images of synovitis, cartilage destruction and bone resorption, in line with the progression of the disease from acute to chronic to long-standing. Changes in fluorescence intensity and distribution were observed only in peripheral small joints, as the researchers determined by comparing results in the chest, knee and hind paw of the same animals.
Toward the Future
The team was able to quantify the fluorescent information and develop a simple scoring index based on signal-to-background ratio and area fraction of the contrast agents. They anticipate that the index will be clinically useful for RA diagnosis and monitoring disease progression in real-time.
For now, the scoring system is rudimentary, but over time the quantitative analysis of multiple data sets could lay the foundation for new treatment plans with the goal of clinical remission.
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