Rheumatoid arthritis (RA) is a chronic, debilitating disease affecting over 1 million people in the United States. RA is characterized by the draining of lymphatic vessels coupled with dynamic changes in lymph node volume and flow. Impaired lymph egress from inflamed synovium is associated with joint flare in murine models of inflammatory-erosive arthritis. Unfortunately, advancements in understanding lymphatic changes have been slow, due to the lack of technology to measure and quantify lymphatic function in vivo. Lymphoscintigraphy is the current standard used in assessing lymphedema and sentinel lymph nodes in cancer patients, but is not adequate to study lymphatics in RA.
High-resolution MRI, power Doppler ultrasound, and near-infrared imaging that permits real-time quantification of lymphatic function have been the largest advancements thus far, and have produced a new paradigm of altered lymphatic function that underlies both accute arthritic flare and chronic inflammation. In accute flare, lymphatic drainage increases several fold, whereas no lymphatic contractions are detected in lymph vessels draining chronic arthritic joints.
In a study done by Homaira Rahimi, Richard Bell, Echoe M. Bouta, Ronald W. Wood, Lianping Xing, Christopher T. Ritchlin and Edward M. Schwarz, they explained the knowledge to date on lymphatics in RA, new in-vivo imaging modalities that have elucidated how lymphatics modulate acute versus chronic joint inflammation, and how these preclinical outcome measures are being translated to study RA inflammation and how effective RA therapies alter lymphatic flow and lymph nodes draining flaring joints. The discoveries were facilitated by novel imaging methods, one being the use of a custom NIR imaging system; FluxData’s FD-1665.
For the purpose of this study, FluxData’s FD-1665 was used to quantify lymphatic flow in the upper extremity. The custom NIR imaging system was used to assess lymphatic contraction frequency in a healthy human subject after ICG injection in the second, third, and fourth web spaces of both hands. The NIR excitation was monitored with a Thorlabs PM16-121 power meter adjacent to the first web space. After the injections, the upper extremities were imaged for 10 minutes to observe lymphatic flow. Visible and NIR images were collected simultaneously. Dysfunctional contractions, or no contractions, could indicate that the arthritic episode is the result of a drainage issue rather than synovial disturbances. The treatment would then be tailored accordingly.
The rationale for using NIR-ICG to evaluate lymphatic contractions is justified because it provides real-time information for the clinician. Using this sytem to test such has been approved by the FDA, therefore there is no major health limitations of the given technique.
The importance of this study is three-fold. The role of lympthatics in RA can now be examined with the advent of in-vivo imaging modalities that quantify lymphatic flow and contraction frequency. Such technical advances can empower investigators to promote understanding in three areas: redefinition of patterns of lymphatic flow anatomically, discovery of the cellular, molecular, and structural mechanisms that regulate lymphatic function and that are closely integrated with local biomechanics, inflammation, and parasympathetic innervation. Lastly, the goal is to identify novel molecular targets that will give rise to new interventions for RA flare. The advancement of noninvasive technologies was a critical first step.
To read the full article from the National Center for Biotechnology Information, click here.