Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared fluorescence imaging.

OBJECTIVE: To investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for lymphedema (LE) management, by using near-infrared (NIR) fluorescence imaging. DESIGN: Exploratory pilot study. SETTING: Primary care unit. PARTICIPANTS: Subjects (N=10; age, 18-68y) with a diagnosis of grade I or II LE and 12 healthy control subjects (age, 22-59y). INTERVENTION: Indocyanine green (25 µg in 0.1 mL each) was injected intradermally in bilateral arms or legs of subjects. Diffused excitation light illuminated the limbs, and NIR fluorescence images were collected by using custom-built imaging systems. Subjects received MLD therapy, and imaging was performed pre- and posttherapy. MAIN OUTCOME MEASURES: Apparent lymph velocities and periods between lymphatic propulsion events were computed from fluorescence images. Data collected pre- and post-MLD were compared and evaluated for differences. RESULTS: By comparing pre-MLD lymphatic contractile function against post-MLD lymphatic function, results showed that average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%) limbs of subjects with LE and control limbs (+28%) of healthy subjects. The average lymphatic propulsion period decreased in symptomatic (-9%) and asymptomatic (-20%) limbs of subjects with LE, as well as in control limbs (-23%). CONCLUSIONS: We showed that NIR fluorescence imaging could be used to quantify immediate improvement of lymphatic contractile function after MLD.

Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema.

BACKGROUND: Lymphedema is a complication that may occur after surgical resection and radiation treatment in a number of cancer types and is especially debilitating in regions where treatment options are limited. Although upper and lower extremity lymphedema may be effectively treated with manual lymphatic drainage (MLD) therapies and devices that use compression to direct proximal flow of lymph fluids, head and neck lymphedema is more challenging. METHODS AND RESULTS: Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, help direct MLD, and use 3-dimensional (3D) surface profilometry to monitor response to therapy in a patient with head and neck lymphedema after surgery and radiation treatment. CONCLUSION: NIR fluorescence imaging provides a mapping of functional lymph vessels for direction of efficient MLD therapy in the head and neck. Additional studies are needed to assess the efficacy of MLD therapy when directed by NIR fluorescence imaging.

Direct evidence of lymphatic function improvement after advanced pneumatic compression device treatment of lymphedema.

Lymphedema affects up to 50% of all breast cancer survivors. Management with pneumatic compression devices (PCDs) is controversial, owing to the lack of methods to directly assess benefit. This pilot study employed an investigational, near-infrared (NIR) fluorescence imaging technique to evaluate lymphatic response to PCD therapy in normal control and breast cancer-related lymphedema (BCRL) subjects. Lymphatic propulsion rate, apparent lymph velocity, and lymphatic vessel recruitment were measured before, during, and after advanced PCD therapy. Lymphatic function improved in all control subjects and all asymptomatic arms of BCRL subjects. Lymphatic function improved in 4 of 6 BCRL affected arms, improvement defined as proximal movement of dye after therapy. NIR fluorescence lymphatic imaging may be useful to directly evaluate lymphatic response to therapy. These results suggest that PCDs can stimulate lymphatic function and may be an effective method to manage BCRL, warranting future clinical trials.

Human Lymphatic Architecture and Dynamic Transport Imaged Using Near-infrared Fluorescence.

BACKGROUND: Although the importance of lymphatic function is well recognized, the lack of real-time imaging modalities limits our understanding of its role in many diseases. In a phase 0 exploratory study, we used dynamic, near-infrared (NIR) fluorescence imaging to assess the extremes of lymphatic architecture and transport in healthy human subjects and in subjects clinically diagnosed with unilateral lymphedema (LE), a disease that can be prevalent in cancer survivors. METHODS AND RESULTS: Active lymphatic propulsion was imaged after intradermal injections of 25 µg of indocyanine green (total maximum dose ≤400 µg) bilaterally in the arms or legs of control and subjects. Images show well-defined lymphatic structures with propulsive dye transport in limbs of healthy subjects. In LE subjects, we observed extravascular dye accumulation, networks of fluorescent lymphatic capillaries, and/or tortuous lymphatic vessels in all symptomatic and some asymptomatic limbs. Statistical models indicate that disease status and/or limb significantly affect parameters of apparent lymph propagation velocity and contractile frequency. CONCLUSIONS: These clinical research studies demonstrate the potential of NIR fluorescence imaging as a diagnostic measure of functional lymphatics and as a new tool in translational research studies to decipher the role of the lymphatic system in cancer and other diseases.

Near-Infrared Fluorescence Imaging in Humans with Indocyanine Green: A Review and Update.

Near-infrared (NIR) fluorescence imaging clinical studies have been reported in the literature with six different devices that employ various doses of indocyanine green (ICG) as a non-specific contrast agent. To date, clinical applications range from (i) angiography, intraoperative assessment of vessel patency, and tumor/metastasis delineation following intravenous administration of ICG, and (ii) imaging lymphatic architecture and function following subcutaneous and intradermal ICG administration. In the latter case, NIR fluorescence imaging may enable new discoveries associated with lymphatic function due to (i) a unique niche that is not met by any other conventional imaging technology and (ii) its exquisite sensitivity enabling high spatial and temporal resolution. Herein, we (i) review the basics of clinical NIR fluorescence imaging, (ii) survey the literature on clinical application of investigational devices using ICG fluorescent contrast, (iii) provide an update of non-invasive dynamic lymphatic imaging conducted with our FDPM device, and finally, (iv) comment on the future NIR fluorescence imaging for non-invasive and intraoperative use given recent demonstrations showing capabilities for imaging following microdose administration of contrast agent.

Dying to play video games: carbon monoxide poisoning from electrical generators used after hurricane Ike.

BACKGROUND: Carbon monoxide (CO) poisoning is common after major storms because of loss of electrical power and use of alternate fuel sources for heat and electricity. In past epidemics of hurricane-related CO poisoning, the source has typically been gasoline-powered electrical generators. Although it is typically believed that generators were used to power air conditioning and refrigeration, this report demonstrates an unsuspected reason for their use. PATIENTS AND METHODS: After Hurricane Ike's landfall in September 2008, major power outages were associated with an epidemic of CO poisoning from electrical generators, as expected. Staff at Memorial Hermann Hospital-Texas Medical Center treated or telephone-triaged cases from the Houston area. A review of the details of those cases forms the basis of this report. RESULTS: Memorial Hermann Hospital-Texas Medical Center staff treated or triaged 37 individuals exposed to CO from gasoline-powered electrical generators in 13 incidents in the first 36 hours after landfall of the hurricane. Notably, 54% (20 of 37) of the patients were under the age of 18 years. Symptoms ranged from mild to severe, with 1 child dying at the scene. Eleven patients were treated with hyperbaric oxygen. Among 9 incidents in which the reason for generator use was determined, 5 were due to generators powering video games or televisions to watch movies or programs. These 5 incidents in which video games were being powered accounted for 75% (15 of 20) of the pediatric poisonings. CONCLUSIONS: Generator-related CO poisoning is indeed common during power outages after hurricanes. However, generators are commonly being used to provide electricity to power entertainment devices for children, such as video games. Additional public education about CO risk is needed, perhaps directed at older children and teenagers through the schools in regions susceptible to hurricanes.