Near-Infrared Fluorescence Lymphography Research Articles

LED-based photoacoustic imaging for preoperative visualization of lymphatic vessels in patients with secondary limb lymphedema

Lymphedema is the accumulation of protein-rich fluid in the interstitium (i.e., dermal backflow (DBF)). Preoperative imaging of the lymphatic vessels is a prerequisite for lymphovenous bypass surgical planning. We investigated the visualization of lymphatic vessels and veins using light-emitting diode (LED)-based photoacoustic imaging (PAI).Indocyanine-green mediated near-infrared fluorescence lymphography (NIRF-L) was done in fifteen patients with secondary limb lymphedema. Photoacoustic images were acquired in locations where lymphatic vessels and DBF were observed with NIRF-L.We demonstrated that LED-based PAI can visualize and differentiate lymphatic vessels and veins even in the presence of DBF. We observed lymphatic and blood vessels up to depths of 8.3 and 8.6 mm, respectively.Superficial lymphatic vessels and veins can be visualized using LED-based PAI even in the presence of DBF showing the potential for pre-operative assessment. Further development of the technique is needed to improve its usability in clinical settings.

Identification of lymph vessels using an indocyanine green camera-integrated operative microscope for lymphovenous anastomosis in the treatment of secondary lymphedema

ObjectiveLymphedema is a debilitating disease that impairs a patient’s quality of life. Although lymphovenous anastomosis (LVA) can cure lymphedema, successful LVAs rely on the precise identification of the lymph vessels. In the present study, we assessed the use of a near-infrared camera-integrated operating microscope for preoperative mapping of the lymphatic vessels and evaluated the outcome of LVAs in patients with secondary lymphedema of a limb. MethodsWe retrospectively reviewed patients with secondary unilateral lymphedema who had undergone LVA surgery with the lymph vessels identified using a near-infrared camera-integrated operating microscope (Moller 3-1000; Möller-Wedel Optical GmbH, Wedel, Germany) between 2020 and 2021. The lymph vessels identified using near-infrared fluorescence lymphography, diameter of the vessels used for anastomosis, anastomosis configuration, and perioperative limb circumference were recorded. ResultsOverall, 35 LVAs were performed in six patients with secondary lymphedema, with a mean number of 5.8 LVAs per limb. The anastomotic configurations were end-to-end in 26 LVAs, side-to-end in 2 LVAs, and end-to-side in 7 LVAs. The diameter of the lymph vessels ranged from 0.3 to 0.9 mm (mean, 0.62 ± 0.18 mm) and that of the vein from 0.4 to 1.2 mm (mean, 0.75 ± 0.21 mm). The changes in the lymphedema index and estimated limb volume indicated a postoperative decrease in edema. ConclusionsWe found a near-infrared camera-integrated operating microscope useful for the preoperative identification of functional lymph vessels. Our results have shown that microsurgical LVAs can be performed using an integrated indocyanine green camera without an independent indocyanine green detector.

The lymphatic system throughout history: From hieroglyphic translations to state of the art radiological techniques.

A comprehensive lymphatic system is indispensable for a well‐functioning body; it is integral to the immune system and is also interrelated with the digestive system and fluid homeostasis. The main difficulty in examining the lymphatic system is its fine‐meshed structure. This remains a challenge, leaving patients with uninterpreted symptoms and a dearth of potential therapies. We review the history of the lymphatic system up to the present with the aim of improving current knowledge. Several findings described throughout history have made fundamental contributions to elucidating the lymphatic system. The first contributions were made by the ancient Egyptians and the ancient Greeks. Vesalius obtained new insights by dissecting corpses. Thereafter, Ruysch (1638–1731) gained an understanding of lymphatic flow. In 1784, Mascagni published his illustration of the whole lymphatic network. The introduction of radiological lymphography revolutionized knowledge of the lymphatic system. Pedal lymphangiography was first described by Monteiro (1931) and Kinmonth (1952). Lymphoscintigraphy (nuclear medicine), magnetic resonance imaging, and near‐infrared fluorescence lymphography further improved visualization of the lymphatic system. The innovative dynamic contrast‐enhanced magnetic resonance lymphangiography (DCMRL) transformed understanding of the central lymphatic system, enabling central lymphatic flow disorders in patients to be diagnosed and even allowing for therapeutic planning. From the perspective of the history of lymph visualization, DCMRL has ample potential for identifying specific causes of debilitating symptoms in patients with central lymphatic system abnormalities and even allows for therapeutic planning.

Thoracoscopic detection of thoracic ducts after ultrasound-guided intrahepatic injection of indocyanine green detected by near-infrared fluorescence and methylene blue in dogs.

To describe and compare onset and intensity of thoracic duct (TD) coloration in healthy dogs after intrahepatic injection of either indocyanine green (ICG) visualized by intraoperative near-infrared fluorescence lymphography (NIRFL) or direct thoracoscopic visualization of methylene blue dye (MB). Prospective study. Healthy adult Beagle dogs (n=5). All dogs had biochemical panels and complete blood counts preoperatively. Computed tomography lymphography (CTL) was performed prior to a standard 3-port thoracoscopic approach. A mixture of MB and ICG was injected by ultrasound-guided percutaneous injection into right or left-sided hepatic lobes. Data collected included dose of contrast agent (MB vs. ICG), injection site, timing, and quality of operative TD identification. Potential hepatic injury was assessed by repeat laboratory evaluation and abdominal ultrasound 14 days postoperatively. Preoperative CTL provided a diagnostic study in 5/5 dogs. After intrahepatic injection of combined dyes, NIRFL allowed visualization of TDs in 5/5 dogs, but MB did not result in visible TD coloration in any dog. Intrahepatic injection of ICG achieved successful NIRFL in a median time of 6minutes and persisted for the 20 minute observation period in all five dogs. All dogs recovered without complication and were subsequently adopted. NIRFL of the TD can be achieved with intraoperative hepatic injection of ICG. Intrahepatic injection of MB did not result in visible TD coloration. Hepatic intra-parenchymal injection is a reliable alternative portal into the TD system for intraoperative visualization of TD anatomy using ICG in dogs.

Use of photoacoustic imaging to determine the effects of aging on lower extremity lymphatic vessel function

ObjectiveAging is one of the causes of primary lymphedema. However, the effects of aging on the lymphatic system are still not completely understood. We investigated the effects of aging on the lymphatic vessels in the lower extremities of healthy volunteers using photoacoustic imaging. MethodsHealthy volunteers who underwent photoacoustic lymphangiography between March 2018 and January 2019 were enrolled. To visualize lymphatics, indocyanine green (ICG, 5.0 mg/mL) was injected subcutaneously into the first and fourth web spaces of the foot and under the lateral malleolus. Subsequently, near-infrared fluorescence lymphography was performed to confirm good ICG flow, and photoacoustic lymphangiography was performed on the medial side of the lower leg. Ti sapphire laser irradiation at 797 and 835 nm, the optimal wavelengths for visualizing ICG and blood, was applied. The number of lymphatic vessels shown at areas 10 cm (L10) and 20 cm (L20) cranially from the internal malleolus was counted. ResultsNineteen healthy volunteers (4 males and 15 females) were enrolled in the study. Their mean age was 42.9 ± 12.8 years. One volunteer was bilaterally imaged; 15 left lower limbs and 5 right lower limbs were imaged. The number of lymphatic vessels visualized increased with age. There were strong positive correlations between age and L10 (R = 0.729, P < .001) and between age and L20 (R = 0.570, P = .009). ConclusionsPhotoacoustic imaging indicates that the number of lymphatic vessels increases with age. Lymphatic stasis resulted in visualization of not only normal drainage pathways but also nonfunctional lymphatic pathways.

Correlations between Tracer Injection Sites and Lymphatic Pathways in the Leg: A Near-Infrared Fluorescence Lymphography Study.

The primary aim of this study was to determine the detailed anatomy of the lymphatics in the lower extremity using fresh human cadavers with indocyanine green fluorescence lymphography. The secondary aim was to apply the anatomical results to establish a new protocol for lymphography based on feasible allocations for tracer injection sites. One hundred lower extremities from 53 fresh human cadavers were used for this study. The authors injected indocyanine green solution subcutaneously at 19 points around the foot along the borderline between the dorsum and planta according to anatomical landmarks. Immediately after the indocyanine green injections, gentle hand massage was applied at each injection site to facilitate indocyanine green uptake into the lymphatic vessels. Fluorescent images of the lymphatics were obtained using a near-infrared camera system. Imaging data of the lymphatics were analyzed to find correlations between the injection sites and the identified lymphatic vessels. The lymphatic system in the lower extremity was divided into four distinct lymphatic groups: anteromedial, anterolateral, posterolateral, and posteromedial. The lymphatic vessels in all except the posterolateral group connected to the inguinal nodes, and those in the posterolateral group connected to the popliteal nodes. The authors successfully elucidated correlations between the injection sites in the foot and each lymphatic group. The new classification of the four lymphatic groups in the lower extremity and identification of their origins in the foot enabled the authors to propose a new protocol for lymphography that includes four injection sites in specific circumflex locations.

Use of direct near-infrared fluorescent lymphography for thoracoscopic thoracic duct identification in 15 dogs with chylothorax.

To describe and assess techniques of intraoperative near-infrared fluorescence lymphography (NIRFL) using indocyanine green (ICG) for lymphatic duct identification during thoracoscopic thoracic duct (TD) ligation in dogs. Retrospective case series. Dogs (n = 15) with naturally occurring chylothorax that underwent TD ligation. Medical records of dogs treated with thoracoscopic TD ligation in which NIRFL was utilized for intraoperative TD identification were reviewed. Data retrieved included CT lymphography (CTL) and surgical data, fluorophore dose and injection site, and timing and quality of operative TD identification. Preoperative CTL was successful in 13/15 dogs and operative NIRFL was successful in 15/15 dogs. Popliteal lymph node injection achieved successful NIRFL within ≤10 minutes in 7/11 in which it was attempted. TDs identified by NIRFL imaging correlated with TDs identified by preoperative CTL in 12/13 cases in which CTL was achieved. In 1/13 cases, NIRFL identified small lymphatics not visible on CTL. In 5/9 cases in which methylene blue (MB) and ICG were combined for operative lymphography, no ducts or fewer ducts were recorded as identifiable by visible MB than by NIRFL or CTL. The median dose of ICG to achieve NIRFL imaging was 0.05 mg/kg. Thoracoscopic TD ligation was successfully achieved in all patients. NIRFL is a viable technique to aid in TD identification during thoracoscopy. High contrast NIRF illumination of the TD can be achieved with successful intraparenchymal injection of ICG into the popliteal lymph node.

The Functional Examination of Lymphedema: Advantage and Limitation of SPECT/CT Lymphoscintigraphy and Near-Infrared Fluorescence Lymphography

The Functional Examination of Lymphedema: Advantage and Limitation of SPECT/CT Lymphoscintigraphy and Near-Infrared Fluorescence Lymphography