Measurement of lymphatic vessel depth using photoacoustic imaging.

OBJECTIVES: Information regarding the depth of lymphatic vessel is important for lymphatic surgeons because rapid identification of functional lymphatic vessels and veins is necessary to perform good lymphaticovenular anastomosis, which is a surgical procedure for lymphedema cases. Photoacoustic lymphangiography (PAL) may be useful for such identification because it allows the assessment of the depth of lymphatic vessels. Thus, we aimed to measure the lymphatic vessel depth using images obtained by PAL. METHODS: This study included healthy individuals and patients with lymphedema. In all participants, indocyanine green dissolved in dextrose was injected subcutaneously into the first and fourth webs of the foot and the lateral malleolus, and PAL was performed on the medial side of the lower leg. The lymphatic vessel depth was measured from the ankle joint, 10 cm above the medial malleolus, and 20 cm above the medial malleolus on PAL in the cross-sectional view and was compared between the participant groups. RESULTS: The healthy group (mean age, 43.3 ± 12.9 years) included 21 limbs of 4 male and 16 female healthy individuals (bilateral limbs of 1 patient were considered). The lymphedema group (mean age, 62.0 ± 11.7 years) included 17 limbs of 3 male and 14 female patients with lymphedema. The average lymphatic vessel depths from the ankle joint, 10 cm above the medial malleolus, and 20 cm above the medial malleolus were 2.6, 4.7, and 5.6 mm in the healthy group and 3.6, 7.3, and 7.4 mm in the lymphedema group, respectively. Lymphatic vessels were significantly deeper in the lymphedema group than in the healthy group at all measurement locations. CONCLUSIONS: Using PAL, we determined the lymphatic vessel depth in living bodies. By searching for the lymphatic vessels based on our findings, even surgeons who are relatively inexperienced with lymphatic surgery may be able to identify functional lymphatic vessels more efficiently.

Photoacoustic lymphangiography is a possible alternative for lymphedema staging.

OBJECTIVE: Photoacoustic imaging is a new technique that uses the photoacoustic effect. In photoacoustic lymphangiography (PAL), images of the lymphatic vessels can be visualized using light-absorbing contrast agents. In the present study, we investigated the efficacy of PAL for lymphedema staging. METHODS: We performed PAL of the lower extremities and examined the clinical implications of using PAL for staging lymphedema by comparing the PAL images with those obtained using lymphoscintigraphy. Of 47 patients with lymphedema who had been outpatients or hospitalized at our institution between May 2018 and September 2020 and had undergone PAL, 15 with 18 limbs who had also undergone lymphoscintigraphy were included in the present study. The lymphoscintigraphy findings were classified using the Maegawa classification. We also investigated whether PAL could clearly visualize the lymphatic vessels and concisely reflect the disease state by counting the number of lymphatic vessels observed using PAL. RESULTS: The PAL findings were categorized into three groups: collecting lymphatic vessels, dermal backflow (DBF), and no lymphatic vessels. The collecting lymphatic vessels group corresponded to types 2 and 3 in the Maegawa classification; DBF corresponded to types 3 and 4, and the no lymphatic vessels group corresponded to type 4. The number of lymphatic vessels visualized using PAL was similar to that with lymphoscintigraphy. As the disease progressed, the number of lymphatic vessels observed decreased, increased DBF was detected, and, eventually, the lymphatic vessels were not visible, corresponding to the general changes observed via lymphoscintigraphy with stage progression. CONCLUSIONS: The findings from PAL and lymphoscintigraphy tended to correspond, suggesting that PAL could be useful for lymphedema staging.

Photoacoustic lymphangiography exhibits advantages over near-infrared fluorescence lymphangiography as a diagnostic tool in patients with lymphedema.

OBJECTIVE: Photoacoustic imaging is a new technique that can evaluate the vascular system using photoacoustic effects. The present study compared the ability of the new photoacoustic lymphangiography (PAL) method and more standard near-infrared fluorescence (NIRF) to image the lymphatic system in patients with secondary lymphedema after gynecological cancer surgery. METHODS: Patients with secondary lymphedema in the lower extremities after gynecologic cancer surgery, who were assessed using PAL between May 2018 and January 2019, were recruited. NIRF was performed first using 5.0 mg/mL of indocyanine green injected using a 0.2-cc 30-gauge needle. Correlations between NIRF and PAL findings on patient images were subsequently examined. RESULTS: Seventeen patients with secondary lymphedema were enrolled. The mean age of the patients was 61 ± 11 years. The imaging sites were the medial lower leg in 15 patients, the posterior lower leg in 9 patients, the lateral lower leg in 7 patients, the medial knee in 4 patients, and other areas in 3 patients. A total of 38 pictures were obtained. Five distinct lymphatic patterns were observed over the entire sample using PAL: straight, winding, spiderweb, nebulous, and black-out pattern. Eighteen of the 24 limbs (75%) that exhibited a linear pattern in NIRF exhibited a straight pattern in PAL, and 19 of the 20 limbs (95%) that exhibited a splash pattern in NIRF exhibited a winding or spiderweb pattern in PAL. Eight limbs exhibiting diffuse patterns without linear or splash patterns with NIRF were all nebulous or black-out patterns in PAL. This suggests that more severe lymphatic degeneration was associated with poorer visualization in PAL. CONCLUSIONS: NIRF plays an important role in lymphedema treatment. In the present study, various PAL patterns were compared with those observed using NIRF. PAL provided clearer images including transectional views, which were not available using NIRF, and may promote further understanding of the changes in the lymphatic structure and function in patients with secondary lymphedema.

Subcutaneous Lymphatic Vessels in the Lower Extremities: Comparison between Photoacoustic Lymphangiography and Near-Infrared Fluorescence Lymphangiography.

Background Detailed visualization of the lymphatic vessels would greatly assist in the diagnosis and monitoring of lymphatic diseases and aid in preoperative planning of lymphedema surgery and postoperative evaluation. Purpose To evaluate the usefulness of photoacoustic imaging (PAI) for obtaining three-dimensional images of both lymphatic vessels and surrounding venules. Materials and Methods In this prospective study, the authors recruited healthy participants from March 2018 to January 2019 and imaged lymphatic vessels in the lower limbs. Indocyanine green (5.0 mg/mL) was injected into the subcutaneous tissue of the first and fourth web spaces of the toes and below the lateral malleolus. After confirmation of the lymphatic flow with near-infrared fluorescence (NIRF) imaging as the reference standard, PAI was performed over a field of view of 270 × 180 mm. Subsequently, the number of enhancing lymphatic vessels was counted in both proximal and distal areas of the calf and compared between PAI and NIRF. Results Images of the lower limbs were obtained with PAI and NIRF in 15 participants (three men, 12 women; average age, 42 years ± 12 [standard deviation]). All participants exhibited a linear pattern on NIRF images, which is generally considered a reflection of good lymphatic function. A greater number of lymphatic vessels were observed with PAI than with NIRF in both the distal (mean: 3.6 vessels ± 1.2 vs 2.0 vessels ± 1.1, respectively; P < .05) and proximal (mean: 6.5 vessels ± 2.6 vs 2.6 vessels ± 1.6; P < .05) regions of the calf. Conclusion Compared with near-infrared fluorescence imaging, photoacoustic imaging provided a detailed, three-dimensional representation of the lymphatic vessels and facilitated an increased understanding of their relationship with the surrounding venules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lillis and Krishnamurthy in this issue.

Photoacoustic lymphangiography.

BACKGROUND AND OBJECTIVES: Photoacoustic lymphangiography, which is based on photoacoustic technology, is an optical imaging that visualizes the distribution of light absorbing tissue components like hemoglobin or melanin, as well as optical absorption contrast imaging agents like indocyanine green (ICG) in the lymphatic channels, with high spatial resolution. In this report, we introduce the three-dimensional (3D) images of human lymphatic vessels obtained with photoacoustic lymphangiography. METHODS: We used the 3D photoacoustic visualization system (PAI-05). Some healthy subjects and lymphedema patients were recruited. To image the lymphatic structures of the limbs ICG was administered subcutaneously as in fluorescence lymphangiography. Photoacoustic images were acquired by irradiating the tissue using a laser at wavelengths of near-infrared region. On the same occasion, fluorescence images were also recorded. RESULTS: The lymphatic vessels up to the diameter of 0.2 mm could be observed three-dimensionally with the venules around them. In the patient-group, dermal backflow patterns were often observed as dense interconnecting 3D structures of lymphatic vessels. Collecting vessels passing below the dermis were also observed, which were not observed by fluorescence lymphography. CONCLUSIONS: Photoacoustic lymphangiography provided the detailed observation of each lymphatic vessel, leading to deeper understanding of 3D structures and physiological state of the vessel.