V ascular and lymphatic vessel networks closely approximate each other in the interstitial environment, and a detailed visualization of these systems is essential to understanding their involvement in both normal physiologic processes and development of pathologic conditions. It is inherently difficult to visualize lymphatic vessels because of their small diameter and because lymph fluid is colorless. Traditionally, lymphatic vessels in the human body are visualized with lymphoscintigraphy, MR lymphangiography, or near-infrared fluorescence (NIRF) lymphography. The primary indication for these technologies is evaluation of lymphedema due to the obstruction of lymph flow (1-7). These modalities, however, do not provide clear visualization of the lymphatic vessels.In this study, we describe a method for detailed three-dimensional visualization of the lymphatic vessels in the lower extremities of healthy individuals by using photoacoustic imaging (PAI). Although the feasibility of PAI technology has been previously documented in case reports and pilot studies (8,9), herein we expand on those preliminary findings with a larger sample size and demonstrate the practical effectiveness and accuracy of PAI lymphangiography in comparison to NIRF lymphangiography.
Materials and Methods
Study ParticipantsIn this prospective study conducted from March 2018 to January 2019, we recruited 15 participants (three men and 12 women; average age 6 standard deviation, 45 years 6 12) at our hospital and imaged the lymphatic vessels of each volunteer by using both NIRF and PAI. This study was conducted with the approval of the appropriate local ethics committee. Oral and written informed
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Lymphaticovenular anastomosis (LVA) is a widely performed surgical procedure for the treatment of lymphedema. For good LVA outcomes, identifying lymphatic vessels and venules is crucial. Photoacoustic lymphangiography (PAL) is a new technology for visualizing lymphatic vessels. It can depict lymphatic vessels at high resolution; therefore, this study focused on how to apply PAL for lymphatic surgery. To visualize lymphatic vessels, indocyanine green was injected as a color agent. PAI-05 was used as the photoacoustic imaging device. Lymphatic vessels and veins were visualized at 797- and 835-nm wavelengths. First, it was confirmed whether the branching of the vasculature as depicted by the PAL was consistent with the actual branching of the vasculature as confirmed intraoperatively. Second, to use PAL images for surgical planning, preoperative photoacoustic images were superimposed onto the patient limb through augmented reality (AR) glasses (MOVERIO Smart Glass BT-30E). Lymphatics and venule markings drawn using AR glasses were consistent with the actual intraoperative images obtained during LVA. To anastomose multiple lymphatic vessels, a site with abundant venous branching was selected as the incision site; and selecting the incision site became easier. The anatomical morphology obtained by PAL matched the surgical field. AR-based marking could be very useful in future LVA.
Background Lymphatic vessels are difficult to identify using existing modalities as because of their small diameter and the transparency of the lymph fluid flowing through them.
Methods Here, we introduce photoacoustic lymphangiography (PAL), a new modality widely used for lymphedema treatment, to observe limb lymphatic vessels. The photoacoustic imaging system used in this study can simultaneously visualize lymphatic vessels and veins with a high resolution (0.2 mm) and can also observe their three-dimensional relationship with each other.
Results High-resolution images of the lymphatic vessels, detailed structure of the dermal back flow, and the three-dimensional positional relationship between the lymphatic vessels and veins were observed by PAL.
Conclusion The clear image provided by PAL could have a major application in pre- and postoperative use during lymphaticovenular anastomosis for lymphedema treatment.
Background A micro-arteriovenous fistula (AVF) is a minute, short shunt between an artery and a vein that does not pass through a capillary. We investigated the association between micro-AVFs and lymphedema using computed tomography angiography (CTA) and venous blood gas analysis.<br/>Methods In 95 patients with lower limb lymphedema, the presence or absence of early venous return (EVR) was compared between patients with primary and secondary lymphedema. Furthermore, we investigated the difference in the timing of edema onset in patients with secondary lymphedema with or without EVR using CTA. In 20 patients with lower limb lymphedema with confirmed early EVR in a unilateral lower limb, the partial pressure of oxygen (PO2) was compared between the lower limb with EVR and the contralateral lower limb.<br/>Results Secondary lymphedema with or without EVR occurred at an average of 36.0±59.3 months and 93.5±136.1 months, respectively; however, no significant difference was noted. PO2 was 57.6±11.7 mmHg and 44.1±16.4 mmHg in the EVR and non-EVR limbs, respectively, which was a significant difference (P=0.005).<br/>Conclusions EVR and venous blood gas analysis suggested the presence of micro-AVFs in patients with lower extremity edema. Further research is warranted to examine the cause of micro-AVFs, to advance technology to facilitate the confirmation of micro-AVFs by angiography, and to improve lymphedema by ligation of micro-AVFs.
Heterochronic parabiosis is used to study the systemic effects of aging and involves surgically connecting two animals of different ages such that they have common blood circulation. Although this technique has been prevalent for a long time, there is no scientific consensus on the age of the animals that should be used. We hypothesized that the younger the animal, the greater would be its rejuvenating effect. Hence, to test this hypothesis, we created parabiosis of 67-week-old mice with younger mice of different ages (4-week-old and 8-week-old). We evaluated the changes in appearance and the expression IL-1A, IL-6, and Cdkn2a (p16) in the liver, kidney, brain, and skin. These cytokines belong to the senescence-associated secretory phenotype (SASP) factors, and are indicators of aging. Although we did not find any significant changes in the appearance of the mice, we found statistically significant differences in some SASP factors between the liver of the 4-week-old and 8-week-old pairs. However, overall, compared to the 8-week-old mice, the 4-week-old does not exert a significantly higher rejuvenation effect on the older mice. Hence, we concluded that the rejuvenation of older mice during heterochronic parabiosis might not be affected by the exact age of the younger mice.
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