Journal Logo

Reconstructive: Ideas and Innovations

Lymph Vessel Mapping Using Indocyanine Green Lymphography in the Nonaffected Side of Lower Leg

Kinugawa, Kei MD; Nuri, Takashi MD, PhD; Iwanaga, Hiroyuki MD; Otsuki, Yuki MD, PhD; Ueda, Koichi MD, PhD

Author Information
Plastic and Reconstructive Surgery - Global Open: June 2020 - Volume 8 - Issue 6 - p e2929
doi: 10.1097/GOX.0000000000002929

Abstract

INTRODUCTION

Lymphaticovenular anastomosis (LVA), which connects the lymphatic and venous systems, is a major treatment option for lymphedema. The amount of lymph drainage through the anastomosis depends on the pressure gradient between the lymphatic and venous systems. Previous studies have revealed that the lymphatic pressure during active contraction far exceeds the venous pressure,1,2 and that choosing lymph vessels with remaining smooth muscle function is ideal for effective LVA. Although anatomical studies have shown the widespread existence of lymphatic vessels throughout the body, indocyanine green near-infrared lymphography (ICGL) early after the injection of indocyanine green shows little linear flow. The lymphatic vessels contract once every few minutes, suggesting that early visualization of linear flow without massage represents a lymphatic vessel with superior smooth muscle function. Lymph vessel mapping using ICGL in living bodies has not been reported to date. Such findings can help to predict the location of lymph vessels without using an infrared camera. We herein report our findings of the course of lymph vessels in healthy lower limbs.

PATIENTS AND METHODS

The unaffected lower limbs of 14 patients who underwent LVA for the treatment of unilateral lower leg lymphedema were evaluated (Table 1). In all patients, preoperative lymphoscintigraphy showed no abnormal findings such as dermal backflow or disruption and expansion of the lymph vessels in the unaffected limb (Fig. 1).

Table 1. - Cases
No. Sex Age Affected Side BMI Primary Disease First Surgery Year Number of Linear Flows
10 cm above the Knee Patellar Lower Pole Middle Lower Leg Dorsum
1 Female 46 Left 21.4 Ovarian cancer 2014 1 3 1 1
2 Female 68 Right 23.5 Cervical cancer 2012 2 1 2 0
3 Female 68 Left 26.0 Fallopian tube cancer 2008 2 1 2 0
4 Female 57 Right 21.0 Cervical cancer 1997 2 3 1 1
5 Female 74 Right 20.2 Ovarian cancer 2012 0 1 1 1
6 Female 86 Left 25.8 Cervical cancer 2005 2 1 1 2
7 Female 67 Left 20.3 Bladder cancer 2015 1 1 2 2
8 Male 73 Right 32.3 Idiopathic lymphedema 2 3 1 1
9 Female 80 Left 19.3 Cervical cancer 1998 1 3 1 1
10 Female 69 Left 21.8 Endometrial cancer 2001 1 3 1 1
11 Female 57 Right 28.1 Endometrial cancer 2012 1 4 1 2
12 Female 80 Left 24.6 Endometrial cancer 1991 1 2 1 1
13 Female 74 Right 29.8 Cervical cancer 2005 3 3 2 1
14 Female 85 Right 25.7 Endometrial cancer 2009 2 2 1 2

Indocyanine Green Near-infrared Lymphography

Use of ICGL to diagnose lymphedema was approved by the Ethical Committee of Osaka Medical College (No. 594). ICGL was performed with the patients under general anesthesia immediately before LVA. After the patients had received 4 injections of 0.2 ml (0.5 mg) of indocyanine green into the lateral and medial ankles and the first and fourth toe web spaces, the lymph vessels were observed using an infrared camera (pde-neo; Hamamatsu Photonics K.K., Hamamatsu, Japan) immediately after the injection without a massage. Images of the lymph vessels were then drawn on the skin using an oil-based pen.

Three-dimensional Measurement of Lymph Vessel Locations

To record the locations of the lymph vessels, images of the lower leg containing the drawn-on lymph courses were recorded using a 3-dimensional (3D) camera (VECTRA H1; Canfield Scientific, Parsippany, N.J.). All patients’ feet were fixed using the same fixture, and all 3D photographs were taken from the same angle. The 3D images were then constructed using VECTRA software (VECTRA H1 camera; Canfield Scientific, Inc., Parsippany-Troy Hills, N.J.). The positions of the lymph vessels were measured from the baseline, which was drawn from the midline of the anterior thigh to the second toe through the middle point of the patella. Measurements were performed using 3D images at the following 4 points: 10 cm above the knee, at the lower pole of the patella, at the middle aspect of the lower leg, and at the dorsum of the foot (first metatarsal–cuneiform joint) (Fig. 2). To minimize errors due to differences in patients’ body shape, the distances from the baseline to the lymph vessels were indicated not only by the measured absolute distance but also by the ratio of the distance to the leg circumference.

Relative position of the lymph vessel (%) = Measured distance (cm)/Circumference (cm) × 100

The position of each lymph vessel in the lateral direction was defined by a negative number, while that in the medial direction was defined by a positive number (Fig. 2).

RESULTS

In every case, multiple linear flows were observed in the unaffected lower limb. Among all 14 cases, the average number of linear flows at each measurement point (10 cm above the knee, at the lower pole of the patella, at the middle aspect of the lower leg, and at the dorsum of the foot) was 1.14 (range, 0–2), 1.14 (range, 1–2), 2.64 (range, 1–6), and 1.5 (range, 0–3), respectively (Table 1). The average distance from the baseline to the linear flow at each point was 11.39 cm (range, 8.61–13.96 cm), 9.82 cm (range, 7.03–13.30 cm), 4.37 cm (range, −6.78 to 11.31 cm), and 0.97 cm (range, −1.58 to 2.76), respectively. The average circumferential diameter at each measurement point was 42.6 cm (range, 32.5–55.0 cm), 32.9 cm (range, 27.5–37.5 cm), 30.7 cm (range, 25.0–37.0 cm), and 21.8 cm (range, 19.5–26.0 cm), respectively. In terms of the ratio of the distance to the leg circumference at each point, the linear flow was observed inside of the baseline at a distance equivalent to 27.2% (range, 21.0%–33.8%), 30.1% (range, 22.5%–40.7%), 14.8% (range, −23.4% to 45.0%), and 4.4% (range, −6.8% to 12.6%) of the leg circumference, respectively. (See figure 1, Supplemental Digital Content 1, which displays graphs that represent the relationship between the number of linear flows and the distance from the baseline, expressed as the ratio of the distance to the circumference of the leg, http://links.lww.com/PRSGO/B413.) (See figure 2, Supplemental Digital Content 2, which displays graphs that represent the relationship between the number of linear flows and the absolute distance from the baseline to each of the 4 measurement points, http://links.lww.com/PRSGO/B414.)

DISCUSSION

The result of LVA is dependent on the amount of lymph drainage, which is defined by the pressure gradient between the lymphatic and venous systems. Previous studies have revealed that under normal conditions, the lymphatic pressure is lower than the venous pressure. However, the lymphatic pressure during active contraction far exceeds the venous pressure.1,2 The key factors that promote lymph drainage are contraction of the skeletal muscles3 and contraction of the smooth muscles of the lymph vessels.4

In this study, we observed the lymph vessels by ICGL immediately after injection. The lower leg was the area in which the highest number of lymph vessels was observed. However, the average number of linear flows in this area was only 2.64. Cadaveric studies of lymphatic vessels have revealed that several lymph vessels run mainly along the great and small saphenous veins.5,6 However, our study showed that the lymph vessels observed by ICGL were low in number and concentrated in a limited area. One cause of this difference between cadavers and living bodies may be that ICGL cannot depict lymph vessels deeper than 1.5 cm. However, the results of radioisotope lymphoscintigraphy, which can reveal deeper lymph vessels, were correlated with the results of ICGL.

Another possible cause is the difference in the examination methods between the cadavers and the living bodies. In our study, the lymph vessels were observed without massage or exercise, whereas massage is required to move the ICG7 through the vessels in cadaveric studies. In lymphoscintigraphy, lymph flow that reaches the groin region early after injection is considered to indicate a lymph vessel with normal smooth muscle function.8 Therefore, lymph vessels observed by ICGL early after injection may indicate lymph vessels with normal smooth muscle function.

In this study, the measurement was performed on the 3D images obtained by using 3D camera. The images can be enlarged, and the measurement was taken several times to improve the accuracy of the measurement. Our results indicate that the middle lower leg was the area in which the highest number of lymph vessels was observed. The linear flow was observed inside of the baseline in 13 cases and outside of the baseline in 1 case. In cases of lymphedema, ICGL often shows linear flow on the lateral side of the lower leg.9 Our results indicate that the main route of lymph flow may be diverted from alongside the great saphenous vein to the lateral side. In contrast, only small areas of linear flow were found at 10 cm above the knee, at the lower pole of the patella, and at the dorsum of the foot. Our results also showed that 62.5% of the observed lymph vessels ran 11–12 cm inward from the baseline at 10 cm above the knee. These results suggest that the lymph vessels are most likely to be found with a small incision in this area. On the other hand, the remaining function of smooth muscle depends on the stage of lymphedema. We believe that our results are particularly useful in early stages of lymphedema where smooth muscle function remains.

LIMITATION

We observed linear flow by ICGL in the unaffected lower leg. Our previous study on ICGL in the affected limb showed that lymph vessels traveled across the usual lymph territories in some cases.9 Although the lateral route was observed in the middle lower leg in the present study, the results cannot perfectly reflect the dynamic changes in lymph flow caused by lymphedema.

CONCLUSIONS

Lymph vessels were observed extensively in the middle lower leg. In contrast, linear flow was limited to a small area at the other measurement points. Among 4 observation points, 10 cm above the knee is where lymph vessels can be identified with a small incision.

Fig. 1.
Fig. 1.:
A 57-year-old woman with right lower leg lymphedema. The results of preoperative lymphoscintigraphy (right) on the unaffected lower limb show no abnormal findings. The results of ICGL were drawn using a green-colored oil-based pen (middle and left). The result of the ICGL of unaffected limb was correlated with the result of lymphoscintigraphy.
Fig. 2.
Fig. 2.:
The positions of lymph vessels were measured from the baseline, which was drawn from the midline of the anterior thigh to the second toe through the middle point of the patella. Measurements were performed on 3D images at the following 4 points: 10 cm above the knee, at the lower pole of the patella, at the middle aspect of the lower leg, and at the dorsum of the foot.

REFERENCES

1. Olszewski WL, Engeset A. Intrinsic contractility of leg lymphatics in man. Preliminary communication. Lymphology. 1979;12:81–84.
2. Nuri T, Iwanaga H, Ueda K. End-to-end lymphaticovenular anastomosis does not disturb the contraction of collecting lymph vessels. Plast Reconstr Surg Glob Open. 2017;5:e1457.
3. Seki Y, Yamamoto T, Yoshimatsu H, et al. The superior-edge-of-the-knee incision method in lymphaticovenular anastomosis for lower extremity lymphedema. Plast Reconstr Surg. 2015;136:665e–675e.
4. Zawieja DC, Weid PY, Gashev AA. Johnson PC. Microlymphatic biology. In: Microcirculation. 2008:2nd ed. Amsterdam: Elsevier; 125–158.
5. Suami H, Scaglioni MF. Anatomy of the lymphatic system and the lymphosome concept with reference to lymphedema. Semin Plast Surg. 2018;32:5–11.
6. Sappey M PC. Anatomie, Physiologie, Pathologie Des Vaisseaux Lymphatiques. 1874.Paris: AdrienDelahaye;
7. Shinaoka A, Koshimune S, Yamada K, et al. A fresh cadaver study on indocyanine green fluorescence lymphography: a new whole-body imaging technique for investigating the superficial lymphatics. Plast Reconstr Surg. 2018;141:1161–1164.
8. Maegawa J, Mikami T, Yamamoto Y, et al. Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis. Microsurgery. 2010;30:437–442.
9. Nuri T, Iwanaga H, Otsuki Y, et al. Effect of variable injection sites for indocyanine green dye on the success of lymphaticovenular anastomosis. J Reconstr Microsurg Open 2019;2:e92–e95.

Supplemental Digital Content

Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.