Three-dimensional analysis of dermal backflow in cancer-related lymphedema using photoacoustic lymphangiography

Background Dermal backflow (DBF), which refers to lymphatic reflux due to lymphatic valve insufficiency, is a diagnostic finding in lymphedema. However, the three-dimensional structure of DBF remains unknown. Photoacoustic lymphangiography (PAL) is a new technique that enables the visualization of the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and can provide three-dimensional images of superficial lymphatic vessels and the venous system. This study reports the use of PAL to visualize DBF structures in the extremities of patients with lymphedema after cancer surgery.

Methods Patients with a clinical or lymphographic diagnosis of lymphedema who previously underwent surgery for cancer at one of two participating hospitals were included in this study. PAL was performed using the PAI-05 system. ICG was administered subcutaneously in the affected hand or foot, and ICG fluorescence lymphography was performed using a nearinfrared camera system prior to PAL.

Results Between April 2018 and January 2019, 21 patients were enrolled and examined using PAL. The DBF was composed of dense, interconnecting, three-dimensional lymphatic vessels. It was classified into three patterns according to the composition of the lymphatic vessels: a linear structure of lymphatic collectors (pattern 1), a network of lymphatic capillaries and lymphatic collectors in an underlying layer (pattern 2), and lymphatic capillaries and precollectors with no lymphatic collectors (pattern 3).

Conclusions PAL showed the structure of DBF more precisely than ICG fluorescence lymphography. The use of PAL to visualize DBF assists in understanding the pathophysiology and assessing the severity of cancer-related lymphedema.

Keywords

Lymphedema - Lymphography - Superficial lymphatic system

This research was funded by the ImPACT Program of Council for Science, Technology and Innovation (Cabinet Office, Government of Japan).

Publikationsverlauf

Eingereicht: 02. Juli 2021

Angenommen: 30. September 2021

Artikel online veröffentlicht:
02. Juni 2022

• REFERENCES

• 1 Rasmussen JC, Tan IC, Marshall MV. et al. Lymphatic imaging in humans with near-infrared fluorescence. Curr Opin Biotechnol 2009; 20: 74-82
• 2 Ter SE, Alavi A, Kim CK. et al. Lymphoscintigraphy: a reliable test for the diagnosis of lymphedema. Clin Nucl Med 1993; 18: 646-54
• 3 Dylke ES, McEntee MF, Schembri GP. et al. Reliability of a radiological grading system for dermal backflow in lymphoscintigraphy imaging. Acad Radiol 2013; 20: 758-63
• 4 Grada AA, Phillips TJ. Lymphedema: pathophysiology and clinical manifestations. J Am Acad Dermatol 2017; 77: 1009-20
• 5 Rockson SG. Lymphedema. Am J Med 2001; 110: 288-95
• 6 Aldrich MB, Rasmussen JC, Fife CE. et al. The development and treatment of lymphatic dysfunction in cancer patients and survivors. Cancers (Basel) 2020; 12: 2280
• 7 Suami H. Anatomical theories of the pathophysiology of cancer-related lymphoedema. Cancers (Basel) 2020; 12: 1338
• 8 Chang DW, Suami H. Discussion: comparison of indocyanine green lymphographic findings with the conditions of collecting lymphatic vessels of limbs in patients with lymphedema. Plast Reconstr Surg 2013; 132: 1619-21
• 9 Karacavus S, Yilmaz YK, Ekim H. Clinical significance of lymphoscintigraphy findings in the evaluation of lower extremity lymphedema. Mol Imaging Radionucl Ther 2015; 24: 80-4
• 10 Suami H, Scaglioni MF. Anatomy of the lymphatic system and the lymphosome concept with reference to lymphedema. Semin Plast Surg 2018; 32: 5-11
• 11 Yamamoto T, Narushima M, Doi K. et al. Characteristic indocyanine green lymphography findings in lower extremity lymphedema: the generation of a novel lymphedema severity staging system using dermal backflow patterns. Plast Reconstr Surg 2011; 127: 1979-86
• 12 Pappalardo M, Lin C, Ho OA. et al. Staging and clinical correlations of lymphoscintigraphy for unilateral gynecological cancer-related lymphedema. J Surg Oncol 2020; 121: 422-34
• 13 Kajita H, Oh A, Urano M. et al. Photoacoustic lymphangiography. J Surg Oncol 2020; 121: 48-50
• 14 Nagae K, Asao Y, Sudo Y. et al. Real-time 3D photoacoustic visualization system with a wide field of view for imaging human limbs. F1000Res 2018; 7: 1813
• 15 Oh A, Kajita H, Matoba E. et al. Photoacoustic lymphangiography before and after lymphaticovenular anastomosis. Arch Plast Surg 2021; 48: 323-8
• 16 Suzuki Y, Kajita H, Konishi N. et al. Subcutaneous lymphatic vessels in the lower extremities: comparison between photoacoustic lymphangiography and near-infrared fluorescence lymphangiography. Radiology 2020; 295: 469-74
• 17 Suzuki Y, Kajita H, Oh A. et al. Photoacoustic lymphangiography exhibits advantages over near-infrared fluorescence lymphangiography as a diagnostic tool in patients with lymphedema. J Vasc Surg Venous Lymphat Disord. 02.08.2021. [Epub]. https://doi.org/10.1016/j.jvsv.2021.07.012
• 18 International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology. 2013 46. 1-11
• 19 Sekiguchi H, Togashi K. Development of rapid MIP viewer for photoacoustic tomography--KURUMI (Kyoto Univ. Rapid and Universal MIP Imager). IEICE Tech Rep 2017; 116: 163-7
• 20 Blum KS, Proulx ST, Luciani P. et al. Dynamics of lymphatic regeneration and flow patterns after lymph node dissection. Breast Cancer Res Treat 2013; 139: 81-6
• 21 Suami H, Scaglioni MF, Dixon KA. et al. Interaction between vascularized lymph node transfer and recipient lymphatics after lymph node dissection: a pilot study in a canine model. J Surg Res 2016; 204: 418-27
• 22 Tashiro K, Shibata T, Mito D. et al. Indocyanine green lymphographic signs of lymphatic collateral formation in lower extremity lymphedema after cancer resection. Ann Plast Surg 2016; 77: 213-6
• 23 Tashiro K, Yamashita S, Saito T. et al. Proximal and distal patterns: different spreading patterns of indocyanine green lymphography in secondary lower extremity lymphedema. J Plast Reconstr Aesthet Surg 2016; 69: 368-75
• 24 Bianchi A, Visconti G, Hayashi A. et al. Ultra-high frequency ultrasound imaging of lymphatic channels correlates with their histological features: a step forward in lymphatic surgery. J Plast Reconstr Aesthet Surg 2020; 73: 1622-9
• 25 Hayashi A, Visconti G, Yamamoto T. et al. Intraoperative imaging of lymphatic vessel using ultra high-frequency ultrasound. J Plast Reconstr Aesthet Surg 2018; 71: 778-80
• 26 Lu Q, Delproposto Z, Hu A. et al. MR lymphography of lymphatic vessels in lower extremity with gynecologic oncology-related lymphedema. PLoS One 2012; 7: e50319
• 27 Neligan PC, Kung TA, Maki JH. MR lymphangiography in the treatment of lymphedema. J Surg Oncol 2017; 115: 18-22