Lymphatic abnormalities in the normal contralateral arms of subjects with breast cancer-related lymphedema as assessed by near-infrared fluorescent imaging

Abstract

Current treatment of unilateral breast cancer-related lymphedema (BCRL) is only directed to the afflicted arm. Near-infrared fluorescent imaging (NIRF) of arm lymphatic vessel architecture and function in BCRL and control subjects revealed a trend of increased lymphatic abnormalities in both the afflicted and unafflicted arms with increasing time after lymphedema onset. These pilot results show that BCRL may progress to affect the clinically "normal" arm, and suggest that cancer-related lymphedema may become a systemic, rather than local, malady. These findings support further study to understand the etiology of cancer-related lymphedema and lead to better diagnostics and therapeutics directed to the systemic lymphatic system.

Keywords: (110.0110) Imaging systems; (170.3880) Medical and biological imaging; (230.0230) Optical devices.

Fig. 1

System used for NIRF lymphatic imaging. (a) Each system consists of a 785-nm excitation light source, a NIR-sensitive image intensifier, and a customized charge-coupled device (CCD) camera outfitted with filters to selectively collect ICG fluorescence at 830 nm. The emitted excitation light covered a maximal tissue surface area of approximately 900 cm². Injected ICG typically entered lymphatic capillaries near injection sites, and then moved into pre-collector and collector lymphatic vessels in subject arms. (b) Indocyanine green (ICG) is injected intradermally for uptake by dermal lymphatic capillaries, which feed into lymphatic pre-collector and collector vessels.

Fig. 2

Near-infrared images of lymphatic vessels in (a) dorsal hand, (b) dorsal forearm, (c) ventral forearm, (d) medial elbow, and (e) axilla of a healthy control subject. Yellow scale bars = 5 cm.

Fig. 3

“Pumping,” or lymphatic propulsion, in a normal healthy control subject arm. Lymph “packets” are visible moving from valve to valve along lymphatic vessels Media 1. Shown are multiple lymphatic vessels in a normal, healthy control ventral forearm.

Fig. 4

Typical lymphatic architectural anomalies observed in BCRL subjects. (a) Hyperplasia/tortuous lymphatic vessels located on the medial elbow of a BCRL subject 13 years after onset (top) and the dorsal forearm of a subject 5 years after BCRL onset (bottom), (b) nonmobile extravascular ICG/hypoplasia on a dorsal hand of a subject 6 months after BCRL onset (top) and a dorsal forearm of a subject 6 months after BCRL onset (bottom), (c) mobile extravascular ICG/hypoplasia on the lateral forearm of a subject 6 months after BCRL onset (top) and on a medial elbow of a subject 6 months after BCRL onset (bottom), (d) punctuated ICG “clusters” located on the lateral forearm of a subject 5 years after BCRL onset (top) and on a lateral forearm of a subject 5 years after BCRL onset (bottom). Yellow scale bars = 5 cm.

Fig. 5

Unaffected and affected (b) arms from one subject in group 3 (5 years since BCRL onset). Blue arrows = tortuous vessels/hyperplasia, yellow arrows = nonmobile extravascular ICG, white arrows = mobile extravascular ICG. Yellow scale bars = 5 cm.

Fig. 6

Percent of images with architectural aberrations. Percent of (a) hands, (b) dorsal forearms, (c) ventral forearms, (d) medial elbows, and (e) axillary regions displaying lymphatic anomalies in groups 1 (6 months or less since onset), 2 (1-2 years since onset), and 3 (more than 5 years since onset).