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Annals of Biomedical Engineering

, Volume 40, Issue 2, pp 408–421 | Cite as

The Role of Lymphatics in Cancer as Assessed by Near-Infrared Fluorescence Imaging

  • John C. RasmussenEmail author
  • Sunkuk Kwon
  • Eva M. Sevick-Muraca
  • Janice N. Cormier
Article

Abstract

The lymphatic system is the secondary circulatory system responsible for fluid homeostasis and protein transport in the body. In addition, because the lymphatic system provides a primary pathway for cancer metastasis, lymph node involvement is routinely used as a determinant in cancer staging. Despite their importance, the lymphatics remain poorly understood, in part because of the historic lack of imaging modalities with sufficient spatial and/or temporal resolution to visualize the fine lymphatic structure and subtle contractile function. In recent years, near-infrared fluorescence (NIRF) imaging has emerged as a new imaging modality to non-invasively visualize the lymphatics and assess contractile lymphatic function in humans following administration of microdose amounts of a NIRF contrast agent. In this contribution, we first review NIRF imaging and its clinical application in sentinel lymph node mapping, intraoperative guidance, and assessing the architecture and contractile function of the lymphatics in health and in cancer-related lymphedema. We then present recent NIRF lymphatic imaging for non-invasive assessment of lymphatics both in preclinical melanoma models and in human subjects with melanoma.

Keywords

Imaging Near-infrared fluorescence Lymphatic Metastasis Lymphangiogenesis Optics 

Abbreviations

ICG

Indocyanine green

NIR

Near-infrared

NIRF

Near-infrared fluorescence

MRI

Magnetic resonance imaging

CCD

Charge coupled device

PET

Positron emission tomography

CT

X-ray computed tomography

p.i.

Post implantation

LN

Lymph node

SLN

Sentinel lymph node

MLD

Manual lymphatic drainage

GD

Gadobenate dimeglumine

ROI

Region of interest

FBS

Fetal bovine serum

IND

Investigational new drug application

IRB

Institutional review board

FDA

Food and Drug Administration

ICCD

Intensified charge coupled device

Notes

Acknowledgments

The authors acknowledge I-Chih Tan and Banghe Zhu for their technical contributions and Melissa B. Aldrich, Kristen E. Adams, Chinmay Darne, Caroline E. Fife, Renie Guilliod, Milton V. Marshall, Erik A. Maus, Latisha A. Smith, I-Chih Tan, and Banghe Zhu for insightful discussions and participation in the clinical studies. This work was supported in parts by grants from the U.S. National Institutes of Health, National Cancer Institute (R01 CA 128919), the National Cancer Institute Network for Translational Research (U54 CA136404), and the National Heart, Lung, and Blood Institute (R01 HL092923).

Conflict of interest

The authors report no financial conflicts of interest.

Supplementary material

10439_2011_476_MOESM1_ESM.avi (3.1 mb)
Supplementary material 1 (AVI 3149 kb)

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Copyright information

© Biomedical Engineering Society 2011

Authors and Affiliations

  • John C. Rasmussen
    • 1
    Email author
  • Sunkuk Kwon
    • 1
  • Eva M. Sevick-Muraca
    • 1
  • Janice N. Cormier
    • 2
  1. 1.Center for Molecular Imaging, The Brown Foundation Institute of Molecular MedicineThe University of Texas Health Science Center, HoustonHoustonUSA
  2. 2.The University of Texas M.D. Anderson Cancer CenterHoustonUSA

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