Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: Feasibility study

Eva M. Sevick-Muraca, Ruchi Sharma, John C. Rasmussen, Milton V. Marshall, Juliet A. Wendt, Hoang Q. Pham, Elizabeth Bonefas, Jessica P. Houston, Lakshmi Sampath, Kristen E. Adams, Darlene Kay Blanchard, Ronald E. Fisher, Stephen B. Chiang, Richard M Elledge, Michel E. Mawad

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

Purpose: To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods: Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results: Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. Conclusion: NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.

Original languageEnglish (US)
Pages (from-to)734-741
Number of pages8
JournalRadiology
Volume246
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

Feasibility Studies
Lymph
Lymph Nodes
Breast Neoplasms
Indocyanine Green
Fluorescence
Axilla
Breast
Optical Imaging
Lymphoscintigraphy
Health Insurance Portability and Accountability Act
Intradermal Injections
Sternum
Molecular Imaging
Research Ethics Committees
Subcutaneous Injections
Informed Consent
Radioactivity
Drainage
Coloring Agents

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Sevick-Muraca, E. M., Sharma, R., Rasmussen, J. C., Marshall, M. V., Wendt, J. A., Pham, H. Q., ... Mawad, M. E. (2008). Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: Feasibility study. Radiology, 246(3), 734-741. https://doi.org/10.1148/radiol.2463070962

Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore : Feasibility study. / Sevick-Muraca, Eva M.; Sharma, Ruchi; Rasmussen, John C.; Marshall, Milton V.; Wendt, Juliet A.; Pham, Hoang Q.; Bonefas, Elizabeth; Houston, Jessica P.; Sampath, Lakshmi; Adams, Kristen E.; Blanchard, Darlene Kay; Fisher, Ronald E.; Chiang, Stephen B.; Elledge, Richard M; Mawad, Michel E.

In: Radiology, Vol. 246, No. 3, 03.2008, p. 734-741.

Research output: Contribution to journalArticle

Sevick-Muraca, EM, Sharma, R, Rasmussen, JC, Marshall, MV, Wendt, JA, Pham, HQ, Bonefas, E, Houston, JP, Sampath, L, Adams, KE, Blanchard, DK, Fisher, RE, Chiang, SB, Elledge, RM & Mawad, ME 2008, 'Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: Feasibility study', Radiology, vol. 246, no. 3, pp. 734-741. https://doi.org/10.1148/radiol.2463070962
Sevick-Muraca, Eva M. ; Sharma, Ruchi ; Rasmussen, John C. ; Marshall, Milton V. ; Wendt, Juliet A. ; Pham, Hoang Q. ; Bonefas, Elizabeth ; Houston, Jessica P. ; Sampath, Lakshmi ; Adams, Kristen E. ; Blanchard, Darlene Kay ; Fisher, Ronald E. ; Chiang, Stephen B. ; Elledge, Richard M ; Mawad, Michel E. / Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore : Feasibility study. In: Radiology. 2008 ; Vol. 246, No. 3. pp. 734-741.
@article{77a40c54f959430190ab9be1b20e2dbe,
title = "Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: Feasibility study",
abstract = "Purpose: To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods: Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results: Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between {"}packets{"} of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. Conclusion: NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.",
author = "Sevick-Muraca, {Eva M.} and Ruchi Sharma and Rasmussen, {John C.} and Marshall, {Milton V.} and Wendt, {Juliet A.} and Pham, {Hoang Q.} and Elizabeth Bonefas and Houston, {Jessica P.} and Lakshmi Sampath and Adams, {Kristen E.} and Blanchard, {Darlene Kay} and Fisher, {Ronald E.} and Chiang, {Stephen B.} and Elledge, {Richard M} and Mawad, {Michel E.}",
year = "2008",
month = "3",
doi = "10.1148/radiol.2463070962",
language = "English (US)",
volume = "246",
pages = "734--741",
journal = "Radiology",
issn = "0033-8419",
publisher = "Radiological Society of North America Inc.",
number = "3",

}

TY - JOUR

T1 - Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore

T2 - Feasibility study

AU - Sevick-Muraca, Eva M.

AU - Sharma, Ruchi

AU - Rasmussen, John C.

AU - Marshall, Milton V.

AU - Wendt, Juliet A.

AU - Pham, Hoang Q.

AU - Bonefas, Elizabeth

AU - Houston, Jessica P.

AU - Sampath, Lakshmi

AU - Adams, Kristen E.

AU - Blanchard, Darlene Kay

AU - Fisher, Ronald E.

AU - Chiang, Stephen B.

AU - Elledge, Richard M

AU - Mawad, Michel E.

PY - 2008/3

Y1 - 2008/3

N2 - Purpose: To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods: Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results: Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. Conclusion: NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.

AB - Purpose: To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods: Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results: Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. Conclusion: NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.

UR - http://www.scopus.com/inward/record.url?scp=40949113163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40949113163&partnerID=8YFLogxK

U2 - 10.1148/radiol.2463070962

DO - 10.1148/radiol.2463070962

M3 - Article

C2 - 18223125

AN - SCOPUS:40949113163

VL - 246

SP - 734

EP - 741

JO - Radiology

JF - Radiology

SN - 0033-8419

IS - 3

ER -