Imaging of Lymph Flow in Breast Cancer Patients after Microdose Administration of a Near-Infrared Fluorophore: Feasibility Study1
Identifieur interne : 006A83 ( Main/Exploration ); précédent : 006A82; suivant : 006A84Imaging of Lymph Flow in Breast Cancer Patients after Microdose Administration of a Near-Infrared Fluorophore: Feasibility Study1
Auteurs : 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 Elledge ; Michel E. MawadSource :
- Radiology [ 0033-8419 ] ; 2008.
Abstract
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).
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
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.
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.
Url:
DOI: 10.1148/radiol.2463070962
PubMed: 18223125
PubMed Central: 3166516
Affiliations:
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Sevick-Muraca</name></author><author><name sortKey="Sharma, Ruchi" sort="Sharma, Ruchi" uniqKey="Sharma R" first="Ruchi" last="Sharma">Ruchi Sharma</name></author><author><name sortKey="Rasmussen, John C" sort="Rasmussen, John C" uniqKey="Rasmussen J" first="John C." last="Rasmussen">John C. Rasmussen</name></author><author><name sortKey="Marshall, Milton V" sort="Marshall, Milton V" uniqKey="Marshall M" first="Milton V." last="Marshall">Milton V. Marshall</name></author><author><name sortKey="Wendt, Juliet A" sort="Wendt, Juliet A" uniqKey="Wendt J" first="Juliet A." last="Wendt">Juliet A. Wendt</name></author><author><name sortKey="Pham, Hoang Q" sort="Pham, Hoang Q" uniqKey="Pham H" first="Hoang Q." last="Pham">Hoang Q. Pham</name></author><author><name sortKey="Bonefas, Elizabeth" sort="Bonefas, Elizabeth" uniqKey="Bonefas E" first="Elizabeth" last="Bonefas">Elizabeth Bonefas</name></author><author><name sortKey="Houston, Jessica P" sort="Houston, Jessica P" uniqKey="Houston J" first="Jessica P." last="Houston">Jessica P. Houston</name></author><author><name sortKey="Sampath, Lakshmi" sort="Sampath, Lakshmi" uniqKey="Sampath L" first="Lakshmi" last="Sampath">Lakshmi Sampath</name></author><author><name sortKey="Adams, Kristen E" sort="Adams, Kristen E" uniqKey="Adams K" first="Kristen E." last="Adams">Kristen E. Adams</name></author><author><name sortKey="Blanchard, Darlene Kay" sort="Blanchard, Darlene Kay" uniqKey="Blanchard D" first="Darlene Kay" last="Blanchard">Darlene Kay Blanchard</name></author><author><name sortKey="Fisher, Ronald E" sort="Fisher, Ronald E" uniqKey="Fisher R" first="Ronald E." last="Fisher">Ronald E. 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Mawad</name></author></analytic><series><title level="j">Radiology</title><idno type="ISSN">0033-8419</idno><idno type="eISSN">1527-1315</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Purpose</title><p id="P1">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).</p></sec><sec sec-type="materials|methods" id="S2"><title>Materials and Methods</title><p id="P2">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 <italic>(a)</italic> the time elapsed between NIR fluorophore administration and resection and <italic>(b)</italic> the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively.</p></sec><sec id="S3"><title>Results</title><p id="P3">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.</p></sec><sec id="S4"><title>Conclusion</title><p id="P4">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.</p></sec></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Adams, Kristen E" sort="Adams, Kristen E" uniqKey="Adams K" first="Kristen E." last="Adams">Kristen E. Adams</name><name sortKey="Blanchard, Darlene Kay" sort="Blanchard, Darlene Kay" uniqKey="Blanchard D" first="Darlene Kay" last="Blanchard">Darlene Kay Blanchard</name><name sortKey="Bonefas, Elizabeth" sort="Bonefas, Elizabeth" uniqKey="Bonefas E" first="Elizabeth" last="Bonefas">Elizabeth Bonefas</name><name sortKey="Chiang, Stephen B" sort="Chiang, Stephen B" uniqKey="Chiang S" first="Stephen B." last="Chiang">Stephen B. Chiang</name><name sortKey="Elledge, Richard" sort="Elledge, Richard" uniqKey="Elledge R" first="Richard" last="Elledge">Richard Elledge</name><name sortKey="Fisher, Ronald E" sort="Fisher, Ronald E" uniqKey="Fisher R" first="Ronald E." last="Fisher">Ronald E. Fisher</name><name sortKey="Houston, Jessica P" sort="Houston, Jessica P" uniqKey="Houston J" first="Jessica P." last="Houston">Jessica P. Houston</name><name sortKey="Marshall, Milton V" sort="Marshall, Milton V" uniqKey="Marshall M" first="Milton V." last="Marshall">Milton V. Marshall</name><name sortKey="Mawad, Michel E" sort="Mawad, Michel E" uniqKey="Mawad M" first="Michel E." last="Mawad">Michel E. Mawad</name><name sortKey="Pham, Hoang Q" sort="Pham, Hoang Q" uniqKey="Pham H" first="Hoang Q." last="Pham">Hoang Q. Pham</name><name sortKey="Rasmussen, John C" sort="Rasmussen, John C" uniqKey="Rasmussen J" first="John C." last="Rasmussen">John C. Rasmussen</name><name sortKey="Sampath, Lakshmi" sort="Sampath, Lakshmi" uniqKey="Sampath L" first="Lakshmi" last="Sampath">Lakshmi Sampath</name><name sortKey="Sevick Muraca, Eva M" sort="Sevick Muraca, Eva M" uniqKey="Sevick Muraca E" first="Eva M." last="Sevick-Muraca">Eva M. Sevick-Muraca</name><name sortKey="Sharma, Ruchi" sort="Sharma, Ruchi" uniqKey="Sharma R" first="Ruchi" last="Sharma">Ruchi Sharma</name><name sortKey="Wendt, Juliet A" sort="Wendt, Juliet A" uniqKey="Wendt J" first="Juliet A." last="Wendt">Juliet A. 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