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, 79 (1), 269-77; discussion 269-77

Intraoperative Sentinel Lymph Node Mapping of the Lung Using Near-Infrared Fluorescent Quantum Dots

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Intraoperative Sentinel Lymph Node Mapping of the Lung Using Near-Infrared Fluorescent Quantum Dots

Edward G Soltesz et al. Ann Thorac Surg.

Abstract

Background: The presence of lymph node metastases is an important prognostic marker with regard to non-small-cell lung cancer (NSCLC). Assessment of the sentinel lymph node (SLN) for the presence of tumor may improve staging. Our objective was to develop an optical noninvasive imaging tool that would permit intraoperative SLN mapping and provide real-time visual feedback for image-guided localization and resection.

Methods: Invisible near-infrared (NIR) light penetrates relatively deeply into tissue and background autofluorescence is low. We have developed a NIR fluorescence imaging system that simultaneously displays color video and NIR images of the surgical field. We recently engineered 15 nm nonradioactive NIR fluorescent quantum dots (QDs) as optimal lymphotrophic optical probes. The introduction of these QDs into lung tissue allows real-time visualization of draining lymphatic channels and nodes.

Results: In 12 Yorkshire pigs (mean weight 35 kg) we demonstrated that 200 pmol of NIR QDs injected into lobar parenchyma accurately maps lymphatic drainage and the SLN. All SLNs were strongly fluorescent and easily visualized within 5 minutes of injection. In 14 separate injections QDs localized to a mediastinal node, whereas in 2 injections QDs localized to a hilar intraparenchymal node. Histologic analysis in all cases confirmed the presence of nodal tissue.

Conclusions: We report a highly sensitive rapid technique for SLN mapping of the lung. This technique permits precise real-time imaging and therefore overcomes many limitations of currently available techniques.

Figures

Fig 1
Fig 1
Intraoperative invisible near-infrared (NIR) fluorescence imaging system. View of the NIR fluorescence imaging system deployed in the operating room.
Fig 2
Fig 2
Sentinel lymph node (SLN) mapping of the right upper lung lobe in a pig using invisible near-infrared (NIR) fluorescent quantum dots (QDs). (A) Depicted from top to bottom are NIR fluorescence images of the surgical field before QD injection (autofluorescence), during QD injection, 45 seconds after injection (lung retracted), 1 minute after injection, and after SLN resection. For each time point, color video (left), NIR fluorescence (middle), and color-NIR merge (right) images are presented. Fluorescence images exhibit identical exposure times and normalization. QDs rapidly localize to the SLN (white arrow). Lack of fluorescence in the nodal basin after resection confirms complete removal of the sentinel nodal tissue. (B) NIR QD retention in the resected SLN compared with regional negative controls. (C) Histologic analysis of frozen sections of the SLN (B). Photomicrographs (×20 and ×40) illustrating the same field with representative hematoxylin and eosin (H + E)-stained sections and consecutive unstained sections photographed on a NIR fluorescence microscope.
Fig 2
Fig 2
Sentinel lymph node (SLN) mapping of the right upper lung lobe in a pig using invisible near-infrared (NIR) fluorescent quantum dots (QDs). (A) Depicted from top to bottom are NIR fluorescence images of the surgical field before QD injection (autofluorescence), during QD injection, 45 seconds after injection (lung retracted), 1 minute after injection, and after SLN resection. For each time point, color video (left), NIR fluorescence (middle), and color-NIR merge (right) images are presented. Fluorescence images exhibit identical exposure times and normalization. QDs rapidly localize to the SLN (white arrow). Lack of fluorescence in the nodal basin after resection confirms complete removal of the sentinel nodal tissue. (B) NIR QD retention in the resected SLN compared with regional negative controls. (C) Histologic analysis of frozen sections of the SLN (B). Photomicrographs (×20 and ×40) illustrating the same field with representative hematoxylin and eosin (H + E)-stained sections and consecutive unstained sections photographed on a NIR fluorescence microscope.
Fig 3
Fig 3
Modified lung schematic. Mapping of sentinel lymph nodes (SLNs) in the pig lung. Invisible near-infrared quantum dots were injected into the right and left upper and lower lobes. A mediastinal SLN was identified after 14 injections (X), whereas an intraparenchymal hilar SLN was identified after 2 injections (Y). (Reprinted with modification from [1] by permission of The C. V. Mosby Co.)
Fig 4
Fig 4
Isosulfan blue colocalization. (A) Depicted from top to bottom are invisible near-infrared (NIR) fluorescence images of the surgical field during quantum dot (QD) injection, 1 minute after QD injection (just before isosulfan blue injection), and 5 minutes after QD injection (i.e., 4 minutes after isosulfan blue injection). For each time point, color video (left), NIR fluorescence (middle), and color-NIR merge (right) images are presented. Fluorescence images exhibit identical exposure times and normalization. QDs rapidly localize to the sentinel lymph node (S) from their injection site (I). Coinjection of isosulfan blue (90 seconds after QD injection) quenches the QD fluorescence as evidenced by the loss of QD fluorescence at 5 minutes. Isosulfan blue colocalizes to the same lymph node as the QDs (S). (B) NIR QD and isosulfan blue retention (arrow) in the resected sentinel lymph node.

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