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In Vivo Optical Imaging of Pleural Space Drainage to Lymph Nodes of Prognostic Significance

From the Department of Surgery (CPP, RL, EGS, YLC, TM, LHC), Brigham & Women’s Hospital; and Division of Hematology/Oncology and Department of Radiology (SO, AMD, JVF) and Department of Cardiology (PK), Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Correspondence: Address correspondence and reprint requests to: John V. Frangioni, M.D., Ph.D., Division of Hematology/Oncology and Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room SL-B05, Boston, MA 02215; Fax: 617-667-0981; e-mail: jfrangio{at}bidmc.harvard.edu

Background: Understanding the spatial and temporal drainage patterns of the pleural space could have profound impact on the treatment of lung cancer and mesothelioma. The purpose of this study was to identify the in vivo pattern of drainage from the pleural space to prognostic lymph node stations.

Methods: Fifty-six rats underwent pleural space injection of a novel lymph tracer composed of recombinant human serum albumin (HSA) covalently conjugated to the near-infrared (NIR) fluorophore IRDye78 via an amide bond (HSA-78). Nodal uptake was imaged at 10, 20, 30, and 60 minutes and 4, 12, and 24 hours after injection with a custom system that simultaneously acquires color video, NIR fluorescence of HSA-78, and a merged picture of the two. Six pigs underwent the same procedure with imaging at 30 minutes, 1 hour, and 24 hours.

Results: In both the rat model and the pig model, HSA-78 drained from the pleural space to superior mediastinal lymph nodes first, followed by other intrathoracic and then extrathoracic lymph nodes over the course of 24 hours.

Conclusion: NIR fluorescence imaging in two species shows that the superior mediastinal lymph nodes are the first to drain the pleural space. Over the course of 24 hours, the pleural space also communicates with other intrathoracic and then extrathoracic lymph nodes. This study also demonstrates an intraoperative method for identifying nodes communicating with the pleural space, with potential utility in the staging and/or resection of lung cancer and mesothelioma.

Key Words: Lymph node • Lymphatic drainage • Mesothelioma • Near-infrared fluorescence • Pleural space • Visceral pleural invasion

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