[Show abstract][Hide abstract] ABSTRACT: Understanding lymph drainage patterns of the peritoneum could assist in staging and treatment of gastrointestinal and ovarian malignancies. Sentinel lymph nodes (SLNs) have been identified for solid organs and the pleural space. Our purpose was to determine whether the peritoneal space has a predictable lymph node drainage pattern.
Rats received intraperitoneal injections of near-infrared (NIR) fluorescent tracers: namely, quantum dots (designed for retention in SLNs) or human serum albumin conjugated with IRDye800 (HSA800; designed for lymphatic flow beyond the SLN). A custom imaging system detected NIR fluorescence at 10 and 20 minutes and 1, 4, and 24 hours after injection. To determine the contribution of viscera to peritoneal lymphatic flow, additional cohorts received bowel resection before NIR tracer injection. Associations with appropriate controls were assessed with the chi(2) test.
Quantum dots drained to the celiac, superior mesenteric, and periportal lymph node groups. HSA800 drained to these same groups at early time points but continued flowing to the mediastinal lymph nodes via the thoracic duct. After bowel resection, both tracers were found in the thoracic, not abdominal, lymph node groups. Additionally, HSA800 was no longer found in the thoracic duct but in the anterior chest wall and diaphragmatic lymphatics.
The peritoneal space drains to the celiac, superior mesenteric, and periportal lymph node groups first. Lymph continues via the thoracic duct to the mediastinal lymph nodes. Bowel lymphatics are a key determinant of peritoneal lymph flow, because bowel resection shifts lymph flow directly to the intrathoracic lymph nodes via chest wall lymphatics.
[Show abstract][Hide abstract] ABSTRACT: Sentinel lymph node (SLN) mapping is an important cancer surgery during which the first lymph node draining the site of a tumor is identified, resected, and analyzed for the presence or absence of malignant cells. Fluorescent semiconductor nanocrystals (quantum dots [QDs]) of the appropriate size, charge, and emission wavelength permit this surgery to be performed rapidly, with high sensitivity and under complete image guidance. We describe the materials and methods necessary for the production and characterization of type-II near-infrared fluorescent QDs, which have been optimized for SLN mapping. They contain a CdTe core, CdSe shell, and a highly anionic, oligomeric phosphine organic coating. We also describe how to utilize such QDs in animal model systems of SLN mapping.
[Show abstract][Hide abstract] ABSTRACT: We have incorporated fluorescent quantum dots (QDs) into polystyrene microspheres using functionalized oligomeric phosphine (OP) ligands. We find that a uniform distribution of quantum dots is loaded inside each polymer bead. Some local close-packing of quantum dots in the beads is attributed to the self-polymerization of the functionalized ligands. The presence of quantum dots disturbs the nucleation and growth processes during the formation of polymer microspheres and results in a wider size distribution of the quantum dot-embedded polystyrene beads than for the control without dots. The change in quantum efficiency of the quantum dots before (approximately 20%) and after (12%) loading into the beads substantiates the protection of oligomeric phosphine ligands yet indicates that the properties of these quantum dots are still affected during processing.
[Show abstract][Hide abstract] ABSTRACT: Because many gastrointestinal (GI) tumors spread by way of lymphatics, histological assessment of the first draining lymph nodes has both prognostic and therapeutic significance. However, sentinel lymph node mapping of the GI tract by using available techniques is limited by unpredictable drainage patterns, high background signal, and the inability to image lymphatic tracers relative to surgical anatomy in real time. Our goal was to develop a method for patient-specific intraoperative sentinel lymph node mapping of the GI tract by using invisible near-infrared light.
We developed an intraoperative near-infrared fluorescence imaging system that simultaneously displays surgical anatomy and otherwise invisible near-infrared fluorescence images of the surgical field. Near-infrared fluorescent quantum dots were injected intraparenchymally into the stomach, small bowel, and colon, and draining lymphatic channels and sentinel lymph nodes were visualized. Dissection was performed under real-time image guidance.
In 10 adult pigs, we demonstrated that 200 pmol of quantum dots quickly and accurately map lymphatic drainage and sentinel lymph nodes. Injection into the mid jejunum and colon results in fluorescence of a single lymph node at the root of the bowel mesentery. Injection into the stomach resulted in identification of a retrogastric node. Histological analysis in all cases confirmed the presence of nodal tissue.
We report the use of invisible near-infrared light for intraoperative sentinel lymph node mapping of the GI tract. This technology overcomes the limitations of currently available methods, permits patient-specific imaging of lymphatic flow and sentinel nodes, and provides highly sensitive, real-time image-guided dissection.
[Show abstract][Hide abstract] ABSTRACT: We have developed a size series of unusually small, water-soluble (InAs)ZnSe (core)shell quantum dots (QDs) that emit in the near-infrared and exhibit new behavior in vivo, including multiple sequential lymph node mapping and extravasation from the vasculature. The biological utility of these fluorescent probes resulted from our intentional choice to match the semiconductor material and water-soluble ligand with a desired final hydrodynamic diameter and emission wavelength.
Journal of the American Chemical Society 04/2006; 128(8):2526-7. DOI:10.1021/ja0579816 · 12.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quantum dots with a core/shell/shell structure consisting of an alloyed core of InAs(x)P(1-x), an intermediate shell of InP, and an outer shell of ZnSe were developed. The InAs(x)P(1-x) alloyed core has a graded internal composition with increasing arsenic content from the center to the edge of the dots. This compositional gradient results from two apparent effects: (1) the faster reaction kinetics of the phosphorus precursor compared to the arsenic precursor, and (2) a post-growth arsenic-phosphorus exchange reaction that increases the arsenic content. The cores have a zinc blend structure for all compositions and show tunable emission in the near-infrared (NIR) region. A first shell of InP leads to a red-shift and an increase in quantum yield. The final shell of ZnSe serves to stabilize the dots for applications in aqueous environments, including NIR biomedical fluorescence imaging. These NIR-emitting core/shell/shell InAs(x)P(1-x)/InP/ZnSe were successfully used in a sentinel lymph node mapping experiment.
Journal of the American Chemical Society 09/2005; 127(30):10526-32. DOI:10.1021/ja0434331 · 12.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the sentinel lymph node (SLN) concept has traditionally been applied to solid organs, we hypothesized that the pleural space might drain into a specific SLN group. The identification of such a nodal group could assist in the staging and treatment of pleural-based diseases, such as mesothelioma, or other lung cancers with visceral pleural invasion. The purpose of this study was to determine whether the pleural space has an SLN group.
Sixteen rats underwent right or left pleural space injection of a novel lymph tracer, quantum dots (QDs), which have a hydrodynamic diameter of 15 nm and fluoresce in the near-infrared (NIR) spectrum. Nodal uptake of the entire thorax was imaged with a custom system that simultaneously acquired color video, NIR fluorescence of the QDs, and a merged picture of the two in real-time. Six pigs underwent right or left pleural space injection of QDs and similar imaging.
In the rat, the QDs drained solely to the highest superior mediastinal lymph node group, corresponding to lymph node station 1, according the regional lymph node classification for lung of the American Joint Committee on Cancer. In one rat, the injection of QDs in the left pleural space resulted in migration to the contralateral station 1 lymph node group. The injection of QDs in the right or left pleural space of the pig resulted in migration solely to the ipsilateral highest superior mediastinal lymph node group.
NIR fluorescence imaging in two species demonstrated that the highest superior mediastinal lymph nodes of station 1 are the SLNs of the pleural space. This study also provides intraoperative feasibility and proof of the concept for identifying lymph nodes communicating with the pleural space on a patient-specific basis, in real-time, and with high sensitivity.
[Show abstract][Hide abstract] ABSTRACT: In esophageal cancer, selective removal of involved lymph nodes could improve survival and limit complications from extended lymphadenectomy. Mapping with vital blue dyes or technetium Tc-99m often fails to identify intrathoracic sentinel lymph nodes. Our purpose was to develop an intraoperative method for identifying sentinel lymph nodes of the esophagus with high-sensitivity near-infrared fluorescence imaging.
Six Yorkshire pigs underwent thoracotomy and received submucosal, esophageal injection of quantum dots, a novel near-infrared fluorescent lymph tracer designed for retention in sentinel lymph nodes. Six additional pigs underwent thoracotomy and received submucosal esophageal injection of CW800 conjugated to human serum albumin, another novel lymph tracer designed for uptake into distant lymph nodes. Finally, 6 pigs received submucosal injection of the fluorophore-conjugated albumin with an endoscopic needle through an esophagascope. These lymph tracers fluoresce in the near-infrared, permitting visualization of migration to sentinel lymph nodes with a custom intraoperative imaging system.
Injection of the near-infrared fluorescent lymph tracers into the esophagus revealed communicating lymph nodes within 5 minutes of injection. In all 6 pigs that received quantum dot injection, only a single sentinel lymph node was identified. Among pigs that received fluorophore-conjugated albumin injection, in 5 of 12 a single sentinel lymph node was revealed, but in 7 of 12 two sentinel lymph nodes were identified. There was no dominant pattern in the appearance of the sentinel lymph nodes either cranial or caudal to the injection site.
Near-infrared fluorescence imaging of sentinel lymph nodes is a novel and reliable intraoperative technique with the power to assist with identification and resection of esophageal sentinel lymph nodes.
Journal of Thoracic and Cardiovascular Surgery 05/2005; 129(4):844-50. DOI:10.1016/j.jtcvs.2004.08.001 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A phosphine oxide polymer was developed using bis(dichlorophosphino)ethane and poly(ethylene glycol). This polymer system was used to transfer various nanoparticles from organic solvents to water, retaining their physical properties and reactivities.
Journal of the American Chemical Society 05/2005; 127(13):4556-7. DOI:10.1021/ja043577f · 12.11 Impact Factor