Edward G. Soltesz

Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping

The use of near-infrared or infrared photons is a promising approach for biomedical imaging in living tissue. This technology often requires exogenous contrast agents with combinations of hydrodynamic diameter, absorption, quantum yield and stability that are not possible with conventional organic fluorophores. Here we show that the fluorescence emission of type II quantum dots can be tuned into the near infrared while preserving absorption cross-section, and that a polydentate phosphine coating renders them soluble, disperse and stable in serum. We then demonstrate that these quantum dots allow a major cancer surgery, sentinel lymph node mapping, to be performed in large animals under complete image guidance. Injection of only 400 pmol of near-infrared quantum dots permits sentinel lymph nodes 1 cm deep to be imaged easily in real time using excitation fluence rates of only 5 mW/cm2. Taken together, the chemical, optical and in vivo data presented in this study demonstrate the potential of near-infrared quantum dots for biomedical imaging.

Sentinel Lymph Node Mapping of the Gastrointestinal Tract by Using Invisible Light

BackgroundBecause 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.MethodsWe 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.ResultsIn 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.ConclusionsWe 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.

Lymphatic drainage of the peritoneal space: a pattern dependent on bowel lymphatics.

BackgroundUnderstanding 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.MethodsRats 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 χ2 test.ResultsQuantum 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.ConclusionsThe 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.

Minimally invasive valve surgery.

Minimally invasive heart valve surgery has evolved significantly over the past 10 years and now comprises safe and efficient operations for most patients. The main goals of minimally invasive heart valve surgery are to reduce surgical trauma, increase patient satisfaction, reduce morbidity, and lower costs while still providing durable and safe valve repair or replacement. After a decade of refinements, studies have shown that minimally invasive heart valve surgery is a safe and effective procedure with similar if not improved perioperative morbidity and mortality rates compared with conventional valve surgery. Patients derive a variety of tangible benefits from these new surgical approaches, including less pain, shorter lengths of hospital stay, and faster return to preoperative functional levels. Minimally invasive heart valve surgery should be an option for any patient undergoing heart valve surgery today.

In vivo optical imaging of pleural space drainage to lymph nodes of prognostic significance.

AbstractBackground: 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.

Transcriptional profiling and growth kinetics of endothelium reveals differences between cells derived from porcine aorta versus aortic valve

OBJECTIVE Valvular tissue and aorta calcify at different rates when placed as fresh homografts or cryopreserved allografts. Furthermore, differences between valvular endothelial cells and aortic endothelial cells are not well appreciated. We established primary cultures of valve and aortic endothelial cells derived from swine and tested transcriptional and proliferative differences on various extracellular matrices. METHODS Transcriptional profiling was performed on primary cultures of porcine valve and aortic endothelial cells. We extracted total RNA from both cell types and created cDNA libraries. We scored for 847 genes important in signal transduction pathways, and measured their expression on valve and aortic endothelial cells. To determine if there were functional differences between aortic and valvular cells, their growth rate was determined by cell counting on various extracellular matrices. RESULTS Of 847 genes investigated, 69 (8.1%) were transcriptionally active on aortic endothelial cells and 89 (10.5%) on valve endothelial cells. Common to both cell types were 55 genes, which represents 79.7% (55/69) of activated genes on aortic endothelial cells and 61.8% (55/89) of those in valve endothelial cells. Remarkable features of the analysis included Ephrin ligand and receptor specificity for cell type, a potential fibroblast growth factor autocrine loop in both cell types, as well as upregulation of the platelet-derived growth factor receptor in valvular cells. Aortic endothelial cells were noteworthy of upregulation of vascular endothelial cell growth factor-B and vascular cell adhesion molecule. Proliferation analysis revealed that valve endothelial cells grew more rapidly (12-fold over control) than aortic endothelial cells (3-fold over control). Furthermore, valve endothelial cells proliferated most rapidly on gelatin or collagen, whereas aortic endothelial cells were most proliferative on lysine or laminin. CONCLUSIONS Valve and aortic endothelial cells have different transcriptional and proliferative profiles. The knowledge of these differences may be an exploitable strategy in the future rational design of artificially engineered valve surfaces and in the study of the valve antigenicity, immunogenicity and structural failure.

Image-Guided Quantification of Cardioplegia Delivery during Cardiac Surgery

BACKGROUND Homogenous distribution of cardioplegia delivered to the myocardium has been identified as an important predictor of post-cardiopulmonary bypass ventricular recovery and function. Presently, a method to determine adequate distribution of cardioplegia in patients during cardiac surgery does not exist. The goal of this study was to evaluate the feasibility of quantifying cardioplegia delivery using a novel, noninvasive optical method. Such a system would permit instantaneous imaging of jeopardized myocardium and allow immediate, intraoperative corrective measures. METHODS We have previously developed a portable, intraoperative near-infrared (NIR) fluorescence imaging system for use in large animal cardiac surgery that simultaneously displays color video and NIR fluorescent images of the surgical field. By introducing exogenous, NIR fluorophores, specific cardiac functions can be visualized in real-time. RESULTS In a porcine cardiopulmonary bypass model, we demonstrate that the FDA-approved intravascular fluorophore indocyanine green (ICG) permits real-time assessment of cardioplegia delivery. ICG was injected into an aortic root and/or transatrial coronary sinus catheter during delivery of crystalloid cardioplegia solution. Segmental distribution was immediately noted at the time of injection. In a subset of animals, simulated coronary occlusions resulted in imaging defects consistent with poor cardioplegia delivery and jeopardized myocardium. Videodensitometric analysis was performed on-line to quantify distribution to the right ventricle and left ventricle. CONCLUSION We report the development of a novel, noninvasive, intraoperative technique that can easily and safely provide a visual assessment of cardioplegia delivery (antegrade and/or retrograde) and that offers the potential to quantify the relative segmental distribution during cardiac surgical procedures.

Valve Surgery in Octogenarians with a “Porcelain” Aorta and Aortic Insufficiency

Abstract  We report the technique of balloon occlusion of the ascending aorta in two patients requiring valve operations. In the first patient, it provided a rapid solution to unexpected and potentially catastrophic severe aortic insufficiency (Al) with the initiation of cardiopulmonary bypass in a patient who required aortic valve replacement using deep hypothermic circulatory arrest due to a “porcelain” aorta. In the second patient, it allowed for a routine mitral valve repair to be performed by providing aortic occlusion in the setting of Al and avoiding the devastating consequences of cross‐clamping a “porcelain” aorta.

Atrial fibrillation in the patient undergoing mitral valve surgery: A once-in-a-lifetime opportunity

From the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio. Disclosures: M.G. has served as a consultant to AtriCure, Medtronic, Edwards Lifesciences, CryoLife, and Abbott. E.G.S. has served as a consultant to Abbott. Received for publication Sept 27, 2017; accepted for publication Sept 27, 2017; available ahead of print Oct 28, 2017. Address for reprints: Marc Gillinov, MD, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Desk J4-1, 9500 Euclid Ave, Cleveland, OH 44195 (E-mail: gillinom@ccf.org). J Thorac Cardiovasc Surg 2018;155:995-6 0022-5223/

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

36.00 Copyright 2017 by The American Association for Thoracic Surgery https://doi.org/10.1016/j.jtcvs.2017.09.125