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Curadel Llc and Beth Israel Deaconess Medical Center | Date: 2012-01-17

Contrast agents for use in surgical and medical imaging and visualization; Fluorescent contrast agents for use in surgical and medical imaging and visualization; Exogenous contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical and medical imaging and visualization; Exogenous near-infrared contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical procedures; Exogenous near-infrared contrast agents for use in surgical procedures; Near-infrared contrast agents for use in medical imaging and visualization; Exogenous near-infrared contrast agents for use in medical imaging and visualization; Near-infrared contrast agents for use in real-time surgical imaging and visualization; Exogenous near-infrared contrast agents for use in real-time surgical imaging and visualization, none of the foregoing being ophthalmic preparations, otorhinolaryngological preparations, or preparations for the treatment of inflammation. Medical and surgical equipment for use in surgical procedures, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical procedures, namely, cameras and near-infrared cameras; Medical and surgical equipment for use in medical imaging and visualization, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical imaging and visualization, namely, visual wavelength imaging cameras, ultraviolet wavelength imaging cameras, radioscintigraphic detection hardware, optical lenses, image detectors, light sources, monitors, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical imaging and visualization, namely, cameras and near-infrared cameras; Medical and surgical equipment for use in real-time surgical imaging and visualization, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in real-time surgical imaging and visualization, namely, cameras and near-infrared cameras; Medical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Surgical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time medical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time surgical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Oncological imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time oncological imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit. Tools for use in the instruction of medical imaging and visualization, namely, imaging phantoms in the nature of replications of human or animal body parts or tissue, anatomical replicas of human bodies, anatomical replicas of animal bodies, synthetic organs and tissue for instructional use.


Hyun H.,Beth Israel Deaconess Medical Center | Hyun H.,Chonnam National University | Owens E.A.,Georgia State University | Wada H.,Beth Israel Deaconess Medical Center | And 9 more authors.
Angewandte Chemie - International Edition | Year: 2015

A novel class of near-infrared fluorescent contrast agents was developed. These agents target cartilage with high specificity and this property is inherent to the chemical structure of the fluorophore. After a single low-dose intravenous injection and a clearance time of approximately 4 h, these agents bind to all three major types of cartilage (hyaline, elastic, and fibrocartilage) and perform equally well across species. Analysis of the chemical structure similarities revealed a potential pharmacophore for cartilage targeting. Our results lay the foundation for future improvements in tissue engineering, joint surgery, and cartilage-specific drug development. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Hyun H.,Beth Israel Deaconess Medical Center | Wada H.,Beth Israel Deaconess Medical Center | Bao K.,Beth Israel Deaconess Medical Center | Gravier J.,Beth Israel Deaconess Medical Center | And 7 more authors.
Angewandte Chemie - International Edition | Year: 2014

The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. A new strategy is based on the incorporation of targeting moieties into the non-delocalized structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals in a model system, two families of bifunctional molecules that target bone without requiring a traditional bisphosphonate are synthesized. With peak fluorescence emissions at approximately 700 or 800 nm, these molecules can be used for fluorescence-assisted resection and exploration (FLARE) dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near-infrared fluorophores remain stable in bone for over five weeks, and histological analysis confirms their incorporation into the bone matrix. Taken together, a new strategy for creating ultra-compact, targeted near-infrared fluorophores for various bioimaging applications is described. Bifunctional molecules with high-affinity binding to bone minerals as well as bright near-infrared fluorescence were obtained by attaching low-affinity pendant groups to the non-delocalized backbone of polymethines. These agents enable the noninvasive assessment of bone development over the course of weeks in living animals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Hyun H.,Beth Israel Deaconess Medical Center | Park M.H.,Beth Israel Deaconess Medical Center | Park M.H.,Chonnam National University | Owens E.A.,Georgia State University | And 8 more authors.
Nature Medicine | Year: 2015

The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake into these glands after a single intravenous (IV) injection of 0.06 mg kg â '1 in a pig. By using a dual-channel NIR imaging system, we observed - in real time and with high sensitivity - the unambiguous distinction of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays a foundation for performing head and neck surgery with increased precision and efficiency along with potentially lower morbidity, and it provides a general strategy for developing targeted NIR fluorophores. Source


Tummers Q.R.J.G.,Leiden University | Schepers A.,Leiden University | Hamming J.F.,Leiden University | Kievit J.,Leiden University | And 4 more authors.
Surgery (United States) | Year: 2015

Background Identification of diseased and normal parathyroid glands during parathyroid surgery can be challenging. The aim of this study was to assess whether near-infrared (NIR) fluorescence imaging using administration of a low-dose Methylene Blue (MB) at the start of the operation could provide optical guidance during parathyroid surgery and assist in the detection of parathyroid adenomas. Methods Patients diagnosed with primary hyperparathyroidism planned for parathyroidectomy were included. Patients received 0.5 mg/kg MB intravenously directly after start of anesthesia. During the operation, NIR fluorescence imaging was performed to identify parathyroid adenomas. Imaging results were compared with a previous published feasibility study in which 12 patients received MB after intraoperative identification of the adenoma. Results A total of 13 patients were included in the current study. In 10 of 12 patients with a histologically proven adenoma, the adenoma was fluorescent. Mean signal to background ratio was 3.1 ± 2.8. Mean diameter of the resected lesions was 17 ± 9 mm (range 5-28 mm). Adenomas could be identified up to 145 minutes after administration, which was the longest timespan until resection. Interestingly, in 3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with a signal to background ratio of 1.8 ± 0.4 were identified using NIR fluorescence imaging. Conclusion Early administration of low-dose MB provided guidance during parathyroidectomy by identifying both parathyroid adenomas and normal parathyroid glands. In patients in whom difficult identification of the parathyroid adenoma is expected or when normal glands have to be identified, the administration of MB may improve surgical outcome. © 2015 Elsevier Inc. Source

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