SBIR-STTR Award

Postsurgical hypoparathyroidism or hypocalcemia are known to frequently occur after all thyroid surgeries due to misidentification and/or accidental disruption of the blood supply to the healthy parathyroid glands. Such accidental removal or injury of the parathyroid glands may lead to complications that result in lifelong sequelae. Because of the small size, variable position, and similar appearance to the surrounding tissues such as the lymph node, fat, and thyroid gland, it is often difficult for low-volume surgeons to distinguish the parathyroid glands from the thyroid tissue. Furthermore, blood supply to the parathyroid glands is fragile and can be easily damaged during dissection. This is a challenging problem because it is clinically difficult to tell by visual inspection if a gland is still viable after manipulation. Currently, there is no standardized or practical equipment available to localize and assess the parathyroid gland viability in real time and in a noninvasive manner during operation. Thus, any viable solution would be considered significant to the endocrine community. In this study, to address these unmet clinical needs, we propose to develop a noninvasive, dual- sensor RGB/NIR handheld imager that will potentially be a paradigm changing tool for patients with thyroid tumors. Our imaging solution, called hANDY-i™, permits 1) noninvasive parathyroid gland identification and 2) seamless display of tissue viability in real time for the preservation of the parathyroid glands during thyroid surgery. This research will be a joint effort combining the technical and clinical expertise of Optosurgical LLC and Johns Hopkins Hospital. To test this hypothesis, we will study the following specific aims: Aim1: To characterize and deliver a compact, operating room-ready hANDY-i device; and Aim 2: To validate hANDY-i to identify the parathyroid glands and assess viability in an early feasibility study (N=10). Upon successful completion of this SBIR Phase I project, we will proceed to the Phase II project, wherein we will engineer a commercial-grade version of the hANDY-i device and execute large-scale multicenter clinical trials. We envision that our technology will open a new door for the digital imaging paradigm of dye-free, temporally unlimited, and quantitative tissue perfusion assessment. Successful translation of this technology will potentially reduce the risk of hypoparathyroidism during thyroid surgery and improve clinical outcomes.

Public Health Relevance Statement:
Narrative The parathyroid glands are small tissues in the neck that play a key role in maintaining the calcium levels in the body. In thyroid surgery, serious complications such as postsurgical hypocalcemia (low calcium levels in the blood plasma) can occur when one or more parathyroid glands are unintentionally injured or removed because of their small size and appearance similar to that of the surrounding tissues. We propose to develop a portable, noninvasive camera to aid surgeons in effectively and safely preserving the parathyroid glands during operation, thus optimizing surgical decision-making and ultimately contributing to improved outcomes.

Project Terms:
Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; Angiography; Angiogram; angiographic imaging; Attention; Calcium; Clinical Research; Clinical Study; Color; Communities; Complication; Decision Making; Diagnosis; Dissection; Dyes; Coloring Agents; Engineering; Equipment; Fatty acid glycerol esters; Fats; Feasibility Studies; Fluorescent Dyes; Fluorescence Agents; Fluorescent Agents; fluorescent dye/probe; Goals; Hospitals; Hypocalcemia result; Hypocalcemia; Hypoparathyroidism; Indocyanine Green; Ujoveridin; Wofaverdin; Joints; Lead; Pb element; heavy metal Pb; heavy metal lead; Light; Photoradiation; lymph nodes; Lymph Node Reticuloendothelial System; Lymph node proper; Lymphatic nodes; lymph gland; lymphnodes; Medical Device; Muscle; Muscle Tissue; muscular; Neck; Operating Rooms; Optics; optical; Parathyroid gland; Parathyroid; Parathyroid Head and Neck; Patients; Perfusion; Plasma; Blood Plasma; Plasma Serum; Reticuloendothelial System, Serum, Plasma; Play; Postoperative Period; Post-Operative; Postoperative; Research; research and development; Development and Research; R & D; R&D; Risk; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Standardization; Technology; Testing; Thyroid Diseases; Thyroid Gland Disease; Thyroid Gland Disorder; thyroid disorder; Thyroid Gland; Thyroid; Thyroid Head and Neck; thyroid neoplasm; Thyroid Gland Neoplasm; Thyroid Gland Tumor; Thyroid Tumor; Thyroidectomy; Time; Tissues; Body Tissues; Translating; Translations; Autologous Transplantation; Autograft; Autotransplant; autologous graft; autotransplantation; Vascularization; Imaging Techniques; Imaging Procedures; Imaging Technics; Unintentional Injury; Accidental Injury; injuries; Injury; Label; sensor; improved; Clinical; Phase; Blood flow; insight; Visual; tool; In Situ; Techniques; System; Endocrine; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; Surgeon; computer imaging; digital imaging; Performance; novel technologies; new technology; Devices; Appearance; Abscission; Extirpation; Removal; Surgical Removal; resection; Excision; Position; Positioning Attribute; portability; blood supply; vascular supply; Vascular blood supply; intra-operative imaging; intraoperative imaging; surgical imaging; Image-Guided Surgery; µfluidic; Microfluidics; Gland; Address; Tissue Viability; Economic Burden; Imaging Instrument; Imaging Tool; Imaging Device; Multi-center clinical trial; Multi-site clinical trial; Multicenter clinical trial; Multisite clinical trial; Multi-Institutional Clinical Trial; Resolution; Surgical Management; Thyroid Gland Tissue; SBIR; Small Business Innovation Research; Small Business Innovation Research Grant; Resected; developmental; Development; Allergic Reaction; imaging; Image; preclinical; pre-clinical; feeding; digital; designing; design; Outcome; optical sensor; prototype; adverse consequence; adverse outcome; operation; NIR imaging; NIR optical imaging; Near-infrared Fluorescence Imaging; near infrared imaging; Near-infrared optical imaging; imaging platform; contrast imaging; improved outcome; clinical translation; sensing technology; sensor technology; Injections; preservation; imager

Post-surgical hypoparathyroidism or hypocalcemia are known to occur frequently after thyroid surgeries due to the misidentification and/or accidental removal of healthy parathyroid glands. Approximately 150,000 thyroidectomies are performed in the US, 27% of these patients suffer from transient or permanent hypocalcemia, which can lead to lifelong sequelae and socioeconomic burden. Because of the small size, the variable position, and the similar appearance to the surrounding tissues such as lymph node, fat, and thyroid gland, it is often difficult for low volume surgeons to distinguish parathyroid glands from thyroid tissue. Furthermore, blood supply to parathyroid glands is fragile and can be damaged easily during dissection. This is a challenging problem because it is clinically hard to tell by visual inspection if a gland is still viable after manipulation. There are currently no standardized or practical equipment available to localize and assess viability of parathyroid glands in real time and in a non-invasive manner during operation. Thus, any viable solution would be considered as significant to the endocrine community. In this research, we propose to develop a non-invasive, handheld imager that will potentially be a paradigm changing tool for patients with thyroid tumors. Our imaging solution, called hANDY-iTM, will permit 1) a non-invasive parathyroid gland identification and 2) seamless display of tissue viability in real-time for the preservation of the parathyroid glands during thyroid surgery. This research will be a joint effort combining the technical and clinical expertise of Optosurgical, LLC and Johns Hopkins Hospital. To validate our hypothesis, we will study the following specific aims; Aim1: Clinically viable prototype development; Aim 2: Clinical trials to validate the proposed system (N=64); Aim3: Premarket device evaluation. We envision that our technology will open a new door for the digital imaging paradigm of dye-free, temporally unlimited, and precise parathyroid detection and preservation. Successful translation of this technology will potentially reduce the risk of hypoparathyroidism during thyroid surgery and improve the clinical outcomes.

Public Health Relevance Statement:
Narrative The parathyroid glands are small tissues in the neck that play a key role in maintaining calcium levels of the body. In thyroid surgery, serious complications such as post-surgical hypocalcemia (low calcium in the blood plasma) can occur when one or more of the parathyroid glands are unintentionally injured or removed due to their small size and similar appearance to the surrounding tissues. We propose to develop a non-invasive camera to aid surgeons to effectively and safely preserve parathyroid glands during operation, thus optimizing surgical decision-making and ultimately contributing to improved outcomes.

Project Terms:
Angiography; Angiogram; angiographic imaging; Attention; Blood Vessels; vascular; Brown Fat; Brown Adipose Tissue; Hibernating Gland; Calcium; Clinical Research; Clinical Study; Clinical Trials; Color; Communities; Complement; Complement Proteins; Complication; Decision Making; Diagnosis; Dissection; Dyes; Coloring Agents; Equipment; Fatty acid glycerol esters; Fats; Feedback; Fluorescent Dyes; Fluorescence Agents; Fluorescent Agents; fluorescent dye/probe; Freezing; Goals; Grant; Hospital Departments; Hospitals; Hypoparathyroidism; Indocyanine Green; Ujoveridin; Wofaverdin; Joints; Lead; Pb element; heavy metal Pb; heavy metal lead; Length of Stay; Number of Days in Hospital; hospital days; hospital length of stay; hospital stay; Light; Photoradiation; lymph nodes; Lymph Node Reticuloendothelial System; Lymph node proper; Lymphatic nodes; lymph gland; lymphnodes; Morbidity - disease rate; Morbidity; Persons; NIH; National Institutes of Health; United States National Institutes of Health; Neck; Nerve; Operating Rooms; optical; Optics; otorhinolaryngology; Otolaryngology; Parathyroid; Parathyroid Head and Neck; Parathyroid gland; Patients; Perfusion; Blood Plasma; Plasma Serum; Reticuloendothelial System, Serum, Plasma; Plasma; Play; Post-Operative; Postoperative; Postoperative Period; Research; Investigators; Researchers; Research Personnel; Risk; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Signal Transduction; Computer Software Development; Computer Software Engineering; Software Engineering; Standardization; Technology; Thyroid Gland Disease; Thyroid Gland Disorder; thyroid disorder; Thyroid Diseases; Thyroid; Thyroid Head and Neck; Thyroid Gland; Thyroid Gland Neoplasm; Thyroid Gland Tumor; Thyroid Tumor; thyroid neoplasm; Thyroidectomy; Time; Tissues; Body Tissues; Translating; Translations; Vascularization; Veterans; Fluorescence Angiography; Data Set; Dataset; Accidental Injury; Unintentional Injury; sensor; improved; Procedures; Clinical; Phase; Evaluation; Blood Serum; Serum; Visual; Funding; tool; Scientist; Stream; Techniques; System; Endocrine; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; meetings; Surgeon; computer imaging; digital imaging; Performance; sterile; Sterility; Devices; Appearance; Abscission; Extirpation; Removal; Surgical Removal; resection; Excision; Position; Positioning Attribute; portability; Vascular blood supply; blood supply; vascular supply; Gland; preventing; prevent; Tissue Viability; Detection; Economic Burden; Head and Neck Surgery; Imaging Instrument; Imaging Tool; Imaging Device; Regulatory Pathway; Thyroid Gland Tissue; Clinical Trials Design; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Monitor; Resected; socioeconomics; socio-economic; socio-economically; socioeconomically; Development; developmental; Allergic Reaction; Image; imaging; feeding; design; designing; Outcome; cost efficient; Imaging technology; translational study; usability; prototype; tumor; operation; imaging platform; improved outcome; sensor technology; sensing technology; Injections; preservation; imager; feasibility testing; Hypocalcemia