Abstract 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.