Development of TIRF based microscopic system with smartphone camera and probe based spectroscopic system as diagnostic tool for intraoperative identification of parathyroid tissue surgeries

The primary aim of surgery in patients with well-differentiated thyroid cancer is complete removal of the tumor. However, preventing complications is as important as removal of the tumor because post-thyroidectomy complications such as permanent hypocalcemia due to inadvertent removal of parathyroid glands can be very painful to both surgeons and patients. Moreover, exact localization of parathyroid glands in hyperparathyroidism patients undergoing surgery is also difficult. There has been no reliable intraoperative method for detection of parathyroid gland(s) during thyroid and parathyroid surgeries. The intraoperative identification of parathyroid glands is challenging because of their small size, variable location, and ambiguous shape as well. Thus, the solution has been mostly based on intuitive visual inspection which can be gained through extensive surgeon experience. However, precise identification and preservation of parathyroid glands can be difficult even for highly skilled surgeons under some situations, such as distorted anatomy from previous surgery, intrathyroidal location, presence of ectopic or super-numerous glands, extensive tumor invasion. To avoid these complications, several techniques such as frozen biopsy, fine needle aspiration (FNA) and parathyroid hormone (PTH) assay, methylene blue staining or indocyanine green (ICG) injection, have been introduced but they showed limited roles in localizing parathyroid glands during thyroidectomy. Since methylene blue and ICG are associated with various side effects, sometimes very severe one, so there is need to find a method, which is cheap and require no use of exogenous fluorophores. Such solution is seen with use of parathyroid’s autofluorescence for intraoperative detection.

Autofluorescence signal of parathyroid gland is difficult to be detected by naked eye but a NIR (Near Infrared) fluorescence imaging system is required to detect this signal. Autofluorescence, or native fluorescence, is a phenomenon that consists of the emission of fluorescence light in a slightly longer spectral range when the biological substrates are excited with light at suitable wavelengths. It has been found that the parathyroid and thyroid glands emit light at a wavelength of 820 nm when illuminated with light around 785 nm wavelength respectively but parathyroid gland has significantly higher autofluorescence as compared to surrounding structures in the neck, regardless of healthy or diseased states. So far, studies on NIR wavelengths that are attractive in biomedicine and clinical applications have mainly been performed by administrating ICG. ICG is an exogenous contrast, which has been widely used as a non-specific agent for the localization of diseased parathyroid glands.