Developing a Clinical Prototype to Guide Surgeons for Intraoperative Label-Free Identification of Parathyroid Glands in Real Time

Abstract

Background: Patients undergoing thyroidectomy may have inadvertent damage or removal of the parathyroid gland(s) due to difficulty in real-time parathyroid identification. Near-infrared autofluorescence (NIRAF) has been demonstrated as a label-free modality for intraoperative parathyroid identification with high accuracy. This study presents the translation of that approach into a user-friendly clinical prototype for rapid intraoperative guidance in parathyroid identification.

Methods: A laboratory (lab)-built spectroscopy system that measures NIRAF in tissue was evaluated for identifying parathyroid glands in vivo across 162 patients undergoing thyroidectomy and/or parathyroidectomy. Based on these results, a clinical prototype called PTeye was designed with a user-friendly interface and subsequently investigated in 35 patients. The performance of the lab-built system and the clinical prototype were concurrently compared side by side by a single user with 20 patients in each group. The influence of (i) intrapatient and interpatient variability of NIRAF in thyroid and parathyroid glands and (ii) thyroid and parathyroid pathology on intraoperative parathyroid identification were investigated. The effect of blood on NIRAF intensity of parathyroid and thyroid was tested ex vivo with the PTeye system to assess if a hemorrhagic surgical field would affect parathyroid identification. Accuracy of both systems were determined by correlating the acquired data with either visual confirmation by a surgeon for unexcised parathyroid glands or histology reports for excised parathyroid glands.

Results: The overall accuracy of the lab-built system in guiding parathyroid identification was 92.5%, while the PTeye system achieved an accuracy of 96.1%. Unlike the lab-built system, the PTeye could guide parathyroid identification even as the operating room lights remained on and required only 25% of the laser power used by the lab-built setup. Parathyroid glands had elevated NIRAF intensity compared to thyroid and other neck tissues, regardless of thyroid or parathyroid pathology. Blood did not seem to affect tissue NIRAF measurements obtained with both systems.

Conclusion: In this study, the clinical prototype PTeye demonstrated high accuracy for label-free intraoperative parathyroid identification. The intuitive interface of the PTeye that can guide in identifying parathyroid tissue in the presence of ambient room lights suggests that it is a reliable and easy-to-use tool for surgical personnel.

Keywords: clinical translation; near-infrared imaging; parathyroidectomy; postsurgical hypocalcemia; real-time guidance; thyroidectomy.

Conflict of interest statement

Professor Anita Mahadevan-Jansen and Vanderbilt University have a licensing agreement with AiBiomed Instruments (Santa Barbara, CA) for developing the clinical prototype system, PTeye, that has been investigated in this study. AiBiomed Instruments is the exclusive licensee of the intellectual property on the described NIRAF detection method from Vanderbilt University.

Figures

FIG. 1.

The lab-built system for near-infrared autofluorescence (NIRAF) detection in tissue. The components involve (1) a spectrometer, (2) a 785-nm diode laser, (3) a sterilizable fiber optic probe, and (4) a laptop to run the software for NIRAF detection.

FIG. 2.

(a) The clinical prototype PTeye for intraoperative guidance in identifying parathyroid tissue. The device consists of (1) the optical probe, (2) the foot pedal that activates the NIR laser, and (3) the PTeye unit that encloses a 785nm laser source and an internal microprocessor board that incorporates visual feedback via (4) the user interface display and an additional auditory feedback mechanism through a loudspeaker. The user display indicates detection percentage, detection ratio (tissue NIRAF intensity normalized to that of thyroid), and detection level (absolute NIRAF counts) as seen for a tissue identified either positively (b) or negatively (c) for parathyroid by the system.

FIG. 3.

Averaged NIRAF intensity normalized to thyroid obtained with the lab-built system in 162 patients for thyroid, parathyroid, fat, neck muscles and trachea. Tissues were classified based on NIRAF intensity at 820 nm (indicated by grey zone) as parathyroid or nonparathyroid by setting a threshold at 1.2 denoted by the dashed purple line.

FIG. 4.

Comparison of normalized NIRAF intensity obtained with the lab-built system in 162 patients and the PTeye in 35 patients for thyroid, parathyroid, fat, neck muscles, and trachea. NIRAF intensity has been normalized to that obtained by the thyroid. **p < 0.001 for normalized NIRAF intensity of parathyroid compared with other neck tissues such as thyroid, fat, muscles, and trachea. Horizontal line in blue box, data median; upper tail, data maxima; lower tail, data minima; red crosses, data outliers.

FIG. 5.

Intrapatient and interpatient variability of normalized NIRAF intensity in parathyroid and thyroid in the 35 patients assessed with the PTeye. No parathyroid glands could be visualized by the surgeon in patient 4, leading to lack of parathyroid measurements. Patients 17 and 26 were postthyroidectomy cases who underwent parathyroidectomy during this study; the NIRAF intensity were normalized to the neck muscle, instead of the thyroid for these cases. Patient 29 was the only renal-induced secondary hyperparathyroidism case assessed with the PTeye. Horizontal line in boxes, data median; upper tails, data maxima; lower tails, data minima; red crosses, data outliers.

FIG. 6.

Variation of normalized NIRAF intensity between normal thyroid, diseased thyroid, normal parathyroid, and diseased parathyroid states among 162 patients tested with the lab-built system and 35 patients tested with the PTeye. **p < 0.001 for normalized NIRAF intensity of parathyroid compared with thyroid. Horizontal line in blue box, data median; upper tails, data maxima; lower tails, data minima; red crosses, data outliers.

FIG. 7.

Influence of blood on NIRAF intensity measured ex vivo from thawed frozen human parathyroid and thyroid specimens with the lab-built system and the PTeye. **p < 0.001 for NIRAF intensity of parathyroid compared with thyroid. Horizontal line in blue box, data median; upper tails, data maxima; lower tails, data minima; red crosses, data outlier.