Introduction

Thyroid cancer accounts for approximately 2.2% of all cancer cases worldwide, and surgical resection is the most important treatment modality [1], [2]. The parathyroid glands (PGs) are located adjacent to the thyroid gland. Exhibiting considerable anatomical variability, the PGs usually weigh 35–45 mg, and measure 5 mm × 3 mm × 1 mm [3]. Because of their small size and vulnerable vascularization, the identification accuracy and preservation of the PGs remain challenging during thyroidectomy. PGs can be inadvertently removed, which leads to postoperative complications, such as hypoparathyroidism and hypocalcemia, affecting patients' long-term quality of life [4], [5]. According to the guidelines of the American Thyroid Association, the incidence of hypoparathyroidism after total thyroidectomy ranges from 23.6% in transient cases to 6.5% in permanent cases [6]. However, conventional strategies for intraoperative identification, including visual inspection, intraoperative frozen section analysis, and the use of lateral flow strips to detect parathyroid hormone (PTH) in fine-needle aspirations, are often limited by subjectivity and time delay. Therefore, novel technologies are being actively explored to improve this situation, with near-infrared autofluorescence (NIRAF) emerging as a novel intraoperative technology aimed at enhancing the visualization of PGs during thyroid surgery [7], [8].

NIRAF is a highly anticipated technology that exploits the unique autofluorescent properties of parathyroid tissue under near-infrared light [9]. Autofluorescence is a process in which biomolecules and tissues are excited by near-infrared light [10]. As reported by Kiernan CM et al., when the excitation light is at 785nm, the PG emits a distinct autofluorescence signal at 820–830 nm, with an intensity 5 to 12 times higher than that of the surrounding tissues [11], [12], [13], [14], [15]. Numerous randomized controlled trials and meta-analyses have confirmed the clinical efficacy of NIRAF, demonstrating a substantial improvement in PG identification rate and a significant reduction in the incidence of transient hypocalcemia from 21.7% to 9.1%, but these studies have not revealed any statistically significant differences in permanent hypoparathyroidism [13], [16], [17].

The identification rate of NIRAF is affected by numerous objective factors, such as false-positive and false-negative interpretations, which fail to meet the expectations of clinicians [8], [18]. For instance, a recent study reported a false-positive rate of 32.1% in parathyroid identification [14]. Similarly, in a study of 19 pediatric patients, it was shown that at a lower threshold (≥1.2), the false-positive rate reached 21.6% [15]. Conversely, false-negative results can also occur. A study showed that NIRAF failed to identify 8 of 264 (3%) glands [19]. There are numerous factors contributing to those false positives and false negatives results. However, the primary cause remains unclear [7], [15].

Therefore, a comprehensive analysis of the specific sources of the errors and their contributing factors is necessary. In view of these critical limitations, this study systematically analyzed the specific factors that affect the accuracy of NIRAF in endoscopic thyroidectomy. Through a comprehensive exploration of these challenges, our research aims to contribute to the development of multimodal verification strategies that can sustainably improve both the discriminatory accuracy and overall safety of surgeries using NIRAF.