Novel techniques for intraoperative parathyroid gland identification: a comprehensive review

ABSTRACT

Introduction

The parathyroid glands (PGs) are critical for calcium regulation and homeostasis. The preservation of PGs during neck surgery is crucial to avoid postoperative hypoparathyroidism. There are no existing guidelines for intraoperative PG identification, and the current approach relies heavily on the experience of the operating surgeon. A technique that accurately and rapidly identifies PGs would represent a useful intraoperative adjunct.

Areas covered

This review aims to assess common dye and fluorescence-based PG imaging techniques and examine their utility for intraoperative PG identification. A literature search of published data on methylene blue (MB), indocyanine green (ICG) angiography, near-infrared autofluorescence (NIRAF), and the PGs between 1971 and 2020 was conducted on PubMed.

Expert opinion

NIRAF and near-infrared (NIR) parathyroid angiography have emerged as promising and reliable techniques for intraoperative PG identification. NIRAF may aid with real-time identification of both normal and diseased PGs and reduce the risk of postoperative complications such as hypocalcemia. Further large prospective multicenter studies should be conducted in thyroid and parathyroid surgical patient populations to confirm the clinical efficacy of these intraoperative NIR-based PG detection techniques.

KEYWORDS:

• Hyperparathyroidism
• indocyanine Green
• methylene Blue
• near-infrared Autofluorescence
• parathyroid Glands

Article highlights

• Failure to identify and preserve PGs during neck surgery may result in permanent hypoparathyroidism [2]. The current workflow for intraoperative PG identification relies on surgeon experience and knowledge of neck anatomy and PG embryology. An intraoperative imaging technique that assists the surgeon with PG identification would represent an important advance in the field.

• OCT, Raman spectroscopy, intraoperative ultrasound imaging, intraoperative gamma probe radio-guidance, and 5-ALA have been evaluated for intraoperative PG identification [12–15,19,21,23,25,29]. However, further study is required to determine the efficacy and feasibility of these approaches. Intraoperative PG visualization using MB, ICG angiography, and NIRAF have been utilized as adjunctive surgical tools with varying degrees of success.

• When administered intravenously, MB stains PGs blue, which allows for their visualization [76]. MB has been used to aid with intraoperative PG identification though variable PG detection rates have been reported [35,57]. Moreover, MB may localize non-specifically to the thyroid [60], photobleach [59], and have other significant adverse effects [61,74].

• ICG is taken up by PGs and fluoresces upon NIR excitation, allowing for PG visualization and perfusion assessment [83,101,102]. ICG angiography has been reported to help preserve PG function as well as aid with pathological PG identification [81]. However, ICG also localizes to the thyroid gland, which may be confounding [139]. Additionally, there is no universal fluorescence intensity scoring system for ICG, and image interpretation is subjective [104,160].

• NIRAF describes the autofluorescent property of PGs upon exposure to NIR light at a wavelength of 785nm [107]. The source of PG AF is unknown though the calcium-sensing receptor has been suggested [107,113,114]. Further study is required to determine the source of PG NIRAF.

• Probe-based methods for NIRAF assessment require a NIR excitation source, a spectrometer to detect AF, and a fiber-optic probe for light collection and delivery [29]. Image-based methods for NIRAF assessment require a NIR excitation source and a camera to display the resulting images on a monitor [115]. There are currently two FDA approved devices for use in the U.S.A., the PTeye (AiBiomed, Santa Barbara, CA), a probe-based device that provides, auditory, visual, and quantitative information, and the Fluobeam-800 (Fluoptics, Grenoble France), an image-based device [17,140].

• Probe-based methods can provide real-time information about PG location [29]. However, they require direct contact between the fiber-optic probe and the tissue being interrogated [136,141]. Image-based systems do not require direct contact with the tissue being evaluated. However, the operating surgeon must correlate images displayed on a monitor with the surgical field. Most image-based methods also require the operating room lights to be turned off [137–139]. PG viability cannot be assed alone by NIRAF imaging [139,142]. NIRAF imaging may help the surgeon identify normal and pathological PGs intraoperatively in real time, allow for visualization and mapping of the PGs, and may help avoid early, and possibly even late postoperative hypoparathyroidism [109,117].

Data Availability Statement

The authors confirm that the data supporting the findings of this study are available within the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have a licensing agreement with Ai Biomed Instruments (Santa Barbara, CA) for developing PTeye, that has been described in this review article. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.