Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery

Subcapsular surgical dissection is not always sufficient to preserve PGs and prevent the considerable morbidity, in some cases mortality, resulting from hypoparathyroidism caused by devascularization or inadvertent removal of PGs during surgery. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Herein,authors comprehensively review PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)—both label free and in combination with indocyanine green (ICG)— based on a comprehensive literature review and provide a manual for possible implementation of these emerging technologies in thyroid surgery.

Given the relative newness of the technology in this field, they sought authors from a diverse range of geographic locations and specialties, including endocrinologists, otolaryngologists, and endocrine surgeons as well as clinicians and researchers with expertise in NIRAF imaging science, parathyroid disease, and research methodology.

Despite surgical advances, preservation of PGs remains challenging due to their small size and variable location. The morbidity associated with hypoparathyroidism following thyroid surgery is substantial and includes decreased quality of life; kidney, neurologic, and musculoskeletal complications; and even increased mortality.

Management of permanent postoperative hypoparathyroidism can be challenging, often requiring calcium supplements and activated vitamin D, and in some patients magnesium, thiazide diuretics, phosphate binders, dietary/lifestyle changes, and recombinant human intact PTH.

Parathyroid Gland Identification

• Comparison of Probe-Based and Camera-Based Technologies

Early PG localization may inform real-time surgical adjustments to minimize manipulation of PGs, thereby preventing injury. Commercially available NIR fluorescence systems for thyroid surgery can be divided into 2 groups: probe based and camera based. In 2018, US Food and Drug Administration clearance was granted to (1) probe-based PTeye (Medtronic) and (2) camera-based Fluobeam 800 and Fluobeam LX (Fluoptics) to serve as label-free NIRAF detection devices to identify PGs intraoperatively. Background discussion of NIRAF and handheld probe-based and With experience and proper calibration, NIRAF technologies enable earlier and improved PG identification compared with the current gold standard, the surgeon’s unaided eye. The NIRAF imaging can identify 90% to 100% of PGs with 90% to 100% sensitivity and accuracy.

The NIRAF detection systems may be used to scan the surface of the surgical field and localize thinly covered PGs much like a nerve monitor probe can identify the path of the recurrent laryngeal nerve. Importantly, NIRAF technology does not supplant sound judgment and surgical experience. There is variability in reports of whether the use of NIRAF reduces postoperative hypocalcemia, and its use has not been shown definitively to reduce permanent post thyroidectomy hypocalcemia. The learning curve of adoption of these nascent technologies requires study, including operator variability and extrinsic variables (such as ambient light), in addition to variables affecting PG autofluorescence intensity and interpretation.

Parathyroid Gland Vascularization

• Intraoperative Assessment of Parathyroid Perfusion

Several intraoperative techniques to evaluate PG perfusion during thyroidectomy have been studied. Provided perfusion is confirmatory of postoperative PG function, intraoperative preservation of PG perfusion could reduce rates of postoperative hypoparathyroidism.

• ICG Fluorescence Imaging

The combination of NIR fluorescence imaging with ICG dye for realtime intraoperative evaluation of PG vascularization is gaining interest; NIRAF in conjunction with ICG imaging may provide information about perfusion and perhaps postoperative PG function. Indocyanine green injection during thyroidectomy can evaluate PG vascularity and perfusion, though ICG is not approved by the US Food and Drug Administration specifically for perfusion assessment in thyroid surgery. Intraoperative injection of ICG for PG localization has been compared with label-free NIRAF imaging with similar identification rates (95% vs 98%, respectively).

Several institutions have described early ICG injection after initial surgical exposure. Once PGs have been identified, ICG fluorescence imaging can be used to assess PG vascular pedicles (real-time vascular mapping) and perfusion. Camera-based NIRAF detection methods and predissection ICG injection may provide a spatial guide of PG and associated vascular anatomy, thereby optimizing PG management. This technique requires correctly timing the ICG injection. The best images are obtained after the first injection due to remnant background ICG fluorescence during subsequent injections. Importantly, NIRAF cannot be detected after ICG administration because the background ICG fluorescence is more intense than the NIRAF.

The most common timing for intraoperative ICG injection is after completion of total thyroidectomy. The ICG injection, however, can occur at various times throughout the procedure, such as after initial PG dissection to aid in preservation of feeding vessels or after completion of the first side to aid in decision-making regarding extent of second-side dissection.

Benefits and limitations for ICG use should be carefully considered. Limitations include lack of distinction from adjacent tissues (especially thyroid). Extravasation of ICG due to bleeding contaminates the surgical field with the fluorescent dye and may “drown” the vascular images. Cameras designed for ICG angiography are not necessarily optimal for PG NIRAF due to laser wavelengths and camera sensitivities. In addition, ICG uptake and washout have not been studied systematically. Sufficiently powered prospective randomized clinical trials evaluating the effect of NIRAF technologies on postoperative hypocalcemia, inadvertent PG resection, and PG autotransplantation (which are surgeon and pathologist dependent) in thyroidectomy are needed.

Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy, and an integrated system enabling early PG identification and prediction of postoperative PG function would be ideal but is not yet available; rate of use of NIRAF technology, specifically in thyroid surgery, is not available, though we expect that it is currently low. Additional research is needed to clarify the variables affecting the degree of fluorescence in NIRAF, standardize NIRAF signal quantification, standardize the parameters of ICG injection (dosing, timing of injection, and signal quantification), enable this technology to predict postoperative PG function, and understand the adoption learning curve and effect on surgical training as well as the financial effect of these emerging technologies on near-term costs (ie, operating time, reduction/ elimination of frozen section) and longer-term costs (ie, medications, surveillance costs). Long-term outcomes of key quality metrics are needed, and adequately powered randomized clinical trials evaluating PG preservation will guide adoption.

Source: Amanda L. Silver Karcioglu, MD; Frédéric Triponez, MD et al; JAMA Otolaryngol Head Neck Surg. 2023;149(3):253-260. doi:10.1001/jamaoto.2022.4421