NIRAF-Guided Parathyroid Identification During Thyroidectomy

Near-Infrared Autofluorescence-Guided Parathyroid Identification During Thyroidectomy

This is a single-site, two-component prospective study evaluating whether near-infrared autofluorescence (NIRAF) imaging can improve intraoperative identification of parathyroid glands during thyroidectomy and reduce postoperative hypocalcemia.

The investigational platform is a modified wearable stereoscopic goggle system configured for label-free NIRAF imaging. Parathyroid tissue is excited with near-infrared light at approximately 780 nm and emits autofluorescence centered near 800 nm. No injected dye or external contrast agent is used. The goggles are used only during a brief mapping interval after thyroid exposure and for ex vivo interrogation of the resected thyroid specimen.

Component A is a prospective observational run-in validation cohort of 30 adults undergoing thyroidectomy of any extent. NIRAF-positive foci on the intact thyroidectomy specimen are suture-marked and correlated with targeted pathology.

Component B is a randomized clinical study of 250 adults undergoing total or completion thyroidectomy. Participants are randomized 1:1 to standard surgery or standard surgery plus brief in vivo NIRAF mapping, ex vivo specimen interrogation, and rescue autotransplantation when indicated. The primary outcome for Component B is transient biochemical hypocalcemia on postoperative day 1, defined using albumin-corrected serum calcium.

Study Overview

• Status: Not yet recruiting
• Conditions: Thyroid Diseases; Hypocalcemia; Goiter, Nodular; Thyroid Nodule; Hypoparathyroidism; Thyroidectomy
• Intervention / Treatment: Device: Wearable Near-Infrared Autofluorescence Imaging System

Detailed Description

Near-infrared autofluorescence (NIRAF) imaging is being evaluated as a structured adjunct to standard thyroidectomy for localization and preservation of parathyroid tissue. Parathyroid tissue emits intrinsic near-infrared autofluorescence without administration of dye or other contrast agent. The study imaging platform is a modified head-mounted stereoscopic goggle system that provides near-infrared excitation at approximately 780 nm and detects autofluorescence centered near 800 nm. Imaging is non-contact and is performed only during a brief prespecified in vivo mapping interval and ex vivo back-table specimen interrogation.

The study includes a run-in validation component followed by a randomized interventional component. In the run-in component, ex vivo imaging of thyroidectomy specimens is used to standardize imaging conditions, documentation, suture marking, specimen mapping, and pathology correlation for NIRAF-positive foci. In the randomized component, participants undergoing total or completion thyroidectomy are randomized to standard surgery or standard surgery plus adjunct NIRAF mapping. In the intervention arm, the surgeon records parathyroid glands identified under white light before mapping, then uses NIRAF information as an adjunct to standard anatomy and surgical judgment. After thyroid removal, ex vivo specimen imaging may be used to identify NIRAF-bright foci that could represent inadvertently excised parathyroid tissue. Rescue autotransplantation may be performed only when clinically appropriate and oncologically safe.

NIRAF findings are intended to supplement, not replace, standard operative assessment, surgical anatomy, pathology review, or oncologic decision-making.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Magdalena Bogdanovska Todorovska, MD, PhD; Phone Number: +389-70960221; Email: magdalena.todorovska@medf.ukim.edu.mk
• Study Contact Backup: Name: Borislav Kondov, MD, PhD; Phone Number: +389.72539003; Email: borislav.kondov@medf.ukim.edu.mk

Study Locations

• North Macedonia
  • Skopje, North Macedonia, 1000
    • University Clinic Hospital
    • Contact: Magdalena Bogdanovska Todorovska, MD, PhD; Phone Number: +389.70.960221; Email: magdalena.todorovska@medf.ukim.edu.mk
    • Principal Investigator: Magdalena Bogdanovska Todorovska, MD, PhD
    • Sub-Investigator: Borislav Kondov, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older.
• For Component A: planned thyroidectomy of any extent with an intact specimen available for ex vivo evaluation.
• For Component B: planned total or completion thyroidectomy.
• Ability to provide written informed consent before surgery.
• Willingness to comply with routine postoperative laboratory testing and follow-up when feasible.

Exclusion Criteria:

• Known pre-existing hypoparathyroidism or prior parathyroid surgery.
• Severe chronic kidney disease or end-stage renal disease expected to substantially confound calcium and parathyroid hormone interpretation, as defined by the site investigator.
• Pregnancy.
• For Component B only: gross nodal disease or a surgical plan requiring extensive nodal packet dissection in the current study phase.
• Any condition that, in the judgment of the investigator, would make participation unsafe or compromise protocol adherence.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Thyroidectomy; Participants undergo standard thyroidectomy under white light and routine surgical judgment. Conventional autotransplantation remains permitted if the surgeon identifies a devascularized or inadvertently excised parathyroid gland by standard methods.
Experimental: Standard Thyroidectomy Plus NIRAF-Guided Parathyroid Mapping; Participants undergo standard thyroidectomy plus a defined interval of in vivo near-infrared autofluorescence (NIRAF) mapping after thyroid exposure and ex vivo interrogation of the resected thyroid specimen. Rescue autotransplantation may be performed when a NIRAF-bright focus on the specimen is judged likely to represent parathyroid tissue and meets predefined oncologic safety criteria.	Device: Wearable Near-Infrared Autofluorescence Imaging System; A modified Meta head-mounted stereoscopic goggle system configured for label-free near-infrared autofluorescence imaging. The system delivers near-infrared excitation at approximately 780 nm and detects parathyroid autofluorescence centered near 800 nm. No injected dye or external contrast agent is administered. The device is used briefly after thyroid exposure for in vivo mapping and after thyroid resection for ex vivo specimen interrogation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Day 1 Biochemical Hypocalcemia	Proportion of randomized Component B participants with transient biochemical hypocalcemia on postoperative day 1, defined as albumin-corrected total serum calcium below the lower limit of the institutional clinical laboratory reference range in use at study activation.	Postoperative Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Intact Parathyroid Hormone	Early intact parathyroid hormone concentration used as an acute physiologic correlate of in situ parathyroid gland function.	2 to 4 hours postoperatively, with optional assessment on Postoperative Day 1
Mapping Yield	Number of parathyroid-consistent NIRAF sites identified during the intraoperative mapping interval.	Intraoperative
Additional NIRAF Sites Beyond White-Light Assessment	Number of NIRAF sites identified that were not included in the surgeon's pre-mapping white-light declaration.	Intraoperative
Mapping Efficiency	Time to first parathyroid identification with NIRAF imaging and total duration of the intraoperative mapping interval.	Intraoperative
Incidental Parathyroid Tissue in the Thyroidectomy Specimen	Presence and number of histologically confirmed parathyroid glands or parathyroid tissue fragments identified in the thyroidectomy specimen, including size when feasible. The number of confirmed parathyroid glands or tissue foci may be summarized categorically as 0, 1, 2, 3, or 4 when applicable.	Postoperative pathology review (up to 30 days postoperatively)
Rescue Autotransplantation Events	Whether rescue autotransplantation was performed, including tissue source, implant site, and number of fragments implanted.	Intraoperative
Longer-Term Albumin-Corrected Serum Calcium	Albumin-corrected total serum calcium concentration measured at postoperative follow-up.	Postoperative week 8 and postoperative month 6
Longer-Term Intact Parathyroid Hormone	Serum intact parathyroid hormone concentration measured at postoperative follow-up.	Postoperative week 8 and postoperative month 6
Calcium or Calcitriol Supplementation at Follow-Up	Use of oral calcium and/or calcitriol supplementation at postoperative follow-up.	Postoperative week 8 and postoperative month 6

Collaborators and Investigators

• Sponsor: Ss. Cyril and Methodius University of Skopje
• Collaborators: University of Illinois at Urbana-Champaign
• Investigators: Principal Investigator: Magdalena Bogdanovska Todorovska, MD, PhD, Ss. Cyril and Methodius University of Skopje

Publications and helpful links

General Publications

• Benmiloud F, Godiris-Petit G, Gras R, Gillot JC, Turrin N, Penaranda G, Noullet S, Chereau N, Gaudart J, Chiche L, Rebaudet S. Association of Autofluorescence-Based Detection of the Parathyroid Glands During Total Thyroidectomy With Postoperative Hypocalcemia Risk: Results of the PARAFLUO Multicenter Randomized Clinical Trial. JAMA Surg. 2020 Feb 1;155(2):106-112. doi: 10.1001/jamasurg.2019.4613.
• Canali L, Russell MD, Sistovaris A, Abdelhamid Ahmed AH, Otremba M, Tierney HT, Triponez F, Benmiloud F, Spriano G, Mercante G, Randolph GW. Camera-based near-infrared autofluorescence versus visual identification in total thyroidectomy for parathyroid function preservation: Systematic review and meta-analysis of randomized clinical trials. Head Neck. 2025 Jan;47(1):225-234. doi: 10.1002/hed.27900. Epub 2024 Aug 5.
• Kim DH, Kim SW, Kang P, Choi J, Lee HS, Park SY, Kim Y, Ahn YC, Lee KD. Near-Infrared Autofluorescence Imaging May Reduce Temporary Hypoparathyroidism in Patients Undergoing Total Thyroidectomy and Central Neck Dissection. Thyroid. 2021 Sep;31(9):1400-1408. doi: 10.1089/thy.2021.0056. Epub 2021 Jun 4.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Thyroidectomy; Total Thyroidectomy; Postoperative Hypocalcemia; NIRAF; iPTH; Parathyroid Identification; Near-Infrared Autofluorescence; Wearable Imaging; Parathyroid Preservation; Completion Thyroidectomy; Intact Parathyroid Hormone; Rescue Autotransplantation; Post-thyroidectomy hypocalcemia
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Metabolic Diseases; Thyroid Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Water-Electrolyte Imbalance; Parathyroid Diseases; Goiter; Calcium Metabolism Disorders; Nutritional and Metabolic Diseases; Thyroid Diseases; Thyroid Nodule; Goiter, Nodular; Hypoparathyroidism; Hypocalcemia
• Other Study ID Numbers: 02-2848/10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be shared with outside researchers. Deidentified aggregate study results may be reported in scientific presentations and publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No