Quantitative Intra-operative Assessment of Parathyroid Perfusion Using Indocyanine Green (ICG) Fluorescence Imaging

Quantitative Intra-operative Assessment of Parathyroid Perfusion Using Indocyanine Green (ICG) Fluorescence Imaging: A Prospective Observational Study

This single-center, prospective, three-phase observational cohort quantifies the relationship between indocyanine green (ICG) fluorescence and early parathyroid function. Adult patients scheduled for unilateral thyroid lobectomy with autotransplantation of the ipsilateral inferior parathyroid gland are enrolled. After intravenous ICG 25 µg/kg, peak fluorescence of the superior parathyroid gland and the common carotid artery (CCA) is recorded at 60-120 seconds to calculate the ratio R = PTG/CCA. Serum parathyroid hormone (PTH) is measured 30 minutes post-operatively. A derivation cohort (~120 patients) generates R-based thresholds for in-situ preservation versus autotransplantation, which are prospectively validated in an independent cohort (60 patients) together with decision-curve analysis of clinical net benefit.

Study Overview

• Status: Recruiting
• Conditions: Thyroid Surgery
• Intervention / Treatment: Diagnostic test: ntra-operative Indocyanine Green (ICG) Fluorescence Quantification

Detailed Description

Post-thyroidectomy hypocalcemia, reported in 5-30 % of cases, is largely attributable to inaccurate assessment of parathyroid perfusion. Conventional intra-operative judgment-based on gland color, capillary bleeding and pulsation-is subjective and non-quantitative. Near-infrared fluorescence imaging with indocyanine green (ICG) allows real-time visualization of tissue perfusion, yet no widely accepted quantitative threshold exists to guide in-situ preservation versus autotransplantation of parathyroid glands.

The PT-ICG study addresses this gap through:

Target population: Patients undergoing unilateral thyroid lobectomy with planned autotransplantation of the ipsilateral inferior parathyroid gland, isolating evaluation to the superior gland.

Pilot phase (n=30): Optimization confirmed an ICG dose of 25 µg/kg and a 60-120 s acquisition window, with the common carotid artery (CCA) providing a stable reference; well-perfused glands exhibited R values ~0.8-3.0.

Derivation phase (n≈120): The relationship between R and 30-min postoperative PTH is modeled; ROC analysis and the Youden index yield R_low and R_high thresholds, internally validated with bootstrap resampling.

Validation phase (n=60): Prospective application of thresholds documents surgeon decisions, postoperative PTH, and hypocalcemia incidence; predictive performance (AUC, sensitivity, specificity) and net clinical benefit (decision-curve analysis) of the R-based strategy are compared with standard clinical judgment.

Sample size and statistics: With an anticipated correlation r≈0.45, α=0.05 (two-sided) and 90 % power, ≥110 patients are required; allowing 10 % attrition, 120-130 will be enrolled.

Data management and safety: REDCap will support double data entry and monitoring; ICG-related adverse events will be recorded; the study adheres to GCP and the Declaration of Helsinki and has received ethics committee approval.

By establishing actionable ICG fluorescence thresholds and a decision algorithm, the study seeks to provide a quantitative tool for real-time intra-operative perfusion assessment, potentially reducing hypocalcemia and informing future multicenter trials.

full SAP available upon request / will be posted as separate document.

• Study Type: Observational
• Enrollment (Estimated): 210

Contacts and Locations

• Study Contact: Name: Bo Wang, MD; Phone Number: +13959123550; Email: wangbo@fjmu.edu.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
      • Contact: Bo Wang, MD; Phone Number: +86 13959123550; Email: wangbo@fjmu.edu.cn
    • Fuzhou, Fujian, China, 350001
      • Not yet recruiting
      • Fujian Medical University Union Hospital
      • Principal Investigator: Bo Wang MD, Principal Investigator
      • Contact: Bo Wang, MD; Phone Number: +13959123550; Email: wangbo@fjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Consecutive adult patients undergoing unilateral thyroid lobectomy with planned autotransplantation of the ipsilateral inferior parathyroid gland at a single tertiary endocrine-surgery center; recruitment limited to cases in which the superior parathyroid gland can be preserved in situ and evaluated intra-operatively with indocyanine-green fluorescence quantification.

Description

Inclusion Criteria:

• Scheduled for unilateral thyroid lobectomy plus central (VI-level) lymph-node dissection.
• Intra-operative findings consistent with:
• Complete identification and in-situ preservation of the ipsilateral superior parathyroid gland;
• Complete identification and autotransplantation of the ipsilateral inferior parathyroid gland.
• Serum 25-hydroxy-vitamin D ≥ 30 ng/mL at baseline; patients below this level may be enrolled after standardized vitamin-D and calcium supplementation with re-test confirming ≥ 30 ng/mL.
• Surgery and all postoperative follow-up performed at the study center.
• Able and willing to provide written informed consent.

Exclusion Criteria:

• Prior surgery on the thyroid or parathyroid glands.
• Severe hepatic or renal impairment, or other serious metabolic bone disease.
• Pregnancy or lactation.
• Known hypersensitivity to indocyanine green or iodine-containing compounds.
• Inability or unwillingness to comply with postoperative visits and blood testing.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Derivation_Cohort; The model-development cohort consisted of 500 consecutive patients drawn from the Thyroid Surgery Department database of Fujian Medical University Union Hospital (Fuzhou, China)	Diagnostic test: ntra-operative Indocyanine Green (ICG) Fluorescence Quantification; After a single intravenous bolus of indocyanine green (25 µg/kg), a near-infrared sensor records raw fluorescence intensity from the superior parathyroid gland and the ipsilateral common carotid artery at 60-120 seconds. No images are stored; only peak intensity values are logged to calculate the perfusion ratio R = PTG / CCA. The measurement is observational, adds ≤2 minutes to operative time, and involves no therapeutic intent.
Validation_Cohort; The external validation cohort comprised 300 patients	Diagnostic test: ntra-operative Indocyanine Green (ICG) Fluorescence Quantification; After a single intravenous bolus of indocyanine green (25 µg/kg), a near-infrared sensor records raw fluorescence intensity from the superior parathyroid gland and the ipsilateral common carotid artery at 60-120 seconds. No images are stored; only peak intensity values are logged to calculate the perfusion ratio R = PTG / CCA. The measurement is observational, adds ≤2 minutes to operative time, and involves no therapeutic intent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parathyroid Gland Fluorescence Intensity	Peak fluorescence intensity of the ipsilateral superior parathyroid gland, captured 60 - 120 seconds after a single intravenous bolus of indocyanine green (25 µg/kg).	Intra-operative (60 - 120 s post-ICG)
Common Carotid Artery (CCA) Fluorescence Intensity	Peak fluorescence intensity of the ipsilateral common carotid artery recorded in the same 60 - 120 second window; serves as the reference signal for perfusion ratio calculations.	Intra-operative (60 - 120 s post-ICG)
Parathyroid Hormone (PTH) at 30 Minutes post-surgery	PTH concentration (pg/mL) measured by chemiluminescent assay 30 minutes after skin closure, reflecting immediate functional status of the preserved superior parathyroid gland.	30 minutes after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Administered ICG Dose	Total dose of indocyanine green (µg/kg) delivered during the procedure.	Intra-operative (time of injection)
PTH at 6 Hours	PTH concentration measured 6 hours after surgery.	6 hours post-surgery
PTH at 2 Weeks	PTH concentration measured 14 ± 2 days after surgery.	2 weeks post-surgery

Collaborators and Investigators

• Sponsor: Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: May 25, 2025
• First Submitted That Met QC Criteria: June 1, 2025
• First Posted (Actual): June 8, 2025

Study Record Updates

• Last Update Posted (Actual): July 15, 2025
• Last Update Submitted That Met QC Criteria: July 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Hypocalcemia; Indocyanine Green; Thyroid surgery; Near-Infrared Fluorescence; Parathyroid Perfusion; Perfusion Threshold; Perfusion Ratio
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases
• Other Study ID Numbers: PT-ICG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: de-identified dataset, SAP and code available upon reasonable request after publication

Drug and device information, study documents

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