Indocyanine green combined with autologous blood and methylene blue for pulmonary nodules localization in 272 cases: a novel localization method - Report - MDSpire

Indocyanine green combined with autologous blood and methylene blue for pulmonary nodules localization in 272 cases: a novel localization method

  • By

  • Quan Du

  • Zijie Wang

  • Jian Chen

  • Hong Chen

  • Yuanrong Tu

  • Min Lin

  • Jianfeng Chen

  • August 11, 2025

  • 0 min

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Clinical Report: Localization of Pulmonary Nodules Using ICG, Autologous Blood, and Methylene Blue

Overview

This study evaluated a novel preoperative CT-guided localization technique for small pulmonary nodules using a mixture of indocyanine green (ICG), autologous blood, and methylene blue in 272 patients. The optimized low-dose ICG mixture provided clear fluorescence visualization, improved localization success, and minimized complications during thoracoscopic wedge resection.

Background

Lung cancer remains a leading cause of cancer mortality worldwide, with early-stage detection increasingly common due to low-dose CT screening. Surgical resection, particularly sub-lobar approaches like wedge resection, offers significant survival benefits for small peripheral nodules ≤ 2 cm. However, small nodules are often difficult to visualize or palpate intraoperatively, increasing the risk of surgical failure. Preoperative localization techniques, including dye marking with ICG, have been developed to improve surgical accuracy. Combining ICG with autologous blood and methylene blue aims to enhance marker stability and visibility while reducing diffusion and complications.

Data Highlights

ParameterValue/Range
Number of patients272 (110 males, 162 females)
Nodule size inclusion5 mm to 30 mm (≤ 2 cm for surgery)
Distance from pleura≤ 2 cm or outer 1/3 lung location
ICG concentration tested0.05 mg/mL
Localization agent volumes tested0.2 mL to 1.0 mL
Localization-surgery intervalApproximately 2 hours
Localization success rating scale1 to 3 points (≥ 2 points = success)

Key Findings

  • The mixture of ICG with autologous blood and methylene blue provided dual protection, increasing localization success and reliability.
  • Optimal localization was achieved using low-dose ICG (0.05 mg/mL) with volumes between 0.2 mL and 1.0 mL, minimizing pleural staining and diffusion.
  • CT-guided percutaneous injection allowed precise delivery of the localization agent near or within 1 cm of the nodule under fluoroscopic guidance.
  • Post-injection CT confirmed marker placement and excluded complications such as pneumothorax or hemothorax.
  • Localization efficacy was independently scored by two surgeons, with scores ≥ 2 indicating successful localization aiding thoracoscopic wedge resection.
  • The technique enabled minimally invasive surgery with reduced conversion rates to thoracotomy and improved surgical outcomes for small peripheral nodules.

Clinical Implications

This localization method using a low-dose ICG-autologous blood-methylene blue mixture is a safe, cost-effective, and reliable approach for preoperative marking of small pulmonary nodules. It facilitates minimally invasive thoracoscopic wedge resections by improving intraoperative visualization and reducing localization failures. Clinicians should consider this technique to optimize surgical planning and outcomes in early-stage lung cancer patients with peripheral nodules.

Conclusion

The combined use of indocyanine green, autologous blood, and methylene blue for CT-guided localization of small pulmonary nodules is effective and safe, enhancing surgical precision and minimizing complications. This approach represents a valuable advancement in the management of early-stage lung cancer requiring sub-lobar resection.

References

  1. Lung cancer statistics and screening context
  2. Surgical outcomes in early-stage lung cancer
  3. Randomized-controlled study comparing lobectomy and segmentectomy
  4. Survival outcomes in sub-lobar resections
  5. Challenges in localizing small pulmonary nodules
  6. Indocyanine green properties and clinical use
  7. ICG-human albumin mixture for localization

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