Nanoparticle-based CT visualization of pulmonary vasculature for minimally-invasive thoracic surgery planning

PLoS One. 2019 Jan 17;14(1):e0209501. doi: 10.1371/journal.pone.0209501. eCollection 2019.

Abstract

Purpose: To evaluate CF800, a novel lipid-based liposomal nanoparticle that co-encapsulates indocyanine green (ICG) and iohexol, for CT imaging of pulmonary vasculature in minimally-invasive thoracic surgery planning.

Methods: CF800 was intravenously administered to 7 healthy rabbits. In vivo CT imaging was performed 15 min post-injection, with a subset of animals imaged at 24h, 48h, and 72h post injection. Signal-to-background ratios (SBR) were calculated at the inferior vena cava and compared across time-points. A similar protocol was applied to 2 healthy pigs to evaluate the feasibility and efficacy in a large animal model. To evaluate the feasibility of clinical application, a survey was completed by 7 surgical trainees to assess pre- and post-injection CT images of rabbits and pigs. Responses on the discernibility of pulmonary vasculature sub-branches and comfort level to use the images for pre-operative planning were collected and analyzed.

Results: CF800 injection improved visualization of pulmonary vessels in both rabbit and pig models. The SBR of rabbit pulmonary vasculature was significantly higher after CF800 injection (range 3.7-4.4) compared to pre-injection (range 3.3-3.8, n = 7; p<0.05). SBR remained significantly different up to 24 hours after injection (range 3.7-4.3, n = 4; p<0.05). Trainees' evaluation found the post-injection CT images had significantly higher discernibility at the second vessel branch generation in both rabbit and pig models. Trainees identified smaller vasculature branch generations in the post-injection images compared to the pre-treatment images in both rabbit (mean 6.7±1.8 vs 5.4±2.1; p<0.05) and pig (mean 6.7±1.8 vs 5.4±2.1; p<0.05). Trainees were significantly more comfortable using post-injection images for surgical planning compared to the pre-injection images (rabbit: 8.1±1.1 vs. 4.7±2.1; pig: 7.6±2.1 vs. 4.9±2.2; p<0.05).

Conclusion: CF800 provides SBR and contrast enhancement of pulmonary vasculature which may assist in pre-surgical CT planning of minimally invasive thoracic surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / administration & dosage
  • Humans
  • Imaging, Three-Dimensional
  • Indocyanine Green / administration & dosage
  • Iohexol / administration & dosage
  • Liposomes / administration & dosage
  • Lung / blood supply*
  • Lung / diagnostic imaging*
  • Lung / surgery
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / surgery
  • Male
  • Minimally Invasive Surgical Procedures
  • Models, Animal
  • Nanoparticles / administration & dosage
  • Rabbits
  • Signal-To-Noise Ratio
  • Sus scrofa
  • Thoracic Surgical Procedures*
  • Tomography, X-Ray Computed / methods*
  • Tomography, X-Ray Computed / statistics & numerical data
  • Translational Research, Biomedical

Substances

  • Contrast Media
  • Liposomes
  • Iohexol
  • Indocyanine Green

Grants and funding

This research was funded by the Canadian Cancer Society (grant 702900).