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Peer-reviewedCC BYPLOS One

Intratracheal microspray delivery of iohexol for sustained lung-parenchymal enhancement in preclinical micro-computed tomography: A feasibility and acute-safety study in mice

8 affiliations
  1. 1Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  2. 2Division of Allergy, Asthma, and Immunology, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
  3. 3TMU Research Center of Thoracic Medicine, Taipei Medical University, Taipei, Taiwan.
  4. 4Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan.
  5. 5Department of Biomedical Engineering, MacKay Memorial Hospital, Taipei, Taiwan.
  6. 6International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  7. 7Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
  8. 8International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, New Taipei City, Taiwan.

Abstract

Preclinical thoracic micro-computed tomography (micro-CT) is constrained by the brief pulmonary enhancement window of intravenously (IV) administered iodinated contrast, which the kidneys clear rapidly. We performed a feasibility study in mice comparing IV tail-vein injection with intratracheal microspray instillation of the clinical agent iohexol. Mice received iohexol (100 µL, 500 mg/mL) by either route. Whole-body projections were acquired to 120 min and thoracic sections to 30 min, each animal scanned before contrast in the same session. Contrast distribution was recorded by compartment and quantified from regions of interest. IV delivery produced vascular and cardiac opacification with progressive bladder accumulation, which was the largest signal in every IV animal by 120 min. Intratracheal delivery produced widespread, comparatively uniform lung-parenchymal opacification at 5, 15 and 30 min with no discrete bladder opacity at any time; coronal thoracic signal was 0.77 at 5 min and 0.72 at 30 min, against 0.09 to 0.19 after IV injection. Acute safety was assessed at 5 and 29 h by serum biochemistry and histopathology against untreated controls. ALT, AST and blood urea nitrogen did not differ among groups. Creatinine was modestly higher than in controls after both routes, with no difference between routes, consistent with renal excretion of absorbed iohexol. Lung, heart, liver, spleen and kidney showed preserved architecture without acute injury. These data identify intratracheal microspray delivery as a practical way to hold iodine in the lung parenchyma across a thoracic micro-CT acquisition and provide the basis for a confirmatory quantitative study.

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BibTeX
@article{lin2026intratracheal,
  title = {{Intratracheal microspray delivery of iohexol for sustained lung-parenchymal enhancement in preclinical micro-computed tomography: A feasibility and acute-safety study in mice}},
  author = {Sheng-Chieh Lin and Kuo-Kai Lin and Kevin Aristyo and Hong-Min Lin and Wei-Hung Liu and Erh-Hsuan Hsieh and Ching-Li Tseng},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0361103},
  url = {https://doi.org/10.1371/journal.pone.0361103},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Intratracheal microspray delivery of iohexol for sustained lung-parenchymal enhancement in preclinical micro-computed tomography: A feasibility and acute-safety study in mice
AU  - Sheng-Chieh Lin
AU  - Kuo-Kai Lin
AU  - Kevin Aristyo
AU  - Hong-Min Lin
AU  - Wei-Hung Liu
AU  - Erh-Hsuan Hsieh
AU  - Ching-Li Tseng
PY  - 2026
DA  - 2026/10/23
JO  - PLOS One
DO  - 10.1371/journal.pone.0361103
UR  - https://doi.org/10.1371/journal.pone.0361103
AB  - Preclinical thoracic micro-computed tomography (micro-CT) is constrained by the brief pulmonary enhancement window of intravenously (IV) administered iodinated contrast, which the kidneys clear rapidly. We performed a feasibility study in mice comparing IV tail-vein injection with intratracheal microspray instillation of the clinical agent iohexol. Mice received iohexol (100 µL, 500 mg/mL) by either route. Whole-body projections were acquired to 120 min and thoracic sections to 30 min, each animal scanned before contrast in the same session. Contrast distribution was recorded by compartment and quantified from regions of interest. IV delivery produced vascular and cardiac opacification with progressive bladder accumulation, which was the largest signal in every IV animal by 120 min. Intratracheal delivery produced widespread, comparatively uniform lung-parenchymal opacification at 5, 15 and 30 min with no discrete bladder opacity at any time; coronal thoracic signal was 0.77 at 5 min and 0.72 at 30 min, against 0.09 to 0.19 after IV injection. Acute safety was assessed at 5 and 29 h by serum biochemistry and histopathology against untreated controls. ALT, AST and blood urea nitrogen did not differ among groups. Creatinine was modestly higher than in controls after both routes, with no difference between routes, consistent with renal excretion of absorbed iohexol. Lung, heart, liver, spleen and kidney showed preserved architecture without acute injury. These data identify intratracheal microspray delivery as a practical way to hold iodine in the lung parenchyma across a thoracic micro-CT acquisition and provide the basis for a confirmatory quantitative study.
SN  - 1932-6203
ER  -