Preclinical thoracic micro-CT is constrained by the brief pulmonary enhancement window of intravenously administered iodinated contrast, which the kidneys clear rapidly. To test an alternative, researchers compared standard tail-vein injection with intratracheal microspray instillation of iohexol, giving mice 100 microliters at 500 milligrams per milliliter by either route. Whole-body projections were acquired out to 120 minutes and thoracic sections to 30 minutes, with each animal scanned before contrast administration in the same session. Contrast distribution was recorded by compartment and quantified from regions of interest.

The two delivery routes produced sharply different imaging outcomes. Intravenous injection yielded vascular and cardiac opacification followed by progressive bladder accumulation, which was the largest signal in every intravenously dosed animal by 120 minutes. Intratracheal microspray instead produced widespread, comparatively uniform lung-parenchymal opacification at 5, 15 and 30 minutes, with no discrete bladder opacity at any time point. Quantification underscored the contrast: coronal thoracic signal reached 0.77 at 5 minutes and 0.72 at 30 minutes after intratracheal delivery, against only 0.09 to 0.19 following intravenous injection.

Acute safety was assessed at 5 and 29 hours using serum biochemistry and histopathology, with untreated mice serving as controls. Alanine aminotransferase, aspartate aminotransferase and blood urea nitrogen did not differ among the groups. Creatinine was modestly higher than in controls after both routes, with no difference between routes, a pattern consistent with renal excretion of iohexol absorbed from the airways. Histological examination of lung, heart, liver, spleen and kidney showed preserved architecture without acute injury.

Because the investigation is explicitly a feasibility and acute-safety study in mice, the results do not establish a validated clinical protocol. Even so, the data identify intratracheal microspray delivery as a practical way to hold iodine within the lung parenchyma across a thoracic micro-CT acquisition, addressing a constraint that has limited high-resolution imaging of the rodent lung while the safety profile is examined further.

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

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

Article References: Lin, S.-C., Lin, K.-K., Aristyo, K., Lin, H.-M., Liu, W.-H., Hsieh, E.-H., & Tseng, C.-L. (2026). Intratracheal microspray delivery of iohexol for sustained lung-parenchymal enhancement in preclinical micro-computed tomography: A feasibility and acute-safety study in mice. PLOS One, 21(10), e0361103. https://doi.org/10.1371/journal.pone.0361103

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0361103

Keywords: Intratracheal, microspray, delivery, iohexol, sustained, lung-parenchymal, enhancement, preclinical, micro-computed, tomography, feasibility, acute-safety