The study team observed that airway delivery of iohexol via a Penn-Century MicroSprayer produced broad, relatively uniform lung-parenchymal opacification on serial thoracic images. Signal quantified in coronal thoracic regions measured 0.77 at 5 minutes and 0.72 at 30 minutes after intratracheal instillation. Those numbers reflect a sustained pulmonary imaging window across a typical preclinical micro-CT acquisition, and the pattern remained distributed rather than focally concentrated. The investigators reported no discrete bladder opacity after airway delivery at any measured time point, indicating limited immediate translocation to a single urinary reservoir on the time scale of the thoracic scans.
Contrast in the lungs was visible at early and late thoracic timepoints in this protocol. The authors documented images at 5, 15 and 30 minutes and noted consistent parenchymal enhancement across that interval, a practical duration for small-animal chest imaging sessions where acquisition times extend beyond the brief circulation windows typical of IV iodinated agents.
IV tail-vein injection produced the expected vascular and cardiac opacification pattern. Early post-injection images showed prominent intravascular signal; as time progressed, bladder accumulation became the dominant feature on whole-body projections. By 120 minutes bladder signal was the largest measured compartmental signal in every IV animal. That progressive renal clearance is consistent with clinical pharmacology of nonionic iodinated agents and illustrates why systemic delivery can limit pulmonary imaging windows for prolonged small-animal CT acquisitions.
The authors contrasted the two routes directly. Where intratracheal instillation held iodine within lung parenchyma for at least 30 minutes, IV administration redistributed contrast to the urine-collecting apparatus and systemic compartments, reducing lung-specific signal at later thoracic timepoints.
Acute safety was assessed at two post-procedure intervals: 5 hours and 29 hours. Investigators measured serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine, and they performed histopathology on lung, heart, liver, spleen and kidney versus untreated controls.
Data indicated no differences among groups for ALT, AST or BUN. Creatinine was modestly higher than in controls after both IV and intratracheal routes, and the study team interpreted that rise as consistent with renal excretion of absorbed iohexol; importantly, there was no creatinine difference between the two delivery routes. Histologic sections revealed preserved architecture across examined organs without acute injury signals attributable to either administration method at the times studied.
These acute-safety observations are limited to the interval studied; the authors report no immediate histologic damage or biochemical hepatoxicity markers, and they document a physiologic pattern of renal handling after pulmonary or systemic exposure.
The feasibility comparison used a matched nominal dose of iohexol (100 µL at 500 mg/mL) administered either by IV tail-vein injection or by intratracheal microspray instillation. The intratracheal procedure employed a MicroSprayer device driven by a high-pressure syringe to produce a microspray plume aimed into the lower airway. Each animal was scanned before contrast in the same session to provide a baseline, then monitored with whole-body projections to 120 minutes and thoracic sections to 30 minutes.
Image analysis recorded contrast distribution by compartment and quantified tissue signal from regions of interest. The study design emphasized within-session longitudinal imaging to compare temporal kinetics between routes while maintaining consistent dosing and scan parameters across animals.
This report is framed as a feasibility and acute-safety study rather than a definitive pharmacokinetic or dose-optimization trial. The authors explicitly present these data as the basis for a confirmatory quantitative study; they did not attempt extended kinetic modeling or dose-ranging beyond the single reported concentration and volume. Long-term safety, repeated dosing effects, and precise pulmonary absorption kinetics after airway instillation were not measured here and remain unanswered. Additionally, the acute endpoints were limited to biochemical assays at 5 and 29 hours and histology at those same intervals; delayed inflammatory or fibrotic responses could not be excluded by the current protocol.
Investigators concluded that intratracheal microspray delivery is a practical approach to retain iodine within lung parenchyma across a thoracic micro-CT acquisition in mice. They recommend a follow-up quantitative study to define kinetics, dose–response behavior, and subacute to chronic safety parameters before broader adoption in preclinical imaging workflows.