Preclinical Quantitative In Vivo MRI Assessment of Exogenous Surfactant Pulmonary Distribution After Clinically Relevant Intratracheal Delivery.

Optimizing pulmonary exogenous surfactant delivery remains a critical challenge in neonatal care, particularly for achieving uniform distal lung deposition while minimizing airway obstruction. This study aimed to establish a preclinical imaging framework for quantitative assessment of exogenous surfactant lung distribution in vivo using contrast-enhanced ultrashort echo time (UTE) MRI and to evaluate the impact of physiological processes on surfactant retention and localization. Six juvenile rabbits received intratracheal instillation of a gadolinium-enhanced surfactant solution under clinically relevant conditions. High-resolution, motion-robust 3D UTE MRI datasets were acquired, enabling voxel-wise quantification of signal enhancement, gadolinium concentration, and spatial surfactant lung distribution. Peripheral volume fraction, laterality index, and distality index were computed to characterize deposition homogeneity and distal penetration. In vivo measurements were compared with previously reported ex vivo data from isolated rabbit thoraces. Quantitative MRI enabled precise mapping of surfactant within peripheral alveolar regions. Forty-two percent of the instilled dose was retained in vivo, compared with 93.5% ex vivo. Laterality indices confirmed balanced right-left distribution, while distality indices demonstrated consistent peripheral deposition. The radial UTE sequence minimized motion artifacts and enabled robust voxel-wise quantification under physiological breathing conditions. Quantitative in vivo MRI provides a sensitive and reliable method for assessing pulmonary surfactant delivery, spatial distribution, distal penetration, and homogeneity of deposition. Comparison with ex vivo data underscores the role of physiological processes in surfactant retention. This framework supports optimization of administration strategies in preclinical models and may be extended to other intrapulmonary therapies, establishing a versatile imaging platform for translational research.