Boschi Federico, Nicolato Elena, Benati Donatella, Marzola Pasquina, Sbarbati Andrea
Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
Biomed Pharmacother. 2008 Jul-Aug;62(6):410-9. doi: 10.1016/j.biopha.2008.01.004. Epub 2008 Feb 20.
Pharmacological MRI at 4.7 T was used to investigate the secretory response to Sylvestris pine oil stimuli in the rat airways, with the aim of developing an in vivo model in a small laboratory animal. The availability of such a model would greatly facilitate the drug discovery process using compounds active on airway surface liquid (ASL) production, and would make it possible to obtain information on chemoreceptoral mechanisms and to test the effects of environmental substances on the airways. T1- and T2-weighted images were acquired in the trachea and larynx before and at various times after exposure to pine oil. Several post-processing procedures were tested in order to improve the visibility of the secretory response and to measure the enhancement of the signal intensity of ASL. A semiautomatic application software was written to localize and to measure the volume involved in the secretory response to a compound administration. A significant effect of the pine oil administration on the secretory response was founded in trachea (p<0.01) and in the salivary glands (p<0.01). 3D reconstructions of MRI data and virtual endoscopy permitted a quick visualization of tracheal morphology and localization of the greatest response to stimulus. The study demonstrated that, despite technical problems due to the air/tissue interface and to the small dimensions of the experimental animals, the secretory response can be evaluated and the pharmacological MRI (phMRI) of the rat airways is feasible. The potential and the limitations of phMRI investigation in drug targeting of ASL are discussed.
采用4.7 T的药物磁共振成像技术研究大鼠气道对樟子松油刺激的分泌反应，目的是在小型实验动物中建立一种体内模型。这样一种模型的建立将极大地促进利用对气道表面液体（ASL）产生有活性的化合物进行药物研发的过程，并且能够获取有关化学感受机制的信息，以及测试环境物质对气道的影响。在暴露于松油之前及之后的不同时间，采集气管和喉部的T1加权和T2加权图像。测试了几种后处理程序，以提高分泌反应的可视性，并测量ASL信号强度的增强。编写了一个半自动应用软件，用于定位和测量对化合物给药的分泌反应所涉及的体积。发现松油给药对气管（p<0.01）和唾液腺（p<0.01）的分泌反应有显著影响。MRI数据的三维重建和虚拟内窥镜检查能够快速可视化气管形态以及对刺激的最大反应的定位。该研究表明，尽管由于空气/组织界面以及实验动物体型较小而存在技术问题，但仍可评估分泌反应，并且大鼠气道的药物磁共振成像（phMRI）是可行的。讨论了phMRI研究在ASL药物靶向方面的潜力和局限性。
