DEVELOPMENT OF A RAPID METHOD FOR IMAGING REGIONAL VENTILATION IN SMALL ANIMALS W/O CONTRAST AGENTS

此R01应用程序的目标是开发一种快速成像区域通风和 未加造影剂的小动物的肺顺应性。我们目前对这一问题的大部分理解 肺的正常功能和肺部疾病的机制来自于小动物的研究。然而， 小动物模型的肺功能成像在技术上具有挑战性，因为运动和相对较小的 肺的大小。使用体积描记的肺功能测试已经被用来评估肺 功能和损伤具有有限的有效性和实用性，特别是在小动物身上。此外，只有聚合 产生了功能表现的测量，并且不能评估任何区域性的肺变化。一个 改进的成像方法可以提供关于以下内容的空间和时间分辨率信息 呼吸机对研究基础肺生理学及肺功能的发生和发展具有重要价值 一系列呼吸系统疾病的进展。它还将促进药物发现和疗效研究。 旨在减轻呼吸道病理。理想的方法将提供定量的区域泛函 信息，适用于纵向研究(低辐射剂量)，并具有简单和负担得起的 允许广泛使用的实现。目前可用的成像方法包括Micro-CT或MRI 不符合这些要求中的一项或多项。 为了满足这一需求，我们将建立和评估一种新颖、易于实施和高效的X- 射线相衬(XPC)法用于小动物模型的通风成像。肺非常适合于 XPC成像，因为它主要由薄组织结构隔开的空气空间组成。空气组织 界面导致X射线束经历无数而强烈的折射，从而产生独特的 在肺部测量的强度的纹理称为斑点。有关地区的详细信息 肺空气容量(RLAV)分布编码在散斑中。开发肺斑块的好处 检测和监测肺功能的方法很多，但对于台式成像仍完全没有探索。 我们的方法涉及到高度的技术创新，成像方法和 这将大大扩展目前在小动物身上进行功能肺成像的界限。建议数 这种方法被称为参数xPC(P-xPC)成像，它将产生描述 预计的RLAV分布。当计算出呼吸中任何给定两点的微分图像时 将实现循环、通风或肺顺应性成像。初步的体内和计算研究 为了支持拟议的研究，已经进行了一些研究。该项目的具体目标如下。 目标1：开发用于估计投影RLAV分布的P-xPC成像方法；目标2： 优化用于P-xPC成像的xPC成像系统。目的3：评价P-XPC的诊断能力 两种临床前疾病动物模型的体内成像。

The objective of this R01 application is to develop a rapid method for imaging regional ventilation and lung compliance in small animals without contrast agents. Much of our current understanding of the normal functioning of the lung and mechanisms of lung disease comes from small animal studies. However, lung function imaging in small animal models is technically challenging due to motion and the relatively small size of the lungs. Pulmonary function testing using plethysmography has been employed to assess lung function and injury with limited validity and utility, particularly in small animals. Additionally, only aggregate measures of functional performance are produced and no regional lung changes can be assessed. An improved imaging method that could provide spatially- and temporally-resolved information regarding ventilation would be of great value to those studying basic pulmonary physiology and the onset and progression of a large range of respiratory diseases. It would also facilitate drug discovery and efficacy studies aimed to mitigate respiratory pathology. The ideal method would provide quantitative regional functional information, be applicable to longitudinal studies (low radiation dose), and have a simple and affordable implementation that permits widespread use. Currently available imaging methods including micro-CT or MRI fall short in one or more of these requirements. To address this need, we will establish and evaluate a novel, easy to implement, and highly effective X- ray phase-contrast (XPC) method for ventilation imaging in small animal models. The lung is ideally suited to XPC imaging because it is comprised mainly of air spaces separated by thin tissue structures. The air-tissue interfaces cause the X-ray beam to experience numerous and strong refractions that produce a distinctive texture in the intensity measured over the lungs known as speckle. Detailed information regarding the regional lung air volume (RLAV) distribution is encoded in the speckle. The benefits of exploiting lung speckle for detecting and monitoring lung function are numerous but remain entirely unexplored for benchtop imaging. Our approach involves a high degree of technical innovation regarding image formation methods and will significantly extend the current boundaries of functional lung imaging in small animals. The proposed method, referred to as parametric XPC (P-XPC) imaging, will produce 2D parametric images that depict the projected RLAV distribution. When differential images are computed for any given two points in the breathing cycle, ventilation or lung compliance imaging will be achieved. Preliminary in vivo and computational studies have been conducted in support of the proposed research. The specific aims of the project are as follows. Aim 1: Develop P-XPC image formation methods for estimating the projected RLAV distribution; Aim 2: Optimize an XPC imaging system for P-XPC imaging. Aim 3: Evaluate the diagnostic capability of P-XPC imaging in two pre-clinical animal models of disease in vivo.