Development of a Rapid Method for Imaging Regional Ventilation in Small Animals w/o Contrast Agents

开发一种无需造影剂的小动物局部通气成像快速方法

基本信息

批准号：
9888370
负责人：
Mark A Anastasio
金额：
$ 41.98万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-28 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9888370
关键词：
Address Air Animal Disease Models Animal Model Animals Breathing Communities Contrast Media Development Diagnostic Evaluation Functional Imaging Image Imaging technology Longitudinal Studies Low Dose Radiation Lung Lung Compliance Lung diseases Magnetic Resonance Imaging Maps Measures Methods Monitor Motion Mus Pathology Performance Phase Physics Physiology Plethysmography Process Pulmonary Emphysema Pulmonary function tests Radiation Radiation Dose Unit Research Resolution Resource Sharing Respiratory physiology Roentgen Rays Scientist Source Structure System Technical Degree Techniques Texture Thinness Time Tissues Translating animal imaging base computer studies contrast imaging cost detector drug discovery drug efficacy efficacy study experience falls imaging modality imaging system improved in vivo in vivo monitoring innovation lung imaging lung injury lung pressure lung volume machine learning method microCT mouse model novel parametric imaging pre-clinical pressure rapid technique respiratory supervised learning ventilation

项目摘要

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.

该 R01 应用的目标是开发一种快速方法，用于对区域通气和无需造影剂的小动物的肺顺应性。我们目前的大部分理解肺部的正常功能和肺部疾病的机制来自小动物研究。然而，由于运动和相对较小，小动物模型的肺功能成像在技术上具有挑战性肺部的大小。使用体积描记法进行肺功能测试已用于评估肺功能功能和损伤的有效性和实用性有限，特别是在小动物中。此外，仅聚合产生了功能表现的测量结果，并且无法评估局部肺部变化。一个改进的成像方法，可以提供空间和时间分辨的信息通气对于研究基础肺生理学以及肺通气的发生和发展具有重要价值。多种呼吸系统疾病的进展。它还将促进药物发现和功效研究旨在减轻呼吸道病理。理想的方法是提供定量的区域功能信息，适用于纵向研究（低辐射剂量），并且具有简单且负担得起的允许广泛使用的实施。目前可用的成像方法包括显微 CT 或 MRI 不符合其中一项或多项要求。为了满足这一需求，我们将建立并评估一种新颖、易于实施且高效的 X- 用于小动物模型通气成像的射线相衬（XPC）方法。肺非常适合 XPC 成像，因为它主要由薄组织结构分隔开的空气空间组成。空气组织界面使 X 射线束经历多次强烈的折射，从而产生独特的在肺部测量的强度纹理称为散斑。有关区域的详细信息肺气量 (RLAV) 分布被编码在散斑中。利用肺斑点的好处检测和监测肺功能的方法有很多，但台式成像尚未完全探索。我们的方法涉及图像形成方法和技术方面的高度技术创新将显着扩展目前小动物功能性肺成像的界限。拟议的称为参数 XPC (P-XPC) 成像的方法将生成描绘预计 RLAV 分布。当计算呼吸中任意给定两点的差分图像时将实现周期、通气或肺顺应性成像。初步体内和计算研究已进行了支持拟议的研究。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 图像形成方法；目标 2：优化 P-XPC 成像的 XPC 成像系统。目标 3：评估 P-XPC 的诊断能力两种临床前疾病动物模型的体内成像。