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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.

本R 01申请的目的是开发一种快速成像局部通气的方法，无造影剂的小动物肺顺应性。我们目前对宇宙的理解肺的正常功能和肺病的机制来自小动物研究。然而，在这方面，在小动物模型中的肺功能成像由于运动和相对小的肺的大小。使用体积描记法的肺功能测试已被用于评估肺功能和损伤，有效性和实用性有限，特别是在小动物中。此外，只有聚合产生功能性能的测量，并且不能评估局部肺变化。一个能够提供空间和时间分辨信息的改进的成像方法通气对于那些研究基础肺生理学和肺功能障碍的发病和一系列呼吸道疾病的进展。它还将促进药物发现和功效研究旨在减轻呼吸道疾病理想的方法将提供定量的区域功能信息，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微型CT或MRI 不符合这些要求中的一个或多个。为了满足这一需求，我们将建立和评估一个新颖的，易于实施的，高效的X- X射线相位衬度（XPC）方法用于小动物模型的通气成像。肺非常适合 XPC成像，因为它主要由薄组织结构分隔的空气空间组成。空气组织界面导致X射线束经历无数次强烈的折射，在肺部测量的强度中的纹理称为斑点。有关区域的详细信息肺空气体积（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很多，但对于台式成像仍然完全未被探索。我们的方法涉及成像方法的高度技术创新，将显著扩展目前小动物肺功能成像的范围。拟议一种称为参数XPC（P-XPC）成像的方法将产生描绘预计的RLAV分布。当针对呼吸中的任何给定两点计算差分图像时，将实现循环、通气或肺顺应性成像。初步的体内和计算研究为支持拟议的研究而进行。该项目的具体目标如下。目标1：开发P-XPC成像方法，用于估计投影RLAV分布;目标2：为P-XPC成像优化XPC成像系统。目的3：评价P-XPC的诊断能力在体内疾病的两种临床前动物模型中进行成像。