Proton MRI to measure lung ventilation and perfusion

描述(申请人提供)：与计算机断层扫描和核医学技术等其他成像方式相比，人类肺的定量功能磁共振成像(MRI)相对较差。这些MRI技术不受电离辐射或对比剂注射的限制，从而打开了无限重复研究的大门，并提供了新领域的可能性，如时间成像。该计划的长期目标是开发和建立人类肺的定量功能性质子磁共振成像，作为一种随时可用的手段，提供与生理和临床相关的灌注、通风和气体交换的区域信息。我们开发的技术使我们能够定量地测量肺密度(空气含量的直接测量)、肺血流量和特定的 通风。这些技术结合在一起，使我们能够定量绘制通风/灌流比图。 (v？A/Q？)，其空间分辨率接近于人类肺的功能气体交换单位的规模。生物工程研究伙伴关系(BRP)头五年的总体目标是使这些研究技术可被更广泛的研究社区翻译，以便它们可以在研究和临床试验中用作生物标记物，未来的目标是临床适用性。为此，这些技术需要：a)加强它们的生理解释，为解释它们产生的结果提供严格的基础；b)进一步开发成高效和可获得的临床研究技术；以及c)进行验证性研究，以证明它们在临床研究中的适用性。为此，我们提出了一系列协调的研究，这些研究将：1)使用高度解剖逼真的硅内建模，将所有成像方式的生理学解释置于可靠的基础上；2)通过与临床前大型动物模型中注射和吸入的微球测量进行比较，验证灌流、通风和VA/Q的成像；3)交叉验证人类的VA/Q成像，从多重惰性气体消除技术的黄金标准非成像方法获得VA/Q的定量测量，包括在正常肺和病变肺中；(4)优化现有的MR方法，通过改进技术扩充肺功能成像的谱系。这项BRP的完成将带来一套可供使用的经验证的定量功能性磁共振肺成像方法，用于商业扫描仪测量密度、灌流、通风和通风/灌流比。

DESCRIPTION (provided by applicant): In comparison to other imaging modalities such as computerized tomography and nuclear medicine techniques, quantitative functional magnetic resonance imaging (MRI) of the human lung is relatively poorly developed. These MRI techniques are not limited by exposure to ionizing radiation or contrast injection and thus open the door to unlimited repeated studies, and offer the possibility of new fields such as temporal imaging. The long-term objective of this program is to develop and establish quantitative functional proton MRI in the human lung as a readily available means of providing regional information on perfusion, ventilation and gas exchange that is physiologically and clinically relevant. Techniques we have developed allow us to quantitatively measure the spatial distributions of lung density (a direct measure of air content), pulmonary blood flow, and specific ventilation. Together these techniques permit us to quantitatively map ventilation- perfusion ratio (V? A/Q?), which uniquely determines pulmonary gas exchange, with a spatial resolution that is close to the scale of the functional gas exchange unit of the human lung. The overall goal of the first five years of this Bioengineering Research Partnership (BRP) is to make these research techniques translatable to the wider research community so that they may be used as biomarkers in research studies and in clinical trials, with a future goal of clinical applicability To do so, these techniques need to: a) have their physiological interpretation strengthened to provide a rigorous basis for interpretation of the results they produce; b) be further developed into efficient and accessible techniques for clinical studies; and c) be subjected to validation studies to prove their applicability for clinical studies. To these ends we propose a coordinated series of studies that will: 1) use highly anatomically-realistic in-silico modeling to place the physiological interpretation of all imaging modalities on a sound footing; 2) validate imaging of perfusion, ventilation and V A/Q by comparing with injected and inhaled microsphere measurements in a pre-clinical large animal model; 3) cross- validate imaging of V A/Q in humans with quantitative measures of VA/Q obtained from the gold-standard non-imaging approach of the multiple inert gas elimination technique, both in the normal and diseased lung; and 4) optimize the current MR methodology and expand the repertoire of functional lung imaging with improved techniques. Completion of this BRP will result in deliverables of an accessible suite of validated quantitative functional MR lung imaging methods for use on commercially available scanners to measure density, perfusion, ventilation, and ventilation-perfusion ratio.