HE3 MR Diffusion & Low Dose CT Quantitation of Emphysema

HE3 MR 扩散

• 批准号: 6768659
• 负责人: DAVID S GIERADA
• 金额: $ 38.25万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-23 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6768659
• 关键词: bioimaging /biomedical imaging; biomarker; clinical research; computed axial tomography; diagnosis design /evaluation; diagnosis quality /standard; emphysema; human subject; image enhancement; lung imaging /visualization /scanning; magnetic resonance imaging; morphometry; patient oriented research; pneumonectomy

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and evaluate hyperpolarized helium-3 diffusion magnetic resonance imaging (He-3 dMRI) and low dose quantitative computed tomography (LD-QCT) indexes of emphysema as noninvasive biomarkers for the presence, severity, and progression of emphysema. Emphysema is a pathologic abnormality of the lungs defined by enlargement of terminal airspaces and destruction of airspace walls, and is commonly present in the millions of patients with chronic obstructive pulmonary disease. Increased knowledge regarding the role of inflammatory mechanisms and proteinases in the pathogenesis of COPD is leading to searches for newer anti-inflammatory strategies and enzyme inhibitors. Though in the early stages of development, some of these new approaches may eventually provide therapy that alters the course of the disease. Accurate biomarkers of emphysema would allow for early diagnosis, intervention, and evaluation of new therapies. Though spirometry is used to diagnose COPD, it is a relatively inaccurate means of assessing for emphysema. Conventional CT is a highly accurate way to assess the severity of emphysema, which can be quantified by the decrease in x-ray attenuation of the lungs that results from airspace enlargement and alveolar destruction. However, CT is performed using relatively high doses of ionizing radiation, which limits its acceptability as a screening and follow-up test, particularly in early or mild disease. In recent years, other noninvasive imaging tests for emphysema have been designed that require no or greatly reduced ionizing radiation. One new test, He-3 dMRI, uses a specially constructed MRI pulse sequence to measure the degree to which diffusivity of inhaled hyperpolarized He-3 gas is restricted by alveolar walls. This measurement, the apparent diffusion coefficient (ADC), is increased (gas diffusion is less restricted) when alveolar spaces are enlarged in emphysema. Another test, low dose CT scanning, allows depiction of substantial lung detail at less than 20 percent of the radiation dose of conventional CT, but has not been developed for quantitation of emphysema. Though promising, the optimal technique and validity of both He-3 dMRI and LD-QCT have yet to be established. We hypothesize that 1) Optimizing He-3 dMRI and LD-QCT techniques will allow sensitive and accurate assessment of emphysema, compared to lung morphometry, 2) The optimized He-3 dMRI and LD-QCT techniques will provide valid biomarkers of emphysema that can be applied to other populations, and 3) He-3 dMRI and LD-QCT will allow identification of emphysema progression over time. We will study three separate groups of subjects. In the first group, we will determine which scanning and analysis parameters provide ADC and LD-QCT biomarkers that most accurately quantify the amount of emphysema present pathologically in lobectomy specimens (Aim I). We will then use the optimized scanning and analysis techniques to validate these measurements in a different group, compared to the amount of emphysema present in lobectomy specimens (Aim II). In a third group of subjects, we will determine ADC and LD-QCT lung attenuation measurements at serial time points to assess for emphysema progression (Aim III).

描述（由申请人提供）： 本提案的目的是开发和评价超极化氦-3扩散磁共振成像（He-3 dMRI）和低剂量定量计算机断层扫描（LD-QCT）肺气肿指数，作为肺气肿存在、严重程度和进展的非侵入性生物标志物。肺气肿是肺的病理异常，其定义为终末气腔扩大和气腔壁破坏，并且通常存在于数百万慢性阻塞性肺疾病患者中。 关于炎症机制和蛋白酶在COPD发病机制中的作用的知识的增加导致对新的抗炎策略和酶抑制剂的搜索。 虽然在发展的早期阶段，这些新方法中的一些可能最终提供改变疾病进程的治疗。 准确的肺气肿生物标志物将允许早期诊断，干预和评估新的治疗方法。 虽然肺量测定法用于诊断COPD，但它是一种相对不准确的评估肺气肿的方法。常规CT是评估肺气肿严重程度的一种高度准确的方法，肺气肿的严重程度可以通过由空气空间扩大和肺泡破坏引起的肺部X射线衰减的减少来量化。 然而，CT使用相对高剂量的电离辐射进行，这限制了其作为筛查和随访测试的可接受性，特别是在早期或轻度疾病中。 近年来，其他非侵入性肺气肿成像测试已被设计，不需要或大大减少电离辐射。 一种新的测试，He-3 dMRI，使用一种特殊构造的MRI脉冲序列来测量吸入的超极化He-3气体的扩散率受到肺泡壁限制的程度。 当肺气肿肺泡腔扩大时，表观扩散系数（ADC）增加（气体扩散受到较少限制）。 另一种测试，低剂量CT扫描，允许描绘实质性的肺细节在不到20%的辐射剂量的传统CT，但尚未开发用于定量肺气肿。 虽然有希望，但He-3 dMRI和LD-QCT的最佳技术和有效性尚未建立。 我们假设：1）与肺形态测量相比，优化He-3 dMRI和LD-QCT技术将允许对肺气肿进行灵敏和准确的评估，2）优化的He-3 dMRI和LD-QCT技术将提供可应用于其他人群的有效肺气肿生物标志物，3）He-3 dMRI和LD-QCT将允许识别肺气肿随时间的进展。 我们将研究三组不同的主题。 在第一组中，我们将确定哪些扫描和分析参数提供ADC和LD-QCT生物标志物，最准确地量化肺叶切除术标本中病理存在的肺气肿量（Aim I）。 然后，我们将使用优化的扫描和分析技术，以验证这些测量在一个不同的组，相比，肺气肿的量存在于肺叶切除标本（目的II）。 在第三组受试者中，我们将确定连续时间点的ADC和LD-QCT肺衰减测量值，以评估肺气肿进展（Aim III）。