HE3 MR Diffusion & Low Dose CT Quantitation of Emphysema

HE3 MR 扩散

• 批准号: 6662557
• 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/6662557
• 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）： 该提案的目标是开发和评估肺气肿的超极化氦 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) 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。气肿。肺气肿是一种肺部病理异常，表现为末梢气腔扩大和气腔壁破坏，常见于数百万慢性阻塞性肺病患者。 随着人们对炎症机制和蛋白酶在慢性阻塞性肺病发病机制中的作用的了解不断增加，人们开始寻找新的抗炎策略和酶抑制剂。 尽管处于发展的早期阶段，其中一些新方法最终可能提供改变疾病进程的治疗方法。 肺气肿的准确生物标志物将有助于早期诊断、干预和新疗法的评估。 尽管肺活量测定法可用于诊断慢性阻塞性肺病，但它是评估肺气肿的相对不准确的方法。传统 CT 是评估肺气肿严重程度的一种高度准确的方法，可以通过气腔扩大和肺泡破坏导致肺部 X 射线衰减的减少来量化肺气肿的严重程度。 然而，CT 是使用相对较高剂量的电离辐射进行的，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，已经设计了其他肺气肿无创成像测试，不需要或大大减少电离辐射。 一项新测试 He-3 dMRI 使用专门构建的 MRI 脉冲序列来测量吸入的超极化 He-3 气体的扩散性受肺泡壁限制的程度。 当肺气肿中肺泡腔扩大时，表观扩散系数 (ADC) 就会增加（气体扩散受到的限制较少）。 另一种测试，即低剂量 CT 扫描，可以用低于传统 CT 20% 的辐射剂量描绘大量肺部细节，但尚未开发用于肺气肿的定量。 He-3 dMRI 和 LD-QCT 虽然前景广阔，但最佳技术和有效性尚未确定。 我们假设 1) 与肺形态测量相比，优化 He-3 dMRI 和 LD-QCT 技术将能够灵敏、准确地评估肺气肿，2) 优化的 He-3 dMRI 和 LD-QCT 技术将提供有效的肺气肿生物标志物，适用于其他人群，3) He-3 dMRI 和 LD-QCT 将能够识别肺气肿随时间的进展情况。 我们将研究三组​​不同的科目。 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，可以最准确地量化肺叶切除标本中病理性存在的肺气肿量（目标 I）。 然后，我们将使用优化的扫描和分析技术来验证不同组中的这些测量结果，并与肺叶切除标本中存在的肺气肿量进行比较（目标 II）。 在第三组受试者中，我们将在连续时间点确定 ADC 和 LD-QCT 肺衰减测量值，以评估肺气肿进展（目标 III）。