HE3 MR Diffusion & Low Dose CT Quantitation of Emphysema

描述(由申请人提供)： 本研究的目的是开发和评估肺气肿的超极化氦-3弥散磁共振成像(He-3dMRI)和低剂量定量计算机断层扫描(LD-QCT)指标，作为肺气肿的存在、严重程度和进展的非侵入性生物标志物。肺气肿是一种肺部的病理异常，以终末空隙扩大和空隙壁破坏为特征，常见于数百万慢性阻塞性肺疾病患者。随着对炎症机制和蛋白水解酶在COPD发病机制中作用的认识的增加，人们正在寻找新的抗炎策略和酶抑制剂。虽然还处于研发的早期阶段，但其中一些新方法可能最终会提供改变疾病进程的治疗方法。准确的肺气肿生物标志物将使早期诊断、干预和新疗法的评估成为可能。虽然肺活量测定被用来诊断COPD，但它是一种相对不准确的评估肺气肿的手段。常规CT是评估肺气肿严重程度的一种非常准确的方法，它可以通过肺泡扩大和肺泡破坏导致的肺部X射线衰减的减少来量化。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，已经设计了其他非侵入性的肺气肿成像测试，这些测试不需要电离辐射或大大减少了电离辐射。一种名为He-3 dMRI的新测试使用了一种特殊构造的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的限制程度。当肺气肿的肺泡间隙扩大时，这种测量，即表观扩散系数(ADC)会增加(气体扩散受到的限制较小)。另一种测试是低剂量CT扫描，它可以在不到常规CT辐射剂量的20%的情况下描绘出实质性的肺部细节，但还没有开发出用于肺气肿定量的测试。尽管前景看好，但He-3dMRI和LD-QCT的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，优化的He-3dMRI和LD-QCT技术将允许对肺气肿进行敏感和准确的评估；2)优化的He-3dMRI和LD-QCT技术将提供有效的肺气肿生物标志物，可应用于其他人群；以及3)He-3dMRI和LD-QCT将允许随着时间的推移识别肺气肿的进展。我们将研究三组不同的科目。在第一组，我们将确定哪些扫描和分析参数提供ADC和LD-QCT生物标记物，最准确地量化肺叶切除标本中病理存在的肺气肿的数量(目标I)。然后，我们将使用优化的扫描和分析技术在另一组中验证这些测量，并与肺叶切除术标本中存在的肺气肿数量进行比较(AIM II)。在第三组受试者中，我们将测定连续时间点的ADC和LD-QCT肺密度测量，以评估肺气肿的进展(目标III)。

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).