Novel Ultrasonic Methods for the Assessment of Pulmonary Edema

我们建议开发新的基于超声的方法来检测和量化肺水肿 由于充血性心力衰竭（HF），影响了620万美国人。常规超声不适合 由于来自数百万个空气-液体界面的大量超声多次散射， 在肺泡壁和充满空气的肺泡之间。我们建议利用这一特点。事实上，每个 散射事件可以被看作是超声波将信息嵌入到微结构上的机会。 肺实质的结构。我们已经开发了新的方法来计算散射平均自由 超声波在肺组织中的传播路径（SMFP）。我们发现肺泡对超声的散射可以 用于表征肺实质。在提议的努力中，我们假设测量的SMFP将 量化肺组织水肿。目前有三种方法用于肺部成像，以诊断和跟踪肺部 疾病：胸部X线（CXR）、CT扫描和核磁共振（NMR）扫描。这些影像 模态通常用于提供关于改善或恶化肺充血的信息 HF。连续定量超声肺部评估（非成像）对于评估以下情况特别有帮助： HF导致的肺水肿进展或消退。我们假设超声散射可以 用于量化肺水肿。这个新的假设将通过完成这些具体的 目标：目标1。建立超声方法，用于评估和分期大鼠模型的水肿， 通过使用肺门钳夹模型产生缺血-再灌注损伤， 肺水肿利用多重散射存在的超声方法将在 体内水肿和正常肺。湿：干重比（W/D）、CT扫描和膨胀固定的肺组织学将 用于量化肺水肿。肺水肿时超声波在肺内的多重散射变化 与水肿类型和蛋白质含量无关。目标2.制定评估方法， 肺水肿在人的肺部在较低的频率。因为心脏病专家通常使用低频 超声探头，目标1中开发的方法如果实施，将更适合用于人类肺部 在3到5 MHz范围内。目标3.为了验证所提出的肺水肿定量方法， 人类病人10例HF患者将在因HF加重入院后接受研究。将测量SMFP 在每侧3个肋间隙连续3-5天，并与其他临床参数进行比较， 肺水肿和正常肺SMFP的5名健康志愿者。在这项研究中，我们 使用超声波生成反映液体量的数字（SMFP），而不是图像。这种平移 该项目对RFA做出了回应，因为它将生物工程师与两名临床科学家配对， 新的，廉价的方法来量化与HF相关的肺水肿。未来的大型多中心研究 可用于评估监测HF患者的廉价新技术的实用性。

We propose to develop novel ultrasound-based methods for the detection and quantification of pulmonary edema due to congestive heart failure (HF), affecting 6.2 million Americans. Conventional ultrasound is unsuitable for imaging the lung, due to the large amount of ultrasound multiple scattering from the millions of air-liquid interfaces between alveolar walls and air filled alveoli. We propose to take advantage of this feature. Indeed, each scattering event can be seen as an opportunity for the ultrasound wave to embed information on the micro- architecture of the lung parenchyma. We have developed novel methods to calculate the scattering mean free path (SMFP) of ultrasound waves in lung tissue. We showed that the scattering of ultrasound by the alveoli can be exploited to characterize lung parenchyma. In the proposed effort, we hypothesize that measured SMFP will quantify edema in lung tissue. Three methods are currently used to image lungs to diagnose and follow lung disease: chest X-rays (CXR), CT scan, and nuclear magnetic resonance (NMR) scan. None of these imaging modalities are typically used to provide information about improving or worsening pulmonary congestion due to HF. Serial quantitative ultrasound lung assessments (not imaging) would be particularly helpful for evaluation of progression or resolution of pulmonary edema due to HF. We hypothesize that ultrasound scattering can be exploited to quantify pulmonary edema. This novel hypothesis will be explored by accomplishing these specific aims: Aim 1. To develop ultrasonic methods for the assessment and staging of edema in a rat model of pulmonary edema by using a lung hilar clamp model creating ischemia-reperfusion injury that reliably results in pulmonary edema. Ultrasound methods exploiting the presence of multiple scattering will be implemented in in- vivo edematous and normal lungs. Wet:dry weight ratio (W/D), CT scans, and inflation-fixed lung histology will be used to quantify pulmonary edema. Changes in multiple scattering of ultrasound waves in lung due to edema are not related to the type of edema and protein content. Aim 2. To develop methods for the assessment of pulmonary edema in human lungs at lower frequency. Because cardiologists commonly use low frequency ultrasound probes, the methods developed in Aim 1 would be better suited for use in human lungs if implemented in the 3 to 5 MHz range. Aim 3. To validate the proposed methods for quantification of pulmonary edema in human patients. Ten HF patients will be studied after admission for a HF exacerbation. SMFP will be measured at 3 intercostal spaces on each side serially over 3-5 days and compared to other clinical parameters of pulmonary edema and to SMFP of normal lung obtained from 5 healthy volunteers. In the proposed study, we use ultrasound to generate a number reflecting the amount of fluid (the SMFP), not an image. This translational project is responsive to this RFA because it pairs a bioengineer with two clinician-scientists to develop innovative, new, inexpensive methods to quantify pulmonary edema associated with HF. Future large multicenter studies could be performed to assess utility of an inexpensive novel technology to monitor patients with HF.