Ultrasound-Induced Pulmonary Hemorrhage During Diagnostic Examination of the Lung

描述（由申请人提供）：在初步研究中，通过7.6 MHz诊断超声（DUS）进行的肺部检查显示，明亮的肺表面图像上出现快速发展的彗星尾伪影。这种进行性伪影表明正在诱导肺出血（PH），这通过观察肺中的PH进行了验证。阈值位于约0.44的低机械指数，其小于美国DUS上限的四分之一。这一令人不安的发现推翻了目前DUS的安全性假设，并意味着患者可能有肺损伤的风险。脉冲超声诱发PH的发现已有20多年的历史。但机制仍不确定。2000年和2008年的权威综述认识到诊断超声（DUS）诱发PH（DUS-PH）的可能性，但尚未制定有用的安全性策略。当时，预期只有意外的肺暴露，这似乎不太可能导致PH。不幸的是，这种安全性的外观是短暂的。DUS肺部检查的新方法现在正迅速成为重症监护医学和其他临床环境中的常规方法，这有利于医生的有效性和患者护理。然而，随着肺部超声在全球范围内成为常规，许多患者将接受故意的肺部暴露并遭受PH的风险。迫切需要针对这种爆炸性安全问题的解决方案。从生物物理学的角度来看，肺是以气体为主的组织，其必须与DUS强烈相互作用。核心假设是DUS-PH始于超声脉冲对肺毛细血管的血气屏障的直接冲击，毛细血管应力导致出血。这导致肺泡隔中的进行性应力，从而导致挫伤样肺损伤。由于高血压或水肿，某些患者的肺泡更脆弱，可能特别容易受到DUS-PH的影响。本项目的目的是详细了解DUS-PH，并纠正肺部超声安全指南的不足。我们的策略有三个具体目标：首先，将使用包括图像反馈在内的新方法，针对不同的DUS模式和频率以及通常由肺部超声诊断的常见患者状况，研究肺部对DUS-PH的相对易感性。其次，DUS-PH的机制将通过使用活体显微镜来表征PH的开始和进展来确定，这将允许对该现象进行物理建模。最后，将开发潜在人类DUS-PH的剂量测定算法，并使用人类DUS肺检查的猪模型进行测试。实现这些目标的预期结果是了解不同患者的肺易感性，表征导致DUS-PH的生物物理过程，以及适合超声医师教育和指导的人类安全策略。这些成就将提高对DUS-PH的认识，并确保患者安全，同时保留获取最佳DUS图像的能力。该项目的总体影响将是启动肺部超声的新安全概念，并积极主动地解决这一紧急公共卫生问题。

DESCRIPTION (provided by applicant): In preliminary research, lung examination by 7.6 MHz diagnostic ultrasound (DUS) showed the rapid development comet-tail artifacts across the bright lung surface image. This progressing artifact was indicative of ongoing induction of pulmonary hemorrhage (PH), which was validated by observation of PH in the lung. A threshold was located at a low Mechanical Index of ~0.44, which is less than one quarter of the DUS upper limit in the United States. This troubling finding overturns present DUS safety assumptions and implies that patients may be at risk of lung injury. Pulsed-ultrasound induced PH was discovered more than 20 yr. ago, but the mechanism remains uncertain. Authoritative reviews in 2000 and 2008 recognized a potential for diagnostic ultrasound (DUS) induced PH (DUS-PH), but no useful safety strategy has been devised. At that time, only accidental lung exposure was expected, which seemed unlikely to cause PH. Unfortunately, this appearance of safety was ephemeral. New methods of DUS lung examination are now rapidly becoming routine in critical care medicine and other clinical settings, which benefits physician effectiveness and patient care. However, as pulmonary ultrasound becomes routine worldwide, many patients will receive deliberate lung exposure and suffer a risk of PH. A solution for this explosive safety issue is urgently needed. From the biophysical perspective, lung is a tissue dominated by gas, which must interact strongly with DUS. The central hypothesis is that DUS-PH starts from the direct impingement of ultrasound pulses on the blood-air barrier of pulmonary capillaries with hemorrhage resulting from capillary stress. This leads to progressive stress in alveolar septa leading to the contusion-like lung injury. Certain patient conditions having more vulnerable alveoli due to hypertension or edema may be particularly susceptible DUS-PH. The objective of this project is to gain a detailed understanding of DUS-PH and to correct the deficiency in safety guidance for pulmonary ultrasound. Our strategy has three specific aims: First, the relative susceptibility of the lung to DUS-PH will be investigated, using novel methods including image feedback, for different DUS modes and frequencies and for common patient conditions often diagnosed by pulmonary ultrasound. Second, mechanisms of DUS-PH will be identified by using intravital microscopy to characterize the initiation and progression of PH, which will allow physical modeling of the phenomena. Finally, a dosimetric algorithm for potential human DUS-PH will be developed and tested using a swine model of human DUS lung examination. The outcomes expected from achieving these aims are an understanding of lung susceptibility in different patients, a characterization of the biophysical processes leading to DUS-PH, and a human safety strategy suitable for sonographer education and guidance. These achievements will raise awareness of DUS-PH and assure patient safety while retaining the ability to acquire optimal DUS images. The overall impact of this project will be the initiation of new safety concepts for pulmonary ultrasound and the proactive solution of this emergent public health problem.