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）检查肺部，在明亮的肺表面图像上显示快速发展的彗星尾伪影。这一渐进的伪影表明正在诱导肺出血（PH），这是通过观察肺PH来验证的。阈值位于~0.44的低机械指数，不到美国DUS上限的四分之一。这一令人不安的发现推翻了目前的DUS安全性假设，并暗示患者可能存在肺损伤的风险。脉冲超声诱导PH是在20多年前发现的，但其机制仍不确定。2000年和2008年的权威评论认识到诊断超声（DUS）诱导PH （DUS-PH）的潜力，但没有制定有用的安全策略。在那个时候，只有意外的肺部暴露是预期的，这似乎不太可能引起ph。不幸的是，这种安全的表象是短暂的。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的护理。然而，随着肺部超声在世界范围内的常规化，许多患者将接受故意的肺部暴露，并承受ph的风险。迫切需要解决这一爆炸性安全问题。从生物物理学的角度来看，肺是一个以气体为主的组织，气体必须与DUS有强烈的相互作用。中心假设是，DUS-PH开始于超声脉冲直接撞击肺毛细血管的血气屏障，导致毛细血管应激导致出血。这导致肺泡间隔进行性应激，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，可能特别容易发生DUS-PH。该项目的目的是获得对DUS-PH的详细了解，并纠正肺部超声安全指导的不足。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，研究肺部对DUS- ph的相对易感性，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病症。其次，将通过使用活体显微镜来表征PH的开始和发展，从而确定DUS-PH的机制，这将允许对该现象进行物理建模。最后，将开发一种潜在的人类DUS- ph的剂量学算法，并使用猪模型进行人类DUS肺部检查。实现这些目标的预期结果是了解不同患者的肺易感性，描述导致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，同时保留获得最佳DUS图像的能力。该项目的总体影响将是开启肺部超声的新安全概念，并积极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.