Ultrasound-Induced Pulmonary Hemorrhage During Diagnostic Examination of the Lung

描述(申请人提供)：在初步研究中，7.6 MHz诊断超声(DUS)的肺部检查显示快速发展的彗星尾状伪影横跨明亮的肺表面图像。这种进行性伪影提示肺出血(PH)的持续诱导，这一点通过对肺出血的观察得到了证实。阈值位于机械指数~0.44的较低水平，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。脉冲超声诱发肺高压已有20多年的历史。但机制仍不确定。2000年和2008年的权威综述承认了诊断超声(DUS)诱导的PH(DUS-PH)的可能性，但还没有设计出有用的安全策略。当时，预计只有意外的肺部暴露，这似乎不太可能导致肺高压。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检查方法，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成为常规，许多患者将接受故意的肺部暴露，并面临肺高压的风险。迫切需要解决这一爆炸安全问题。从生物物理学的角度来看，肺是一个以气体为主的组织，必然与DUS发生强烈的相互作用。中心假设是DUS-PH始于超声脉冲对肺毛细血管血气屏障的直接冲击，并由毛细血管压力引起出血。这会导致肺泡间隔的进行性应力，导致挫伤样肺损伤。某些因高血压或浮肿而易患肺泡的患者可能特别易患DUS-PH。本项目的目的是为了对DUS-PH有一个详细的了解，并纠正目前对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，针对不同的DUS模式和频率以及经常通过肺部超声诊断的常见患者情况，调查肺对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确定，以表征PH的发生和发展，这将允许对现象进行物理模拟。最后，将开发潜在的人DUS-PH的剂量学算法，并使用人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部易感性，描述导致DUS-PH的生物物理过程，以及适合于超声师教育和指导的人类安全策略。这些成就将提高人们对DUS-PH的认识，确保患者的安全，同时保留获取最佳DUS图像的能力。该项目的总体影响将是肺部超声新的安全概念的启动，以及这一紧急公共卫生问题的积极解决。

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.