Development of a lung ultrasound therapy system for acute respiratory distress syndrome

急性呼吸窘迫综合征（ARDS）是重症监护病房的一种常见疾病，死亡率接近40%，其治疗是一项相当大的挑战。在ARDS中，肺部充满液体，导致患者在自己的液体中溺水。急性呼吸窘迫综合征是最难治疗的疾病之一，因为它呈斑片状分布，肺部充满液体的区域散布在正常肺中，导致常规治疗主要影响正常肺，而不是损伤肺。例如，机械呼吸机虽然可以挽救生命，但它优先向肺的正常区域充气，导致正常肺本身过度膨胀和损伤。同样，通过吸入或注射给予的药物优先影响正常的肺部或身体的其他器官。在这里，我们提出了一种革命性的基于超声技术和微气泡（临床上已用于诊断目的的微小气泡）的个性化和靶向药物治疗ARDS的形式。虽然肺部的正常区域会散射超声波（因为超声波被空气阻挡），但超声波能够穿透受伤（充满液体或塌陷）的区域，从而增强抗生素等药物向受损肺部的输送。这种方法是个性化医疗的一种革命性形式，因为它将允许将药物和基因准确地输送到每个病人需要的地方。在这个项目中，我们将开发一个专门针对肺部的超声治疗系统的临床原型，并使用大型ARDS动物模型优化治疗方案。在项目结束时，我们将把这项研究转化为一期人体临床试验。

Treatment of acute respiratory distress syndrome (ARDS), a common disorder in intensivecare units with a mortality rate approaching 40%, is a considerable challenge. In ARDS, thelungs are filled with fluid resulting in patients drowning in their own fluids. ARDS is one of themost difficult conditions to treat because of its patchy distribution, where the fluid-filled regionsof the lung are interspersed within the normal lungs, causing conventional treatments topreferentially affect the normal lungs rather than the injured regions. For instance, mechanicalventilators, although life-saving, preferentially inflate the normal regions of the lung resultingin overdistension and injury of the normal lung itself. Similarly, medicines given by inhalationor injection preferentially affect the normal lungs or other organs in the body. Here wepropose a revolutionary form of personalized and targeted medicine to treat ARDS based onultrasound technology and microbubbles (tiny gas bubbles already used clinically fordiagnostic purposes). While the normal regions of lung scatter ultrasound waves (becauseultrasound is blocked by air), the ultrasound waves are able to penetrate the injured (fluidfilledor collapsed) regions, allowing enhanced delivery of drugs like antibiotics to thedamaged lung. This approach is a revolutionary form of personalized medicine, since it willallow the delivery of medicines and genes exactly where they are needed in each patient. Inthis project, we will develop a clinical prototype of an ultrasound therapy system specificallyfor the lungs and optimize treatment protocols using large animal models of ARDS. At the endof the project, we will translate the study to a Phase I clinical trial in humans.