Development of Theranostic Ultrasound

超声治疗诊断的发展

• 批准号: 8605539
• 负责人: THOMAS R PORTER
• 金额: $ 14.6万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8605539
• 关键词: Acoustics; Acute; Acute myocardial infarction; Animal Model; Area; Arrhythmia; Arterial Fatty Streak; Attenuated; Beds; Blood Vessels; Blood capillaries; Blood coagulation; Carotid Artery Thrombosis; Cause of Death; Cell Death; Clinical; Clinical Trials; Coagulation Process; Detection; Development; Devices; Diagnostic; Disease; Effectiveness; Ensure; Failure; Family suidae; Feedback; Healthcare; Hemorrhage; Image; Imagery; Infusion procedures; Injury; Intervention; Ischemic Stroke; Lead; Mechanics; Methods; Microbubbles; Microcirculatory Bed; Modeling; Monitor; Myocardial Infarction; Obstruction; Outcome; Outcomes Research; Patients; Physiologic pulse; Preparation; Rattus; Risk; Rupture; Signal Transduction; Simulate; Site; Stroke; System; Techniques; Testing; Therapeutic; Therapeutic Effect; Thick; Thrombolytic Therapy; Thrombosis; Thrombus; Time; Tissues; Transducers; Ultrasonic Therapy; Ultrasonography; acute coronary syndrome; acute stroke; arteriole; attenuation; base; capillary; cost effective; detector; disability; improved; in vivo; indexing; interest; pre-clinical; pressure; public health relevance; response; restoration; simulation; theranostics; thrombolysis; tool; vascular bed

DESCRIPTION (provided by applicant): High mechanical index impulses from a diagnostic ultrasound system have been utilized in small animal models to efficiently enhance thrombolysis in the presence of intravenously infused microbubbles. These high acoustic pressures induce inertial cavitation (IC) of the microbubbles, which may also cause unwanted bioeffects such as hemorrhage, cell death, and cardiac arrhythmias when using transthoracic impulses. At a lower mechanical index (MI), lower to moderate levels of IC as well as high levels of stable cavitation (SC) of microbubbles are induced which may produce equivalent thrombus dissolution as that achieved with high IC levels, but without unwanted bioeffects. Unfortunately, there are no methods by which one can monitor the type, or level, of cavitation within a region of interest. It s the central hypothesis of this project that the different forms and levels of cavitation can be detected and monitored with a feedback cavitation detection system (FCDS). When combined with image-guided ultrasound, we postulate that the dynamic assessment of cavitation signals will permit one to identify what is required for optimal thrombus dissolution both within medium sized vessels as well as the microvasculature. To correctly identify feedback, we predict that the response of the cavitating microbubble in the treatment region can be inferred from the non-linear acoustic signature of the local bubble response signals that return to the interrogating transducer, and that the local bubble response signature, in turn, can be used to adjust the transmitted ultrasound energy to compensate for attenuation, ensuring the energy delivered at the site of the desired bioeffect. We further postulate that the transmit amplitude required to achieve the desired level of cavitation will be different at microvascular level when compared to a medium-sized vessel. To test this hypothesis, a FCDS has been developed which can image microbubbles, apply therapeutic impulses, and correctly provide real time feedback as to whether the transmitted impulses are producing different forms of SC (non-destructive and destructive) versus IC. After validating its discriminative ability, the theranostic system will be tested during a microbubble infusion with an ex vivo model of normal microvasculature. Following this, microvascular and vascular thrombi will be created where varying levels of attenuation are created with tissue mimicking phantoms to mimick transthoracic and transcranial attenuation. In these models, we will determine a) whether the FCDS can still identify and effectively monitor the desired cavitation response; and b) the degree of thrombus dissolution achieved when either a consistent IC or SC feedback is achieved. The impact of such a non-invasive therapeutic tool will be significant, as development of a FCDS to non-invasively treat acute ischemic stroke and acute myocardial infarction would lead to more rapid treatment of these two disease entities, which remain the leading causes of death and disability in the world. The developed FCDS would also permit a cost-effective, safe, and immediate treatment that could potentially be initiated at the point of patient contact.

描述（由申请人提供）：在小动物模型中使用了诊断超声系统的高机械指数脉冲，可在静脉注入的微泡中有效增强溶栓。这些高声压力诱导微泡的惯性空化（IC），这也可能引起不必要的生物效应，例如使用经胸腔冲动时出血，细胞死亡和心律不齐。在较低的机械指数（MI）下，诱发了微泡的较低至中等水平的IC以及高水平的稳定的空化（SC），可能会产生等效的血栓溶解，因为它具有高IC水平，但没有不必要的生物效应。不幸的是，没有一种方法可以监视感兴趣区域内空化的类型或水平。该项目的中心假设是，可以通过反馈空化检测系统（FCD）检测和监测不同形式和水平。当与图像引导的超声检查结合使用时，我们假设空化信号的动态评估将允许人们确定中等大小的血管以及微脉管系统中最佳血栓溶解所需的内容。为了正确识别反馈，我们预测，可以从返回到询问的换能器的局部气泡响应信号的非线性声学信号来推断，可以推断出治疗区域中的浮雕微泡的响应，并且可以使用局部气泡反应的响应，而局部气泡响应又可以用来调整超级量的超声来补偿能量，以弥补能量的促进，以促进促进的促进效果，以促进促进促进的促进。我们进一步假设，与中型容器相比，在微血管水平上达到所需的空化水平所需的发射幅度将有所不同。为了检验这一假设，已经开发了FCD，可以对微泡，应用治疗性脉冲进行成像，并正确提供有关传播冲动是否生产出不同形式的SC（非破坏性和破坏性）与IC相对于IC的实时反馈。在验证其判别能力之后，疗法系统将是 在微气泡输注过程中用正常微脉管系统的离体模型进行了测试。此后，将创建微血管和血管血栓形成，在模仿幻影以模仿经胸腔和经颅衰减的组织中产生不同水平的衰减。在这些模型中，我们将确定a）FCD是否仍然可以识别并有效地监测所需的空化响应； b）当达到一致的IC或SC反馈时，达到的血栓溶解程度。这种非侵入性治疗工具的影响将是显着的，因为FCD的发展是非侵入性治疗急性缺血性中风和急性心肌梗死的影响，这将导致对这两种疾病实体的更快治疗，这仍然是世界上死亡和残疾的主要原因。开发的FCD还将允许一种具有成本效益，安全和立即治疗的治疗方法，可以在患者接触时开始。