权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

PiV Ultra 12 - 24 Ultra High Speed Camera for Ultrasound Microbubble Research

PiV Ultra 12 - 24 用于超声微泡研究的超高速相机

基本信息

批准号：
7595606
负责人：
John A Hossack
金额：
$ 49.88万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2010-09-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Contrast microbubbles offer unique versatility in medical imaging. First generation agents were used as tracers of blood flow permitting assessment of perfusion defects. More recently, research has focused on molecular targeted agents that enable the detection of the molecular signature of disease. Finally, the use of contrast microbubbles as a means of precipitating drug and gene delivery in a highly focal manner - potentially under real-time ultrasound imaging guidance - provides a technology that encompasses molecular imaging, functional imaging and therapy. In each of these technologies, it is critical to understand the behavior of the microbubble in response to high intensity incident ultrasound pulses. Existing bubble models assume spherical symmetry and over time it is anticipated that these models will be replaced by models accounting for asymmetric modes of vibration. These models are only credible if supported by the experimental validation that the proposed camera will provide. The camera will also enable analysis of the response of microbubbles to radiation force effects that the collaborators have previously established as being vital to the efficacy of microbubble-based molecular imaging and drug delivery. The camera will also facilitate understanding of the behavior of "next generation" multilayered bubbles that include a drug payload in the shell. Additional research will investigate the vessel, and cell, permeabilization process that is believed to be important to successful drug and gene delivery, which is practically impossible to visualize except by means of the combined high speed camera and inverted research microscope that is contemplated in this proposal. Current ultra-high-speed video microscopy systems designed for microbubble imaging include the Brandaris at Erasmus University in Rotterdam and the Imacon 468 systems at the University of Michigan and UC Davis. While these older technology systems have enabled a substantial body of preliminary research, physical constraints in their time and spatial resolution, dynamic range, and light sensitivity have limited the ability of these systems to be useful to microbubble researchers interested in high-frequency or high amplitude bubble imaging, or situations where bubbles oscillate non-symmetrically or in low-light environments such as in-vivo. The 12 bit dynamic range, with an intensifier gain of up to 2000 will yield 4 bits more dynamic range than prior systems and a factor of 4 fold more sensitivity than the Imacon 468 system. These substantial improvements will allow imaging in reduced light conditions (i.e. in-vivo) and imaging with maximum frame rate at higher optical magnification than previously possible. The 3 ps streak time resolution will allow recording of bubble events much over 1000 times faster than previously possible. PUBLIC HEALTH RELEVANCE: The proposed high speed camera with microscope will enable fundamental research into the complex behavior of ultrasound contrast agents with fine spatial resolution and approximately five nanosecond temporal resolution. Using the knowledge gained, we plan to improve the design of ultrasound contrast agents used in both disease detection and in disease treatment. A long term goal involving ultrasound contrast is to enable detection and treatment of disease using early detection of molecular signatures of disease rather than waiting to detect late stage anatomic responses to disease - at which point treatment may involve higher risk, more side effects, higher patient and societal cost and greater patient discomfort.

描述（由申请人提供）：对比微泡在医学成像中提供独特的多功能性。第一代药物被用作血流示踪剂，用于评估灌注缺陷。最近，研究集中在能够检测疾病分子特征的分子靶向药物上。最后，利用造影剂微泡作为一种高度聚焦的药物和基因传递手段——可能在实时超声成像引导下——提供了一种涵盖分子成像、功能成像和治疗的技术。在这些技术中，了解微泡响应高强度入射超声脉冲的行为是至关重要的。现有的气泡模型假定为球对称，随着时间的推移，预计这些模型将被考虑非对称振动模式的模型所取代。这些模型只有在实验验证的支持下才可信。该相机还可以分析微泡对辐射力效应的响应，合作者先前已经确定这对于基于微泡的分子成像和药物输送的有效性至关重要。该摄像机还将有助于了解“下一代”多层气泡的行为，这些气泡的外壳中包含药物有效载荷。额外的研究将调查血管和细胞的渗透过程，这被认为是成功的药物和基因传递的重要因素，这实际上是不可能可视化的，除非通过结合高速相机和倒置研究显微镜，这是在这个提议中考虑的。目前为微泡成像设计的超高速视频显微镜系统包括鹿特丹伊拉斯谟大学的Brandaris和密歇根大学和加州大学戴维斯分校的Imacon 468系统。虽然这些较老的技术系统已经实现了大量的初步研究，但它们在时间和空间分辨率、动态范围和光灵敏度方面的物理限制限制了这些系统对高频或高振幅气泡成像、气泡非对称振荡或低光环境（如体内）的微泡研究人员有用的能力。12位动态范围，具有高达2000的增强增益，将产生比以前的系统多4位的动态范围和比Imacon 468系统多4倍的灵敏度。这些实质性的改进将允许在较弱的光照条件下（即在体内）成像，并在比以前可能的更高的光学放大倍率下以最大帧速率成像。3秒的条纹时间分辨率将允许记录气泡事件比以前可能的快1000倍以上。公共卫生相关性：提出的带显微镜的高速摄像机将使对超声造影剂复杂行为的基础研究具有精细的空间分辨率和大约5纳秒的时间分辨率。利用所获得的知识，我们计划改进用于疾病检测和疾病治疗的超声造影剂的设计。超声造影的长期目标是通过早期发现疾病的分子特征来检测和治疗疾病，而不是等待发现疾病的晚期解剖反应——此时治疗可能涉及更高的风险、更多的副作用、更高的患者和社会成本以及更大的患者不适。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Liquid Flooded Flow-Focusing Microfluidic Device for in situ Generation of Monodisperse Microbubbles.

DOI：
10.1007/s10404-012-1064-x
发表时间：
2013-03-01
期刊：
Microfluidics and nanofluidics
影响因子：
2.8
作者：
Dhanaliwala AH;Chen JL;Wang S;Hossack JA
通讯作者：
Hossack JA

Efficacy of Sonothrombolysis Using Microbubbles Produced by a Catheter-Based Microfluidic Device in a Rat Model of Ischemic Stroke.

在缺血性中风大鼠模型中使用基于导管的微流体装置产生的微泡进行声溶栓的功效。

DOI：
10.1007/s10439-019-02209-0
发表时间：
2019
期刊：
Annals of biomedical engineering
影响因子：
3.8
作者：
Dixon,AdamJ;Li,Jun;Rickel,John-MarschnerRobert;Klibanov,AlexanderL;Zuo,Zhiyi;Hossack,JohnA
通讯作者：
Hossack,JohnA

Improving the performance of phase-change perfluorocarbon droplets for medical ultrasonography: current progress, challenges, and prospects.