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。第一代试剂用作血流示踪剂，允许评估灌注缺陷。最近，研究重点是能够检测疾病分子特征的分子靶向药物。最后，使用对比微泡作为一种以高度聚焦的方式沉淀药物和基因递送的手段（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。在每种技术中，了解微泡响应高强度入射超声波脉冲的行为至关重要。现有的气泡模型假设球对称，随着时间的推移，预计这些模型将被考虑不对称振动模式的模型所取代。只有得到所提议的相机提供的实验验证的支持，这些模型才是可信的。该相机还将能够分析微泡对辐射力效应的响应，合作者之前已经确定这种效应对于基于微泡的分子成像和药物输送的功效至关重要。该相机还将有助于了解“下一代”多层气泡的行为，这些气泡的外壳中包含药物有效负载。其他研究将调查血管和细胞的透化过程，该过程被认为对成功的药物和基因递送很重要，除了通过本提案中设想的组合高速相机和倒置研究显微镜之外，实际上不可能将其可视化。目前专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姆斯大学的 Brandaris 以及密歇根大学和加州大学戴维斯分校的 Imacon 468 系统。虽然这些较旧的技术系统已经实现了大量的初步研究，但其时间和空间分辨率、动态范围和光灵敏度方面的物理限制限制了这些系统对对高频或高振幅感兴趣的微泡研究人员的有用能力。气泡成像，或气泡非对称振荡或在低光环境（例如体内）中振荡的情况。 12 位动态范围以及高达 2000 的增强器增益将产生比以前的系统多 4 位的动态范围，以及比 Imacon 468 系统高 4 倍的灵敏度。这些重大改进将允许在弱光条件下（即体内）成像，并在比以前更高的光学放大倍率下以最大帧速率成像。 3 ps 的连续时间分辨率将使气泡事件的记录速度比以前快 1000 倍以上。公共健康相关性：所提出的带有显微镜的高速相机将使对具有精细空间分辨率和大约五纳秒时间分辨率的超声造影剂的复杂行为的基础研究成为可能。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。涉及超声造影的长期目标是通过早期检测疾病的分子特征来检测和治疗疾病，而不是等待检测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、更高的患者负担。以及社会成本和更大的患者不适。