Ultrasonic Imaging of LIOB in Dendrimer Nanocomposites

描述（由申请人提供）： 该提案的中心目标是了解高频超声监测下的超快光与 DNC 相互作用。特别是，我们将使用超声波显微镜来监测将定点纳米颗粒转变成可检测微泡的光破裂过程。我们的短期目标是检测针对鳞状细胞癌的分子制剂并监测应用于这些细胞的治疗。我们建议研究两种光破坏机制：一种是接近阈值，可以仔细控制 UOB 过程以产生可检测的微泡，而细胞损伤很小（即微创）；第二个是在一组不同的光学参数下，其中​​ UOB 过程可能具有高度破坏性，杀死标记细胞以达到治疗目的，如果可以建立两种机制，那么 DNC 促进的光破坏的超声检测可以为定点分子成像和分子治疗提供灵敏的工具。 因此，这里提出的工作的目的是详细解决以下问题。 1.) 使用高频超声波表征水、水基凝胶和组织培养物中的 LIOB 和由此产生的微泡。具体地，超声系统将监测光破裂阈值、用于微创瞬时气泡产生的系统参数、用于侵入性和稳定气泡产生的系统参数、确定气泡尺寸的系统参数以及确定气泡温度的系统参数。 2.) 确定具有最小 LIOB 阈值的 DNC 颗粒的必要组成和结构。将对所有显示出增强的击穿特性的组合物进行详细的结构研究。 3.) 确定 DNC 溶液和 DNC 加载的组织等效明胶模型中控制 LIOB 阈值和光致破裂特性的光学参数范围，包括波长、每个脉冲的光通量、重复率和脉冲总数。 如果这些研究证明我们可以控制 DNC 促进的 LIOB 作为微创传感器或高度局部干扰器运行，并且我们可以用高频超声灵敏地监测这两个过程，我们将开发一项 RO1 建议，用于鳞状细胞癌的定点分子成像和治疗监测，鳞状细胞癌是一个快速增长且非常重要的临床问题。

DESCRIPTION (provided by applicant): The central aim of this proposal is to understand ultrafast light-DNC interactions as monitored by high frequency ultrasound. In particular, we will use ultrasonic micrsocopy to monitor the photodisruption process transducing site-targeted nanoparticles into a detectable microbubble. Our short-term goal is to detect molecular agents targeted to squamous cell cancers and to monitor therapy applied to these cells. We propose to investigate two photodisruption regimes: one near threshold in which the UOB process can be carefully controlled to produce detectable microbubbtes with little cellular injury (i.e., minimally invasive); the second at a different set of optical parameters where the UOB processes can be highly destructive, killing labeled cells for therapeutic purposes, ff both regimes can be established, then ultrasonic detection of DNC promoted photodisruption can provide a sensitive tool for both site-targeted molecular imaging and molecular therapeutics. It is the aim, therefore, of the work proposed here to address the following issues in detail. 1.) Characterize LIOB and resultant microbubbles in water, water-based gels, and tissue culture using high-frequency ultrasound. In particular, the ultrasound system will monitor photodisruption thresholds, system parameters for minimally invasive transient bubble creation, system parameters for invasive and stable bubble creation, system parameters determining bubble size, and system parameters determining bubble temperature. 2.) Determine the necessary composition and structure of DNC particles that have minimal LIOB thresholds. Detailed structural studies will be performed on all compositions showing enhanced breakdown characteristics. 3.) Determine the range of optical parameters controlling LIOB thresholds and photodisruption characteristics in DNC solutions and DNC loaded tissue-equivalent gelatin phantoms, including wavelength, optical fluence per pulse, repetition rate, and total number of pulses. If these studies demonstrate that we can control DNC-promoted LIOB to operate either as a minimally invasive sensor or a highly localized disruptor, and we can sensitively monitor both processes with high frequency ultrasound, we will develop an RO1 proposal for site-targeted molecular imaging and therapy monitoring of squamous cell cancers, a rapidly growing and very important clinical problem.