Ultrasonic Imaging of LIOB in Dendrimer Nanocomposites

描述（由申请人提供）： 该提案的中心目的是了解高频超声监测的超快光-DNC相互作用。特别是，我们将使用超声波显微镜来监测光致破裂过程，将靶向位点的纳米颗粒转换成可检测的微泡。我们的短期目标是检测靶向鳞状细胞癌的分子药物，并监测应用于这些细胞的治疗。我们建议研究两种光致破裂机制：一种接近阈值，其中UOB过程可以被仔细控制以产生可检测的微泡，而细胞损伤很小（即，微创）;第二种是在不同的光学参数组，其中UOB过程可以是高度破坏性的，杀死标记的细胞用于治疗目的，如果两种方案都可以建立，则DNC促进的光致破裂的超声检测可以为位点靶向分子成像和分子治疗提供灵敏的工具。 因此，本报告所建议的工作的目的是详细讨论下列问题。 1.）使用高频超声在水中、水基凝胶和组织培养物中表征LIOB和所得微泡。特别地，超声系统将监测光致破裂阈值、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.）第三章确定控制LIOB阈值和DNC溶液和DNC加载的组织等效明胶模型中的光致破裂特性的光学参数的范围，包括波长、每个脉冲的光通量、重复率和脉冲总数。 如果这些研究表明，我们可以控制DNC促进的LIOB作为微创传感器或高度局部化的干扰器运行，并且我们可以用高频超声灵敏地监测这两个过程，我们将开发一个RO 1提案，用于鳞状细胞癌的位点靶向分子成像和治疗监测，这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.