Ultrasonic Imaging of LIOB in Dendrimer Nanocomposites

描述(由申请人提供)： 这项提议的中心目标是了解高频超声波监测的超快光与DNC的相互作用。特别是，我们将使用超声波显微镜来监测光破坏过程，将定位靶向的纳米颗粒转化为可检测的微泡。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：一种是在接近阈值的情况下，UOB过程可以得到仔细控制，以产生可检测到的微泡，细胞损伤很小(即，微创)；第二种是在不同的光学参数下，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，如果这两种机制都可以建立，那么超声检测DNC促进的光破坏可以为靶向分子成像和分子治疗提供一种灵敏的工具。 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中的LIOB和生成的微泡。特别是，超声系统将监测光破坏阈值、用于微创瞬时气泡创建的系统参数、用于有创且稳定的气泡创建的系统参数、确定气泡大小的系统参数以及确定气泡温度的系统参数。 2.)确定具有最低LIOB阈值的DNC颗粒的必要组成和结构。将对所有具有增强击穿特性的成分进行详细的结构研究。 3.)确定控制DNC溶液和DNC组织等效明胶模体中的LIOB阈值和光破坏特性的光学参数范围，包括波长、每脉冲的光通量、重复频率和脉冲总数。 如果这些研究表明，我们可以控制DNC推动的LIOB作为微创传感器或高度局部干扰物运行，并且我们可以使用高频超声灵敏地监控这两个过程，我们将制定一项针对鳞癌的现场靶向分子成像和治疗监测的RO1建议，这是一个迅速增长的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.