2 & 3D Imaging of Contrast Agents in Animal Models

近红外（NIR）光学成像技术使用固有吸收（mua）和散射（mus '）提供对人类乳房内深处的小异质性的灵敏定位。 为了实现进一步增强的灵敏度和特异性（S/S）的癌症检测的光学方法，我们建议重新集中我们的活动，在这种竞争性的更新应用程序对外源性对比的癌症动物模型。 拟议的工作将首先确定外部试剂的品质因数M，并使用动物肿瘤中非常少量（20 pmole）的外部探针的荧光和吸光度检测来量化NIR造影剂的M增加。 这些研究需要几种仪器方案，包括：1）提出了一种改进的相控阵系统，其在模型系统中将吲哚菁绿色（ICG）定位于0.2 mm和9 L胶质瘤20 μ mol ICG，用于动物肿瘤，包括前列腺癌和人乳腺癌检测，其中可以在早期小肿瘤中评估S/S。 将使用两种适合于动物模型的其他工具。2)用于浅表肿瘤的1 mm分辨率的飞点扫描仪（仅小鼠），适用于NIR荧光信号成像。3)需要快速冷冻肿瘤的分辨率小于50微米的三维成像器将用于定位所有非人肿瘤中的造影剂。 后一种系统对于相控阵系统的关键评估是必不可少的。将使用上述检测方法在动物模型中比较基于ICG并包括分子信标的七种NIR造影剂。 将使用基于肿瘤/组织造影剂（C）、保留时间（R）（min）和荧光量子产率比（Q）的品质因数（M）进行定量比较。 M是基于线性模型计算的（即，这三个量的乘积）。因此，对目前可用的造影剂进行密集的、雄心勃勃的定量评价，将提供一种动物模型数据库转移到人类乳腺肿瘤，使用FDA批准的ICG（以及后来的其他方法）和相控阵定位，在“工作台到床边”研究中与钆螯合物肿瘤MRI图像共同配准（NIH研讨会，2000年9月14-17日）。

Near Infrared (NIR) optical imaging technologies provide sensitive localization of small heterogeneities deep within the human breast using intrinsic absorption (mua) and scattering (mus'). In order to achieve a further enhancement of the sensitivity and specificity (S/S) of cancer detection by the optical method, we propose to refocus our activity in this competitive renewal application towards extrinsic contrast in cancers in animal models. The proposed work will first determine the Figure of Merit, M, of the extrinsic agents and to quantify the increase in M with NIR contrast agents using both fluorescence and absorbance detection of the very small (20 pmole) amounts of extrinsic probes in animal tumors. Several instrumentation schemes are required for these studies and include: 1) An improved phased array system with localization of indocyanine green (ICG) demonstrated in model systems to 0.2 mm and 9L glioma 20 p moles of ICG is proposed for animal tumors including prostate cancer and human breast cancer detection where S/S can be evaluated in early, small tumors. Two other instruments appropriate to the animal models will be employed. 2) A flying spot scanner of 1 mm resolution for superficial tumors (mouse only) and adapted to imaging the NIR fluorescence signals. 3) a three-dimensional imager with less than 50 micron resolution requiring snap freezing of the tumor will be used to localize contrast agents in all non-human tumors. The latter system is essential to a critical evaluation of the phased array system. Seven NIR contrast agents based upon ICG and including molecular beacons will be compared in animal models using the above mentioned detection methods. Quantitative comparison will be afforded using the Figure of Merit(M) based upon tumor/tissue contrast agent (C), retention time (R)(min), and fluorescence quantum yield ratio (Q). M is calculated on the basis of a linear model (i.e., the product of these three quantities). Thus, an intensive, ambitious quantitative evaluation of currently available contrast agents will afford an animal model data base transfer to human breast tumors using FDA approved ICG (and others later) and phased array localization co-registered with gadolinium chelate tumor MRI images in "bench to bedside" studies (NIH Workshop, September 14-17, 2000).