High Resolution 3-D Imaging of Molecular Beacons

分子信标的高分辨率 3D 成像

• 批准号: 6782588
• 负责人: SHOKO NIOKA
• 金额: $ 39.39万
• 依托单位: OPTICAL DEVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-11 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6782588
• 关键词: angiogenesis; animal tissue; bioimaging /biomedical imaging; biomarker; cryoscopy; diagnosis design /evaluation; fiber optics; flavoproteins; fluorescent dye /probe; glucose metabolism; hemodynamics; hemoglobin; image processing; imaging /visualization /scanning; infrared radiation; neoplasm /cancer blood supply; neoplasm /cancer diagnosis; nicotinamide adenine dinucleotide; physical model; structural biology; three dimensional imaging /topography

DESCRIPTION (provided by applicant): The maturation of molecular imaging of cancers emphasizes the high tumor tissue ratios above ten which, when approved by FDA, are expected to revolutionize the sensitivity/specificity of, for example, breast and prostate cancer detection. The development of molecular beacons from collaborating laboratories has provided the two key types of beacons, one being the affinity binding, for example somatostatin, LDL, folate and the stealth or silent beacons (Cathepsin B, etc.) that depend upon recognition and unmasking of the fluorochrome attached to the beacon. Most recently, a fluorescent glucose generally applicable to all rapidly growing cancers has incorporated a NIR fluorochrome. While the NADH and flavoprotein signals are the gold standard of recognition of cancer by the greater glycolytic flow and enhanced reduction state of the tumor, these markers can be greatly enhanced by multi-photon technologies. In addition, the time shared wavelengths characteristically include reflectance spectophotometry of deoxy and total hemoglobin affording a direct links to hypermetabolism and angiogenesis. However, the most important aspect of the technology is its 3-D capability since ice crystal formation which characterizes the freeze trap state, impedes penetration of light through the highly scattering crystal matrix is very limited and fluorescent signals deeper than tens of microns do not interfere with planar images. Finally, fiber optic technology will permit reduction of the size of the voxel from 50 x 50 x 10 to 30 x 30 x 10 mu or even smaller depending upon the light guide construction. As a result of Phase I funding, a greatly improved, simplified and more economical design of the 3-D light pen imager has been completed. A vastly improved system which employs a time multiplex LED source system and silicon diode detector system which will permit a much greater throughput because of the increased duty cycle from roughly 20% to 75%. The operation is automatic and its authenticity is validated by the experiments carried out under Phase I support. Finally, a timetable and milestone exhibit assures production of the second phase model within 8 months at the funding of Phase II and exhaustive validation tests and tech transfer to occur in the remaining 16 months of the Phase II study.

描述（由申请人提供）： 癌症的分子成像的成熟强调了高于十的高肿瘤组织比率，该比率在FDA批准时将彻底改变乳腺癌和前列腺癌检测的敏感性/特异性。合作实验室的分子信标的发展提供了两种关键类型的信标，一种是亲和力结合，例如生长抑素，LDL，叶酸，叶酸，隐形或静音信标（Catherpsin b等），取决于识别和未掩盖与信标的荧光体的识别和掩盖。最近，通常适用于所有快速生长的癌症的荧光葡萄糖已掺入了NIR荧光色体。虽然NADH和黄蛋白信号是通过更大的糖酵解流量和增强肿瘤还原状态识别癌症的金标准，但通过多光子技术可以大大增强这些标记。此外，共享波长的时间特征包括脱氧和总血红蛋白的反射率分光光法，与超级代谢和血管生成有直接联系。但是，该技术最重要的方面是其3D能力，因为冰晶形成表征了冻结陷阱状态的冰晶形成，阻碍光穿透高度散射的晶体基质的穿透非常有限，并且比数十微米的荧光信号不会干扰平面图像。最后，光纤技术将允许将体素的尺寸从50 x 50 x 10到30 x 30 x 10 mu甚至更小的，具体取决于光导向的构造。由于第一阶段的资金，已经完成了3-D轻笔成像仪的大大改进，简化和更经济的设计。一个大大改进的系统，它采用了时间多路复用LED源系统和硅二极管检测器系统，该系统将允许更大的吞吐量，因为占空比的增加到大约20％增加到75％。该操作是自动的，其真实性通过I阶段支持下进行的实验验证。最后，一个时间表和里程碑在8个月内证明了第二阶段模型的生产，在II期的资金以及详尽的验证测试和技术转移中，将在II期研究的其余16个月内进行。