Nanoparticles as OCT Contrast Agents

纳米颗粒作为 OCT 造影剂

• 批准号: 7738774
• 负责人: Gadi Wollstein
• 金额: $ 20.68万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738774
• 关键词: Address; Adult; Affect; Antibodies; Appearance; Biological Markers; Blood Circulation; Cells; Contrast Media; Detection; Development; Disease; Electroretinography; Engineering; Eye; Fluorescence Microscopy; Glaucoma; Goals; Gold; Health; Histology; Hour; Image; Imaging Techniques; Individual; Inflammatory; Injection of therapeutic agent; Label; Light; Malignant Neoplasms; Measurement; Measures; Microscopic; Molecular; Mus; Nanotechnology; Optic Nerve; Optical Coherence Tomography; Optics; Pattern; Property; Resolution; Retina; Retinal; Retinal Ganglion Cells; Scheme; Signal Transduction; Speed; Staging; Structure; Surface; T-Lymphocyte; Testing; Thick; Time; Tissues; Transmission Electron Microscopy; Transportation; Visual system structure; antibody conjugate; base; biomaterial compatibility; cell type; design; imaging Segmentation; improved; in vivo; innovation; interest; nanoparticle; nanoscience; particle; phantom model; public health relevance; receptor; research study; response; tumor

DESCRIPTION (provided by applicant): Optical coherence tomography (OCT) provides real-time, objective, in-vivo, high resolution optical cross- sections of the retina and optic nerve. Recent innovations in OCT image acquisition, including the incorporation of Fourier/spectral-domain detection, have improved imaging speed, sensitivity and resolution. Still, there remain specific structures within ocular OCT images, such as retinal ganglion cells (RGCs), which are of interest to clinicians but consistently have low contrast. This makes it difficult to differentiate between surrounding layers and structures. Our goal, therefore, is to engineer molecular OCT contrast agents suitable for enhancing contrast between structures of interest in the retina in order to improve the detection and measurement of these structures that are associated with disease. We will focus on RGCs, which are lost at an accelerated rate in glaucoma. We are proposing gold nanoparticles for ophthalmic contrast agents because their design can be tailored to augment the scattering response at the same wavelengths of light used in current ophthalmic OCT imaging schemes and their surfaces can be coated with antibodies that will facilitate targeting of specific structures. Our hypotheses are that nanoparticles can be directed to retinal tissue using antibodies specific to cellular receptors and that they will improve contrast by modulating the intensity of backscattered light detected by OCT. We will initially use gold nanorods conjugated with antibodies specifically targeting the retinal ganglion cells. The optimal concentration of nanoparticles for detection by OCT will be defined by using a phantom model and the time course of circulation of particles will be determined in mice eyes. A baseline intravitreal injection of nanoparticles will be performed and a subset of mice will be evaluated at each time point (time zero, one hour, six hours, one day, three days, and one week) and fluorescence microscopy and transmission electron microscopy will be performed on excised eyes to determine the time sequence of the nanorods transportation. The biocompatibility of the nanoparticles will be evaluated by pattern electroretinogram for functional assessment, inflammatory biomarkers and histology. At each time point during this experiment, we will also evaluate the ability of our antibody-coated nanoparticles to enhance OCT signal intensity level by performing high-speed, ultrahigh resolution retinal OCT imaging on mice prior to sacrificing them for microscopic examination. We will use these OCT images to compare nanoparticle contrast enhancement over time as well as to quantify RGC thickness by image segmentation. PUBLIC HEALTH RELEVANCE: In this study we propose to design particles that will be able to attach to specific layers in the retina and through changes in optical properties enhance the appearance of the layer in optical coherence tomography. This might improve the ability to detect pathological structural changes at an early stage and might enable targeting treatment to specific retinal layers.

描述（由申请人提供）：光学相干断层扫描（OCT）提供视网膜和视神经的实时、客观、体内、高分辨率光学横截面。 OCT 图像采集的最新创新，包括傅里叶/谱域检测的结合，提高了成像速度、灵敏度和分辨率。尽管如此，眼部 OCT 图像中仍然存在特定结构，例如视网膜神经节细胞 (RGC)，临床医生对此很感兴趣，但对比度始终较低。这使得很难区分周围的层和结构。因此，我们的目标是设计适合增强视网膜感兴趣结构之间对比度的分子 OCT 造影剂，以改善对这些与疾病相关的结构的检测和测量。我们将重点关注视网膜神经节细胞，它在青光眼中加速丢失。我们提议将金纳米粒子用于眼科造影剂，因为它们的设计可以定制，以增强当前眼科 OCT 成像方案中使用的相同光波长下的散射响应，并且它们的表面可以涂有抗体，从而有助于靶向特定结构。我们的假设是，可以使用细胞受体特异性抗体将纳米颗粒引导至视网膜组织，并且它们将通过调节 OCT 检测到的反向散射光的强度来提高对比度。我们首先将使用与专门针对视网膜神经节细胞的抗体结合的金纳米棒。通过使用体模模型来确定 OCT 检测的纳米颗粒的最佳浓度，并确定颗粒在小鼠眼中循环的时间过程。将进行纳米粒子的基线玻璃体内注射，并在每个时间点（零时间、一小时、六小时、一天、三天和一周）评估一部分小鼠，并使用荧光显微镜和透射电子显微镜进行评估。对切​​除的眼睛进行以确定纳米棒运输的时间顺序。纳米颗粒的生物相容性将通过视网膜电图进行功能评估、炎症生物标志物和组织学评估。在本实验期间的每个时间点，我们还将通过在处死小鼠进行显微镜检查之前对小鼠进行高速、超高分辨率视网膜 OCT 成像来评估抗体包被的纳米颗粒增强 OCT 信号强度水平的能力。我们将使用这些 OCT 图像来比较纳米颗粒对比度随时间的增强情况，并通过图像分割来量化 RGC 厚度。 公共健康相关性：在这项研究中，我们建议设计能够附着在视网膜特定层上的颗粒，并通过光学特性的变化增强该层在光学相干断层扫描中的外观。这可能会提高早期检测病理结构变化的能力，并可能能够针对特定的视网膜层进行靶向治疗。