Mid-infrared molecular imaging

鉴于他们作为西方世界头号杀手的地位，开发新的工具来评估新的治疗方法并解决心血管疾病和风险是至关重要的。在这些工具中，成像科学和技术正在成为关键贡献者，因为它们使药物疗效的早期测量和纵向研究成为可能。由于其无创性和报告特定过程的能力，心血管疾病的分子成像因此为更好地描述心血管事件提供了一个有吸引力的途径。本项目的目标是开发一种新型的、高分辨率的分子中红外(MIR)成像平台，用于体内动脉粥样硬化斑块的检测和表征。目前可用于研究外周血管功能和疾病的成像技术仍然不是最理想的，主要是因为需要对大体积组织下的小血管结构进行成像。显微光学成像技术(共聚焦、双光子、光学相干层析成像)受到穿透深度的限制，而更传统的全身成像技术，如MRI和Micro-CT，扫描时间长，分辨率有限(100um)，需要长时间的后处理。此外，它们评估血流动力学(结构之外)的能力仍然有限。为了同时表征功能成像和分子成像，光学技术仍然很有吸引力，但受到高扩散的困扰。最近备受瞩目的研究表明，除了通常用于光学信号生物成像的‘治疗窗口’(650-900 nm)之外，第二个窗口提供了新的机会。中红外区(1200-1500 nm)的光子吸收和扩散显著降低，导致穿透深度和图像分辨率增加，自发荧光减弱，增加了分子成像的特异性。然而，开发MIR成像需要跨学科的努力，将探头开发与为MIR成像量身定做的新仪器相结合。该项目结合了三位共同申请者在纳米技术、生物结合和成像方面的专业知识，以研究和开发新的分子纳米探针和血管疾病背景下的分子MIR成像平台。

Given their status as the number one killer in the western world, the development of new tools to evaluate novel therapies and address cardiovascular (CV) diseases and risk is essential. Among those tools, imaging science and technology are becoming key contributors as they enable early measures of drug efficacy and longitudinal studies. Due to its non-invasive nature and ability to report on specific processes, molecular imaging of cardiovascular diseases thus provides an attractive avenue towards better characterization of CV events. The goal of this project is to develop a novel, high-resolution, molecular mid-infrared (MIR) imaging platform for atherosclerotic plaque detection and characterization in vivo. Current available imaging technologies to investigate peripheral vascular function and disease remain sub-optimal, mostly due to the necessity of imaging small vascular structures under a large bulk of tissue. Microscopic optical imaging techniques (confocal, two-photon, optical coherence tomography) are limited by penetration depth, while more conventional whole body techniques, such as MRI and micro-CT lead to long scanning times, have limited resolution (100um), and require long post-processing. Furthermore, they remain limited in their ability to assess hemodynamics (beyond structure). To characterize both functional and molecular imaging, optical techniques remain attractive but are plagued by high diffusion. Recent high-profile work has shown that beyond the usual ‘therapeutic window’ (650-900nm) used for bio imaging with optical signals, a second window offered new opportunities. The mid-infrared region (1200-1500nm) is associated with significantly lower photon absorption and diffusion, leading to increased penetration depth and image resolution, and reduced autofluorescence, increasing its specificity for molecular imaging. However, exploiting MIR imaging requires an interdisciplinary effort combining probe development with new instrumentation tailored to MIR imaging. This project combines the expertise of the three co-applicants in nanotechnology, bio-conjugation and imaging to investigate and develop new molecular nanoprobes and a platform for molecular MIR imaging in the context of vascular disease.