Vibrational Photoacoustic Microscopy for Bond-selective Tissue Analysis

用于键选择性组织分析的振动光声显微镜

• 批准号: 8302351
• 负责人: Ji-Xin Cheng
• 金额: $ 20.33万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8302351
• 关键词: 3-Dimensional; Acoustics; Animals; Arterial Fatty Streak; Arteries; Atherosclerosis; Ballistics; Biological; Biology; Blood; Cardiovascular Diseases; Cells; Chemicals; Collection; Detection; Development; Dietary Fats; Diffuse; Disease; Endoscopy; Fiber Optics; Goals; Health; Hydrogen Bonding; Image; Imaging Device; In Situ; Label; Lesion by Stage; Life; Lipids; Measurement; Medicine; Methods; Microscope; Microscopy; Molecular; Near-Infrared Spectroscopy; Optics; Patients; Penetration; Photons; Principal Component Analysis; Research; Resolution; Sampling; Scanning; Signal Transduction; Slice; Small Intestines; Specimen; Spectrum Analysis; Speed; Stretching; System; Techniques; Tissues; absorption; adaptive optics; base; chemical bond; disease diagnosis; in vivo; molecular imaging; pressure; tissue phantom; vibration

DESCRIPTION (provided by applicant): A long term goal of our research is pursuing new understanding of molecular functions in health and disease via development of label-free microscopy. In this R21 application, we develop a new method termed vibrational photoacoustic (VPA) microscopy for 3-D vibrational imaging of tissues with a field of view and a penetration depth both in the mm scale. Our method is based on excitation of molecular overtone vibration and acoustic detection of the resultant pressure waves in the tissue. Our approach is significant in the following aspects: (i) Overtone excitation provides chemical bond selectivity and spectroscopic information in a label-free manner. (ii) Acoustic detection eliminates the tissue scattering problem encountered in near-infrared spectroscopy and enables depth-resolved signal collection in one scan. (iii) Our method provides a tissue penetration depth of a few mm, which is not accessible with existing vibrational microscopies. By excitation of the second overtone of the C-H bond stretch around 8300 cm-1, where blood interference is minimal, we have demonstrated preliminary VPA imaging of tissue phantoms and atherosclerotic plaques in arteries with a penetration depth in mm scale. These results show the great potential of developing VPA microscopy and endoscopy for label-free molecular imaging and spectroscopic analysis of lipid-related disorders in live animals and eventually in patients. The two specific aims are (1) developing high-speed VPA microscopy for in vivo molecular imaging and quantitative analysis and (2) developing VPA spectroscopy and endoscopy for in situ, depth resolved characterization of atherosclerotic plaques. Successful development of VPA microscopy should provide a new platform enabling label-free molecular imaging and spectroscopic analysis of biological specimen ex vivo and in vivo. Towards diagnosis of diseases such as atherosclerosis, VPA spectroscopy aided with principal component analysis should allow determination of lesion stages owing to the capability of identifying different pathophysiological compositions throughout deep tissues. Furthermore, our endoscopy development is expected to push the VPA method towards intravital imaging of plaques.

描述（由申请人提供）：我们研究的长期目标是通过开发无标签显微镜来追求对健康和疾病分子功能的新理解。在此R21应用中，我们开发了一种称为振动光声（VPA）显微镜的新方法，用于对具有视野和渗透深度的组织的3-D振动成像。我们的方法基于分子泛音振动的激发和组织中所得压力波的声学检测。我们的方法在以下方面很重要：（i）泛音激发以无标签的方式提供化学键选择性和光谱信息。 （ii）声学检测消除了在近红外光谱中遇到的组织散射问题，并在一次扫描中实现深度分辨信号收集。 （iii）我们的方法提供了几毫米的组织穿透深度，现有的振动显微镜无法访问。通过激发C-H键的第二个泛音，在8300 cm-1左右，血液干扰很小，我们已经证明了组织幻像和动脉动脉粥样硬化斑块的初步VPA成像，其渗透深度为MM尺度。这些结果表明，开发VP​​A显微镜和内窥镜检查，用于无标记的无标记分子成像以及对活动物和患者最终脂质相关疾病的光谱分析。这两个具体目的是（1）开发用于体内分子成像和定量分析的高速VPA显微镜，以及（2）为原位的VPA光谱和内窥镜检查，深度分析了动脉粥样硬化斑块的深度表征。 VPA显微镜的成功开发应提供一个新的平台，从而实现无标记的分子成像以及对生物样本的Ex Vivo和In Vivo的光谱分析。为了诊断诸如动脉粥样硬化之类的疾病，通过主成分分析的VPA光谱法应允许确定由于能力鉴定深层组织中不同病理生理学组成的能力，因此可以确定病变阶段。此外，我们的内窥镜发育有望将VPA方法推向斑块的浸润成像。