RECOVERY OF OPTICAL ABSORPTION COEFFICIENT IN QUANTITATIVE PHOTOACOUSTIC IMAGING

定量光声成像中光吸收系数的恢复

• 批准号: 7671211
• 负责人: Lihong Wang
• 金额: $ 59.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7671211
• 关键词: Animal Experimentation; Animals; Ballistics; Biological; Biotechnology; Blood Vessels; Brain; Cellular biology; Confocal Microscopy; Contrast Media; Functional Imaging; Hemoglobin; Image; In Situ; Malignant neoplasm of brain; Malignant neoplasm of cervix uteri; Measures; Microscopy; Molecular; Molecular Probes; Morphologic artifacts; Nature; Optical Coherence Tomography; Optical Tomography; Optics; Oxygen; Physiological; Publishing; Recovery; Research; Resolution; Skin Cancer; System; Technology; Tissues; Ultrasonics; Ultrasonography; Work; absorption; angiogenesis; base; clinical Diagnosis; clinical practice; diffuse optical tomography; drug discovery; imaging modality; in vivo; malignant breast neoplasm; molecular imaging; optical imaging; reconstruction; tissue phantom; tomography; two-photon

DESCRIPTION (provided by applicant): The objective of the proposed research is to recover the optical absorption coefficient for in vivo quantitative photoacoustic imaging (PAI) of biological tissue. PAI can image intact biological tissues with optical absorption contrast at high spatial resolution beyond the optical quasi-ballistic regime (~1 mm). Since optical absorption is sensitive to physiological parameters such as the total concentration and oxygen saturation of hemoglobin, PAI can provide functional imaging. With the aid of functionalized contrast agents (molecular probes), PAI can also provide molecular imaging. PAI has potentially broad applications in both small-animal research and clinical practice, including, for example, (1) the animal study of angiogenesis, brain function, drug discovery, and molecular cell biology, (2) the clinical diagnosis of skin cancer, cervical cancer, and breast cancer, and (3) the intra-operative demarcation of brain cancer and function. Although optical contrast is high, conventional high-resolution optical imaging modalities cannot penetrate more than ~1 mm in scattering biological tissue, a fundamental limit for high-resolution pure optical imaging owing to strong scattering. PAI, combining optical contrast with ultrasonic resolution, breaks through the 1-mm depth limit and provides high-resolution optical imaging, as demonstrated by the applicants' works published in Nature Biotechnology. No other optical technology can image blood vessels and functions at this resolution and depth. PAI is also free of speckle artifacts, which exist in optical coherence tomography and ultrasonography. Furthermore, the maximum imaging depth and spatial resolution of PAI can be scaled with the ultrasonic parameters. Some potential applications were highlighted by Nature Reviews Drug Discovery and Nature Reviews Molecular Cell Biology. PAI directly measures, however, specific optical absorption (absorbed energy per unit volume) rather than absorption coefficient; the former is the product of the latter and the local fluence. Quantitative PAI currently depends on ex vivo or invasive estimation of fluence so that tissue-intrinsic optical absorption coefficient can be retrieved. Central to this proposed research is to develop non-invasive in situ estimation of fluence. Two complementary forms of quantitative PAI are to be investigated: reconstruction-based photoacoustic tomography (PAT) and direct-imaging photoacoustic microscopy (PAM). In this proposed technology-driven research, we will focus on the following specific aims: (1) To quantify optical fluence for quantitative PAT using diffuse optical tomography (DOT); (2) To quantify optical fluence for quantitative PAT using transport optical tomography (TOT); (3) To quantify optical fluence for quantitative PAM using TOT; (4) To validate and evaluate the quantitative PAI systems with tissue phantoms; and (5) To validate and evaluate the quantitative PAI systems in vivo.

描述（由申请人提供）：所提议研究的目的是恢复生物组织体内定量光声成像（PAI）的光吸收系数。 PAI 可以以超出光学准弹道状态（~1 毫米）的高空间分辨率对完整的生物组织进行光学吸收对比度成像。由于光学吸收对血红蛋白总浓度和氧饱和度等生理参数敏感，PAI可以提供功能成像。借助功能化造影剂（分子探针），PAI 还可以提供分子成像。 PAI 在小动物研究和临床实践中具有潜在广泛的应用，包括（1）血管生成、脑功能、药物发现和分子细胞生物学的动物研究，（2）皮肤癌、宫颈癌和乳腺癌的临床诊断，以及（3）术中脑癌和功能的划分。尽管光学对比度很高，但传统的高分辨率光学成像模式无法在散射生物组织中穿透超过~1毫米，由于强散射，这是高分辨率纯光学成像的基本限制。 PAI将光学对比度与超声分辨率相结合，突破了1毫米的深度限制，提供了高分辨率光学成像，正如申请人在《自然生物技术》上发表的作品所证明的那样。没有其他光学技术能够以这种分辨率和深度对血管和功能进行成像。 PAI 也不存在光学相干断层扫描和超声检查中存在的散斑伪影。此外，PAI 的最大成像深度和空间分辨率可以根据超声参数进行缩放。 《自然评论药物发现》和《自然评论分子细胞生物学》强调了一些潜在的应用。然而，PAI 直接测量比光吸收（每单位体积吸收的能量）而不是吸收系数；前者是后者与当地影响力的产物。定量 PAI 目前依赖于离体或侵入性的注量估计，以便可以检索组织固有的光吸收系数。这项研究的核心是开发非侵入式原位注量估计。定量 PAI 的两种互补形式有待研究：基于重建的光声断层扫描 (PAT) 和直接成像光声显微镜 (PAM)。在这项技术驱动的研究中，我们将重点关注以下具体目标：（1）使用漫射光学断层扫描（DOT）量化光学注量以实现定量 PAT； (2) 使用传输光学断层扫描 (TOT) 量化光通量以进行定量 PAT； (3) 使用TOT量化光通量以实现定量PAM； (4) 利用组织模型验证和评估定量PAI系统； (5) 验证和评估体内定量PAI系统。