Rapid-scanning optical-resolution photoacoustic microscopy

描述（由申请人提供）：我们建议开发快速扫描光学分辨率光声显微镜（OR-PAM），该显微镜能够对非荧光光学吸收剂进行无标签成像。由于内源性强光吸收血红蛋白的存在，光学吸收对比对于微血管成像和表征是非常理想的。所提出的成像系统可以提供5微米的横向分辨率，15微米的轴向分辨率，1.2毫米的成像深度和30赫兹的b扫描帧率。提出以下具体目标。目的1。系统设计和实现：提出的快速扫描OR-PAM预计在成像速度上比当前版本高出10倍。采用近衍射极限光学聚焦实现横向分辨率。由于热弹性膨胀，聚焦光的吸收产生光声波。利用高频聚焦超声换能器检测光声波，测量内部光吸收分布，从而提供光学结构的三维映射。OR-PAM能够以100%的相对灵敏度测量光学吸收，这是任何线性效应成像方法的理论极限。为了实现高成像率，需要对双光-超声焦点进行快速扫描。目标2。在幻影和活鼠身上测试成像系统：将在幻影和活鼠身上测试所提出的OR-PAM系统，以量化B扫描成像的最大成像深度、空间分辨率、信噪比和帧率。

DESCRIPTION (provided by applicant): We propose to develop rapid-scanning optical-resolution photoacoustic microscopy (OR-PAM), which is capable of label- free imaging of non-fluorescent optical absorbers. Optical absorption contrast is highly desirable for microvascular imaging and characterization because of the presence of endogenous strongly light-absorbing hemoglobin. The proposed imaging system can provide a 5-micron lateral resolution, a 15-micron axial resolution, a 1.2-mm imaging depth, and a 30-Hz B-scan frame rate. The following specific aims are proposed. Aim 1. System design and implementation: The proposed rapid-scanning OR-PAM is expected to outperform the current version in imaging speed by a factor of 10. Nearly diffraction-limited optical focusing is employed to achieve the lateral resolution. Absorption of the focused light produced photoacoustic waves due to thermoelastic expansion. Detection of the photoacoustic waves using a high-frequency focused ultrasonic transducer measures the internal light absorption distribution and hence provides a 3D mapping of the optical structure. OR-PAM is able to measure optical absorption with a relative sensitivity of 100%, the theoretical limit of any linear-effect imaging methods. Rapid scanning of the dual optical-ultrasonic foci is required to achieve a high imaging rate. Aim 2. Testing the imaging system in phantoms and living mice: The proposed OR-PAM system will be tested with phantoms and living mice to quantify the maximum imaging depth, spatial resolution, SNR, and the frame rate for B- scan imaging. PUBLIC HEALTH RELEVANCE: Microcirculation, the distal functional unit of the cardiovascular system, provides exchange sites for gases, nutrients, metabolic wastes, and thermal energy between the blood and the tissues. Pathologic microcirculation reflects the breakdown of homeostasis in organisms, which ultimately leads to tissue inviability. Therefore, the proposed in vivo microvascular imaging and characterization is of significant physiological, pathophysiological, and clinical importance.