Wavelength agile photoacoustic microscopy for video-rate functional imaging

1133153光声显微镜（PAM）是一种依赖于脉冲光激发和超声检测的有前途的技术。精细的组织微血管系统，包括个别毛细血管，在体内的图像已经获得了良好的对比度的基础上的光吸收，而不是反射。生理变化可以改变光吸收的波长依赖性，使得功能性PAM（fPAM）可能具有多个波长的光激发。fPAM已经在肿瘤微血管的氧合研究和监测小动物模型中的脑活动中受到相当大的关注。fPAM的一个主要限制是成像速度。虽然单波长图像可以快速采集，但多波长图像需要过长的采集时间。因此，常规fPAM不能产生快速动态事件（例如，发育中的胚胎心脏中的血氧合）的功能图像。传统脉冲激光器的慢波长调谐使得不可能获得视频速率fPAM图像。有希望的初步研究表明，高速fPAM是可能的，与基于受激拉曼散射的电光光源。该提议的基本假设是波长敏捷性可以彻底改变fPAM的能力。PI建议开发这种紧凑的光源，在不到1毫秒的时间内切换波长，这意味着比传统激光器的切换速度提高了1000倍。该波长捷变源为实现视频速率fPAM提供了必要的突破。他们还建议将我们的高速fPAM系统与他们现有的光学相干断层扫描（OCT）系统相结合。该组合系统将以视频帧速率提供微脉管系统和周围组织的高分辨率结构和功能图像。

1133153BumaPhotoacoustic microscopy (PAM) is a promising technique that relies on pulsed optical excitation and ultrasonic detection. Exquisite in vivo images of tissue microvasculature, including individual capillaries, have been obtained with excellent contrast based on optical absorption rather than reflectance. Physiological changes can alter the wavelength dependence of optical absorption, making functional PAM (fPAM) possible with optical excitation at multiple wavelengths. fPAM has received considerable interest for oxygenation studies of tumor microvasculature and monitoring brain activity in small animal models. A major limitation of fPAM is imaging speed. Although single-wavelength images can be acquired quickly, multi-wavelength images require excessively long acquisition times. Therefore, conventional fPAM cannot produce functional images of fast dynamical events (e.g. blood oxygenation in a developing embryonic heart). The slow wavelength tuning of conventional pulsed lasers makes it impossible to obtain video-rate fPAM images. Promising preliminary studies suggest that high speed fPAM is possible with a multicolor optical source based on stimulated Raman scattering. The fundamental hypothesis of this proposal is that wavelength agility can revolutionize the capabilities of fPAM. The PIs propose to develop this compact source to switch wavelengths in less than 1 millisecond, representing a 1000-fold improvement in switching speed over conventional lasers. This wavelength agile source provides the breakthrough necessary to realize video-rate fPAM. They further propose to combine our high speed fPAM system with their existing optical coherence tomography (OCT) system. This combined system will provide high resolution structural and functional images of both microvasculature and surrounding tissue at video frame rates.