All-Optical and Endoscopic Photoacoustic Microscopy

Optical-resolution photoacoustic microscopy (OR-PAM) is a novel imaging technology providing high micron-scale lateral spatial resolution to visualize superficial structures in vivo with optical-absorption contrast. The term “optical resolution” is used since the lateral resolution of the system is defined by the optically-focused spot size, which is limited by the diffraction-limit of light. The axial resolution of the system is still inversely related to the bandwidth of transducer, typical of other photoacoustic microscopy (PAM) systems. Due to limitations of light transport, OR-PAM is used for imaging superficial structures to depths of about 1 mm in tissue. OR-PAM is able to image capillary networks and quantify morphological and functional parameters such as number of vessels, diameter and length of the vessels, total hemoglobin concentration and hemoglobin oxygen saturation. A tumor needs to develop angiogenesis in order to consume more oxygen and nutrients to grow. These blood vessels can provide imaging contrast for photoacoustic imaging, making OR-PAM a useful tool for tumor imaging. However there are several limitations with current OR-PAM systems. One of the limitations is their lack of flexibility. The present OR-PAM systems are mostly mounted as a table-top device with a large footprint. In this dissertation we introduce a label free optical-resolution photoacoustic micro-endoscopy to enable access to internal body cavities and a flexible handheld probe. Also, a multi-wavelength fiber laser with tunable repetition rates as high as 600 kHz, and high pulse-to pulse stability is demonstrated for in vivo real time functional imaging. This has been done by taking advantage of stimulated Raman scattering (SRS) in a single mode fiber. This system is also modified to perform a multi-focus OR-PAM by taking advantage of chromatic aberration in the collimating/objective lens pair to refocus light from a fiber into an object so that each iii wavelength is focused at a slightly different depth location. Design and fabrication of a novel Fabry-Perot etalon- based ultrasound detectors by using glancing angle deposition (GLAD) nanostructured thin-films is shown as well. Finally a novel all optical non-contact photoacoustic remote sensing (PARS) microscopy system is demonstrated with a lateral resolution as low as 2 μm. This system offers optical absorption contrast without the need of bulky ultrasound transducers or coupling medium and can provide performance comparable to previous OR-PAM systems but in a non-contact setting.