Photoacoustic endoscopy shows promise in the detection of gastrointestinal cancer, inflammation, and other lesions. High-resolution endoscopic imaging of the hemodynamic response necessitates a small-sized, high-sensitivity ultrasound sensor. Here, we utilize a laser ultrasound sensor to develop a miniaturized, optical-resolution photoacoustic endoscope. The sensor can boost the acoustic response by a gain factor of ω_o/Ω (the frequency ratio of the signal light and measured ultrasound) by measuring the acoustically induced optical phase change. As a result, we achieve a noise-equivalent pressure density (NEPD) below 1.5 mPa·Hz^−1/2 over the measured range of 5 to 25 MHz. The heterodyne phase detection using dual-frequency laser beams of the sensor can offer resistance to thermal drift and vibrational perturbations. The endoscope is used to in vivo image a rat rectum and visualize the oxygen saturation changes during acute inflammation, which can hardly be observed with other imaging modalities.

Fast functional photoacoustic microscopy requires multi-wavelength pulsed laser sources with high pulse repetition rates, short wavelength switching time, and sufficient pulse energies. Here, we report the development of a stimulated-Raman-scattering-based multi-wavelength pulsed laser source for fast functional photoacoustic imaging. The new laser source is pumped with a 532 nm 1 MHz pulsed laser. The 532 nm laser beam is split into two: one pumps a 5 m optical fiber to excite a 558 nm wavelength via stimulated Raman scattering; the other goes through a 50 m optical fiber to delay the 532 nm pulse by 220 ns. The two beams are combined and coupled into an optical fiber for photoacoustic excitation. As a result, the new laser source can generate 2 million pulses per second, switch wavelengths in 220 ns, and provide hundreds of nanojoules pulse energy for each wavelength. Using this laser source, we demonstrate optical-resolution photoacoustic imaging of microvascular structures and oxygen saturation in the mouse ear. The ultrashort wavelength switching time enables oxygen saturation imaging of flowing red blood cells, which is valuable for high-resolution functional imaging.

Photoacoustic imaging, especially for intravascular and endoscopic applications, requires ultrasound probes with miniature size and high sensitivity. In this paper, we present a new photoacoustic sensor based on a small-sized fiber laser. Incident ultrasound waves exert pressures on the optical fiber laser and induce harmonic vibrations of the fiber, which is detected by the frequency shift of the beating signal between the two orthogonal polarization modes in the fiber laser. This ultrasound sensor presents a noise-equivalent pressure of 40 Pa over a 50-MHz bandwidth. We demonstrate this new ultrasound sensor on an optical-resolution photoacoustic microscope. The axial and lateral resolutions are 48 μm and 3.3 μm. The field of view is up to 1.57 mm². The sensor exhibits strong resistance to environmental perturbations, such as temperature changes, due to common-mode cancellation between the two orthogonal modes. The present fiber laser ultrasound sensor offers a new tool for all-optical photoacoustic imaging.

We report the development of a head-mounted photoacoustic fiberscope for cerebral imaging in a freely behaving mouse. The 4.5-gram imaging probe has a 9-µm lateral resolution and 0.2-Hz frame rate over a 1.2-mm wide area. The probe can continuously monitor cerebral oxygenation and hemodynamic responses at single-vessel resolution, showing significantly different cerebrovascular responses to external stimuli under anesthesia and in the freely moving state. For example, when subjected to high-concentration CO₂ respiration, enhanced oxygenation to compensate for hypercapnia can be visualized due to cerebral regulation in the freely moving state. Comparative studies exhibit significantly weakened compensation capabilities in obese rodents. This new imaging modality can be used for investigating both normal and pathological cerebrovascular functions and shows great promise for studying cerebral activity, disorders and their treatments.

Optical-resolution photoacoustic microscopy (OR-PAM) images biological tissue with sub-cellular resolution and optical absorption contrast. OR-PAM is limited by the tradeoff among imaging speed, field of view, and sensitivity. In this work, we present an OR-PAM technique based on an unfocused side-looking fiber optic ultrasound (FOUS) sensor, which achieves high imaging speed, large field of view, and good sensitivity for in vivo imaging. The FOUS sensor is developed based on a dual-polarized fiber laser and read out with real-time frequency demodulation. Via minimizing the readout noise, the sensor offers a noise-equivalent pressure of 43.6 Pa, enabling high detection sensitivity over a large field of view. High imaging speed is achieved via scanning the laser beam with a 2D galvo mirror in the ultrasound detection area. Microvascular imaging with a frame rate of 2 Hz over a 2 × 2 mm² area has been demonstrated in the mouse ear. The new OR-PAM technique may be used in the visualization of biological and physiologic dynamics.