Development of optical resolution photoacoustic microscopy with sub-micron lateral resolution for visualization of cells and their structures

Abstract

Photoacoustic (PA) imaging is a hybrid imaging technique with light-dependent contrast and ultrasound-dependent depth. In previous studies, the interest of PA imaging was mainly clinical research. However, in recent years, PA imaging that targets cells also has attracted attention. Cells are the smallest unit in our body, and cell abnormalities cause various diseases. Therefore, PA imaging of cells is important for elucidating the relationship between diseases and PA properties and linking the results to the clinical application of PA imaging. For PA imaging of cells and its internal structures, sub-micron lateral resolution is required. In this study, we have developed an optical resolution photoacoustic microscopy (OR-PAM) system using a high NA objective lens and a single-mode fiber to achieve sub-micron lateral resolution. With the OR-PAM, it was confirmed that the lateral resolution was better than 700 nm, and the characteristic shapes of red blood cells and melanoma cells could be visualized.

High-speed optical resolution photoacoustic microscopy with MEMS scanner using a novel and simple distortion correction method

“…It uses tightly focused laser irradiation with a much smaller focus area than that of the acoustic reception beam. As a result, OR-PAM has achieved an optical-dependent high lateral resolution of 0.2–10 µm with a penetration depth of up to 1 mm 20 – 24 , furthermore its high resolution indicates the potential to perform (1) clinical imaging of capillaries and their metabolic activity, (2) preclinical imaging of small animals such as mice 21 , 25 .…”

Deformation measurement of liquid-filled elastic tube embedded in soft material using optimal pulse width method under photoacoustic excitation

“…It has been demonstrated that the photoacoustic measurement can reach the diameters down to 0.1 mm order by employing high power pulsed laser source and 10 MHzorder ultrasound transducer array. An attempt to give optical resolution to photoacoustic microscopy was reported [31]. Photoacoustic tomography of vascular compliance was also studied [32].…”

“…Different from the imaging-based phase-delay thoughts, the authors have investigated the relationship between the excitation pulse width and the acoustic resonance inside a tube [31,32]. The acoustic resonance is caused by a light pulse, and then monitored as photoacoustically induced ultrasound.…”

Optical and ultrasonic dual-sensitive sensor and its application in photoacoustic microscopy

“…Based on the photoacoustic effect, biomedical imaging technology like photoacoustic microscopy (PAM), photoacoustic tomography (PAT) and photoacoustic endoscope (PAE) has developed rapidly. [11][12][13][14] The photoacoustic effect has also been used to make optoacoustic transducers. [15][16][17][18][19][20] This kind of transducer can generate high-frequency ultrasound (>50 MHz) while achieving element size and spacing on the order of several microns.…”