Ultralow energy photoacoustic microscopy for ocular imaging in vivo

Abstract

Significance: The development of ultralow energy photoacoustic microscopy (PAM) on the clinically relevant pigmented rabbit eye model paves a road toward translation of the emerging PAM technology in ophthalmology clinics. Aim: Since the eye is particularly vulnerable to laser damage, we aim to develop an ultralow energy PAM system to significantly improve the laser safety of PAM by increasing the sensitivity of the system and reducing the incident laser energy for imaging. Approach: A multichannel data acquisition circuit with two-stage signal amplification was specially designed, which, in combination with the application of 3 by 3 median filter in the spatial domain, significantly improved the signal-to-noise ratio of the PAM system. The safety of this system was validated by histopathology, fluorescein angiography, and fundus photography. Results: Experiments performed on pigmented rabbits demonstrated that, when using this ultralow energy PAM system, satisfactory image quality can be achieved in the eye with an incident laser fluence that is only 1% of the American National Standards Institute safety limit. Fundus photography, fluorescein angiography, and histopathology were performed after the imaging procedure, and no retinal or ocular damage was observed. Conclusions: The proposed ultralow energy PAM system has excellent safety and holds potential to be developed into a clinical tool for ocular imaging.

Advanced nanomaterials for imaging of eye diseases

“…PAM serves as a safe imaging modality because it does not produce ionizing radiation, and the energy levels emitted from the laser diode can be significantly below American National Standards Institute (ANSI) laser safety limits. Recent studies by Li et al and Zhang et al performed a comprehensive safety evaluation of a PAM imaging system used to visualize retinal blood vessels and showed that pulsed-laser energy levels at 1.6 nJ (1 % of the ANSI safety limit) were able to generate defined images of the retinal vasculature without damage as per histological analysis [ 88 , 89 ], demonstrating that ultralow energy PAM systems can likely be applied safely in the future in clinical eye settings. In addition to uses in ophthalmology, PAM can be used for a variety of imaging applications, including oncology [ 90 , 91 ], neurology [ 92 , 93 ], dermatology [ 94 ], and gastroenterology [ 95 ].…”

“…While still a new and ongoing development, PAM imaging shows promise as an ophthalmic modality capable of safely producing images of high resolution and penetrance for the diagnosis and tracking of a variety of eye conditions. Multiple animal studies have shown excellent PAM imaging outcomes [ 88 , 96-98 ]. For example, in a study evaluating the progression of choroidal vascular occlusion (CVO), PAM imaging was able to successfully visualize CVO at high resolution over the course of 28 days [ 82 ].…”

Sensitivity in laser scanning photoacoustic microscopy

“…The laser light is then raster scanned point by point, within the field-of-view (FOV) of the transducer onto the target to be imaged [19]. LS-PAM has been implemented vigorously by many research groups working in the field of dermatology [20], oncology [21], neurology [22], and ophthalmology [23]. However, LS-PAM has a disadvantage of low signal-to-noise ratio (SNR) compared to traditional PAM configurations [17,18].…”

Non-invasive and low-artifact in vivo brain imaging by using a scanning acoustic-photoacoustic dual mode microscopy

“…Photoacoustic microscopy (PAM) is a potential brain imaging modality, benefitting from the advantages of rich functional information in biological tissue. [1][2][3][4][5][6][7][8][9][10] PAM is based on the photoacoustic (PA) effect. Short laser pulse illuminates the biological tissues.…”