Abstract

Combining different contrast mechanisms to achieve simultaneous multimodal imaging is always desirable but is challenging due to the various optical and hardware requirements for different imaging systems. We developed a multimodal microscopic optical imaging system with the capability of providing comprehensive structural, functional and molecular information of living tissues. This imaging system integrated photoacoustic microscopy (PAM), optical coherence tomography (OCT), optical Doppler tomography (ODT) and confocal fluorescence microscopy in one platform. By taking advantage of the depth resolving capability of OCT, we developed a novel OCT-guided surface contour scanning methodology for dynamic focusing adjustment. We have conducted phantom, in vivo, and ex vivo tests to demonstrate the capability of the multimodal imaging system for providing comprehensive microscopic information of biological tissues. Integrating all the aforementioned imaging modalities with OCT-guided dynamic focusing for simultaneous multimodal imaging has promising potential for preclinical research and clinical practice in the future.

Highlights

  • Over the past years, various optical microscopy techniques, such as optical coherence tomography (OCT) [1,2], confocal fluorescence microscopy (CFM) [3,4,5], photoacoustic microscopy (PAM) [6,7,8], and optical Doppler tomography (ODT) [9,10,11], have been established and broadly applied in biomedical research and preclinical/clinical studies

  • ODT is a branch of OCT, which is used to characterize the functional information, i.e. the blood flow velocity, of biological samples with high resolution [10,11]

  • Blood flow is an important functional parameter for biological tissues, for example, various ocular diseases are associated with alterations in blood flow, such as glaucoma, age-related macular degeneration and diabetic retinopathy [18,19,20]

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Summary

Introduction

Various optical microscopy techniques, such as optical coherence tomography (OCT) [1,2], confocal fluorescence microscopy (CFM) [3,4,5], photoacoustic microscopy (PAM) [6,7,8], and optical Doppler tomography (ODT) [9,10,11], have been established and broadly applied in biomedical research and preclinical/clinical studies All these optical imaging techniques have been shown to be a powerful tool for revealing structural, functional and molecular features of biological specimens noninvasively [12,13,14,15,16,17]. Blood flow is an important functional parameter for biological tissues, for example, various ocular diseases are associated with alterations in blood flow, such as glaucoma, age-related macular degeneration and diabetic retinopathy [18,19,20]

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