학술논문

Throughput-Speed Product Augmentation for Scanning Fiber-Optic Two-Photon Endomicroscopy
Document Type
Periodical
Source
IEEE Transactions on Medical Imaging IEEE Trans. Med. Imaging Medical Imaging, IEEE Transactions on. 39(12):3779-3787 Dec, 2020
Subject
Bioengineering
Computing and Processing
Structural beams
Focusing
Optical fibers
Lenses
Image resolution
Silicon compounds
Biomedical optical imaging
biophotonics
endomicroscope
in vivo imaging
nonlinear optics
optical microscopy
two-photon microscopy
Language
ISSN
0278-0062
1558-254X
Abstract
Compactness, among several others, is one unique and very attractive feature of a scanning fiber-optic two-photon endomicroscope. To increase the scanning area and the total number of resolvable pixels (i.e., the imaging throughput), it typically requires a longer cantilever which, however, leads to a much undesired, reduced scanning speed (and thus imaging frame rate). Herein we introduce a new design strategy for a fiber-optic scanning endomicroscope, where the overall numerical aperture (NA) or beam focusing power is distributed over two stages: 1) a mode-field focuser engineered at the tip of a double-clad fiber (DCF) cantilever to pre-amplify the single-mode core NA, and 2) a micro objective of a lower magnification (i.e., $\sim 2\times $ in this design) to achieve final tight beam focusing. This new design enables either an ~9-fold increase in imaging area (throughput) or an ~3-fold improvement in imaging frame rate when compared to traditional fiber-optic endomicroscope designs. The performance of an as-designed endomicroscope of an enhanced throughput-speed product was demonstrated by two representative applications: (1) high-resolution imaging of an internal organ (i.e., mouse kidney) in vivo over a large field of view without using any fluorescent contrast agents, and (2) real-time neural imaging by visualizing dendritic calcium dynamics in vivo with sub-second temporal resolution in GCaMP6m-expressing mouse brain. This cascaded NA amplification strategy is universal and can be readily adapted to other types of fiber-optic scanners in compact linear or nonlinear endomicroscopes.