High-resolution resonant and nonresonant fiber-scanning confocal microscope

Hendriks, Benno H. W.; Bierhoff, Walter; Horikx, J. J. L.; Desjardins, Adrien E.; Hezemans, Cees A.; Hooft, G. W. ’t; Lucassen, Gerald W.; Mihajlović, Nenad

doi:10.1117/1.3534781

Cited by 22 publications

(17 citation statements)

References 23 publications

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“…A number of groups have demonstrated miniaturized instruments capable of confocal, optical coherence tomography (OCT), TPF, and SHG imaging (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The primary constituents of these devices are typically a miniaturized scanning mechanism and lens assembly that is encapsulated in a protective housing with dimensions suitable for minimally invasive procedures (i.e., a probe outer diameter on the order of a few millimeters with a rigid length of several centimeters).…”

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confidence: 99%

“…The primary constituents of these devices are typically a miniaturized scanning mechanism and lens assembly that is encapsulated in a protective housing with dimensions suitable for minimally invasive procedures (i.e., a probe outer diameter on the order of a few millimeters with a rigid length of several centimeters). Within these microendoscopes, various distal miniaturized scanners have been demonstrated, including resonant-based [e.g., Lissajous (10,11) or spiral (12)(13)(14)(15)(16) scan pattern] and non-resonant-based cantilever fiber scanners (16)(17)(18)(19) as well as microelectromechanical systems (MEMS) scanning mirrors (20)(21)(22)(23)(24)(25). Of these scanners, the resonant-based spiral scanners are the most successful in terms of their miniaturized dimensions (e.g., o:d: ≈ 1 mm) and fast image acquisition speeds [e.g., 8 frames∕s with 512 × 512 pixels per frame, approximately 200-μm diameter field-of-view (FOV xy )] (14); however, these resonant devices are fundamentally limited by nonuniform spatial coverage and sampling time in comparison to current miniaturized raster scanners.…”

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Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue

Rivera

Brown

Ouzounov

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

251

174

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We present a compact and flexible endoscope (3-mm outer diameter, 4-cm rigid length) that utilizes a miniaturized resonant/nonresonant fiber raster scanner and a multielement gradient-index lens assembly for two-photon excited intrinsic fluorescence and second-harmonic generation imaging of biological tissues. The miniaturized raster scanner is fabricated by mounting a commercial double-clad optical fiber (DCF) onto two piezo bimorphs that are aligned such that their bending axes are perpendicular to each other. Fast lateral scanning of the laser illumination at 4.1 frames∕s (512 lines per frame) is achieved by simultaneously driving the DCF cantilever at its resonant frequency in one dimension and nonresonantly in the orthogonal axis. The implementation of a DCF into the scanner enables simultaneous delivery of the femtosecond pulsed 800-nm excitation source and epi-collection of the signal. Our device is able to achieve a field-of-view (FOV xy ) of 110 μm by 110 μm with a highly uniform pixel dwell time. The lateral and axial resolutions for two-photon imaging are 0.8 and 10 μm, respectively. The endoscope's imaging capabilities were demonstrated by imaging ex vivo mouse tissue through the collection of intrinsic fluorescence and second-harmonic signal without the need for staining. The results presented here indicate that our device can be applied in the future to perform minimally invasive in vivo optical biopsies for medical diagnostics.nonlinear optical endoscopy | real-time optical diagnosis | scanning fiber endoscopy | microendoscopy | endogenous fluorescence M ultiphoton imaging techniques such as two-photon fluorescence (TPF) and second-harmonic generation (SHG) microscopy hold great promise for the future of medical diagnosis because of their potential to replace surgical biopsies with minimally invasive optical diagnosis of tissue health (1-7). In a clinical setting, these diagnostic techniques will be capable of acquiring real-time, high-resolution, in vivo images without the need for contrast agents. However, a challenge in translating these beneficial imaging technologies into the clinic lies in successfully miniaturizing bulky tabletop microscope components into a compact probe without degrading the overall imaging performance of the system. These microendoscopes would not only have the potential to be used as diagnostic tools capable of early cancer detection, but could also be used for such applications as photodynamic therapy and microsurgery (8,9).A number of groups have demonstrated miniaturized instruments capable of confocal, optical coherence tomography (OCT), TPF, and SHG imaging (10-25). The primary constituents of these devices are typically a miniaturized scanning mechanism and lens assembly that is encapsulated in a protective housing with dimensions suitable for minimally invasive procedures (i.e., a probe outer diameter on the order of a few millimeters with a rigid length of several centimeters). Within these microendoscopes, various distal miniaturized scanners have been demonstr...

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confidence: 99%

mentioning

confidence: 99%

Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue

Rivera

Brown

Ouzounov

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

251

174

View full text Add to dashboard Cite

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“…Their size prevents their use in a clinical settings, where a small, portable probe is usually required. Currently, hand-held confocal microscopes have been demonstrated, but their FOV is generally very small, usually much less than 0.5 mm [1,2]. Speed is also a major limitation of confocal microscopy.…”

Section: Introductionmentioning

confidence: 98%

System design and evaluation of the array confocal fluorescence microscope

et al. 2014

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The scanning speed for conventional confocal fluorescence imaging systems is limited due to several factors. To improve the speed of scanning, we develop an array confocal fluorescence microscope (ACFM) that can image large 3D volumes faster than conventional confocal microscopes over a large field of view (FOV). This paper will discuss the design and evaluation of the array confocal fluorescence microscope.

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“…For example, a MEMS scanner can be used to scan the light beam [8,9] or the fiber tip itself can be scanned [10][11][12]. Such devices can reach diffraction-limited resolution, but have large probes of several millimeters.…”

Section: Fiber-based Confocal Endoscopesmentioning

confidence: 99%

Digital confocal microscopy through a multimode fiber

Loterie¹,

Farahi²,

Papadopoulos³

et al. 2015

Opt. Express

151

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Acquiring high-contrast optical images deep inside biological tissues is still a challenging problem. Confocal microscopy is an important tool for biomedical imaging since it improves image quality by rejecting background signals. However, it suffers from low sensitivity in deep tissues due to light scattering. Recently, multimode fibers have provided a new paradigm for minimally invasive endoscopic imaging by controlling light propagation through them. Here we introduce a combined imaging technique where confocal images are acquired through a multimode fiber. We achieve this by digitally engineering the excitation wavefront and then applying a virtual digital pinhole on the collected signal. In this way, we are able to acquire images through the fiber with significantly increased contrast. With a fiber of numerical aperture 0.22, we achieve a lateral resolution of 1.5µm, and an axial resolution of 12.7µm. The point-scanning rate is currently limited by our spatial light modulator (20Hz). wide-field endoscopic imaging by using a single multimode optical fiber," Phys.

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High-resolution resonant and nonresonant fiber-scanning confocal microscope

Cited by 22 publications

References 23 publications

Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue

Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue

System design and evaluation of the array confocal fluorescence microscope

Digital confocal microscopy through a multimode fiber

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