In vivo brain imaging using a portable 29 g two-photon microscope based on a microelectromechanical systems scanning mirror

Piyawattanametha, Wibool; Cocker, Eric D.; Burns, Laurie D.; Barretto, Robert P. J.; Jung, Juergen C.; Ra, Hyejun; Solgaard, Olav; Schnitzer, Mark J.

doi:10.1364/ol.34.002309

Cited by 154 publications

(101 citation statements)

References 19 publications

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“…We anticipate that with advances in surgical techniques and further miniaturization of equipment, 7,52 such high-resolution measurements will be routinely performed in even awake animals to chart the effects of stroke and recovery. Recent data also suggest that these methods may be important for evaluating the transient effect of peri-infarct depolarizations.…”

Section: Resultsmentioning

confidence: 99%

In Vivo 2-Photon Imaging of Fine Structure in the Rodent Brain

Sigler

Murphy

2010

Stroke

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Abstract-The recent application of 2-photon microscopy to biological specimens has allowed investigators to examine individual synapses within live animals. The gain in resolution over conventional in vivo imaging techniques has been several orders of magnitude. We outline steps for the preparation and maintenance of animals for 2-photon microscopy of fine brain structure. We discuss the in vivo resolution of the method and the ability to image blood flow and synaptic structure in vivo. Applications of in vivo 2-photon microscopy include the study of synapse turnover in adult animals under normal conditions and during pathology such as stroke. In the case of stroke, 2-photon imaging has revealed marked swelling of dendrites and loss of spines within minutes of ischemic onset. Surprisingly, restoration of blood flow during reperfusion was associated with a return of relatively normal structure. Over longer time scales, 2-photon imaging revealed elevated rates of synaptogenesis within peri-infarct tissues recovering from stroke. These results provide an example of how high-resolution in vivo microscopy can be used to provide insight into both the acute pathology and recovery from stroke damage. (Stroke. 2010;41[suppl 1]:S117-S123.)Key Words: 2-photon microscopy Ⅲ anatomy Ⅲ blood flow Ⅲ brain recovery Ⅲ dendritic spine morphology Ⅲ excitotoxicity Ⅲ fluorescent proteins Ⅲ focal ischemia Ⅲ imaging Ⅲ microscopy Ⅲ mouse model Ⅲ neuropathology

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Section: Resultsmentioning

confidence: 99%

In Vivo 2-Photon Imaging of Fine Structure in the Rodent Brain

Sigler

Murphy

2010

Stroke

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“…Similarly, various point-of-care diagnostic devices have been developed and among them optical imaging and sensing techniques are highly advantageous as they can provide real-time, highresolution and highly sensitive quantitative information, potentially assisting rapid and accurate diagnosis. [30][31][32][33][34][35][36][37][38][39][40] To date, a number of optical techniques have been proposed for point-of-care diagnostics such as in vitro optical devices, [41][42][43][44][45][46][47][48][49][50][51][52][53] including portable optical imaging systems, optical microscopes integrated to cell phones or in vivo optical devices, [54][55][56][57][58][59][60][61][62][63] involving confocal microscopy, microendoscopy and optical coherence tomography techniques. Among these approaches, lens-free computational on-chip imaging 64 has been an emerging technique that can eliminate the need for bulky and costly optical components while also preserving (or even enhancing in certain cases) the image resolution, field of view and sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Handheld high-throughput plasmonic biosensor using computational on-chip imaging

et al. 2014

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We demonstrate a handheld on-chip biosensing technology that employs plasmonic microarrays coupled with a lens-free computational imaging system towards multiplexed and high-throughput screening of biomolecular interactions for point-of-care applications and resource-limited settings. This lightweight and field-portable biosensing device, weighing 60 g and 7.5 cm tall, utilizes a compact optoelectronic sensor array to record the diffraction patterns of plasmonic nanostructures under uniform illumination by a single-light emitting diode tuned to the plasmonic mode of the nanoapertures. Employing a sensitive plasmonic array design that is combined with lens-free computational imaging, we demonstrate label-free and quantitative detection of biomolecules with a protein layer thickness down to 3 nm. Integrating large-scale plasmonic microarrays, our on-chip imaging platform enables simultaneous detection of protein mono-and bilayers on the same platform over a wide range of biomolecule concentrations. In this handheld device, we also employ an iterative phase retrieval-based image reconstruction method, which offers the ability to digitally image a highly multiplexed array of sensors on the same plasmonic chip, making this approach especially suitable for high-throughput diagnostic applications in field settings.

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“…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 (12-16) scan pattern] and non-resonant-based cantilever fiber scanners (16-19) 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.…”

mentioning

confidence: 99%

“…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).…”

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

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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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In vivo brain imaging using a portable 29 g two-photon microscope based on a microelectromechanical systems scanning mirror

Cited by 154 publications

References 19 publications

In Vivo 2-Photon Imaging of Fine Structure in the Rodent Brain

In Vivo 2-Photon Imaging of Fine Structure in the Rodent Brain

Handheld high-throughput plasmonic biosensor using computational on-chip imaging

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

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