Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues

Wu, Yicong; Leng, Yuxin; Xi, Jiefeng; Li, Xingde

doi:10.1364/oe.17.007907

Cited by 132 publications

(97 citation statements)

References 22 publications

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“…As SHG microscopy is nondestructive, the unaltered paraffin blocks can be returned to the pathology archive after SHG microscopic investigation. Another major advantage of SHG microscopy is that it can be performed through an ultra-compact fiber-optic endomicroscope, [40][41][42][43][44][45] which can be integrated with a 14-gauge breast biopsy needle. Such "throughneedle" SHG endomicroscopy may, in the future, allow for SHG Col1 imaging to be performed during the initial diagnostic mammography-guided breast biopsy in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Collagen I fiber density increases in lymph node positive breast cancers: pilot study

et al. 2012

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Abstract. Collagen I (Col1) fibers are a major structural component in the extracellular matrix of human breast cancers. In a preliminary pilot study, we explored the link between Col1 fiber density in primary human breast cancers and the occurrence of lymph node metastasis. Col1 fibers were detected by second harmonic generation (SHG) microscopy in primary human breast cancers from patients presenting with lymph node metastasis (LN þ ) versus those without lymph node metastasis (LN − ). Col1 fiber density, which was quantified using our in-house SHG image analysis software, was significantly higher in the primary human breast cancers of LN þ (fiber volume ¼ 29.22% AE 4.72%, inter-fiber distance ¼ 2.25 AE 0.45 μm) versus LN − (fiber volume ¼ 20.33%AE 5.56%, inter-fiber distance ¼ 2.88 AE 1.07 μm) patients. Texture analysis by evaluating the co-occurrence matrix and the Fourier transform of the Col1 fibers proved to be significantly different for the parameters of co-relation and energy, as well as aspect ratio and eccentricity, for LN þ versus LN − cases. We also demonstrated that tissue fixation and paraffin embedding had negligible effect on SHG Col1 fiber detection and quantification. High Col1 fiber density in primary breast tumors is associated with breast cancer metastasis and may serve as an imaging biomarker of metastasis.

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Section: Discussionmentioning

confidence: 99%

Collagen I fiber density increases in lymph node positive breast cancers: pilot study

et al. 2012

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“…25,45 Even without a detailed understanding of the molecular origin of the changes in SHG images during pregnancy, the information obtained by SHG imaging may have value as a diagnostic tool for detecting premature cervical ripening and impending preterm birth in women earlier and with greater accuracy than current measurements of cervical length by sonography. 46 Application of SHG endoscopes 47,48 and more sophisticated image analysis algorithms to distinguish the stages of gestation will be required to utilize backscattered SHG as a clinical tool in the obstetrics clinic. The ability to better identify women at risk for preterm birth along with improved therapies could have a significant impact in reducing the incidence of prematurity.…”

Section: Discussionmentioning

confidence: 99%

Second harmonic generation imaging as a potential tool for staging pregnancy and predicting preterm birth

2010

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Abstract. We use second harmonic generation ͑SHG͒ microscopy to assess changes in collagen structure of murine cervix during cervical remodeling of normal pregnancy and in a preterm birth model. Visual inspection of SHG images revealed substantial changes in collagen morphology throughout normal gestation. SHG images collected in both the forward and backward directions were analyzed quantitatively for changes in overall mean intensity, forward to backward intensity ratio, collagen fiber size, and porosity. Changes in mean SHG intensity and intensity ratio take place in early pregnancy, suggesting that submicroscopic changes in collagen fibril size and arrangement occur before macroscopic changes become evident. Fiber size progressively increased from early to late pregnancy, while pores between collagen fibers became larger and farther apart. Analysis of collagen features in premature cervical remodeling show that changes in collagen structure are dissimilar from normal remodeling. The ability to quantify multiple morphological features of collagen that characterize normal cervical remodeling and distinguish abnormal remodeling in preterm birth models supports future studies aimed at development of SHG endoscopic devices for clinical assessment of collagen changes during pregnancy in women and for predicting risk of preterm labor which occurs in 12.5% of all pregnancies.

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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).…”

mentioning

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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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.

247

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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Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues

Cited by 132 publications

References 22 publications

Collagen I fiber density increases in lymph node positive breast cancers: pilot study

Collagen I fiber density increases in lymph node positive breast cancers: pilot study

Second harmonic generation imaging as a potential tool for staging pregnancy and predicting preterm birth

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

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