In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems

Huland, David M.; Brown, Christopher M.; Howard, Scott S.; Ouzounov, Dimitre G.; Pavlova, Ina; Wang, Ke; Rivera, David R.; Webb, Watt W.; Xu, Chris

doi:10.1364/boe.3.001077

Cited by 116 publications

(91 citation statements)

References 28 publications

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“…29,30 These studies have shown the feasibility of performing MPM in vivo. Thus, from our encouraging results and the availability of miniaturized MPM probes, we foresee MPM as a potential tool for the detection and differentiation of CIS from other benign flat lesions during cystoscopy.…”

Section: Commentmentioning

confidence: 99%

“…24,25 The benchtop MPM system has been used successfully to identify benign and malignant lesion in ex vivo tissues from various organs, including the urinary bladder, in human subjects. [26][27][28] While miniaturized MPM endoscopes (MPEs) 29,30 are being developed and tested in animal models, we aim to determine the potential of MPM to detect malignant flat lesions, especially CIS, using ex vivo human bladder samples. The ultimate goal of this project is to integrate MPM during cystoscopy for the detection of malignant cells in superficial urothelial carcinomas.…”

mentioning

confidence: 99%

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Multiphoton Microscopy: A Potential Intraoperative Tool for the Detection of Carcinoma In Situ in Human Bladder

Jain

Robinson²,

Shevchuk³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Urothelial carcinoma in situ (CIS) is a precursor of invasive bladder cancer, which if left untreated, will likely progress to more aggressive disease. Approximately 50% of CIS lesions are missed on routine cystoscopy owing to their flat architecture. Furthermore, many benign but abnormal-appearing areas may be biopsied owing to lack of cellular resolution of cystoscopes. Multiphoton microscopy (MPM) is an optical imaging technique that generates subcellular-resolution three-dimensional images from unfixed tissue without using exogenous dyes.Objective.-To assess the diagnostic potential of MPM in identifying and differentiating benign from malignant flat bladder lesions, especially CIS.Design.-Seventy-eight specimens (benign ¼ 46, CIS ¼ 23, invasive ¼ 9, as diagnosed on histopathology) were obtained from flat bladder mucosa via transurethral resection of bladder, cold cup biopsy, or cystectomy, imaged fresh with a commercial benchtop MPM, and submitted for routine histopathology. Multiphoton microscopy and hematoxylin-eosin diagnoses were compared.Results.-In 77 of 78 specimens (99%), accurate MPM diagnoses (benign/malignant) were given on the basis of their architectural and cytologic features (nuclear to cytoplasmic ratio, pleomorphism, polarity/organization of urothelial layers, etc). The sensitivity and specificity were 97% and 100%, respectively, with positive (malignant) and negative (benign) predictive values of 100% and 98%, respectively. The interobserver agreement, j, was 0.93.Conclusions.-Our study demonstrates the capability of MPM to identify and differentiate benign from malignant flat bladder lesions, especially CIS. With the advent of MPM endoscopes, we foresee their potential as a biopsy guidance tool for early detection and treatment of CIS, thus reducing the rate of biopsies with benign diagnoses and their associated complications.

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Section: Commentmentioning

confidence: 99%

mentioning

confidence: 99%

Multiphoton Microscopy: A Potential Intraoperative Tool for the Detection of Carcinoma In Situ in Human Bladder

Jain

Robinson²,

Shevchuk³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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“…Other multi-photon endomicroscopes have used GRIN lenses for focusing [17][18][19][20]. These objectives are limited by chromatic aberration for fluorescence imaging [21]. We used a compound lens because our MEMS mirror can achieve high reflectivity over a broad spectral range from 450 to 780 nm.…”

Section: Discussionmentioning

confidence: 99%

MEMS-based multiphoton endomicroscope for repetitive imaging of mouse colon

Duan

Qiu

et al. 2015

Biomed. Opt. Express

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Abstract:We demonstrate a handheld multiphoton endomicroscope with 3.4 mm distal diameter that can repetitively image mouse colon in vivo. A 2D resonant MEMS mirror was developed to perform beam scanning in a Lissajous pattern. The instrument has an effective numerical aperture of 0.63, lateral and axial resolution of 2.03 and 9.02 μm, respectively, working distance of 60 μm, and image field-of-view of 300 × 300 μm 2 . Hoechst was injected intravenously in mice to stain cell nuclei. We were able to collect histology-like images in vivo at 5 frames/sec, and distinguish between normal and pre-malignant colonic epithelium.

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“…Therefore, especially technological improvements are required for miniaturization, improvement of the ease of handling and automated data processing and extraction of relevant information. An important step toward this goal is the modification of standard clinical endoscopes [158] for multimodal nonlinear imaging suited for in vivo applications [159][160][161][162][163].…”

Section: Discussionmentioning

confidence: 99%

Accumulating advantages, reducing limitations: Multimodal nonlinear imaging in biomedical sciences – The synergy of multiple contrast mechanisms

Meyer

Schmitt

Dietzek

et al. 2013

Journal of Biophotonics

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Journal of BIOPHOTONICSMultimodal nonlinear microscopy has matured during the past decades to one of the key imaging modalities in life science and biomedicine due to its unique capabilities of label-free visualization of tissue structure and chemical composition, high depth penetration, intrinsic 3D sectioning, diffraction limited resolution and low phototoxicity. This review briefly summarizes first recent advances in the field regarding the methodology, e.g., contrast mechanisms and signal characteristics used for contrast generation as well as novel image processing approaches. The second part deals with technologic developments emphasizing improvements in penetration depth, imaging speed, spatial resolution and nonlinear labeling strategies. The third part focuses on recent applications in life science fundamental research and biomedical diagnostics as well as future clinical applications.Multimodal nonlinear microscopy of tissue.

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In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems

Cited by 116 publications

References 28 publications

Multiphoton Microscopy: A Potential Intraoperative Tool for the Detection of Carcinoma In Situ in Human Bladder

Multiphoton Microscopy: A Potential Intraoperative Tool for the Detection of Carcinoma In Situ in Human Bladder

MEMS-based multiphoton endomicroscope for repetitive imaging of mouse colon

Accumulating advantages, reducing limitations: Multimodal nonlinear imaging in biomedical sciences – The synergy of multiple contrast mechanisms

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