Intraluminal là gì


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A Real-Time Clinical Endoscopic System for Intraluminal, Multiplexed Imaging of Surface-Enhanced Raman Scattering Nanoparticles
A Real-Time Clinical Endoscopic System for Intraluminal, Multiplexed Imaging of Surface-Enhanced Raman Scattering Nanoparticles Ellis Garai, Steven Sensarn, Cristimãng cầu L. Zavaleta, Nathan O. Loewke, Stephan Rogalla, Michael J. Mandella, Stephen A. Felt, Snhì Friedl&, Jonathan T. C. Liu, Sanjiv S. Gambhir





The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to lớn improve sầu early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the thiết kế and in vivo demonstration of a miniature, non-liên hệ, opto-electro-mechanical Raman device as an accessory lớn clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon & esophagus) và produces quantitative sầu images of the relative concentrations of SERS NPs that are present. Human & swine studies have sầu demonstrated the tốc độ & simplithành phố of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the chất lượng spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential lớn improve sầu diagnosis và to guide therapy by enabling sensitive sầu quantitative sầu molecular detection of small & otherwise hard-to-detect lesions in the context of white-light endoscopy.

Citation: Garai E, Sensarn S, Zavaleta CL, Loewke NO, Rogalla S, Mandella MJ, et al. (2015) A Real-Time Clinical Endoscopic System for Intraluminal, Multiplexed Imaging of Surface-Enhanced Raman Scattering Nanoparticles. ONE 10(4): e0123185.

Academic Editor: Xianfeng Chen, City University of Hong Kong, HONG KONG

Received: November 18, 2014; Accepted: February 16, 2015; Published: April 29, 2015

Data Availability: All relevant data are within the paper và its Supporting Information files.

Funding: This work was funded, in part, by The Canary Foundation (SSG), generous support from the Chambers Family Foundation (CHC), & grant support from the National Institute of Biomedical Imaging and Bioengineering: R21 EB015016 (JTCL), and the National Cancer Institute: ICMIC P50 CA114747 (SSG), CCNE U54 CA119367 (SSG), and NTR U54 CA136465 (CHC). The funders had no role in study thiết kế, data collection and analysis, decision khổng lồ publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.


Endoscopy is currently the gold standard for cancer screening in the gastrointestinal (GI) tract. This white-light imaging modality enables clinicians to inspect the esophagus, stomach, and colon khổng lồ detect lesions such as adenomas and carcinomas. GI endoscopy relies upon an examiner’s ability lớn detect gross anomalies on an otherwise healthy luminal surface. In the colon, many precancerous lesions present as polyps that protrude from the surface by more than 2 mm and are reliably detected by visual inspection. However, the detection of precancerous lesions in the esophagus and stomach is considerably more challenging because most of these lesions bởi vì not elevate inlớn a polypoid shape. There exists an increasing recognition of the importance of detecting non-polypoid precancerous lesions in the colon và the contribution of missed lesions to the failure of colonoscopy-based cancer prevention programs <1–4>.

Endoscopic detection of small polyps và flat lesions in the colon could be improved by adding an imaging modality that is capable of providing functional (i.e., molecular) information in addition to lớn the structural macroscopic information provided by white-light imaging. Incorporating a molecular imaging modality could help clinicians lớn locate, diagnose, & stage small và otherwise hard-to-detect lesions, as well as khổng lồ improve the characterization of these lesions.

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Raman spectroscopy can be used as a label-free modality providing information about basic chemical bonds (e.g., hydrocarbons or nucleic acids) through the analysis of the nominally weak inelastic scattering of photons by such molecular motifs in vitro or in living tissues <5>. Unfortunately, the detection of weak inelastic scattering of photons in tissues (commonly referred to lớn as intrinsic Raman spectroscopy) typically requires long integration times (minutes) and physical liên hệ between the optical probe và the target tissue. However, with surface enhanced Raman scattering (SERS) nanoparticles (NPs) (~120 nm in diameter), the weak inelastic scattering of specific Raman-active molecules can be increased by many orders of magnitude through a plasmonic enhancement effect, thereby allowing SERS NPs lớn serve as a source of significant Raman signal. This enhancement (by as much as 1014) is possible due khổng lồ the multilayer (metallic core surrounded by a layer of Raman-active sầu molecules) structure of SERS particles <6–8>. An outer layer of silica encapsulates the NPs, preventing unwanted chemical interactions with surrounding tissue, such that the NPs emit a Raman spectrum that is quality & independent of the surrounding environment. Moreover, by varying the Raman active sầu layer, a panel of different SERS NPs types can be created, each emitting a characteristic fingerprint-lượt thích spectrum <7,8>. Since each type, or flavor, of NPhường has a quality and complex spectral signature they can be readily multiplexed. The advantage of multiplexing is that it allows for the simultaneous detection of multiple biomarkers if each flavor of NPhường. preferentially binds lớn a different protein target. In light of the large variability in the molecular phenotypes of diseases, multiplexed molecular detection has the potential khổng lồ improve sầu specificity of disease detection. An additional advantage of SERS NPs is that one of the multiplexed NP flavors can be used as a negative control to lớn account for nonspecific sources of contrast such as nonspecific binding, uneven contrast-agent delivery, & varying working distances between the optical device & the sample <9>. These two features, high sensitivity & multiplexing capability, make SERS NPs ikhuyến mãi candidates as tumor-targeted contrast agents.

Our group, as well as others, have demonstrated the tumor targeting capabilities of several types of conjugated Raman nanoparticles in preclinical animal models và with preclinical systems <7,8,10–17>. However, a clinically relevant device for detecting & imaging these tumor targeting SERS NPs has not yet been described, precluding the translation of this potentially significant molecular imaging approach to lớn the clinic. Therefore, we have focused on the development of an entirely new accessory device that capable of intraluminal SERS imaging during GI endoscopy.

We previously described a point-detection device that demonstrated its potential use with SERS NPs as a screening tool for cancers of the esophagus, colon, cervix, or skin in circumstances where small areas of tissue need to lớn be examined. However as a point-detection device, images could only be created on-the-bench by physically moving the sample <9,18>, which is not a viable approach for in-vivo imaging of large, complex surfaces. In order to lớn comprehensively scan a portion of the GI tract, such as within the colon or esophagus, within a clinically relevant period of time, a new scanning imaging system needed lớn be developed.

Here, we describe the kiến thiết, development và testing of a new opto-electro-mechanical device that has the capability to lớn rapidly và systematically scan large tissue surfaces & produce images of structural và multiplexed functional data within the context of the traditional endoscopic-imaging procedure. In addition, we developed software to display the images in a manner that is readily interpretable by the clinician. The data can be displayed as flat 2-D images, or rendered onlớn a cylindrical surface to depict organs lượt thích the colon and esophagus, where the user can rotate the volume renderings & view the data from any direction khổng lồ further improve interpretation.

The size factor of our imaging device was designed lớn allow it to be inserted through the accessory channel of a clinical endoscope và khổng lồ be used in parallel with white-light endoscopy screening. Circumferential scanning could then rapidly assess the binding of functionalized SERS NPs lớn tumor targets, thus providing multiplexed molecular information from the entire tissue surface. Here we demonstrate that signals from a panel of SERS flavors can be simultaneously collected và processed inkhổng lồ quantitative multiplexed images to inkhung & guide the endoscopist.

A chất lượng feature of this device is that it is a non-tương tác system, which has been designed và optimized for efficient use over a wide range of clinically relevant working distances. The human colon has an average radius of 25 mm when insufflated <19>. Assuming the endoscope is held near the center axis of the colon, the average working distance between the device & the colon wall is 25 mm. The non-contact feature also enables rapid scanning of topologically complex tissue surfaces such as the GI tract that consists of folds & bends.

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The approving committee for the human study is the Stanford University IRB; the IRB protocol ID is 15766. Written informed consent for the study was obtained from all patients. The IRB approved written informed consent as the consent procedure.