Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus

Wang, Yu “Winston”; Khan, Altaz; Leigh, Steven Y.; Wang, Danni; Chen, Ye; Meza, Daphne; Liu, Jonathan

doi:10.1364/boe.5.002883

Cited by 39 publications

(55 citation statements)

References 42 publications

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“…Spectral signals from the NPs were measured periodically between each of the 10 serial rinses (spray with 0.1 mL of PBS solution followed by gentle removal). Concentrations of the two NPs were then extracted from the raw signals by spectral decomposition (Wang et al , 2014a). …”

Section: Methodsmentioning

confidence: 99%

“…Recent work has established the potential for paired-agent methods to overcome the limitations of direct topical staining of thick tissues (Davis et al , 2013; Liu et al , 2009; Sinha et al , 2015; Wang et al , 2014a; Wang et al , 2016; Wang et al , 2015). Such methods utilize the signal from a control (untargeted) imaging agent that is co-administered with one or more targeted agent(s) to account for background staining and variable optical properties (Tichauer et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

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Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues

Wang

Xiang

et al. 2017

Phys. Med. Biol.

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Conventional molecular assessment of tissue through histology, if adapted to fresh thicker samples, has the potential to enhance cancer detection in surgical margins and monitoring of 3D cell culture molecular environments. However, in thicker samples, substantial background staining is common despite repeated rinsing, which can significantly reduce image contrast. Recently, “paired-agent” methods—which employ co-administration of a control (untargeted) imaging agent—have been applied to thick-sample staining applications to account for background staining. To date, these methods have included (1) a simple ratiometric method that is relatively insensitive to noise in the data but has accuracy that is dependent on the staining protocol and the characteristics of the sample; and (2) a complex paired-agent kinetic modeling method that is more accurate but is more noise-sensitive and requires a precise serial rinsing protocol. Here, a new simplified mathematical model—the rinsing paired-agent model (RPAM)—is derived and tested that offers a good balance between the previous models, is adaptable to arbitrary rinsing-imaging protocols, and does not require calibration of the imaging system. RPAM is evaluated against previous models and is validated by comparison to estimated concentrations of targeted biomarkers on the surface of 3D cell culture and tumor xenograft models. This work supports the use of RPAM as a preferable model to quantitatively analyze targeted biomarker concentrations in topically stained thick tissues, as it was found to match the accuracy of the complex paired-agent kinetic model while retaining the low noise-sensitivity characteristics of the ratiometric method.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues

Wang

Xiang

et al. 2017

Phys. Med. Biol.

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“…Finally, recent studies have utilized multiplexed surface enhanced Raman scattering (SERS) nanoparticles that do not photobleach. More importantly, these agents can all be excited at a single illumination wavelength, and all emit within a similar wavelength band (Wang et al , 2014a; Wang et al , 2014b; Zavaleta et al , 2013). The two assumptions mentioned above are therefore both true for this new class of optical imaging agents.…”

Section: Paired-imaging-agent Approachesmentioning

confidence: 99%

“…Furthermore, these glass-encapsulated gold-core nanoparticles (~120 nm in diameter) are largely identical in terms of size and surface chemistry, and therefore should exhibit similar delivery and retention characteristics in tissue. Recent studies with topically applied SERS NPs conjugated to targeted monoclonal antibodies and isotype-control antibodies (untargeted) have shown that the nonspecific behavior of these targeted and untargeted NPs is virtually identical (Wang et al , 2014a; Wang et al , 2014b). The unique spectral “fingerprint” of SERS NPs offer exquisite signal-to-background properties (Kircher et al , 2012) and the potential to simultaneously image a large multiplexed panel of biomarker targets with laser illumination at a single wavelength (Zavaleta et al , 2008; Zavaleta et al , 2013; Zavaleta et al , 2009), which will be advantageous for identifying and stratifying tumors with greater accuracy in light of the known variability in molecular phenotypes between tumors and even within a single tumor over space and time (Gerlinger et al , 2012).…”

Section: Paired-imaging-agent Approachesmentioning

confidence: 99%

Quantitativein vivocell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging

et al. 2015

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The development of methods to accurately quantify cell-surface receptors in living tissues would have a seminal impact in oncology. For example, accurate measures of receptor density in vivo could enhance early detection or surgical resection of tumors via protein-based contrast, allowing removal of cancer with high phenotype specificity. Alternatively, accurate receptor expression estimation could be used as a biomarker to guide patient-specific clinical oncology targeting of the same molecular pathway. Unfortunately, conventional molecular contrast-based imaging approaches are not well adapted to accurately estimating the nanomolar-level cell-surface receptor concentrations in tumors, as most images are dominated by nonspecific sources of contrast such as high vascular permeability and lymphatic inhibition. This article reviews approaches for overcoming these limitations based upon tracer kinetic modeling and the use of emerging protocols to estimate binding potential and the related receptor concentration. Methods such as using single time point imaging or a reference-tissue approach tend to have low accuracy in tumors, whereas paired-agent methods or advanced kinetic analyses are more promising to eliminate the dominance of interstitial space in the signals. Nuclear medicine and optical molecular imaging are the primary modalities used, as they have the nanomolar level sensitivity needed to quantify cell-surface receptor concentrations present in tissue, although each likely has a different clinical niche.

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“…dimension of this instrument (5.3 mm) precludes its use in the distal lung (alveoli) and other anatomical sites where miniaturization is required for access and safety. An endoscopic imaging system (lateral dimension 2.5 mm) using 37 optical fibers was recently demonstrated to visualize topically applied SERS nanoparticles in the rat esophagus [16]. Although using more collection paths enables higher signal collection efficiency, there is clearly a trade-off between increased signal collection and engineering a sufficiently compact distal probe that can be accommodated within the alveolar microenvironment.…”

Section: Sensing Mechanism Instrument Design and Fabricationmentioning

confidence: 99%

Endoscopic sensing of alveolar pH

Choudhury¹,

Tanner²,

McAughtrie³

et al. 2016

Biomed. Opt. Express

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Previously unobtainable measurements of alveolar pH were obtained using an endoscope-deployable optrode. The pH sensing was achieved using functionalized gold nanoshell sensors and surface enhanced Raman spectroscopy (SERS). The optrode consisted of an asymmetric dual-core optical fiber designed for spatially separating the optical pump delivery and signal collection, in order to circumvent the unwanted Raman signal generated within the fiber. Using this approach, we demonstrate a ~100-fold increase in SERS signal-tofiber background ratio, and demonstrate multiple site pH sensing with a measurement accuracy of ± 0.07 pH units in the respiratory acini of an ex vivo ovine lung model. We also demonstrate that alveolar pH changes in response to ventilation.

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Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus

Cited by 39 publications

References 42 publications

Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues

Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues

Quantitativein vivocell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging

Endoscopic sensing of alveolar pH

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