Dataset Information

Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles.

ABSTRACT: There is a need for intraoperative imaging technologies to guide breast-conserving surgeries and to reduce the high rates of re-excision for patients in which residual tumor is found at the surgical margins during postoperative pathology analyses. Feasibility studies have shown that utilizing topically applied surface-enhanced Raman scattering (SERS) nanoparticles (NPs), in conjunction with the ratiometric imaging of targeted versus untargeted NPs, enables the rapid visualization of multiple cell-surface biomarkers of cancer that are overexpressed at the surfaces of freshly excised breast tissues. In order to reliably and rapidly perform multiplexed Raman-encoded molecular imaging of large numbers of biomarkers (with five or more NP flavors), an enhanced staining method has been developed in which tissue surfaces are cyclically dipped into an NP-staining solution and subjected to high-frequency mechanical vibration. This dipping and mechanical vibration (DMV) method promotes the convection of the SERS NPs at fresh tissue surfaces, which accelerates their binding to their respective biomarker targets. By utilizing a custom-developed device for automated DMV staining, this study demonstrates the ability to simultaneously image four cell-surface biomarkers of cancer at the surfaces of fresh human breast tissues with a mixture of five flavors of SERS NPs (four targeted and one untargeted control) topically applied for 5 min and imaged at a spatial resolution of 0.5 mm and a raster-scanned imaging rate of >5 cm2 min-1 .

SUBMITTER: Wang YW

PROVIDER: S-EPMC5462459 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles.

Wang Yu W YW Doerksen Josh D JD Kang Soyoung S Walsh Daniel D Yang Qian Q Hong Daniel D Liu Jonathan T C JT

Small (Weinheim an der Bergstrasse, Germany) 20160829 40

There is a need for intraoperative imaging technologies to guide breast-conserving surgeries and to reduce the high rates of re-excision for patients in which residual tumor is found at the surgical margins during postoperative pathology analyses. Feasibility studies have shown that utilizing topically applied surface-enhanced Raman scattering (SERS) nanoparticles (NPs), in conjunction with the ratiometric imaging of targeted versus untargeted NPs, enables the rapid visualization of multiple cel ...[more]

PMID: 27571395

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Project description:PurposeRapid, intra-operative identification of tumor tissue in the margins of excised specimens has become an important focus in the pursuit of reducing re-excision rates, especially for breast conserving surgery. Dual-probe difference specimen imaging (DDSI) is an emerging approach that uses the difference in uptake/clearance kinetics between a pair of fluorescently-labeled stains, one targeted to a biomarker-of-interest and the other an untargeted isotype, to reveal receptor-specific images of the specimen. Previous studies using antibodies labeled with either enhanced Raman particles or organic fluorophores have shown promising tumor vs. normal diagnostic performance. Yet, the unique properties of quantum dot-labeled antibody complexes (QDACs), which provide spectrally-distinct fluorescence emission from a common excitation source, make them ideal candidates for this application. Herein, we evaluate the diagnostic performance of QDAC-based DDSI in excised xenografts.ProceduresExcised fresh specimens of normal tissue and human tumor xenografts with elevated expression of HER2 were stained with a HER2-targeted QDAC and an untargeted QDAC isotype. Stained specimens were imaged on a custom hyperspectral imaging system capable of spectrally separating the quantum dot signatures, and images processed using the DDSI approach. The diagnostic performance of this technique under different incubation temperatures and probe concentrations was evaluated using receiver-operator characteristic analysis.ResultsHER2-targeted QDAC-DDSI was able to distinguish HER2(+) tumors from normal tissue with reasonably high diagnostic performance; however, this performance was sensitive to temperature during the staining procedure. Area under the curve values were 0.61 when staining at room temperature but increased to over 0.81 when staining at 37 °C. Diagnostic performance was not affected by increasing stain concentration.ConclusionsThis study is the first to report dual-probe difference imaging of specimens using QDACs and hyperspectral imaging. Our results show promising diagnostic performance under certain conditions, and compel further optimization and evaluation of this intra-operative margin assessment technique.

Dataset Information

Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles.

Publications

Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles.

Similar Datasets

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