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      A Brain Tumor Molecular Imaging Strategy Using A New Triple-Modality MRI-Photoacoustic-Raman Nanoparticle

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          Abstract

          The vexing difficulty in delineating brain tumor margins represents a major obstacle toward better outcome of brain tumor patients. Current imaging methods are often limited by inadequate sensitivity, specificity, and spatial resolution. Here we show that a unique triple-modality Magnetic resonance imaging - Photoacoustic imaging – surface enhanced Raman scattering (SERS) nanoparticle (MPR) can accurately help delineate the margins of brain tumors in living mice both pre- and intra-operatively. The MPRs were detected by all three modalities with at least picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to specific MPR accumulation and retention by the tumors, allowing for non-invasive tumor delineation by all three modalities through the intact skull. Raman imaging allowed guidance of intra-operative tumor resection, and histological correlation validated that Raman imaging is accurately delineating brain tumor margins. This novel triple-modality nanoparticle approach holds promise to enable more accurate brain tumor imaging and resection.

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          Most cited references41

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          AMIDE: a free software tool for multimodality medical image analysis.

          Amide's a Medical Image Data Examiner (AMIDE) has been developed as a user-friendly, open-source software tool for displaying and analyzing multimodality volumetric medical images. Central to the package's abilities to simultaneously display multiple data sets (e.g., PET, CT, MRI) and regions of interest is the on-demand data reslicing implemented within the program. Data sets can be freely shifted, rotated, viewed, and analyzed with the program automatically handling interpolation as needed from the original data. Validation has been performed by comparing the output of AMIDE with that of several existing software packages. AMIDE runs on UNIX, Macintosh OS X, and Microsoft Windows platforms, and it is freely available with source code under the terms of the GNU General Public License.
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            Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy.

            Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 different types of surface enhanced Raman scattering (SERS) nanoparticles in a living mouse after s.c. injection. Based on these spectral results, we simultaneously injected the five most intense and spectrally unique SERS nanoparticles i.v. to image their natural accumulation in the liver. All five types of SERS nanoparticles were successfully identified and spectrally separated using our optimized noninvasive Raman imaging system. In addition, we were able to linearly correlate Raman signal with SERS concentration after injecting four spectrally unique SERS nanoparticles either s.c. (R(2) = 0.998) or i.v. (R(2) = 0.992). These results show great potential for multiplexed imaging in living subjects in cases in which several targeted SERS probes could offer better detection of multiple biomarkers associated with a specific disease.
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              Noninvasive molecular imaging of small living subjects using Raman spectroscopy.

              Molecular imaging of living subjects continues to rapidly evolve with bioluminescence and fluorescence strategies, in particular being frequently used for small-animal models. This article presents noninvasive deep-tissue molecular images in a living subject with the use of Raman spectroscopy. We describe a strategy for small-animal optical imaging based on Raman spectroscopy and Raman nanoparticles. Surface-enhanced Raman scattering nanoparticles and single-wall carbon nanotubes were used to demonstrate whole-body Raman imaging, nanoparticle pharmacokinetics, multiplexing, and in vivo tumor targeting, using an imaging system adapted for small-animal Raman imaging. The imaging modality reported here holds significant potential as a strategy for biomedical imaging of living subjects.
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                Author and article information

                Journal
                9502015
                8791
                Nat Med
                Nat. Med.
                Nature medicine
                1078-8956
                1546-170X
                18 October 2011
                15 April 2012
                01 November 2012
                : 18
                : 5
                : 829-834
                Affiliations
                [1 ]Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, California, USA
                [2 ]Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
                [3 ]Department of Radiology, Weill-Cornell Medical College, New York, New York, USA
                [4 ]Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
                [5 ]Department of Electrical Engineering, Stanford University, Stanford, California, USA
                [6 ]Department of Materials Science & Engineering, Stanford University, Stanford, California, USA
                [7 ]Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
                [8 ]Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
                [9 ]Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
                [10 ]Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
                [11 ]Department of Neurosurgery, Weill-Cornell Medical College, New York, New York, USA
                [12 ]Department of Pharmacology, Weill-Cornell Medical College, New York, New York, USA
                [13 ]Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
                [14 ]Department of Bioengineering and Bio-X Program, Stanford University, Stanford, California, USA
                Author notes
                Corresponding Author: Sanjiv S Gambhir, MD PhD, The James H Clark Center, 318 Campus Drive, Stanford, CA 94305-5427, sgambhir@ 123456stanford.edu , Fax: 650-724-4948
                [15]

                These authors contributed equally to this work.

                Article
                NIHMS331893
                10.1038/nm.2721
                3422133
                22504484
                fc2ab333-42b6-40dc-b4c9-9ef2c94316c5

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Cancer Institute : NCI
                Award ID: U54 CA151459-02 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: U54 CA151459-01 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: U54 CA119367-01 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: R25 CA118681-05 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: R25 CA118681-04 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: R25 CA118681-03 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: R25 CA118681-01A1 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: P50 CA114747-06 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: P50 CA114747-05 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: P50 CA114747-04 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: P50 CA114747-03 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: P50 CA114747-02 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: P50 CA114747-01 || CA
                Categories
                Article

                Medicine
                contrast agent,sers,photoacoustic,nanoparticle,molecular imaging,silica,surgery,mri,tumor margin,gold,multimodality,raman,in vivo,brain tumor,cancer

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