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WIREs Nanomed Nanobiotechnol
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Image‐guided surgery using multimodality strategy and molecular probes

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The ultimate goal of cancer surgery is to maximize the excision of tumorous tissue with minimal damage to the collateral normal tissues, reduce the postoperative recurrence, and improve the survival rate of patients. In order to locate tumor lesions, highlight tumor margins, visualize residual disease in the surgical wound, and map potential lymph node metastasis, various imaging techniques and molecular probes have been investigated to assist surgeons to perform more complete tumor resection. Combining imaging techniques with molecular probes is particularly promising as a new approach for image‐guided surgery. Considering inherent limitations of different imaging techniques and insufficient sensitivity of nonspecific molecular probes, image‐guided surgery with multimodality strategy and specific molecular probes appears to be an optimal choice. In this article, we briefly describe typical imaging techniques and molecular probes followed by a focused review on the current progress of multimodal image‐guided surgery with specific molecular navigation. We also discuss optimal strategy that covers all stages of image‐guided surgery including preoperative scanning of tumors, intraoperative inspection of surgical bed and postoperative care of patients. WIREs Nanomed Nanobiotechnol 2015, 8:46–60. doi: 10.1002/wnan.1352 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
(a) The first clinical trial of fluorescence image‐guided surgery in ovarian cancer. Color image of abdominal cavity (left) and the corresponding fluorescence image (right). (Reprinted with permission from Ref . Copyright 2011 Nature Publishing Group) (b) In vivo photoacoustic images of breast tumor lesions with different thickness (5, 12, 16, 25, and 31 mm) of chicken breast added between the detector and tumor at 24 h post the injection of near‐infrared (NIR) labeled iron oxide nanoparticles (IONPs) (Reprinted with permission from Ref . Copyright 2014 John Wiley & Sons)
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Demonstration of multimodality image‐guided surgery using photoacoustic imaging (PAI), fluorescence molecular tomography (FMT), and fluorescence imaging (FI). (a) B‐scan (top row) and maximum amplitude projection (MAP) (bottom row) PAI images of a tumor in a representative mouse that received near‐infrared (NIR)‐labeled iron oxide nanoparticles (IONPs). The back flank of the mouse was overlaid with 0, 10, and 19 mm thickness of chicken breast to mimic the normal tissue in humans. (b) Dual modality imaging of the same tumor located at different depth (3, 6, and 10 mm). From the MAP and cross sections of PAI and FMT, both the lateral and axial resolutions of PAI were higher than that of FMT (Reprinted with permission from Ref . Copyright 2014 Elsevier). (c, d) Fluorescent detection of residual disease in the surgical bed after incomplete resection. The residual diseases that could not be visualized by surgeons were clearly detected by the FI and no residual disease was detected after the second surgery. The histological analysis showed the residual nodule interface. (Reprinted with permission from Ref . Copyright 2014 Springer)
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Triple modality detection and Raman guided resection of brain tumors with injection of multifunctional nanoprobes. (a) Two‐dimensional (2D) magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and Raman imaging of brain tumors before and after the injection of nanoprobes. (b) Three‐dimensional (3D) MRI, PAI, and Raman imaging of brain tumors before and after the injection of nanoprobes. (c) Intraopearive Raman imaging was performed after each resection of the brain tumor. After the gross removal of the major tumor, several small residual diseases were detected by Raman imaging. The histological analysis of the residual diseases was included in the dashed rectangle. (Reprinted with permission from Ref . Copyright 2012 Nature Publishing Group)
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Dual modal ultrasonography (US) and photoacoustic (PA) images of the sentinel lymph node (SLN) with S5‐1 probe (80 elements, 1–5 MHz) (a), L8‐4 (128 elements, 4–8 MHz) (b), and L15‐7io (128 elements, 7–15 MHz) (c) before (left images of a–c) and 20 min after (middle images of a–c) the injection of Indocyanine green (ICG). The right images of (a–c) are the co‐registered photoacoustic and US images. (Reprinted with permission from Ref . Copyright 2010)
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Small animal positron emission tomography (PET) (a) and photoacoustic imaging (PAI) (b) images of U87MG human glioblastoma tumors at 1, 4, 24, and 48 h post injection of RGD‐functionalized and RGD‐blocking tripods. The tumors of the mice with injection of RGD‐functionalized tripods have stronger signals in both PET and photoacoustic (PA) images compared with the animal group with injection of RGD‐blocking tripods. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society)
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Imaging of SKOV3 tumor‐bearing mice by hybrid magnetic resonance imaging (MRI) and near‐infrared (NIR) fluorescence imaging (FI). NIR FI of the primary tumor after the administration of specific and nonspecific NIR‐labeled iron oxide nanoparticles (IONPs) (left column) and corresponding MRI of the same mice before and after the injection of the nanoprobes. (Reprinted with permission from Ref . Copyright 2014 John Wiley & Sons)
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Intraoperative hybrid nuclear and fluorescence identification of sentinel node using indocyanine green (ICG)‐99mTc‐nanocolloid. (a) Preoperative mapping of metastases in sentinel lymph node (SLN). There are four SLNs around the injection site (IS). (b) Integrated three‐dimensional (3D) rendered single‐photon‐emission computed tomography (SPECT) and computed tomography (CT) showed that the most caudal SLN on the right side was located in an inferior Daseler zone. (c, d) Intraoperative detection of metastases in SLN using color camera (c) and fluorescence imaging (FI) (d). (e, f) Post inspection of the excision area using portable γ camera after removing three SLN (e) and the remaining SLN (f). (Reprinted with permission from Ref . Copyright 2014)
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