Dataset Information

Liver segment imaging using monocyte sequestration: a potential tool for fluorescence-guided liver surgery.

ABSTRACT: Background: The accurate determination of liver segment anatomy is essential to perform liver resection without complications and to ensure long-term outcomes after this operation. There are several perioperative methods for segment identification and surgical navigation, such as intraoperative ultrasound, indigo carmine and near-infrared imaging with indocyanine green. The present study experimentally analyzed the usefulness of monocyte sequestration for liver segment labeling and imaging. Methods: Human monocytes were isolated from peripheral blood and directly or indirectly labeled with calcein or IRDye 800CW. Potential toxicity, labeling stability, and adhesion to ICAM-1 were analyzed in vitro. Monocyte sequestration in the liver microvasculature and liver segment labeling and boundary demarcation were studied using isolated mouse and pig liver perfusion and via intraportal injection in mouse liver tumor models. Results: The highest monocyte labeling efficiency was achieved using direct labeling with IRDye 800CW. Labeling was stable and did not influence cell viability. The labeled monocytes were highly sequestrated in the liver microvasculature, both after ex vivo perfusion and after injection in vivo , resulting in excellent labeling of selected liver segments and strong segment boundary demarcation. In contrast to results to a normal liver, monocyte sequestration was very low in tumor-associated blood vessels. Conclusions: The present experimental study shows that sequestration of labeled monocytes after superselective application demarcates the selected liver segment. These results illustrate potential of this technique for surgical navigation during liver surgery.

SUBMITTER: Qian B

PROVIDER: S-EPMC6299692 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Liver segment imaging using monocyte sequestration: a potential tool for fluorescence-guided liver surgery.

Qian Baifeng B Kyuno Daisuke D Schäfer Michael M Gross Wolfgang W Mehrabi Arianeb A Ryschich Eduard E

Theranostics 20181129 22

<b>Background</b>: The accurate determination of liver segment anatomy is essential to perform liver resection without complications and to ensure long-term outcomes after this operation. There are several perioperative methods for segment identification and surgical navigation, such as intraoperative ultrasound, indigo carmine and near-infrared imaging with indocyanine green. The present study experimentally analyzed the usefulness of monocyte sequestration for liver segment labeling and imagin ...[more]

PMID: 30613285

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Project description:BackgroundSurgery is the cornerstone of colorectal cancer (CRC) treatment, yet complete removal of the tumour remains a challenge. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescent molecular imaging is a novel technique, which has broad application prospects in tumour surgical navigation. We aimed to evaluate the ability of CEACAM5-targeted probe for CRC recognition and the value of NIR-II imaging-guided CRC resection.MethodsWe constructed the probe 2D5-IRDye800CW by conjugated anti-CEACAM5 nanobody (2D5) with near-infrared fluorescent dye IRDye800CW. The performance and benefits of 2D5-IRDye800CW at NIR-II were confirmed by imaging experiments in mouse vascular and capillary phantom. Then mouse colorectal cancer subcutaneous tumour model (n = 15), orthotopic model (n = 15), and peritoneal metastasis model (n = 10) were constructed to investigate biodistribution of probe and imaging differences between NIR-I and NIR-II in vivo, and then tumour resection was guided by NIR-II fluorescence. Fresh human colorectal cancer specimens were incubated with 2D5-IRDye800CW to verify its specific targeting ability.Findings2D5-IRDye800CW had an NIR-II fluorescence signal extending to 1600 nm and bound specifically to CEACAM5 with an affinity of 2.29 nM. In vivo imaging, 2D5-IRDye800CW accumulated rapidly in tumour (15 min) and could specifically identify orthotopic colorectal cancer and peritoneal metastases. All tumours were resected under NIR-II fluorescence guidance, even smaller than 2 mm tumours were detected, and NIR-II had a higher tumour-to-background ratio than NIR-I (2.55 ± 0.38, 1.94 ± 0.20, respectively). 2D5-IRDye800CW could precisely identify CEACAM5-positive human colorectal cancer tissue.Interpretation2D5-IRDye800CW combined with NIR-II fluorescence has translational potential as an aid to improve R0 surgery of colorectal cancer.FundingsThis study was supported by Beijing Natural Science Foundation (JQ19027), the National Key Research and Development Program of China (2017YFA0205200), National Natural Science Foundation of China (NSFC) (61971442, 62027901, 81930053, 92059207, 81227901, 82102236), Beijing Natural Science Foundation (L222054), CAS Youth Interdisciplinary Team (JCTD-2021-08), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16021200), the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703), the Fundamental Research Funds for the Central Universities (JKF-YG-22-B005) and Capital Clinical Characteristic Application Research (Z181100001718178). The authors would like to acknowledge the instrumental and technical support of the multi-modal biomedical imaging experimental platform, Institute of Automation, Chinese Academy of Sciences.

Project description:SignificanceExpanded use of fluorescence-guided surgery with devices approved for use with indocyanine green (ICG) has led to a range of commercial systems available. There is a compelling need to be able to independently characterize system performance and allow for cross-system comparisons.AimThe goal of this work is to expand on previous proposed fluorescence imaging standard designs to develop a long-term stable phantom that spectrally matches ICG characteristics and utilizes 3D printing technology for incorporating tissue-equivalent materials.ApproachA batch of test targets was created to assess ICG concentration sensitivity in the 0.3- to 1000-nM range, tissue-equivalent depth sensitivity down to 6 mm, and spatial resolution with a USAF test chart. Comparisons were completed with a range of systems that have significantly different imaging capabilities and applications, including the Li-Cor® Odyssey, Li-Cor® Pearl, PerkinElmer® Solaris, and Stryker® Spy Elite.ResultsImaging of the ICG-matching phantoms with all four commercially available systems showed the ability to benchmark system performance and allow for cross-system comparisons. The fluorescence tests were able to assess differences in the detectable concentrations of ICG with sensitivity differences >10× for preclinical and clinical systems. Furthermore, the tests successfully assessed system differences in the depth-signal decay rate, as well as resolution performance and image artifacts. The manufacturing variations, photostability, and mechanical design of the tests showed promise in providing long-term stable standards for fluorescence imaging.ConclusionsThe presented ICG-matching phantom provides a major step toward standardizing performance characterization and cross-system comparisons for devices approved for use with ICG. The developed hybrid manufacturing platform can incorporate long-term stable fluorescing agents with 3D printed tissue-equivalent material. Further, long-term testing of the phantom and refinements to the manufacturing process are necessary for future implementation as a widely adopted fluorescence imaging standard.

Dataset Information

Liver segment imaging using monocyte sequestration: a potential tool for fluorescence-guided liver surgery.

Publications

Liver segment imaging using monocyte sequestration: a potential tool for fluorescence-guided liver surgery.

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