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Electromagnetic Tracking and Optical Molecular Imaging Guidance for Liver Biopsy and Point-of-Care Tissue Assessment in Phantom and Woodchuck Hepatocellular Carcinoma

  • Laboratory Investigation
  • Non-Vascular Interventions
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate an integrated liver biopsy platform that combined CT image fusion, electromagnetic (EM) tracking, and optical molecular imaging (OMI) of indocyanine green (ICG) to target hepatocellular carcinoma (HCC) lesions and a point-of-care (POC) OMI to assess biopsy cores, all based on tumor retention of ICG compared to normal liver, in phantom and animal model.

Material

A custom CT image fusion and EM-tracked guidance platform was modified to integrate the measurement of ICG fluorescence intensity signals in targeted liver tissue with an OMI stylet or a POC OMI system. Accuracy was evaluated in phantom and a woodchuck with HCC, 1 day after administration of ICG. Fresh biopsy cores and paraffin-embedded formalin-fixed liver tissue blocks were evaluated with the OMI stylet or POC system to identify ICG fluorescence signal and ICG peak intensity.

Results

The mean distance between the initial guided needle delivery location and the peak ICG signal was 5.0 ± 4.7 mm in the phantom. There was complete agreement between the reviewers of the POC-acquired ICG images, cytology, and histopathology in differentiating HCC-positive from HCC-negative biopsy cores. The peak ICG fluorescence intensity signal in the ex vivo liver blocks was 39 ± 12 and 281 ± 150 for HCC negative and HCC positive, respectively.

Conclusion

Biopsy guidance with fused CT imaging, EM tracking, and ICG tracking with an OMI stylet to detect HCC is feasible. Immediate assessment of ICG uptake in biopsy cores with the POC OMI system is feasible and correlates with the presence of HCC in the tissue.

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Fig. 1

source is entering the light-blocking box by cable. D Integrated interface for co-display of the CT-fused EM-tracked cannula triplanar position and ICG signal read-out of the OMI stylet. E ICG fluorescence intensity while withdrawing the OMI stylet through the ICG injection site with measurements at approximately 5-mm intervals. Gaussian distribution is accurate and was added to demonstrate rough orientation only. Note that the OMI stylet data sampling is directional. Thus, the signal distribution would not be circumferential nor Gaussian with mirrored shoulders, even if the ICG distribution was spherical and uniform

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Funding

This work was supported by the NIH Center for Interventional Oncology and the Intramural Research Program of the National Institutes of Health, via intramural NIH Grants Z1A CL040015, 1ZID BC011242; also supported by NIH UO1 (NCI Collaborative Grant) # 1U01CA202934-01A1. Dr. Mauda-Havakuk is supported by the Intramural Program of the National Institute of Biomedical Imaging and Bioengineering. NIH has a Materials Transfer Agreement with Northeastern Wildlife.

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Authors and Affiliations

  1. Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA

    Quirina M. B. de Ruiter, Sheng Xu, Ming Li, William F. Pritchard, Andrew S. Mikhail, Michal Mauda-Havakuk, Juan A. Esparza-Trujillo, Ivane Bakhutashvili, John W. Karanian & Bradford J. Wood

  2. Division of Veterinary Resources, National Institutes of Health, Bethesda, MD, 20892, USA

    Matthew F. Starost

  3. Laboratory of Pathology, Center for Cancer Research, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Armando Filie

  4. Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, 02129, USA

    Pedram Heidari

  5. Center for Cancer research, National Institutes of Health, Bethesda, MD, 20892, USA

    Umar Mahmood

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  1. Quirina M. B. de Ruiter
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  2. Sheng Xu
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  3. Ming Li
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Correspondence to Bradford J. Wood.

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Conflict of interest

NIH may have intellectual property in the field. BW is Principal Investigator on a CRADA (Cooperative Research & Development Agreement) between NIH and Philips and Philips Research. Licensed Patents / Royalties: Philips pays royalties to NIH for a licensing agreement with NIH, who then pays royalties to BW for licensed patents from Philips. UM has co-invented quantitative optical imaging methods and activatable optical imaging agents, for which MGH was issued patents. He is a cofounder, shareholder, consultant, and grant recipient of Cytosite Biopharma, focused on immuno-oncology PET imaging. All other authors declare that they have no conflict of interest: QR, SX, ML, WP, MS, AF, AM, MM, JE, IB, PH, and JK.

Ethical Approval

This article does not contain any studies with human participants. All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. FDA (± CE Mark): Off-label use of drugs or devices may be discussed. The content of this manuscript does not necessarily reflect the views, policies, or opinions of the U.S. Department of Health and Human Services. The mention of commercial products, their source, or their use in connection with material reported herein is not to be construed as an actual or implied endorsement of such products by the United States Government. Opinions expressed are those of the authors, not necessarily the NIH.

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de Ruiter, Q.M.B., Xu, S., Li, M. et al. Electromagnetic Tracking and Optical Molecular Imaging Guidance for Liver Biopsy and Point-of-Care Tissue Assessment in Phantom and Woodchuck Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 44, 1439–1447 (2021). https://doi.org/10.1007/s00270-021-02853-x

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  • DOI: https://doi.org/10.1007/s00270-021-02853-x

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