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Early detection and staging of chronic liver diseases with a protein MRI contrast agent

Author

Listed:
  • Mani Salarian

    (Georgia State University)

  • Ravi Chakra Turaga

    (Georgia State University)

  • Shenghui Xue

    (Georgia State University)

  • Maysam Nezafati

    (Emory University and Georgia Institute of Technology)

  • Khan Hekmatyar

    (University of Georgia)

  • Jingjuan Qiao

    (Georgia State University)

  • Yinwei Zhang

    (Georgia State University)

  • Shanshan Tan

    (Georgia State University)

  • Oluwatosin Y. Ibhagui

    (Georgia State University)

  • Yan Hai

    (Georgia State University)

  • Jibiao Li

    (Georgia State University)

  • Rao Mukkavilli

    (Georgia State University)

  • Malvika Sharma

    (Georgia State University)

  • Pardeep Mittal

    (Augusta University)

  • Xiaoyi Min

    (Georgia State University)

  • Shella Keilholz

    (Emory University and Georgia Institute of Technology)

  • Liqing Yu

    (Georgia State University)

  • Gengshen Qin

    (Georgia State University)

  • Alton Brad Farris

    (Emory University School of Medicine)

  • Zhi-Ren Liu

    (Georgia State University
    Georgia State University)

  • Jenny J. Yang

    (Georgia State University
    Georgia State University)

Abstract

Early diagnosis and noninvasive detection of liver fibrosis and its heterogeneity remain as major unmet medical needs for stopping further disease progression toward severe clinical consequences. Here we report a collagen type I targeting protein-based contrast agent (ProCA32.collagen1) with strong collagen I affinity. ProCA32.collagen1 possesses high relaxivities per particle (r1 and r2) at both 1.4 and 7.0 T, which enables the robust detection of early-stage (Ishak stage 3 of 6) liver fibrosis and nonalcoholic steatohepatitis (Ishak stage 1 of 6 or 1 A Mild) in animal models via dual contrast modes. ProCA32.collagen1 also demonstrates vasculature changes associated with intrahepatic angiogenesis and portal hypertension during late-stage fibrosis, and heterogeneity via serial molecular imaging. ProCA32.collagen1 mitigates metal toxicity due to lower dosage and strong resistance to transmetallation and unprecedented metal selectivity for Gd3+ over physiological metal ions with strong translational potential in facilitating effective treatment to halt further chronic liver disease progression.

Suggested Citation

  • Mani Salarian & Ravi Chakra Turaga & Shenghui Xue & Maysam Nezafati & Khan Hekmatyar & Jingjuan Qiao & Yinwei Zhang & Shanshan Tan & Oluwatosin Y. Ibhagui & Yan Hai & Jibiao Li & Rao Mukkavilli & Malv, 2019. "Early detection and staging of chronic liver diseases with a protein MRI contrast agent," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11984-2
    DOI: 10.1038/s41467-019-11984-2
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    Cited by:

    1. Jiahao Gao & Ya Wang & Xianfu Meng & Xiaoshuang Wang & Fang Han & Hao Xing & Guanglei Lv & Li Zhang & Shiman Wu & Xingwu Jiang & Zhenwei Yao & Xiangming Fang & Jiawen Zhang & Wenbo Bu, 2024. "A FAPĪ±-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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