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

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; Malvika Sharma; Pardeep Mittal; Xiaoyi Min; Shella Keilholz; Liqing Yu; Gengshen Qin; Alton Brad Farris; Zhi Ren Liu; Jenny J. Yang

doi:10.1038/s41467-019-11984-2

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

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, Malvika Sharma, Pardeep Mittal, Xiaoyi Min, Shella Keilholz, Liqing Yu, Gengshen Qin, Alton Brad Farris, Zhi Ren LiuJenny J. Yang

Diagnostic

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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.

Original language	English (US)
Article number	4777
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11984-2
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Salarian, M., Turaga, R. C., Xue, S., Nezafati, M., Hekmatyar, K., Qiao, J., Zhang, Y., Tan, S., Ibhagui, O. Y., Hai, Y., Li, J., Mukkavilli, R., Sharma, M., Mittal, P., Min, X., Keilholz, S., Yu, L., Qin, G., Farris, A. B., ... Yang, J. J. (2019). Early detection and staging of chronic liver diseases with a protein MRI contrast agent. Nature communications, 10(1), Article 4777. https://doi.org/10.1038/s41467-019-11984-2

Salarian, M, Turaga, RC, Xue, S, Nezafati, M, Hekmatyar, K, Qiao, J, Zhang, Y, Tan, S, Ibhagui, OY, Hai, Y, Li, J, Mukkavilli, R, Sharma, M, Mittal, P, Min, X, Keilholz, S, Yu, L, Qin, G, Farris, AB, Liu, ZR & Yang, JJ 2019, 'Early detection and staging of chronic liver diseases with a protein MRI contrast agent', Nature communications, vol. 10, no. 1, 4777. https://doi.org/10.1038/s41467-019-11984-2

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title = "Early detection and staging of chronic liver diseases with a protein MRI contrast agent",

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.",

author = "Mani Salarian and Turaga, {Ravi Chakra} and Shenghui Xue and Maysam Nezafati and Khan Hekmatyar and Jingjuan Qiao and Yinwei Zhang and Shanshan Tan and Ibhagui, {Oluwatosin Y.} and Yan Hai and Jibiao Li and Rao Mukkavilli and Malvika Sharma and Pardeep Mittal and Xiaoyi Min and Shella Keilholz and Liqing Yu and Gengshen Qin and Farris, {Alton Brad} and Liu, {Zhi Ren} and Yang, {Jenny J.}",

note = "Funding Information: We thank Dr. Peter Caravan for his discussion and advice. Dr. Micheal Kirberger for carefully editing the paper. Drs. Qun Zhao, and Yubin Zhou for their helpful discussion. This work was supported in part by a Molecular Basis of Disease fellowship (to M. Salarian) and National Institute of Health (NIH) Research Grants EB007268, CA183376 and AA025863 (to J.J.Y.), CA118113 (to Z.-R. L.) and S10RR023706 (instrumentation grant for the University of Georgia Bio-Imaging Research Center). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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doi = "10.1038/s41467-019-11984-2",

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AU - Salarian, Mani

AU - Turaga, Ravi Chakra

AU - Xue, Shenghui

AU - Nezafati, Maysam

AU - Hekmatyar, Khan

AU - Qiao, Jingjuan

AU - Zhang, Yinwei

AU - Tan, Shanshan

AU - Ibhagui, Oluwatosin Y.

AU - Hai, Yan

AU - Li, Jibiao

AU - Mukkavilli, Rao

AU - Sharma, Malvika

AU - Mittal, Pardeep

AU - Min, Xiaoyi

AU - Keilholz, Shella

AU - Yu, Liqing

AU - Qin, Gengshen

AU - Farris, Alton Brad

AU - Liu, Zhi Ren

AU - Yang, Jenny J.

N1 - Funding Information: We thank Dr. Peter Caravan for his discussion and advice. Dr. Micheal Kirberger for carefully editing the paper. Drs. Qun Zhao, and Yubin Zhou for their helpful discussion. This work was supported in part by a Molecular Basis of Disease fellowship (to M. Salarian) and National Institute of Health (NIH) Research Grants EB007268, CA183376 and AA025863 (to J.J.Y.), CA118113 (to Z.-R. L.) and S10RR023706 (instrumentation grant for the University of Georgia Bio-Imaging Research Center). Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 10

JO - Nature communications

JF - Nature communications

IS - 1

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ER -

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

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