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

48 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

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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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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.",

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AU - Qiao, Jingjuan

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AU - Ibhagui, Oluwatosin Y.

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AU - Farris, Alton Brad

AU - Liu, Zhi Ren

AU - Yang, Jenny J.

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

Abstract

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