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

Nat Commun. 2019 Oct 29;10(1):4777. doi: 10.1038/s41467-019-11984-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Contrast Media / chemistry*
  • Early Diagnosis
  • Gadolinium / chemistry*
  • Humans
  • Hypertension, Portal / diagnostic imaging*
  • Liver / diagnostic imaging*
  • Magnetic Resonance Imaging / methods*


  • Contrast Media
  • Gadolinium