Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent

Oluwatosin Y. Ibhagui, Dongjun Li, Hongwei Han, Guangda Peng, Maureen L. Meister, Zongxiang Gui, Jingjuan Qiao, Mani Salarian, Bin Dong, Yi Yuan, Yiting Xu, Hua Yang, Shanshan Tan, Ganesh Satyanarayana, Shenghui Xue, Ravi Chakra Turaga, Malvika Sharma, Yan Hai, Yuguang Meng, Khan HekmatyarPhillip Sun, Gabriel Sica, Xiangming Ji, Zhi Ren Liu, Jenny J. Yang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.collagen) to specifically bind to collagen I overexpressed in multiple lung diseases. When compared to clinically approved Gd3+ contrast agents, hProCA32.collagen exhibits significantly better r1 and r2 relaxivity values, strong metal binding affinity and selectivity, and transmetalation resistance. Here, we report the robust detection of early and late-stage lung fibrosis with stage-dependent MRI signal-to-noise ratio (SNR) increase, with good sensitivity and specificity, using a progressive bleomycin-induced IPF mouse model. Spatial heterogeneous mapping of usual interstitial pneumonia (UIP) patterns with key features closely mimicking human IPF, including cystic clustering, honeycombing, and traction bronchiectasis, were noninvasively detected by multiple MR imaging techniques and verified by histological correlation. We further report the detection of fibrosis in the lung airway of an electronic cigarette-induced COPD mouse model, using hProCA32.collagen-enabled precision MRI (pMRI), and validated by histological analysis. The developed hProCA32.collagen is expected to have strong translational potential for the noninvasive detection and staging of lung diseases, and facilitating effective treatment to halt further chronic lung disease progression.

Original languageEnglish (US)
Pages (from-to)268-285
Number of pages18
JournalChemical and Biomedical Imaging
Volume1
Issue number3
DOIs
StatePublished - Jun 26 2023

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

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