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Review
. 2024 Jul 1:28:0042.
doi: 10.34133/bmr.0042. eCollection 2024.

Advances in Noninvasive Molecular Imaging Probes for Liver Fibrosis Diagnosis

Shaofang Chen  1 , Danping Zhuang  1 , Qingyun Jia  1 , Bing Guo  2 , Genwen Hu  1
Affiliations
Review

Advances in Noninvasive Molecular Imaging Probes for Liver Fibrosis Diagnosis

Shaofang Chen et al. Biomater Res. .

Abstract

Liver fibrosis is a wound-healing response to chronic liver injury, which may lead to cirrhosis and cancer. Early-stage fibrosis is reversible, and it is difficult to precisely diagnose with conventional imaging modalities such as magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and ultrasound imaging. In contrast, probe-assisted molecular imaging offers a promising noninvasive approach to visualize early fibrosis changes in vivo, thus facilitating early diagnosis and staging liver fibrosis, and even monitoring of the treatment response. Here, the most recent progress in molecular imaging technologies for liver fibrosis is updated. We start by illustrating pathogenesis for liver fibrosis, which includes capillarization of liver sinusoidal endothelial cells, cellular and molecular processes involved in inflammation and fibrogenesis, as well as processes of collagen synthesis, oxidation, and cross-linking. Furthermore, the biological targets used in molecular imaging of liver fibrosis are summarized, which are composed of receptors on hepatic stellate cells, macrophages, and even liver collagen. Notably, the focus is on insights into the advances in imaging modalities developed for liver fibrosis diagnosis and the update in the corresponding contrast agents. In addition, challenges and opportunities for future research and clinical translation of the molecular imaging modalities and the contrast agents are pointed out. We hope that this review would serve as a guide for scientists and students who are interested in liver fibrosis imaging and treatment, and as well expedite the translation of molecular imaging technologies from bench to bedside.

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Conflict of interest statement

Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1.
Fig. 1.
Schematic illustration of potential targets of liver fibrosis and molecular probes and imaging modalities used in liver fibrosis.
Fig. 2.
Fig. 2.
Schematic representation of capillarization of LSECs and cellular and molecular processes involved in liver fibrosis.
Fig. 3.
Fig. 3.
Schematic representation of type I collagen synthesis and covalent cross-linking formation.
Fig. 4.
Fig. 4.
Targeting HA receptors on aHSCs and structures on macrophages for imaging liver fibrosis. (A) Schematic structure of HA-NPs/SMV and CV-NPs/siCol1α1. (B) SEM compares the number of fenestrations and sieve plates in primary LSECs and those treated with HA-NPs/SMV or VEGF. Scale bar, 1 μm. (C) Near-infrared fluorescence images of fibrotic mice treated or not with HA-NPs/SMV for 4 weeks followed by injection of indicated formulations. Reproduced with permission [110]. 2022, American Chemical Society. (D) Schematic representation of Cur-mNLCs synthesized and targeted to fibrotic liver. (E) In vitro fluorescence images of major organs of rats with liver fibrosis at 2 and 4 h after injection of DiR-loaded NLCs without PS (DiR-NLCs) or with PS (DiR-mNLCs). Reproduced under terms of the CC-BY license [126]. 2017 The Authors, Published by [Informa UK Limited].
Fig. 5.
Fig. 5.
Assessment of fibrogenesis using probes targeting oxidized collagen. (A) Schematic structure of Gd-Hyd and Gd-DiMe (control). (B) MRI-enhanced imaging of liver fibrosis progression and regression in hepatic fibrosis mice before and after Gd-Hyd injection compared to controls. Reproduced with permission [135]. 2017, American Society for Clinical Investigation. (C) Schematic representation of the binding process of the hydrazide moiety on Gd-Hyd to allysine on collagen. Reproduced under terms of the CC-BY license [134]. 2021 The Authors. (D) Schematic chemical structures of Gd-1,4, Gd-1,7, Gd-1,4C, and Gd-CHyd. (E) Compared with Gd-1,7, the O-O distance between 2 LysAld residues in type I collagen is more consistent with the N-N distance in piperazino-hydrazine groups in Gd-1,4. (F) Liver MRI of CCl4 mouse before and after injection of different probes. (G) Translation potential of Gd-1,4 in detecting human liver fibrogenesis. Reproduced with permission [137]. 2022, The American Association for the Advancement of Science.
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