دورية أكاديمية
Molecular magnetic resonance imaging of liver inflammation using an oxidatively activated probe.
العنوان: | Molecular magnetic resonance imaging of liver inflammation using an oxidatively activated probe. |
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المؤلفون: | Jordan VC; Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Sojoodi M; Harvard Medical School, Boston, MA, USA.; Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital, Boston, MA, USA., Shroff S; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Pagan PG; Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Barrett SC; Harvard Medical School, Boston, MA, USA.; Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital, Boston, MA, USA., Wellen J; Bristol Meyers Squibb, Cambridge, MA, USA., Tanabe KK; Harvard Medical School, Boston, MA, USA.; Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital, Boston, MA, USA., Chung RT; Harvard Medical School, Boston, MA, USA.; Gastroenterology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Caravan P; Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Gale EM; Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA. |
المصدر: | JHEP reports : innovation in hepatology [JHEP Rep] 2023 Jul 18; Vol. 5 (10), pp. 100850. Date of Electronic Publication: 2023 Jul 18 (Print Publication: 2023). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101761237 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-5559 (Electronic) Linking ISSN: 25895559 NLM ISO Abbreviation: JHEP Rep Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2019]- |
مستخلص: | Background & Aims: Many liver diseases are driven by inflammation, but imaging to non-invasively diagnose and quantify liver inflammation has been underdeveloped. The inflammatory liver microenvironment is aberrantly oxidising owing in part to reactive oxygen species generated by myeloid leucocytes. We hypothesised that magnetic resonance imaging using the oxidatively activated probe Fe-PyC3A will provide a non-invasive biomarker of liver inflammation. Methods: A mouse model of drug-induced liver injury was generated through intraperitoneal injection of a hepatoxic dose of acetaminophen. A mouse model of steatohepatitis was generated via a choline-deficient, l-amino acid defined high-fat diet (CDAHFD). Images were acquired dynamically before and after intravenous injection of Fe-PyC3A. The contrast agent gadoterate meglumine was used as a non-oxidatively activated negative control probe in mice fed CDAHFD. The (post-pre) Fe-PyC3A injection change in liver vs. muscle contrast-to-noise ratio (ΔCNR) recorded 2 min post-injection was correlated with liver function test values, histologic scoring assigned using the NASH Clinical Research Network criteria, and intrahepatic myeloid leucocyte composition determined by flow cytometry. Results: For mice receiving i.p. injections of acetaminophen, intrahepatic neutrophil composition correlated poorly with liver test values but positively and significantly with ΔCNR (r = 0.64, p <0.0001). For mice fed CDAHFD, ΔCNR generated by Fe-PyC3A in the left lobe was significantly greater in mice meeting histologic criteria strongly associated with a diagnosis NASH compared to mice where histology was consistent with likely non-NASH ( p = 0.0001), whereas no differential effect was observed using gadoterate meglumine. In mice fed CDAHFD, ΔCNR did not correlate strongly with fractional composition of any specific myeloid cell subpopulation as determined by flow cytometry. Conclusions: Magnetic resonance imaging using Fe-PyC3A merits further evaluation as a non-invasive biomarker for liver inflammation. Impact and Implications: Non-invasive tests to diagnose and measure liver inflammation are underdeveloped. Inflammatory cells such as neutrophils release reactive oxygen species which creates an inflammatory liver microenvironment that can drive chemical oxidation. We recently invented a new class of magnetic resonance imaging probe that is made visible to the scanner only after chemical oxidation. Here, we demonstrate how this imaging technology could be applied as a non-invasive biomarker for liver inflammation. Competing Interests: EMG holds equity in, and receives consulting income from Reveal Pharmaceuticals, and receives consulting income from Collagen Medical, LLC. PC holds equity in, and receives consulting income from Collagen Medical LLC, holds equity in Reveal Pharmaceuticals, and has research funding from Takeda, Pliant Therapeutics, and Janssen. Please refer to the accompanying ICMJE disclosure forms for further details. (© 2023 The Authors.) |
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معلومات مُعتمدة: | K25 HL128899 United States HL NHLBI NIH HHS; R01 DK120663 United States DK NIDDK NIH HHS |
فهرسة مساهمة: | Keywords: Drug-induced liver injury; Reactive oxygen species; Steatohepatitis |
تواريخ الأحداث: | Date Created: 20231011 Latest Revision: 20240515 |
رمز التحديث: | 20240515 |
مُعرف محوري في PubMed: | PMC10561122 |
DOI: | 10.1016/j.jhepr.2023.100850 |
PMID: | 37818152 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2589-5559 |
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DOI: | 10.1016/j.jhepr.2023.100850 |