Abstract #3063

Molecular MRI reveals atherosclerotic plaque fibrogenesis and stabilization in ApoE-/- mice with steatotic liver disease

Brianna F. Moon¹, Yin-Ching I. Chen², Iris Y. Zhou^2,3, Yingying Ning^2,3, Eman Akam-Baxter¹, Mariane Le Fur^2,3, Hua Ma^2,3, Jonah Weigand-Whittier², Nicholas Rotile^2,3, Pamela Pantazopoulos^2,3, Matthew Tyros^2,3, Chunxiang Zhang^2,3, Christian T. Farrar², Jesse D. Roberts Jr¹, Yoshiko Iwamoto⁴, David Rohde^1,4, David E. Sosnovik^1,2,4, Kathleen Corey⁵, Matthias Nahrendorf^1,2,4, and Peter Caravan^2,3

¹Medicine, Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ²Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ³Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ⁴Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ⁵Medicine, Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States

Synopsis

Keywords: Molecular Imaging, Atherosclerosis

Motivation: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease, but identifying at-risk patients and evaluating therapeutic response remains challenging.

Goal(s): We aimed to develop a fibrogenesis (active fibrosis) targeted molecular MRI protocol to detect hepatic and atherosclerotic disease activity.

Approach: ApoE-/- mice were fed a high-cholesterol diet inducing atherosclerosis or low-cholesterol choline-deficient high-fat diet generating hepatic steatosis and fibrosis. In vivo MRI included inversion recovery sequences before/after administration of a fibrogenesis-targeted probe (Gd-1,4).

Results: Hepatic Gd-1,4 R1-mapping depicted significant liver fibrogenesis during MASLD progression in mice, while aortic R1 changes reflected atherosclerotic plaque stabilization.

Impact: An innovative fibrogenesis-targeted molecular MR probe revealed that reducing cholesterol resulted in atherosclerotic plaque stabilization even in a high-risk metabolic milieu of steatotic liver disease.

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