Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

Autor: Moon BF; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Zhou IY; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Ning Y; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Chen YI; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA., Le Fur M; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Shuvaev S; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Akam EA; Department of Medicine, Division of Cardiology, Massachusetts General Hospital and Harvard Medical School Boston MA USA., Ma H; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Solsona CM; Bruker BioSpin, Preclinical Imaging Billerica MA USA., Weigand-Whittier J; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA., Rotile N; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Hariri LP; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Department of Pathology, Massachusetts General Hospital, Harvard Medical School Boston MA USA., Drummond M; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School Boston MA USA., Boice AT; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Zygmont SE; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Sharma Y; Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center Boston MA USA., Warburton RR; Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center Boston MA USA., Martin GL; Molecular Cardiology Research Institute, Tufts Medical Center Boston MA USA., Blanton RM; Molecular Cardiology Research Institute, Tufts Medical Center Boston MA USA., Fanburg BL; Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center Boston MA USA., Hill NS; Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center Boston MA USA., Caravan P; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School Boston MA USA.; Institute for Innovation in Imaging, Massachusetts General Hospital Boston MA USA., Penumatsa KC; Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center Boston MA USA.
Jazyk: angličtina
Zdroj: Journal of the American Heart Association [J Am Heart Assoc] 2024 Jul 16; Vol. 13 (14), pp. e034363. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1161/JAHA.124.034363
Abstrakt: Background: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model.
Methods and Results: Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart ( P =0.02) and lungs ( P =0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase ( P <0.0001) and Δlung-to-muscle ratio ( P <0.0001). Hydroxyproline in the heart ( P <0.0001) and lungs ( P <0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, P =0.02) and lung (lung-to-muscle ratio, P <0.001) PET measurements. Pressure-volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice.
Conclusions: Administration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-magnetic resonance imaging protocol.
Databáze: MEDLINE
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