Isabel T Ramos1,2, Markus Henningsson1, Maryam Nezafat1, Begoña Lavin1,2, Silvia Lorrio1,2, Pierre Gebhardt1,3, Andrea Protti1, Thomas R Eykyn1, Marcelo E Andia4, Ulrich Flögel5, Alkystis Phinikaridou1,2, Ajay M Shah2, René M Botnar1,6. 1. School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom. 2. School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre of Excellence, London, United Kingdom. 3. Department of Physics of Molecular Imaging Systems, Institute for Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany. 4. Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile. 5. Department of Molecular Cardiology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. 6. Escuela de Ingeniería, Pontificia Universidad Católica de Chile, Santiago, Chile.
Abstract
Background: Optimal healing of the myocardium following myocardial infarction (MI) requires a suitable degree of inflammation and its timely resolution, together with a well-orchestrated deposition and degradation of extracellular matrix (ECM) proteins. Methods and Results: MI and SHAM-operated animals were imaged at 3,7,14 and 21 days with 3T magnetic resonance imaging (MRI) using a 19F/1H surface coil. Mice were injected with 19F-perfluorocarbon (PFC) nanoparticles to study inflammatory cell recruitment, and with a gadolinium-based elastin-binding contrast agent (Gd-ESMA) to evaluate elastin content. 19F MRI signal co-localized with infarction areas, as confirmed by late-gadolinium enhancement, and was highest 7days post-MI, correlating with macrophage content (MAC-3 immunohistochemistry) (ρ=0.89,P<0.0001). 19F quantification with in vivo (MRI) and ex vivo nuclear magnetic resonance (NMR) spectroscopy correlated linearly (ρ=0.58,P=0.020). T1 mapping after Gd-ESMA injection showed increased relaxation rate (R1) in the infarcted regions and was significantly higher at 21days compared with 7days post-MI (R1[s-1]:21days=2.8 [IQR,2.69-3.30] vs 7days=2.3 [IQR,2.12-2.5], P<0.05), which agreed with an increased tropoelastin content (ρ=0.89, P<0.0001). The predictive value of each contrast agent for beneficial remodeling was evaluated in a longitudinal proof-of-principle study. Neither R1 nor 19F at day 7 were significant predictors for beneficial remodeling (P=0.68;P=0.062). However, the combination of both measurements (R1<2.34Hz and 0.55≤19F≤1.85) resulted in an odds ratio of 30.0 (CI95%:1.41-638.15;P=0.029) for favorable post-MI remodeling. Conclusions: Multinuclear 1H/19F MRI allows the simultaneous assessment of inflammation and elastin remodeling in a murine MI model. The interplay of these biological processes affects cardiac outcome and may have potential for improved diagnosis and personalized treatment.
Background: Optimal healing of the myocardium following myocardial infarction (MI) requires a suitable degree of inflammation and its timely resolution, together with a well-orchestrated deposition and degradation of extracellular matrix (ECM) proteins. Methods and Results: MI and SHAM-operated animals were imaged at 3,7,14 and 21 days with 3T magnetic resonance imaging (MRI) using a 19F/1H surface coil. Mice were injected with 19F-perfluorocarbon (PFC) nanoparticles to study inflammatory cell recruitment, and with a gadolinium-based elastin-binding contrast agent (Gd-ESMA) to evaluate elastin content. 19F MRI signal co-localized with infarction areas, as confirmed by late-gadolinium enhancement, and was highest 7days post-MI, correlating with macrophage content (MAC-3 immunohistochemistry) (ρ=0.89,P<0.0001). 19F quantification with in vivo (MRI) and ex vivo nuclear magnetic resonance (NMR) spectroscopy correlated linearly (ρ=0.58,P=0.020). T1 mapping after Gd-ESMA injection showed increased relaxation rate (R1) in the infarcted regions and was significantly higher at 21days compared with 7days post-MI (R1[s-1]:21days=2.8 [IQR,2.69-3.30] vs 7days=2.3 [IQR,2.12-2.5], P<0.05), which agreed with an increased tropoelastin content (ρ=0.89, P<0.0001). The predictive value of each contrast agent for beneficial remodeling was evaluated in a longitudinal proof-of-principle study. Neither R1 nor 19F at day 7 were significant predictors for beneficial remodeling (P=0.68;P=0.062). However, the combination of both measurements (R1<2.34Hz and 0.55≤19F≤1.85) resulted in an odds ratio of 30.0 (CI95%:1.41-638.15;P=0.029) for favorable post-MI remodeling. Conclusions: Multinuclear 1H/19F MRI allows the simultaneous assessment of inflammation and elastin remodeling in a murine MI model. The interplay of these biological processes affects cardiac outcome and may have potential for improved diagnosis and personalized treatment.
Authors: Hiromi Yanagisawa; Elaine C Davis; Barry C Starcher; Takashi Ouchi; Masashi Yanagisawa; James A Richardson; Eric N Olson Journal: Nature Date: 2002-01-10 Impact factor: 49.962
Authors: S D Solomon; R J Glynn; S Greaves; U Ajani; J L Rouleau; F Menapace; J M Arnold; C Hennekens; M A Pfeffer Journal: Ann Intern Med Date: 2001-03-20 Impact factor: 25.391
Authors: U Flögel; S Su; I Kreideweiss; Z Ding; L Galbarz; J Fu; C Jacoby; O Witzke; J Schrader Journal: Am J Transplant Date: 2011-01-07 Impact factor: 8.086
Authors: Zakir H Sahul; Rupak Mukherjee; James Song; Jarod McAteer; Robert E Stroud; Donald P Dione; Lawrence Staib; Xenophon Papademetris; Lawrence W Dobrucki; James S Duncan; Francis G Spinale; Albert J Sinusas Journal: Circ Cardiovasc Imaging Date: 2011-04-19 Impact factor: 7.792
Authors: Michael Lichtenauer; Michael Mildner; Andrea Baumgartner; Matthias Hasun; Gregor Werba; Lucian Beer; Patrick Altmann; Georg Roth; Mariann Gyöngyösi; Bruno Karl Podesser; Hendrik Jan Ankersmit Journal: Basic Res Cardiol Date: 2011-03-17 Impact factor: 17.165
Authors: Maryam Nezafat; Isabel T Ramos; Markus Henningsson; Andrea Protti; Tamer Basha; René M Botnar Journal: PLoS One Date: 2017-11-09 Impact factor: 3.240
Authors: Amin M Cheikhi; Zariel I Johnson; Dana R Julian; Sarah Wheeler; Carol Feghali-Bostwick; Yvette P Conley; James Lyons-Weiler; Cecelia C Yates Journal: PLoS One Date: 2020-10-23 Impact factor: 3.240