@article {Glasenapp590, author = {Aylina Glasenapp and Katja Derlin and Yong Wang and Marion Bankstahl and Martin Meier and Kai C. Wollert and Frank M. Bengel and James T. Thackeray}, title = {Multimodality Imaging of Inflammation and Ventricular Remodeling in Pressure-Overload Heart Failure}, volume = {61}, number = {4}, pages = {590--596}, year = {2020}, doi = {10.2967/jnumed.119.232488}, publisher = {Society of Nuclear Medicine}, abstract = {Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although 18F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with 18F-FDG can be serially imaged in the early stages of pressure-overload{\textendash}induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. 18F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 {\textpm} 10.2 μL vs. 23.8 {\textpm} 1.7 μL, P \< 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9\% {\textpm} 9.7\% vs. 59.2\% {\textpm} 4.4\%, P \< 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = -0.669, P = 0.010). PET imaging identified significantly higher left ventricular 18F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 {\textpm} 4.1 percentage injected dose [\%ID]/g vs. 3.8 {\textpm} 0.9 \%ID/g, P \< 0.001) and on day 7 (7.8 {\textpm} 3.7 \%ID/g vs. 3.0 {\textpm} 0.8 \%ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The 18F-FDG signal correlated with ejection fraction (r = -0.75, P = 0.01) and ventricular volume (r = 0.75, P \< 0.01). Western immunoblotting demonstrated a 60\% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using 18F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/61/4/590}, eprint = {https://jnm.snmjournals.org/content/61/4/590.full.pdf}, journal = {Journal of Nuclear Medicine} }