Molecular Contrast Agents for Post-infarct Cardiac Remodeling: A Contemporary Review

Figures

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  Figure 1. Visualizing macrophage-driven inflammatory activity using USPIONs. R2* colour maps in MI patients at i) baseline and ii) 24 h in A) control patients and B) patients who underwent USPION infusion. iii) Corresponding R2* values in the liver (blue), infarct region (red) and remote myocardium (green) in control patients vs. patients who received USPIONs. R2* increased in the liver and myocardium in patients who received USPIONs, but remained unchanged in control patients. Reproduced from Alam et al., copyright permission obtained from Wolters Kluwer Health Inc. (CC-BY-NC).11

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  Figure 2. Tracking myocardial inflammation using 68Ga-DOTATATE PET/MRI at baseline vs. 3-month follow-up. Baseline PET/MRI (left): A) LGE-MRI showing subendocardial MI (white asterisk) in the mid inferolateral segment, with corresponding C) high signal (white arrowhead) on T2-weighted imaging, and G) increased 68Ga-DOTATATE uptake (white dashed arrow). E) Colour map shows myocardium-to-muscle T2 ratio. Follow-up PET/MRI (right): B) T2-mapping; D) resolution of oedema on T2-weighted imaging; F) myocardium-to-muscle T2 ratio; H) residual 68Ga-DOTATATE uptake indicating ongoing macrophage activity (white dashed arrow). Reproduced from Ćorović et al., open access under Creative Commons CC-BY 4.0.49

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  Figure 3. Visualizing myocardial inflammation using 64Cu-DOTA-ECL1i PET/CT. A) Tc-99m SPECT/CT and 64Cu-DOTA-ECL1i PET/CT images from healthy controls and STEMI patients. Regions with increased 64Cu-DOTA-ECL1i uptake strongly correlated with infarct areas of reduced perfusion in Tc-99m SPECT/CT (red and green arrowheads). B, C) 64Cu-DOTA-ECL1i signal intensity (SUVmean) was significantly increased in the infarct myocardium of STEMI patients compared to healthy controls. No significant difference in intensity was observed in the skeletal muscle. D) 64Cu-DOTA-ECL1i signal as a function of time after STEMI (days). Each data point represents an individual STEMI patient, while the line and grey zones represent the mean value of healthy controls with SD. E) 17-segment model polar maps representing areas of perfusion and myocardial wall motion from Tc-99m SPECT/CT. F) Linear regression analysis showed a significant association between 64Cu-DOTA-ECL1i uptake and wall motion score (r2 = 0.40, P = 0.03). Reproduced from Lavine et al., copyright permission obtained from Springer Nature (CC-BY-NC).29

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  Figure 4. Visualizing acute and chronic fibroblast activity in the infarct and remote myocardium using 68Ga-FAPI-46 PET/MRI. Short-axis and 2-chamber PET and LGE-MRI overlay images at A) 23 days and B) 3 days post-MI. Intense FAPI-46 activity was observed in the infarct zone coinciding with areas of late gadolinium enhancement (blue arrows), and also extending into the peri-infarct regions. C) Long-axis and short-axis PET and LGE-MRI images, taken at 2.5 years (top) and 20 years (bottom) post-MI respectively. Low levels of persistent fibroblast activation was detected by FAPI-46 that was confined within areas of chronic infarction. Reproduced from Barton et al., open access under Creative Commons CC-BY 4.0.34

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  Figure 5. Quantification of ɑ7nAChR expression in the infarct myocardium with NS14490-PET. A) Histological H&E staining of non-infarcted (sham) and MI hearts from day 2 to day 28. Scale bar = 1 mm. B) Corresponding NS14490-PET images. Enhanced uptake was observed on days 14 to 28 in the infarct regions in the left ventricle of MI mice. Reproduced from Reid et al., open access under Creaetive Commons CC-BY 4.0.39

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  Figure 6. Quantification of elastin with MRI using Gd-ESMA vs. Gd-DTPA in late adverse modelling. A) Consecutive imaging on day 7 and day 21 with Gd-DTPA vs. Gd-ESMA. While no significant difference in uptake of Gd-DTPA was observed between day 7 and day 21, uptake of Gd-ESMA was significantly increased on day 21. Furthermore, the Gd-ESMA signal was persistent up to 90 min after injection, while Gd-DTPA was quickly flushed out 30 min after injection. B) Dot plot diagram of contrast-to-noise ratio (CNR) values (mean and 95% confidence interval) on day 7 vs. day 21 post-MI. While CNR values did not differ significantly for Gd-DTPA, they were significantly higher on day 21 compared to day 7 for Gd-ESMA (P = 0.0032). This corresponded with increase in elastin deposition within the infarct as verified by ex vivo C) Western blot analysis, and D, E) histological haematoxylin and eosin (HE) and elastica van Gieson (EvG) staining. *P < 0.05. Reproduced from Wildgruber et al., copyright permission obtained from Wolters Kluwer Health Inc. (CC-BY-NC).42