First Ultra-High-Field 19F MRI in large animal model after Acute Myocardial infarction at 7T MR-scanner

Introduction
The ischemic injury that occurs during acute myocardial infarction (AMI) triggers a rapid immune response which comes along with myeloid cell infiltration of the injured heart.¹⁹F labelled nanoparticles are taken up by myeloid cells (mainly neutrophils and monocytes) and can be detected by MRI in combination with ¹H without background. Here, we investigate the emergence of myeloid cells using ¹⁹F MRI at ultra-high-field (UHF) in a large animal model of AMI. Our results introduce the first ¹⁹F MR inflammation imaging at 7T MRI after AMI in large animal with reliable-short time acquisition.

Methods

Pigs were subjected to ¹H/¹⁹F MRI protocol at baseline and between days 2-21  after AMI for determination of MI as shown in Figure 1, b. For monitoring of myeloid cells by ¹⁹F in pigs, home-generated perflurocarbone nanoemulsion (PFCEs-NE) was injected intravenously into pigs after a body weight-adjusted volume (5mL/kg) at day 3 of AMI. Heart and surrounding tissues were visualized before and after MI by combined ¹H/¹⁹F MRI.

Results and Discussion

The designed in-house ¹H and ¹⁹F arrays (implemented by Rapid Biomedical) were optimized using a pig thorax phantom (Figure1 ,a) to achieve homogeneity of B₁⁺ field in the pig heart region. The 3D TrueFISP pulse sequence (TR/TE=2.2ms, FA=55⁰, voxel=5x5x5mm) was considered for ¹⁹F MRI because it provided highest signal intensity in the phantom measurements among the other tested pulse sequences as shown in Figure a,4. Our results demonstrate the feasibility of imaging cardiac inflammation in vivo (Figure1, c) and ex vivo (Figure 1,d) using ¹⁹F MRI at 7 T MRI in pigs. The rise of the ¹⁹F signal between 4-7 days after PFCEs-NE injection (as in Figure1 e&f) is indicative of myeloid cell infiltration after AMI. Specifically, this raise correlated with the functional impairment after AMI. Overall, our results introduce the first in vivo and ex vivo approach for ¹⁹F MRI at UHF with acquisition time TA≈5min. Furthermore, more investigations are required whether the ¹⁹F specific-intensity differences between days 4 and 7 after AMI are indeed influenced by the time of PFCEs-NE intravenous administration.

Conclusion

Here, we report the first ¹⁹F MRI myeloid cell imaging of the heart after infarction in a large animal model. Our results show a difference of ¹⁹F intensity signal between day 4-7 PFCEs-NE injection. 

 

Figures:

 

Figure1. a) Pulse sequence selection for PFCEs-NE. a1) Image of used surface ¹⁹F coil;  a2) Phantom of PFCEs  (500 mL) diluted in 7L Polyvinylpyrrolidone (PVP) to imitate living tissues; a3) ¹⁹F signal with TruFISP (TR=5ms, TE=2.5ms, Slice, TA=1:36s) in PFCES-NE phantom; a4) Signal-to-noise ratio (SNR) with different flip angels of PFCES-NE. b) Design diagram of the our study by MRI. Pigs were exposed to high-resolution 7 T MRI at baseline and on 5-21 days after AMI. Injection of 150 mL PFCEs followed by 2 days of AMI. c) Heart in vivo at day 7 after AMI, indicating an egress of fluorinated immune cells into the infarcted heart ; d) Heart ex vivo at day 14 after AMI. Hyperintensity on ¹⁹F MRI is compatible with immune cell recruitment in the inflammation area near the apex of the heart.  e) ¹⁹F MRI in vivo after 2 days of PFCEs-NE injection and 4 days of AMI; f) ¹⁹F MRI in vivo after 5 days of PFCEs-NE injection and 7 days of AMI. For all images, a TruFISP pulse sequence was used with  TR/TE=5/2.5ms, Nslice=10, Sthickness=5mm, averages=32, , flip angle=65, and TA=5 min.