Preclinical InvestigationDelayed Echo Enhancement Imaging to Quantify Myocardial Infarct Size
Section snippets
Definity Droplet Formulation
Definity (Lantheus Medical, North Billerica, MA) was used in all the studies.13 Definity microbubbles were activated via mechanical agitation (Vialmix shaker, Bristol-Myers-Squibb, New York, NY) for 45 seconds. Definity nanodroplets (DD) were then formulated according to a previously described protocol.1, 2, 3 A 1:1 (with normal saline) dilution of one vial of Definity (total volume 5 mL) was drawn into a 10 mL syringe and cooled in an isopropyl alcohol bath (–10°C) for 3 minutes. The cooled
Definity Droplet Size and Concentration
The mean size of the DD (prior to 1:1 dilution) was 180 ± 70 nm, with over 90% of the droplets being <275 nm. The mean concentration prior to the 1:1 dilution (using the Nanosight N5300 Particle Analyzer) was 8.1 × 1010 droplets/mL.
Hemodynamic Effects of Droplet Injection and Activation
Table 2 depicts mean arterial pressure (MAP), heart rate (HR), and oxygen saturation following IVI of droplets. There were no changes in any of these parameters following droplet injections.
Acoustic Activation Imaging
There was a wide range of infarct size noted by DE-MRI, ranging from 0% to
Discussion
Using an “activate-image” sequence on the same diagnostic transducer, we observed delayed echo myocardial contrast enhancement at 2-4 minutes following IVI of perfluoropropane droplets. At this time period post-IVI, there were minimal residual left ventricular cavity droplets, indicating the contrast emanated from activation of droplets within extravascular spaces. The presence of droplets within these extravascular spaces was confirmed by TEM. With SPHI-induced activation, we observed
Conclusion
Using FNLI with harmonic subtraction, we were able to selectively enhance and quantify the infarct zone with acoustic activation imaging of extravascular DD. Delayed enhancement of the infarct zone was achieved with FNLI, while only viable myocardial segments were enhanced with SPHI. The mechanism for this different droplet acoustic response within the scar zone needs to be further elucidated, in order to utilize this technique for both targeted imaging and targeted therapy.
References (22)
- et al.
Acoustic behavior of a reactivated, commercially available ultrasound contrast agent
J Am Soc Echocardiogr
(2017) - et al.
On the acoustic properties of vaporized submicron perfluorocarbon droplets
Ultrasound Med Biol
(2014) - et al.
Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation
Ultrasound Med Biol
(2015) - et al.
Contrast-enhancing ultrasound imaging and in vivo circulatory kinetics with low-boiling-point nanoscale phase-change perfluorocarbon agents
Ultrasound Med Biol
(2015) Application of acoustic droplet vaporization in ultrasound therapy
J Ther Ultrasound
(2015)- et al.
Design of ultrasonically-activatable nanoparticles using low boiling point perfluorocarbons
Biomaterials
(2012) - et al.
Pulse sequences for uniform perfluorocarbon droplet vaporization and ultrasound imaging
Ultrasonics
(2014) - et al.
Acoustic cavitation-mediated delivery of small interfering ribonucleic acids with phase-shift nano-emulsions
Ultrasound Med Biol
(2015) - et al.
Targeted transthoracic acoustic activation of systemically administered nanodroplets to detect myocardial perfusion abnormalities
Circ Cardiovasc Imaging
(2016) - et al.
Selective infarct zone imaging with intravenous acoustically activated droplets
PLoS One
(2018)
Dual-frequency acoustic droplet vaporization detection for medical imaging
IEEE Trans Ultrason Ferroelectr Freq Control
Cited by (4)
Current Status of Sub-micron Cavitation-Enhancing Agents for Sonothrombolysis
2023, Ultrasound in Medicine and BiologyAcoustic Detection of Retained Perfluoropropane Droplets Within the Developing Myocardial Infarct Zone
2022, Ultrasound in Medicine and BiologyCitation Excerpt :The MCI ratio of signal enhancement within the DSZ compared with the remote zone was significantly higher with FNLI (Fig. 7D), and corresponded to the differences in myocardial fluorescence intensity observed on confocal microscopy in rats at this period post-injection. Droplet activation with high-MI diagnostic transthoracic impulses has recently been reported to produce delayed enhancement within the infarct zone (Zeng et al. 2021). The optimal pulse sequences for activation and the period during which activation impulses should be applied after intravenous injection have not been evaluated.
Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia
2021, Journal of the American College of CardiologyCitation Excerpt :This difference can be explained by patients with ACS having larger body mass and comorbidities that affect signal intensity (obesity and lung disease) and the use of supplemental oxygen, which can influence MB gas exchange and signal intensity over time (26). When considering nonspecific retention, it is interesting to speculate that the retention of agent in the microcirculation in nonacute settings could provide a simple method to assess myocardial vascular integrity after a single injection without concern for cavity attenuation, similar to what has recently been described with phase-transition ultrasound enhancing agents (27). In the ACS population, MBPS signal on MCE molecular imaging was more than 5-fold higher in the adjudicated postischemic risk area than the remote region.
Phase-Conversion Nanodroplets: Good Things Coming in Small Packages
2021, Journal of the American Society of Echocardiography
This study was supported by National Institutes of Health, United States Application 1 RO1 HL 146489-01A1 with additional support from the Theodore F. Hubbard Foundation.