0406
Magnetic susceptibility and T2* of myocardial reperfusion injury at 3 and 7 T1Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, 2Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 3Physics and Astronomy, Wheaton College, Norton, MA, United States, 4Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 5Surgery, Columbia University, New York City, NY, United States, 6Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Synopsis
Intramyocardial hemorrhage is a frequent complication of acute myocardial infarction (MI) after reperfusion therapy. This study investigated the relationship between T2* and susceptibility and how they are affected by magnetic field strength. We compare cardiac quantitative susceptibility mapping (QSM) and T2* at 3 and 7 T and demonstrate improved detection of hemorrhage and infarct regions at 7 T in a large animal model correlating with infarct pathophysiology.
Purpose:
Myocardial hemorrhage is a complication of reperfusion for myocardial infarction and recent MRI studies have shown that it is prognostic for major adverse cardiovascular events1,2. Using cardiac quantitative susceptibility mapping (QSM), it was shown that there is a magnetic susceptibility paramagnetic shift in reperfusion injury associated with elevated tissue iron content3. Yet there remains limited understanding of the relationship between relaxation times and susceptibility or how they are affected by magnetic field strength. We sought to compare magnetic susceptibility and T2* at 3 and 7 T. We hypothesized that larger iron-induced magnetic field gradients at 7 T would reduce myocardial infarction T2*, but not magnetic susceptibility, and 7 T would show better sensitivity for detection of hemorrhage and infarct regions. To test this hypothesis, we compared cardiac QSM and T2* at 3 and 7 T in a large animal model of myocardial infarction.Methods:
Myocardial infarction was induced by coronary surgical ligation and released after 45 (N=1), 90 (N=1), 180 (N=3) minutes or permanent ligation (N=2) in male Yorkshire swine. At 7 days post-infarction, the heart was explanted, bathed in non-1H magnetic susceptibility-matched fluid (Fomblin) and multi-echo gradient-echo images of whole heart specimens were obtained at 3 T (0.7 mm3 resolution, TEfirst/TElast/ΔTE=42/3.3/38.5/3.2 ms) and 7 T (0.03 mm3 resolution, TEfirst/TElast/ΔTE=24/2.8/19.9/3.4 ms) (Siemens Healthcare). T2*-maps were obtained using a 3-parameter fit with least squares minimization. QSM images were reconstructed using morphology-enabled dipole inversion3-5. Three volumes-of-interest (VOIs) were obtained from T2*-weighted (T2*w) images using threshold active contour segmentation (ITK-SNAP, University of Pennsylvania)6 including remote myocardium: (1)-isointense, infarct: (2)-hyperintense (3)-hypointense (‘hemorrhage’), where (2) and (3) were combined for an overall infarct measurement. Iron content and fibrosis was validated by histopathological staining (Trichrome, Prussian blue, H&E). Linear regression and student’s t-test comparisons were performed for all VOIs (results reported as mean±SD, significance if P<0.05).Results:
Figure 1A compares T2*-weighted (T2*w), T2*-maps and QSM at 3 and 7 T. The magnetic susceptibility of the remote myocardium and infarct at 3 T was 0.013±0.01 and 0.051±0.04 ppm (P<0.05) and at 7 T was -0.0003±0.01 and 0.061±0.08 ppm (P<0.05). The VOI magnetic susceptibility showed a larger paramagnetic shift at 7 T compared to 3 T (slope=1.69, R2=0.83, P<0.001, Figure 1B, dashed regression line), but was not significantly different when infarct VOIs were combined (slope=0.96, R2=0.85, P<0.001, solid regression line). T2* of remote and infarct regions at 3 T was 46.7±1.1 and 42.4±25.2 ms (P=0.6) and at 7 T was 29.1±1.0 and 19.6±10.4 ms (P<0.05). T2* was lower at 7 T compared to 3 T (slope=0.39, R2=0.65, P<0.001, Figure 1C). There was good linearity between transverse relaxation rate (R2*) and magnetic susceptibility (Δχ) above 50 ppb at 3 and 7 T (7 T: slope=0.58, R2=0.89, P<0.001, 3 T: slope=0.53, R2=0.75, P<0.001, Figure 1D). There was spatial correspondence between T2*w images (Figure 2A) and histological features of fibrosis with patchy viable myocardium (Figure 2Ba). QSM also corresponded with iron at the transition zone of myocyte necrosis (Figure 2Bb) and red blood cells (Figure 2Bc).Discussion and Conclusion:
T2* is sensitive to microscopic magnetic field gradients but is also affected by intravoxel signal dephasing due to large macroscopic gradient fields. After mitigating macroscopic field contributions to T2* using small voxel sizes7, explant imaging, and magnetic susceptibility-matched fluid, there was a significant reduction in T2* in infarct and remote myocardium at 7 T compared to 3 T, suggesting the presence of microscopic internal magnetic fields amplified by the applied 7 T field. The difference in T2* between 3 and 7 T for non-hemorrhagic MI was larger than anticipated, which may be explained in part by elevated tissue iron compared to remote myocardium. This result is consistent with total iron quantification studies of reperfusion injury using inductively coupled plasma optical emission spectrometry3. In distinction to T2*, QSM utilizes MR signal phase to measure magnetic susceptibility, which is more specific to iron because it alters the induced field, whereas edema and fibrosis do not appear to have a similar effect. We found comparable regression slopes between R2* and magnetic susceptibility8,9, where R2* appears to be independent of magnetic susceptibility to approximately 50 ppb, after which it increases linearly. This suggests that fibrosis or edema increases T2* and competes with moderately elevated tissue iron, which decreases T2*, in non-hemorrhagic MI. In summary, magnetic susceptibility appears to be relatively conserved between 3 and 7 T and shows sensitivity to low to moderate iron, whereas T2* shows a tissue-dependent change with field strength.Acknowledgements
We gratefully acknowledge support from R00-HL108157, R01-HL137984, NRSA in interdisciplinary Cardiovascular Biology NIH T32-HL007954, and HHMI-NIBIB Interfaces Program NIH T32-EB009384.References
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