Brianna F. Moon1, Srikant Kamesh Iyer2, Nicholas J. Josselyn2, James J. Pilla2, Joseph H. Gorman III3, Robert C. Gorman3, Cory Tschabrunn4, Giovanni Ferrari5, Yuchi Han4, Harold I. Litt2, and Walter R. Witschey2
1Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, 2Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 3Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 4Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 5Surgery, Columbia University Irving Medical Center, New York City, NY, United States
Synopsis
Intramyocardial hemorrhage is a complication of reperfused myocardial
infarction. Quantitative susceptibility
mapping (QSM), R2*-mapping and T2*-weighted images provide quantitative
assessment and image contrast based on the presence of iron. We sought to
determine the relationship between magnetic susceptibility and R2* with varying
voxel size at 3 and 7 T, where tissue magnetic susceptibility showed independence of field strength but dependence on voxel size. At high resolution
the detection of heterogeneous infarct magnetic susceptibility improved in a
large animal model of myocardial infarction.
Purpose
Intramyocardial hemorrhage is a complication of reperfusion therapy for
myocardial infarction (MI) and studies have shown that it is a prognostic for
major adverse cardiac outcomes1,2. A paramagnetic
shift in tissue magnetic susceptibility was shown to be associated with elevated
iron content in intramyocardial hemorrhage3, where magnetic susceptibility was independent
of field strength unlike relaxation rate (R2*)4. When comparing magnetic susceptibility at 3
and 7 T, it was important to maintain the same voxel size5 at both field strengths
to show independence in field strength. For this study, we sought to determine
the relationship between magnetic susceptibility, R2* and voxel size at 3 and 7
T. We hypothesized that a magnetic field gradient across a larger voxel size
would increase myocardial infarct R2* and potentially affect magnetic
susceptibility and at high resolution there would be improved detection of
heterogeneous infarct magnetic susceptibility. To test this hypothesis, we
compared quantitative susceptibility mapping (QSM) and R2*-mapping at varying
voxel size and field strength in a large animal model of MI.Methods
MI was
induced by coronary surgical ligation and released after 90- or 180-min in male
Yorkshire swine. Ex vivo 3D multi-echo gradient-echo image
acquisition occurred at 3-day (n=1) and 1-week (n=7) post-MI, whole heart
specimens were imaged at 7 and 3 T at varying voxel size. 7 T: 0.03 (n=4), 0.13 (n=4), 0.42 (n=4), 0.72 (n=1) mm3 voxel
size, TR/TEfirst/TElast/ΔTE=24/2.8/16.5/3.4 msec, FA=28
degrees, BW=725 Hz/pixel, NEX=3. 3 T:
0.42 (n=4), 0.72 (n=8), 1.13 (n=1), 1.72 (n=1) mm3 voxel size, TR/TEfirst/TElast/ΔTE=31-42/2.7-3.3/16.1-16.5/3.2-3.4
msec, FA=16 degrees, BW=610 Hz/pixel, NEX=1 (Siemens Healthcare). R2*-maps were
obtained using a 2-parameter fit with least squares minimization. QSM was
reconstructed using the MEDI image processing pipeline6. Three volumes-of-interest (VOIs) were obtained from T2*-weighted
(T2*w) images using threshold active contour segmentation (ITK-SNAP7) including remote myocardium: isointense (‘iso’),
infarct: hyperintense (‘hyper’) and hypointense (‘hypo’). Statistics included linear regressions
from VOI
measurements and student’s t-test, significance
if P<0.05.Results
Figure
1 displays the changes
in T2*w images, R2*-maps and QSM at 7 and 3 T with varying voxel
size. Hypointense regions correspond to an elevation in R2* and tissue magnetic
susceptibility. As voxel size increased and field strength decreased, there was a reduction in distinguishing heterogeneous regions of elevated tissue magnetic
susceptibility. Figure 2 shows hypointense VOI measurements at 7 T, as voxel size increased there was a linear increase in R2* (slope: 102 sec-1 per mm3, R2=0.92, 2A) and decrease in
magnetic susceptibility (slope: -80.8 ppb per mm3, R2=0.77, 2B). Hyperintense and isointense VOI had a non-significant linear
regression coefficient for all regressions. After adding 3 T VOI measurements,
there was poor linearity between R2* vs. voxel size (R2=0.29, 2C) and a significant linear decrease in
magnetic susceptibility vs. voxel size (slope: -85.4 ppb per mm3, R2=0.9,
P=0.013, 2D). Specifically, at 0.42 mm3 there was a significant difference
between R2* measurements at 7 and 3 T (177.5±2.1 vs. 108.7±3.9 sec-1,
P<0.001) that was not seen with
magnetic susceptibility (P=0.66), highlighting
that magnetic susceptibility shows independence of field strength but
dependence on voxel size. At 7 T, there was an increasing change in slope in R2*
vs. magnetic susceptibility (0.61 to 1.10 sec-1 per ppb) as voxel size
increased (0.03 to 0.42 mm3) (2E).
At 3 T, there was a decreasing change in slope (0.83 to 0.56 sec-1
per ppb) as voxel size increased (0.42 to 0.72 mm3) (2F). Figure 3 displays a representative 90-min reperfused infarct at
3-day post-MI, where more images were acquired with larger voxel size. The
heterogeneous distribution of tissue magnetic susceptibility at high resolution
dissipated at lower resolution and infarct magnetic susceptibility appears to decrease with increasing voxel size.Discussion and Conclusion
R2* is sensitive to iron-induced
magnetic field gradients but also affected by intravoxel signal dephasing due
to large macroscopic gradient fields, where larger voxel size increases R2*. R2* was shown to be dependent on field
strength4 which could be from amplified
microscopic internal magnetic fields at 7 T elevating R2* compared to at 3 T8,9. We saw an R2* dependence on both voxel
size and field strength in myocardial infarcts. Tissue magnetic susceptibility
showed a significant decreasing regression with respect to voxel size independent
of field strength. 7 and 3 T had opposite trends in slope (R2* vs. magnetic
susceptibility, [sec-1 per ppb]) as voxel size increased, which could
be from amplified internal iron-induced magnetic fields and a larger
macroscopic gradient field with increased voxel size at 7 T causing an increase
in R2*, whereas at 3 T without amplification of iron-induced magnetic fields, increased
voxel size may cause more signal averaging and a decrease in R2*. In
distinction to R2*, QSM utilizes MR signal phase to measure magnetic
susceptibility, which is more specific to iron because iron alters the induced
field, but there could be an averaging effect, where at increased voxel size,
regions with high iron content and signal dephasing are being averaged with
surrounding regions of lower iron content causing an overall decrease in
magnetic susceptibility per voxel. In summary, it appears voxel size influences
magnetic susceptibility independent of field strength, whereas R2* shows a
tissue-dependent change with field strength and voxel size.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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