Li-Ting Huang1,2, Xinheng Zhang3,4, Xinqi Li2, Archana Malagi2, Yuheng Huang4,5, Xinming Guan3, Ghazal Yoosefian3, Hao Ho6, Alan Kwan7, Anthony Christodoulou2,4,8, Debiao Li2, Hui Han2, Yen-Wen Liu9, Rohan Dharmakumar3,4, and Hsin-jung Yang2
1Department of Medical Imaging, National Cheng Kung University Hospital, Tainan, Taiwan, 2Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States, 3Krannert Cardiovascular Research Center, Indiana University, Bloomington, IN, United States, 4Department of Bioengineering, University of California at Los Angeles, Los Angeles, CA, United States, 5Krannert Cardiovascular Research Center, Indiana University School of Medicine, Indianapolis, IN, United States, 6Department of Statistics, University of California at Los Angeles, Los Angeles, CA, United States, 7Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States, 8Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States, 9Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
Synopsis
Keywords: Heart Failure, Cardiomyopathy, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
Motivation: Late gadolinium enhancement (LGE) CMR‘s wider clinical adoption is hindered by its prolonged wait time and imaging protocol dependence.
Goal(s): Develop a delayed dynamic contrast enhancement (dDCE) model to shorten the LGE wait time and provide a quantitative characterization of the myocardium contrast washout process.
Approach: Dynamic T1 maps were acquired in the contrast washout period in dogs with myocardial infarctions. dDCE maps and synthesized LGE images were derived from data collected within 5-minute post-contrast injection.
Results: The 5-minute dDCE maps provide physiologically reasonable measurements and comparable myocardial viability assessment ability to standard LGE images.
Impact: The
shortened LGE wait time from the quantitative dDCE maps may benefit patients
unable to tolerate long CMR examination time and open new dimensions for
quantitative myocardium viability assessment.
Introduction
Late gadolinium enhancement (LGE) cardiac
magnetic resonance (CMR) provides differential diagnosis between ischemic
and non-ischemic heart diseases with high accuracy1 and predicts adverse
cardiac events in cardiomyopathy2,3. However, its wider clinical
adoption is limited by prolonged contrast washout wait
time, suboptimal blood pool to lesion contrast, and imaging protocol dependency.
In this study, we aimed to develop a time-efficient viability imaging technique
using a delayed dynamic contrast enhancement(dDCE) model, quantifying the contrast washout process in the myocardium
with a shortened wait time.Method
N = 10 dogs with acute myocardial infarction(AMI)
were studied at 1 week after myocardial infarction under IACUC approval. Clinical
T1 MOLLI maps of the heart were
repeatedly acquired at 1-2 minute intervals after contrast injection for up
to 30 minutes (8 inversion times [TI] with 2 Look-Locker cycles of 3 + 5 images, minimum TI = 120ms, TI increment = 80ms, flip angle = 35°, readout bandwidth = 1371 Hz/pixel, and voxel size in 1.5×1.5×8 mm). Standard LGE (LGEstandard) images with PSIR reconstruction (balanced SSFP readouts
with TR/TE=3.42/1.47; inversion time to null viable myocardium; readout
bandwidth= 586 Hz/pixel; Flip angle=20˚) were acquired 15 minutes after
contrast administration. A modified two-compartment exchange model was fit to the dynamic T1 maps to model the contrast washout. Separate dDCE maps were reconstructed
using the whole dataset (dDCE30min) and a subset of the T1 maps within 5 minutes post-contrast injection (dDCE5min). To test the dDCE
model's ability to shorten the LGE wait time, LGEdDCE images were synthesized
using the dDCE5min maps and compared to the LGEstandard
images. The pipeline used for this study is illustrated in Figure 1.Results
The dDCE30min map demonstrated a good spatial
correspondence to the MI zone, displaying signal differences between remote myocardium and MI, that reflect the pathophysiology changes (Figure 2A). MI had
significantly higher ve and PS values than the remote region (61.12±13.65% vs.13.43±5.00%,
p=0.018; 44.62±21.40 mL·g-1·min-1 vs. 0.42±0.55 mL·g-1·min-1,
p=0.018). The dDCE5min map values in each region showed no
significant difference compared to dDCE30min (Figure 2B).
Representative LGEstandard images and dDCE5min images presented in Figure 3A show high agreement in the presence of MI and
microvascular obstruction. Bland-Altman analysis showed good agreement between
LGEstandard images and the dDCE5min images for infarct
area (bias, -1.74 ± 6.60 %, Figure 3B) and transmuraltiy (bias, 1.86 ± 2.73%,
Figure 3C). The linear regression revealed strong correlations between the
LGEstandard images and the dDCE5min images for infarct
area (R2, 0.95; slope, 0.93, p < 0.01; intercept, 0.11%, p = 0.692;
Figure 3D) and transmurality (R2, 0.97; slope, 0.93, p < 0.01;
intercept, 5.50%; p = 0.05; Figure 3E). ROC analysis showed that the AUC was 0.97 (95%
CI: 0.94 to 1.00) (Figure 3F). In addition, we observe an improved
lesion-blood pool contrast in dDCE images. This is important for evaluating
subendocardial MI, which was previously difficult to evaluate in LGEstandard
images due to its close signal intensity to the blood pool. dDCE CMR can now be
identified with strong image contrast in the ve map and synthesized
late gadolinium enhancement image with prolonged washout time using dDCE5min
maps (Figure 4).Discussion
The ve(extravascular extracellular volume) and PS(permeability-surface area) measured on dDCE maps were significantly higher
in the MI than the remote, which demonstrated an increase in extravascular
extracellular space (EES) or fibrosis4 and vascular permeability5 in the injured myocardium. The remote ve
and PS values were within previously reported value ranges6-8. The lack of significant
difference between the dDCE5min and dDCE30min maps
implied that the dDCE5min map may provide comparative ve
and PS information in 5 minutes after contrast medium administration. The visual
and quantitative evaluation of MI showed a high correlation between LGEstandard
imaging and LGEdDCE imaging, which was synthesized from the dDCE5min
map. The highly similar LGEdDCE images between LGEstandard indicated that the ischemic
injury may be confidently evaluated in a shortened post-contrast wait time. In
cases where small subendocardial lesions are being evaluated, the close T1
value between the lesion and blood has been a long-standing issue for standard
LGE imaging. This may result in an underestimation of MI or a false negative
diagnosis. Because dDCE CMR can measure the EES, it provides extracellular contrast not confounded by the blood
pool signal. This improves subendocardial MI detection and prevents missing
small lesions that are clinically important.Conclusions
The
developed dDCE CMR technique shows comparable MI detection ability to standard LGE without the prolonged wait time. It can address the major
drawbacks of conventional LGE CMR and provide a rapid and quantitative
myocardial viability evaluation with boosted lesions-blood contrast. Acknowledgements
Hsin-Jung Yang and Rohan Dharmakumar contributed equally to this work. This work is supported by 1R01HL136578; 1R01HL165211; 1R01HL148788; 1R01HL156818. References
1. Aquaro GD, De Gori
C, Faggioni L, Parisella ML, Cioni D, Lencioni R, Neri E. Diagnostic and
prognostic role of late gadolinium enhancement in cardiomyopathies. Eur Heart J Suppl. 2023;25:C130-c136.
doi: 10.1093/eurheartjsupp/suad015
2. Alba AC, Gaztañaga
J, Foroutan F, Thavendiranathan P, Merlo M, Alonso-Rodriguez D, Vallejo-García
V, Vidal-Perez R, Corros-Vicente C, Barreiro-Pérez M, et al. Prognostic Value
of Late Gadolinium Enhancement for the Prediction of Cardiovascular Outcomes in
Dilated Cardiomyopathy. Circulation:
Cardiovascular Imaging. 2020;13. doi: 10.1161/circimaging.119.010105
3. Kuruvilla S, Adenaw N, Katwal AB, Lipinski MJ, Kramer CM, Salerno M.
Late Gadolinium Enhancement on Cardiac Magnetic Resonance Predicts Adverse
Cardiovascular Outcomes in Nonischemic Cardiomyopathy. Circulation: Cardiovascular Imaging. 2014;7:250-258. doi:
10.1161/circimaging.113.001144
4. Croisille
P, Revel D, Saeed M. Contrast agents and cardiac MR imaging of myocardial
ischemia: from bench to bedside. European
Radiology. 2006;16:1951-1963. doi: 10.1007/s00330-006-0244-z
5. Murakami
M, Simons M. Regulation of vascular integrity. Journal of Molecular Medicine. 2009;87:571-582. doi:
10.1007/s00109-009-0463-2
6. Haunsø
S, Paaske WP, Sejrsen P, Amtorp O. Capillary permeability in canine myocardium
as determined by bolus injection, residue detection. Acta Physiol Scand. 1980;108:389-397. doi:
10.1111/j.1748-1716.1980.tb06549.x
7. Overholser
KA, Bhatte MJ, Laughlin MH. Modeling the effect of flow heterogeneity on
coronary permeability-surface area. J
Appl Physiol (1985). 1991;71:758-769. doi: 10.1152/jappl.1991.71.2.758
8. Pack
NA, Dibella EV, Wilson BD, McGann CJ. Quantitative myocardial distribution
volume from dynamic contrast-enhanced MRI. Magn
Reson Imaging. 2008;26:532-542. doi: 10.1016/j.mri.2007.10.003