Non-contrast Vasodilatory Response Assessment in a porcine model of Acute Myocardial Infarction using Arterial Spin Labeled CMR
Hung Phi Do1, Venkat Ramanan2, Graham A Wright2,3, Nilesh R Ghugre2,3, and Krishna S Nayak4

1Department of Physics and Astronomy, University of Southern California, Los Angeles, CA, United States, 2Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada, 3Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, 4Ming Hsieh Department of Electrical Engineering, University of Southern California, Los Angeles, CA, United States


Myocardial vasodilatory response is an important indicator of microvascular function and viability. Arterial spin labeled (ASL) CMR is a non-contrast method that can quantify myocardial blood flow making it attractive to study vasodilatory response. In this work, we demonstrate the feasibility of ASL in the assessment of regional vasodilatory response in a porcine model of acute myocardial infarction (AMI) using a pharmacological stress agent. Quantitative monitoring of microvascular function in the infarcted, salvageable and remote myocardial territories may potentially help identify patients who are prone to adverse long-term remodeling post-AMI.


Following acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilatory dysfunction.1-3 It has been observed that both infarct and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with abnormal vasodilatory response.4 Arterial spin labeled CMR (ASL-CMR) is a non-contrast MR based technique that can quantify myocardial perfusion.5-7 This study aims to investigate the feasibility of ASL-CMR in the quantitative assessment of myocardial blood flow and vasodilator response in the infarct and remote myocardial territories following AMI in a porcine model of ischemic injury.


Our Institute’s Animal Care Committee approved the protocol. The porcine AMI model involved a 90 min left anterior descending (LAD) artery occlusion followed by reperfusion. Animals underwent a CMR examination on a 3T scanner (MR750, GE Healthcare) at baseline (N=7, healthy state) and post-AMI (N=3, week 1 and week 4). The imaging protocol involved ASL-CMR, first-pass perfusion, and late gadolinium enhancement (LGE) imaging. ASL-CMR was performed using our investigational pulse sequence 7 that uses flow-sensitive alternating inversion recovery (FAIR) labeling and steady state free precession (SSFP) image acquisition (parameters: TE/TR=1.5/3.2ms, FA = 50o, slice thickness = 10mm, FOV=18-24cm, matrix size of 96x96, parallel imaging factor of 2). ASL-CMR was performed on one (3 animals) and two (7 animals) mid-ventricular slices at the infarct location resulting in 12 slices at baseline and 5 slices at post-AMI. The ASL scan was repeated following an intravenous injection of Dipyridamole (0.56 mg/kg over 4 min) to assess vasodilatory function. Finally, first-pass perfusion and (LGE) imaging were performed using product sequences following injection of gadolinium-DTPA (Magnevist, 0.2 mmol/kg) to identify perfusion abnormalities and the infarcted tissue; LGE was initiated at 8 min post-injection. ASL-CMR was analyzed in a manner previously described7 to obtain global and per-segment myocardial blood flow (MBF), physiological noise (PN), and myocardial perfusion reserve (MPR=MBFstress/MBFrest); values were reported as mean±SD. Segments with temporal signal-to-noise ratio (tSNR=MBF/PN) < 2 were excluded from analysis.


Figure 1 shows myocardial ASL maps at rest and during stress in comparison with first-pass CMR and LGE. Area with low perfusion at rest and during stress (arrows) are in good agreement with perfusion deficit in first-pass perfusion and MVO in LGE.

Figure 2 shows global MBF and MPR at baseline and post-AMI. Global stress MBF values were significantly elevated compared to rest at both baseline (resting MBF = 0.99 ± 0.28 and stress MBF = 1.52 ± 0.29 ml/g/min, p< 0.001) and post-AMI (rest MBF = 0.62 ± 0.18 and stress MBF = 1.19 ± 0.44, p < 0.001). When compared between baseline and post-AMI, global rest MBF (baseline MBF = 0.99 ± 0.28 and post-AMI MBF = 0.62 ± 0.18, p = 0.02) was significantly different, stress MBF (baseline MBF = 1.30 ± 0.33 and post-AMI MBF = 1.22 ± 0.40, p = 0.08) and MPR (baseline MPR = 1.62 ± 0.46 and post-AMI MPR = 1.96 ± 0.72, p = 0.26) were not significantly different.

Differences in regional flow and stress patterns were apparent. Figure 3 shows regional MBF from remote and infarcted segments at rest and stress. Resting MBF in the infarcted territory was significantly depressed when compared to baseline values (post-AMI MBF = -0.06 ± 0.24 and baseline MBF = 0.85 ± 0.28 ml/g/min with p<0.001) indicative of severe microvascular damage. Under stress conditions, the infarcted region showed a marginal vasodilatory response (resting MBF = -0.06 ± 0.24 and stress MBF = 0.56 ± 0.08, p <0.001) potentially indicative of vascular activity in the salvageable myocardium; this response was however less than that at baseline (baseline stress MBF = 1.45 ± 0.31 and post-AMI stress MBF = 0.56 ± 0.08, p <0.001).

Interestingly, resting MBF in the remote myocardium post-AMI was also compromised when compared to baseline (baseline resting MBF = 1.05 ± 0.44 and post-AMI resting MBF = 0.55 ± 0.18 ml/g/min, p=0.03) potentially indicative of vasoconstriction (neurosympathetic or due to edema). With stress, the remote tissue post-AMI appeared to respond very similar to baseline (baseline stress MBF = 1.62 ± 0.46 and post-AMI stress MBF = 1.48 ± 0.67, p=0.61) possibly due to a compensatory mechanism.


Our study demonstrates the feasibility of ASL-CMR in the assessment of regional and serial vasodilatory response following acute myocardial infarction. ASL-CMR could potentially be a useful non-contrast imaging tool to detect and monitor microvascular function not only in the infarcted region but also the salvageable and remote regions, which may be early indicators of downstream adverse remodeling processes post-injury.


The Ontario Research Fund; American Heart Association 13GRNT13850012; Wallace H. Coulter Foundation Clinical Translational Research Award.


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5. Zun Z et al., Magn Reson Med. 2009; 62(4):975-83.

6. Zun Z et al., iJACC. 2011; 4(12):1253-61.

7. Do HP et al., J Cardiovasc Magn Reson. 2014; 16:15.


Figure 1: Myocardial ASL at rest and stress, first-pass CMR, and LGE from a representative animal.

Figure 2: (A) MBF at rest and stress and (B) MPR at baseline and post AMI. Baseline and post-AMI both shows significant elevation in MBF during vasodilation (p<0.001). At rest, MBF is significantly higher in baseline compared to post-AMI (0.02). NS = Not Significant.

Figure 3: Regional MBF at rest and stress in the infarcted (mid anteroseptal) (A) and remote (mid inferior+mid inferolateral+mid anterolateral) (B) regions at baseline and post AMI.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)