Characterization of myocardial ischemia-reperfusion injury in a pig model with novel CW T1r and RAFF2 MRI methods in 1.5T
Authors: Yla-Herttuala E , Kiviluoto R , Husso M , Liukkonen M , Tietavainen S , Puimalainen S , Wang H , Maatta A , Liljestrom J , Kuivalainen J , Heikkila M , Ruotsalainen A K , Yla-Herttuala S 
Published: October 2024

Abstract

Introduction
Myocardial ischemia-reperfusion injury (IRI) occurs after myocardial infarction when reperfusion aggravates the initial damage in myocardium by vast infiltration of inflammatory cells and elevated oxidative stress in myocardium that may lead to cardiac remodeling, heart failure and even death [1]. Magnetic resonance imaging (MRI) can accurately determine the anatomy of the heart and to characterize myocardial tissue. Novel endogenous rotating frame MRI methods, including continuous wave (CW) T1r and relaxation along a fictitious field with rank 2 (RAFF2), have been shown to characterize MI and other CVD in mouse and human myocardium with high sensitivity and specificity [2,3]. CW T1r and RAFF2 contrasts are occurring during radio frequency (RF) pulse (in kHz range) making them to be sensitive to slow molecular motions [2]. Comparing to conventional endogenous T1 and T2 methods, these are occurring after the RF pulse (in Larmor frequency (MHz) range) and therefore, these are non-selectively sensitive to different correlation times [4]. Golden standard to image MI is to use contrast agent (CA) in late gadolinium enhancement (LGE) method [2,4]. Using CA has drawbacks and therefore, there is an urgent need for optimizing the endogenous MRI methods in clinical practice.

Purpose
To characterize myocardial IRI in a pig model and to determine the sensitivity of both novel and conventional cardiac MRI methods.

Methods
IRI operation was done in 7 pig (30-35 kg) by occluding the LAD with a balloon catheter for 50 minutes. Imaging was done with 1.5T (MAGNETOM Aera) at 3 days and 28 days after the operation. Pig hearts were imaged with conventional native T1, T2, LGE, and with novel CW T1r and RAFF2 methods in both time points. These were imaged before CA injection and LGE was done 25 minutes after CA injection. Relaxation time mappings were done in a pixel-by-pixel manner with monoexponentially fitting. Region-of-interest (ROI) analysis was done to determine the relaxation times in IRI and remote areas. LGE was used to confirm the IRI areas in the myocardium. Relative relaxation time difference (RRTD)-values were calculated with the function of (((Relaxation Time of IRI area) – (Relaxation Time of Remote Area))/ (Relaxation Time of Remote Area)) to determine the contrast difference between IRI and remote areas.

Results
Relaxation times were elevated in IRI areas compared to remote areas (Figure 1A). Novel rotating frame RRTD-values were significantly higher than RRTD-values in conventional methods. This means that novel methods have larger contrast difference between IRI and remote areas compared to conventional methods, which indicates that novel methods are sensitive to characterize IRI area (Figure 1B). The location of MI areas was similar in both novel rotating frame and conventional methods compared to LGE (Figure 2).

Conclusion
Novel rotating frame relaxation time methods are sensitive to characterize the IRI area in pig model.Relaxation times, RRTD-valuesRelaxation times maps and LGE