Myocardial viability of the peri-infarct region measured by T1 mapping post manganese-enhanced MRI correlates with LV dysfunction

Abstract

Background: Manganese-enhanced MRI (MEMRI) detects viable cardiomyocytes based on the intracellular manganese uptake via L-type calcium-channels. This study aimed to quantify myocardial viability based on manganese uptake by viable myocardium in the infarct core (IC), peri-infarct region (PIR) and remote myocardium (RM) using T1 mapping before and after MEMRI and assess their association with cardiac function and arrhythmogenesis. Methods: Fifteen female swine had a 60-minute balloon ischemia-reperfusion injury in the LAD. MRI (Signa 3T, GE Healthcare) and electrophysiological study (EPS) were performed 4 weeks later. MEMRI and delayed gadolinium-enhanced MRI (DEMRI) were acquired on LV short axis. The DEMRI positive total infarct area was subdivided into the regions of MEMRI-negative nonviable IC and MEMRI-positive viable PIR. T1 mapping was performed to evaluate native T1, post-MEMRI T1, and delta R1 (R1 post-R1 pre , where R1 equals 1/T1) of each territory. Their correlation with LV function and EPS data was assessed. Results: PIR was characterized by intermediate native T1 (1530.5±75.2ms) compared to IC (1634.7±88.4ms, p=0.001) and RM (1406.4±37.9ms, p<0.0001). Lower post-MEMRI T1 of PIR (1136.3±99.6ms) than IC (1262.6±126.8ms, p=0.005) and higher delta R1 (0.23±0.08 s −1) of PIR than IC (0.18±0.09 s −1 , p=0.04) indicated higher myocardial manganese uptake of PIR compared to IC. Post-MEMRI T1 (r=−0.57, p=0.02) and delta R1 (r=0.51, p=0.04) of PIR correlated significantly with LVEF. Conclusions: PIR is characterized by higher manganese uptake compared to the infarct core. In the subacute phase post-IR, PIR viability measured by post-MEMRI T1 correlates with cardiac function.

Assessment of Cardiac Toxicity of Manganese Chloride for Cardiovascular Magnetic Resonance

“…Indeed, assessing myocardial viability can be assessed as only living cells will uptake manganese via L-type Ca 2+ channel. MEMRI has been used at the pre-clinical level to allow quantification of infarcted area in animal models ranging from mouse to pig ( Daire et al, 2008 ; Dash et al, 2011 ; Tada et al, 2019 ; Jasmin et al, 2021 ; Spath et al, 2021 ). Recently, two clinical trials were initiated to evaluate MEMRI in various types of cardiomyopathies.…”

“…Recently, cardiac MRI using manganese have started in animals but also in humans in clinical trials ( Daire et al, 2008 ; Dash et al, 2011 ; Tada et al, 2019 ; Jasmin et al, 2021 ; Spath et al, 2021 ). It is therefore crucial to investigate the possible cardiac toxicity of manganese.…”

Spatiotemporal single-cell analysis reveals critical roles of mechano-sensing genes at the border zone in remodeling after myocardial infarction

“…In the present study, we comprehensively investigated the spatiotemporal gene expression of the heart after MI and identi ed several gene programs which were precisely regulated in a spatiotemporal manner. It has been well known that LV remodeling after MI including expansion of the BZ causes LV dysfunction and dilatation, resulting in heart failure 17,18 . However, the cellular and molecular mechanisms underlying remodeling processes in the BZ remain unclear.…”

T1 Mapping for Quantifying Myocardial Viability in the Peri-Infarct Regions

“…Furthermore, the rapid first pass uptake of manganese by the cardiomyocytes measures the R1 change (delta R1) before and after MEMRI to represent the specific viability of the cardiomyocytes [20,21]. Thus, myocardial injury in the heterogeneous infarct zones can be assessed based on the differential myocardial cellular viability using T1 mapping before and after MEMRI [22]. The LAD IR injury model was created in a swine and MRI was performed 4 weeks later.…”