Yuesong Yang

Quantitative tracking of edema, hemorrhage, and microvascular obstruction in subacute myocardial infarction in a porcine model by MRI.

Pathophysiological responses after acute myocardial infarction include edema, hemorrhage, and microvascular obstruction along with cellular damage. The in vivo evolution of these processes simultaneously throughout infarct healing has not been well characterized. The purpose of our study was to quantitatively monitor the time course of these mechanisms by MRI in a porcine model of myocardial infarction. Ten pigs underwent MRI before coronary occlusion with subgroups studied at day 2 and weeks 1, 2, 4, and 6 post‐infarction. Tissue characterization was performed using quantitative T2 and T2* maps to identify edema and hemorrhage, respectively. Contrast‐enhanced MRI was used for infarct/ microvascular obstruction delineation. Inflammation was reflected by T2 fluctuations, however at day 2, edema and hemorrhage had counter‐acting effects on T2. Hemorrhage (all forms) and mineralization (calcium) could be identified by T2* in the presence of edema. Simultaneous resolution of microvascular obstruction and T2* abnormality suggested that the two phenomenon were closely associated during the healing process. Our study demonstrates that quantitative T2 and T2* mapping techniques allow regional, longitudinal, and cross‐subject comparisons and give insights into histological and tissue remodeling processes. Such in vivo characterization will be important in grading severity and evaluating treatment strategies for myocardial infarction, potentially improving clinical outcomes. Magn Reson Med, 2011.

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI

Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 +/- 1.5 to 4.9 +/- 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 +/- 2.1 to 4.39 +/- 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 +/- 5.2% preinjection to 34.5 +/- 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 +/- 4.7 to 31.9 +/- 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.

Correlation of late gadolinium enhancement MRI and quantitative T2 measurement in cardiac sarcoidosis

To investigate the potentially improved detection and quantification of cardiac involvement using novel late‐gadolinium‐enhancement (LGE) cardiac magnetic resonance imaging (MRI) and quantitative T2 measurement to achieve better myocardial tissue characterization in systemic sarcoidosis.

Myocardial BOLD imaging at 3 T using quantitative T2: application in a myocardial infarct model.

Left ventricular remodeling as a result of acute myocardial infarction (AMI) is associated with significant morbidity, leading to cardiovascular dysfunction, disability, and death. Despite successful revascularization, coronary vasodilatory dysfunction has been shown in infarcted and remote myocardium of patients following AMI. Our study explored the utility of a T2‐based blood‐oxygen‐level‐dependent approach in probing regional and longitudinal fluctuations in vasodilatory function in a porcine model of AMI at 3 T. Ten pigs underwent MRI in control state and at day 2, weeks 1–6 following 90 min occlusion followed by reperfusion. The remote myocardium exhibited vasodilatory dysfunction at weeks 1 and 2 that gradually recovered, whereas the infarct zone showed no vasodilatory alterations. Our study suggests that microvascular alterations occurring in infarcted and remote myocardium after AMI might serve as an indicator of adverse left ventricular remodeling. The blood‐oxygen‐level‐dependent technique using quantitative T2 could potentially be a useful noninvasive tool to evaluate novel therapeutic strategies aimed at limiting vasoconstriction and improving coronary flow reserve after AMI. Magn Reson Med, 2011.

Magnetic resonance estimates of the extent and heterogeneity of scar tissue in ICD patients with ischemic cardiomyopathy predict ventricular arrhythmia

BACKGROUND The majority of patients receiving implantable cardioverter-defibrillator (ICD) implantation under current guidelines never develop sustained ventricular arrhythmia; therefore, better markers of risk for sustained ventricular tachycardia and/or ventricular fibrillation are needed. OBJECTIVE The purpose of this study was to identify cardiac magnetic resonance arrhythmic risk predictors of ischemic cardiomyopathy before ICD implantation. METHODS Forty-three subjects (mean age, 64.5 ± 11.9 years) with previous myocardial infarction who were referred for ICD implantation were evaluated by cardiac magnetic resonance imaging (MRI). The MRI protocol included left ventricular functional parameter assessment using steady-state free precession and late gadolinium enhancement MRI using inversion recovery fast gradient echo. Left ventricular functional parameters were measured using cardiac magnetic resonance software. Subjects were followed up for 6-46 months, and the events of appropriate ICD treatments (shocks and antitachycardia pacing) were recorded. RESULTS Twenty-eight patients experienced 46 spontaneous episodes during a median follow-up duration of 30 months. The total myocardial infarct (MI) size (18.05 ± 11.44 g vs 38.83 ± 19.87 g; P = .0006), MI core (11.63 ± 7.14 g vs 24.12 ± 12.73 g; P = .0002), and infarct gray zone (6.43 ± 4.64 g vs 14.71 ± 7.65 g; P = .0004) were significantly larger in subjects who received appropriate ICD therapy than in those who did not experience an episode of ventricular tachycardia and/or ventricular fibrillation. Multivariate regression analyses for the infarct gray zone and MI core adjusted for New York Heart Association class, diabetes, and etiology (primary or secondary prevention) revealed that the gray zone and MI core were predictors of appropriate ICD therapies (P = .0018 and P = .007, respectively). CONCLUSION The extent of MI scar may predict which patients would benefit most from ICD implantation.

Papillary muscle involvement in myocardial infarction: Initial results using multicontrast late‐enhancement MRI

We hypothesized that multicontrast late‐enhancement (MCLE) MRI would improve the identification of papillary muscle involvement (PM‐MI) in patients with myocardial infarction (MI), compared with conventional late gadolinium enhancement (LGE) MRI using the inversion recovery fast gradient echo (IR‐FGRE) technique. Cardiac LGE‐MRI studies using both MCLE and IR‐FGRE pulse sequences were performed on a 1.5 Tesla (T) MRI system in 23 patients following MI. In all patients, PM‐MI was confirmed by the diagnostic criteria as outlined below: (a) the increased signal intensity of PM was the same or similar to that of adjacent hyper‐enhanced left ventricular (LV) infarct segments; and (b) the hyper‐enhanced PM region was limited to the PM area defined by precontrast cine images of steady‐state free precession (SSFP). Visual contrast score was rated according to the differentiation between LV blood pool and hyper‐enhanced infarct myocardium. Quantitative contrast‐noise ratios (CNR) of infarct relative to blood pool and viable myocardium were also measured on MCLE and IR‐FGRE images. Of these 23 patients, 13 studies demonstrated primarily involvement of the territories of the right coronary (RCA, 8 patients) and/or left circumflex (LCX, 5 patients) arteries and 10 involved the territories of left anterior descending artery (LAD) with some LCX involvement. Although both IR‐FGRE and MCLE determined the presence and extent of LV MI, better visual contrast scores were achieved in MCLE (2.9 ± 0.3) compared with IR‐FGRE (1.6 ± 0.8, P < 0.001). The CNRs of infarct relative to LV blood pool showed a significant statistical difference (n = 23, P < 0.00001) between MCLE (16.2 ± 7.2) and IR‐FGRE images (4.8 ± 4.1), which is consistent with the result of visual contrast scores between infarct and LV blood pool. The CNRs of infarct versus viable myocardium did not demonstrate a significant statistical difference (n = 23, P = 0.61) between MCLE (14.4 ± 7.0) and IR‐FGRE images (13.6 ± 6.1). MCLE clearly demonstrated PM‐MI in all cases (100%, 23/23) while only 39% ( 9/23 ) could be visualized on the corresponding IR‐FGRE images. In conclusion, MCLE imaging provides better contrast between blood pool and infarct myocardium, thus improving the determination of PM‐MI. J. Magn. Reson. Imaging 2011;33:211–216.

Noninvasive quantitative measurement of myocardial and whole-body oxygen consumption using MRI : initial results

The purpose of this study was to investigate the feasibility of a noninvasive approach that combines magnetic resonance imaging (MRI) oximetry and flow measurement to obtain the oxygen consumption in the myocardium and in the whole body. Thirteen healthy male volunteers [mean (+/-S.D.) age: 35+/-7 years] underwent this MR study, which included myocardial oxygen consumption (MVO(2)) measurements in 11 subjects and whole-body oxygen consumption (VO(2)) measurements in 8 subjects. In six subjects, both measurements were obtained. Five subjects had repeated MRI measurements of global MVO(2) in order to verify the reproducibility of this approach. The protocol included in vitro blood sample T(2)-%O(2) calibration, coronary sinus (CS) and main pulmonary artery (MPA) T(2) and phase contrast flow measurement and left ventricular (LV) mass calculation. Based on Ficks law, a global measurement of LV MVO(2) and whole-body VO(2) using MRI was feasible. The MVO(2) values were 11+/-3 ml/min per 100 g LV mass. For repeated measurements, differences in MVO(2) of 1 ml/min per 100 g LV mass appear detectable. The whole-body VO(2) values were 3.8+/-0.8 ml/min/kg body weight. MRI techniques that combine CS and MPA T(2), flow and LV mass measurements to quantify MVO(2) and whole-body VO(2) noninvasively in healthy subjects appear feasible, based on their correspondence to previously published work.

MRI evaluation of microvascular obstruction in experimental reperfused acute myocardial infarction using a T1 and T2 preparation pulse sequence

To investigate a T1 and T2 preparation pulse sequence to evaluate microvascular obstruction (MO) in a porcine model of reperfused acute myocardial infarction (AMI).

MRI manifestations of persistent microvascular obstruction and acute left ventricular remodeling in an experimental reperfused myocardial infarction

PURPOSE To investigate varied manifestations of persistent microvascular obstruction (PMO) and acute left ventricular (LV) remodeling in an experimental reperfused myocardial infarction (MI) using MRI. METHODS In eleven Yorkshire pigs an acute MI was produced through a 90-minute balloon occlusion of the middle left anterior descending coronary artery, followed by reperfusion. All animals underwent MRI examinations on a 1.5T system including a SSFP functional study, first pass myocardial perfusion (FPMP), T1 preparation Look-Locker and delayed contrast-enhanced MRI (DE-MRI). Imaging was performed immediately post-intervention (day 0) and at days 7-9. In four animals a repeat MRI examination was performed at day 2 as well. Upon study completion, animals underwent histological analysis including infarct assessment with triphenyltetrazolium chloride (TTC). RESULTS Following reperfusion, Thrombolysis In Myocardial Infarction (TIMI) Flow grade 3 was achieved in all animals, demonstrated by repeat angiography following balloon deflation (day 0). Various MR appearances of PMO were noticed including predominance in the subendocardial region, a central core within the infarcted tissue and also multiple separate clusters. In ten of eleven animals PMO was demonstrated as a persistent hypo-enhanced area in FPMP and DE-MRI, and identified as bright regions in later T1 difference images. In one animal PMO was identified only at day 2. At day 7-9 PMO could be identified on early DE-MRI at 5-15 minutes post Gd injection but not on late DE-MRI and T1 difference images after 45-60 minutes post-contrast. A larger volume of PMO and MI at day 2 was noted in comparison to data from day 0 but the difference was not statistically significant. An increased end-diastolic LV volume (EDV) without changes in end-systolic LV volume (ESV) and LV mass at end-diastolic phase (LVM) was observed at day 7-9 in comparison to data from day 0. There was good correlation between the relative extent of persistent MO in the infarcted myocardium (% MO/MI) and EDV at day 7-9 (r=0.83, n=10, P=0.003). MI was confirmed in all animals by TTC staining and/or histology. CONCLUSION A variable MR appearance of persistent microvascular obstruction is observed during a short time course MRI study of reperfused acute MI. Acute negative LV remodeling was closely related to the relative extent of persistent microvascular obstruction within the infarct myocardium.

Characterization of Post-infarct Scars in a Porcine Model --- A Combined Experimental and Theoretical Study

Arrhythmias are often associated with healing infarcts and could arise from the border zone of the scars. The main purpose of this work was to characterize the infarct scars using in vivo electro-anatomic CARTO maps (recorded in sinus rhythm) and high-resolution ex-vivo MR images in a porcine model of chronic infarct. The MR images were segmented into scar, peri-infarct and healthy ventricular tissue, and, in select slices, the results of segmentation were validated against histology. Further, the segmented volumes and associated fiber directions (derived from diffusion-weighted (DW) MRI as well as from synthetic models), were used as input to a simple two-variable mathematical model that calculates the propagation of depolarization waves and isochronal maps; and these isochronal maps were compared to the measured ones. We further correlated the size of the scar measured during the electrophysiology (EP) study with scar dimensions obtained from MRI using ex-vivo DW-MRI methods. Finally, we present preliminary results from a qualitative comparison between the scar delineation from ex vivo and in vivo MR images.