Major prognostic impact of persistent microvascular obstruction as assessed by contrast-enhanced cardiac magnetic resonance in reperfused acute myocardial infarction

The aim of this study was to compare the prognostic significance of microvascular obstruction (MO) and persistent microvascular obstruction (PMO) as assessed by cardiac magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). CMR was performed in 184 patients within the week following successfully reperfused first AMI. First-pass images were performed to evaluate extent of MO and late gadolinium-enhanced images to assess PMO and infarct size (IS). Major adverse cardiac events (MACE) were collected at 1-year follow-up. MO and PMO were found in 127 (69%) and 87 (47%) patients, respectively. By using univariate logistic regression analysis, high Global Registry of Acute Coronary Events (GRACE) risk score (odds ratio [OR] 95% confidence interval [CI]: 3.6 [1.8–7.4], p < 0.001), IS greater than 10% (OR [95% CI]: 2.7 [1.1–6.9], p = 0.036), left ventricular ejection fraction less than 40% (OR [95% CI]: 2.4 [1.1–5.2], p = 0.027), presence of MO (OR [95% CI]: 3.1 [1.3–7.3], p = 0.004) and presence of PMO (OR [95% CI]:10 [4.1–23.9], p < 0.001) were shown to be significantly associated with the outcome. By using multivariate analysis, presence of MO (OR [95% CI]: 2.5 [1.0–6.2], p = 0.045) or of PMO (OR [95% CI]: 8.7 [3.6–21.1], p < 0.001), associated with GRACE score, were predictors of MACE. Presence of microvascular obstruction and persistent microvascular obstruction is very common in AMI patients even after successful reperfusion and is associated with a dramatically higher risk of subsequent cardiovascular events, beyond established prognostic markers. Moreover, our data suggest that the prognostic impact of PMO might be superior to MO.     

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. © 2011 Wiley‐Liss, Inc.     

Blood pool contrast-enhanced MRI detects suppression of microvascular permeability in early postinfarction reperfusion after nicorandil therapy.

Nicorandil is an adenosine triphosphate-sensitive potassium channel opener with a nitrate-like effect. It is approved for clinical use in Europe and Japan as an antianginal drug. The purpose of this investigation was to assess the acute effects of nicorandil therapy on microvascular injury using the blood pool MR contrast medium, NC100150 injection (Clariscan). Microvascular injury was produced in 24 rats using 45 min of coronary occlusion / 3 hr reperfusion. Nicorandil was infused at 15 min of occlusion and during reperfusion. Control animals received a saline solution. MR imaging was used to characterize microvascular permeability, quantify the extent of microvascular injury, LV volume, and wall thickness. Hyperenhancement at 30 min after administration of 0.05 mmol/kg Clariscan mapped the extent of ischemia-induced loss of microvascular integrity. The accumulation of Clariscan in the injured region was significantly suppressed in nicorandil compared to control rats. Nicorandil reduced the extent of microvascular injury from 44 +/- 2% to 18 +/- 2% (P < 0.01) and true infarction size from 29 +/- 2% to 12 +/- 1%. The extent of the hyperenhanced region correlated with the true size of area at risk at autopsy. On spin-echo MRI during end-diastole, nicorandil reduced LV end-diastolic volume and preserved wall thickness in remote myocardium; both parameters are markers of LV dilatation caused by acute infarction (remodeling). In conclusion, blood pool contrast-enhanced MRI has the potential to depict and quantify the extent of microvascular permeability and injury. Nicorandil suppressed microvascular permeability, reduced infarction size, and improved LV function in early postinfarction reperfusion.     

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.     

Serial MRI evaluation of cardiac structure and function in mice after reperfused myocardial infarction.

This study evaluated the utility of cardiac MRI for assessing the impact of myocardial infarction (MI) on cardiac structure and function in mice following reperfused 1- or 2-hr occlusions of the left anterior descending coronary artery (LAD). When assessed 1 day after MI, the left ventricular ejection fraction (LVEF) had declined by more than half, and remained depressed for the duration of the study. Furthermore, MI initiated dramatic increases in both LV end-systolic volume (LVESV) and end-diastolic volume (LVEDV), with a greater than threefold increase in LVESV and a twofold increase in LVEDV by 4 weeks post-MI. Transmural LV wall thickening (WTh) analysis revealed that noninfarcted myocardium in the remote septal region exhibited an early deficit in contractile function after MI that transiently resolved by day 7, only to be followed by a late phase of dysfunction that became fully manifest by day 28 post-MI. In conclusion, MRI allows the serial assessment of cardiac structure and function after MI in mice, with a resolution adequate to document both regional and temporal changes. The application of these imaging techniques in transgenic and knock-out mice will greatly expedite research aimed at defining the functional roles of individual genes in the pathophysiology of LV remodeling (LVR) after reperfused MI.     

Evaluation of heart perfusion in patients with acute myocardial infarction using dynamic contrast-enhanced magnetic resonance imaging

PURPOSE: To investigate the diagnostic ability of quantitative magnetic resonance imaging (MRI) heart perfusion in acute heart patients, a fast, multislice dynamic contrast-enhanced MRI sequence was applied to patients with acute myocardial infarction. MATERIALS AND METHODS: Seven patients with acute transmural myocardial infarction were studied using a Turbo-fast low angle shot (FLASH) MRI sequence to monitor the first pass of an extravascular contrast agent (CA), gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Quantitation of perfusion, expressed as Ki (mL/100 g/minute), in five slices, each having 60 sectors, provided an estimation of the severity and extent of the perfusion deficiency. Reperfusion was assessed both by noninvasive criteria and by coronary angiography (CAG). RESULTS: The Ki maps clearly delineated the infarction in all patients. Thrombolytic treatment was clearly beneficial in one case, but had no effect in the two other cases. Over the time-course of the study, normal perfusion values were not reestablished following thrombolytic treatment in all cases investigated. CONCLUSION: This study shows that quantitative MRI perfusion values can be obtained from acutely ill patients following acute myocardial infarction. The technique provides information on both the volume and severity of affected myocardial tissue, enabling the power of treatment regimes to be assessed objectively, and this approach should aid individual patient stratification and prognosis.     

Histologic confirmation of microvascular hyperpermeability to macromolecular MR contrast medium in reperfused myocardial infarction

A macromolecular MR contrast medium (MMCM) designed to permit histochemical staining and specific tissue localization, albumin-(biotin)10-(Gd-DTPA)25 (Bio-Alb-Gd), was used in a rat model of reperfused myocardial infarction to confirm the presence and distribution of microvascular hyperpermeability. T1-weighted spin-echo images were acquired before and after administration of Bio-Alb-Gd. An avidin-biotin-complex (ABC) stain, specific for the biotinylated MR contrast medium, was used to define the MMCM distribution and to detect any regional change in micro-vascular permeability related to infarction. Immediately after Bio-Alb-Gd administration, the infarcted region was enhanced, with greatest signal intensity noted at the rim and less at the center. There was a gradual increase in signal intensity of the initially hypointense central region. The steady increase in signal intensity of the central region suggested convection transport of MMCM through the interstitial space and its influx into cellular compartment after leakage from the vascular compartment. Histologic findings confirmed regional microvascular hyperpermeability corresponding to the site of infarction and a predominant rim distribution of the MMCM. Bio-Alb-Gd was identified at high microscopic power in the intravascular, interstitial, and intracellular spaces at the periphery of reperfused infarcted myocardium. Bio-Alb-Gd can be used as an MR contrast medium in reperfused infarcted myocardium to confirm the existence and to localize altered microvascular permeability to macromolecules. Bio-Alb-Gd contrast technique removes all the ambiguity between the distribution of the MR or other imaging contrast agent and the distribution of the substrate for histochemical staining.     

Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). ΔR1 was repeatedly measured over 30 min. Gd-BOPTA caused greater ΔR1 for blood and myocardium than did Gd-DTPA clearance of both agents from normal and infarcted myocardium was similar to blood clearance; plots of ΔR1myocardium/ΔR1blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater ΔR1 than Gd-DTPA in regions which contain serum albumin.     

Noninvasive quantification of total sodium concentrations in acute reperfused myocardial infarction using 23Na MRI.

The transport of sodium and potassium between the intra- and extracellular pools and the maintenance of the transmembrane concentration gradients are important to cell function and integrity. The early disruption of the sodium pump in myocardial infarction in response to the exhaustion of energy reserves following ischemia and reperfusion results in increased intracellular (and thus total) sodium levels. In this study a method for noninvasively quantifying myocardial sodium levels directly from sodium (23Na) MRI is presented. It was used to measure total myocardial sodium on a clinical 1.5T system in six normal dogs and five dogs with experimentally-induced myocardial infarction (MI). The technique was validated by comparing total sodium content measured by 23Na MRI with that measured by atomic absorption spectrophotometry (AAS) in biopsied tissue. Total sodium measured by 23Na MRI was significantly elevated in regions of infarction (81.3 +/- 14.3 mmol/kg wet wt, mean +/- SD) compared to noninfarcted myocardial tissue from both infarcted dogs (36.2 +/- 1.1, P < 0.001) and from normal controls (34.4 +/- 2.8, P < 0.0001). Myocardial tissue sodium content as measured by 23Na MRI did not vary regionally in the lateral, anterior, or inferior regions in normal hearts (ANOVA, P = NS). Sodium content measured by 23Na MRI agreed with the mean AAS estimates of 31.3 +/- 5.6 mmol/kg wet wt (P = NS) in normal hearts, and did not differ significantly from AAS measurements in MI (P = NS). Thus, local tissue sodium levels can be accurately quantified noninvasively using 23Na MRI in normal and acutely reperfused MI. The detection of regional myocardial sodium elevations may help differentiate viable from nonviable, infarcted tissue.     

Complementary displacement-encoded MRI for contrast-enhanced infarct detection and quantification of myocardial function in mice.

MRI is emerging as an important modality for assessing myocardial function in transgenic and knockout mouse models of cardiovascular disease, including myocardial infarction (MI). Displacement encoding with stimulated echoes (DENSE) measures myocardial motion at high spatial resolution using phase-reconstructed images. The current DENSE technique uses inversion recovery (IR) to suppress T(1)-relaxation artifacts; however, IR is ill-suited for contrast-enhanced infarct imaging in the heart, where multiple T(1) values are observed. We have developed a modified DENSE method employing complementary acquisitions for T(1)-independent artifact suppression. With this technique, displacement and strain are measured in phase-reconstructed images, and contrast-enhanced regions of infarction are depicted in perfectly coregistered magnitude-reconstructed images. The displacement measurements and T(1)-weighted image contrast were validated with the use of a rotating phantom. Modified DENSE was performed in mice (N = 9) before and after MI. Circumferential (E(cc)) and radial (E(rr)) strain were measured, and contrast-enhanced infarcted myocardium was detected by DENSE. At baseline, E(cc) was -0.16 +/- 0.01 and E(rr) was 0.39 +/- 0.07. After MI, E(cc) was 0.04 +/- 0.02 and E(rr) was 0.03 +/- 0.04 in infarcted regions, whereas E(cc) was -0.12 +/- 0.02 and E(rr) was 0.38 +/- 0.09 in noninfarcted regions. In vivo E(cc) as determined by DENSE correlated well with E(cc) obtained by conventional tag analysis (R = 0.90).     

Tissue characterization of myocardial infarction using T1rho: influence of contrast dose and time of imaging after contrast administration

PURPOSE: To determine whether contrast between acutely infarcted and normal myocardia in T1-rho-weighted cine TFE (T1rho-TFE) and delayed-enhancement (DE) images (measured using a metric percent enhancement (PE)) varied with the dose or time of imaging after contrast administration. MATERIALS AND METHODS: Eighteen patients with acute myocardial infarction (AMI) were randomly divided into three groups according to the dose of gadoversetamide (0.1, 0.2, or 0.3 mmol/kg) administered. After contrast administration, T1rho-TFE images were acquired at five and 40 minutes, and DE images were acquired at 10 and 30 minutes. RESULTS: For T1rho-TFE imaging the PE values at 40 minutes were 70+/-14, 98+/-14, and 105+/-41 at 0.1, 0.2, and 0.3 mmol/kg dose levels, which were significantly greater than the corresponding PEs at five minutes after contrast administration (44+/-12, 71+/-14, and 36+/-13). For DE and T1rho-TFE imaging the dose of contrast agent did not significantly affect the PE. However, with DE the PE tended to increase with the dose. At all dose levels, irreversible injury was more conspicuous in T1rho-TFE images acquired at 40 minutes than at five minutes after contrast. CONCLUSION: In T1rho-TFE, acute infarction was more conspicuous in images acquired at a later time point, and the PE did not vary with the contrast dose.     

Determining the extent to which delayed-enhancement images reflect the partition-coefficient of Gd-DTPA in canine studies of reperfused and unreperfused myocardial infarction.

MRI after a constant infusion (CI) of Gd-DTPA has been used to identify the extent of myocardial infarction (MI). However, Gd-DTPA-enhanced "viability" imaging is more commonly performed with a bolus (for "delayed-enhancement" (DE) imaging). This study sought to determine how image delay time and time postinfarction influence the assessment of necrosis by DE. Both infusion and DE imaging was performed in dogs with reperfused (N = 6) or unreperfused (N = 4) MI. Estimates of the partition-coefficient of Gd-DTPA (lambda) with DE were compared with those calculated after 60 min of infusion, and the comparisons were repeated until 4 (reperfused) or 8 (unreperfused) weeks postinfarction. In reperfused animals, the concordance (Rc) between DE and infusion estimates of lambda was > 0.90 for most image delays > 8 min postinjection, for day 0 through week 3, with Rc at day 0 greater than at week 4 (P = 0.022). In unreperfused animals, there was an interaction between image delay time and time postinfarction (P < 0.001): Rc > 0.90 corresponded to longer image delays at week 1 than at weeks 4-8. Therefore, when image delays are selected appropriately, DE images can strongly reflect lambda and identify irreversibly injured myocardium.     

Novel application of breath-hold turbo spin-echo T2 MRI for detection of acute myocardial infarction

To assess the clinical utility of the breath-hold turbo spin-echo T2-weighted MRI in patients with acute myocardial infarction, the results of MRI were compared with those of electrocardiography, coronary angiography, and thallium-201 single photon emission tomography (SPECT) in 23 patients and 5 healthy volunteers. To compare MRI and thallium-SPECT, the left ventricle was divided into five segments, and the presence of myocardial infarction was determined in each segment. MRI demonstrated an abnormally bright signal in 49 of 140 segments (five segments each from 23 patients and 5 volunteers); thallium-SPECT showed a fixed perfusion defect in 52 segments, for an 85% diagnostic concordance rate. The size of the myocardial infarction measured on MRI corresponded well to that measured on thallium-SPECT (r = .70, P < .01). Breath-hold turbo spin-echo T2 MRI can be used for detection of acute myocardial infarction in conjunction with thallium-SPECT, especially when accurate localization of lesion, increased spatial resolution, and anatomic landmarks are needed.     

T2-prepared SSFP improves diagnostic confidence in edema imaging in acute myocardial infarction compared to turbo spin echo.

T2-weighted MRI of edema in acute myocardial infarction (MI) provides a means of differentiating acute and chronic MI, and assessing the area at risk of infarction. Conventional T2-weighted imaging of edema uses a turbo spin-echo (TSE) readout with dark-blood preparation. Clinical applications of dark-blood TSE methods can be limited by artifacts such as posterior wall signal loss due to through-plane motion, and bright subendocardial artifacts due to stagnant blood. Single-shot imaging with a T2-prepared SSFP readout provides an alternative to dark-blood TSE and may be conducted during free breathing. We hypothesized that T2-prepared SSFP would be a more reliable method than dark-blood TSE for imaging of edema in patients with MI. In patients with MI (22 acute and nine chronic MI cases), T2-weighted imaging with both methods was performed prior to contrast administration and delayed-enhancement imaging. The T2-weighted images using TSE were nondiagnostic in three of 31 cases, while six additional cases rated as being of diagnostic quality yielded incorrect diagnoses. In all 31 cases the T2-prepared SSFP images were rated as diagnostic quality, correctly differentiated acute or chronic MI, and correctly determined the coronary territory. Free-breathing T2 prepared SSFP provides T2-weighted images of acute MI with fewer artifacts and better diagnostic accuracy than conventional dark-blood TSE.     

Detection of myocarditis by contrast-enhanced MRI in patients presenting with acute coronary syndrome but no coronary stenosis

PURPOSE: To prospectively assess the use of cardiac MRI with delayed contrast enhancement (DCE) for identifying patients with active myocarditis among those presenting with acute coronary syndrome (ACS) but no coronary stenosis. MATERIALS AND METHODS: A total of 27 consecutive patients (age = 45 +/- 17 years; 14 male) presenting with ACS (chest pain, positive troponin-I) and no coronary stenosis, underwent cardiac MRI 9 +/- 7 days after pain onset and 8 +/- 5 months later (N = 19). Steady-state free-precession pulse (SSFP) sequence was applied for the assessment of myocardial function and both inversion-recovery (IR) and SSFP sequences were used for analyzing the topography and extent of DCE areas. Rest sestamibi-gated-single photon emission CT (SPECT) was also systematically performed. RESULTS: Subepicardial DCE pattern typical of acute myocarditis was documented in 12 patients (44%). Ischemic DCE pattern (transmural or subendocardial focal DCE) was documented in 12 of the 15 remaining patients (44%). Patients with subepicardial DCE had: higher C-reactive protein (CRP) levels (38 +/- 32 vs. 14 +/- 24 mg/mL; P = 0.04), lower Framingham cardiovascular risk (3 +/- 3% vs. 9 +/- 5%; P < 0.001), lower incidence of perfusion SPECT defects (17% vs. 73%; P = 0.01), higher left ventricular (LV) end-diastolic volume (77 +/- 16 vs. 64 +/- 10 mL/m(2); P = 0.02), and higher regression of DCE areas at follow-up (-65 +/- 17% vs. -18 +/- 23%; P = 0.002). CONCLUSION: DCE pattern of active myocarditis can be seen in patients presenting with ACS but no coronary stenosis.     

Dynamic contrast-enhanced quantitative perfusion measurement of the brain using T1-weighted MRI at 3T

PURPOSE: To develop a method for the measurement of brain perfusion based on dynamic contrast-enhanced T(1)-weighted MR imaging. MATERIALS AND METHODS: Dynamic imaging of the first pass of a bolus of a paramagnetic contrast agent was performed using a 3T whole-body magnet and a T(1)-weighted fast field echo sequence. The input function was obtained from the internal carotid artery. An initial T(1) measurement was performed in order to convert the MR signal to concentration of the contrast agent. Pixelwise and region of interest (ROI)-based calculation of cerebral perfusion (CBF) was performed using Tikhonov's procedure of deconvolution. Seven patients with acute optic neuritis and two patients with acute stroke were investigated. RESULTS: The mean perfusion value for ROIs in gray matter was 62 mL/100g/min and 21 mL/100g/min in white matter in patients with acute optic neuritis. The perfusion inside the infarct core was 9 mL/100g/min in one of the stroke patients. The other stroke patient had postischemic hyperperfusion and CBF was 140 mL/100g/min. CONCLUSION: Absolute values of brain perfusion can be obtained using dynamic contrast-enhanced MRI. These values correspond to expected values from established PET methods. Furthermore, at 3T pixelwise calculation can be performed, allowing construction of CBF maps.