Maythem Saeed

Magnetic Resonance Characterization of the Peri-Infarction Zone of Reperfused Myocardial Infarction With Necrosis-Specific and Extracellular Nonspecific Contrast Media

Background —Because ischemically injured myocardium is frequently composed of viable and nonviable portions, a method to discriminate the two is useful for clinical management. Methods and Results —Ischemically injured myocardium was characterized with extracellular nonspecific (Gd-DTPA) and necrosis-specific (mesoporphyrin) MR contrast media in rats. Relaxation rates (R1) were measured on day 1 and day 2 by inversion-recovery echoplanar imaging. Spin-echo imaging was used to define contrast-enhanced regions and regional wall thickening. Gadolinium concentration, area at risk, and infarct size were measured at postmortem examination. &Dgr;R1 ratio (&Dgr;R1myocardium/&Dgr;R1blood) after administration of Gd-DTPA was greater in ischemically injured myocardium (1.20±0.15) than in normal myocardium (0.47±0.05, P <0.05), which was attributed to differences in gadolinium concentration and water content. The Gd-DTPA–enhanced region on day 2 was larger (32.8±0.9%) than true infarction as demonstrated by triphenyltetrazolium chloride (TTC) (24.6±1.4%, P <0.001, r =0.21). Bland-Altman analysis revealed that the Gd-DTPA–enhanced region overestimated true infarct size by 7.8±5.9%. On the other hand, the mesoporphyrin-enhanced region (26.9±1.8%, P =NS, r =0.87) and true infarct size were identical. The difference in the areas demarcated by the 2 agents is the peri-infarction. Systolic and diastolic MR images revealed no wall thickening in the mesoporphyrin-enhanced region (0.3±3.3%) but reduced thickening in the Gd-DTPA–enhanced rim (8.5±5.5%, P <0.05). Conclusions —The Gd-DTPA–enhanced region encompasses both viable and nonviable portions of the ischemically injured myocardium. The Gd-DTPA–enhanced area overestimated infarct size, but the mesoporphyrin-enhanced area matched true infarct size. The salvageable peri-infarction zone can be characterized with double-contrast–enhanced and functional MR imaging; the mismatched area of enhancement between the 2 agents shows residual wall thickening.

Influence of Severity of Myocardial Injury on Distribution of Macromolecules: Extravascular Versus Intravascular Gadolinium-Based Magnetic Resonance Contrast Agents☆

OBJECTIVES This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns. BACKGROUND Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity). METHODS To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesla system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing. RESULTS Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA-enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/ normal myocardium increased with increasing duration of ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin-enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (overall p value < 0.0001, ANOVA). CONCLUSIONS At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.

Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy

OBJECTIVES Various approaches to myocardial reconstruction have been developed for the treatment of congestive heart failure resulting from ischemic cardiomyopathy. METHODS In this study we determined whether in situ application of polymers could reshape left ventricular geometry in a chronic rodent model of ischemic cardiomyopathy. RESULTS We demonstrate that alginate and fibrin can augment left ventricular wall thickness, resulting in reconstruction of left ventricular geometry and improvement of cardiac function. Echocardiographic results at 5 weeks after injection of alginate demonstrated persistent improvement of left ventricular fractional shortening and prevention of a continued enlargement of left ventricular dimensions, whereas fibrin glue demonstrated no progression of left ventricular negative remodeling. There was increased arteriogenesis in both the alginate and fibrin glue groups compared with that seen in the phosphate-buffered saline control group. Infarct size was significantly reduced in the fibrin group (P < .05), and there was a trend toward a smaller myocardial infarction in the alginate group. CONCLUSION Intramyocardially injected polymers can be used to reshape the aneurysmal left ventricle and might therefore be an approach for myocardial reconstruction and a potential option in treating chronic heart failure in human subjects.

Effects of Pulmonary Insufficiency on Biventricular Function in the Developing Heart of Growing Swine

Background—This study was conducted to determine the effects of chronic pulmonary insufficiency (PI) on right (RV) and left (LV) ventricular function in young growing swine. Methods and Results—Six PI and 5 control animals were studied. PI was induced by transcatheter placement of stents across the pulmonary valve. Indices of systolic function (ejection fraction, cardiac output, and cardiac functional reserve), diastolic function (compliance), and myocardial contractility (the slope of the relationship of end-systolic pressure versus end-systolic volume [Emax] and the slope of the dP/dtmax–end-diastolic volume relationship [MdP/dt]) were assessed within 2 days of intervention and 3 months later. MRI was used to quantify PI and ventricular volumes. Conductance catheter techniques were used to obtain indices of contractility and diastolic compliance from pressure-volume relations at rest and under dobutamine infusion. In the PI group, pulmonary regurgitant fraction was 49.2±5.9% at 3-month follow-up. RV cardiac functional reserve was limited, diastolic function was preserved, and myocardial contractility was altered (Emax=2.6±0.3 mm Hg/mL for the PI group versus 3.5±0.4 mm Hg/mL for control; P <0.01). LV cardiac functional reserve was limited, ventricular compliance decreased, and myocardial contractility was preserved. Conclusions—In the young developing heart, chronic PI alters biventricular systolic function, RV myocardial contractility, and LV diastolic performance.

A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm

A non-invasive method for estimating regional myocardial contractility in vivo would be of great value in the design and evaluation of new surgical and medical strategies to treat and/or prevent infarction-induced heart failure. As a first step towards developing such a method, an explicit finite element (FE) model-based formal optimization of regional myocardial contractility in a sheep with left ventricular (LV) aneurysm was performed using tagged magnetic resonance (MR) images and cardiac catheterization pressures. From the tagged MR images, 3-dimensional (3D) myocardial strains, LV volumes and geometry for the animal-specific 3D FE model of the LV were calculated, while the LV pressures provided physiological loading conditions. Active material parameters (T(max_B) and T(max_R)) in the non-infarcted myocardium adjacent to the aneurysm (borderzone) and in myocardium remote from the aneurysm were estimated by minimizing the errors between FE model-predicted and measured systolic strains and LV volumes using the successive response surface method for optimization. The significant depression in optimized T(max_B) relative to T(max_R) was confirmed by direct ex vivo force measurements from skinned fiber preparations. The optimized values of T(max_B) and T(max_R) were not overly sensitive to the passive material parameters specified. The computation time of less than 5 hours associated with our proposed method for estimating regional myocardial contractility in vivo makes it a potentially very useful clinical tool.

Identification of myocardial reperfusion with echo planar magnetic resonance imaging. Discrimination between occlusive and reperfused infarctions.

BackgroundThe current treatment of many cases of acute myocardial infarction involves the use of thrombolytic agents. Evaluation of this therapy requires determination of the success of reperfusion and assessment of the presence and extent of infarction in the reperfused territory. The present study was designed to simulate in rat models several possible outcomes of reperfusion therapy: (1) successful reperfusion and absence of myocardial infarction, (2) successful reperfu-sion and presence of myocardial infarction, and (3) unsuccess-ful reperfusion. The usefulness of contrast-enhanced fast magnetic resonance (MR) imaging in defining the success of reperfusion was investigated. The dynamic effects were examined of low and high doses of gadolinium-BOPTA/dimeglu-mine (Gd-BOPTA/dimeg) on myocardial signal using MR inversion recovery echo planar imaging (IR-EPI) and gradient recalled echo planar imaging (GR-EPI), respectively. Methods and ResultsRats were subjected to one of the following regimens: reperfused reversible myocardial injury (n=9), reperfused irreversible myocardial injury (n=9), and occlusive infarction (n=9). MR echo planar images were acquired every 1 or 2 seconds before, during, and after administration of Gd-BOPTA/dimeg. In all groups, normal myocardial signal was sharply increased on IR-EPI and decreased on GR-EPI at the peak of the bolus, followed by a gradual decline to baseline. In animals subjected to reperfused reversible myocardial injury, normal and previously ischemic regions were indistinguishable during and after the passage of Gd-BOPTA/dimeg. On the other hand, enhancement of reperfused irreversibly injured myocardium was delayed but increased steadily to a higher level than normal myocardium on IR-EPI. The reperfused irreversibly injured myocardium was identified on IR-EPI as a zone of high signal (hot spot). On GR-EPI, signal loss in reperfused irreversibly injured myocardium was significantly less compared with normally perfused myocardium. In animals with occlusive infarctions, there was no change in signal intensity over the ischemic region on either IR-EPI or GR-EPI. Occlusive infarction was identified as zones of either low (cold spot) or high (hot spot) signal compared with normal myocardium, depending on MR pulse sequence and dose of the contrast medium. ConclusionsThe transit of Gd-BOPTA/dimeg monitored by fast MR imaging techniques can be used to distinguish between reperfused reversibly and reperfused irreversibly injured myocardium and between occlusive and reperfused infarctions.

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.

Microvascular injury in reperfused infarcted myocardium: noninvasive assessment with contrast-enhanced echoplanar magnetic resonance imaging

OBJECTIVES The purpose of this study was to measure the accumulation of labeled albumin and to visualize its distribution pattern in reperfused infarcted myocardium as a function of time between onset of reperfusion and administration of the tracer. BACKGROUND Myocardial microvascular injury leads to leakage of albumin from the intravascular space. Quantitative measurements of GdDTPA-albumin with inversion recovery echoplanar imaging (IR-EPI) may allow noninvasive monitoring of microvascular injury. METHODS After 1 h of coronary artery occlusion, 56 rats were injected with GdDTPA-albumin or 123I-GdDTPA-albumin either immediately before reperfusion or 1/2, 1 or 24 h after reperfusion. GdDTPA-albumin in blood, normal myocardium and reperfused infarction was dynamically measured with IR-EPI during 1 h postinjection (PI). Autoradiograms were obtained at 15 min PI. Accumulation of labeled albumin in myocardium was expressed as the ratio of myocardial to blood content. RESULTS In normal myocardium, the ratio of changes of relaxation rate-ratio (deltaR1-ratio) was 0.12+/-0.01 and did not change over 1 h. In reperfused infarction, however, the deltaR1-ratio increased after administration. Animals given GdDTPA-albumin before reperfusion exhibited fastest accumulation (deltaR1-ratio 15 min PI: 0.56+/-0.03) and essentially homogeneous distribution. The accumulation was slower when administered at 1/2, 1 and 24 h after reperfusion (deltaR1-ratios 15 min PI: 0.39+/-0.03; 0.31+/-0.04; 0.16+/-0.01; p < 0.001 compared to administration before reperfusion). Moreover, the tracer accumulated predominantly in the periphery of the injury zone. CONCLUSIONS Amount and distribution pattern of labeled albumin in reperfused infarction are modulated by duration of reperfusion. The accumulation of GdDTPA-albumin can be quantified by IR-EPI. Thus, IR-EPI may be useful to noninvasively monitor myocardial microvascular injury in reperfused infarction.

Magnetic Resonance–Guided Cardiac Catheterization in a Swine Model of Atrial Septal Defect

Background—Radiation exposure during cardiac catheterization, limited image planes, and poor soft tissue definition are disadvantages of x-ray fluoroscopy that could be overcome with the use of MRI. This study evaluates the feasibility of real-time MRI (MR fluoroscopy) to guide left and right heart catheterization. Methods and Results—Anesthetized pigs (n=7) with defects of the atrial septum were catheterized using venous and arterial access. A prototype active tracking catheter was used to obtain blood pressures and samples from cardiac chambers and great vessels using antegrade, transseptal, and retrograde approaches. MR fluoroscopy was used for catheter steering. Velocity-encoded cine MRI was used to measure pulmonary and aortic blood flow to calculate vascular resistances. Image planes used during catheter manipulation used rapid sequencing to planes directed by the operator to include the tip of the catheter and the chamber to be entered. All areas of interest were effectively entered, and samples were obtained. In the presence of an acute atrial septal defect, a Qp/Qs ratio of 1.3±0.2 was measured, and no significant differences in pressure between inferior vena cava, right atrium, and left atrium were found. Pulmonary and aortic flow were 4.9±0.6 and 3.7±0.4 L/min, and pulmonary and systemic vascular resistance were 312±134 and 2006±336 dyne · s · cm−5. Conclusions—Left and right heart catheterization using MR guidance is feasible. The combination of hemodynamic catheterization data with anatomic and functional MRI may significantly improve the evaluation of patients with congenital heart disease while avoiding radiation exposure.

Contrast-enhanced MRI for quantification of myocardial viability

During the past 10 years substantial advances have taken place in magnetic resonance imaging (MRI) capabilities and in contrast media development. Furthermore, knowledge of in vivo contrast media interactions with surrounding water and distribution into tissue has increased, permitting regional quantification of concentration‐time profiles in the myocardium. The combination of these advances has substantially improved the capability of contrast‐enhanced MRI characterization of myocardial ischemic injury, including its ability to discriminate viable from nonviable zones. Discrimination of viable from nonviable myocardial subregions is important for patient management and for research applications. This review addresses recent progress toward the goal of defining viable and nonviable myocardium based on MRI detection of contrast media effects. J. Magn. Reson. Imaging 1999;10:694–702.