Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar

Abstract

Background: The ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction.

Methods and results: Ten dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm x 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1+/-7.2% versus 20.4+/-7.4%, mean difference 0.7%; chronic infarcts 4.15+/-1.93% versus 4.92+/-2.06%, mean difference -0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred approximately 5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow.

Conclusions: The spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.

Conflict of interest statement

Disclosures

Drs Lardo and Lima receive research support from Toshiba, Inc. The other authors report no conflicts.

Figures

Figure 1

Experimental protocol for (a) acute and (b) chronic experiments. HR indicates heart rate (in beats per minute).

Figure 2

Typical contrast-enhanced myocardial MDCT images showing axial slices (a) at baseline (preinfarct) 5 minutes after contrast, (b) postinfarct during first-pass contrast injection, and (c) postinfarct 5 minutes after contrast injection. The infarcted region is represented by the subendocardial anterior hyperintense region (arrows).

Figure 3

a, Axial contrast-enhanced myocardial MDCT image showing orthogonal slice prescriptions representing (b) short-axis and (c) long-axis multiplanar reconstructions, respectively. The infarcted region is represented by the subendocardial anterolateral hyperintense region. LA indicates long axis; SA, short axis.

Figure 4

a–h, Axial temporal image series demonstrating postreperfusion contrast agent kinetics after 150-mL injection of contrast. The first image (a) represents the first-pass image during contrast agent injection. Note that the signal density of the infarct in the first pass is substantially lower than that of the remote myocardium and indicates a subendocardial microvascular obstruction. Five minutes after injection (b), the signal density of the damaged myocardial region is significantly greater than that of the remote myocardium and washes out over time. The plot in (i) represents quantitative contrast kinetics for the LV chamber, remote myocardium, and infarct after contrast injection. As can be appreciated from (b), the infarct becomes well delineated and reaches peak enhancement at 5 minutes after injection and then washes out in proportion to the chamber (blood pool) and remote myocardial signal.

Figure 5

MDCT and histopathologic staining comparison of infarct morphology. a, Reconstructed short-axis MDCT slice 5 minutes after contrast injection demonstrating a large anterolateral infarct (hyperenhanced region) with discrete endocardial regions of microvascular obstruction (4 arrows). b, TTC-stained slice; c, Thioflavin S and TTC staining of the same slice, which confirms the size and location of microvascular obstruction regions. d, Quantitative MDCT and TTC measurements of infarct size yielded good agreement, with points distributed around the line of identity. e, Mean difference of 0.7% by Bland-Altman analysis.

Figure 6

a, Axial cardiac MDCT image 2 hours after LAD occlusion/reperfusion showing an orthogonal slice prescription. The large anterior region of low signal density represents a region of microvascular obstruction at the endocardial portion of the infarct. b through e, Short-axis reconstruction of the same slice over time to characterize changes in the region of microvascular obstruction (arrows). As can be appreciated, the region of low signal density is surrounded by a region of high signal density early after contrast injection and then slowly increases over time and eventually reaches the level of surrounding high signal density myocardium. f, Plot of both normalized size and signal density of the microvascular obstruction (MO) region over time.

Figure 7

a, Sagittal cardiac MDCT image of an 8-week-old infarct in a porcine model 5 minutes after contrast injection. b, Short-axis MDCT image and (c) corresponding gross examination photograph. d and e, Quantitative comparison of MDCT and gross examination/ TTC infarct size.

Figure 8

TTC (a) and MDCT (b) images and hematoxylin and eosin histopathology analysis (c–e) from myocardial samples extracted ≈2 hours after the ischemic event. Samples were taken from remote, infarcted, and border regions. Remote myocardial areas (TTC-negative) demonstrate no change to the normal canine myocardial elements, including unremarkable myocytes and blood vessels (c). The TTC-negative (infarct) region demonstrated multiple changes that were consistent with acute myocyte necrosis, including extensive contraction band necrosis without evidence of nuclear changes (arrow) and waves of neutrophils leaving small blood vessels and collecting within interstitial spaces (arrow, d). In the border-zone region, normal myocytes were separated by large waves of neutrophilic infiltrate and contraction band necrosis (e).

Figure 9

Comparison of (a) low (50 mL) and (b) high dose (150 mL) MDCT infarct images 5 minutes after contrast injection. Panels c and d show identical slices acquired with 2 different imaging protocols to demonstrate the effect of radiation dose on image quality. The image in (c) was acquired with a relatively high radiation dose (135 kV and 400 mA, approximately equivalent to 3 REM), whereas the image in (b) was acquired with the clinical protocol used at our institution for CT coronary angiography (120 kV and 250 mA). Lower contrast and radiation does had no effect on the accuracy of quantitative infarct-size measurements.