Differential MR Delayed Enhancement Patterns of Chronic Myocardial Infarction between Extracellular and Intravascular Contrast Media

<div><p>Objectives</p><p>Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media.</p><p>Materials and Methods</p><p>Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson's trichrome method.</p><p>Results</p><p>Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn’t significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen.</p><p>Conclusions</p><p>Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn’t provide delayed enhancement.</p></div

Histopathology of chronic myocardial infarction at four weeks after myocardial infarction.

<p>A. Cardiomyocytes were the major structural elements in normal myocardium. B. Scar tissue was characterized by the discrete collagen fibers and loss of cellularity. Collagen fibers were stained blue using Masson’s trichrome staining (Arrowhead, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g007" target="_blank">Fig. 7B</a>). C. Dilated remodeled vessels were frequently observed in the territory of the infarction (Arrowheads, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g007" target="_blank">Fig. 7C</a>). D. Large thick-walled blood vessels were apparent at the peri-infarction zones (Arrowheads, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g007" target="_blank">Fig. 7D</a>).</p

Representative ³¹P spectra acquired from scarred and normal myocardium.

<p>³¹P spectra from scarred myocardium exhibited a more striking PPA peak (the extracellular compartment) as compared with normal myocardium (a and b). The ratio of extracellular volume to the entire space was significantly greater in scarred myocardium than in normal myocardium (c). The ATP content was substantially lower in scarred myocardium than in normal myocardium (d).</p

ΔR1 relaxation times measured after the administration of Gd-DTPA (a) and P792 (b).

<p>Administration of Gd-DTPA was associated with a higher ΔR1 relaxation time of scarred myocardium compared to normal myocardium, whereas there was not difference in ΔR1 relaxation time between scarred and normal myocardium post injection of P792.</p

Representative contrast agent delayed enhanced T₁ imagings with a photomicrograph of TTC-stained tissue.

<p>Scarred myocardium exhibited the hyperenhancement at Gd-DTPA enhanced T₁ imaging, whereas homogeneous hyperenhancement was observed in scarred and normal myocardium after the administration of P792. Upper panel: Gd-DTPA enhanced T₁ imaging; Lower panel: P792 enhanced T₁ imaging; First vertical line: precontrast T₁ imaging; Second vertical line: T₁ imaging 5 min post injection; Third vertical line: T₁ imaging 15 min post injection; Fourth vertical line: TTC stained section.</p

Representative contrast agent first pass T₂^* imagings with a photomicrograph of TTC-stained tissue.

<p>The extent of T₂^* signal hypoenhancement caused by entry of Gd-DTPA and P792 in scarred myocardium were comparable to those in normal myocardium. There were no differences in T₂^* signal loss between scarred and normal myocardium at wash-in and peak T₂^* imaging. Upper panel: T₂^* imaging during the first pass of Gd-DTPA; Lower panel: T₂^* imaging during the first pass of P792; First vertical line: precontrast T₂^* imaging; Second vertical line: wash-in T₂^* imaging; Third vertical line: peak T₂^* imaging; Fourth vertical line: TTC stained section.</p

First-pass perfusion MR images and time intensity curves of P792.

<p>A. Gd-DTPA delayed enhancement image. B. Corresponding TTC staining picture. C. Time intensity curves obtained from the first passage of P792. D. Corresponding P792 first-pass perfusion images. The chronic anterior-lateral wall infarction was hyper-enhanced in Gd-DTPA delayed enhanced image (Arrowhead, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g004" target="_blank">Fig. 4A</a>) and was confirmed in TTC staining picture (Arrowhead, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g004" target="_blank">Fig. 4B</a>). The bolus of P792 caused a rapid and equivalent signal increase in chronic infarction and normal myocardium (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g004" target="_blank">Fig. 4C</a>). The chronic infarction did not show perfusion abnormalities with fewer enhancements relative to normal myocardium (Arrowheads, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g004" target="_blank">Fig. 4D</a>).</p

Histological staining sections: normal myocardium (upper panel) and scarred myocardium (lower panel), Masson's trichrome stain (right panel) and H&E stain (left panel).

<p>Cadiomyocytes are the major structural elements and interstitial volume only account for a small part of extravascular space of normal myocardium (a and b). The discrete compartment of collagen fiber is major framework of extracellular space in scarred myocardium (c). Cadiomyocytes have almost disappeared and vessels of different sizes were seen frequently (d).</p

Myocardial blood flow and microvessel density.

<p>Scarred myocardium exhibited the dilated vessels and numerous microvessels (a), which resembled those observed in normal myocardium (b). Myocardial blood flow and microvessel density were significantly recovered to 0.92±0.18 ml/g/min (c) and 197.6±55.3 vessels/mm² (d) despite slightly lower than these observed measured in normal myocardium.</p

P792 delayed enhancement MR images and signal intensities.

<p>A. TTC staining picture. B. Corresponding Gd-DTPA delayed enhancement image. C. P792 enhanced signal intensities at various time points post-injection. D. Corresponding left ventricular short-axis P792 delayed enhancement images obtained at different time points post injection. The chronic anterio-lateral wall infarction was confirmed in TTC staining picture (Arrowhead, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g006" target="_blank">Fig. 6A</a>). The chronic MI displayed the delayed hyper-enhancement in Gd-DTPA delayed enhancement images (Arrowhead, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g006" target="_blank">Fig. 6B</a>). However, the P792 enhanced signal intensity in chronic infarction did not differ from that in normal myocardium (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g006" target="_blank">Fig. 6C</a>). Thus, the P792 did not produce differentiated hyper-enhancement of chronic MI (Arrowheads, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121326#pone.0121326.g006" target="_blank">Fig. 6D</a>).</p