Characterization of peri-infarct zone heterogeneity by contrast-enhanced multidetector computed tomography: a comparison with magnetic resonance imaging

Abstract

Objectives: This study examined whether multidetector computed tomography (MDCT) improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to magnetic resonance imaging (MRI).

Background: The PIZ as characterized by delayed contrast-enhancement (DE)-MRI identifies patients susceptible to ventricular arrhythmias and predicts outcome after myocardial infarction (MI).

Methods: Fifteen mini-pigs underwent coronary artery occlusion followed by reperfusion. Both MDCT and MRI were performed on the same day approximately 6 months after MI induction, followed by animal euthanization and ex vivo MRI (n = 5). Signal density threshold algorithms were applied to MRI and MDCT datasets reconstructed at various slice thicknesses (1 to 8 mm) to define the PIZ and to quantify partial volume effects.

Results: The DE-MDCT reconstructed at 8-mm slice thickness showed excellent correlation of infarct size with post-mortem pathology (r2 = 0.97; p < 0.0001) and MRI (r2 = 0.92; p < 0.0001). The DE-MDCT and -MRI were able to detect a PIZ in all animals, which correlates to a mixture of viable and nonviable myocytes at the PIZ by histology. The ex vivo DE-MRI PIZ volume decreased with slice thickness from 0.9 +/- 0.2 ml at 8 mm to 0.2 +/- 0.1 ml at 1 mm (p = 0.01). The PIZ volume/mass by DE-MDCT increased with decreasing slice thickness because of declining partial volume averaging in the PIZ, but was susceptible to increased image noise.

Conclusions: A DE-MDCT provides a more detailed assessment of the PIZ in chronic MI and is less susceptible to partial volume effects than MRI. This increased resolution best reflects the extent of tissue mixture by histopathology and has the potential to further enhance the ability to define the substrate of malignant arrhythmia in ischemic heart disease noninvasively.

Figure 1. Comparison of infarct morphology by MDCT with post mortem pathology and MRI

Example images in short axis orientation for (A) de-MDCT at 2mm, (B) post mortem pathology at 2mm, (C) ex-vivo and (D) in-vivo MRI at 4mm slice thickness show a similar location and distribution pattern of the chronic collagenous scar in the anterior-septal LV wall.

Figure 2. Characterization of tissue heterogeneity in peri-infarct zone by MDCT

Example of matching 8mm slice section in chronic infarcts for de-MDCT (A, B) and de-MRI (D,E).(A, B) The viable myocardium(*) shows lower attenuation values, than enhanced scar tissue (white arrows). The PIZ is visualized between two black arrows by intermediate signal intensity (white circle) in de-MDCT images. (D,E) Viable myocardium (*), delayed enhanced infarct scar (white arrows), and the PIZ (white circle) show different signal intensity in de- MRI. The viable myocardium is darker in the MRI acquisition, and the PIZ appears larger in de-MDCT images compared to de-MRI. C, F) Masson’s trichrome stain depicts viable myocardium in red (*) from non-viable tissue in blue. At higher magnification the densely packed collagenous extra-cellular matrix (white arrows) in the chronic infarct scar can be appreciated. Island of viable myocytes (red) within the scar tissue are visualized demonstrating the heterogeneity of the PIZ (area between black arrows). (G, H) Scanning electron microscope images of the densely packed collagen fibers six months post MI (G) and viable myocytes (H) characterize the ultra-structure of the chronic infarct and the PIZ. (I) Transmission electron microscopy of the PIZ demonstrates the clear delineating of the collagenous scar (white arrows) and viable tissue (*).

Figure 3. Peri-infarct zone assessment by ex-vivo MRI (n=5)

(A) Long-axis orientation showing the extent of 1 and 8mm slice thickness for short axis images. The presence of both viable and non-viable tissues in the 8 mm slice results in partial volume averaging. (B) For the 8mm slice thickness, the septal infarct appears transmural (arrows) and the PIZ is less defined with a wide range of gray values. (C) In the 1mm short axis slice at the same region it can be appreciated that infarct is not transmural and has well-delineated borders (D, E) The same myocardial slices with computer –generated mask depicting the core infarct (red) and PIZ (yellow). The PIZ is larger at 8mm. (F) Ex-vivo and in-vivo MRI showed different assessment of the PIZ at 8mm and 4 mm *p< 0.01 and ^†p= 0.01, respectively) The PIZ mass in ex-vivo MRI acquisitions as a function of slice thickness showed marked differences (^‡p=0.004) and decreased with thinner slice thickness; 2mm versus 8mm ^§p= 0.01, and 1mm vs 4 and 8mm, ^¶p< 0.01 and ^#p< 0.001, respectively

Figure 4. Comparison of PIZ assessment with ex-vivo de-MRI and de-MDCT

The volume of the PIZ (A) and PIZ expressed as percentage of the total infarct size (B) decreases in a linear fashion with reduced slice thickness evaluated by ex-vivo MRI suggesting a pronounced partial volume effect, while the amount of PIZ volume is less affected by slice thickness in MDCT acquisitions until a slice thickness of 1mm is reached. This implies that MDCT assessment of the PIZ is less susceptible to partial volume effects, but affected by image noise at 1mm. There are marked differences in the PIZ volume and percentage assessment between MDCT and ex-vivo MRI assessment at 1 and 8mm *p<0.01 and ^†p<0.001, respectively. Differences between slice thicknesses: 1mm versus 4 and 8mm, ^‡ p< 0.01 and ^§p< 0.001, respectively; 2mm versus 8mm, ^¶p= 0.01 for ex-vivo MRI, and 8mm versus 2 mm 4 mm ^# p< 0.05 and **p< 0.05, respectively

Figure 5. Effect of Slice Thickness on de-MDCT PIZ

(A) Long-axis orientation of de-MDCT showing the location of the short axis images (white line). (B, C) De-MDCT images in short axis reconstructed at 8 and 1 mm. Note the smooth appearance of the tissue versus the more heterogeneous appearance at 1 mm. (D,E) The same myocardial slices with computer –generated mask depicting the core infarct (red) and the peri-infarct zone (PIZ) (yellow). The increase of the PIZ (yellow) can be appreciated with decreased slice thickness.

Figure 6. Effect of slice thickness on de-MDCT density and signal to noise ratios (SNR) and contrast to noise ratios (CNR).(

A) Signal density in Hounsfield Units (HU) for the left ventricular blood pool (LVBP), infarcted myocardium (IN), the peri-infarct zone (PIZ) and the remote myocardium (RE), LVBP and RE do not show different attenuation values at different slice thickness, while IN values (*p<0.05, 1 versus 4mm and 2 versus 4mm; ^† p=0.01,1 versus 8mm, 2 versus 8mm) and PIZ values (^‡ p<0.01, 1 versus 4mm and 8mm, and 2 mm versus 8mm)change with the reconstructed slice thickness parameters(^§p=0.007 and ^¶ p=0.002, respectively). (B) Mean MDCT SNR (8 versus 2mm and 1mm, (^† p=0.01 and ^‡ p<0.01 respectively; and 4 versus 1mm, *p<0.05; ‡ p=0.003) and (C) mean MDCT CNR (8 versus 2mm and 1mm, ‡ p<0.01; ** p=0.008) change with the reconstructed slice thickness, which reflects reduced imaging quality of thinner reconstructed slices.