Magnetic resonance imaging and multi-detector computed tomography assessment of extracellular compartment in ischemic and non-ischemic myocardial pathologies

Abstract

Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume (ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular (approximately 10% of tissue volume), interstitium (approximately 15%) and intracellular (approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types I/III collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis (e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy (hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging (MRI) has the ability to characterize tissue proton relaxation times (T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI (DE-MRI) and multi-detector computed tomography (DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary catheterization and possibility of tissue sampling error. Similar to delayed contrast enhancement, equilibrium contrast enhanced MRI/MDCT and T1 mapping is completely noninvasive and may play a specialized role in diagnosis of subclinical and other myocardial pathologies. DE-MRI and when T1-mapping demonstrated sub-epicardium, sub-endocardial and patchy mid-myocardial enhancement in myocarditis, Behcet's disease and sarcoidosis, respectively. Furthermore, recent studies showed that the combined technique of cine, T2-weighted and DE-MRI technique has high diagnostic accuracy for detecting myocarditis. When the tomographic techniques are coupled with myocardial perfusion and left ventricular function they can provide valuable information on the progression of myocardial pathologies and effectiveness of new therapies.

Keywords: Cellular compartments; Contrast media; Ischemic/non-ischemic heart diseases; Magnetic resonance imaging; Multi-detector computed tomography; Myocardial viability.

Figure 1

Schematic presentation of various types (patchy and contiguous) and locations (epicardium, midmyocardium and endocardiu) of myocardial infarct in different cardiac diseases. In acute myocardial infarct > 30% of the patients have a hypoenhanced microvascular zone in the core of contiguous infarct. Reactive interstitial fibrosis is seen in hypertension, valvular, diabetic and genetic diseases as well as aging, while infiltrative interstitial fibrosis is evident in amyloidosis and Anderson-Fabry disease. The replacement of myocardium with scar tissue is seen in inflammatory disease, chronic ischemia/coronary occlusion (contiguous), chronic renal insufficiency (patchy) and genetic and toxic diseases.

Figure 2

The three fluid compartments in healthy myocardium, namely intravascular (approximately 10% of tissue volume), interstitial (approximately 15%) and intracellular (approximately 75%) compartments. ECV: Extracellular volume; HCT: Hematocrit; Gd: Gadolinium; I: Iodine; Tc: Technetium; MECV: Myocardial extracellular volume.

Figure 3

Schematic presentation of diffuse myocardial fibrosis in non-ischemic heart diseases (left) and contiguous chronic infarct (right) in ischemic heart disease. HCT: Hematocrit; Gd: Gadolinium; I: Iodine; Tc: Technetium.

Figure 4

The top left plot shows the time course of equilibrium state of iodinated contrast media distribution in the extracellular volume of the blood (dashed line), healthy myocardium (solid line) and skeletal muscle (dotted line) over the course of 10 min using multi-detector computed tomography. The plots also demonstrate the remarkable difference in myocardial extracellular volume (MECV) in regions subjected to different insults. Differential increase in ECV was observed in ischemic myocardium after microembolization using 16 mm³ (top right), 32 mm³ (bottom left) or 90 min left anterior descending coronary artery occlusion/reperfusion (bottom right) compared with undamaged remote myocardium in all groups (dotted lines). MDCT: Multi-detector computed tomography.

Figure 5

Delayed contrast enhanced magnetic resonance imaging of acute reperfused myocardial infarction (3 d) showing the hyperenhanced infarct and microvascular obstruction (arrows).

Figure 6

Delayed contrast enhanced magnetic resonance imaging (A and C) and histochemical triphenyltetrazplium chloride stain (B and D) show patchy microinfarct (arrows) 3 d after delivering 16 mm³ (A and C) and 32 mm³ (B and D) microemboli in the LAD coronary artery in a swine model.

Figure 7

Delayed contrast enhanced multi-detector computed tomography 3 d after microembolization using 16 mm³ (A) and 32 mm³ (B) microemboli.

Figure 8

Gradient increase in myocardial extracellular volume as a function of microemboli volume (16 mm³ vs 32 mm³) and left anterior descending coronary artery occlusion time (45 min vs 90 min). ^bP < 0.01 vs 16 mm³, ^dP < 0.01 vs 32 mm³ and ^fP < 0.01 vs 45 min left anterior descending coronary artery occlusion/reperfusion. MECV: Myocardial extracellular volume; MDCT: Multi-detector computed tomography.

Figure 9

Acute (top row, hematoxylin and eosin stain) and chronic (bottom row, Masson trichrome stain) patchy microinfarct (white arrows) and microemboli (black arrowhead) distribution between viable myocardium at 3 d and 5 wk after embolization, respectively. Intramyocardial hemorrhage (red arrow) and calcium deposition (black arrow) are evident at 3 d on HE stain, but not at 5 wk. The magnifications are 40 × (A and C) and 100 × (B and D).