A non-contrast CMR index for assessing myocardial fibrosis

Abstract

Purpose: Safe, sensitive, and non-invasive imaging methods to assess the presence, extent, and turnover of myocardial fibrosis are needed for early stratification of risk in patients who might develop heart failure after myocardial infarction. We describe a non-contrast cardiac magnetic resonance (CMR) approach for sensitive detection of myocardial fibrosis using a canine model of myocardial infarction and reperfusion.

Methods: Seven dogs had coronary thrombotic occlusion of the left anterior descending coronary arteries followed by fibrinolytic reperfusion. CMR studies were performed at 7days after reperfusion. A CMR spin-locking T₁ρ mapping sequence was used to acquire T₁ρ dispersion data with spin-lock frequencies of 0 and 511Hz. A fibrosis index map was derived on a pixel-by-pixel basis. CMR native T₁ mapping, first-pass myocardial perfusion imaging, and post-contrast late gadolinium enhancement imaging were also performed for assessing myocardial ischemia and fibrosis. Hearts were dissected after CMR for histopathological staining and two myocardial tissue segments from the septal regions of adjacent left ventricular slices were qualitatively assessed to grade the extent of myocardial fibrosis.

Results: Histopathology of 14 myocardial tissue segments from septal regions was graded as grade 1 (fibrosis area, <20% of a low power field, n=9), grade 2 (fibrosis area, 20-50% of field, n=4), or grade 3 (fibrosis area, >50% of field, n=1). A dramatic difference in fibrosis index (183%, P<0.001) was observed by CMR from grade 1 to 2, whereas differences were much smaller for T₁ρ (9%, P=0.14), native T₁ (5.5%, P=0.12), and perfusion (-21%, P=0.05).

Conclusion: A non-contrast CMR index based on T₁ρ dispersion contrast was shown in preliminary studies to detect and correlate with the extent of myocardial fibrosis identified histopathologically. A non-contrast approach may have important implications for managing cardiac patients with heart failure, particularly in the presence of impaired renal function.

Keywords: CMR; Myocardial diffuse fibrosis; Myocardial infarction; Spin-lock T(1)ρ.

Fig. 1.

Schematic diagrams of the cardiac T₁ρ -preparation sequence with three 180° refocusing pulses and rotary echo scheme for the reduction of B₀ and B₁ inhomogeneity. Three T₁ρ-weighted images are acquired at three different TSL (10, 30, 50 ms) to form one T₁ρ map. The sequence uses a segmented data acquisition scheme to acquire data and a trigger delay time is varied to ensure data acquisition time to occur at the mid-diastole for the reduction of cardiac motion.

Fig. 2.

Examples of various contrasts of images and maps for fibrosis grade 1 (top), grade 2 (middle), and grade 3 (bottom). From left to right, LGE images, zoomed LGE images on septal regions, T₁ρ maps (510 Hz), T₁ρs map (0 Hz), and mFI maps (ms) in the same septal regions, as well as corresponding trichrome-stained histopathological images (blue = fibrosis). The green rectangles in mFI maps indicate approximate areas where the histopathological slides were located. The values in mFI maps indicated the mean mFI measured in the green rectangle covered regions. The dashed circles in the LGE images point to the artifacts induced by metal needles. The collagen deposit was shown in blue in histopathological slides. The units of color scale for T₁ρ and mFI maps are ms. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)