Person:

Ruskin, Jeremy

Background: The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Methods: Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. Results: In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p<0.05). This was confirmed histologically by the reduction of HA in the subepicardium from −52.03° ± 2.94° in normal hearts to −37.48° ± 4.05° in the remote zone of the remodeled hearts (p < 0.05). Conclusions: A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward) shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

A cardiac-tailored framework for 3D Diffusion Tensor MRI tractography is developed and used to characterize myofiber architecture in normal and remodeled myocardium. We show that myofibers in the subepicardium of the remote infarct zone become less oblique (more circumferential) as the heart dilates and remodels. This fiber realignment may play an important role in the loss of contractile function in the remote zone over time.

Background: Late gadolinium enhancement (LGE) is the current standard for myocardial scar delineation. In this study, we introduce the tractographic propagation angle (PA), a metric of myofiber curvature (degrees/unit distance) derived from diffusion tensor imaging (DTI), and compare its use to LGE and invasive scar assessment by endocardial voltage mapping. Methods and Results: DTI was performed on 7 healthy human volunteers, 5 patients with myocardial infarction, 6 normal mice, and 7 mice with myocardial infarction. LGE to delineate the infarct and border zones was performed with a 2‐dimensional inversion recovery gradient‐echo sequence. Ex vivo DTI was performed on 5 normal human and 5 normal sheep hearts. Endocardial electroanatomic mapping and subsequent ex vivo DTI was performed on 5 infarcted sheep hearts. PA in the normal human hearts varied smoothly and was generally <4. The mean PA in the infarct zone was significantly elevated (10.34±1.02 versus 4.05±0.45, P<0.05). Regions with a PA ≤4 consistently had a bipolar voltage ≥1.5 mV, whereas those with PA values between 4 and 10 had voltages between 0.5 and 1.5 mV. A PA threshold >4 was the most accurate DTI‐derived measure of infarct size and demonstrated the greatest correlation with LGE (r=0.95). Conclusions: We found a strong correlation between infarct size by PA and LGE in both mice and humans. There was also an inverse relationship between PA values and endocardial voltage. The use of PA may enable myocardial scar delineation and characterization of arrhythmogenic substrate without the need for exogenous contrast agents.