Person:

Dai, Guangping

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.

Multicontrast MRI with T1, T2 and Ultrashort TE (UTE) sequences is used to image atherosclerotic plaque in human coronary arteries. MRI classification of the plaques is compared with their histological classification and found to correlate extremely well. The addition of UTE MRI adds significant value to the imaging of human coronary artery plaque by MRI.

Objective: Human myocardium has a complex and anisotropic 3D fiber pattern. It remains unknown, however, when in fetal life this anisotropic pattern develops and whether the human heart is structurally fully mature at birth. We aimed here to use diffusion tensor MRI (DTI) tractography to characterize the evolution of fiber architecture in the developing human fetal heart. Methods: Human fetal hearts (n = 5) between 10–19 weeks of gestation were studied. The heart from a 6-day old neonate and an adult human heart served as controls. The degree of myocardial anisotropy was measured by calculating the fractional anisotropy (FA) index. In addition, fiber tracts were created by numerically integrating the primary eigenvector field in the heart into coherent streamlines. Results: At 10–14 weeks the fetal hearts were highly isotropic and few tracts could be resolved. Between 14–19 weeks the anisotropy seen in the adult heart began to develop. Coherent fiber tracts were well resolved by 19 weeks. The 19-week myocardium, however, remained weakly anisotropic with a low FA and no discernable sheet structure. Conclusions: The human fetal heart remains highly isotropic until 14–19 weeks, at which time cardiomyocytes self-align into coherent tracts. This process lags 2–3 months behind the onset of cardiac contraction, which may be a prerequisite for cardiomyocyte maturation and alignment. No evidence of a connective tissue scaffold guiding this process could be identified by DTI. Maturation of the heart’s sheet structure occurs late in gestation and evolves further after birth.

Histological studies have shown that the myocardium consists of an array of crossing helical fiber tracts. Changes in myocardial fiber architecture occur in ischemic heart disease and heart failure, and can be imaged non-destructively with diffusion-encoded MR. Several diffusion-encoding schemes have been developed, ranging from scalar measurements of mean diffusivity to a 6-dimensional imaging technique known as diffusion spectrum imaging or DSI. The properties of DSI make it particularly suited to the generation of 3-dimensional tractograms of myofiber architecture. In this article we review the physical basis of diffusion-tractography in the myocardium and the attributes of the available techniques, placing particular emphasis on DSI. The application of DSI in ischemic heart disease is reviewed, and the requisites for widespread clinical translation of diffusion MR tractography in the heart are discussed.