# Cardiac Diffusion Tensor Biomarkers of Chronic Infarction Based on In Vivo Data
## 4 Discussion  
In this work, MRI data acquired in vivo in swine subjects with chronic MI were used to quantitatively analyze and compare ECV, native T1, diffusion tensor invariants, radial diffusivity, and eigenvalues across the remote, border, and infarcted myocardium. Among all analyzed quantities, RD, e\({}_{2}\), e\({}_{3}\), and ECV showed the highest percentage increase in the border and infarct regions with respect to the remote myocardium. ECV has been identified as a potential biomarker to characterize affected myocardial tissue due to various cardiac diseases such as myocardial infarction [27] and hypertension [33]. After administration, Gadolinium-based contrast agents diffuse into the extracellular space. This causes the T1-relaxation time of the myocardium to depend on local gadolinium concentration [34]. The increased extracellular space in infarcted myocardium allows retention of a higher amount of gadolinium-based contrast. Hence, myocardial regions such as the border and infarct zones, where the extracellular space is higher due to the presence of replacement fibrosis, are expected to exhibit higher ECV compared to the remote myocardium [27]. The increased median ECV of the infarct (0.47) and border (0.38) regions compared to the remote (0.31) region observed in this work agrees with this mechanism. Although widely used, ECV maps require the use of contrast agents, which are not indicated for patients suffering from pre-existing renal conditions. Among the existing non-contrast-based imaging techniques, native T1 has been considered to be an alternative biomarker for myocardial infarction detection [35], as well as for detecting myocardial edema and diffuse fibrosis [36; 37; 38]. In the current study, native T1 values in the infarct and border regions were 21.2% and 8.4% higher than the remote myocardium, respectively. As with the case for native T1, diffusion tensor invariants and eigenvalues can also be computed without the use of contrast agents, and convey additional information regarding microstructural changes (e.g., myocardium anisotropy and inter-cellular spacing) occurring in the infarcted tissue. Among these quantities, FA decreased whereas MD, eigenvalues, and RD increased in the border and infarct regions when compared to the remote myocardium. Across all subjects, the percent increase or decrease of these parameters was higher in the infarct region compared to the border region. These trends concur with previous findings [9; 10; 11]. [PERSON] et al. [39] validated histologically that after chronic myocardial infarction, the infarct region is largely comprised of replacement fibrosis, and the border region is a mixture of viable myocardium and replacement fibrosis. The presence of replacement fibrosis is reflected by an increased ECV. Due to the increase in extracellular space [40], the diffusion of water molecules increases. This is reflected by the increased MD values in the infarct and border regions computed in this study from experimental in vivo cDTI data. However, the observed increase in diffusion is not isotropic; instead, the increase in e\({}_{2}\) and e\({}_{3}\) is more significant than the increase in e\({}_{1}\). This unequal increase in diffusion agrees with previous studies, suggesting that replacement fibrosis maintains the preferential direction of the replaced cardiomyocytes [41], and larger extracellular space is now present [40]. This corresponds to a larger diffusion increase in the e\({}_{2}\) and e\({}_{3}\) directions with respect to the increase in the e\({}_{1}\) direction. The larger increase in the e\({}_{2}\) and e\({}_{3}\) directions concurs with a decrease in FA and agrees with histological findings [40]. As expected, due to a smaller amount of replacement fibrosis in the border zone, the increase in e\({}_{2}\), e\({}_{3}\), MD, and ECV and decrease in FA are less significant in the border region with respect to the infarct region. To present diffusion values in the radial direction in a concise manner, radial diffusivity (RD) was used.