# Cardiac Diffusion Tensor Biomarkers of Chronic Infarction Based on In Vivo Data
## 4 Discussion
Higher resolution and SNR allow for a more accurate segmentation and subdivision of myocardium into remote, border, and infarct regions, therefore emphasizing the differences between regions. Overall, the diffusion tensor invariants reported in this study are in good agreement with values reported in previous studies. [PERSON] et al. [43] conducted a study on 30 patients with myocardial infarction. The mean MD and FA values computed in vivo by [PERSON] et al. compared to the values computed in current study (reported in parenthesis), were: 1.83 \(\times\) 10\({}^{-3}\) (1.81 \(\times\) 10\({}^{-3}\)) mm\({}^{2}\)/s for MD and 0.22 (0.25) for FA in the infarct region; 1.53 \(\times\) 10\({}^{-3}\) (1.69 \(\times\) 10\({}^{-3}\)) mm\({}^{2}\)/s for MD and 0.33 (0.28) for FA in the border zone, and 1.45 \(\times\) 10\({}^{-3}\) (1.46 \(\times\) 10\({}^{-3}\)) mm\({}^{2}\)/s for MD and 0.35 (0.29) for FA in the remote myocardium. The computed mean ECV in [PERSON] et al. [43] was 0.60, 0.29, and 0.29 in the infarct, border, and remote regions, respectively, compared to 0.49, 0.39, and 0.32 in the current study. The discrepancies in the reported ECV values could be due to the different methods used to subdivide the myocardium into remote, border, and infarct regions. Moreover, [PERSON] et al. used in vivo human data, whereas in vivo swine data were used in the current study. The much larger cohort size (N = 30 vs. N = 5) compared to the current study could also be a reason for the observed discrepancies. [PERSON] et al. [9] conducted a study on five swine subjects with myocardial infarction. At nine weeks post-MI, reported mean MD and FA values in the infarct and remote zone were (values from the current study are reported in parenthesis): 1.66 \(\times\) 10(1.81 \(\times\) 10\({}^{-3}\)) mm\({}^{2}\)/s for MD and 0.28 (0.25) for FA in the infarct region; 1.34 \(\times\) 10\({}^{-3}\) (1.46 \(\times\) 10\({}^{-3}\)) mm\({}^{2}\)/s for MD and 0.38 (0.29) for FA in the remote myocardium. Mean ECV values reported by [PERSON] et al. were 0.83 and 0.31 in the infarct and remote regions, and in the current study, the mean ECV was 0.49 and 0.32, respectively. This discrepancy could be due to the uncertainty associated with native T1 scans and the computed ECV [44]. Differences in imaging modalities and data processing could also play a role. This study also presents several limitations. First, in vivo cDTI data for only five subjects was considered. Although key results agree with other studies in the literature and our own ex vivo study and simulations, a larger cohort size in future studies will allow a strengthening of the current findings. As infarct size varied significantly across the imaged subjects, a larger cohort with varying infarct size will allow a better understanding of the dependence of diffusion tensor quantities on infarct size. Second, myocardial segmentation to determine the ground truth infarct, border, and remote regions based on LGE-PSIR data was carried out following the thresholding method described by [PERSON] et al. [22]. Although previously adopted, uncertainties remain regarding the choice of the threshold values, which could result in small variations of the determined myocardial regions. Histological validation of the segmented remote, border, and infarct regions was not possible due to lack of histological data. Third, the difference in resolution, field of view (FOV), and cardiac phase between in vivo cDTI and LGE required interpolation and a non-rigid registration step. This might have led to the mislabeling of a small number of voxels in the boundary of the adjacent myocardial regions. Further work is required to quantify the uncertainty associated with non-rigid registration [45] along with the uncertainty due to the noise in the MRI images and observer error. Finally, regarding the diffusion simulation, a simplified geometric model was used to generate cellular structures, and simulations were carried out without considering cell permeability and intracellular diffusion.