70 Chapter 5 Cardiovascular Magnetic Resonance: Myocardial native T1, Postcontrast T1 and ECV To assess whether radiation dose to the heart could cause myocardial fibrosis, we performed T1 mapping to characterize the myocardial tissue of the LV. The mean native myocardial T1 relaxation time was 959.2 ± 34.7 ms for patients who received nCRT and 949.9 ± 28.4 ms for control patients (p = 0.40). The radiologist (NP) reported intramural LGE in 4 irradiated patients versus 1 control patients (p = 0.17). In addition, the post-contrast T1 values were 404.9 ± 25.1 ms and 431.6 ± 33.7 ms for nCRT and control patients respectively (p = 0.02), which indicates more diffuse LGE in the nCRT group. ECV measurements, as a surrogate for histologic collagen burden of the myocardium, were higher in nCRT patients compared with control patients (28.4% ± 1.0% vs 24.0% ± 0.9%; P < .001). This increased mean global ECV indicates diffuse myocardial fibrosis in nCRT patients, which may be attributed to the cardiac co-irradiation. When focusing on the LV myocardial segment level, mean ECV was quite similar in all segments of the control patients (figure 3). Large ECV deviations between segments were seen in the nCRT group, with the highest ECV values measured in the basal and mid septal and inferior segments (e.g. segment 2, 3, 4, 5, 8, 9, 10), which is typically the area of the left ventricular wall that is located near the esophagus and nodal regions (radiotherapy target volume) and therefore receives the highest radiation dose. For the nCRT group, the mean dose in the LV segments with elevated ECV (>27.7 %) was on average 24 Gy versus 11 Gy in segments with normal ECV (p = 0.03). However, even segments that received low radiation doses showed increased ECV compared to control segments. For instance, we found on average 26.3 % ECV in segments with a mean dose ≤ 5 Gy (n = 55), which is significantly higher than the mean ECV of 24.0% in the control group (p=0.03). Figure 4 indicates the mean LV segmental ECV for nCRT (A2) and control (A1) patients. For the nCRT patients, the dose distribution (B) is shown as an average mean segment dose for the corresponding segments. Mean segment dose and ECV for each individual LV myocardial segment (nCRT patients) are presented in figure 5. Mixed model analyses show a significant effect of myocardial segment mean dose on ECV (0.136, 95%CI 0.114 – 0.158, p<0.001). Variables such as age, hypertension, atrial fibrillation, diabetes mellitus and hypercholesterolemia, time after treatment and lung dose(mean lung dose, V5 an V20 lung) were no confounders. The final random intercept model in the irradiated group, after internal validation using 2500 semiparametric bootstrap samples, was ECV = 25.88 + (0.136*mean myocardial
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