Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

BACKGROUND: Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured. METHOD: In five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method. RESULTS: MBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories. CONCLUSION: In this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.

Detection and quantification of myocardial reperfusion hemorrhage using T2*-weighted CMR.

OBJECTIVES: The purpose of this study was to validate T2*-weighted cardiac magnetic resonance (T2*-CMR) for the detection and quantification of reperfusion hemorrhage in vivo against an ex vivo gold standard, and to investigate the relationship of hemorrhage to microvascular obstruction, infarct size, and left ventricular (LV) functional parameters. BACKGROUND: Hemorrhage can contribute to reperfusion injury in myocardial infarction and may have significant implications for patient management. There is currently no validated imaging method to assess reperfusion hemorrhage in vivo. T2*-CMR appears suitable because it can create image contrast on the basis of magnetic field effects of hemoglobin degradation products. METHODS: In 14 mongrel dogs, myocardial infarction was experimentally induced. On day 3 post-reperfusion, an in vivo CMR study was performed including a T2*-weighted gradient-echo imaging sequence for hemorrhage, standard sequences for LV function, and post-contrast sequences for microvascular obstruction and myocardial necrosis. Ex vivo, thioflavin S imaging and triphenyl-tetrazoliumchloride (TTC) staining were performed to assess microvascular obstruction, hemorrhage, and myocardial necrosis. Images were analyzed by blinded observers, and comparative statistics were performed. RESULTS: Hemorrhage occurred only in the dogs with the largest infarctions and the greatest extent of microvascular obstruction, and it was associated with more compromised LV functional parameters. Of 40 hemorrhagic segments on TTC staining, 37 (92.5%) were positive for hemorrhage on T2*-CMR (kappa = 0.96, p < 0.01 for in vivo/ex vivo segmental agreement). The amount of hemorrhage in 13 affected tissue slices as determined by T2*-CMR in vivo correlated strongly with ex vivo results (20.3 ± 2.3% vs. 17.9 ± 1.6% per slice; Pearson r = 0.91; r(2) = 0.83, p < 0.01 for both). Hemorrhage size was not different between in vivo T2*-CMR and ex vivo TTC (mean difference 2.39 ± 1.43%; p = 0.19). CONCLUSIONS: T2*-CMR accurately quantified myocardial reperfusion hemorrhage in vivo. Hemorrhage was associated with more severe infarct-related injury.