Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina.
Int J Radiat Oncol Biol Phys. 2014 Mar 1;88(3):686-93. doi: 10.1016/j.ijrobp.2013.11.238.
To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT).
To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53(FL/+) and Tie2Cre; p53(FL/-) mice, where 1 or both alleles of p53 are deleted in endothelial cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion.
After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53(FL/-) mice. In Tie2Cre; p53(FL/-) mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53(FL/+) mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R(2) = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53(FL/-) mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated.
Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches complementary to microSPECT for noninvasive assessment of the change in myocardial vascular permeability and cardiac function of mice in whom myocardial injury develops after PHI.
开发一种心脏部分照射（PHI）后心肌损伤的小鼠模型，并验证双能（DE）-microCT 和 4 维（4D）-microCT 是否可用于评估 PHI 后的心肌损伤，以补充微单光子发射计算机断层扫描（microSPECT）的心肌灌注成像。
为了研究切线野照射对小鼠心脏的损伤，我们使用小视野生物辐照器向 Tie2Cre；p53（FL/+）和 Tie2Cre；p53（FL/-）小鼠的左心室（LV）的约三分之一部位单次给予 12 Gy X 射线剂量，其中内皮细胞中 p53 的 1 个或 2 个等位基因缺失。照射后 4 周和 8 周，小鼠注射金和碘基纳米颗粒对比剂，分别用 DE-microCT 和 4D-microCT 进行成像，以评估心肌血管通透性和心功能。此外，对同一只小鼠进行 microSPECT 成像以评估心肌灌注。
在 PHI 用切线野照射后，DE-microCT 扫描显示 Tie2Cre；p53（FL/-）小鼠心肌中纳米金（AuNp）的蓄积呈时间依赖性增加。在 Tie2Cre；p53（FL/-）小鼠中，AuNp 在照射的 LV 内漏出，而在 Tie2Cre；p53（FL/+）小鼠的心肌中，AuNp 局限于血管内。此外，DE-microCT 和 microSPECT 的数据显示，LV 内 AuNp 蓄积分数与 LV 灌注缺陷分数之间呈线性相关（R2=0.97）。此外，4D-microCT 扫描显示 PHI 导致 Tie2Cre；p53（FL/-）小鼠射血分数明显降低，舒张末期和收缩末期容积增加，这与未照射的心脏代偿性心肌肥厚有关。
我们的结果表明，DE-microCT 和基于纳米颗粒的对比剂的 4D-microCT 是一种新的成像方法，可与 microSPECT 互补，用于非侵入性评估 PHI 后小鼠心肌血管通透性和心功能的变化。
