title: Assessing cardiac injury in mice with dual energy-microCT, 4D-microCT, and microSPECT imaging after partial heart irradiation.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
authors: Chang-Lung
authors: CL
authors: Lee
authors: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
authors: Hooney
authors: H
authors: Min
authors: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors: Nicholas
authors: N
authors: Befera
authors: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors: Darin
authors: D
authors: Clark
authors: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors: Yi
authors: Y
authors: Qi
authors: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
authors: Shiva
authors: S
authors: Das
authors: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors: G Allan
authors: GA
authors: Johnson
authors: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors: Cristian T
authors: CT
authors: Badea
authors: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina. Electronic address: david.kirsch@duke.edu.
authors: David G
authors: DG
authors: Kirsch
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000528:radiation effects; D003287:Contrast Media; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000528:radiation effects; D004195:Disease Models, Animal; D056973:Four-Dimensional Computed Tomography / Q000379:methods*; D006046:Gold; D006321:Heart / Q000000981:diagnostic imaging / Q000528:radiation effects*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000528:radiation effects; D051379:Mice; D053758:Nanoparticles; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D003287:Contrast Media; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; C078700:technetium tc-99m tetrofosmin; D006046:Gold