Assessing cardiac injury in mice with dual energy-microCT, 4D-microCT, and microSPECT imaging after partial heart irradiation.

Lee, Chang-Lung

Min, Hooney

Befera, Nicholas

Clark, Darin

Qi, Yi

Das, Shiva

Johnson, G Allan

Badea, Cristian T

Kirsch, David G

United States

2016-08-04T14:05:54Z

2014-03-01

PURPOSE: 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 AND MATERIALS: 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.

http://www.ncbi.nlm.nih.gov/pubmed/24521682

S0360-3016(13)03599-2

1879-355X

https://hdl.handle.net/10161/12625

eng

Elsevier BV

Int J Radiat Oncol Biol Phys

10.1016/j.ijrobp.2013.11.238

Animals

Capillary Permeability

Contrast Media

Coronary Vessels

Disease Models, Animal

Four-Dimensional Computed Tomography

Gold

Heart

Heart Ventricles

Mice

Nanoparticles

Organophosphorus Compounds

Organotechnetium Compounds

Radiation Injuries, Experimental

Tomography, Emission-Computed, Single-Photon

X-Ray Microtomography

Assessing cardiac injury in mice with dual energy-microCT, 4D-microCT, and microSPECT imaging after partial heart irradiation.

Journal article

Lee, Chang-Lung|0000-0002-0673-633X

Befera, Nicholas|0000-0002-3035-7081

Johnson, G Allan|0000-0002-7606-5447

Badea, Cristian T|0000-0002-1850-2522

http://www.ncbi.nlm.nih.gov/pubmed/24521682

686

693

3

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Pharmacology & Cancer Biology

Physics

Radiation Oncology

Radiology

School of Medicine

Trinity College of Arts & Sciences

Published

88