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

Abstract

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.

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Citation

Published Version (Please cite this version)

10.1016/j.ijrobp.2013.11.238

Publication Info

Lee, Chang-Lung, Hooney Min, Nicholas Befera, Darin Clark, Yi Qi, Shiva Das, G Allan Johnson, Cristian T Badea, et al. (2014). Assessing cardiac injury in mice with dual energy-microCT, 4D-microCT, and microSPECT imaging after partial heart irradiation. Int J Radiat Oncol Biol Phys, 88(3). pp. 686–693. 10.1016/j.ijrobp.2013.11.238 Retrieved from https://hdl.handle.net/10161/12625.

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Scholars@Duke

Lee

Chang Lung Lee

Assistant Professor in Radiation Oncology

The overall goal of the Lee lab’s research program is to improve the therapeutic window of radiation therapy and the survivorship of cancer patients by minimizing acute and late effects of radiation. Our current NIH-funded projects primarily focus on defining the mechanisms underlying the regeneration of epithelial cells in the oral mucosa and the small intestines in response to radiation injury. In addition, we are developing novel medical countermeasures for gastrointestinal acute radiation syndrome as well as radiation-induced intestinal fibrosis in the scenarios of nuclear terrorism.

Befera

Nicholas Befera

Assistant Professor of Radiology
Clark

Darin Clark

Assistant Professor in Radiology

Shiva Kumar Das

Adjunct Professor in the Department of Radiation Oncology

Intensity Modulated Radiotherapy optimization. Functional Image-guided radiotherapy (PET, SPECT). Modeling of Radiation-induced normal tissue complications (lung, cardiac) using neural nets, MART, self organizing maps, etc. Optimal selection of beam orientations for radiotherapy. Hyperthermia modeling.

Current Funded Grants:
NCI P01 CA042745-19: Hyperthermia and Perfusion Effects in Cancer Therapy Project 2: Real Time Modeling and Control Using Finite Elements and MRI (Program Director).
NCI 1R01 CA115748-01A1: Accurate Prediction of Cardiac and Lung Radiation Injury (Principal Investigator).
Varian Medical Systems: Incorporation of Functional Image-guidance in Radiotherapy Planning (Principal Investigator).

Graduate School Teaching:
MP322: Advanced Photon Beam Radiation Therapy Planning (Fall Semester)

Postdoctoral Research Associates (Past and Current):
Alan Baydush, Ph.D.
Shifeng Chen, Ph.D.
Kung-Shan Cheng, Ph.D.
Sarah McGuire, Ph.D.
Vadim Stakhursky, Ph.D.

Johnson

G. Allan Johnson

Charles E. Putman University Distinguished Professor of Radiology

Dr. Johnson is the Charles E. Putman University Professor of Radiology, Professor of Physics, and Biomedical Engineering, and Director of the Duke Center for In Vivo Microscopy (CIVM). The CIVM is an NIH/NIBIB national Biomedical Technology Resource Center with a mission to develop novel technologies for preclinical imaging (basic sciences) and apply the technologies to critical biomedical questions. Dr. Johnson was one of the first researchers to bring Paul Lauterbur's vision of magnetic resonance (MR) microscopy to practice as described in his paper, "Nuclear magnetic resonance imaging at microscopic resolution" (J Magn Reson 68:129-137, 1986). Dr. Johnson is involved in both the engineering physics required to extend the resolution of MR imaging and in a broad range of applications in the basic sciences.

Badea

Cristian Tudorel Badea

Professor in Radiology

  • Our lab's research focus lies primarily in developing novel quantitative imaging systems, reconstruction algorithms and analysis methods.  My major expertise is in preclinical CT.
  • Currently, we are particularly interested in developing novel strategies for spectral CT imaging using nanoparticle-based contrast agents for theranostics (i.e. therapy and diagnostics).
  • We are also engaged in developing new approaches for multidimensional CT image reconstruction suitable to address difficult undersampling cases in cardiac and spectral CT (dual energy and photon counting) using compressed sensing and/or deep learning.


Kirsch

David Guy Kirsch

Adjunct Professor in the Department of Radiation Oncology

My clinical interests are the multi-modality care of patients with bone and soft tissue sarcomas and developing new sarcoma therapies. My laboratory interests include utilizing mouse models of cancer to study cancer and radiation biology in order to develop new cancer therapies in the pre-clinical setting.


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