Nitroxide-enhanced MRI of cardiovascular oxidative stress

Soham A. Shah, Sophia X. Cui, Christopher D. Waters, Soichi Sano, Ying Wang, Heather Doviak, Jonathan Leor, Kenneth Walsh, Brent A. French, Frederick H. Epstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In vivo imaging of oxidative stress can facilitate the understanding and treatment of cardiovascular diseases. We evaluated nitroxide-enhanced MRI with 3-carbamoyl-proxyl (3CP) for the detection of myocardial oxidative stress. Methods: Three mouse models of cardiac oxidative stress were imaged, namely angiotensin II (Ang II) infusion, myocardial infarction (MI), and high-fat high-sucrose (HFHS) diet-induced obesity (DIO). For the Ang II model, mice underwent MRI at baseline and after 7 days of Ang II (n = 8) or saline infusion (n = 8). For the MI model, mice underwent MRI at baseline (n = 10) and at 1 (n = 8), 4 (n = 9), and 21 (n = 8) days after MI. For the HFHS-DIO model, mice underwent MRI at baseline (n = 20) and 18 weeks (n = 13) after diet initiation. The 3CP reduction rate, Kred, computed using a tracer kinetic model, was used as a metric of oxidative stress. Dihydroethidium (DHE) staining of tissue sections was performed on Day 1 after MI. Results: For the Ang II model, Kred was higher after 7 days of Ang II versus other groups (p < 0.05). For the MI model, Kred, in the infarct region was significantly elevated on Days 1 and 4 after MI (p < 0.05), whereas Kred in the noninfarcted region did not change after MI. DHE confirmed elevated oxidative stress in the infarct zone on Day 1 after MI. After 18 weeks of HFHS diet, Kred was higher in mice after diet versus baseline (p < 0.05). Conclusions: Nitroxide-enhanced MRI noninvasively quantifies tissue oxidative stress as one component of a multiparametric preclinical MRI examination. These methods may facilitate investigations of oxidative stress in cardiovascular disease and related therapies.

Original languageEnglish
Article numbere4359
JournalNMR in Biomedicine
Volume33
Issue number9
DOIs
StatePublished - 1 Sep 2020

Keywords

  • MRI
  • cardiovascular
  • heart
  • nitroxides
  • oxidative stress
  • preclinical

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