Investigation of relayed nuclear Overhauser enhancement effect at -1.6 ppm in an ischemic stroke model

Lee Sze Foo; James R Larkin; Brad A Sutherland; Kevin J Ray; Wun-She Yap; Choon-Hian Goh; Yan Chai Hum; Khin Wee Lai; George Harston; Yee Kai Tee

doi:10.21037/qims-23-510

Investigation of relayed nuclear Overhauser enhancement effect at -1.6 ppm in an ischemic stroke model

Quant Imaging Med Surg. 2023 Dec 1;13(12):7879-7892. doi: 10.21037/qims-23-510. Epub 2023 Oct 25.

Authors

Affiliations

¹ Lee Kong Chian Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Kajang, Malaysia.
² Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.
³ Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Australia.
⁴ Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur, Malaysia.
⁵ Acute Stroke Service, Oxford University Hospitals National Health Service Foundation Trust, Oxford, UK.

Abstract

Background: When an ischemic stroke happens, it triggers a complex signalling cascade that may eventually lead to neuronal cell death if no reperfusion. Recently, the relayed nuclear Overhauser enhancement effect at -1.6 ppm [NOE(-1.6 ppm)] has been postulated may allow for a more in-depth analysis of the ischemic injury. This study assessed the potential utility of NOE(-1.6 ppm) in an ischemic stroke model.

Methods: Diffusion-weighted imaging, perfusion-weighted imaging, and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) data were acquired from five rats that underwent scans at 9.4 T after middle cerebral artery occlusion.

Results: The apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and apparent exchange-dependent relaxations (AREX) at 3.5 ppm and NOE(-1.6 ppm) were quantified. AREX(3.5 ppm) and NOE(-1.6 ppm) were found to be hypointense and exhibited different signal patterns within the ischemic tissue. The NOE(-1.6 ppm) deficit areas were equal to or larger than the ADC deficit areas, but smaller than the AREX(3.5 ppm) deficit areas. This suggested that NOE(-1.6 ppm) might further delineate the acidotic tissue estimated using AREX(3.5 ppm). Since NOE(-1.6 ppm) is closely related to membrane phospholipids, NOE(-1.6 ppm) potentially highlighted at-risk tissue affected by lipid peroxidation and membrane damage. Altogether, the ADC/NOE(-1.6 ppm)/AREX(3.5 ppm)/CBF mismatches revealed four zones of increasing sizes within the ischemic tissue, potentially reflecting different pathophysiological information.

Conclusions: Using CEST coupled with ADC and CBF, the ischemic tissue may thus potentially be separated into four zones to better understand the pathophysiology after stroke and improve ischemic tissue fate definition. Further verification of the potential utility of NOE(-1.6 ppm) may therefore lead to a more precise diagnosis.

Keywords: Ischemic stroke; amide proton transfer (APT); chemical exchange saturation transfer (CEST); penumbra; relayed nuclear Overhauser enhancement (NOE).

Grants and funding

WT_/Wellcome Trust/United Kingdom