Elucidating metabolite and pH variations in stroke through guanidino, amine and amide CEST MRI: A comparative multi-field study at 9.4T and 3T

Kexin Wang; Licheng Ju; Guanda Qiao; Yajie Liang; Yihan Wu; Chengyan Chu; Joshua Rogers; Yuguo Li; Suyi Cao; Valina L Dawson; Ted M Dawson; Piotr Walczak; Jiadi Xu

doi:10.1016/j.neuroimage.2024.120993

Elucidating metabolite and pH variations in stroke through guanidino, amine and amide CEST MRI: A comparative multi-field study at 9.4T and 3T

Neuroimage. 2025 Jan:305:120993. doi: 10.1016/j.neuroimage.2024.120993. Epub 2024 Dec 31.

Authors

Kexin Wang¹, Licheng Ju², Guanda Qiao³, Yajie Liang³, Yihan Wu¹, Chengyan Chu³, Joshua Rogers³, Yuguo Li², Suyi Cao⁴, Valina L Dawson⁵, Ted M Dawson⁶, Piotr Walczak³, Jiadi Xu⁷

Affiliations

¹ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
² F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Neuroregeneration and Stem Cell Programs, The Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Neuroregeneration and Stem Cell Programs, The Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Neuroregeneration and Stem Cell Programs, The Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: [email protected].

PMID: 39746412
DOI: 10.1016/j.neuroimage.2024.120993

Abstract

This study aims to investigate the variations in guanidino (Guan), amine and amide chemical exchange saturation transfer (CEST) contrasts in ischemic stroke using permanent middle cerebral artery occlusion (pMCAO) and transient MCAO (tMCAO) models at high (9.4T) and clinical (3T) MRI fields. CEST contrasts were extracted using the Polynomial and Lorentzian Line-shape Fitting (PLOF) method. Both pMCAO and tMCAO models were utilized to examine the B₁-dependence patterns and pH sensitivity of the different CEST contrasts in ischemic lesions compared to contralateral region. At 9.4T, GuanCEST showed the highest signal in the contralateral hemisphere for both stroke models, followed by lower signals from amideCEST and amineCEST, with maximum signals at B₁=1.2 μT for all CEST contrasts. In both stroke models, GuanCEST exhibited a significant decrease of 1.15-1.5 % in stroke lesions compared to the contralateral hemisphere (ΔGuanCEST) at an optimal B₁ range of 1.2-1.6 μT at 9.4T. This represents more than double the pH sensitivity compared to amideCEST, which showed a reduction of 0.5-0.62 % under the same B₁ conditions. In the tMCAO model, amineCEST increased by 3.85 % in the stroke lesion compared to the contralateral hemisphere at an optima B₁ range of 1.6-2.5 μT. In contrast, for the pMCAO model, amineCEST increased by 0.87-1.0 % in the stroke lesion. At lower B₁ values (<0.8 μT at 9.4T and <0.4 μT at 3T), the GuanCEST changes in the stroke lesion were dominated by creatine concentration changes, which increased in the pMCAO and remained stable in the tMCAO. While GuanCEST and amineCEST are highly sensitive for delineating stroke lesions, amideCEST is more suitable for precise pH mapping as it is not influenced by metabolite changes within the stroke lesion. Additionally, at low B₁ values, amideCEST and GuanCEST can be used to map protein and creatine concentrations separately, since they are independent of pH changes at these lower B₁ values. Lastly, amineCEST serves as a highly sensitive MRI contrast for detecting reperfusion damage at high MRI fields.

Keywords: AmideCEST; Amine CEST (amineCEST); Arginine CEST (ArgCEST); Chemical Exchange Saturation Transfer (CEST); Creatine CEST (CrCEST); Creatine mapping; Guanidino or guanidinium CEST (GuanCEST); Permanent middle cerebral artery occlusion (pMCAO); Polynomial Lorentzian Line-shape Fitting (PLOF); Reperfusion; Stroke; Transient middle cerebral artery occlusion (tMCAO); pH mapping.

Publication types

Comparative Study

MeSH terms

Amides*
Amines* / metabolism
Animals
Brain / diagnostic imaging
Brain / metabolism
Hydrogen-Ion Concentration
Infarction, Middle Cerebral Artery / diagnostic imaging
Infarction, Middle Cerebral Artery / metabolism
Ischemic Stroke / diagnostic imaging
Ischemic Stroke / metabolism
Magnetic Resonance Imaging* / methods
Male
Rats
Rats, Sprague-Dawley
Stroke / diagnostic imaging
Stroke / metabolism

Substances

Amides
Amines