Journal Article

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

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

2025

Overview

•Permanent MCAO mice exhibited increased GuanCEST in stroke lesions with low B1 CEST, along with a significant decrease in Guan and amide CEST with high B1, due to pH changes.•AmineCEST is a highly sensitive MRI contrast for detecting reperfusion damage at high MRI fields, as demonstrated in transient MCAO mice.•At lower B1 values, the changes in GuanCEST within stroke lesions were primarily driven by increased creatine concentrations in permanent MCAO mice, which remained stable in transient MCAO mice.•While Guan and amineCEST are highly sensitive in delineating stroke lesions, amideCEST is better suited for precise pH mapping. 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.

• Publisher: Elsevier Inc,Elsevier Limited,Elsevier
• Subject: Adenosine triphosphate / AmideCEST / Amides - metabolism / Amine CEST (amineCEST) / Amines - metabolism / Animals / Arginine CEST (ArgCEST) / Brain / Brain - diagnostic imaging / Brain - metabolism / Carotid arteries / Cerebral blood flow / Chemical Exchange Saturation Transfer (CEST) / Creatine / Creatine CEST (CrCEST) / Creatine mapping / Field study / Guanidino or guanidinium CEST (GuanCEST) / Hydrogen-Ion Concentration / Infarction, Middle Cerebral Artery - diagnostic imaging / Infarction, Middle Cerebral Artery - metabolism / Ischemia / Ischemic Stroke - diagnostic imaging / Ischemic Stroke - metabolism / Lesions / Magnetic resonance imaging / Magnetic Resonance Imaging - methods / Male / Metabolism / Metabolites / Peptide mapping / Permanent middle cerebral artery occlusion (pMCAO) / pH effects / pH mapping / Polynomial Lorentzian Line-shape Fitting (PLOF) / Proteins / Rats / Reperfusion / Stroke / Stroke - diagnostic imaging / Stroke - metabolism / Transient middle cerebral artery occlusion (tMCAO) / Veins & arteries