Comparison of Chemical Exchange Saturation Transfer Imaging with Diffusion-weighted Imaging and Magnetic Resonance Spectroscopy in a Rat Model of Hypoxic-ischemic Encephalopathy

Abstract

Purpose: This study aimed to evaluate the effect of chemical exchange saturation transfer (CEST) on the ischemic regions in hypoxic-ischemic encephalopathy (HIE) in comparison with diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) using a 7T-MRI.

Methods: We used neonatal rats (n = 8), aged 8 days, to clarify the progression of HIE. The rat model of HIE was developed by ligating and severing the left common carotid artery, followed by 45 minutes of recovery, and 60 minutes of hypoxia (8% O₂/92% N₂; 34°C). At 0-2 and 24 hours after the onset of HIE, CEST imaging, DWI, and MRS were performed with a 7T-MRI. The magnetization transfer ratio (MTR) asymmetry curves and four MTR asymmetry maps at 0.5, 1.0, 2.0, and 3.5 ppm were calculated using the CEST images. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were calculated by DWI, and brain metabolites were assessed by MRS.

Results: In the ischemic regions of neonatal rats, FA was significantly increased at 0-2 hours and decreased at 24 hours after the onset of HIE. ADC in the ipsilateral side was significantly lower than that of contralateral side. All rats with HIE showed hypointense areas on MTR asymmetry maps (2.0 and 3.5 ppm), that did not correspond with the hyperintense areas on DWI. In addition, a significant increase in lactate levels was observed at 0-2 and 24 hours after the onset of HIE.

Conclusion: CEST MTR maps did not correspond with the hyperintense areas on DWI at 0-2 and 24 hours after the onset of HIE. The change of multi offset CEST signal may be primarily related to the brain metabolites and pH alterations, such as that caused by lactate, after the onset of HIE.

Keywords: chemical exchange saturation transfer; hypoxic-ischemic encephalopathy; magnetic resonance spectroscopy.

Fig. 1

Serial magnetic resonance images of a rat model of HIE on DWI, FA maps, ADC maps, and T₂-weighted imaging. (c and g) Scale × 10⁻³ mm²/s. HIE, hypoxic-ischemic encephalopathy; DWI, diffusion-weighted imaging; FA, fractional anisotropy; ADC, apparent diffusion coefficient.

Fig. 2

FA and ADC values at 0–2 and 24 h after the onset of HIE. FA, fractional anisotropy; ADC, apparent diffusion coefficient; HIE, hypoxic-ischemic encephalopathy; ^*P < 0.0001.

Fig. 3

Serial MTR maps of rats at 0–2 and 24 h after the onset of HIE. MTR asymmetry maps at 0.5, 1.0, 2.0, and 3.5 parts per million. Same slice position as Fig. 1. MTR, magnetization transfer ratio; HIE, hypoxic-ischemic encephalopathy.

Fig. 4

MTR curves at (a) 0–2 and (b) 24 h after the onset of HIE. MTR values of (c) 0.5, (d) 1.0, (e) 2.0, and (f) 3.5 ppm at 0–2 and 24 h after the onset of HIE. MTR, magnetization transfer ratio; HIE, hypoxic-ischemic encephalopathy; ^*P < 0.05.

Fig. 5

Conventional MRS at 0–2 and 24 h after the onset of hypoxic-ischemic encephalopathy. (a) Ipsilateral MRS spectrum at 0–2 h, (b) Contralateral MRS spectrum at 0–2 h, (c) Ipsilateral MRS spectrum at 24 h, and (d) Contralateral MRS spectrum at 24 h. MRS, magnetic resonance spectroscopy.

Fig. 6

Concentrations of five metabolites by MRS at 0–2 and 24 h after the onset of HIE. MRS, magnetic resonance spectroscopy; HIE, hypoxic-ischemic encephalopathy; GPC, glycerophosphocholine; PCh, phosphocholine; NAA, N-acetylaspartate; NAAG, N-acetylaspartylglutamate; Cr, creatine; PCr, phosphocreatine; Glu, glutamate; Gln, glutamine; ^*P < 0.05.