Mapping Exchangeable Protons to Monitor Protein Alterations in the Brain of an Alzheimer’s Disease Mouse Model by Using MRI

Objective: The study aimed to investigate exchangeable proton signals of Aβ proteins of the brains of Alzheimer’s disease (AD) model mice by using a chemical exchange-sensitive spin-lock (CESL) MR imaging technique. Method: Eight non-transgenic (Tg) mice (5 young and 3 old) and twelve Tg-APPswe/PSdE9 mice (5 young and 7 old) were used in this study. CESL Z-spectra were obtained by using two saturation powers, which were ω1 = 25 Hz with TSL = 3.0 s and ω1 = 500 Hz with TSL = 150 ms, at 71 offsets with uneven intervals between the offset frequencies at Ω = ±7.0 ppm at a 9.4-T animal MRI system. For Zspectrum analyses, regions of interest (ROIs) were drawn in the cortex, hippocampus, and thalamus of both hemispheres. Magnetization transfer ratio asymmetry (MTRasym) curves were obtained from the Zspectra. The Mann-Whitney test was used to compare the MTRasym values between the Tg and non-Tg mice for each offset frequency and for each ROI. Results: The water saturation width of the full Z-spectrum was narrow with the 25-Hz saturation power, but relatively broad with the 500-Hz saturation power. With the 25-Hz CESL saturation power, most of the MTRasym values were negative for 3.5-, 3.0-, 2.0-, and 0.9-ppm offset frequencies and the MTRasym values were significantly different between the control and Tg groups only in the left thalamus region at 3.5 ppm offset (p=0.0487). The MTRasym values were -6% to -7% for both 3.5 and 3.0 ppm, but less than -2% for both 2.0 and 0.9 ppm. With 500-Hz CESL saturation power, all the MTRasym values were positive for the 3.5-, 3.0-, 2.0-, and 0.9-ppm offset frequencies and the MTRasym values were not significantly different between the control and Tg groups at all ROIs and at all offset frequencies. However, a trend towards a significant difference was observed between the control and Tg groups in the right cortex at 3.5 ppm (p=0.0578). The MTRasym values were 6% to 9% for 3.5, 3.0, and 2.0 ppm, but less than 2% for 0.9 ppm. Conclusion: In an in-vivo AD model experiment, MTRasym values increased with the high saturation power than with the low saturation power. The MTRasym values were not significantly different, except in the left thalamus region at 3.5 ppm offset. The CESL technique should be further developed to enable its application in the brain of patients with neurodegenerative diseases.