CEST MRI with distribution‐based analysis for assessment of early stage disease activity in a mouse model of multiple sclerosis: An initial study

Abstract

Imaging biomarkers that can detect pathological changes at an early stage of multiple sclerosis (MS) may allow earlier therapeutic intervention with an improved outcome. Using a mouse model of MS, termed as experimental autoimmune encephalomyelitis (EAE), we performed chemical exchange saturation transfer (CEST) MRI at a very early stage before symptom onset (6 days post‐induction) for assessment of changes in tissues that appear “normal” with conventional MRI. The collected CEST Z‐spectra signals (Ssat/S0) were analyzed using a histogram‐guided method to determine the contributions from various offset frequencies. Histogram analysis showed that EAE mice exhibit a more heterogeneous distribution with lower peak heights in the hindbrain compared with naïve mice at saturation offsets of 1 and 2 ppm. At these two offsets, both the mean Ssat/S0 and the mean MTRasym values in the cerebellum and brain stem are significantly different between EAE and naïve mice (P < 0.05). Immunofluorescent staining validated the presence of neuroinflammation, with IBA1‐positive cells detected throughout the hindbrain including the cerebellum and brain stem. Follow‐up MRI at the symptom onset (score = 1.5–2.5, 13 days post‐induction) confirmed gadolinium‐enhanced periventricular lesions. CEST Z‐spectra signals also changed by this time. The proposed three‐level histogram‐oriented analysis is simple to execute and robust for detecting subtle changes in Z‐spectra signals, which does not require a priori knowledge of damage locations or contributing offset components. CEST MRI signals at 1 and 2 ppm were sensitive to the subtle pathological changes at an early stage in EAE mice, and have potential as novel imaging biomarkers complementary to functional and physiological MRI measures.

Enhanced CEST MRI Using the Residual of Inversed Z-Spectra for Ischemia Detection

“…To estimate signal contribution from multiple interested offsets (~1 ppm, ~2 ppm, ~3 ppm, ~3.5 ppm and -2 to -4 ppm), the raw Z-spectra images (S sat /S 0 ) for the stroke rats and the normal rats were evaluated using a previous histogram method [24]. Briefly, at each offsets the histogram of stroke group by pooling all stroke rats brain voxels, was plotted together with that for normal group for comparison.…”

“…Cytotoxic edema and nuclear condensation were well observed in the stroke hemisphere of Rat3, which suggested severer damage compared with Rat1. This study used Z-spectrum with a saturation B 1-sat of 1 μT, which allowed detection of multiple exchanging species, including amines, glutamate, slow exchanging amide protons and NOEs [24]. To fully explore the Z-spectra at the early stage of ischemia, we firstly assessed the contribution of multiple offsets using a previous histogram-guided method [24].…”

“…This study used Z-spectrum with a saturation B 1-sat of 1 μT, which allowed detection of multiple exchanging species, including amines, glutamate, slow exchanging amide protons and NOEs [24]. To fully explore the Z-spectra at the early stage of ischemia, we firstly assessed the contribution of multiple offsets using a previous histogram-guided method [24]. During MCAO, it is known that the effect of APT may decrease due to a drop in tissue pH [26], along with the altered cerebral metabolic rates of oxygen and glucose [27].…”

Glutamate Chemical Exchange Saturation Transfer Imaging and Functional Alterations of Hippocampus in Rat Depression Model: A Pilot Study

“…CEST analysis consisted of three levels: level 1 quantitatively compares the “averaged GluCEST value” of the regions of interest (ROIs, Fig. 2a) drawn by WZ with 5 years of experience in researching rats, level 2 statistically compared the “averaged Z spectra” with selected frequency offsets, and level 3 analyzed the “averaged MTR asym spectra” highlighted in the S sat / S 0 maps of the selected offsets by using traditional methods 24 . The hippocampus was analyzed using Z‐spectra and asymmetric analysis with respect to water frequency (MTR asym = [ S sat (−3 ppm) − S sat (+3 ppm)]/ S 0 ).…”

Correlations of amide proton transfer-weighted MRI of cerebral infarction with clinico-radiological findings

“…Histogram analysis is a quantitative technique has been used in previous CEST studies, e.g. Liu et al applied a histogram distribution-based analysis for CEST signals of a mouse model of multiple sclerosis [24].…”