In Vivo Proton Exchange Rate (k_ex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

Abstract

BackgroundCurrently available radiological methods do not completely capture the diversity of multiple sclerosis (MS) lesion subtypes. This lack of information hampers the understanding of disease progression and potential treatment stratification. For example, inflammation persists in some lesions after gadolinium (Gd) enhancement resolves. Novel metabolic and molecular imaging methods may improve the current assessments of MS pathophysiology.PurposeTo compare the in vivo proton exchange rate (kex) MRI with Gd‐enhanced MRI for characterizing MS lesions.Study TypeRetrospective.SubjectsSixteen consecutively diagnosed relapsing‐remitting multiple sclerosis (RRMS) patients.Field Strength/Sequence3.0T MRI with T2‐weighted imaging, postcontrast T1‐weighted imaging, and single‐slice chemical exchange saturation transfer imaging.AssessmentMS lesions in white matter were assessed for Gd enhancement and kex elevation compared to normal‐appearing white matter (NAWM).Statistical TestsStudent's t‐test was used for analyzing the difference of kex values between lesions and NAWM, with statistical significance set at 0.05.ResultsOf all 153 MS lesions, 78 (51%) lesions were Gd‐enhancing and 75 (49%) were Gd‐negative. Without exception, all 78 Gd‐enhancing lesions showed significantly elevated kex values compared to NAWM (924 ± 130 s–1 vs. 735 ± 61 s–1, P < 0.05). Of 75 Gd‐negative lesions, 18 lesions (24%) showed no kex elevation (762 ± 29 s–1 vs. 755 ± 28 s–1, P = 0.47) and 57 (76%) showed significant kex elevation (950 ± 124 s–1 vs. 759 ± 48 s–1, P < 0.05) compared to NAWM. MS lesions with kex elevation appeared nodular (118, 87.4%), ring‐like (15, 11.1%), or irregular‐shaped (2, 1.5%).Data ConclusionFor Gd‐enhancing lesions, kex MRI is highly consistent with Gd‐enhanced images by showing 100% of elevated kex. For all Gd‐negative lesions, the discrepancy on kex MRI may further differentiate active slowly expanding lesions or chronic inactive lesions, supporting kex as an imaging biomarker for tissue oxidative stress and inflammation.Level of Evidence 2Technical Efficacy Stage 3J. MAGN. RESON. IMAGING 2021;53:408–415.

B1 inhomogeneity corrected CEST MRI based on direct saturation removed omega plot model at 5T

“…Note that a tiny peak mounting on residual spectrum was shown around 0 ppm, as observed in previous studies 20,38,39 . One of the possible reasons may be that the adopted conventional multi‐Lorentzian model does not account for the interaction between CEST pools and water.…”

“…Note that a tiny peak mounting on residual spectrum was shown around 0 ppm, as observed in previous studies. 20,38,39 One of the possible reasons may be that the adopted conventional multi-Lorentzian model does not account for the interaction between CEST pools and water. Therefore, the sum of fitted Lorentzians would slightly deviate from the acquired signal near 0 ppm where the tails of multiple Lorentzians overlap.…”

Oxidative stress in multiple sclerosis—Emerging imaging techniques

“…The resulting proton exchange rate is significantly altered by the presence of ROS and less so by temperature, metabolite concentrations, and pH of the tissue ( 60 ). In a study of 16 subjects with RRMS, k ex was elevated in gadolinium enhancing lesions, but also in gadolinium-negative, slowly expanding MS lesions which suggests it may be a feasible technique to detect “smoldering” chronically inflamed gadolinium-negative lesions with higher levels of oxidative stress ( 45 ). However, this technique may be limited by long scan duration requirements which limits acquisition to single slices.…”

Combining in vivo proton exchange rate (kex) MRI with quantitative susceptibility mapping to further stratify the gadolinium-negative multiple sclerosis lesions

“…The proton exchange rate ( k ex ) MRI approach ( Shaghaghi et al, 2019 ), derived from chemical exchange saturation transfer (CEST) imaging, has recently been proposed as a non-invasive approach to assess tissue oxidative stress since endogenous ROS have been shown to promote in vivo k ex in tissue ( Tain et al, 2019 ; Shaghaghi and Cai, 2022 ). Our team has previously conducted a preliminary study on k ex MRI showing its potential to further characterize Gd-negative MS lesions ( Ye et al, 2020 ). However, the contrast mechanism of k ex -enhanced MRI as a surrogate biomarker for ROS has not been fully validated.…”