Abstract
BACKGROUND: The differential diagnosis of multiple sclerosis (MS) and cerebral small vessel disease (SVD) is challenging on conventional sequences. This study aimed to explore the utility of in vivo proton exchange rate (k(ex) ) magnetic resonance imaging (MRI) and quantitative susceptibility mapping (QSM) in distinguishing MS from SVD. METHODS: This Institutional Review Board (IRB)-approved retrospective study included 40 relapsing-remitting MS patients, 23 SVD patients, and 25 healthy controls (HCs), who underwent QSM and k(ex) MRI. The susceptibility and k(ex) values were compared among MS white matter lesions (MS-WMLs), lacunes, and white matter hyperintensities (WMHs) of SVD, with receiver operating characteristic (ROC) analysis performed. RESULTS: Susceptibility increase (ΔSusceptibility) and k(ex) elevation (Δk(ex) ) were both higher in MS-WMLs than they were in WMHs (31.60±21.76 vs. 4.96±9.30 ppb, P<0.001; 147.01±100.34 vs. 58.37±43.81 s(-1), P<0.001). The k(ex) values were higher in normal appearing white matter of MS and SVD than in normal white matter (NWM) of HCs (650.74±42.84 or 645.00±23.62 vs. 608.99±23.77 s(-1), P<0.001). No WMHs presented ring hyperintensity on QSM. The percentage of ring QSM hyperintensity of lacunes was larger than that of MS-WMLs. The rings of MS-WMLs were more regular and evenly thickened than those of lacunes. A significantly positive correlation between k(ex) elevation and susceptibility increase was noticed only in MS. Compared with women, men showed slightly higher Δk(ex) of WMLs and NAWM in MS, WMHs, and lacunes in SVD and higher ΔSusceptibility of MS-WMLs. The accuracy for differentiating MS-WMLs from WMHs and lacunes with Δk(ex) and ΔSusceptibility together [area under the curve (AUC) =0.910, 95% confidence interval (CI): 0.875-0.938] was higher than that when using them alone. CONCLUSIONS: The in vivo visualization and quantification of oxidative stress and iron deposition via k(ex) MRI and QSM are potential biomarkers to promote the early differential diagnosis of MS and SVD.