Use of ultrasmall superparamagnetic particles of iron oxide (USPIO)‐enhanced MRI to demonstrate diffuse inflammation in the normal‐appearing white matter (NAWM) of multiple sclerosis (MS) patients: An exploratory study

Abstract

Purpose:To explore ultrasmall superparamagnetic particles of iron oxide (USPIO) as a marker for diffuse inflammation in multiple sclerosis (MS) normal-appearing white matter (NAWM), using quantitative MRI. Disease activity in the NAWM of MS patients partly explains why MRI lesion burden correlates only moderately with disability. USPIO have been shown to visualize the cellular component of inflammation in focal MS lesions. In this study, we aimed to explore USPIO as a marker for the more diffuse inflammation in MS NAWM, using quantitative MRI. Materials and Methods:In this prospective MRI study, 16 MS patients (eight relapsing-remitting MS [RRMS] and eight primary-progressive MS [PPMS] cases) and five healthy control (HC) subjects were included. Using a flipangle (FA) array, B1-corrected T1 maps were generated before and 24 hours after USPIO (SHU555C) injection. White-matter (WM) T1 histogram and region-of-interest (ROI) characteristics were compared between both time points using Wilcoxon signed-rank test.Results: Both NAWM ROI and histogram analyses showed T1 shortening after USPIO injection in MS patients (P Ͻ 0.01), but not in HCs (P ϭ 0.68). Conclusion:This exploratory study suggests that USPIOenhanced MRI may be a new potential marker for subtle inflammatory activity in MS NAWM. Further studies should focus on relating diffuse inflammation to clinical disease activity and treatment efficacy.

Novel MRI and PET markers of neuroinflammation in multiple sclerosis

“…[27] Furthermore, global changes in the T1 signal in normal appearing brain tissue can demonstrate subtle generalized inflammatory activity without apparent BBB damage. [28] Clinical pilot trials have demonstrated that the use of both GBCA and USPIO in MS patients identifies more inflammatory lesions than gadolinium alone, range from a 4% to 244% increase. [27,29,30] The subgroup of lesions that enhanced with both contrast agents were characterized by a more severe evolution.…”

Anomalous Venous Blood Flow and Iron Deposition in Multiple Sclerosis

“…In addition, USPIO-enhanced MRI seems to be a new marker for diffuse inflammation in MS normalappearing white matter (Vellinga et al, 2009). Interestingly, three patterns of USPIO-enhancement have been observed, contrary to routine Gd-DTPA, showing that sensitivity and specificity of MRI in MS can be improved using USPIO.…”

Neuroimaging in Multiple Sclerosis

“…Moreover, the same lesions can change their pattern of enhancement over time (Vellinga et al, 2008). Furthermore, USPIO-enhanced MRI may not only disclose a greater number of 'active' MS lesions but may also detect subtle and diffuse inflammatory activity in MS patients not visible on conventional T2-weighted MR sequences and unrelated to Gd-DTPA enhancement (Vellinga et al, 2009 …”