Longitudinal Magnetic Resonance Imaging of Cerebral Microbleeds in Multiple Sclerosis Patients.

Karthikeyan Subramanian,Rajasimhan Rajagovindan,Jesper Hagemeier,Ferdinand Schweser,Deepa P Ramasamy,David Utriainen,John Beaver,Robert Zivadinov,Ewart Mark Haacke,Sean K Sethi,Bianca Weinstock-Guttman

doi:10.3390/diagnostics10110942

Abstract

We hypothesized that cerebral microbleeds (CMBs) in multiple sclerosis (MS) patients will be detected with higher prevalence compared to healthy controls (HC) and that quantitative susceptibility mapping (QSM) will help remove false positives seen in susceptibility weighted imaging (SWI). A cohort of 100 relapsing remitting MS subjects scanned at 3T were used to validate a set of CMB detection guidelines specifically using QSM. A second longitudinal cohort of 112 MS and 25 HCs, also acquired at 3T, was reviewed across two time points. Both cohorts were imaged with SWI and fluid attenuated inversion recovery. Fourteen subjects in the first cohort (14%, 95% CI 8–21%) and twenty-one subjects in the second cohort (18.7%, 95% CI 11–27%) had at least one CMB. The combined information from SWI and QSM allowed us to discern stable CMBs and new CMBs from potential mimics and evaluate changes over time. The longitudinal results demonstrated that longer disease duration increased the chance to develop new CMBs. Higher age was also associated with increased CMB prevalence for MS and HC. We observed that MS subjects developed new CMBs between time points, indicating the need for longitudinal quantitative imaging of CMBs.

Highlights

Cerebral microbleeds (CMBs) are small foci of chronic blood products in normal or near normal brain tissue [1]
Susceptibility Weighted Imaging (SWI) is more sensitive compared to 2D T2* gradient echo (GRE) imaging [16,17,18] in detecting cerebral microbleeds (CMBs); it is limited in its ability to distinguish the magnetic state of an object
None of the CMBs in cohort 1 were co-localized with existing multiple sclerosis (MS) lesions such as acute breakdown of the blood-brain barrier (BBB) as observed by parenchymal contrast agent leakage in T1 weighted imaging (T1WI), T1WI hypo-intensities, or hyper-intensities in T2 fluid attenuated inversion recovery (FLAIR)

Summary

Introduction

Cerebral microbleeds (CMBs) are small foci of chronic blood products in normal or near normal brain tissue [1]. They represent a radiologic construct which correlates with histopathology [2,3], hemosiderin deposition from past hemorrhages that manifest as focal hypo-intense lesions on T2*-weighted gradient echo (GRE) images. CMBs have been associated with decreased cognitive performance in both traumatic brain injury (TBI) [14] and stroke patients [15]. The use of phase information and iterative Susceptibility Weighted Imaging and Mapping (iSWIM) [19,20] (a form of Quantitative Susceptibility Mapping (QSM) [21]) can overcome this limitation and, the signal source type (calcium or iron) can be differentiated and quantified [21]

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