MRI in multiple sclerosis : early detection, cortical lesions and gadolinium retention

Abstract

Background: Multiple sclerosis (MS) is a common neuroinflammatory and -degenerative disease. Magnetic Resonance Imaging (MRI) facilitates the diagnosis of MS, providing means to initiate early treatment and improving the long-term outcome. MRI can unveil MS in a pre-/subclinical phase as incidental findings in persons without typical MS symptoms, a condition called Radiologically Isolated Syndrome (RIS). New MRI techniques like synthetic MRI and phase-sensitive inversion recovery (PSIR) can further improve the visualization of MS pathology. Gadolinium-based contrast agents (GBCAs) are used in MS to evaluate disease activity but lead to retention of small amounts of gadolinium in the brain. These new developments highlight the need to constantly evaluate current and new MRI methods in an evidence-based manner to make informed decisions on how to optimize MS diagnostics.

Study I investigated the incidence of RIS from a population-based perspective, in a Swedish region with high MS-. All 2272 brain MRI scans performed in the county during one year were assessed by a senior radiologist and neuroradiologist for RIS. Only two cases of RIS was found, constituting merely 0.8 cases per 100,000 person-years, which is low compared to the MS-incidence in Sweden of 10.2 cases per 100,000 person-years. Study II compared the ability of conventional and synthetic PSIR to detect leukocortical lesions in 21 MS patients and studied the clinical relevance of the findings. The study showed that conventional and synthetic PSIR have comparable sensitivity for leukocortical MS lesions with excellent inter-rater agreement. Furthermore, the detected leukocortical lesion volumes were associated with lower cognitive scores, highlighting the clinical relevance. Study III retrospectively investigated gadolinium retention with conventional T1-weighted brain MRI. The dentate nucleus and globus pallidus were assessed in an 18-year follow-up study of 23 patients and 23 cross-sectional controls. Possible associations with cognitive deficits were also explored. The study showed that a higher number of GBCA administrations was associated with higher T1-signal intensity index in both the dentate nucleus and globus pallidus. After correcting for several factors related to MS disease severity, an association remained between higher signal intensity and lower verbal fluency performance. Study IV used simultaneous T1- and T2-relaxometry (synthetic MRI) to quantitatively assess the relationship between GBCA administrations and MRI relaxation rates (R1 and R2) in a prospective cohort of 85 MS patients along with 21 healthy controls without GBCA exposure. A higher number of administrations of linear, but not macrocyclic, GBCAs was associated with a dose-dependent increase in R1 and R2 in the studied structures (dentate nucleus, globus pallidus, caudate nucleus and thalamus). Furthermore, higher relaxation rates were associated with lower cognitive performance, but not increased physical disability or fatigue.

Conclusions: RIS is a relatively rare phenomenon in a region with high MS-incidence. The RIS-incidence may, however, increase with improved MRI technologies and availability. Synthetic MRI provides PSIR that allows detection of leukocortical lesions with a similar sensitivity to conventional PSIR, without additional scan time. Linear GBCAs are associated with brain gadolinium retention that causes both T1 and T2 effects on MRI. These MRI signal changes are associated with lower cognitive performance, but that does not necessarily imply causality since the correlations may be confounded by MS pathology.