Younger patients with MS have more tissue destruction in white matter lesions but also a higher capacity for remyelination.
Iron plays a critical role in myelin formation and repair, as well as in neurodegenerative processes that occur in multiple sclerosis (MS). However, the specific quantification of iron and myelin using MRI in vivo remains a challenge. The χ-separation is a novel biophysical model based on quantitative susceptibility mapping. It is a recently proposed method that allows for a separate assessment of myelin and iron distribution in the brain. A group of scientists, including Dr. Jannis Müller (University of Basel, Switzerland) applied χ-separation to longitudinally distinguish between the contributions of iron and myelin to the susceptibility of MS lesions [1]. They applied the χ-separation to acquire multi-echo (T2*) and fast acquisition with spiral trajectory and adiabatic T2-prep (T2). This allowed them to generate myelin-sensitive and iron-sensitive susceptibility maps. FLAIR and MP2RAGE images were used to segment WML, cortical lesions, and surrounding normal-appearing tissue.
The study included 168 patients with MS; 101 (64%) were women, median age was 47.3 years, and the median EDSS score was 3.0. Of this group, 108 were followed up for a median of 2 years. At baseline, significant differences were found between lesions and surrounding normal-appearing tissue. After 2 years, changes in myelin content correlated with disability improvement, while iron levels overall remained stable. Remyelination was associated with:
- Younger age (β = -5.111 x 10-5; aR2 = 0.003; P<001);
- Lower disability (β -2.664 x 10-4; aR2 = 0.001; P<0.001);
- RRMS phenotype (compared with PMS, 0.0026 vs 0.0011, P<0.001).
Changes in myelin-sensitive susceptibility maps correlated with clinical improvement as measured by EDSS score (β = -6.686 x 10-4, aR2 = 0.004; P=0.015).
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