χ-separation can assess the effects of tissue destruction in early MS lesions

Applying a novel mathematical algorithm called the chi (χ)-separation to MRI images showed that younger MS patients, particularly those with low disability and a low Expanded Disability Status Scale (EDSS) score, have more tissue destruction in white matter lesions, but also a higher capacity for remyelination. Changes in myelin content were linked to disability over time.

Iron plays a critical role in myelin formation and repair, as well as in neurodegenerative processes that occur in 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 separate assessment of myelin and iron distribution in the brain. Dr Jannis Müller (University of Basel, Switzerland) and colleagues 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 white matter lesions, cortical lesions, and surrounding normal-appearing tissue.

The researchers included 168 MS patients; 101 (64%) were women, the 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=-5.111×10⁻⁵; aR²=0.003; P<0.001);
• lower disability (β=-2.664×10⁻⁴; aR²=0.001; P<0.001); and
• relapsing-remitting MS phenotype (compared with progressive MS, 0.0026 vs 0.0011; P<0.001).

Changes in myelin-sensitive susceptibility maps correlated with clinical improvement as measured by EDSS score (β=-6.686×10⁻⁴; aR²=0.004; P=0.015).

1. Müller J, et al. Magnetic susceptibility source separation shows longitudinal changes in myelin and iron in white matter and cortical lesions in multiple sclerosis patients. P168, MSMilan 2023, 11–13 October, Milan, Italy.

 

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Posted on 4 December 20234 December 2023