Key result
In RRMS, rising mI/tNAA ratio in normal-appearing white matter is linked to paramagnetic rim lesion count.
Why the study?
Myo-inositol and total N-acetylaspartate are potential MR spectroscopic imaging biomarkers of smouldering-associated worsening in multiple sclerosis, prompting exploration of metabolic changes in normal-appearing white matter using 7 T MRSI.
Does 7T MRSI detect metabolic changes associated with disease burden in patients with relapsing-remitting MS?
Observational (n=40)
No
Does 7T MRSI detect metabolic changes associated with disease burden in patients with relapsing-remitting MS?
Effect estimate: β 0.014
p-value: p=0.022
7T MRSI reveals that metabolic alterations in normal-appearing white matter, particularly increased mI/tNAA, are associated with paramagnetic rim lesions and progressive white matter damage in relapsing-remitting MS.
Suggests ultra-high-field imaging may detect early neurodegeneration in normal-appearing white matter.
Myo-inositol (mI) and total N-acetylaspartate (tNAA) are potential MR spectroscopic imaging (MRSI) biomarkers of smouldering-associated worsening in multiple sclerosis (MS). In this study, we explored metabolic changes in normal-appearing white matter (NAWM) in patients with relapsing–remitting MS (pwRRMS) using 7 T MRSI. 20 pwRRMS were scanned annually with 2D-MRSI, with follow-up ranging up to three years. Metabolic ratios were calculated within NAWM for each measurement and assessed cross-sectionally and longitudinally with established and emerging MRI measures of disease burden, including paramagnetic rim lesions (PRLs), brain atrophy, and T2 lesion load. At baseline, pwRRMS showed higher mI/tNAA (β = 0.058; p = 0.047) and lower tNAA/total creatine (tCr) (β = − 0.106; p = 0.029) compared to controls. tNAA/tCr was further reduced in pwRRMS with PRLs (β = − 0.138; p = 0.022). mI/tNAA was associated negatively with cerebral WM volume (β = − 0.001, p = 0.015) and positively with T2 lesion volume (β = 0.009; p = 0.044). mI/tNAA increased longitudinally in pwRRMS (β = 0.014; p = 0.022), especially with higher PRL count (β timepoint:PRLcount = 0.016; p = 0.045). An association between tNAA/tCr and the interaction of time with total GM volume was observed but did not survive FDR-correction (β = 0.001; p = 0.078). These findings further support the clinical relevance of mI and tNAA alterations as imaging biomarkers of underlying pathology in MS. They highlight the value of 7 T MRSI in capturing subclinical disease burden and underscore the association of PRLs with overall widespread WM damage.
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Zöchner et al. (2026) conducted an observational in Relapsing-remitting multiple sclerosis (n=40). 7T 2D-MRSI vs. Healthy controls was evaluated on Longitudinal change in mI/tNAA ratio in normal-appearing white matter (β 0.014, p=0.022). In patients with relapsing-remitting multiple sclerosis, the mI/tNAA ratio in normal-appearing white matter increased significantly over three years (β=0.014) and was associated with paramagnetic rim lesion count.
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