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Updated: Jul 1, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Metabolic changes in normal-appearing white matter associate with MRI measures of disease burden in
Anna Zöchner1,2, Wolfgang Bogner1,2,3, Assunta Dal-Bianco4
1High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Lazarettgasse 14, 1090, Vienna, Austria.
Abstract:
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 (βtimepoint: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.
Insights
Myo-inositol and N-acetylaspartate levels in normal-appearing white matter show promise as biomarkers for multiple sclerosis progression. These metabolic changes, detected by 7T MRSI, correlate with disease burden and worsening over time.
Area of Science:
- Neuroimaging
- Biochemistry
- Neurology
Background:
- Multiple sclerosis (MS) involves smouldering-associated worsening, with potential biomarkers like myo-inositol (mI) and total N-acetylaspartate (tNAA) needing further investigation.
- Normal-appearing white matter (NAWM) in patients with relapsing-remitting MS (pwRRMS) may harbor subclinical metabolic changes indicative of disease progression.
Purpose of the Study:
- To explore metabolic alterations in NAWM of pwRRMS using high-field 7 Tesla (7T) MR spectroscopic imaging (MRSI).
- To assess the longitudinal changes in mI/tNAA and tNAA/total creatine (tCr) ratios and their association with established MRI measures of MS disease burden.
Main Methods:
- 2D-MRSI at 7T was performed annually on 20 pwRRMS for up to three years.
- Metabolic ratios (mI/tNAA, tNAA/tCr) in NAWM were calculated and correlated with cross-sectional and longitudinal MRI data, including paramagnetic rim lesions (PRLs), brain atrophy, and T2 lesion load.
Main Results:
- At baseline, pwRRMS exhibited higher mI/tNAA and lower tNAA/tCr compared to controls.
- Lower tNAA/tCr was associated with the presence of PRLs.
- Higher mI/tNAA correlated with greater T2 lesion volume and lower white matter volume.
- Longitudinally, mI/tNAA increased in pwRRMS, particularly in those with a higher PRL count.
Conclusions:
- Alterations in mI and tNAA are relevant imaging biomarkers reflecting underlying pathology in MS.
- 7T MRSI is valuable for detecting subclinical disease burden in MS.
- Paramagnetic rim lesions are associated with widespread white matter damage in MS.
