Extensive Brain Pathologic Alterations Detected with 7.0-T MR Spectroscopic Imaging Associated with Disability in Multiple Sclerosis, 2022, Heckova+

[SNT Gatchaman]

Extensive Brain Pathologic Alterations Detected with 7.0-T MR Spectroscopic Imaging Associated with Disability in Multiple Sclerosis
Eva Heckova; Assunta Dal-Bianco; Bernhard Strasser; Gilbert J. Hangel; Alexandra Lipka; Stanislav Motyka; Lukas Hingerl; Paulus S. Rommer; Thomas Berger; Petra Hnilicová; Ema Kantorová; Fritz Leutmezer; Egon Kurča; Stephan Gruber; Siegfried Trattnig; Wolfgang Bogner

Background
MR spectroscopic imaging (MRSI) allows in vivo assessment of brain metabolism and is of special interest in multiple sclerosis (MS), where morphologic MRI cannot depict major parts of disease activity. Purpose To evaluate the ability of 7.0-T MRSI to depict and visualize pathologic alterations in the normal-appearing white matter (NAWM) and cortical gray matter (CGM) in participants with MS and to investigate their relation to disability.

Materials and Methods
Free-induction decay MRSI was performed at 7.0 T. Participants with MS and ageand sex-matched healthy controls were recruited prospectively between January 2016 and December 2017. Metabolic ratios were obtained in white matter lesions, NAWM, and CGM regions. Subgroup analysis for MS-related disability based on Expanded Disability Status Scale (EDSS) scores was performed using analysis of covariance. Partial correlations were applied to explore associations between metabolic ratios and disability.

Results
Sixty-five participants with MS (mean age ± standard deviation, 34 years ± 9; 34 women) and 20 ageand sex-matched healthy controls (mean age, 32 years ± 7; 11 women) were evaluated. Higher signal intensity of myo-inositol (mI) with and without reduced signal intensity of N-acetylaspartate (NAA) was visible on metabolic images in the NAWM of participants with MS. A higher ratio of mI to total creatine (tCr) was observed in the NAWM of the centrum semiovale of all MS subgroups, including participants without disability (marginal mean ± standard error, healthy controls: 0.78 ± 0.04; EDSS 0–1: 0.86 ± 0.03 [P = .02]; EDSS 1.5–3: 0.95 ± 0.04 [P < .001]; EDSS ≥3.5: 0.94 ± 0.04 [P = .001]). A lower ratio of NAA to tCr was found in MS subgroups with disabilities, both in their NAWM (marginal mean ± standard error, healthy controls: 1.46 ± 0.04; EDSS 1.5–3: 1.33 ± 0.03 [P = .03]; EDSS ≥3.5: 1.30 ± 0.04 [P = .01]) and CGM (marginal mean ± standard error, healthy controls: 1.42 ± 0.05; EDSS ≥3.5: 1.23 ± 0.05 [P = .006]). mI/NAA correlated with EDSS (NAWM of centrum semiovale: r = 0.47, P < .001; parietal NAWM: r = 0.43, P = .002; frontal NAWM: r = 0.34, P = .01; frontal CGM: r = 0.37, P = .004).

Conclusion
MR spectroscopic imaging at 7.0 T allowed in vivo visualization of multiple sclerosis pathologic findings not visible at T1 or T2-weighted MRI. Metabolic abnormalities in the normal-appearing white matter and cortical gray matter were associated with disability.

Link | PDF (Radiology)

 

[SNT Gatchaman]

Focal white matter lesions (WML) of demyelination are the most readily detectable manifestation of multiple sclerosis (MS) at morphologic MRI. However, they represent only macroscopic tissue damage and are therefore unable to fully explain the topographic origin and severity of many clinical symptoms of MS, particularly in the progressive phase of the disease. A more subtle yet extensive pathologic manifestation has been found in the normal appearing white matter (NAWM) and the gray matter by using advanced imaging techniques.

The most widely reported abnormality in MS is reduced N-acetylaspartate (NAA) with elevated myo-inositol (mI). Because NAA is almost exclusively present in neurons, lower levels of this metabolite have been interpreted as evidence of impaired axonal and/ or neuronal integrity and as a marker for reversible mitochondrial dysfunction in MS.

Axonal loss and brain atrophy are believed to play a substantial role in the progression of neurologic disability. The mI is preferentially concentrated in glial cells and associated with reactive astrogliosis, indicative of substantial inflammatory disease activity.

Most spectroscopic studies to date have been limited by low spatial resolution and small volume coverage [...] Nevertheless, they have assumed that the investigated volumes are globally representative.

Recent progress in 7.0-T free-induction decay (FID) MR spectroscopic imaging (MRSI) with matrix sizes of 100 x 100 reduces partial volume errors of previous studies

We therefore hypothesize that similarly, the mI and NAA alterations outside WML are less diffuse than previously reported, and when precisely estimated, they correlate with the clinically measured disability.

 

[SNT Gatchaman]

This study used high field strength MRI to look at the white matter which appears structurally normal. Also the regions adjacent to cortex. 7T magnets are becoming more available to research but not yet in clinical practice.

They looked at patients diagnosed with MS (who may have had structurally apparent lesions as well), with a range of disability from asymptomatic to moderate (EDSS 0-6) — see Expanded Disability Status Scale. Vs HCs.

In the analysis of segmented regions in the NAWM, the largest differences between participants with MS and healthy controls were observed in centrum semiovale. In detail, mI/NAA, as well as mI/tCr, were higher even at the earliest clinical extents of the disease—in other words, in participants with MS with EDSS 0–1 (ie, without disability) when compared with healthy controls

The neurometabolite alterations, as observed in the NAWM, were more pronounced in WML. Specifically, the greatest difference in mI/NAA was found in participants with EDSS 0–1[...], followed by participants with EDSS 1.5–3 [...] and participants with EDSS of at least 3.5.

 

[SNT Gatchaman]

In this prospective study of 65 participants with multiple sclerosis (MS) and 20 healthy controls, we demonstrated that 7.0-T free-induction decay MR spectroscopic imaging with approximately 2 x 2 mm in-plane spatial resolution can help depict and visualize selectively and simultaneously focal and widespread pathologic manifestations in the normal-appearing white matter (NAWM), cortical gray matter (CGM), and white matter lesions.

We found localized elevated signal intensity of myoinositol (mI) in the NAWM, which may indicate early pathologic changes related to neuroinflammation that remain undetected at morphologic MRI. This hypothesis is supported by the fact that these regions did not (as of yet) show a reduced signal intensity of N-acetylaspartate (NAA).

Findings from previous studies provide robust evidence that elevated mI in NAWM is a consistent finding in MS and is of functional importance. However, their major limitation was the application of single-voxel MR spectroscopy; hence, it was inconclusive whether elevated mI occurs generally throughout the NAWM or is more heterogeneous.

Inconsistent findings about reduced NAWM NAA or NAA/tCr have been reported in participants with no disabilities or with neurologic signs only [...] Our results confirm that NAWM NAA/tCr is significantly reduced in participants with disability, and that axonal pathologic manifestations appear early, before the conversion into progressive MS.

in our study, the strongest correlations were found between disability and mI/NAA. Higher mI/NAA levels in MS are likely to reflect the combination of inflammation-induced astrogliosis and axonal damage, confirming that both have an important role in MS progression.

Our results further support the findings of the longitudinal follow-up study by Llufriu et al, which showed that baseline mI/NAA in the NAWM is a predictor of brain atrophy and disability progression over time. The missing correlation between mI/NAA and EDSS score in WML can be explained by the fact that despite their similar appearance at morphologic MRI, WML show more heterogeneous histopathologic features, including areas of demyelination and remyelination where NAA recovery is possible.

 

[ToneAl]

Does this study push back th idea of functinal overlay or would it be swept under the carpet

 

[livinglighter]

Does this study push back th idea of functinal overlay or would it be swept under the carpet

This question was similarly raised here recently https://www.s4me.info/threads/funct...edia-and-discussion.23802/page-15#post-481648

@DigitalDrifter posted a meta-analysis/review published in the journal titled Brain, which includes brain imaging as proof that functional conditions have organic brain pathology.

 

[Hutan]

@DigitalDrifter posted a meta-analysis/review published in the journal titled Brain, which includes brain imaging as proof that functional conditions have organic brain pathology.

Thread for that paper here:
The neuroimaging evidence of brain abnormalities in functional movement disorders, 2021, Sasikumar and Strafella