Synopsis
We compared ultra-high
field, high resolution quantitative T1 and T2*
measurements in the cerebellum of MS patients to that of healthy controls. A
correlation between the multiple sclerosis functional scale scores and local T2*
values was found for several motor and cognitive related lobules. No
significant differences between groups were found.Target
audience
Physisists, neuroscientists and clinicians interested in multiple
sclerosis biomarkers, the cerebellum and quantitative MR.
Purpose
We investigated quantitative gray matter
cerebellar changes at a lobule level in multiple sclerosis (MS) patients and correlated
these with clinical assessment. MS, a global brain pathology, does not spare the cerebellum, where both focal
white and grey matter lesions have been observed
1. In addition, more subtle
changes already occur in normal-appearing tissue
2. Quantitative imaging, such
as T
1 and T
2* relaxometry, provide information
about the macromolecular structure, water and iron content of brain tissue
3,4, and may support metrics to
monitor disease progression. High-resolution quantitative measurements at 7T were
used to study the normal-appearing gray matter (NAGM) in MS patients.
Methods
Eighteen early-stage MS patients (<5 years disease duration) were
enrolled (4 females, median EDSS 1, 5; range: 1-2), age=33±7 (mean±SD)
and nine healthy controls (2 females, age=31±7). Patients and controls
underwent cognitive and behavioral testing as in
4, including the MS functional
composite score
5 (MSFC), which is a combined
score of three individual measurements independently assessing motor and
cognitive function. Whole-brain T
1 and T
2*maps
were acquired using the MP2RAGE
6 (TR/TE/TI1/TI2=6000/2.84/750/2350ms,
matrix=300x320x160, 0.75x0.75x0.9mm
3) and 3D multi gradient echo
(MGE; TR=45ms TE1/ΔTE/TE9=4.59/4.59/41.3ms, matrix=300x320x160, 0.75x0.75x0.9mm
3)
sequences at 7T (Siemens Health, Germany)
using a 32 channel head coil (Nova Medical, USA). Three dielectric pads were
placed around the cerebellum to improve B
1 homogeneity. A
mono-exponential fit to the MGE data was used to obtain S
0 and T
2*maps. A SA2RAGE B
1 map
7 (TR/TE=2400/0.72ms, matrix=116x128x64,
2.3x2.3x4mm
3) was used to correct the MP2RAGE for B
1
homogeneity
8. T
2* was registered
to the MP2RAGE using Elastix
9. The SUIT toolbox
10 was used to normalize the MP2RAGE
T
1-weighted images and segment the individual cerebelli. An in-house
semi-automatically generated mask for the focal lesions was used to exclude
lesion sites from the atlas. A T
1-map based mask (<2400ms) was
used to remove CSF voxels from the atlas. Final segmentation quality was visually
inspected (see Figure 1 for an example). NAGM T
1 and T
2*values
were lobule-wise extracted. MS patient values were
compared to controls’ with a repeated measure MANOVA (lobules as
within-subject factor;patients/controls as between-subject
factor). The MFSC score was correlated with
lobule T
1 and T
2*values in the MS patients (Spearman
correlation, FDR-adjusted).
Results
The multivariate analysis MS patients against controls did not reveal
any main effects. The outcome was similar for tests performed at univariate
level. There was a trend for longer T
1 values in the vermis rather
than in the lateral regions, but this did not differ between controls and
patients (Figure 2). Vermis and anterior
lobules (IV, V, VI) showed on average the highest T
2*values
(Figure 3). In MS patients, the mean T
2*value of several lobules
showed a negative correlation with the MSFC score (Figure 4). More precisely,
for these lobules, a lower performance during the clinical assessment was
related to longer T
2*values. These lobules were: left Crus I (rs=-.7 p=.044 FDR-corrected), left VIIb (rs=-.6, p=.049 FDR-corrected)
and right VIIb (rs=-.6, p=.036 FDR-corrected). In addition, several
other lobules showed a weaker negative correlation (rs=-.5, p<.05 uncorrected) with T
2*.
They were: right Crus I, vermis Crus II,
left VIIIa, right VIIIa and right X. In the T
1 maps, only a weak negative correlation was obtained
for vermis VIIIb and IX (p<.05 uncorrected, rs=-.5; Figure 5). No significant correlations were obtained for
controls.
Discussion
MS patients showed higher T
2*values in several bilateral cerebellar
NAGM subparts for lower performances in the MSFC assessment whereas controls
did not show any correlations. The nature of the T
2*contrast would suggest
a loss of macromolecules or a local decrease of tissue iron content
4. The different regions
affected are involved in several functional domains
11, namely motor, executive
function and working memory and reflect the composite nature of the MFSC which jointly
assesses motor function of arm and leg as well as processing speed and working
memory. We did not observe any significant differences in T
1 and T
2* properties
of the cerebellar cortex between patients and controls. This may be due to
insufficient power or to the fact that we studied early stage and minimally
impaired patients, whereas demyelination and changes in cerebellar cortex
volume have been so far reported in patients at more advanced disease stages.
Conclusion
This study showed that, even at early MS stages, mild alterations in the
cerebellar cortex, as measured by quantitative T
2* at ultra-high field, are
related to cognitive and motor performances in subjects with mild clinical
impairment. Future studies should assess the value of quantitative T
1 and T
2*
in larger cohorts of MS patients including more advanced stages and clinical
deficits.
Acknowledgements
No acknowledgement found.References
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