Yicun Wang1, Peter van Gelderen1, Jacco A de Zwart1, and Jeff H Duyn1
1AMRI, LFMI, NINDS, NIH, Bethesda, MD, United States
Synopsis
Keywords: Relaxometry, Brain
Gradient Echo Sampling of Spin Echo signal was used to
obtain R
2 maps in nine adults at 3 T and 7 T. These were analyzed
using anatomically defined ROIs, across most of the brain. Comparison between
the two field strengths shows in most brain regions the R
2 increases
by about a factor of 1.62, with the notable exception of regions high in iron.
Linear fits of R
2 versus estimated iron concentration yielded 50.6
and 132 1/s/(mg/g) for 3 T and 7 T respectively, in line with prior reports at
lower fields for the field dependence of iron related relaxation.
Introduction
Quantitative measures of relaxation in brain tissue have
long been of interest as a potential surrogate of iron concentration, which is
a major contributor to brain R2* relaxivity (1,2).
Abnormal brain iron concentration is thought to be related to many
neurodegenerative diseases, including MS, Parkinson’s, and Alzheimer’s disease (3-6).
While R2 and R2* are both sensitive to the field
inhomogeneities caused by iron, R2* is also sensitive to other
sources of inhomogeneity, such as deoxyhemoglobin in the venous vasculature.
Measurement of R2 therefore may be a more reproducible and sensitive
marker of iron. The field dependence is of interest to understand the nature of
the relaxation and to potentially separate iron from other sources of R2
relaxation, as their field dependent relaxivity maybe different (7-9).
Here we used a Gradient Echo Sampled Spin Echo (GESSE(10,11))
approach to quantify the R2 relaxation, with minimal sensitivity to
both B0 and B1 inhomogeneities. The same subjects were
measured at 3 and 7 T with the same imaging method and parameters. The aim was
to quantify the field dependence of R2 relaxation and its relation of
iron concentration.Methods
Nine subjects were measured on both a 3 T Prisma and a 7 T
Magnetom scanner (both Siemens Healthineers), both with 32-channel receive
coil. The average age was 25.3 (SD 3.3) years. GESSE images were acquired
axial-oblique, approximately parallel to AC-PC, with a FOV of 240x180 mm2, 1.1x1.1
mm2 resolution, 2 mm nominal slice thickness, 2 mm gap. Twenty
slices were scanned at 3 T, 16 at 7 T (due to SAR limitations). The TR was
chosen at 2 s, the spin echo TE at 40 ms, the gradient echo spacing as 1.21 ms
at 3 T, 1.06 ms at 7 T. A navigator was included in the acquisition prior to
the refocusing pulse to reduce ghosting from respiratory (and other) field
changes. The slice thickness of the refocusing pulse was set to 3 mm to reduce effects
of slice profile imperfections. A 3D-MPRAGE was acquired as anatomical
reference.
The images were corrected for distortion/displacement in the
acquisition direction to allow combination of positive and negative gradient
images. The gradient echoes symmetric around the spin echo were used to fit the
R2, using a linear fit to the logarithm of the (magnitude) data.
Freesurfer software was used to create ROIs in the 3 T
MPRAGE space, and to calculate the alignment between the GESSE images from both
field strengths and the 3 T MPRAGE.
The inverse of this
transform was then applied to the separate ROI maps, generating interpolated
ROI masks in each subject’s R2 space. A threshold of 0.9 was applied
to select voxels with minimum partial volume effects. The Freesurfer parcellations
for white matter and cortex were combined into frontal, precentral,
postcentral, parietal, occipital and temporal areas. In addition to the Freesurfer
ROIs, the substantia nigra and red nucleus were defined manually on the GESSE
images. The R2 values were averaged within ROIs and combined for
left and right hemisphere measures.Results
The R2 values for both field strengths are shown
in Figure 1 in the 38 resulting ROIs. The slope of the fitted line was 1.62.
Most of the data is consistent with this line, with the notable exception of
the pallidum and substantia nigra. Fig. 2 shows the relation with the estimated
iron concentration for the average subject’s age (from Hallgren (12)),
for those regions corresponding to the Hallgren study. The red nucleus is not
included here, as the absence of age-dependent data prevented estimation of
iron content for our relatively young subject group. The slope of the fitted
lines was 50.6 and 132 1/s/(mg/g) for 3 T and 7 T, respectively. Fig. 3 compares
these findings to a study of R2 field dependence showing data for
0.5 T and 1.5 T (7).
While the iron containing regions appear consistent with that study, the white
matter values are not, as our 7 T value is higher than
predicted following (7).
Fig.4 shows the comparison of the slope of R2
versus iron with two other studies (at 0.5 T, 1.5 T and 3 T (13,14)).
The slopes as fitted in Fig. 2 are consistent with these reports. The combined
data shows the field dependence of this slope to be 17 1/s/(mg/g)/T.Discussion
The R2 depends on iron content and other tissue
characteristics, like the exchange with high R2 components in
myelin. Like iron, myelin also has a susceptibility related contribution to R2
(through diffusion), but at a different spatial scale. The differences in
mechanism would be expected to show a different field dependence of R2,
which is substantiated by the data shown.
Combining this data with an independent estimation of myelin,
e.g. based on the R1, it may be possible to establish both iron and non-iron contributions
to R2. A combined measurement of R1 and R2 at a single field strength then
maybe sufficient to estimate both myelin and iron concentrations in brain
tissues.
Acknowledgements
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