N. Jon Shah1,2,3, Zaheer Abbas1, Dominik Ridder1, Markus Zimmermann1, and Ana-Maria Oros-Peusquens1
1Medical Imaging Physics, Institute of Neuroscience and Medicine 4, Jülich, Germany, 2Institute of Neuroscience and Medicine 11, INM 11, JARA, Jülich, Germany, 3Department of Neurology, Faculty of Medicine, Aachen, Germany
Synopsis
Measurement of quantitative, tissue-specific MR properties such as water
content or relaxation times using quantitative-MRI at clinical field strength
is a well-explored topic. However, none of the commonly used standard brain
atlases, e.g., MNI or JHU, provide quantitative information. Utilising the
framework of quantitative-MRI of the brain, this work reports on the
development of the first quantitative in-vivo
water content atlas based on twenty healthy volunteers datasets. Additionally, water content maps
from patients with pathological changes in the brain were compared voxel-wise.
These results suggest that quantitative-MRI in combination with water content atlas allows careful
and quantitative interpretation of disease.
Introduction
MRI is a very sensitive method to detect focal changes in
the in vivo brain.1-6 Usually, this involves defining healthy standard brain
atlases as a basis for the comparison of pathological brains. Currently, the use of such standard
brain atlases is well established in the mapping community, but none of the
commonly utilised standard brain or atlases7-9 provides
quantitative information. This is remarkable; given that measurement of
quantitative, tissue-specific MR properties, e.g., water content and relaxation
times (T1, T2*) using quantitative MRI at
clinical field strength (1.5 Tesla to 3 Tesla) is a well explored topic.
In this work, a methodology
to create the first quantitative atlas of the in vivo brain water content based on 20 healthy volunteers is
presented; preliminary practical examples of its potential applications are
also shown.Methods
Twenty right-handed, healthy, male subjects (age 25.3 ± 2.5 years) were
scanned on a Siemens Magnetom Tim-Trio scanner. A two-point method with
intermediate TR (Method A)10,11 and a long TR method (Method B)12, which involve the Siemens gradient echo multiple echo sequence (GRE), were used for
mapping the cerebral water content as well as the relaxation times (T1
and T2*). T1-weighted
MPRAGE images and water content maps of all subjects were further registered to
the MNI template (MNI-avg152T1-Brain template) using the Automatic
Registration Toolbox (ART) (http://www.nitrc.org/projects/art).13
The normalized water
content images (FW) were used for atlas generation in the following
way. Voxel-wise trim mean value, coefficient of variance (CoV =
standard deviation/trim mean value), and standard deviation using normalized water
content maps over all subjects were calculated. The final result is a 1mm
isotropic water content atlas with a probability for water content of each
voxel based on the standard deviation.
Patients suffering from
brain tumour (Glioblastoma, male, 32 years) and multiple sclerosis (MS) (male,
38 years) were scanned with similar imaging protocols as the healthy
volunteers.
The patients’ water content
maps were smoothed with a kernel of 12 mm Gaussian full width at half maximum
(FWHM) and voxel-wise
z-score maps were calculated using z-score = (FWPatient
- FWAtlas) / Standard deviation FWAtlas
and the differences were analysed using the two-tail t-test14.Results
The workflows and entire
post-processing chain to calculate the water content maps of all volunteers
using Method A and Method B are schematically illustrated in Figure 1.
Transverse slices of
measured water content maps using both methods from a representative
participant are shown in Figure 2a. Histograms of the whole brain water content
maps are displayed in Figure 2b. Segmentation of the brain was performed and
Gaussian fits over white matter (WM), grey matter (GM) and cerebrospinal fluid
(CSF) regions are shown in the histogram. The average water content values over
all volunteers obtained from the entire WM and the entire GM for Method A are
70.7(±3.6) and 80.7(±4.8), whereas the entire WM and entire GM using Method B
obtained are 70.2(±3.7) and 80.9(±4.8).
A schematic diagram for the
generation of a quantitative water content brain atlas in MNI space coordinates
is shown in Figure 3.
Transverse slices from
quantitative water content atlases acquired using water content maps from the
healthy volunteers, the coefficient of variation map and the standard deviation
map using Method A and Method B are displayed in Figure 4.
Water maps of a MS patient
acquired using Method A and from a tumour patient using Method B are compared
to the water content atlas. Three slices of the water content from the MS patient and
tumour patient and the voxel-wise z-score maps were computed14 and used to access the structural difference displayed in Figure 5.
The tmean water content
atlas values accessed in WM and GM ROIs are in good agreement within methods
and are also in agreement with the valutes reported in the literature.10-12Discussion and conclusion
In this work, previously validated experimental protocols for water
content mapping were used to develop and introduce the first quantitative water
content brain atlas in vivo in the MNI domain (1mm3). This
approach helped to minimise the effect of brain sizes and intra-subject
cortical variations.
The
atlases generated by both experimental methods were evaluated and analysed in
order to investigate systematic differences between them and the input water
maps (e.g., from patient). Both experimental approaches studied here provide
stable and reliable results, representing the average cerebral water content of a
healthy population.Acknowledgements
We thank Ms. Claire Rick for proof reading the manuscript.References
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