Volume Estimation of the Thalamus Using Freesurfer
and Stereology: Consistency between Methods
Simon S. Keller & Jan S. Gerdes &
Siawoosh Mohammadi & Christoph Kellinghaus &
Harald Kugel & Katja Deppe & E. Bernd Ringelstein &
Stefan Evers & Wolfram Schwindt & Michael Deppe
Published online: 6 April 2012
#The Author(s) 2012. This article is published with open access at Springerlink.com
Abstract Freely available automated MR image analysis
techniques are being increasingly used to investigate neuro-
anatomical abnormalities in patients with neurological disor-
ders. It is important to assess the specificity and validity of
automated measurements of structure volumes with respect to
reliable manual methods that rely on human anatomical
expertise. The thalamus is widely investigated in many
neurological and neuropsychiatric disorders using MRI, but
thalamic volumes are notoriously difficult to quantify given
the poor between-tissue contrast at the thalamic gray-white
matter interface. In the present study we investigated the
urements obtained using FreeSurfer software with respect to a
manual stereological technique on 3D T1-weighted MR
images obtained from a 3 T MR system. Further to demon-
strating impressive consistency between stereological and
FreeSurfer volume estimates of the thalamus in healthy sub-
jects and neurological patients, we demonstrate that the extent
of agreeability between stereology and FreeSurfer is equal to
the agreeability between two human anatomists estimating
thalamic volume using stereological methods. Using patients
with juvenile myoclonic epilepsy as a model for thalamic
atrophy, we also show that both automated and manual meth-
ods provide very similar ratios of thalamic volume loss in
patients.This workpromotesthe use ofFreeSurfer for reliable
estimation of global volume in healthy and diseased thalami.
The thalamus is of central interest in many disorders of the
nervous system (Andreasen 1997; Dom, et al. 1976; Lee and
Marsden 1994; Meador-Woodruff, et al. 2003; Speedie and
Heilman 1983; Williams 1965; Xuereb, et al. 1991). The
functioning of the thalamus is crucial to many sensory,
motor and cognitive systems, and therefore has also been
subject to a great deal of investigation in the cognitive
neurosciences (Basso, et al. 2005; Engelborghs, et al.
1998; Herrero, et al. 2002). It is in these capacities that
S. S. Keller:J. S. Gerdes:E. B. Ringelstein:S. Evers:M. Deppe
Department of Neurology, University of Münster,
S. S. Keller
Department of Clinical Neuroscience, Institute of Psychiatry,
King’s College London,
Wellcome Trust Centre for Neuroimaging,
UCL Institute of Neurology,
University College London,
Department of Neurology, Klinikum Osnabrück,
H. Kugel:W. Schwindt
Department of Clinical Radiology, University of Münster,
Department of Radiology, Klinikum Osnabrück,
M. Deppe (*)
Universität Münster, Klinik und Poliklinik für Neurologie,
Albert-Schweitzer-Campus 1, Gebäude A1,
48129 Münster, Germany
Neuroinform (2012) 10:341–350
analysis of thalamic structure and function is a continually
researched theme in neuroimaging investigations, particu-
larly using magnetic resonance imaging (MRI). Analysis of
volume or shape using MRI techniques may provide impor-
tant information with respect to the involvement of the
thalamus in neurological and neuropsychiatric disorders,
including generalized (Du, et al. 2011; Pulsipher, et al.
2009) and partial (Gong, et al. 2008; Pulsipher, et al.
2007) epilepsy, schizophrenia (Adriano, et al. 2010),
Huntington’s disease (Douaud, et al. 2006; Kassubek, et
al. 2005), Parkinson’s disease (McKeown, et al. 2008), and
Alzheimer’s disease (de Jong, et al. 2008). Reliable mea-
surement of thalamic structure is, however, notoriously dif-
ficult to achieve, particularly given the typically poor
between-tissue MR contrast of the thalamic nuclei and
adjacent white matter (Amini, et al. 2004). It is there-
fore important to develop new and improve and validate
existing methodologies that provide thalamic metrics.
Like for other subcortical brain structures, there are
several approaches freely available to estimate thalamic
volume from MR images. At either end of the MR
image analysis spectrum, there are manual and automat-
ed approaches; manual approaches are user-dependent,
time consuming but are considered to be the gold stan-
dard of MR image analysis techniques (Bonilha, et al.
2004; Collins and Pruessner 2010; Crum, et al. 2001;
Pruessner, et al. 2000). Automated approaches remove
the need of an expert anatomist, are dependent on
computer algorithms, and are time efficient, but require
a great deal of validation against manual methods to
determine the specificity and validity of measurements
(Chupin, et al. 2009; Morra, et al. 2008). The primary
goal of the present study was to evaluate the validity of
thalamic volume measurements obtained from a frequently
used automated approach with respect to a reputable manual
approach widely used in the imaging, anatomical and
The fully automated approach investigated in the present
study was the subcortical segmentation and volume estima-
tion techniques (Fischl, et al. 2002) incorporated into
FreeSurfer software (http://surfer.nmr.mgh.harvard.edu/),
which provide observer-independent volumes for individual
subcortical nuclei from conventional MR images. Similarly
to other methods that automatically segment and estimate
subcortical volume such as FIRST (Patenaude, et al. 2011)
incorporated into FSL software (http://www.fmrib.ox.ac.uk/
fsl/first/index.html), there has been a recent proliferation of
studies using FreeSurfer methods for volumetric studies,
some of which have included comparison with manual
methods, most notably for the hippocampus (Cherbuin, et
al. 2009; Dewey, et al. 2010; Morey, et al. 2009; Pardoe, et
al. 2009; Shen, et al. 2010; Tae, et al. 2008). To our knowl-
edge, there has been no independent comparison between
manual methods and FreeSurfer methods for volume esti-
mation of the thalamus. The manual approach used to eval-
uated FreeSurfer-based thalamic volumes in the present
study was the Cavalieri method of design-based stereology
in conjunction with point counting (Gundersen and Jensen
1987; Gundersen, et al. 1999; Mayhew 1992; Roberts, et al.
2000), which is a 100% investigator interactive technique
that requires manual determination of sampling density for a
given brain structure (i.e. the stereological parameters nec-
essary to produce a reliable volume estimate) and investiga-
tor decisions on whether or not sampling probes (i.e. points)
intersect the brain region-of-interest (ROI). Stereology
requires the use of a human anatomist with expert knowl-
edge of anatomical boundaries that divide legitimate (i.e.
thalamic) and illegitimate (i.e. non-thalamic) brain tissue.
Manual approaches such as stereology are considered gold
standard because it is assumed that human knowledge and
perception is superior to computer algorithms that determine
regional brain boundaries.
We examined the consistency between manual and auto-
mated thalamic volume estimation in two ways. Firstly, we
compared thalamic volume estimates in a sample of neuro-
logically and psychiatrically healthy subjects. Secondly, we
compared the methods in their sensitivity in detecting tha-
lamic atrophy in patients with juvenile myoclonic epilepsy
(JME). JME is an electro-clinical syndrome that by defini-
tion is non-lesional and without abnormality on convention-
al magnetic resonance imaging (MRI) (Berg, et al. 2010;
ILAE 1989), but has previously been shown to be associated
with thalamic structural alterations (Deppe, et al. 2008; Kim,
et al. 2007; Mory, et al. 2011; Pulsipher, et al. 2009), and is
generally considered to be intimately associated with tha-
lamic dysfunction (Holmes, et al. 2010). We therefore com-
pared morphometric approaches for volume estimation of
both healthy and diseased thalami.
We studied a neurologically and psychiatrically healthy
control group that was composed of 62 adult volunteers
(32 females, mean age 27.9±4.3 SD, range 21–43), all of
whom had normal neurological examination and normal
MRI (T1-, T2-weighted, and FLAIR). We also studied ten
patients (6 females, mean age 28.6±8.8 SD, range 19–42)
with JME. Clinical information for these patients can be
found elsewhere (Deppe, et al. 2008; Keller, et al. 2011a).
There was no statistical difference in age between patients
and controls (t00.38, p00.70). All subjects gave written
informed consent and the local ethics committee approved
342Neuroinform (2012) 10:341–350
Magnetic Resonance Imaging
All participants underwent high resolution MRI T1-
weighted, T2-weighted and FLAIR imaging at 3 T (Philips
Intera T30, T/R head coil). All MRI modalities were used to
exclude the possibility of brain lesions in patients and con-
trols. For volumetric analysis, we acquired T1-weighted
structural MRIs using a high-resolution 3D turbo-field-
echo sequence (matrix 256×256×160 over a field of view
of 25.6×25.6×16 cm3reconstructed after zero filling to
512×512×320 cubic voxels with an edge length of
0.5 mm). Prior to morphometric analyses, all MR images
were intensity inhomogeneity corrected and resampled to
isotropic voxels of 1×1×1 mm (256×256×160 slices) us-
ing in-house software (Eval 3.0). To confirm that there was
no systematic difference in head size between patient and
control groups, we automatically obtained relative brain
size, VSCALE (global tissue volumes normalized for head
size) and CSF volume estimates from the 3D T1-weighted
images of all subjects using the SIENAX protocol
(Smith, et al. 2002) integrated into FSL software (http://
www.fmrib.ox.ac.uk/fsl/siena/index.html). There were no
inter-group differences in relative brain size (p00.40),
VSCALE (p00.96) or CSF volume (p00.95).
The Cavalieri method of design-based stereology in con-
junction with point counting (Gundersen and Jensen 1987;
Gundersen, et al. 1999; Mayhew 1992; Roberts, et al. 2000)
was used as an unbiased estimator of the volume of the left
and right thalamus in all subjects. By using the Cavalieri
method, volume is directly estimated from equidistant and
parallel MR images of the brain with a uniform random
starting position. A second level of sampling is required to
estimate the section area from each image by applying point
counting within the ROI. The mathematical justification and
implementation of the methodology is simple and it can be
applied to structures of arbitrary shape (Garcia-Finana, et al.
2009). This technique has been frequently applied to reli-
ably estimate brain volume and surface area on MR images
(Acer, et al. 2010; Bas, et al. 2009; Cowell, et al. 2007;
Eriksen, et al. 2010; Hallahan, et al. 2011; Howard, et al.
2003; Jelsing, et al. 2005; Keller, et al. 2009; Keller, et al.
2007; Keller, et al. 2002a; Keller, et al. 2009b; Keller, et al.
2002b; Lux, et al. 2008; Mackay, et al. 1998; Mackay, et al.
2000; Ronan, et al. 2006; Salmenpera, et al. 2005; Sheline,
et al. 1996), and more widely applied to study other aspects
of anatomy with and without the use of MRI. Stereology has
been shown to be at least as precise as tracing and thresh-
olding volumetry techniques and substantially more time
efficient, with validation relative to post-mortem measure-
ments (Garcia-Finana, et al. 2003; Garcia-Finana, et al. 2009;
Keller and Roberts 2009; Keshavan, et al. 1995). Windows-
compatible Easymeasure software (Keller, et al. 2007;
Puddephat 1999) was used for point counting on MR images.
Given that the borders of different thalamic nuclei are
almost indistinguishable on conventional MRI, the thalamus
was sampled as an entire complex, including the anterior
thalamic nucleus, mediodorsal thalamic nucleus, lateral
dorsal thalamic nucleus, ventral lateral thalamic nucleus,
ventral postero-lateral/medial thalamic nuclei, and pulvinar
(Duvernoy 1999). The lateral and medial geniculate nuclei
were not included in measurements, similar to previous
studies (Natsume, et al. 2003; Qiu, et al. 2009). On axial
sections, point counting began on the dorsal most section,
where the area of the lateral dorsal thalamic nucleus was
demarcated laterally by the corona radiata and medially by
the lateral ventricles. As measurements progressed ventrally,
the posterior limb of the internal capsule bordered the tha-
lamus laterally. On ventral sections, care was taken to de-
lineate the thalamic nuclei from the neighbouring pars
medialis of the globus pallidus, and at the most ventral
sections, to segregate the pulvinar and area of the ventral
posterolateral nucleus from the emerging hypothalamus an-
teriorly, superior colliculus posteromedially, and the hippo-
campus posteriorly / posterolaterally. Figure 1 shows point
counting within the thalamic ROI relative to the automated
FreeSurfer approach described below. More information on
the MRI-based anatomy of the thalamus with respect to
post-mortem sections can be found at http://www.psychia-
The sampling density (i.e. size of points, distance be-
tween sections) were optimized to achieve a coefficient of
error (CE) of less that 5% (Roberts, et al. 2000), an ap-
proach that has been adopted in our stereological analysis of
the hippocampus (Keller, et al. 2002a; Keller, et al. 2002b),
putamen (Keller, et al. 2011a), prefrontal region (Keller, et
al. 2009a), planum temporale (Keller, et al. 2007; Keller, et
al. 2011b), Broca’s area (Keller, et al. 2007; Keller, et al.
2009b) and insula (Keller, et al. 2011b). The CE is essen-
tially a statistical estimate of how accurate the stereological
volume estimation is for each structure. Separation between
test points on the square grid used for point counting was
0.312 cm (i.e., 4 pixels) and slice interval was 1 mm (sin-
gular axial MR sections). Thalamic transect area was
obtained by multiplying the total number of points recorded
by the area corresponding to each test point. An estimate of
thalamic volume was obtained as the sum of the estimated
areas of the structure transects on consecutive systematic
sections multiplied by the distance between sections.
Between approximately 400–550 points were recorded on
approximately 20 systematic random sections.
FreeSurfer software (http://surfer.nmr.mgh.harvard.edu/)
was used to obtain thalamic volumes for all subjects using
Neuroinform (2012) 10:341–350343
an observer-independent approach, which could be con-
trasted with the manual stereological measurements of the
thalamus. Thalamic segmentations are based on the assign-
ment of neuroanatomical labels to each voxel in an MR
image based on the probabilistic information automatically
estimated from a manually labelled training set. The meth-
ods of the automated volumetric approach have been de-
scribed in detail previously (Fischl, et al. 2002), and the
accuracy of automated labelling and volumetry of subcorti-
cal structures have been independently validated with re-
spect to ‘gold standard’ manual volumetric techniques,
predominantly for the hippocampus (Cherbuin, et al. 2009;
Dewey, et al. 2010; Morey, et al. 2009; Pardoe, et al. 2009;
Shen, et al. 2010; Tae, et al. 2008), and also of the amgydala
(Dewey, et al. 2010; Morey, et al. 2009) and striatum
(Dewey, et al. 2010). To our knowledge, there has been no
independent comparisonofthe automatedthalamicvolumetry
offered by FreeSurfer and a manual volumetric method (al-
though thalamic tracings were compared with the perfor-
mance of FreeSurfer in the original methods paper by Fischl
et al. (2002)). Figure 1 shows the comparison of automated
labelling of the thalamus (and extra-thalamic structures) in an
individual control subject using FreeSurfer relative to stereo-
logical volumeestimationofthe thalamusinthe samesubject.
FreeSurferanalyseswere performedona Mac Pro(Version
OS X 10.6.6, 32 GB, 2×2.93 GHz 6-Core Intel Xeon (HT)),
which permitted the FreeSurfer ‘recon-all’ function (for corti-
cal reconstruction and brain segmentation; http://surfer.
nmr.mgh.harvard.edu/fswiki/recon-all) to complete 23 partic-
ipants in less than 20 h. After the ‘recon-all’ function, the
neuroanatomical labels were inspected for accuracy in all
patients and controls. Despite that FreeSurfer permits manual
editing to improve subcortical segmentation, no obvious
errors in the automatic labelling were observed for any sub-
ject, and so all data obtained from FreeSurfer analyses were
100% automated and not influenced by manual intervention.
Two-way mixed intra-class correlation coefficients for ab-
solute agreement (Shrout and Fleiss 1979) were used to
determine inter-rater agreement between two human raters
using manual stereology and FreeSurfer for volume estima-
tion of the thalamus in ten randomly selected controls using
the statistics software SPSS (Version 18, www.spss.com).
Intra-class correlations were subsequently performed be-
tween stereological volumes obtained by one human rater
and FreeSurfer volumes for the entire sample of patients and
Fig. 1 Stereological and FreeSurfer methods used to estimate thalamic
volume shown at approximately the same axial sections. Both methods
are shown for the same hemisphere (the FreeSurfer axial sections are
flipped to show maximal correspondence between techniques) of the
same randomly selected subject. The sagittal MR section illustrates the
approximate levels of the axial sections shown. Abbreviations: di,
ventral diencephalon (peach); pa, pallidum (violet); put, putamen (li-
lac); th, thalamus (dark green); thp, pulvinar of the thalamus (dark
Fig. 2 Inter-rater consistency in stereological volume estimation of the
left (blue) and right (red) thalamus, and relation to volume estimates
obtained from FreeSurfer. Stereological volume estimates are repro-
ducible, and FreeSurfer is entirely consistent with the volumes
obtained with both rater one and rater two. Error bars indicate the
95% confidence intervals
344 Neuroinform (2012) 10:341–350
controls (n072). Univariate ANOVAs were used to investi-
gate patient-control differences in volumes, and corrected
for multiple comparisons using Statistica version 9.1, (Stat
Soft. Inc, www.statsoft.com).
A. Stereology vs FreeSurfer: Consistency between volu-
Figure 2 shows the comparison of the three approaches
(rater one (R1) for stereology, rater two (R2) for stereology
and FreeSurfer) to estimate thalamic volume in the randomly
selected ten subjects. This inter-rater / between-technique
analysis indicates consistency across measures, and most no-
tably, that FreeSurfer performed at least as consistent as R2
relative to R1. Mean (SD) left and right thalamic volume was
7339.6 mm3(567.3) and 7339.2 mm3(489.3) for R1,
7456.3 mm3(597.3) and 7444.3 mm3(590.6) for R2, and
7365.0 mm3(641.3) and 7317.6 mm3(610.0) for FreeSurfer,
respectively. Intra-class correlations across raters and
approaches are presented in Table 1. Measurements between
R1 and R2, and between manual raters and FreeSurfer,
achieve high intra-class correlations (all >0.9).
Figure 3 presents the relationship between stereological
(R1) and FreeSurfer estimates of left and right thalamus
volume across the entire sample of 72 subjects investigated
in the present study. It is immediately obvious that the two
methods yield consistent thalamic volumes. Intra-class corre-
lations revealed a slightly reduced level of consistency be-
tween human and FreeSurfer analysis of the entire sample
relative to the sub-sample of ten subjects (left thalamus0
0.812, right thalamus00.881). Mean (SD) left and right tha-
lamic volume was 7422.4 mm3(824.3) and 7390.1 mm3
(805.8) for stereology and 7343.6 mm3(824.3) and
7388.3 mm3(844.0) for FreeSurfer. There was no difference
subjects using stereology (F00.09, p00.82) or FreeSurfer
(F00.10, p00.75) (and no differences when patients and
controls were separated, p>0.80). Although there were occa-
ic volume asymmetry in individual cases between stereology
and FreeSurfer (Fig. 3, right panel), this did not represent a
statistically significant group effect (F01.46, p00.23).
B. Stereology vs Freesurfer: Identification of thalamic at-
rophy in JME
thalamic volume atrophy in patients with JME relative to
controls (Fig. 4). Using stereology, mean (SD) left and right
thalamic volume was 6843.2 mm3(746.6) and 6763.3 mm3
(824.0) in patients with JME, and 7507.8 mm3(805.6) and
7482.6 mm3(767.2) in controls, respectively. Volume reduc-
tion in patients was found to be statistically significant for the
left (F(1,70)05.43, p00.02) and right (F(1,70)06.77, p00.01)
thalamus compared to controls. Using FreeSurfer, mean (SD)
left and right thalamic volume was 6803.4 mm3(732.8) and
6750.0 mm3(714.3) in patients with JME, and 7430.7 mm3
(809.9) and 7491.3 mm3(822.3) in controls, respectively.
Table 1 Inter-rater intra-class coefficients for volumetric measures
Rater 1Rater 2FS
Fig. 3 Relationship between stereological and FreeSurfer volume esti-
mates of the left a and right b thalamus in the whole study sample. The
relationship between left-right asymmetries determined for each individ-
ual participant by each technique is shown in c. Although stereology and
FreeSurfer determined left-right asymmetries of the thalamus in the same
direction for the vast majority of subjects (lower left and upper right
quandrants), there were some disassociations (top left quadrant)
Neuroinform (2012) 10:341–350345
FreeSurfer thalamic volumeswere similarly smaller in patients
(F(1,70)07.36, p00.008) hemispheres.
The volume of the thalamus is a notoriously difficult metric
to estimate reliably given the low contrast between thalamic
gray matter and adjacent white matter on T1-weighted MR
images, which is a particular challenge for automated MR
image analysis methods (Amini, et al. 2004). Only by com-
paring such automated methods with manual investigator-
intensive methods can we establish the reliability of volume
estimates. The present study provides important data indi-
cating the specificity and validity of automated thalamic
volume estimation using FreeSurfer software. In particular,
further to demonstrating consistency between stereological
and FreeSurfer volume estimates of the thalamus in healthy
subjects and neurological patients, we demonstrate that the
extent of agreeability between stereology and FreeSurfer is
equal to the agreeability between two human anatomists
estimating thalamic volume using stereological methods.
FreeSurfer software is now a frequently used tool for the
estimation of subcortical structure volume. At the time of
writing, a pubmed search using “Freesurfer” and “volume”
yields 87 articles (October 2011). The vast majority of these
articles are application studies, particularly in neurological
disorders, and only a few have sought to evaluate the valid-
ity of volume measurements. Various levels of consistency
between FreeSurfer and manual ROI methods have been
reported for the hippocampus (Cherbuin, et al. 2009;
Dewey, et al. 2010; Morey, et al. 2009; Pardoe, et al.
2009; Shen, et al. 2010; Tae, et al. 2008), amgydala
(Dewey, et al. 2010; Morey, et al. 2009) and striatum
(Dewey, et al. 2010). Dewey et al. (2010) performed a series
of comparisons between the fully automated techniques of
FreeSurfer and Individual Brain Atlases using Statistical
Parametric Mapping (IBASPM) with auto-assisted manual
tracings of the hippocampus, amygdala, putamen and cau-
date. The authors report that FreeSurfer segmentations
exhibited significantly higher mean spatial overlap with
auto-assisted tracings in all structures compared to
IBASPM using dice coefficients. We were not in a position
to perform spatial overlap analyses of the thalamus given
that stereology and FreeSurfer are two inherently distinct
MR image analysis approaches. However, this is one of the
primary strengths of the data presented here, insomuch that
a reliable volume estimate obtained using a gold-standard
(non-voxel labelling) manual approach on MR images with-
out automated spatial transformations (i.e. in native space) is
comparable to a fully automated approach that requires
spatial transformations in order to label an ROI and obtain
a volume. Our interest was with respect to the reliability of
the volume estimate of the thalamus.
To our knowledge, the present study is the first to inde-
pendently provide data validating the application of
FreeSurfer to obtain automated volumes of the left and right
thalamus. Based on the congruence between the data
obtained from FreeSurfer and manual stereology—the latter
of which is considered to represent the ‘gold standard’
approach due to the requirement of an expert anatomist—
we recommend the use of FreeSurfer software for accurate
volumetric quantification of the thalamus using high-
resolution T1-weighted MRI. The removal of an expert
Fig. 4 Volume reduction of the left (blue circles) and right (red squares)
thalamus in patients with JME relative to healthy controls using stereol-
ogy a and FreeSurfer b. Error bars indicate the 95% confidence intervals
346 Neuroinform (2012) 10:341–350
anatomist for volumetric analyses is cost effective and time
efficient, particularly in large-scale volumetric studies.
Importantly, we demonstrate that the automated technique
is as sensitive in detecting pathological alterations of the
thalamus relative to stereology, which promotes the use of
FreeSurfer in neurological contexts.
There are two additional issues that should be highlight-
ed. Measurements made in the present study were of global
thalamic volume. The thalamus is composed of lamellae that
segregate multiple nuclei with distinct connections and
functions, which are likely to be differentially affected in
various neurological and neuropsychiatric disorders. For
example, in disorders where the thalamus is implicated in
patients also exhibiting deficits in frontal lobe functioning—
such as in JME (Pulsipher, et al. 2009)—it would be
expected that anterior thalamic nuclei that project to the
frontal lobe would be preferentially affected (Deppe, et al.
2008). In such circumstances it will be interesting to inves-
tigate structural alterations of differential thalamic subre-
gions, which are measures that the techniques applied in
the present study cannot provide. There are other techniques
that may provide the basis for quantitative measurements of
thalamic subregions based on DTI and quantitative T1 and
T2 imaging (Behrens, et al. 2003; Johansen-Berg, et al.
2005; Traynor, et al. 2011). Secondly, the global estimates
of thalamic volume using FreeSurfer in the present study
was obtained on a Philips Intera T30 3 T MRI system,
requiring no additional manual edits for (obvious) incorrect
labelling of the thalamic ROI after the application of our in-
house image inhomogeneity and resampling algorithm.
Different MRI systems and head coils may have different
image contrast characteristics that can potentially affect the
performance of automated MR image analysis techniques.
However, reproducibility of FreeSurfer estimated thalamic
volume from serially acquired MR images on the same MR
system is high (Jovicich, et al. 2009; Morey, et al. 2010),
and MR system manufacturer has been shown to have little
effect on volume estimates (Jovicich, et al. 2009).
In summary, this study provides convincing evidence for
the reliability of global thalamic measurements using
FreeSurfer in healthy and damaged thalami. The use of this
software is cost effective and particularly advantageous in
large-scale cross-sectional studies and longitudinal investi-
gations in neurological settings.
Information Sharing Statement
FreeSurfer software is publicly and freely available from the
FreeSurferWiki resource (http://surfer.nmr.mgh.harvard.edu/
fswiki/FreeSurferWiki), which is developed and maintained
at the Martinos Center for Biomedical Imaging (http://
software, information and support are provided online at the
FreeSurferWiki webpage. Easymeasure software for volume
estimation using stereology is freely available from the
authors of this manuscript upon request. Dr. Mike
Puddephat developed Easymeasure software at the
University of Liverpool, UK. Further information can be
found at (http://www.easymeasure.co.uk/).
Collaborative Research Centre SFB/TR 3 (Project A8) of the Deutsche
Forschungsgemeinschaft (DFG). EBR acknowledges support from the
Neuromedical Foundation (Stiftung Neuromedizin), Münster. SM
were supported by the Wellcome Trust grant number 091593/Z/10/Z.
This work was supported by the Transregional
Creative Commons Attribution License which permits any use, distri-
bution, and reproduction in any medium, provided the original author
(s) and the source are credited.
This article is distributed under the terms of the
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