FLAIR diffusion-tensor MR tractography: comparison of fiber tracking with conventional imaging.
ABSTRACT Partial volume with CSF is known to contaminate the quantification of white matter anisotropy depicted by diffusion tensor imaging (DTI). We hypothesized that the FLAIR technique helps to improve DTI white matter tractography in the normal adult brain by eliminating CSF partial volume effects.
Seven healthy adults aged 23-37 underwent both conventional and FLAIR DTI at 1.5T. Each subject was imaged five times. Neural fiber tractography was performed with both sequences by using two algorithms: a voxel-based method (EZ-tracing) with global seed points and another based on subvoxel tractography (tensor deflection) by using manual encircling of local seed points. Total volume of the fibers tracked was compared for the two types of images.
Fiber tracking was substantially most successful on FLAIR DTI near the lateral ventricles and the sulci, where CSF partial volume effects were likely present. Minor false tracts on FLAIR images, possibly due to a reduced signal-to-noise ratio, were found in regions relatively free of CSF contamination; however, they did not affect tracking of major periventricular white matter bundles, such as those related to the corpus callosum or the corona radiata. When we excluded false tracts, the FLAIR technique depicted an average of 17% more fibers in volume than conventional DTI in the periventricular regions (P < .0005, paired Student t test).
Despite the reduction of signal-to-noise ratio and longer imaging times, FLAIR improved tractography by eliminating CSF partial volume effects.
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ABSTRACT: Our purpose was to test a new variant of the fluid-attenuated inversion-recovery (FLAIR) sequence that was designed to reduce CSF and blood flow artifacts by use of a non-slice-selective inversion pulse and k-space reordered by inversion time at each slice position (KRISP). With the KRISP FLAIR sequence, the slice order was cycled so that each inversion time (TI) was associated with a region of k-space rather than a particular slice, and the effective inversion time (TI(eff)) was chosen to null the signal from CSF. Scans were obtained with both conventional and KRISP FLAIR sequences. Studies were performed in 20 adult patients with a variety of brain diseases. Images were evaluated for artifacts from patient motion, CSF, and blood flow, and scored on a four-point scale. The conspicuity of the cortex, meninges, ventricular system, brain stem, and cerebellum was evaluated, as was lesion number and conspicuity. The KRISP FLAIR sequence showed more patient motion artifacts but had a pronounced advantage over the conventional sequence in control of CSF artifacts around the foramen of Munro, in the third ventricle, aqueduct, and fourth ventricle, as well as in the basal cisterns and around the brain stem and cerebellum. Blood flow artifacts from the internal carotid, basilar, and vertebral arteries were also much better controlled. Spurious high signal in the sylvian branches of the middle cerebral artery was eliminated. The meninges, cortex, ventricular system, brain stem, and cerebellum were better seen due to improved artifact suppression and an edge enhancement effect. The KRISP FLAIR sequence can suppress CSF and blood flow artifacts and improve the conspicuity of the meninges, cortex, brain stem, and cerebellum. Its major disadvantage is its duration, which may be reducible with a fast spin-echo version.American Journal of Neuroradiology 06/2001; 22(5):896-904. · 3.17 Impact Factor
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ABSTRACT: A cerebrospinal fluid (CSF)-suppressed flow-attenuated inversion recovery (FLAIR) double-shot diffusion echo-planar imaging (EPI) sequence was developed and used, along with a non-CSF-suppressed version of the sequence, to determine the extent of the contribution of CSF partial-volume averaging to the apparent diffusion coefficients (ADCs) of normal human brain in vivo. Regional analysis indicates that cortical gray matter and parenchymal tissues bordering the ventricles are most affected by CSF contamination, leading to elevated ADC values. Only slight differences in gray- and white-matter average ADCs were detected after CSF suppression. The human brain average ADCs calculated from high-resolution CSF-suppressed diffusion-weighted images in these studies are similar to those reported in animals. FLAIR diffusion sequences remove CSF as a source of error in ADC determination and ischemic lesion discrimination in diffusion-weighted images (DWI) and ADC maps.Magnetic Resonance in Medicine 02/1997; 37(1):119-23. · 3.27 Impact Factor
FLAIR Diffusion-Tensor MR Tractography:
Comparison of Fiber Tracking with
Ming-Chung Chou, Yi-Ru Lin, Teng-Yi Huang, Chao-Ying Wang, Hsiao-Wen Chung,
Chun-Jung Juan, and Cheng-Yu Chen
BACKGROUND AND PURPOSE: Partial volume with CSF is known to contaminate the
quantification of white matter anisotropy depicted by diffusion tensor imaging (DTI). We
hypothesized that the FLAIR technique helps to improve DTI white matter tractography in the
normal adult brain by eliminating CSF partial volume effects.
METHODS: Seven healthy adults aged 23–37 underwent both conventional and FLAIR DTI
at 1.5T. Each subject was imaged five times. Neural fiber tractography was performed with both
sequences by using two algorithms: a voxel-based method (EZ-tracing) with global seed points
and another based on subvoxel tractography (tensor deflection) by using manual encircling of
local seed points. Total volume of the fibers tracked was compared for the two types of images.
RESULTS: Fiber tracking was substantially most successful on FLAIR DTI near the lateral
ventricles and the sulci, where CSF partial volume effects were likely present. Minor false tracts
on FLAIR images, possibly due to a reduced signal-to-noise ratio, were found in regions
relatively free of CSF contamination; however, they did not affect tracking of major periven-
tricular white matter bundles, such as those related to the corpus callosum or the corona
radiata. When we excluded false tracts, the FLAIR technique depicted an average of 17% more
fibers in volume than conventional DTI in the periventricular regions (P < .0005, paired
Student t test).
CONCLUSION: Despite the reduction of signal-to-noise ratio and longer imaging times,
FLAIR improved tractography by eliminating CSF partial volume effects.
White matter tractography by means of diffusion ten-
sor imaging (DTI) has raised clinical attention, be-
cause tractography can noninvasively reveal func-
tional connectivity of the neuronal pathways (1, 2).
One potential problem in the quantitative derivation
of diffusion-related parameters from MR imaging
data is contamination from CSF (3–5). Because CSF
has a relatively large diffusion coefficient compared
with that of the brain parenchyma, partial volume
effects in the periventricular regions and in the sulci
could result in overestimation of the apparent diffu-
sion coefficient (ADC) by about 15–30% (3). In ad-
dition, because CSF diffusion is largely isotropic,
ADC overestimation could lead to underestimation
of diffusion anisotropy in regions of brain paren-
chyma prone to partial volume effects (4–6).
Inaccuracy in the derivation of diffusion-related
parameters due to CSF contamination can be elimi-
nated with the suppression of CSF signals by using the
fluid-attenuated inversion recovery (FLAIR) tech-
nique incorporated into a diffusion imaging sequence
(4, 5, 7, 8). However, questions remain whether sim-
ilar arguments hold true for DTI white matter trac-
tography (3–5). In particular, the accuracy of fiber
tracking algorithms strongly relies on the image sig-
nal-to-noise ratio (SNR) in addition to the anisotropy
measurements (9). Because FLAIR diffusion imaging
has an intrinsically lower SNR than that of conven-
tional diffusion imaging with the same imaging time
(5, 6), use of the FLAIR technique in diffusion trac-
tography could result in a trade-off between the ben-
Received April 20, 2004; accepted after revision July 6.
From the Department of Electrical Engineering, National Tai-
wan University (M.-C.C., Y.-R.L., T.-Y.H., C.-Y.W., H.-W.C., C.-
J.J.), and the Department of Radiology, Tri-Service General Hos-
pital (M.-C.C., C.-Y.W., H.-W.C., C.-J.J., C.-Y.C.), Taipei, Taiwan,
Supported in part by the National Science Council under grant
NSC-90-2213-E-002-102 Taiwan, ROC.
Presented at the 12th Annual Meeting of the International So-
ciety for Magnetic Resonance in Medicine, July 14–21, 2004,
Address reprint requests to Cheng-Yu Chen, MD, Department
of Radiology, Tri-Service General Hospital and National Defense
Medical Center, No 325, Sec 2, Cheng-Kung Road, Neihu 114,
Taipei, Taiwan, ROC.
© American Society of Neuroradiology
AJNR Am J Neuroradiol 26:591–597, March 2005
efits of reduced partial volume effects and the inher-
ently inferior SNR. Therefore, the purpose of our
study was to investigate the effects of FLAIR CSF
suppression on white matter tractography in the nor-
mal adult brain. Specifically, we hypothesized that
FLAIR DTI could depict a larger volume of neural
fiber tracts than that obtained with conventional DTI
Seven healthy volunteers (aged 23–37 years, all men) par-
ticipated in this study. None of these volunteers had history of
neurologic diseases, and all of their brain MR images were
normal. Our institutional review board approved the entire
study, including the MR imaging protocol, and all subjects
provided written informed consent. MR examinations were
performed using a 1.5T MR system (Siemens Vision; Erlangen,
Germany) with a single-channel circularly polarized head coil.
The maximal gradient strength was 25 mT/m.
Axial conventional DTIs were acquired by using a spin-echo
echo-planar imaging sequence. The diffusion-sensitizing gradi-
ents were applied along six directions: (?x)–(?y), (?x)–(?y),
(?y)–(?z), (?y)–(?z), (?z)–(?x), and (?z)–(?x), with the
diffusion weighting factor b ? 1400 s/mm2, plus one reference
image with b ? 0 s/mm2. Spatial misregistrations due to eddy
current effects were removed by using a twice-refocused spin-
echo technique (10) with bipolar gradient waveforms (11).
Imaging parameters, unless otherwise noted, were as follows:
TR/TE/NEX ? 5000/120/4, FOV? 24 cm, section thickness ?
3–5 mm (no intersection gap), and matrix size ? 128 ? 128.
Total imaging time was 2 minutes 20 seconds, with 16 sections
FLAIR DTIs were obtained by using the same spin-echo
echo-planar imaging sequence as stated before, with the excep-
tion that a section selective 180° inversion radio-frequency
pulse was added before the 90° excitation pulse. Multisection
acquisition was achieved with sequential-order section inter-
leaving during the TI. The section thickness for the inversion
pulse was adjusted to about 1.4 times that of the excitation
pulse to minimize incomplete CSF suppression due to through-
section CSF flow (12). To obtain gapless sections and to simul-
taneously avoid cross-talk for the inversion pulses, the image
acquisition process was completed in two steps: first for odd-
numbered sections and second for even-numbered sections.
These steps increased the total imaging time by a factor of 2. In
our study, the TI was 2300 ms, with TR increased to 9000 ms.
All other imaging parameters were kept identical to those used
in the conventional DTI sequence as stated before. The total
imaging time for 16 sections was 2 minutes 6 seconds for each
signal acquired. Magnitude reconstruction was used for the
FLAIR images, as all tissues other than CSF have already
relaxed to positive longitudinal magnetization at this long TI.
In addition, the use of real component reconstruction provides
no advantages in terms of SNR (13).
Each subject underwent five imaging sessions with both
conventional and FLAIR DTI. Therefore, the total number of
examinations was 35 for the seven subjects.
After data acquisition, image calculations were performed
on a personal computer after digital transfer of the DTIs from
the MR operating console. The diffusion tensor was calculated
on a voxel-by-voxel basis by using the known relationship with
the b matrix (14). The principal fiber direction was derived
from the diffusion tensor as the eigenvector associated with the
largest eigenvalue. Fractional anisotropy (FA) was computed
(6, 15), and FA maps were generated as gray-scale images. In
addition, vector-encoded FA maps were created to assist in
visualization; on these maps, every voxel in the gray-scale FA
maps was overlaid with a color-coded line segment represent-
ing the principal fiber direction.
Two methods were used for fiber tracking. The first one was
the EZ-tracing algorithm (16), which can be viewed as a voxel-
based counterpart of other subvoxel tractography methods (2,
9). In EZ-tracing, global tracking was used (i.e., with seed
points of the tracts were automatically searched within the
entire 3D imaging region). Thresholds for fiber connection
were set as follows: FA ? 0.2, angle between principal eigen-
vectors in adjacent voxels ?18°, and angle between principal
eigenvector and the vector connecting neighboring voxels ?18°
within a 5 ? 5-pixel window (16). For a fair comparison to
address only the effects of CSF suppression by using FLAIR
imaging, these settings were kept identical for both the con-
ventional DTI and FLAIR DTI. The resulting fiber tracts in
yellow color were superimposed on the original echo-planar
images acquired with b ? 0 s/mm2.
The second tractography method was a subvoxel fiber-track-
ing algorithm based on tensor deflection (17), with seed points
manually selected to start automatic tracking of the fibers. The
stepping parameter for the tensor deflection algorithm was set
at 0.5 voxel, meaning that the tracked fiber was allowed to
“turn” its orientation twice within one single image voxel (17).
The purpose for using different tractography algorithms was
twofold. First, the output of the EZ-tracing algorithm was a 2D
single-section display on which the possible false tracts could be
better visualized, whereas the output of the subvoxel algorithm
yielded 3D colored fiber bundles superimposed on the original
MR images in gray scale, facilitating visual examination at
different viewing angles. Second, the large amount of fiber
tracts detected with the global EZ-tracing algorithm helped in
detecting all possible false tracts within the entire imaging
region, whereas the local fiber-tracking method based on ten-
sor deflection allowed one to see whether the possible false
tracts affected the examination of major neural pathways. Spe-
cifically in the tensor deflection algorithm, we adopted the
fundamental assumption of all tractography algorithms, which
treated adjacent voxels by showing consistent directions in their
principal eigenvectors as being really connected by some neural
fibers. Therefore, any tracts oriented consistently with the ma-
jor pathways were regarded as true tracts, because the presence
of noise could only result in increased directional deviations.
Those inconsistent with knowledge of normal anatomy were
regarded as false.
Comparison of the effects of CSF suppression on tractography
was carried out for the voxel-based EZ-tracing algorithm by com-
puting the total volume of the fibers found in selected regions of
interest near the lateral ventricles. To simplify matters, the total
volume of fibers detected was defined as the total number of
voxels that were assigned as containing some neural fibers. Also
(as its rationale will become clear later), a restriction of regions of
interest to a rectangular volume about 8 ? 6 ? 4 cm encompass-
ing the lateral ventricles was used in this comparison. In this
manner, the reported increase in the total fiber volumes for
FLAIR versus conventional DTI tractograms reflected the overall
influence from both an elimination of partial volume effects and a
reduction in SNR but not from the apparent false tracts. As a
consequence, the comparison results reported were mostly con-
fined to the periventricular white matter tracts related to the
corpus callosum and the corona radiata.
We chose not to compare total fiber volume by using the
tensor deflection tractography algorithm because tensor deflec-
tion tractography is by its nature a subvoxel algorithm (17),
meaning that the computation of total number of voxels is
meaningless when a certain voxel of interest contains some
592CHOUAJNR: 26, March 2005
locally tortuous fiber tracts. In other words, fiber volume com-
putation for the tensor deflection algorithm may likely reflect
indirect influences from the subvoxel tractography algorithm
itself, in addition to the effects from FLAIR CSF suppression.
Figure 1 shows the comparison of a section of white
matter tractograms (obtained with global EZ-tracing)
by using conventional DTI (Fig 1A) and FLAIR DTI
(Fig 1B), respectively. Tracking was substantially
more successful on FLAIR DTI in the regions of the
corpus callosum and near the sulci, where the partial
volume effects with CSF were likely to be present. (As
a side note, some yellow fibers in Figure 1 that ap-
peared relatively isolated usually mean that they were
connected to voxels in an adjacent section.)
Figure 2 shows the anterior aspects of an image
section, demonstrating the difference between con-
ventional (Fig 2A, C, and E) and FLAIR (Fig B, D
and F) DTI tractograms in terms of partial volume
effects. FA maps (Fig 2C and D) were displayed at
the same window level to allow for a side-by-side
comparison of the FA values (i.e., brightness). We
clearly observed a larger amount of white matter
tracts in the corpus callosum on the FLAIR DTI
tractogram (Fig 2B) than on the conventional DTI
tractogram (Fig 2A). On conventional DTI tracto-
grams, partial volume effects with adjacent CSF in the
lateral ventricles resulted in underestimation of FA at
the edge of the corpus callosum, compared with the
FLAIR DTI tractogram (Fig 2D vs. C). The under-
estimation of FA in conventional DTI further led to
uncertainty of the major fiber orientations in the genu
of the corpus callosum (Fig 2E).
Arranged in a similar manner, Figure 3 shows the
posterior aspect of the same image section as Figure
2, demonstrating tractographic differences due both
to partial volume and SNR effects. Although the
FLAIR DTI tractogram again showed more tracts in
the splenium of the corpus callosum than the conven-
tional DTI tractogram, some amount of false tracts
was found in the occipital lobes (Fig 3B). These tracts
were regarded as artificial because they continuously
traversed across the cerebral midline where no cross-
ing fibers should exist in the anatomically normal
brain. Closer examination indicated a noisier appear-
ance of the FA map obtained by using FLAIR DTI
(Fig 3D), which possibly led to incidentally consistent
orientations of the eigenvectors (Fig 3F).
Although false tracts were sometimes found in the
FLAIR tractograms, the locations and occurrence of
these tracts were not highly reproducible, suggesting
random effects possibly due to noise. In our initial
experience, scattered false tracts tended to appear in
regions prone to susceptibility-related geometric dis-
tortions, such as the superior frontal gyri. In addition,
the false tracts identified on the tractograms by using
global seed points appeared focal and had no obvious
connections with major fiber tracts that are consistent
with our knowledge of normal neuroanatomy. Figure
4 shows the white matter tracts originating from only
the entire corpus callosum on a left anterior oblique
view superimposed on the original axial image. The
fiber tracts from FLAIR DTI (Fig 4B) were visually
larger in volume than those obtained with conven-
tional DTI (Fig 4A), suggesting that a reduction in
partial volume effects by using FLAIR helped in iden-
tifying white matter fibers near the lateral ventricles.
Visual verification on these images showed that the
focal false tracts in FLAIR DTIs (as seen in Fig 3)
seemed to exhibit minimal influence on the major
white matter tracts when the seed points were specif-
Figure 5 shows the comparison of total volumes of
fibers tracked from conventional versus FLAIR DTIs.
FLAIR DTI depicted significantly larger volumes of
fiber tracts than conventional DTI for all our subjects.
Because some minor false tracts were found near the
superior frontal gyrus and in the occipital lobes, we
restricted our regions of interest in a central rectan-
gular volume about 8 ? 6 ? 4 cm3, so that the
comparison was confined to periventricular white
matter tracts mostly in the corpus callosum and the
corona radiata. In addition, we browsed through all
individual sections of the tractograms to ensure that
false tracts were not included in the comparison. On
average, about 17% additional volume of fiber tracts
were detected on FLAIR DTI compared with con-
ventional DTI. The group difference was statistically
grams in a 24-year-old man. Images show
the white matter tracts (yellow) superim-
posed on images obtained with b ? 0
A, Tractogram obtained by using con-
B, Tractogram obtained by FLAIR DTI
shows a larger area of white matter fiber
tracts in both the genu and the splenium of
the corpus callosum.
White matter EZ-tracing tracto-
AJNR: 26, March 2005MR TRACTOGRAPHY 593
White matter tractography is potentially a useful
technique for assessing neural fiber connectivity (18)
in traumatic axonal injury (19), brain maturation (20),
and so forth (21). In the presence of CSF partial
volume effects, a seemingly reduced volume of the
tracked fibers might mimic partially destroyed integ-
rity or underdevelopment of the neural fiber archi-
tecture, leading to misleading findings. Our results,
therefore, have important implications in that they
address the efficacy of the FLAIR DTI technique by
eliminating the problems from CSF partial volume
effects, particularly in regions near the ventricles and
the sulci. Consequently, when brain regions prone to
magnified from the rectangular region-of-interest (solid rectangles). Partial volume effects near adjacent CSF lead to underestimation of
FA in the genu of the corpus callosum on conventional DTI (left column and dashed rectangles in E.) Note the less consistent fiber
directions and the darker gray level, which indicates lower FA values. These effects account for the smaller amount of fibers found with
the tracking algorithm on conventional DTI than on FLAIR DTI (right column, dashed rectangles in F). Note the more consistent fiber
directions and the brighter gray level, which indicates higher FA values.
A and B, Images obtained with b ? 0 s/mm2by using the EZ-tracing algorithm.
C and D, FA maps in gray scale displayed in the identical window level.
E and F, Vector-encoded FA maps. Red indicates left-right; green, anteroposterior; and blue, superoinferior.
Anterior aspects of an image section obtained in an 23-year-old man show white matter tracts superimposed on images A–F
594 CHOU AJNR: 26, March 2005
CSF contamination are of clinical interest, FLAIR
DTI should be the method of choice for white matter
Our results suggest that an elimination of CSF
partial volume effects by using FLAIR is helpful for
white matter tractography in regions near the ventri-
cles and brain surfaces. Specifically, an average of
17% increase in the volume of neural fiber tracts
could be found by using FLAIR images rather than
conventional DTIs. In the corpus callosum near the
lateral ventricles, the increase in fiber tract volumes
found on FLAIR images was due to FA values higher
than those on conventional DTI. This finding is in
good agreement with results of previous studies,
magnified from the rectangular region-of-interest (solid rectangles). Although the FLAIR DTI tractogram shows more tracts in the
splenium of the corpus callosum (B and dashed oval in F, with more consistent fiber directions) than the conventional DTI tractogram
(A and dashed oval in E, with less consistent fiber direction near the lateral ventricle), false tracts are found in the occipital lobes (B).
A and B, Images obtained with b ? 0 s/mm2by using the EZ-tracing algorithm.
C and D, FA maps in gray scale displayed in identical window level obtained by using conventional (C) and FLAIR DTI (D). D is noisier
than C, suggesting uncertainty in FA values.
E and F, Vector-encoded FA maps show that the false tracts in B are due to incidentally consistent orientations of the eigenvectors
(rectangle in F), which is absent in E (rectangle in E). Red indicates left-right; green, anteroposterior; and blue, superoinferior.
Posterior aspects of the same image section as in Figure 2 show white matter tracts superimposed on the images in A–F
AJNR: 26, March 2005MR TRACTOGRAPHY 595