Intracranial Arterial Wall Imaging Using
Three-Dimensional High Isotropic Resolution
Black Blood MRI at 3.0 Tesla
Ye Qiao, PhD,1David A. Steinman, PhD,2Qin Qin, PhD,1,3Maryam Etesami, MD,1
Michael Scha ¨r, PhD,1,4Brad C. Astor, PhD,5,6and Bruce A. Wasserman, MD1*
Purpose: To develop a high isotropic-resolution sequence
to evaluate intracranial vessels at 3.0 Tesla (T).
Materials and Methods: Thirteen healthy volunteers and
4 patients with intracranial stenosis were imaged at 3.0T
using 0.5-mm isotropic-resolution three-dimensional (3D)
Volumetric ISotropic TSE Acquisition (VISTA; TSE, turbo
spin echo), with conventional 2D-TSE for comparison.
VISTA was repeated for 6 volunteers and 4 patients at
0.4-mm isotropic-resolution to explore the trade-off between
SNR and voxel volume. Wall signal-to-noise-ratio (SNRwall),
wall-lumen contrast-to-noise-ratio (CNRwall-lumen), lumen
area (LA), wall area (WA), mean wall thickness (MWT), and
maximum wall thickness (maxWT) were compared between
3D-VISTA and 2D-TSE sequences, as well as 3D images
acquired at both resolutions. Reliability was assessed by
intraclass correlations (ICC).
Results: Compared with 2D-TSE measurements, 3D-
VISTA provided 58% and 74% improvement in SNRwall
and CNRwall-lumen, respectively. LA, WA, MWT and maxWT
from 3D and 2D techniques highly correlated (ICCs of
0.96, 0.95, 0.96, and 0.91, respectively). CNRwall-lumen
using 0.4-mm resolution VISTA decreased by 27%, com-
pared with 0.5-mm VISTA but with reduced partial-vol-
ume-based overestimation of wall thickness. Reliability
for 3D measurements was good to excellent.
Conclusion: The 3D-VISTA provides SNR-efficient, highly
reliable measurements of intracranial vessels at high
isotropic-resolution, enabling broad coverage in a clini-
cally acceptable time.
Key Words: 3D; intracranial; isotropic; MRI; plaque; ves-
J. Magn. Reson. Imaging 2011; 34:22–30.
C 2011 Wiley-Liss, Inc.
THE PRESENCE OF intracranial vascular disease is
highly predictive of stroke (1). However, disease prev-
alence may be underestimated due to the lack of an
appropriate diagnostic tool to depict the intracranial
vessel wall (2). Black blood MR imaging (BBMRI) has
emerged as an effective method to measure wall
thickness and identify pathological features of extrac-
ranial vessels (3–5). Recently, its application has
been extended to evaluate intracranial vessels, specif-
ically to detect atherosclerosis (6–9) and vasculitis
(7,10). Measuring intracranial vessel wall thickness
remains a technical challenge given the small size of
these vessels. Furthermore, the techniques intro-
duced thus far have been standard two-dimensional
(2D) black blood sequences, which are prone to par-
tial volume artifacts amplified by the inherent curv-
ing course of intracranial vessels (11). This adds to
the challenge of covering the numerous intracranial
sites that are prone to atherosclerosis formation (e.g.,
basilar artery [BA], middle cerebral artery [MCA], and
petrous internal carotid artery [ICA]) (12) by 2D
Three-dimensional acquisitions enable high iso-
tropic resolution that can minimize the overestimation
of wall thickness as a consequence of the tortuosity of
these small vessels; however, 3D techniques suffer
from long scan times and suboptimal flow suppres-
sion (13). For example, double inversion recovery
techniques (14,15) typically used in 2D acquisitions
generally provide inadequate flow suppression in 3D
acquisitions because of the relatively thick re-inver-
sion pulse required. Furthermore, the long echo train
length (ETL) used to suppress flow by dephasing
effects in 2D turbo spin echo (TSE) techniques (16)
are not possible at 3D without impractically long scan
times. A recently proposed 3D technique, Volumetric
1The Russell H. Morgan Department of Radiology and Radiological
Sciences, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
2Biomedical Simulation Laboratory, Department of Mechanical and
Industrial Engineering, University of Toronto, Toronto, Ontario,
3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy
Krieger Institute, Baltimore, Maryland, USA.
4Philips Healthcare, Cleveland, Ohio, USA.
5Department of Epidemiology, The Johns Hopkins Bloomberg School of
Public Health, Baltimore, Maryland, USA.
6Department of Medicine, The Johns Hopkins University School of
Medicine, Baltimore, Maryland, USA.
Contract grant sponsor: Yousem Family Research Fund.
*Address reprint requests to: B.A.W., Johns Hopkins Hospital, 367
East Park Building, 600 North Wolfe Street, Baltimore, MD 21287.
Received November 11, 2010; Accepted March 7, 2011.
View this article online at wileyonlinelibrary.com.
JOURNAL OF MAGNETIC RESONANCE IMAGING 34:22–30 (2011)
C 2011 Wiley-Liss, Inc.
ISotropic TSE Acquisition (VISTA, Philips), uses vari-
able-flip-angle refocusing pulses to achieve a longer
ETL for more effective flow suppression without com-
promising signal and at relatively short scan times
(17). In fact, this technique has been shown to have
higher signal-to-noise ratio (SNR) efficiency and stron-
ger black-blood effects compared with conventional
3D TSE sequences (17–19).
A 3D variable flip-angle refocusing pulse sequence
has been used to image carotid (19) and peripheral
(20) arterial walls. However, one cannot intuit the suc-
cessful application of this technique to intracranial
wall imaging because these vessels are structurally
unique. For example, they are surrounded by cerebro-
spinal fluid (CSF) rather than soft tissue (e.g., fat).
Thus, our aim was to develop and optimize a high,
isotropic resolution 3D BBMRI (i.e., VISTA) protocol to
measure intracranial arterial wall size in a clinically
acceptable scan time, using a conventional 2D BBMRI
sequence (i.e., double inversion TSE) as a reference.
Three-dimensional VISTA - Technical
The applied 3D isotropic resolution VISTA sequence is
a variant of TSE with variable-flip-angle (FA) nonselec-
tive refocusing RF pulses and radial view ordering.
The variable refocusing FA modulation is designed to
achieve a target signal level by a precipitous drop in
the initial FAs, and then maintain a pseudo-steady-
state signal level over the remainder of the echo train
by gradually increasing FAs. This minimizes signal
blurring from T2 decay while reducing RF power (21).
The primary mechanisms for the intrinsic black-
blood effects of 3D VISTA include the following: (i)
Intravoxel dephasing of moving blood spins. Blood
with a spectrum of velocities and accelerations flowing
across a magnetic field gradient leads to widespread
phase dispersion that results in signal loss. In partic-
ular, the complex state of motion such as turbulence
or pulsation contributes to the spread of velocities
and accelerations, and serendipitously induces addi-
tional signal attenuation (16). Furthermore, the flow
suppression is more effective for vessels with small
diameters, such as cerebral vessels (22). (ii) The use
of low FA refocusing pulses causes the formation of
simulated echoes, which store magnetization along
the longitudinal axis and exhibits a complicated
phase evolution between the longitudinal and trans-
verse planes that results in signal loss (17). Further-
more, the FA impacts flow-related signal loss, and a
smaller FA leads to greater flow suppression (17,23).
The signal of the vessel wall achieved using the
VISTA sequence can be optimized by enabling radial-
ordering modulation in which the center of K space is
sampled at the beginning of the echo train (17). This
has the added benefit of minimizing the T2-weighting
of the image, thereby darkening the signal of the sur-
The VISTA pulse sequence implemented herein was
based on the 3D proton density (PD)-weighted TSE
technique described by Busse et al (17), that uses a
variable FA refocusing control, autocalibrating 2D-
accelerated parallel imaging, and radial view ordering
to produce isotropic high-resolution images. Parame-
ters (e.g., TE, ETL, and resolution) were modified to
facilitate intracranial wall imaging.
Thirteen healthy volunteers (8 males; ages, 22–82
years; mean, 44 years) with no history of intracranial
vascular disease were recruited. Four patients (1
male; ages, 38, 42, 44, and 61 years) with intracranial
stenosis based on a preceding MR angiogram (MRA)
or CTA were recruited (one BA stenosis, three MCA
stenoses). Institutional review board approval was
obtained and participants provided informed consent.
All exams were performed on a 3T MRI scanner
(Achieva; Philips Healthcare, The Netherlands) using
the body coil for transmission and an eight-channel
head coil for reception. A 3D time-of-flight (TOF) MRA
was first acquired to localize the intracranial arteries.
3D VISTA images were then acquired in a coronal
plane (45-mm-thick slab) to cover the major intracra-
nial vessels as identified on the TOF MRA. Imaging
parameters were as follows: repetition time/echo time
(TR/TE), 2000 ms/38 ms; TSE factor, 60 including 4
startup echoes; echo spacing, 6.1 ms; sense factor, 2
(right–left direction); oversampling factor, 1.8; and
number of averages, 1. The FOV was 200 ? 166 ? 45
mm3at a matrix of 400 ? 332 ? 90 for an acquired
voxel volume of 0.5 ? 0.5 ? 0.5 mm3(scan time, 7.9
min). To explore the trade-off between SNR and voxel
volume, a VISTA sequence was repeated with an
acquired resolution of 0.4 ? 0.4 ? 0.4 mm3for 6 vol-
unteers and 4 patients using a half scan factor (par-
tial Fourier) of 0.6 to approximate the same coverage
and scan time (scan time, 7.6 min). The variable-flip-
angle scheme for the VISTA acquisitions is illustrated
in Figure 1. Radial k-space ordering was used in the
and no fat suppression or electrocardiography (ECG)
trigger was applied.
The 2D BBMRI images were acquired for all volun-
teers using an ECG-gated double inversion recovery
TSE sequence with the following parameters: TR/
Turbo factor/TE: 2 RR/10/9 ms; FOV, 120 ? 90 mm2;
1 excitation; slice thickness, 2 mm with 0 gap; number
of averages, 2. Two sets of 2D BBMRI images were
acquired with resolutions of 0.25 ? 0.25 ? 2 mm3and
0.5 ? 0.5 ? 2 mm3, and scan times of 74 s /slice and
37 s /slice, respectively. The MRI slices were oriented
perpendicular to the vessel axis at three standard loca-
tions that represent common sites for intracranial ath-
erosclerosis (12) (Fig. 2): (a) basilar trunk, 5–6 mm
proximal to its terminal bifurcation; (b) M1 segment of
MCA, 5–6 mm beyond the origin of M1; (c) horizontal
petrous segment of the ICA, 4–5 mm proximal to the
cavernous segment. The side of the MCA and ICA used
for imaging was randomly chosen before imaging for
Intracranial Arterial Wall 3D MRI at 3T23
each segment. Two MRI slices were obtained at each
location. For patients, three to five 2D BBMRI slices
were acquired centered at the most stenotic regions.
In addition, a 3D fluid-attenuated inversion recov-
ery (FLAIR) VISTA sequence (acquired resolution, 0.5
? 0.5 ? 0.5 mm3), was also acquired in 2 volunteers
to study the effect of CSF suppression on SNR and
the visual conspicuity of the vessel wall.
Comparison Between 3D VISTA and 2D TSE
MRI images were processed using customized soft-
ware (VesselMass, Leiden University Medical Center,
the Netherlands). The 3D VISTA images (acquired re-
solution, 0.5-mm isotropic) were reconstructed to 0.5-
mm and 2-mm slice thicknesses at orientations iden-
tical to the 2D TSE slices using the Multi-Planar Ref-
ormations (MPR) tool (Fig. 3). For signal comparison,
the reconstructed 0.5-mm-thick VISTA images (0.5 ?
0.5 ? 0.5 mm3) were matched with the native 2D TSE
images (0.2 5 ? 0.25 ? 2 mm3), having identical voxel
volumes. For morphologic comparison, the recon-
structed 2-mm-thick VISTA images (0.5 ? 0.5 ? 2
mm3) were matched with the native 2D images (0.5 ?
0.5 ? 2 mm3) for the same in-plane resolution and
slice thickness to test whether they provided compa-
rable wall thickness and lumen and wall area meas-
urements. To minimize recall bias, the 2D TSE and
reconstructed VISTA images were analyzed in sepa-
rate sessions by at least 2 weeks.
Figure 2. The 3D TOF MRA collapsed Maximum Intensity
Projection (MIP) image (AP view) demonstrates normal intra-
cranial vessels in a 38-year-old male (a). 2D black blood MRI
(BBMRI) images were acquired at two in-plane resolutions
(0.25 ? 0.25 mm2versus 0.5 ? 0.5 mm2) and oriented or-
thogonal to the M1 segment of the MCA (b,c), distal BA (d,e)
and horizontal petrous ICA (f,g) as prescribed on the TOF
MRA (a, lines). Cross-sectional view of vessel of interest is
identified by arrow.
Figure 1. Refocusing variable-flip-angle scheme used for
VISTA acquisitions. Parameters: amin ¼ 50?, amax ¼ 120?,
ETL ¼ 56 þ 4 startup echoes.
Figure 3. The 3D VISTA images (0.5-mm isotropic resolu-
tion) of a BA in a 38-year-old healthy volunteer. A 3D VISTA
image is reconstructed to visualize the long axis of the BA
(arrows, a). Short axis VISTA images are reconstructed to
0.5-mm-thickness (b) and 2-mm-thickness (c) at the same
position as the 2D TSE image (Fig. 2d,e) using the Multi-Pla-
nar Reformations (MPR) tool (dashed line, a). Cross-sectional
view of BA is identified by arrow (b,c).
24Qiao et al.
Images were analyzed by two readers using a semi-
automated contouring feature of VesselMass software.
Contours were generated using a gradient image that
displays the spatial derivatives in image intensity (i.e.,
edges) extracted from the original gray-scale image.
These edges provide an objective definition for soft tis-
sue boundaries, which eliminates the influence of
subjective window/level settings for vessel contour
detection (24). Lumen and outer wall contours were
drawn using the gradient image by bisecting the band
of high intensity that represents the lumen and wall
interface, as well as the band representing the inter-
face between the wall and surrounding tissue (Fig.
4d). Lumen area (LA), wall area (WA), mean wall thick-
ness (MWT), and maximum wall thickness (maxWT)
values were generated (Fig. 4). For regions without a
clear boundary (e.g., 2–4 clock in Fig. 4d), the contour
was traced to maintain the continuity of the vessel’s
curvature based on the magnitude image.
The SNR of lumen (SNRlumen) and wall (SNRwall) meas-
urements were calculated: SNR ¼ S/SDnoise, where S is
the averaged signal intensity of the region of interest,
and SDnoiseis the standard deviation of noise. Because
of the inhomogeneous noise distribution encountered in
parallel imaging, we measured noise from an ROI of 25
mm2manually placed in the adjacent white matter
(20,25) instead of using the air. The contrast-to-noise
ratio (CNR) of wall versus lumen (CNRwall-lumen) was cal-
culated as CNRwall-lumen¼ SNRwall-SNRlumen. The CNR
efficiency (CNReff) was determined to account for differ-
ences in scan times between 2D and 3D techniques to
enable a fair comparison. CNReff was calculated as:
CNReff¼ CNR/(VOXEL(TAslice)1/2), where VOXEL is the
voxel volume (in mm3) and TAsliceis the scan time per
slice (in minute) (20).
Comparison Between VISTA Acquired at 0.4 and 0.5
The 3D VISTA dataset acquired at 0.4-isotropic reso-
lution was reconstructed at 0.4-mm-thick slices at
three standard locations as prescribed for the 0.5-
Figure 4. The 3D VISTA images (0.5-mm isotropic resolution) of a basilar artery in an 82-year-old healthy volunteer. Long-
axis view of the basilar artery (a) to orient short axis view (b, reconstructed at line shown in a). A gradient image (c) is gener-
ated using Sobel operator (24) to guide contour placement (d) using VesselMass software (Leiden University, the Netherlands).
Contours are transferred to the magnitude image (e), and then used to divide the vessel wall into 12 radial segments with
thickness and area measurements generated by VesselMass software (f). Basilar artery, arrow.
Intracranial Arterial Wall 3D MRI at 3T 25
isotropic 3D VISTA images (i.e., based on the position-
ing of the 2D slices). In addition, the native coronal
view image that best displayed the supraclinoid ICA
segment in cross section was selected from the two
3D datasets, and the slice locations were matched.
Therefore, four vessel segments were analyzed from
the participants who underwent both 0.4-isotropic
and 0.5-isotropic VISTA imaging. Signal and morpho-
logic measurements were assessed in the same man-
ner as described in the previous section.
Data were analyzed using SPSS 18.0 (SPSS Inc, Chi-
cago, IL). All signal-based measurements (SNRlumen,
SNRwall, CNRwall-lumenand CNReff(wall-lumen)) were deter-
mined for each slice (n ? 6) and a single value was used
for each participant based on the average of all slices.
Morphological variables (LA, WA, MWT, and maxWT)
were reported as the average of both slices for each ves-
sel segment (i.e., MCA, BA, petrous ICA, and supracli-
noid ICA), as wall thickness may vary by location. All
signal-based and morphological measurements were
compared between 3D VISTA and 2D TSE sequences
using two-tailed paired t-tests. The same test was
conducted to compare the VISTA images acquired at
0.4-isotropic versus 0.5-isotropic resolution. Agree-
ment between MRI measurements obtained from 2D
and 3D techniques were assessed using Bland-Altman
plots (26) and intraclass correlation coefficients (ICC)
(27). Inter- and intra-reader variability was assessed
using ICC, and reliabilities below 0.4 were character-
ized as poor, 0.4 to 0.75 as fair to good, and above 0.75
as excellent (28). Repeated measures analysis of var-
iance was used to calculate between-subject variance
and between-reader variance for MWT of each vessel
segment and each spatial resolution. Data are pre-
sented as means 6 standard deviations.
The 3D VISTA images were successfully acquired from
17 participants (13 volunteers and 4 patients). The
major intracranial vessel walls were clearly visualized
in all participants, and no atherosclerotic plaques
were noted in healthy volunteers. Minimal flow arti-
fact was identified in two cases as a wisp of faint sig-
nal projecting into the lumen from the inferior vessel
wall at the junction between the horizontal and verti-
cal segments of the petrous ICA, but not elsewhere
including in the MCA, BA, and ICA beyond the pet-
rous segments for all participants.
Comparison Between VISTA and 2D TSE
The 3D VISTA 0.5-mm isotropic-resolution images
were reconstructed and matched with corresponding
2D MRI images in 12 volunteers. One volunteer
moved between the VISTA and 2D TSE sequences,
adequate image quality on the 2D TSE sequence were
compared. A total of 54 pairs of 2D and 3D images at
the MCA, BA and petrous ICA locations were used for
Compared with 2D TSE (0.25 ? 0.25 ? 2.0 mm3)
image measurements, 3D VISTA images acquired at
the same voxel volume (0.5 ? 0.5 ? 0.5 mm3) and
reconstructed to the same location provided 58%
improvement in SNRwall(6.34 6 1.84% versus 10.01 6
2.45; P < 0.01), 74% improvement in CNRwall-lumen
(3.70 6 1.20 versus 6.45 6 1.84; P < 0.01), and 484%
improvement in CNReff (wall-lumen)(45.69 6 13.26 versus
266.93 6 65.33; P < 0.01). A difference in SNRlumen
could not be detected between the 3D and 2D acquisi-
tions (3D VISTA, 2.89 6 1.40 versus 2D TSE, 2.68 6
0.82). For a comparison of morphology, the 3D VISTA
images reconstructed to the same voxel dimension as
the 2D TSE images (0.5 ? 0.5 ? 2.0 mm3) revealed
excellent agreement between measurements of LA, WA,
MWT and maxWT for each vessel segment (ICCs of
0.96, 0.95, 0.96, and 0.91, respectively; Table 1). There
was no difference in LA, WA, MWT and maxWT meas-
urements for BA, petrous ICA and MCA segments com-
pared between 2D and 3D acquisitions (P value not sig-
agreement without a bias between techniques (mean
wall thickness shown in Fig. 5).
Comparison Between 0.4-mm and 0.5-mm
Isotropic Resolution VISTA Sequences
The 3D VISTA images acquired at 0.4-mm resolution in
six volunteers were reconstructed at four locations (BA,
MCA, petrous ICA, and supraclinoid ICA) and matched
with corresponding images reconstructed at 0.5-mm
resolution (37 image pairs). Compared with 0.5-mm re-
solution image measurements, 0.4-mm resolution
images showed a 27% decrease in CNRwall-lumen(6.43 6
2.16 versus 4.67 6 1.25; P < 0.01). For morphologic
Morphologic Measurements for Intracranial Vessel Segments From 3D VISTA and 2D TSE Images*
2D TSE (0.5x0.5x2 mm3)3D VISTA (0.5x0.5x2 mm3)
MCABA Petrous ICAMCA BAPetrous ICA
Lumen area (mm2)
Wall area (mm2)
Mean wall thickness (mm)
Maximum wall thickness (mm)
*P not significant for paired (2D TSE-3D VISTA) measurements.
26 Qiao et al.
location for all participants obtained from 0.4-mm
images decreased by an average of 10.2% compared
with corresponding 0.5-mm images (paired differences
were significant, P < 0.05). We observed a qualitative
improvement in plaque delineation for the patient
exams due to diminished partial volume effects related
to the improved resolution at 0.4 mm (Figs. 6 and 7).
Comparison Between FLAIR-VISTA and VISTA at
0.5-mm Isotropic Resolution
CSF suppression was applied to the VISTA sequence
and resulted in poor conspicuity of the vessel wall
with a 76% reduction in SNRwall(15.88 6 1.69 versus
3.81 6 0.09; P < 0.05) and an 83% reduction in
CNRwall-lumen(11.87 6 0.13 versus 2.03 6 0.14; P <
0.05). We simulated the wall signal using the formulas
for steady-state excitation and inversion recovery (29)
and calculated a 72% signal reduction when using
CSF suppression (assuming a TR of 2000 ms, a T1CSF
of 4300 ms (30), and a T1wallof 1198 ms) (31,32).
MRI Measurement Reproducibility
Intra- and inter-reader reliability (ICC) for MRI meas-
urements (e.g., MWT, LA, and WA) of petrous ICA,
supraclinoid ICA, and BA segments ranged from 0.84
to 0.98 (Table 2). Reliability estimates were lower for
MCA measurements, which seemed due to its conflu-
ence with adjacent brain parenchyma with little sur-
rounding CSF reducing conspicuity of its outer wall.
Between-subject variance of MWT was 0.125 mm,
0.042 mm, 0.068 mm, and 0.064 mm based on 0.5-iso-
tropic VISTA images, and was 0.122 mm, 0.022 mm,
0.048 mm, and 0.033 mm based on 0.4-isotropic
VISTA images for petrous ICA, supraclinoid ICA, BA,
and MCA segments, respectively. Between-reader var-
iance was approximately 0.04 mm for all segments at
both resolutions: 0.035 mm, 0.041 mm, 0.037 mm,
and 0.040 mm based on 0.5-isotropic VISTA images,
and 0.0.041 mm, 0.044 mm, 0.037 mm, and 0.041 mm
based on 0.4-isotropic VISTA images for petrous ICA,
supraclinoid ICA, BA, and MCA segments, respectively.
We introduce a new MRI method for high-isotropic re-
solution imaging of intracranial arterial walls at 3T
without the anticipated difficulties of suboptimal flow
suppression. This acquisition can cover a large vol-
ume of intracranial vessels, inclusive of the typical
sites of atherosclerosis formation, in a clinically ac-
ceptable scan time of approximately 7 min to provide
highly reliable measurements of vessel wall size. In
particular, the superior SNR efficiency afforded by the
variable-flip-angle refocusing pulses, along with the
inherent ability to reconstruct this isotropic imaging
volume in any plane, enable better vessel wall visual-
ization compared with 2D TSE black blood sequences
used for intracranial arterial imaging.
Once thought to be uncommon, intracranial athero-
sclerotic disease is now known to be as prevalent as
extracranial atherosclerosis (33,34). Despite a growing
recognition of the importance of identifying intracra-
nial atherosclerosis (34), only a few studies have
attempted to image intracranial atherosclerosis using
MRI (7–9,35,36). Until now a 2D BBMRI technique
has been the only approach used, but its application
is limited by (i) low spatial resolution in the slice-
select direction (in general, 2 or 3 mm), thus making
2D images more prone to obliqueness artifact from
partial volume effects, which is particularly trouble-
some for the inherently tortuous intracranial vessels;
(ii) long acquisition times needed to achieve high reso-
lution with sufficient SNR to measure the wall and
depict fine intracranial lesions; (iii) difficulty position-
ing 2D slices in one scan to capture multiple intracra-
nial vessels with varying orientations (basilar, MCA,
or ICA segments). In comparison, our 3D VISTA
sequence has demonstrated high intrinsic SNR/CNR
efficiency, allowing for volume acquisitions with 0.4-
to 0.5-mm resolution along the slice direction and
with broad coverage (45-mm) in one acquisition. Our
test against the 2D technique was particularly rigor-
ous considering there were some 2D–3D paired cases
not analyzed because of inadequate 2D image quality.
Of note, with the aid of MPR, 3D acquisitions enable
retrospective visualization of the vessel wall and
lumen in flexible planes, therefore allowing for accu-
rate monitoring of disease progression and regression.
The 3D BBMRI techniques have been developed for
extracranial arterial wall imaging and are commonly
steady-state free precession (SSFP) sequences com-
bined with a black blood preparation pulse (37,38).
However, SSFP for intracranial vessel wall imaging is
hampered by strong susceptibility effects from air
(e.g., sinuses) and adjacent bony structures (e.g.,
Figure 5. Bland-Altman plot of the percent difference versus
mean for the 2D and 3D paired MWT measurements. 3D
images (0.5-mm isotropic resolution) were reconstructed to
match the voxel dimensions of the 2D sequence (0.5 ? 0.5 ?
2 mm3). Measurement pairs show good agreement.
Intracranial Arterial Wall 3D MRI at 3T 27
skull base), particularly at high fields such as 3.0T. In
contrast, a 3D TSE technique with a dedicated refo-
cusing sweep and a long echo train (e.g., VISTA) is
less sensitive to these field inhomogeneities (19,20).
Our study is the first application of the VISTA
sequence for intracranial vessel wall imaging.
It is known that 3D TSE has intrinsic black-blood
effects from the dephasing of moving blood spins
(16,22). With VISTA, the intrinsic black-blood effect is
further enhanced by the long echo train. Additionally,
the low-flip-angle refocusing pulses induce stimulated
echoes that increase the phase dispersion (17). The
appreciable secondary flows that lead to increased
dephasing of spins, particularly when the vessels are
small (22). In our study, blood signal was effectively
suppressed through the 4.5-cm slab with flow sup-
pression comparable to that of the 2D TSE sequence
and even provided superior contrast between wall and
lumen compared with that achieved by 2D TSE.
improve the conspicuity of the intracranial vessel wall,
our results demonstrated a deleterious effect because
of the SNR penalty. To gain contrast between the wall
and CSF, we chose radial instead of linear view ordering
to obtain T1/PD-weighted images where CSF appeared
dark (17). Surrounding CSF seemed to improve wall
conspicuity, which was the reason we found MCA thick-
ness measurement reliability to be less than for other
vascular segments. We would expect this to improve for
the MCA in older individuals with more CSF surround-
ing the vessel due to age-related brain involution, espe-
cially compared with the relatively young volunteers in
Our results show the 3D VISTA sequence can detect
lesions and measure the intracranial vessel wall in
Figure 6. TOF MRA MIP (acquired resolution, 0.52 ? 0.70 ? 1.4 mm3) of the basilar artery demonstrates a high-grade steno-
sis of its mid segment (arrow, a) in a 42-year-old patient. A multiplanar reconstruction of the MRA dataset oriented through
the long axis of the basilar artery depicts the narrowing at its mid segment (arrow, b). Reconstructed 3D VISTA image at 0.5-
mm isotropic resolution (c) at the same position as the MRA reconstruction (b) demonstrates wall thickening responsible for
the high-grade stenosis (arrow, c). Reconstructed 3D VISTA image at 0.4-mm isotropic resolution (d) at the same position
shows improved delineation of the lumen at the point of narrowing (arrow, d) due to reduced partial volume effects. A 2D
BBMRI slice (0.25 ? 0.25 ? 2.0 mm3) acquired coronally at this location (not for the purpose of this study) is also shown (e)
for comparison, but suffers from insufficient SNR. Magnified long-axis 3D VISTA 0.4-mm-resolution reconstruction image
shows the slice orientation (line, f) used to position a short axis reconstruction of the VISTA dataset through the mid-basilar
plaque (g, arrowheads delineate outer wall, arrow points to lumen).
28Qiao et al.
normal human arteries. It may provide a reference
standard of the normal vessel wall to discern patho-
reducing the resolution from 0.5-mm to 0.4-mm iso-
tropic should allow for a reduction in partial-volume-
based overestimation of wall thickness and a sharper
depiction of wall features (Figs. 6 and 7). As illus-
trated in Figure 8, for a typical normal cerebral artery
wall thickness of 0.5–0.7 mm, the measured thick-
ness decreases by 15–20% in going from 0.5- to 0.4-
mm resolution. This is broadly consistent with our
measured 10–20% reductions. More importantly, as
can be seen by the leveling off of the curves in Figure
8, inadequate spatial resolution serves to ‘‘compress’’
decreasing the ability to resolve actual differences in
wall thickness. Consider, for example, the task of dis-
criminating between a 0.5- and 0.6- or 0.6- and 0.7-
mm wall. Referring to Figure 8, at 0.5-mm spatial re-
solution, the apparent difference would be on the
order of 0.02 mm, well below the precision of the
measurements. At 0.4-mm spatial resolution, how-
ever, the apparent difference is on the order of 0.4
mm, close to the inter-reader variability. In other
words, for discriminating differences in cerebrovascu-
lar wall thickness, 0.4-mm spatial resolution appears
to offer a two-fold increase in apparent resolving
power compared with 0.5-mm spatial resolution.
Limitations to our study include the following: (i) The
inability to effectively resolve small intracranial vessels
(distal branches of the Circle of Willis). This limitation
is more theoretical than clinically relevant because
atherosclerosis is a disease of large arteries and our
targets (BA, M1 segment MCA, and intracranial por-
tions of the ICA) are typical sites of plaque formation;
(ii) Small sample size. We only included a small num-
ber of healthy volunteers varied in age and race,
though the thin vessels encountered in our healthy
and relatively young group of volunteers poses a
greater technical challenge than might be encountered
in a population more susceptible to atherosclerosis. A
large population study will establish the association of
risk factors (i.e., age, race) with vessel wall thickness;
(iii) We report excellent observer reliability but did not
test scan reliability. However, based on the largest
investigation reported on extracranial carotid wall MRI
measurement reliability (5), overall scan reliability was
found to be primarily related to reader variability. Fur-
thermore, the 3D nature of our sequence obviates the
need for prospective slice placement by the MRI tech-
nologist, which is the most important reason for scan
variability (39); (iv) Lack of a standard reference for
Figure 7. The 3D VISTA image of the basilar artery (arrow)
shown in Figure 4 reconstructed in the same long-axis plane
but acquired at a higher resolution (0.4-mm isotropic). Note
the sharper delineation of the wall compared with Figure 4a.
Also noteworthy is the slight asymmetry in wall thickness of
this curved vessel, with the thicker side along its concave
bend where there is compensatory thickening likely due to the
greater tensile stresses as described for bending vessels (40).
MRI Measurement Reliability Based on VISTA Acquired at 0.5-mm
Figure 8. Effect of spatial resolution on wall thickness mea-
surement. Curves obtained using the techniques outlined in
Antiga et al (11) for the case of vessel segmented without
using Gaussian smoothing. Symbols are placed at true thick-
nesses of 0.5, 0.6, and 0.7 mm, with horizontal dashed lines
identifying the thickness that would be measured at that
true wall thickness.
Intracranial Arterial Wall 3D MRI at 3T29
intracranial vessels. Future studies with autopsy spec-
imen correlation are necessary to test the agreement
between MRI measurements and histology. In conclu-
sion, the 3D VISTA sequence offers high isotropic spa-
tial resolution with excellent flow suppression to reli-
ably measure intracranial vessel wall thickness and
depict lesions with broad coverage in approximately 7
min at 3.0T. This technique may provide important
insight into stroke risk by enabling the assessment of
plaque burden not otherwise achievable by conven-
tional angiographic techniques.
D.A.S. acknowledges salary support from his Heart
and Stroke Foundation Career Investigator Award.
The authors would like to thank Dr. YiuCho Chung
for his input that helped lead to this study.
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