Synopsis
Carotid neovascularization and lumen surface morphology both play important roles in the progression of atherosclerotic
plaque. This study uses a high-spatial and temporal
resolution dynamic 3D contrast-enhanced (CE) imaging technique to simultaneously
acquire and explore the relationship between the two factors. Results demonstrate
that carotid luminal stenosis and appearance of ulceration are correlated with
the plaque neovascularization. The study shows the ability to perform
high-resolution carotid plaque morphology and functional assessment within a reasonable
scanning time.Introduction
Carotid neovascularization plays an important role in the progression of
atherosclerotic plaque, which is strongly associated with plaque
inflammation, hemorrhage and instability
[1,2]. Dynamic contrast enhanced (DCE) MRI
has demonstrated the ability to quantify plaque neovascularization and
inflammation
[3]. Plaque ulceration is also believed to be a
sensitive marker of plaque instability, which showed strong association with
plaque rupture, intraplaque hemorrhage and large lipid core
[4]. This
study uses a high-spatial and temporal resolution dynamic 3D contrast-enhanced
(CE) imaging technique to provide simultaneous 4D CE-MRA and
Ktrans mapping.
Methods
Nine patients (seven males, mean age 67.7 years [range: 58 to 79 years]), eight
symptomatic with a recent history of transient ischemic attack (less than 6
month), one asymptomatic who had at least 50% carotid stenosis on screening
Doppler ultrasound, were recruited for DCE and multi contrast MRI scanning.
Imaging was performed on a 3T system (MR750, GE Healthcare, Waukesha, WI),
using a 4 channel phased-array neck coil (PACC, MachNet, The Netherlands). The
study protocol was reviewed and approved by the local ethics committee and
written informed consent was obtained.
Scan protocol
3D
time-resolved imaging of contrast kinetics (TRICKS) was performed to obtain
both DCE and CE-MRA at the same time with the following parameters: TR/TE:
3.9/1.5ms, flip angle= 20°, FOV = 140*140mm, matrix = 224*224, 44 coronal
slices with slice thickness
= 1.4mm. The imaging slab was centered on the carotid bifurcation. Acquisition time
was 6min23s, to obtain 30 temporal phases with a time interval of 10.6s. Coincident
with the third phase, a bolus of 0.1mmol/kg Gd-DPTA (Gadovist, Bayer Schering,
Berlin, Germany) was administered using a power injector at the rate of 3mL/s
followed by a 20ml saline flush. The CE-MRA data was obtained by subtracting the
baseline scan from the multi-phase acquisition. In addition, for plaque
component determination the following 3D sequences were performed: pre- and
post-contrast T
1w DANTE-prepared fast spin echo, variable flip angle
T
1 mapping, time of flight and direct thrombus imaging (DTI). Total
scanning time was ~37mins.
Image analysis
DCE images were reformatted into the axial plane
resulting in a
0.7mm slice thickness. Plaque wall and lumen boundary at each slice were
manually drawn on the pre-contrast T
1w image. Quantitative DCE
analysis was performed using an established pharmaco-kinetic (PK) modeling
approach
[1], which uses a two-compartment Patlak model to generate a
“vasa vasorum image (VVI)” showing partial plasma volume (
vp) in red and transfer constant (
Ktrans) in green. Adventitial
measurements were calculated by averaging all the pixels along the wall boundary. Plaque
measurements were calculated by averaging all the pixels between the wall and
lumen boundary. The PK parameters
of each plaque were calculated as the mean value across the slices. Plaque
surface morphology was classified as either ulcerated or smooth using the CE-MRA
images
[4]. Luminal stenosis was measured for each plaque according
to the North American Symptomatic Carotid Endarterectomy Trial (NASCET)
criteria
[5]. Statistical analysis was performed using R. A Student’s
t test was used to compare the difference between smooth versus ulcerated
plaques. Pearson’s correlation was used to study the correlation between PK parameters
and luminal stenosis.
Results
Two out of 18 arteries
were excluded due to poor image quality. Mean luminal stenosis was 44% [range 15
to 65%]. Nine of the plaques were classified as ulcerated and seven were
classified as smooth. Both adventitial and plaque
Ktrans in ulcerated plaques were
significantly higher compared with smooth
ones
(Figure 2, adventitial
Ktrans: 0.085±0.014 vs. 0.063±0.014,
p = 0.009, plaque
Ktrans: 0.070±0.014
vs. 0.054±0.014, p = 0.049). A positive correlation between adventitial
Ktrans/
vp and degree of stenosis were observed (Figure 3, r =
0.53, p = 0.03
for adventitial
Ktrans, r = 0.60,
p = 0.01 for adventitial
vp, respectively).
Discussion and conclusion
This
study for the first time uses a 4D CE acquisition sequence to acquire high spatial
and temporal resolution DCE and CE-MRA of the carotid artery allowing for simultaneous
morphological and functional assessment of carotid atherosclerosis. The results
show that adventitial and plaque
Ktrans were higher in ulcerated plaques compare
with smooth ones. Adventitial
Ktrans and
vp were also positively
correlated with the luminal stenosis. These results demonstrate that there is a
relationship between lumen surface morphology and plaque neovascularization. This combination of sequences illustrates the
ability to perform 3D high resolution carotid plaque morphology and functional assessment
in a clinically feasible scan time.
Acknowledgements
The Vasa Vasorum Image tool was kindly
provided by Dr William Kerwin of the Vascular Imaging Lab of the University of
Seattle. We acknowledge funding from NIHR BRC. References
[1] Kerwin W et al., Magn Reson
Med, 2008, 59: 507-514. [2] Qiao Y et al., Am J Neuroradiol, 2012, 33:755-760.
[3] Chen H et al., Quant Imaging Med Surg, 2013,3(6):298-301. [4] Lovett J et
al., Circulation, 2004, 110:2190-2197. [5] Barnett H et al, N Eng J Med, 1991,
325:445-453.