Pim van Ooij1, Merih Cibis2, Wouter V. Potters1, Oscar H Franco3, Meike Vernooij4, Aad van der Lugt4, Frank J Gijsen2, Jolanda J Wentzel2, and Aart J Nederveen1
1Radiology, Academic Medical Center, Amsterdam, Netherlands, 2Biomedical Engineering, Erasmus MC, Rotterdam, Netherlands, 3Epidemiology, Erasmus MC, Rotterdam, Netherlands, 4Radiology, Erasmus MC, Rotterdam, Netherlands
Synopsis
The
purpose of this study is to investigate if, already in early disease, a correlation
exists between wall thickness (WT) and wall shear stress (WSS) in the carotid
bifurcation. Eleven subjects with plaques in the left carotid arteries
underwent 3D-flow-MRI and proton-density-weighted-EPI for WSS and WT
quantification, respectively. Relationships between WT and WSS were
investigated on an individual basis and using cohort-averaged maps (atlases). Spearman’s
ρ averaged over all subjects was -0.28, which was
significantly different from 0 (p<0.001). For the atlases, ρ was -0.66 (p<0.001). The atlas approach
facilitates more statistical power to show that wall thickening occurs in low
WSS regions.Purpose
Vessel
wall thickening and low wall shear stress are known as indicators of the
development of atherosclerosis in the carotid bifurcation
1. The
purpose of this study is to investigate if, already in early disease, a correlation
exists between wall thickness (WT) and wall shear stress (WSS), both derived
from MRI data, in the carotid bifurcation in an asymptomatic population. For
this purpose, the individual relations between 3D WT and WSS maps are
investigated, as well as the relation between the cohort-averaged 3D WT and WSS
maps (as created with the atlas approach, as previously described for the aorta
2).
Furthermore, the atlases are downsampled to investigate the influence of
resolution on the amount of spatial autocorrelation of the atlases
3.
Methods
Eleven
subjects (mean age: 73±7 years, range: 55-78 years) with plaques in the left
carotid arteries were selected from the Rotterdam study
4. The MRI
examination, performed on a 1.5 GE Scanner (GE Signa Excite II; GE Healthcare,
Milwaukee, WI, USA) included non-gated (time-averaged) 3D flow MRI (spatial
resolution: 0.7x0.7x1 mm
3, TE/TR: 4.3ms/13ms, Venc: 60 cm/s) and Proton
Density weighted-EPI (PDw-EPI, spatial resolution: 0.5x0.5x1.2 mm
3,
TE/TR: 24.3ms/12000ms). The 3D flow MRI images were corrected for background
phase offsets by subtraction of the velocity in static tissue. The lumen and
vessel wall were manually segmented from the PDw-EPI images using ITK-snap. The
segmentation of the wall was converted to a mesh to enable 3D WT calculations
(quantified as the shortest distance between a mesh point and the outer wall).
Rigid co-registration of the PDw-EPI and 3D flow MRI images was performed in
Elastix to ensure that the identical lumen segmentation was used for 3D WSS. WSS
was quantified using the 3D flow MRI images with the method that was described
previously
5. A ‘shared’ geometry of the 11 carotid bifurcations was
created using a combination of rigid registration and varying thresholds of
overlap as previously described for aortas
2. Subsequently, the WSS and
WT values for each subject were interpolated (nearest neighbor) onto the
‘shared geometry’ followed by averaging over the number of subjects, such that
each WT and WSS value on the map is an average of the 11 subjects, yielding WT
and WSS atlases. Spearman’s correlation coefficient ρ was determined both for subject-specific WT and
WSS maps, followed by a Fisher z-transformation (normalizing ρ) to enable a student’s t-test to test if the z-values averaged over the subjects was significantly different from 0. The
p-value was considered significant when lower than 0.05. ρ was also calculated for the full and
downsampled WT and WSS atlases. Downsampling was performed with factors 2, 4, 8
and 16.
Results
Figure
1 displays the WSS and WT maps for the subjects with the highest and lowest ρ. The carotid bifurcation geometries included
the common carotid artery (CCA), the external carotid artery (ECA) and the
internal carotid artery (ICA). Note that the lowest ρ was the only one indicating a positive relation
between WT and WSS. All other ρ’s were negative. All individual relationships
were significant with p<0.001. The averaged ρ over all subjects was -0.28, which, after the
Fisher z-transformation, was significantly different from 0 (p<0.001). In
figure 2 the WSS and WT atlases are shown. Regions of high WT show good
co-localization with regions of low WSS. The ρ for the atlases was -0.66. For all downsampled
atlases, as displayed in figure 3, the regions of low WSS corresponded with
regions of high WT. The change in ρ was minimal for all downsampled atlases (table
1).
Discussion
The
co-localization of regions of low WSS and high WT confirms that wall thickening
occurs in regions of low WSS in early disease. For both the individual and
atlas statistical analyses, this relationship was significant. The increased ρ compared to the individual analysis shows that
the atlas approach, even after downsampling, facilitates statistical power to such
observations. Extension of our database with more healthy and diseased subjects
would facilitate a comparison of the individual atherosclerotic patient with a cohort
of healthy subjects, to quantify and visualize the severity of atherosclerotic
disease.
Conclusion
The
atlas approach for WT and WSS mapping is feasible in the carotid bifurcation
and robust for resolution-related spatial autocorrelation. Individual and atlas-based
WT measurements correlated negatively with individual and atlas-based WSS
measurements. The techniques as presented may prove useful for the diagnosis
and monitoring of plaque development in patients with atherosclerosis.
Acknowledgements
The
author would like to acknowledge Ethan Rowland of the Department of
Bioengineering and Aeronautics of the Imperial College London for his advice on
the statistical analyses carried out in this work.References
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