4D flow MRI-derived Wall Shear Stress Correlates with Vessel Wall Thickness: Atlases of the Carotid Bifurcation
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 bifurcation1. 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 aorta2). Furthermore, the atlases are downsampled to investigate the influence of resolution on the amount of spatial autocorrelation of the atlases3.

Methods

Eleven subjects (mean age: 73±7 years, range: 55-78 years) with plaques in the left carotid arteries were selected from the Rotterdam study4. 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 mm3, TE/TR: 4.3ms/13ms, Venc: 60 cm/s) and Proton Density weighted-EPI (PDw-EPI, spatial resolution: 0.5x0.5x1.2 mm3, 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 previously5. 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 aortas2. 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

1. Malek A, Alper SL, Izumo S, Hemodynamic Shear Stress and Its Role in Atherosclerosis, JAMA 1999;282:2035-2042

2. van Ooij P, Potters WV, Nederveen AJ et al. A methodology to detect abnormal relative wall shear stress on the full surface of the thoracic aorta using four-dimensional flow MRI, Magn Res Med. 2015 Mar; 73(3):1216-27

3. Rowland EM, Mohamied Y, Yean Chooi K et al. Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps of Different Arterial Properties, J Biomech Eng. 2015 Oct; 137(10): 101003

4. Hofman A, Brusselle GG, Darwish Murad S et al. The Rotterdam Study: 2016 objectives and design update, Eur J Epidemiol. 2015 Aug; 30(8):661-708

5. Potters WV, van Ooij P, Marquering H et al. Volumetric Arterial Wall Shear Stress Calculation Based on Cine Phase Contrast MRI, J Magn Reson Imaging, 2015, Feb;41(2):505-16

Figures

Figure 1. Left column: the subject with the lowest Spearman’s ρ (which was the only positive ρ) for the relation between wall thickness and wall shear stress. Right column: the subject with the highest ρ for the relation between wall thickness and wall shear stress.

Figure 2. The atlases of the carotid bifurcation for (a) wall thickness and (b) wall shear stress. Insets show the 180° view. Spearman’s ρ for the relationship between the maps is given as well.

Figure 3. The wall thickness and wall shear stress atlases downsampled with factors 2, 4, 8 and 16

Table 1. Spearman’s ρ and the p-value for the relationships between wall thickness and wall shear stress for the downsampled atlases



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
2700