Abnormal aortic motion corresponds with abnormal wall shear stress in Marfan patients: a combined 4D bSSFP and 4D flow CMR study

Background: Marfan patients that underwent root replacement surgery (RR) have an increased risk of type B aortic dissection (TBAD), hypothetically because the noncompliant graft is unable to absorb systolic forces leading to undampened flow in the proximal descending aorta (pDA)¹. Recently we found with 4D balanced steady-state free precession (bSSFP) MRI that in 40% of the cases aortic motion in the proximal descending aorta is abnormally elevated². In this study we investigate how abnormal motion relates to abnormal 4D flow MRI-derived wall shear stress (WSS) as a marker for disturbed flow.

Methods: 81 Marfan patients (33 with RR, 35 [24-50] years, 37 women) and 45 age- and sex-matched volunteers underwent ECG- or PPU-gated 4D bSSFP and flow MRI with identical spatial resolution acquired at (1.6mm)³ and reconstructed to (1.0mm)³. Scans were accelerated with free-running Prospective Undersampling in Multiple Dimensions with bSSFP/4D flow scan times of 4m25s/7m14s³. All data was reconstructed to 30 cardiac phases, resulting in a bSSFP/4D flow undersampling factor of ~20/~14. nnU-net⁴ was used to segment all cardiac phases of the bSSFP data⁵ and the time-averaged phase contrast MRA. Peak systolic motion and WSS were calculated^5,6. By creating 95% confidence interval maps of the volunteers, abnormal motion and WSS maps of the patients were created⁷ (figure 1). The surface area of abnormal motion and WSS were quantified in five regions of interest: the proximal and distal ascending aorta (pAA and dAA), the arch, the pDA and distal descending aorta (dDA). By combining the abnormal maps, incidence maps⁸ were created for the RR cohort and non-RR cohort showing the percentage of the cohort with abnormalities in the aorta. Linear regression was used to investigate agreement between abnormal motion and WSS. P< 0.05 was considered significant.

Results: Table 1 shows that the surface area of decreased aortic motion was significantly increased for the pAA and the dDA for RR compared to non-RR patients. Similarly, the surface area of both elevated and decreased WSS were increased for most of the regions. For all subjects, decreased motion correlated with decreased WSS in the pAA (R=0.37), dAA (R=0.51), arch (R=0.58), pDA (R=0.64), and dDA (R=0.44). For RR patients these correlation coefficients were R=0.53, R=0.57, R=0.61, R=0.74 and R=0.42. For non-RR patients these were R=0.46, R=0.14 (not significant), R=0.57, R=0.43 and R=0.50. In figure 2 the incidence maps are shown for abnormal motion and WSS for the RR and non-RR cohorts. RR patients showed more abnormalities than non-RR patients, with 100% of the RR-patients having decreased motion of the pAA.

Conclusion: The surface areas with decreased motion and decreased WSS were higher for RR patients compared to non-RR patients and correlated in all aortic regions. As aortic stiffness and WSS are indicators for aortopathy, these markers and their relation may have predictive value for adverse outcomes in Marfan patients such as TBAD.

Table 1. Median (interquartile range) for surface area of elevated and decreased motion and WSS for the five regions for RR and non-RR patients and the p-values for their differences.
	Region	Elevated surface area (cm2)			Decreased  surface area (cm2)
Motion		No RR	RR	P*	No RR	RR	P*
	pAA	0 (1)	0 (0)	0.045	0.5 (29)	50 (23)	< 0.001
	dAA	0 (6)	0 (2)	0.343	0 (1)	2 (9)	0.002
	Arch	0  (9)	1  (10)	0.539	0  (0)	0  (2)	0.772
	pDA	0  (4)	2  (12)	0.033	0  (0)	0  (1)	0.172
	dDA	0  (3)	0  (7)	0.667	0  (3)	13  (19)	< 0.001
WSS	pAA	1  (1)	6  (9)	< 0.001	2  (4)	3  (4)	0.535
	dAA	1  (1)	4  (6)	< 0.001	0  (0)	0  (1)	0.006
	Arch	1  (1)	2  (4)	0.048	1  (1)	2  (5)	< 0.001
	pDA	0  (0)	0  (1)	0.534	2  (3)	4  (8)	0.004
	dDA	1  (2)	1  (2)	0.844	1  (2)	2  (3)	0.009
*Wilcoxon rank sum test, P< 0.05 considered significant WSS = wall shear stress, RR = root replacement, pAA = proximal ascending aorta, dAA = descending ascending aorta, pDA = proximal descending aorta, dDA = distal descending aorta

Figure 1. Creation of abnormal motion maps: a) 3D bSSFP images for one slice at the systolic and diastolic timeframe, b) peak systolic displacement of volunteer 1 and c) volunteer 2, d) displacement of volunteer 2 projected to volunteer 1, insets show pre- and post-registration, e) the average displacement and standard deviation of all 44 volunteers, f) displacement of an exemplary Marfan patient, g) the upper and lower limits of the volunteer 95% confidence interval projected on the patient geometry, insets show pre- and post-registration, h) red/blue regions show higher/lower systolic displacement than upper/lower thresholds of the volunteers.
Figure 2. Incidence maps for elevated (left) and decreased (right) motion (top) and WSS (bottom) for patients that underwent root replacement surgery (RR) and those with native aortas. The location with the maximum percentage of patients with abnormal motion and WSS is indicated.