Continuous measurement of aortic dimensions in Turner syndrome: a cardiovascular magnetic resonance study

Abstract

Background: Severity of thoracic aortic disease in Turner syndrome (TS) patients is currently described through measures of aorta size and geometry at discrete locations. The objective of this study is to develop an improved measurement tool that quantifies changes in size and geometry over time, continuously along the length of the thoracic aorta.

Methods: Cardiovascular magnetic resonance (CMR) scans for 15 TS patients [41 ± 9 years (mean age ± standard deviation (SD))] were acquired over a 10-year period and compared with ten healthy gender and age-matched controls. Three-dimensional aortic geometries were reconstructed, smoothed and clipped, which was followed by identification of centerlines and planes normal to the centerlines. Geometric variables, including maximum diameter and cross-sectional area, were evaluated continuously along the thoracic aorta. Distance maps were computed for TS and compared to the corresponding maps for controls, to highlight any asymmetry and dimensional differences between diseased and normal aortae. Furthermore, a registration scheme was proposed to estimate localized changes in aorta geometry between visits. The estimated maximum diameter from the continuous method was then compared with corresponding manual measurements at 7 discrete locations for each visit and for changes between visits.

Results: Manual measures at the seven positions and the corresponding continuous measurements of maximum diameter for all visits considered, correlated highly (R-value = 0.77, P < 0.01). There was good agreement between manual and continuous measurement methods for visit-to-visit changes in maximum diameter. The continuous method was less sensitive to inter-user variability [0.2 ± 2.3 mm (mean difference in diameters ± SD)] and choice of smoothing software [0.3 ± 1.3 mm]. Aortic diameters were larger in TS than controls in the ascending [TS: 13.4 ± 2.1 mm (mean distance ± SD), Controls: 12.6 ± 1 mm] and descending [TS: 10.2 ± 1.3 mm (mean distance ± SD), Controls: 9.5 ± 0.9 mm] thoracic aorta as observed from the distance maps.

Conclusions: An automated methodology is presented that enables rapid and precise three-dimensional measurement of thoracic aortic geometry, which can serve as an improved tool to define disease severity and monitor disease progression.

Trial registration: ClinicalTrials.gov Identifier - NCT01678274 . Registered - 08.30.2012.

Keywords: Aorta; Cardiovascular magnetic resonance; Centerlines; Continuous measures; Euclidean distance; Iterative closest point; Maximum diameter; Turner syndrome.

Figures

Fig. 1

Procedure to generate 3D patient-specific geometries of the thoracic aorta, exemplied for a subject with Turner sydrome (Subject 6). The CMR images were segmented to identify a rough geometry which is subsequently smoothed and clipped for analysis. Centerlines were then identified using VMTK (highlighted in black, overlayed on corresponding aorta geometry) and planes could be sampled normal to the centerline (highlighted in yellow, centerline also shown for reference)

Fig. 2

Visit based variation in maximum aortic diameter for three aortic phenotypes in TS comprised of aortic valve regurgitation (Subject 1), elongation of the transverse aortic arch (Subject 9) and aortic coarctation (Subject 7). Visit 1 – solid blue line, Visit 2 – solid red line, Visit 3 – solid black line. Diamond markers indicate corresponding manual measures. Data at locations of the inominate artery (IA), left common carotid artery (LCCA), left subclavian artery (LSCA) (shaded in black) excluded from analysis. All values are in mm. Aortas for the three visits aligned at the branches

Fig. 3

Visit based variation in cross-sectional area for three aortic phenotypes in TS comprised of aortic valve regurgitation (Subject 1), elongation of the transverse aortic arch (Subject 9) and aortic coarctation (Subject7). Visit 1 – solid blue line, Visit 2 – solid red line, Visit 3 – solid black line. Diamond markers indicate corresponding manual measures. Data at locations of the inominate artery (IA), left common carotid artery (LCCA), left subclavian artery (LSCA) (shaded in black) excluded from analysis. All values are in mm2. Aortas for the three visits aligned at the branches

Fig. 4

Scatter plot and linear regression lines for maximum diameter at select locations along the thoracic aorta for all cases and visits. Visit 1 - blue diamond markers and solid line, Visit 2 - red diamond markers and solid line, Visit 3 - black diamond markers and solid line. Forty-five degrees dashed green line also shown to indicate deviation of manual measures relative to the corresponding continuous values

Fig. 5

Bland-Altman analysis comparing maximum aortic diameter obtained using manual and continuous methods for individual visits and all visits considered. Visit 1 - blue diamond markers, solid blue line – mean, light blue lines - ±1.96SD, Visit 2 – red diamond markers, solid red line – mean, light red lines - ±1.96SD, Visit 3, All Visits - black diamond markers, solid black line – mean, gray lines - ±1.96SD

Fig. 6

Passing-Bablok regression plots comparing manual and continuous methods for individual visits and all visits considered. Visit 1 - blue diamond markers, solid blue line – regression line, light blue dashed lines – upper and lower bounds, Visit 2 – red diamond markers, solid red line – regression line, light red lines – upper and lower bounds, Visit 3, All Visits - black diamond markers, solid black line – regression line, gray lines – upper and lower bounds

Fig. 7

Color plots indicating circumferential and axial variation in Euclidean distance from centerlines for controls included in this study. All dimensions are in mm. Anterior and posterior views of the aorta are shown for each case

Fig. 8

Color plots indicating circumferential and axial variation in Euclidean distance from centerlines for 10 TS patients (patient nos. 1, 4, 5, 6, 8, 9, 10, 11, 13 and 15). All dimensions are in mm. Anterior and posterior views of the aorta are shown for each subject

Fig. 9

Three dimensional visit-to-visit variation in aorta geometry (Subject 9). a Color plots indicating circumferential and axial variation in Euclidean distance from centerlines. All dimensions are in mm. Anterior and posterior views of the aorta are shown for each visit. b Color plots indicating circumferential and axial variation in visit-by-visit change, obtained using point registration. Positive indicates increasing and negative indicates decreasing dimension of Visit 2 / Visit 3 relative to Visit 1 / Visit 2. Reference aortic surface (Visit 1 or 2) and registered aorta (Visit 2 or 3) are shown in blue and white, respectively. All values in mm. Anterior views shown for the three cases. Arrows shown to indicate location of progressive coarctation

Fig. 10

Sensitivity of continuous measurements to choice of segmentation software and smoothing algorithm, exemplified for a subject with Turner syndrome (Subject 6). a Software 1 (solid blue line) – Mimics, Software 2 (solid red line) – ITK-Snap, Software 3 (solid black line) – 3D Slicer. b Smoothing Algorithm 1 (solid blue line) – C0 Smoothing, Smoothing Algorithm 2 (solid red line) – C1 Smoothing, Smoothing Algorithm 3 (solid black line) – Simple Smoothing. Aorta geometries were smoothed using OpenFlipper

Fig. 11

Sensitivity of continuous measurements to choice of smoothing software and user, exemplified for a patient with Turner syndrome (Subject 6). a Segmentation of aorta performed using Mimics. Smoothing Software 1 (solid blue line) – Mimics, Smoothing Software 2 (solid red line) – OpenFlipper. bSolid blue line – User 1, Solid red line – User 2