Aortic enlargement and impaired bioelasticity are of interest in several cardiac and non-cardiac diseases as they can lead to cardiovascular complications. Cardiovascular magnetic resonance (CMR) is increasingly accepted as a noninvasive tool in cardiovascular evaluation. Assessment of aortic anatomy and bioelasticity, namely aortic distensibility and pulse wave velocity (PWV), by CMR is accurate and reproducible and could help to identify anatomical and bioelastic abnormalities of the aorta. However, normal CMR values for healthy children and young adults are lacking.
Methods
Seventy-one heart-healthy subjects (age 16.4 ± 7.6 years, range 2.3 - 28.3 years) were examined using a 3.0 Tesla CMR scanner. Aortic cross-sectional areas and aortic distensibility were measured at four positions of the ascending and descending thoracic aorta. PWV was assessed from aortic blood flow velocity measurements in a aortic segment between the ascending aorta and the proximal descending aorta. The Lambda-Mu-Sigma (LMS) method was used to obtain percentile curves for aortic cross-sectional areas, aortic distensibility and PWV according to age.
Results
Aortic areas, PWV and aortic distensibility (aortic cross-sectional areas: r = 0.8 to 0.9, p < 0.001; PWV: r = 0.25 to 0.32, p = 0.047 to 0.009; aortic distensibility r = -0.43 to -0.62, p < 0.001) correlated with height, weight, body surface area, and age. There were no significant sex differences.
Conclusions
This study provides percentile curves for cross-sectional areas, distensibility and pulse wave velocity of the thoracic aorta in children and young adolescents between their 3rd and 29th year of life. These data may serve as a reference for the detection of pathological changes of the aorta in cardiovascular disease.
Background
The thoracic aorta plays an important role in the cardiovascular system. It’s elastic buffering capacity transforms the pulsatile effect caused by ventricular ejection into a continuous blood flow[1, 2]. In children and young adults several cardiac and non-cardiac diseases manifest themselves by aortic enlargement and impaired aortic bioelastic function[3–6]. These changes may be of clinical relevance as they can lead to cardiovascular complications such as left ventricular dysfunction[7], aneurysm formation, atherosclerosis, myocardial infarction and stroke[8–10] in later life.
Aortic distensibility and aortic pulse wave velocity (PWV) are two parameters closely related to the bioelastic function of the aorta and serve as pathogenic markers in cardiovascular disease[11]. Quantification of aortic distensibility and PWV by cardiovascular magnetic resonance (CMR) has been shown to be accurate and reproducible and could help in identifying early cardiovascular disease in asymptomatic patients[1, 12, 13].
However, reference ranges from childhood to adulthood are lacking. Therefore we sought to establish CMR normal ranges of aortic distensibility and aortic PWV as well as of aortic cross-sectional areas in heart-healthy children and young adults.
Methods
Study population
71 children and young adults aged 2.3 - 28.3 years underwent a CMR study for the assessment of aortic dimensions, distensibilty and PWV. Table 1 shows the sex and age distribution of the total study group.
Table 1
Sex and age distribution of the study group
Age classes (years)
Total
-5
5 - 10
10-15
15-20
20-25
25-30
Sex
male
n
2
10
7
2
6
3
30
%
6.7%
33.3%
23.3%
6.7%
20.0%
10.0%
100.0%
female
n
2
7
7
6
11
8
41
%
4.9%
17.1%
17.1%
14.6%
26.8%
19.5%
100.0%
Total study group
n
4
17
14
8
17
11
71
%
5.6%
23.9%
19.7%
11.3%
23.9%
15.5%
100.0%
The study participants were recruited among medical students and healthy children of hospital staff. Five children were recruited from the department of pediatric neurology. They underwent diagnostic magnetic resonance imaging (MRI) of the central nervous system (CNS) because of psychomotor retardation and epilepsy. Immediately after CNS MRI, non-contrast enhanced CMR was performed. All study subjects were free from cardiovascular disease. During the study, heart rate, respiratory motion, oxygen saturation and non-invasive blood pressure were monitored.
The study protocol was approved by the local research ethics committee and conformed to the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from participants older than 17 years and all persons responsible for care and custody of the child.
Image acquisition
All CMR studies were performed with a 3.0 Tesla CMR scanner (Achieva 3.0 T, Philips Medical Systems, Netherlands) using a phased-array coil for cardiac imaging (SENSE™ Cardiac coil, Philips Medical Systems, Netherlands).
Gradient echo cine CMR with retrospective gating was applied to assess aortic cross-sectional areas, which were used to describe the normal dimensions of the aorta and for distensibility calculation. We collected axial and coronal stacks of parallel, contiguous, views perpendicular to the aortic axis. The scan parameters were as follows: 280 × 224 mm, voxel size (read-, phase-encoding, and slice directions) 1.88 × 1.94 × 6 mm, TR/TE = 4.4/2.5 ms, 25 cardiac phases, no inter-slice gap, non-breath-hold, number of repetitions: 2, scan duration: 3-6 min.
Phase-contrast cine CMR was performed to evaluate aortic PWV and to quantify aortic flow. PWV was assessed in a segment including the ascending aorta, the aortic arch and the proximal descending aorta up to the level of the pulmonary artery bifurcation (Figure1). The slice plane intersected the ascending aorta at the sinutubular level, and the proximal descending aorta, both at an approximately right angle. Imaging parameters were as follows: FOV 270 × 270 mm, voxel size 1.64 × 1.4 × 7 mm, TR/TE = 4.4/2.7 ms, 40 cardiac phases, velocity encoding = 200 cm/s. To determine the aortic segment length between the two aortic levels, sagittally angulated views of the aortic arch were acquired.
Figure 1
Aortic PWV, A) Sagittal CMR image that shows the sites where phase contrast cine images were acquired: 1) ascending aorta, 2) descending aorta. The distance between both locations (Δx) was measured along a midline through the aortic arch. B) This graph shows the transit delay (Δt) of the systolic flow curves in the descending relative to the ascending aorta. The transit time (Δt) was determined from the midpoints of the systolic up-slope (ta1 and ta2) on the flow versus time curves. The difference of ta for ascending (ta1) and descending aorta (ta2) locations defined Δt. Pulse wave velocity was estimated as Δx/Δt.
Image analysis
The images were analyzed with commercially available CMR software (ViewForum release 6.3, Philips Medical Systems, Netherlands).
Aortic cross-sectional areas were determined on axial and coronal gradient-cine images at four positions (Figure2): ascending aorta, transverse aortic arch, aortic isthmus and descending aorta above the diaphragm. All measurements were made at the time of the maximal distension of the aorta. Aortic cross-sectional areas were preferred compared to diameters, because the aorta is not necessarily circular in all segments.
Figure 2
Cross-sectional aortic areas were assessed from axial and coronal CMR images at four different locations of the thoracic aorta: ascending aorta (1), transverse aortic arch (2), aortic isthmus (3), descending aorta above the diaphragm (4).
Aortic distensibility was measured from two-dimensional cine images in the ascending aorta, the transverse aortic arch and at two levels in the descending aorta. The latter were located at the aortic isthmus, and above the diaphragm. Distensibility was calculated[14] as:
Amax and Amin represent the maximal and minimal cross-sectional area of the aorta on cine CMR images, and Pmax and Pmin represent the systolic and diastolic blood pressures (in millimetres of mercury), respectively. Blood pressure was obtained non-invasively using a CMR-compatible patient monitor with sphygmomanometer (Invivo Precess™ 3160, Invivo, Orlando, USA). The sphygmomanometer cuff was placed around the right arm.
Aortic flow measurements in the ascending and proximal descending aorta with the CMR phase-contrast technique were used to assess PWV in the aortic arch. Aortic flow versus time curves from phase-contrast cine images were obtained to determine the time delay of the distal flow curve (in the descending aorta), relative to the flow curve in the proximal ascending aorta.
The PWV was calculated by the following equation:
whereas Δx is the aortic segment length (in meters) along an intra-luminal center-line between the two measurement locations, measured in a sagittally angulated view of the aortic arch, and Δt is the time delay of the distal flow curve, relative to the proximal flow curve (in seconds, Figure1). Furthermore mean aortic blood flow and peak systolic velocity were assessed in the ascending aorta (Table2).
Table 2
Mean blood flow and maximal flow velocity in the ascending aorta
Age classes
Mean blood flow (l/min)
Maximal velocity (cm/s)
-5 years
2.8 ± 0.1
130.3 ± 2.8
5-10 years
3.9 ± 0.8
131.8 ± 18.3
10-15 years
4.4 ± 0.9
119.7 ± 15.8
15-20 years
6.1 ± 1.4
111.9 ± 23.7
20-25 years
5.6 ± 1.1
121.0 ± 16.0
25-30 years
5.5 ± 1.2
118.5 ± 23.9
Data are expressed as mean and standard deviation.
Statistical analysis
Statistical analysis was performed using MedCalc® Version 11.5.1.0. The quantitative data were expressed as mean and standard deviation. The Mann–Whitney-U test for independent samples was used to compare female and male subgroups. Associations between variables were examined using Spearman’s rank correlation. P values below 0.05 were considered to indicate statistical significance.
Reference curves for the aortic measurements were estimated with the Lambda-Mu-Sigma (LMS)-method from Cole and Green[15, 16] for each gender. This method characterizes the age dependent distribution of a target parameter based on a quantile regression fit by three different components: the median (M), the variance (S) and the skewness of the distribution, which is evaluated by an exponential factor (L) from a Box-Cox transformation. L, M and S values can be used to construct reference curves by the following equation:
where zα is the α-quantile in the standard normal distribution, e. g. z0,95 = 1,64. The z-score can be calculated from the LMS values and the measurement value for aortic cross-sectional area, diststensibility or PWV (X):
Results
The study group characteristics are presented in Table3. There were no significant differences between female and male subgroups.
Table 3
Characteristics of the study population
Parameter
Total study group
Female volunteers
Male volunteers
P value
(n = 71)
(n = 41)
(n = 30)
Age (years)
16.4 ± 7.6
17.5 ± 7.4
14.9 ± 7.7
0.18
Weight (kg)
50.9 ± 21.9
51.4 ±19.3
50.2 ± 25.1
0.73
Height (cm)
156.6 ± 25.6
157.5 ± 23.0
156.1 ± 29.1
0.86
BSA (m2)
1.5 ± 0.4
1.5 ± 0.4
1.5 ± 0.5
0.84
BMI (kg/m2)
19.4 ± 3.5
19.7 ± 3.4
19.1 ± 3.8
0.57
SBP (mm Hg)
104.9 ± 9.5
103.7 ± 9.3
106.2 ± 9.7
0.48
DBP (mm Hg)
59.2 ± 11.0
58.8 ± 10.9
59.4 ± 11.2
0.91
PP (mm Hg)
45.7 ± 8.4
44.9 ± 6.6
46.8 ± 10.4
0.14
Data are expressed as mean and standard deviation. P-values are from the Mann–Whitney-U test.
BMI, body mass index; BSA, body surface area; DBP, diastolic blood pressure; PP, pulse pressure; SBP, systolic blood pressure.
Aortic dimensions
Table4 shows the mean ± SD of the aortic cross-sectional areas for each position classified by gender. No significant differences were found between males and females. All cross-sectional areas correlated well with the age, height, weight, and body surface area (BSA) (Table5). Gender specific percentile curves between aortic cross-sectional areas and age are shown in Figure3. Additionally, Tables6 and7 shows the L, M and S values relative to age and gender.
Table 4
Cross-sectional areas, distensibility and PWV of the thoracic aorta by gender
Parameter
Total study group
Female volunteers
Male volunteers
P value
(n = 71)
(n = 41)
(n = 30)
Cross-sectional area (mm2)
- Ascending aorta
515.3 ± 186.3
516.1 ± 171.4
514.0 ± 208.3
0.68
- Aortic arch
376.9 ± 148.5
383.0 ± 139.1
368.2 ± 163.7
0.51
- Aortic isthmus
257.9 ± 89.5
250.4 ± 76.2
268.3 ± 105.6
0.64
- Descending aorta above the diaphragm
214.2 ± 75.0
213.6 ± 68.9
214.9 ± 84.0
0.81
Distensibility (10-3 mm Hg-1)
- Ascending aorta
8.9 ± 3.6
9.2 ± 3.0
8.5 ± 4.2
0.11
- Aortic arch
7.7 ± 3.3
8.0 ± 3.3
7.2 ± 3.4
0.2
- Aortic isthmus
7.4 ± 2.5
7.7 ± 2.3
7.0 ± 2.7
0.11
- Descending aorta above the diaphragm
8.3 ± 3.0
8.8 ± 3.1
7.7 ± 2.7
0.1
PWV (m/s)
3.6 ± 0.7
3.5 ± 0.6
3.7 ± 0.9
0.14
Data are expressed as mean and standard deviation. P-values are from the Mann–Whitney-U test.
PWV, pulse wave velocity.
Table 5
Correlation of cross-sectional areas with study group characteristics
Cross-sectional area (mm2)
Parameter
Ascending aorta
Aortic arch
Aortic isthmus
Descending aorta above the diaphragm
Age (years)
0.80†
0.80†
0.81†
0.87†
Height (cm)
0.84†
0.81†
0.81†
0.82†
Weight (kg)
0.90†
0.85†
0.88†
0.89†
BSA (m2)
0.89†
0.84†
0.87†
0.88†
Spearman correlation coefficients rho were calculated for the total study group; †p < 0.01.
BSA, body surface area.
Figure 3
Gender-specific reference percentiles for aortic cross-sectional areas at four locations: a) ascending aorta, b) aortic arch, c) aortic isthmus and d) descending aorta above the diaphragm.
Table 6
LMS parameters for aortic cross-sectional areas relative to age for girls
Ascending aorta
Aortic arch
Aortic isthmus
Descending aorta above the diaphragm
Age
L
M
S
L
M
S
L
M
S
L
M
S
0
-0,7876
121,1903
0,2152
-2,1750
73,6299
0,2114
0,1033
60,0696
0,1621
0,9371
41,0795
0,1398
1
-0,7876
145,9923
0,2140
-2,1750
92,7307
0,2089
0,1033
72,6142
0,1617
0,9371
52,4930
0,1398
2
-0,7876
170,7944
0,2127
-2,1750
111,8315
0,2064
0,1033
85,1587
0,1613
0,9371
63,9065
0,1398
3
-0,7876
195,5999
0,2114
-2,1750
130,9296
0,2039
0,1033
97,7032
0,1609
0,9371
75,3185
0,1398
4
-0,7876
220,4539
0,2102
-2,1750
149,9904
0,2013
0,1033
110,2465
0,1605
0,9371
86,7100
0,1398
5
-0,7876
245,4281
0,2089
-2,1750
168,9588
0,1988
0,1033
122,7870
0,1601
0,9371
98,0510
0,1398
6
-0,7876
270,5738
0,2076
-2,1750
187,8089
0,1963
0,1033
135,3263
0,1597
0,9371
109,3784
0,1398
7
-0,7876
295,9027
0,2064
-2,1750
206,5696
0,1938
0,1033
147,8724
0,1593
0,9371
120,8531
0,1398
8
-0,7876
321,3290
0,2051
-2,1750
225,2367
0,1913
0,1033
160,3915
0,1588
0,9371
132,5201
0,1398
9
-0,7876
346,5367
0,2038
-2,1750
243,7024
0,1887
0,1033
172,7395
0,1584
0,9371
144,0843
0,1398
10
-0,7876
371,3379
0,2026
-2,1750
261,8643
0,1862
0,1033
184,8049
0,1580
0,9371
155,3776
0,1398
11
-0,7876
395,6874
0,2013
-2,1750
279,6207
0,1837
0,1033
196,5286
0,1576
0,9371
166,4608
0,1398
12
-0,7876
419,5583
0,2000
-2,1750
296,8402
0,1812
0,1033
207,8452
0,1572
0,9371
177,3057
0,1398
13
-0,7876
442,8024
0,1988
-2,1750
313,4236
0,1787
0,1033
218,7232
0,1568
0,9371
187,8984
0,1398
14
-0,7876
465,1326
0,1975
-2,1750
329,2852
0,1761
0,1033
229,1136
0,1564
0,9371
198,1163
0,1398
15
-0,7876
486,2071
0,1962
-2,1750
344,3674
0,1736
0,1033
238,9630
0,1560
0,9371
207,7776
0,1398
16
-0,7876
505,7398
0,1950
-2,1750
358,6387
0,1711
0,1033
248,2461
0,1556
0,9371
216,7982
0,1398
17
-0,7876
523,5836
0,1937
-2,1750
372,0983
0,1686
0,1033
256,9723
0,1552
0,9371
225,1710
0,1398
18
-0,7876
539,7165
0,1924
-2,1750
384,7434
0,1661
0,1033
265,1479
0,1547
0,9371
232,7857
0,1398
19
-0,7876
554,1764
0,1912
-2,1750
396,5833
0,1635
0,1033
272,7929
0,1543
0,9371
239,5830
0,1398
20
-0,7876
567,1207
0,1899
-2,1750
407,6567
0,1610
0,1033
279,9469
0,1539
0,9371
245,6109
0,1398
21
-0,7876
578,7817
0,1886
-2,1750
418,0442
0,1585
0,1033
286,6730
0,1535
0,9371
251,0496
0,1398
22
-0,7876
589,4770
0,1873
-2,1750
427,8971
0,1560
0,1033
293,0630
0,1531
0,9371
256,1671
0,1398
23
-0,7876
599,5300
0,1861
-2,1750
437,3887
0,1534
0,1033
299,2101
0,1527
0,9371
261,1406
0,1398
24
-0,7876
609,3164
0,1848
-2,1750
446,7229
0,1509
0,1033
305,2232
0,1523
0,9371
266,1367
0,1398
25
-0,7876
619,1593
0,1835
-2,1750
456,0570
0,1484
0,1033
311,2003
0,1518
0,9371
271,2515
0,1398
26
-0,7876
629,1747
0,1822
-2,1750
465,4360
0,1459
0,1033
317,2057
0,1514
0,9371
276,5640
0,1398
27
-0,7876
639,3019
0,1810
-2,1750
474,8382
0,1433
0,1033
323,2314
0,1510
0,9371
281,9813
0,1398
28
-0,7876
649,4860
0,1797
-2,1750
484,2530
0,1408
0,1033
329,2650
0,1506
0,9371
287,4341
0,1398
29
-0,7876
659,6776
0,1784
-2,1750
493,6694
0,1383
0,1033
335,2995
0,1502
0,9371
292,8916
0,1398
30
-0,7876
669,8691
0,1772
-2,1750
503,0858
0,1358
0,1033
341,3341
0,1498
0,9371
298,3491
0,1398
LMS, L = skewness of the distribution, M = median, and S = variance.
Table 7
LMS parameters for aortic cross-sectional areas relative to age for boys
Ascending aorta
Aortic arch
Aortic isthmus
Descending aorta above the diaphragm
Age
L
M
S
L
M
S
L
M
S
L
M
S
0
0,3091
91,5360
0,1207
0,8668
80,1737
0,1898
0,1267
53,0050
0,1987
1,5823
44,6080
0,1100
1
0,3091
120,6960
0,1274
0,8668
101,7001
0,1897
0,1267
68,7198
0,1974
1,5823
57,0317
0,1115
2
0,3091
149,8560
0,1341
0,8668
123,2265
0,1895
0,1267
84,4347
0,1960
1,5823
69,4554
0,1129
3
0,3091
179,0160
0,1408
0,8668
144,7529
0,1894
0,1267
100,1495
0,1946
1,5823
81,8791
0,1143
4
0,3091
208,1812
0,1475
0,8668
166,2791
0,1893
0,1267
115,8653
0,1932
1,5823
94,3035
0,1158
5
0,3091
238,3791
0,1542
0,8668
187,7555
0,1891
0,1267
131,7743
0,1918
1,5823
106,8833
0,1172
6
0,3091
272,8715
0,1604
0,8668
208,8732
0,1890
0,1267
148,2790
0,1904
1,5823
119,9057
0,1186
7
0,3091
311,2493
0,1660
0,8668
229,2411
0,1888
0,1267
164,9648
0,1891
1,5823
133,0488
0,1201
8
0,3091
346,8686
0,1707
0,8668
248,8676
0,1887
0,1267
180,7624
0,1877
1,5823
145,5984
0,1215
9
0,3091
380,0230
0,1748
0,8668
268,0557
0,1886
0,1267
195,7825
0,1863
1,5823
157,5124
0,1229
10
0,3091
413,8181
0,1782
0,8668
287,2956
0,1884
0,1267
210,6578
0,1849
1,5823
169,3366
0,1244
11
0,3091
446,7220
0,1812
0,8668
306,7317
0,1883
0,1267
225,5414
0,1835
1,5823
181,3951
0,1258
12
0,3091
476,5703
0,1841
0,8668
326,2205
0,1881
0,1267
240,3324
0,1822
1,5823
193,8192
0,1272
13
0,3091
501,7973
0,1870
0,8668
345,4511
0,1880
0,1267
254,6975
0,1808
1,5823
206,4812
0,1287
14
0,3091
524,0769
0,1902
0,8668
364,2701
0,1879
0,1267
268,8289
0,1794
1,5823
219,2939
0,1301
15
0,3091
546,3695
0,1937
0,8668
382,7610
0,1877
0,1267
282,9653
0,1780
1,5823
232,0152
0,1316
16
0,3091
569,8955
0,1972
0,8668
400,9805
0,1876
0,1267
296,9424
0,1766
1,5823
244,3629
0,1330
17
0,3091
594,7536
0,2003
0,8668
418,9724
0,1875
0,1267
310,5833
0,1752
1,5823
256,2294
0,1344
18
0,3091
620,9611
0,2025
0,8668
436,7805
0,1873
0,1267
323,7094
0,1739
1,5823
267,5155
0,1359
19
0,3091
647,1204
0,2034
0,8668
454,4484
0,1872
0,1267
336,0814
0,1725
1,5823
278,0681
0,1373
20
0,3091
670,2706
0,2030
0,8668
472,0177
0,1871
0,1267
347,4348
0,1711
1,5823
287,6962
0,1387
21
0,3091
690,0681
0,2014
0,8668
489,5219
0,1869
0,1267
357,7775
0,1697
1,5823
296,3958
0,1402
22
0,3091
706,8583
0,1990
0,8668
506,9924
0,1868
0,1267
367,1860
0,1683
1,5823
304,2102
0,1416
23
0,3091
720,9831
0,1960
0,8668
524,4603
0,1866
0,1267
375,7366
0,1670
1,5823
311,1823
0,1430
24
0,3091
732,2902
0,1926
0,8668
541,9124
0,1865
0,1267
383,4824
0,1656
1,5823
317,3075
0,1445
25
0,3091
740,4053
0,1889
0,8668
559,3076
0,1864
0,1267
390,6086
0,1642
1,5823
322,5658
0,1459
26
0,3091
747,1815
0,1849
0,8668
576,7470
0,1862
0,1267
397,7409
0,1628
1,5823
327,1568
0,1473
27
0,3091
754,8518
0,1805
0,8668
594,3196
0,1861
0,1267
405,3735
0,1614
1,5823
331,4000
0,1488
28
0,3091
763,4054
0,1758
0,8668
611,9863
0,1860
0,1267
413,3799
0,1601
1,5823
335,4719
0,1502
29
0,3091
772,1960
0,1711
0,8668
629,6783
0,1858
0,1267
421,4867
0,1587
1,5823
339,4979
0,1516
30
0,3091
780,9891
0,1663
0,8668
647,3706
0,1857
0,1267
429,5945
0,1573
1,5823
343,5234
0,1531
LMS, L = skewness of the distribution, M = median, and S = variance.
Aortic distensibility and PWV
The mean values of aortic distensibility and PWV are presented in Table4. Figures4 and5 show the gender specific percentiles for aortic distensibility and PWV. In Tables8,9,10 the original L, M and S values for aortic distensibility and PWV are given. An age-related decrease of aortic distensibility was found for all anatomical locations (r = -0.43 to -0.52, p < 0.001). Aortic distensibility also correlated with height (r = -0.47 to -0.62, p < 0.001) and body weight (r = -0.45 to -0.59, p < 0.001), BSA (r = -0.47 to -0.61, p < 0.001). Univariate regression analysis showed a modest association between PWV and the following parameters: age, height, weight and BSA (r = 0.25 to 0.32, p = 0.047 to 0.009).
Figure 4
Gender-specific reference percentiles for aortic distensibility at four locations: a) ascending aorta, b) aortic arch, c) aortic isthmus and d) descending aorta above the diaphragm.
Figure 5
Gender-specific reference percentiles for PWV in the aortic arch.
Table 8
LMS parameters for aortic distensibility relative to age for girls
Ascending aorta
Aortic arch
Aortic isthmus
Descending aorta above the diaphragm
Age
L
M
S
L
M
S
L
M
S
L
M
S
0
-0,0721
12,7303
0,2388
0,2825
10,1659
0,2971
-0,2728
12,7827
0,2097
0,3847
11,6928
0,2263
1
-0,0721
12,5028
0,2396
0,2825
10,0908
0,3006
-0,2728
12,3919
0,2100
0,3847
11,5113
0,2297
2
-0,0721
12,2753
0,2403
0,2825
10,0157
0,3041
-0,2728
12,0010
0,2102
0,3847
11,3298
0,2331
3
-0,0721
12,0477
0,2411
0,2825
9,9404
0,3076
-0,2728
11,6098
0,2104
0,3847
11,1483
0,2366
4
-0,0721
11,8176
0,2419
0,2825
9,8619
0,3110
-0,2728
11,2134
0,2106
0,3847
10,9668
0,2400
5
-0,0721
11,5817
0,2427
0,2825
9,7752
0,3145
-0,2728
10,8041
0,2108
0,3847
10,7853
0,2434
6
-0,0721
11,3421
0,2435
0,2825
9,6765
0,3180
-0,2728
10,3772
0,2110
0,3847
10,6038
0,2469
7
-0,0721
11,1121
0,2443
0,2825
9,5629
0,3215
-0,2728
9,9344
0,2112
0,3847
10,4223
0,2503
8
-0,0721
10,9051
0,2451
0,2825
9,4311
0,3250
-0,2728
9,4780
0,2114
0,3847
10,2408
0,2537
9
-0,0721
10,7290
0,2459
0,2825
9,2748
0,3285
-0,2728
9,0114
0,2117
0,3847
10,0593
0,2572
10
-0,0721
10,5679
0,2467
0,2825
9,0871
0,3320
-0,2728
8,5463
0,2119
0,3847
9,8778
0,2606
11
-0,0721
10,3851
0,2474
0,2825
8,8635
0,3354
-0,2728
8,1077
0,2121
0,3847
9,6963
0,2640
12
-0,0721
10,1582
0,2482
0,2825
8,6056
0,3389
-0,2728
7,7159
0,2123
0,3847
9,5149
0,2675
13
-0,0721
9,8884
0,2490
0,2825
8,3257
0,3424
-0,2728
7,3784
0,2125
0,3847
9,3334
0,2709
14
-0,0721
9,5911
0,2498
0,2825
8,0371
0,3459
-0,2728
7,0939
0,2127
0,3847
9,1519
0,2743
15
-0,0721
9,2905
0,2506
0,2825
7,7528
0,3494
-0,2728
6,8625
0,2129
0,3847
8,9705
0,2777
16
-0,0721
9,0033
0,2514
0,2825
7,4850
0,3529
-0,2728
6,6852
0,2131
0,3847
8,7890
0,2812
17
-0,0721
8,7345
0,2522
0,2825
7,2434
0,3563
-0,2728
6,5631
0,2134
0,3847
8,6076
0,2846
18
-0,0721
8,4850
0,2529
0,2825
7,0315
0,3598
-0,2728
6,4885
0,2136
0,3847
8,4262
0,2880
19
-0,0721
8,2574
0,2537
0,2825
6,8508
0,3633
-0,2728
6,4533
0,2138
0,3847
8,2448
0,2915
20
-0,0721
8,0546
0,2545
0,2825
6,6995
0,3668
-0,2728
6,4449
0,2140
0,3847
8,0635
0,2949
21
-0,0721
7,8749
0,2553
0,2825
6,5740
0,3703
-0,2728
6,4447
0,2142
0,3847
7,8822
0,2983
22
-0,0721
7,7106
0,2561
0,2825
6,4710
0,3738
-0,2728
6,4391
0,2144
0,3847
7,7008
0,3017
23
-0,0721
7,5479
0,2569
0,2825
6,3882
0,3772
-0,2728
6,4264
0,2146
0,3847
7,5195
0,3052
24
-0,0721
7,3842
0,2577
0,2825
6,3235
0,3807
-0,2728
6,4171
0,2148
0,3847
7,3382
0,3086
25
-0,0721
7,2113
0,2584
0,2825
6,2744
0,3842
-0,2728
6,4170
0,2150
0,3847
7,1570
0,3120
26
-0,0721
7,0343
0,2592
0,2825
6,2371
0,3877
-0,2728
6,4317
0,2152
0,3847
6,9757
0,3155
27
-0,0721
6,8647
0,2600
0,2825
6,2084
0,3912
-0,2728
6,4666
0,2154
0,3847
6,7944
0,3189
28
-0,0721
6,6951
0,2608
0,2825
6,1806
0,3947
-0,2728
6,5104
0,2156
0,3847
6,6132
0,3223
29
-0,0721
6,5250
0,2616
0,2825
6,1527
0,3981
-0,2728
6,5550
0,2158
0,3847
6,4319
0,3257
30
-0,0721
6,3550
0,2624
0,2825
6,1249
0,4016
-0,2728
6,5997
0,2160
0,3847
6,2506
0,3292
LMS, L = skewness of the distribution, M = median, and S = variance.
Table 9
LMS parameters for aortic distensibility relative to age for boys
Ascending aorta
Aortic arch
Aortic isthmus
Descending aorta above the diaphragm
Age
L
M
S
L
M
S
L
M
S
L
M
S
0
-0,1879
12,3602
0,3680
0,0801
10,2881
0,3061
-0,2022
9,4472
0,3533
-0,0079
9,4241
0,3478
1
-0,1879
11,9220
0,3680
0,0801
10,1050
0,3061
-0,2022
9,2308
0,3494
-0,0079
9,2938
0,3441
2
-0,1879
11,4838
0,3680
0,0801
9,9218
0,3061
-0,2022
9,0144
0,3454
-0,0079
9,1635
0,3404
3
-0,1879
11,0456
0,3680
0,0801
9,7386
0,3061
-0,2022
8,7980
0,3415
-0,0079
9,0331
0,3367
4
-0,1879
10,6075
0,3680
0,0801
9,5554
0,3061
-0,2022
8,5816
0,3375
-0,0079
8,9028
0,3330
5
-0,1879
10,1700
0,3680
0,0801
9,3705
0,3061
-0,2022
8,3685
0,3335
-0,0079
8,7730
0,3293
6
-0,1879
9,7343
0,3680
0,0801
9,1780
0,3061
-0,2022
8,1629
0,3296
-0,0079
8,6433
0,3256
7
-0,1879
9,2990
0,3680
0,0801
8,9719
0,3061
-0,2022
7,9576
0,3256
-0,0079
8,5103
0,3219
8
-0,1879
8,8602
0,3680
0,0801
8,7467
0,3061
-0,2022
7,7410
0,3216
-0,0079
8,3694
0,3182
9
-0,1879
8,4151
0,3680
0,0801
8,4980
0,3061
-0,2022
7,4918
0,3177
-0,0079
8,2157
0,3145
10
-0,1879
7,9776
0,3680
0,0801
8,2310
0,3061
-0,2022
7,2033
0,3137
-0,0079
8,0497
0,3108
11
-0,1879
7,5683
0,3680
0,0801
7,9577
0,3061
-0,2022
6,8970
0,3098
-0,0079
7,8764
0,3071
12
-0,1879
7,2051
0,3680
0,0801
7,6865
0,3061
-0,2022
6,6042
0,3058
-0,0079
7,7035
0,3034
13
-0,1879
6,9030
0,3680
0,0801
7,4220
0,3061
-0,2022
6,3480
0,3018
-0,0079
7,5379
0,2997
14
-0,1879
6,6697
0,3680
0,0801
7,1669
0,3061
-0,2022
6,1310
0,2979
-0,0079
7,3831
0,2959
15
-0,1879
6,5089
0,3680
0,0801
6,9220
0,3061
-0,2022
5,9529
0,2939
-0,0079
7,2400
0,2922
16
-0,1879
6,4138
0,3680
0,0801
6,6851
0,3061
-0,2022
5,8175
0,2899
-0,0079
7,1082
0,2885
17
-0,1879
6,3729
0,3680
0,0801
6,4532
0,3061
-0,2022
5,7175
0,2860
-0,0079
6,9844
0,2848
18
-0,1879
6,3745
0,3680
0,0801
6,2234
0,3061
-0,2022
5,6445
0,2820
-0,0079
6,8653
0,2811
19
-0,1879
6,4062
0,3680
0,0801
5,9926
0,3061
-0,2022
5,5886
0,2781
-0,0079
6,7467
0,2774
20
-0,1879
6,4551
0,3680
0,0801
5,7579
0,3061
-0,2022
5,5400
0,2741
-0,0079
6,6246
0,2737
21
-0,1879
6,5111
0,3680
0,0801
5,5167
0,3061
-0,2022
5,4988
0,2701
-0,0079
6,4987
0,2700
22
-0,1879
6,5646
0,3680
0,0801
5,2667
0,3061
-0,2022
5,4678
0,2662
-0,0079
6,3697
0,2663
23
-0,1879
6,6062
0,3680
0,0801
5,0054
0,3061
-0,2022
5,4496
0,2622
-0,0079
6,2384
0,2626
24
-0,1879
6,6277
0,3680
0,0801
4,7261
0,3061
-0,2022
5,4328
0,2583
-0,0079
6,1017
0,2589
25
-0,1879
6,6242
0,3680
0,0801
4,4155
0,3061
-0,2022
5,3874
0,2543
-0,0079
5,9498
0,2552
26
-0,1879
6,5975
0,3680
0,0801
4,0684
0,3061
-0,2022
5,3095
0,2503
-0,0079
5,7759
0,2515
27
-0,1879
6,5577
0,3680
0,0801
3,6929
0,3061
-0,2022
5,2154
0,2464
-0,0079
5,5826
0,2478
28
-0,1879
6,5116
0,3680
0,0801
3,3021
0,3061
-0,2022
5,1114
0,2424
-0,0079
5,3785
0,2441
29
-0,1879
6,4643
0,3680
0,0801
2,9079
0,3061
-0,2022
5,0026
0,2384
-0,0079
5,1722
0,2404
30
-0,1879
6,4170
0,3680
0,0801
2,5137
0,3061
-0,2022
4,8936
0,2345
-0,0079
4,9658
0,2367
LMS, L = skewness of the distribution, M = median, and S = variance.
Table 10
LMS parameters for PWV relative to age and gender
Male
Female
Age
L
M
S
L
M
S
0
1,4844
3,4147
0,2122
-1,5196
2,7808
0,1468
1
1,4844
3,4367
0,2122
-1,5196
2,8144
0,1469
2
1,4844
3,4587
0,2122
-1,5196
2,8481
0,1469
3
1,4844
3,4808
0,2122
-1,5196
2,8817
0,1469
4
1,4844
3,5028
0,2122
-1,5196
2,9154
0,1470
5
1,4844
3,5248
0,2122
-1,5196
2,9490
0,1470
6
1,4844
3,5469
0,2122
-1,5196
2,9827
0,1470
7
1,4844
3,5689
0,2122
-1,5196
3,0163
0,1470
8
1,4844
3,5909
0,2122
-1,5196
3,0499
0,1471
9
1,4844
3,6129
0,2122
-1,5196
3,0836
0,1471
10
1,4844
3,6350
0,2122
-1,5196
3,1172
0,1471
11
1,4844
3,6570
0,2122
-1,5196
3,1509
0,1471
12
1,4844
3,6790
0,2122
-1,5196
3,1845
0,1472
13
1,4844
3,7011
0,2122
-1,5196
3,2182
0,1472
14
1,4844
3,7231
0,2122
-1,5196
3,2518
0,1472
15
1,4844
3,7451
0,2122
-1,5196
3,2855
0,1473
16
1,4844
3,7672
0,2122
-1,5196
3,3192
0,1473
17
1,4844
3,7892
0,2122
-1,5196
3,3528
0,1473
18
1,4844
3,8112
0,2122
-1,5196
3,3865
0,1473
19
1,4844
3,8333
0,2122
-1,5196
3,4201
0,1474
20
1,4844
3,8553
0,2122
-1,5196
3,4538
0,1474
21
1,4844
3,8773
0,2122
-1,5196
3,4875
0,1474
22
1,4844
3,8994
0,2122
-1,5196
3,5211
0,1475
23
1,4844
3,9214
0,2122
-1,5196
3,5548
0,1475
24
1,4844
3,9434
0,2122
-1,5196
3,5885
0,1475
25
1,4844
3,9655
0,2122
-1,5196
3,6221
0,1476
26
1,4844
3,9875
0,2122
-1,5196
3,6558
0,1476
27
1,4844
4,0096
0,2122
-1,5196
3,6895
0,1476
28
1,4844
4,0316
0,2122
-1,5196
3,7231
0,1476
29
1,4844
4,0536
0,2122
-1,5196
3,7568
0,1477
30
1,4844
4,0757
0,2122
-1,5196
3,7905
0,1477
LMS, L = skewness of the distribution, M = median, and S = variance.
Discussion
This CMR study describes the quantile distribution of cross-sectional areas, distensibility and PWV of the thoracic aorta in heart-healthy children and young adults between their 3rd and 29th year of life. Defining the normal range for aortic size and bio-elastic properties is an important aid in the early detection of adverse aortic changes.
Aortic dimensions
Knowledge of the size of the thoracic aorta is important for the treatment of patients with congenital and acquired cardiovascular diseases. CMR allows an exact assessment of the aortic anatomy, independent of acoustic windows, and is therefore an optimal tool to detect anatomic abnormalities of the aorta such as dilatation or aneurysm formation[17]. We provide normal data for aortic cross-sectional areas in the form of percentile curves by age and gender. Normal data for aortic dimensions in children have been reported in various echocardiographic[18], angiocardiographic[19, 20] and CMR studies[21, 22].
The CMR study from Kaiser et al.[20] reported aortic diameters measured by contrast-enhanced (CE) CMR angiography in 53 children. This method was limited by the fact that CE-CMR images are static and represent a summation of all cardiac phases which may affect a comparison to ECG-gated acquisitions such as in echocardiography or in our study. Furthermore, they measured aortic diameters instead of cross-sectional areas.
Another early CMR-study from Mohiaddin et al.[22] assessed aortic cross-sectional areas from enddiastolic spin echo images in 70 predominantly adult volunteers between the ages of 10 and 83 years. We confirmed their finding that aortic dimensions are positively correlated with age, but our study also covers children younger than 10 years, an age range where aortic dimensions and cardiac structures change rapidly according to somatic growth in prepubertal children[23]. Normal data for aortic cross-sectional areas have been reported by Rammos et al using angiocardiography[19]. As in our study, they showed a good correlation between BSA and aortic cross-sectional areas. However, their reported data are smaller than in our study, which may be mainly caused by the different technique.
However, the data from the mentioned studies are not exactly comparable to our measurements. Most studies used different imaging modalities[18–20]. Furthermore, they report aortic diameters, or measured them in order to calculate cross-sectional areas[18]. CMR allows a direct measurement of aortic cross-sectional areas which is a more accurate approach to assess aortic size, since vessels are not circular in all segments and show an inter-individual anatomic variability.
The observed quantile distributions for aortic dimensions are of clinical value to detect pathologic anatomical changes of the aorta in children and young adults and will serve as reference values for future CMR research studies.
Aortic distensibility and PWV
This is the first study to provide reference CMR values for aortic distensibility and PWV in children and young adults, in conjunction with measurements of aortic size. The percentile ranges show that aortic distensibility decreases with age, whereas PWV increases with age. Age-associated changes and reference values of aortic distensibility and PWV in children and adults have also been reported in studies using different techniques. Senzaki et al. examined 112 patients with an age range from 6 months to 20 years by cardiac catherization. They showed that the arterial compliance normalized to body surface area significantly decreased with age[24]. The study by Avioli et al. used transcutaneous Doppler techniques to assess aortic PWV in subjects with an age range from 3 to 89 years. In their study aortic PWV significantly increased with age[25]. Another study measured PWV with ultrasound methods in 206 patients aged 0–15 years. Their median PWV was 3.04 m/s which is comparable to our data. However, in contrast to our study PWV was independent of age, which may be caused by the young age of their study group[26]. CMR assessment of aortic PWV showed good agreement with PWV obtained from invasive pressure measurements as the gold standard[27]. Unlike in ultrasound CMR is not limited to acoustic windows and does not only provide an estimation of aortic PWV[1, 27].
The aorta acts as a conduit delivering blood to the peripheral organs and transforms the pulsatile effect caused by ventricular ejection into a continuous blood flow[1]. As shown aortic distensibility decreases and PWV increases during age. The decreasing aortic elasticity observed in our young cohort may be related to normal structural wall changes during aging[28]. An increase in intimal-medial thickness after birth has been demonstrated in an earlier study[28]. The aortic elastic properties depend largely on the presence of elastic fibres in the vessel wall, which have a maximum rate in the perinatal period followed by a fast decrease already during childhood[29]. Besides these developmental changes aortic wall mechanics and stress seems to play an important role in aortic stiffening. In the course of a lifetime the human aorta will undergo billions of cycles of expansion and contractions. This cyclic mechanical stress leads to fragmentation of elastic fibres and causes a transfer of stress to the stiffer collagen fibres. The loss of elastin results in a reduction of aortic elasticity[30]. In adults, decreased aortic elasticity has adverse effects on cardiac systolic and diastolic function, due to increased left ventricular afterload and myocardial oxygen consumption as well as impaired coronary perfusion[31].
Our data may be of interest in various diseases and pathological conditions that can affect aortic bioelasticity already in children and young adults. Impaired aortic bioelasticity has been reported for instance in patients with Marfan syndrome[14], tetralogy of Fallot[5], Turner’s syndrome[32] and aortic coarctation[4]. In a recently published study we could show that patients with hypoplastic left heart syndrome have severly reduced aortic distensibility[3]. Furthermore, some functional vascular parameters are impaired in obese children[33]. Considering the increasing use of CMR for non-invasive scientific and clinical studies, the presented data may help in evaluating aortic bioelastic function and cardiovascular risk stratification with these diseases.
Limitations
As it is difficult to recruit healthy children as volunteers for a CMR study, the sample size of our cohort is small in comparison to echocardiographic studies but fulfills the demand for statistical evaluation.
Conclusions
We provide percentiles for aortic cross-sectional areas, aortic distensibilty and PWV for children at various ages. They can be of clinical value in patients with various cardiac and vascular diseases and may serve as reference values for further CMR research studies.
Notes
Declarations
Acknowledgements
We thank the Fördergemeinschaft Deutsche Kinderherzzentren e.V. (Friedrich-Wilhelm-Straße 45, 53113 Bonn,http://www.kinderherzen.de) for their financial support.
Authors’ Affiliations
(1)
Department of Congenital Heart Disease and Pediatric Cardiology, University Hospital of Schleswig-Holstein, Campus Kiel
(2)
Department for Medical Informatics and Statistics, University Hospital of Schleswig-Holstein
(3)
Department of Radiology, Brigham & Women's Hospital, Harvard University
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