Abstract
Introduction:
Doppler ultrasound of the portal vein peak systolic velocity and hepatic artery peak systolic velocity and resistive index in children is often performed during abdominal ultrasound for the assessment of liver and other abdominal pathology. However, evidence-based reference values are not available. We aimed to determine these reference values and to investigate whether they are age-dependent.
Methods:
Children who underwent abdominal ultrasound between 2020 and 2021 were retrospectively identified. Patients without hepatic or cardiac abnormalities at the time of ultrasound or during at least 3 months follow-up were eligible for the study. Ultrasound without hepatic hilum portal vein peak systolic velocity and/or hepatic artery peak systolic velocity and resistive index measurements were excluded. Age-dependent changes were analyzed using linear regression. Normal range reference values were described using percentiles for all ages, and for age subgroups.
Results:
One-hundred ultrasound examinations performed in 100 healthy children aged 0–17.9 years (median 7.8 years, interquartile range 1.1–14.1 years) were included. Ninety-nine portal vein peak systolic velocity and 80 hepatic artery peak systolic velocity and resistive index measurements were obtained. There was no significant association between portal vein peak systolic velocity and age (β = −0.056, p = 0.68). There were significant associations between age and hepatic artery peak systolic velocity, and between age and hepatic artery resistive index (β = −0.873, p = 0.04 and β = −0.004, p < 0.001, respectively). Detailed reference values were provided for all ages, and for age subgroups.
Conclusion:
Reference values for the hepatic hilum portal vein peak systolic velocity, hepatic artery peak systolic velocity, and hepatic artery resistive index in children were established. Portal vein peak systolic velocity is not age-dependent, whereas hepatic artery peak systolic velocity and hepatic artery resistive index decrease when children get older.
Introduction
Abdominal ultrasound (US) is the primary imaging study for the assessment of abdominal pathology in children. It may be performed at the bedside, is harmless, and in most cases not painful. Accuracy of US is generally high for the evaluation of solid organs, bowel walls, and ascites.1,2 During a US examination, Doppler techniques may be applied, which allow for the visualisation of blood flow direction, measurement of flow velocity (cm/s), and assessment of the spectral Doppler blood flow waveform. 3
In the portal vein (PV), blood flow directed toward the liver is normal, whereas blood flow directed away from the liver may suggest portal hypertension or an arteriovenous fistula. 4 While qualitative assessment of portal venous flow may be useful, a more comprehensive evaluation is done when the peak systolic velocity (PSV) is added to quantify the direction of flow, for example, a normal flow direction but a very slow velocity may already suggest pathology in the appropriate clinical setting.
For the assessment of hepatic artery (HA) flow, both the PSV and the resistive index (RI, defined as PSV minus end diastolic velocity (EDV), divided by PSV) can be obtained. The RI provides insight into the resistance of the capillary network supplied by the artery, for example, if the arterioles relax the EDV is high, and this results in a relatively low RI which may be normal. 3 A low RI can also be seen in distal vascular shunting, or in case of normal EDV combined with a decreased systolic upstroke in the presence of a more proximal arterial stenosis. 2 A high RI is associated with several chronic liver diseases such as cirrhosis. 3
Both PV and HA blood flow measurements are dynamic and may be highly dependent on fasting versus postprandial state,5,6 the HA buffer phenomenon, 7 and other homeostatic factors. As such, these measurements should not be interpreted in isolation, but in conjunction with other US observations like liver parenchyma structure and hepatosplenomegaly. Doppler US reference values are crucial to determine whether US findings are normal or abnormal. 3 For children, PV and HA flow reference values based on appropriate populations are not available yet; those currently applied are derived from adults or based on experience of the sonographer. In addition, it is unknown whether normal ranges change from neonate to adolescent.
The aim of this study was to obtain reference values for the PV PSV, HA PSV, and HA RI in healthy children from 0 to 17 years old, and to determine whether these reference values are age-dependent.
Materials and methods
This single-center retrospective study was performed in a national pediatric liver transplant and liver surgery center. The study was approved by the local research ethics committee, and informed consent was waived.
At our institute, children without abdominal pathology are rarely seen and many have liver pathology; therefore, a standard abdominal US examination includes Doppler assessment of the PV and HA at the hepatic hilum. As a consequence, when a child without liver pathology does undergo a US, these measurements are also performed as part of standard practice, and these were used in this study.
All abdominal US studies in children <18 years old between January 2020 and December 2021 were retrospectively identified form our institutional database. Inclusion criteria were (1) no history of liver or cardiac pathology and (2) no liver or cardiac pathology during at least 3 months follow-up. Children were subsequently excluded if there were no available hepatic hilum PV PSV and/or HA PSV and RI measurements.
All stored US images were reviewed by a pediatric radiologist (7 years dedicated pediatric radiology experience) to ensure Doppler measurements were performed with an angle of <60° to avoid errors produced by the Doppler formula, as is standard practice. 3 The correct region of sampling was also confirmed. Examples of correct PV and HA Doppler measurements at the hepatic hilum are given in Figure 1. Any incorrect measurements were excluded and registered as missing data. If either PV PSV or HA PSV and RI measurements were not performed, these were also registered as missing data. Each patient was only included once.
Doppler measurements of the portal vein (a) and hepatic artery (b) at the hepatic hilum in a 16-year-old male, with the Doppler measurement angle <60° (exact angle in top right corners) to avoid errors produced by the Doppler formula.
US studies were performed using Toshiba Aplio 500 (Canon, Ōtawara, Japan) or Fujifilm ARIETTA 850 (Fujifilm, Tokyo, Japan) machines by dedicated pediatric radiologists or sonographers. According to our local protocol, children fasted 4 hours prior to the US examination, and for children aged <1 year, parents were asked to postpone feeding until after the US whenever possible.
Demographic data were summarized using median and interquartile range (IQR). Linear regression was performed using SPSS for Windows (version 26; IBM, New York, NY, USA) to investigate the presence of age-dependent changes per year of PV PSV, HA PSV, and HA RI. The 95% confidence interval (CI) of the linear regression and the 95% prediction bands were illustrated in graphs. The level of significance was set at α < 0.05. Reference values were also illustrated using percentiles (5th–95th) for all patients and categorized according to age groups (⩽2 years, >2–12 years, and >12 years old) based on ICH guidelines (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use). 8 We accepted the range between 5th and 95th percentile as the normal range suitable for clinical practice. 9
Results
One-hundred-three abdominal US examinations in 103 patients were identified, of which 3 were subsequently excluded because no PV PSV and/or HA PSV and RI measurements had been performed. One out of 100 (1%) PV PSV measurements was missing. For HA PSV and RI, 18/100 (18%) measurements were missing (Figure 2: flowchart study population). No measurements were excluded based on technically incorrect measurements.
Flowchart study population.
Median age was 7.8 years (IQR 1.1–14.1 years, range 0.01–17.9 years), and 53 out of 100 patients were male (53%) (Table 1). General reasons for US are listed in Table 1.
Patient characteristics and reasons for US.
N: number; IQR: interquartile range; US: ultrasound.
PV PSV was not significantly associated with age (β = −0.0556, 95% CI: −0.322 to 0.211, p = 0.68). Median PSV was 26 cm/s, the 5th–95th percentile was 14–41 cm/s (Table 2, Figure 3).
DUS reference values of the hepatic artery and portal vein in children.
DUS: Doppler ultrasound; HA: hepatic artery; N: number; PSV: peak systolic velocity; PV: portal vein; RI: resistive index.
Scatter plots of data points and illustration of linear regression. Hepatic hilum portal vein peak systolic velocity (a, PSV, cm/s), hepatic artery PSV (b), and hepatic artery resistive index (c, RI). Each dot represents one measurement. The continuous lines represent the linear regression, with the associated 95% confidence intervals represented as the shaded region. The linear regression formulas are given in the top right corners. The dotted lines indicated the 95% prediction bands based on the linear regression.
Age was significantly associated with HA PSV (β = −0.873, 95% CI: −1.713 to −0.032, p = 0.04). HA PSV decreased from a median of 60 cm/s (5th−95th percentile 30−123 cm/s) in the age group ⩽2 years to a median of 46 cm/s (5th−95th percentile 25−108 cm/s) in the age group >12 years (Table 2, Figure 3).
Age was also significantly associated with HA RI (β = −0.004, 95% CI: −0.007 to −0.002, p < 0.001). HA RI decreased from a median of 0.74 (5th−95th percentile 0.55−0.89) in the age group ⩽2 years old to a median of 0.70 (5th−95th percentile 0.55−0.81) in the age group >12 years old (p < 0.001; Table 2, Figure 3).
Discussion
For optimal interpretation of liver Doppler US in children, reference values of the hilar PV PSV and HA PSV and RI may help to decide whether there is pathology, and, when present, may aid in assessing its severity. However, these reference values are currently not available. Therefore, this study determined these reference values in children aged 0−17 years, and also showed that while PV PSV is not age-dependent, HA PSV and RI decrease significantly with increasing age.
Doppler US measurements outside the presented 5th−95th percentile normal range will require further consideration by those involved in the child’s care. Abnormal values may be an apparent part of a known pathology, may indicate early disease, but may also still represent physiological variation (e.g. after a meal). Therefore, these measurements should always be interpreted in the appropriate clinical setting and together with other US findings, because a measurement outside the normal percentiles in absence of other US abnormalities may not necessarily indicate pathology.
Hepatic hilum PV PSV reference values have been scarcely reported. In one study performed among 48 fasted adults, a mean of 21 cm/s (SD 8 cm/s) was described. 10 Another paper suggested a PV PSV normal range in adults of 16−40 cm/s. 3 In children, reference values based on large populations are not available. However, one small study did report a PV PSV of 30 cm/s based on 10 children aged between 3 months and 13 years old. 11 The 5th−95th percentile normal range of 14−41 cm/s found in this study corresponds well with the reported adult values. Importantly, no age-dependent change was found in this study, which is an important finding for the interpretation of US Doppler measurements in children.
The HA PSV may be highly variable due to hemodynamic changes, for example, the hepatic buffer phenomenon where the HA PSV decreases in response to a PV PSV increase which can happen after a meal.5,7,12 This variability is reflected in our study, ranging from 22 to 123 cm/s. Nevertheless, we still found a significant decrease in HA PSV when children get older, from a median of 60 cm/s in the age group ⩽2 years old to a median of 46 cm/s in children aged >12 years old. Although the normal range is large, a HA PSV above the 95th percentile may represent pathology such as acute hepatic dysfunction, 13 and a very-low-flow velocity could indicate a more proximal arterial stenosis. 2
Hepatic hilum HA RI normal ranges in adults have been reported to vary between 0.55 and 0.81, based on studies with fasted healthy adults.3,14 In children, one study reported a mean RI of 0.7 in 19 healthy individuals with a mean age of 7.4 years, and after pediatric liver transplantation, an arterial RI of 0.5−0.7 has been suggested. 15 In our study, in the age group >12 years old, the 5th−95th percentile normal range exactly resembles that reported in adults. This study also showed a significant decrease of the arterial RI when children get older, although the absolute difference is small, and in individual cases such small variations could also be attributed to measurement variation. Nevertheless, we suggest to apply age-group-specific reference values to ensure optimal care.
The main limitation of this study was its retrospective nature. This resulted in several missing values for HA PSV and HA RI, and three patients without measurements. However, a considerable number of measurements was still available, spread out over all ages. Therefore, we believe this has not significantly impacted our study. Furthermore, the retrospective design could have introduced some heterogeneity in measurement methods. However, to overcome this limitation, we included only measurements performed at the hepatic hilum, which had to be performed with a Doppler angle <60°. In addition, the relatively large number of patients included in this study further decreases the influence of measurement variability.
In conclusion, this study provides reference values for the hepatic hilum PV PSV, HA PSV, and HA RI based on a healthy pediatric population, from neonates to adolescents. PV PSV was not age-dependent, and therefore, one normal range can be applied to all children. HA PSV and HA RI decrease significantly when children get older, and we suggest to use the provided age-appropriate reference values.
Footnotes
Contributors
MVV: conceptualization, methods, data collection, analysis, writing. TCK: methods, analysis, supervision. RJdH: conceptualization, methods, writing, supervision.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical approval
The study was assessed by the Medical Ethics Review Board of the University Medical Center Groningen (registry number 202200233) and declared as non-WMO.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Permission from patient(s) or subject(s) obtained in writing for publishing their case report
All data were anonymous and untraceable. In addition, in this study it concerned normal values. Obtaining informed consent for untraceable normal values was considered too intrusive, and not necessary.
Permission obtained in writing from patient or any person whose photo is included for publishing their photographs and images:
Not applicable.
Confirm that you are aware that permission from a previous publisher for reproducing any previously published material will be required should your article be accepted for publication and that you will be responsible for obtaining that permission.
YES (Not applicable).
Guarantor
RJdH
