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REVIEW ARTICLE |
https://doi.org/10.5005/jp-journals-11002-0077
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Transcranial Doppler: A New Stethoscope–Voiceover Tool for Neonatal Brain
1Department of Neonatology, National Institute of Medical Sciences, Jaipur, Rajasthan, India
2Department of Neonatology, Hope Children Hospital, Jaipur, Rajasthan, India
3Department of Neonatology, Shishu Bhawan Hospital, Bilaspur, Chattisgarh, India
4Department of Pediatrics, Louisville State University, Shreveport, Louisville, United States of America
5Global Newborn Society, Clarksville, Maryland, United States of America
6Department of Neonatology, Bharati Vidyapeeth University Medical College, Pune, Maharashtra, India
Corresponding Author: Pradeep Suryawanshi, Department of Neonatology, Bharati Vidyapeeth University Medical College Hospital and Research Center, Pune, Maharashtra, India, Phone: +91 9923540500, e-mail: drpradeepsuryawanshi@gmail.com
How to cite this article: Kumar G, Patodia J, Padhan NC, et al. Transcranial Doppler: A New Stethoscope—Voiceover Tool for Neonatal Brain. Newborn 2023;2(4):279–290.
Source of support: Nil
Conflict of interest: Dr Akhil Maheshwari is associated as Editor-in-Chief of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of the Editor-in-Chief and his research group.
Received on: 20 October 2023; Accepted on: 20 November 2023; Published on: 05 January 2024
ABSTRACT
Background: Cerebral Doppler ultrasound is an emerging bedside tool to measure cerebral perfusion in premature and critically ill neonates. The review focused on maturation and disease-associated Doppler spectra in neonates for diagnostic and prognostic relevance and to identify relevant research areas.
Methods: A comprehensive literature search was conducted to review cerebral Doppler parameters noted in specific disease states. Further efforts were focused to understand the clinical relevance of these indices in the management of neonates and to predict their long-term neurodevelopmental outcomes.
Results: The review focused on routinely used cerebral Doppler parameters in normal and diseased states. Resistive index (RI) in the anterior cerebral artery (ACA) is a frequently used parameter in infants with primary brain injury and in preterm neonates with hemodynamically significant patent ductus arteriosus (HsPDA).
Conclusion: Despite extensive use, major gaps remain in our understanding of cerebral Doppler parameters for diagnosis, monitoring, and prediction of neurodevelopmental outcomes in neonates. Further studies are needed to decode these data in a more precise manner.
Keywords: Acoustic windows, Anterior cerebral artery, Anterior fontanelle, Area under the velocity curve, Basilar artery, Brain injury, Continuous-wave Doppler, Convex probe, Cerebral autoregulation, Cerebral blood flow, Cerebral Doppler, Cerebral Doppler ultrasound, Doppler index, Doppler waveform, Hemodynamically significant patent ductus arteriosus, End-diastolic velocity, High-frequency linear transducer, Hypoxic–ischemic encephalopathy, Neuroanatomy, Intrauterine growth restriction, Intraventricular hemorrhage, Kangaroo mother care, Line of insonation, Liquefactive necrosis, Neonate, Peak-systolic velocity, Plial arterioles, Pulse-wave Doppler signal, Pulsatility index, Resistive index, Vein of Galen malformation.
KEY POINTS
Cerebral Doppler ultrasound is an emerging bedside tool for measuring cerebral perfusion in premature and critically ill neonates.
Several parameters of cerebral Doppler are important in distinguishing normal from diseased states. Resistive index (RI) in the anterior cerebral artery (ACA) is frequently used to monitor primary brain injury in term and preterm neonates with hemodynamically significant patent ductus arteriosus.
The article summarizes maturation- and disease-associated Doppler spectra in neonates for diagnostic and prognostic relevance and to identify relevant research areas.
Further information is needed to determine the impact of cerebral Doppler indices on long-term neurodevelopmental outcomes.
INTRODUCTION
Cerebral Doppler ultrasound, a comprehensive clinical vital appliance of neonatal intensive care practice, has been utilized extensively to assess the vascular anatomy and hemodynamics of the brain in small and sick neonates. It has been used to diagnose and predict outcomes of neonatal diseases like intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), hemodynamically significant patent ductus arteriosus (HsPDA), hydrocephalus, sepsis, shock, hypoxic–ischemic encephalopathy (HIE), and vascular malformations. Consequently, Doppler imaging has gained importance in day-to-day clinical practice, especially in infants with impaired cerebral autoregulation.1 A basic understanding of neuroanatomy through acoustic windows of fontanelles using appropriate Doppler techniques in cerebral arteries is a reliable method to predict cerebral injury; real-time snapshot assessments can enable longitudinal accessibility and ensure response to treatment and follow-up.
Four decades ago, Bada et al.2 outlined the role of cerebral Doppler imaging in diagnosing neonatal brain injury. Since then, various studies have evaluated the role of Doppler parameters and their correlation with the risk and severity of brain injury. However, we still need a systematic approach to apply Doppler evaluation of cerebral vascular anatomy and hemodynamics in clinical practice. In this article, we reviewed the available literature to identify these gaps for further study.
Physiology of Cerebral Blood Flow (CBF) Autoregulation and its Effect on Cerebral Doppler
Changes in CBF play a vital role in causing perinatal brain injury. Disturbances in cerebral circulation and autoregulation before, during, and after birth are believed to be major determinants of the severity of cerebral hemorrhage and HIE. Interestingly, systemic disorders such as shock, sepsis, and patent ductus arteriosus, which alter somatic hemodynamics, also affect cerebral circulation due to poorly defined autoregulatory mechanisms. Cerebral flow velocity is dependent on variables such as blood viscosity, cardiac output, pCO2, pO2, blood glucose levels, and the total oxygen content of arterial blood. Fluctuations in cerebral dynamics are driven mainly at the level of plial arterioles, and to a lesser extent, by large arteries.3
CBF = Cerebral perfusion pressure (CPP)/Cerebrovascular resistance (CVR) = [mean arterial pressure (MAP) – intracranial pressure (ICP)]/cerebrovascular resistance
The classic cerebral autoregulation is a sigmoid curve (Fig. 1), and the range of autoregulatory plateau is bound by the upper and lower limits of autoregulation (LA). Cerebral vasoreactivity functions only when mean arterial pressure (MAP) or cerebral perfusion pressure (CPP) is along this plateau. Above and below the range, CBF is passive to blood pressure, and the brain is at risk of hyperemic or hypoperfusion injury.4 With the gradual development of this autoregulation from 26 to 33 weeks of gestation, the range of the autoregulation plateau is much narrower in preterm neonates (Fig. 1: red dotted line).
Fig. 1: Cerebral autoregulation sigmoid curve in term (blue) and preterm neonates (red): The flat area of the sigmoid curve is the autoregulatory plateau where cerebral perfusion pressure (CPP) is maintained by cerebral vasoreactivity. Beyond the upper limit of autoregulation (ULA) and the lower limit of autoregulation (LLA), cerebral blood flow (CBF) is passive to blood pressure due to impaired vasoreactivity. This infact is worse in preterm infants with a narrow plateau depicting poor autoregulation (red dotted line) (x-axis: mean arterial blood pressure, y-axis: CBF)
Technique and Parameters Used for Doppler Flow Measurements
To study the real-time blood flow patterns in the neonatal brain, we need a basic understanding of the altered anatomy and pathophysiology of the various disease conditions. Keeping the infant calm and comfortable while performing a Doppler flow study is important.
The professionals need to be familiar with ultrasound machines. Understanding the layout of these machines, particularly the components needed for color Doppler imaging (CDI), is important. Protocols are needed to correctly move the color box, obtain the pulse-wave (PW) Doppler signals, and correctly place the flow sample volumes on the artery to be investigated. In practice, we prefer high-frequency convex probes of 8–5 MHz. High-frequency linear transducers are useful to visualize superficial vessels at or near the brain’s convexity, such as the superior sagittal and transverse sinuses. The acoustic windows for obtaining the images depend on the vessel and sinus of interest, anterior fontanelle, and temporal windows (Table 1).
| Acoustic window | Artery visualized |
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| Anterior fontanelle sagittal plane |
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| Temporal window |
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Assessing CBF Pattern and Velocities
Doppler assesses the flow and not the velocity. One must always remember that blood flow in the cerebral artery should be in the forward direction: any reversal of flow is typically abnormal. Depending on the location, the color window superimposed on the gray scale depicts the blood flow in various cerebral vessels. The professionals should be familiar with the placement of the probe position according to the direction of blood flow in various cerebral vessels. Blood flowing toward the probe is seen as a red signal, whereas blood flowing away from the probe appears blue.
There are some important points to remember:
Selection of the correct blood vessel for assessment;
Placement of the color map over the area of interest. The measurements should be performed on a vessel running parallel to the line of insonation. This is because the angle between the axis of the blood vessel and the Doppler beam can affect the Doppler frequency shift and result in suboptimal quality of spectra. The angle of insonation must be kept close to zero by adjusting the angle of the probe;
The most-frequently assessed blood vessels are the ACA and internal carotid artery via the anterior fontanelle (Figs 2 and 3), and the middle cerebral artery from the temporal window. The temporal window can also be used to visualize the posterior cerebral artery (Figs 4 and 5);
The pulse-wave, not the continuous-wave Doppler, is better for studying vessels in the path of the ultrasound beam. Choosing continuous-wave Doppler can confuse the origin of the signal (Fig. 6);
The Doppler waveform should be optimized to have a good-quality spectrum with fairly uniform signals;
The peak-systolic and end-diastolic velocities are identified and the Doppler indices are measured. A mean of 3–5 cardiac cycles is usually taken for the measurement. Most ultrasound systems will automatically or semiautomatically generate the indices (Figs 5 and 6).
The resistive index (RI) is the most frequently used Doppler index. It is defined as:
Figs 2A and B: Anterior fontanelle (AF) midsagittal view: (A) Position of the probe in the sagittal plane with the probe marker towards the nose; (B) Midline sagittal view showing the anterior cerebral artery (ACA) and its two branches, the pericallosal (pC) and marginal (mACA), along with the visualization of the internal carotid artery (ICA)
Figs 3A and B: Anterior fontanelle (AF) coronal view: (A) Note the position of the probe in the coronal plane with the probe marker towards the right (green arrow); (B) Coronal plane showing internal carotid artery (ICA)
Figs 4A and B: Temporal window: (A) Please note the position of the probe in the temporal area to visualize the middle cerebral artery (MCA) and posterior cerebral artery (PCA), probe marker (green arrow); (B) Temporal window showing a circle of Willis, MCA and PCA
Figs 5A and B: Temporal window showing Doppler study: (A) Doppler study of middle cerebral artery (MCA); red color of the flow shows its direction toward the probe. Pulse wave Doppler (PWD) showing peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI); (B) Temporal window showing posterior cerebral artery (PCA). PWD shows normal PSV, EDV, and RI
Figs 6A to D: Doppler measurements: (A) Pulse wave Doppler (PWD) of the anterior cerebral artery (ACA) in midsagittal view seen via the anterior fontanelle (AF); (B) PWD in the internal cerebral vein (ICV) in midsagittal view (AF); (C) Forward flow positive deflection of the artery and its various measurements: a = PSV (peak systolic velocity, 35 cm/s) and b = EDV (end-diastolic velocity, 10 cm/s); (D) Reversed flow (negative deflection) in vein with velocity of 5 cm/s
Serial measurements in the same vessel at the same location are useful in early identification of changes in the condition of the neonate. Some other flow parameters are described in Table 2.
| Doppler parameters | Explanation |
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| Resistive index (RI) | Peak systolic velocity (PSV) – end diastolic velocity (EDV)/PSV |
| Pulsatility index (PI) | Peak systolic velocity – end diastolic velocity/mean velocity |
| Mean velocity (MV) | Mean velocity calculated over the series of cardiac cycles |
| Peak systolic velocity (PSV) | Highest velocity in the cardiac cycle |
| End diastolic velocity (EDV) | Lowest velocity in the cardiac cycle |
| Area under the velocity curve (AUVC) | Represents mean flow velocity |
| Cerebral blood flow fluctuation (CBFF) | Interquartile range of velocity |
| Vmean ratio | MV in first 12 h/MV at 12–168 h |
| Time averaged velocity (TAV) | Vmax/2 |
| Coefficient of variability (CV%) | Coefficient of variation of AUVC values of 20 consecutive cardiac cycles |
| Cerebral blood flow resistance | Cerebral perfusion pressure/RI |
Some Clinically Relevant Aspects of Cerebral Doppler
In the neonatal intensive care unit (NICU), factors such as gestational age, birth weight, postnatal day, small for gestational age,5 pCO2,6 hematocrit,7 sedation,8 position of the baby,9,10 and hypoglycemia11 may influence the CBF and may lead to inconsistent results. Gestational age can affect CBF; some studies show a clear correlation with RI,12 whereas others do not.13 The RI in the ACA drops from a mean of 0.78 (range 0.65–0.85) in preterm infants to 0.7 (range 0.6–0.8) in the full-term neonates.14–18 The increase in diastolic flow with postnatal age may result from decreasing cerebrovascular resistance or diminishing shunting as a result of ductal closure. Further, these data relate to the known downward trend of the RI during the first year after birth, especially after the closure of fontanelle when the mean RI decreases between 0.5 and 0.6.18,19
Impact of Gestational Age and Postnatal Days
Couture et al.20 reported a progressive increase in peak-systolic velocity (PSV) and end-diastolic velocity (EDV) in the ACA, internal carotid artery (ICA), and the basilar artery from 32 weeks of gestation to 8 months of postnatal age, evolving both in parallel with gestational and postnatal age. In the clinical setting, relying only on RI could be misleading as a normal RI could be associated with low blood velocities (Fig. 7). Archer et al.14 studied 24 full-term infants and reported a fall in the pulsatility index (PI) and increasing diastolic velocity in the first 5 days after birth.
Figs 7A and B: Interpretation of flow velocities. (A) Case 1: seven-day-old term neonate with encephalopathy, PSV: 35 cm/s, EDW: 7 cm/s, and RI -0.8; (B) Case 2: Five-day-old 32 weeks preterm, PSV: 40 cm/s, EDV: 10 cm/s, and RI: 0.74. However, RI appears to be normal in both cases, measurement of velocities in case (A) represents low cerebral blood flow
EDV, end-diastolic velocity; PSV, real systolic velocity; RI, resistive index
Oxygen, CO2, and Mean Arterial Pressure
With impaired cerebral autoregulation, the preterm brain is exposed to various stress responses, including those associated with changes in pO2, pCO2, and mean arterial blood pressure (MABP). Menke et al.21 quantified the influence of these parameters in mechanically ventilated preterm infants (gestational age <33 weeks) on cerebral blood flow velocity (CBFV) measured in ICA, with a MABP reactivity of 7.5% (–12.5 to 20.1%), a rise in CBFV per 1 kPa rise in MABP was observed. Similarly, a pCO2 reactivity of 32.7% (–8.1 to 79.5%) rise in CBFV/1 kPa rise in pCO2, and a minimal pO2 reactivity of –3.1% (–14.2 to 7.9%) fall in CBFV/1 kPa rise in pO2 was reported. These findings show altered pCO2 to be a major determinant of CBFV and hence, raise a possibility of its being one of the major causes of preterm brain injury.
Cerebral Doppler in Various Pathological Conditions (Table 3)
| Pulse-wave ACA Doppler | Interpretation | Clinical conditions | Implication/Prognostication |
|---|---|---|---|
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RI: 0.74–0.85 Normal |
Normal term/preterm | Abnormal RI <0.6 or >0.85 |
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RI: 0.6 Decreased A low RI: Lower vascular resistance and higher CBFV (increased diastolic flow) are a marker of a reperfusion injury. |
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RI <0.6 in the initial 24 hours in case of birth asphyxia has 100% sensitivity and 86% specificity for adverse outcomes. Low RI in the first <72 hours of life could be associated with PVL or adverse neurological outcomes in preterm neonates. Serial monitoring of RI is more useful than a single reading. |
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RI = 1 Increased A high RI indicates increased resistance and lower CBFV (decreased diastolic flow). |
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RI value >0.85 is seen in severe cases of asphyxia. Increased RI (>0.8) is associated with HsPDA or hydrocephalus. |
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RI >1 Increased Reversed-diastolic flow: Loss of cerebral autoregulation. |
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Reversed flow always a bad prognosticating marker. |
Intraventricular/Intracerebral Hemorrhage
The absence of CBF autoregulation with hypoxic-reperfusion injury due to systemic hemodynamic instability has been implicated in the pathogenesis of IVH. A recent systematic review (2020, 5 studies) reported no significant correlation among Doppler parameters (PSV, RI, PI, MV, or cerebral blood flow fluctuation) with preterm IVH or intracranial hemorrhage.22 On the contrary, Van Bel et al. studied 60 preterm infants born prior to 34 weeks and noted the RI as being significantly lower and a reasonable correlation with the area under the velocity curve (AUVC). Infants who developed severe IVH had considerably higher variation in RI and AUVC in the first postnatal week.23 A conclusive temporal relationship between Doppler changes and the onset of bleeding has not be established so far (Fig. 8).
Figs 8A to C: Intracranial hemorrhage Doppler: (A) Term infant with large intraparenchymal hemorrhage measuring 3.5 × 2.3 cm in size; (B) PWD Doppler in ACA in midsagittal view; (C) Increased RI (reversed diastolic flow)
ACA, anterior cerebral artery; RI, resistive index; PWD, pulse wave Doppler
Measurements of velocity changes in the perfusion waveform of the internal cerebral vein (ICV) have shown a promising association with IVH in ELBW babies.24 The IVH rate is significantly higher in those with severe pulsatile flow or interrupted or reverse flow patterns in ICV than in others with normal, continuous flow (Fig. 9). Hence, changes in ICV Doppler may be a promising tool to predict severe IVH in preterm neonates and require further studies for its future implications.
Figs 9A to E: (A) Pulse wave Doppler of the internal cerebral vein (blue flow) in sagittal view showing various venous waveform patterns; (B) Continuous flow pattern; (C) Mild pulsatile flow pattern; (D) Severe pulsatile flow pattern; (E) Show (i) interrupted or (r) reversed flow pattern. B and C patterns are normal, whereas the D and E patterns suggest decreased cerebral blood flow in neonates with a high risk of intraventricular hemorrhage
Periventricular Leukomalacia (PVL)
Okumura et al.25 reported that ventilated preterm infants (27–34 weeks) who developed PVL had lower RI in the ACA during the first 72 hours after birth. In contrast, the CBFVs do not fall until beyond the 1st week after birth in the posterior cerebral artery and the ICA, and until beyond the 2nd week in the ACA, MCA, and basilar artery.26 The total cerebral blood supply and the mean velocity fell soon after birth in all major cerebral arteries and continued to be low until 1–2 months in infants who went on to develop cystic PVL. A systematic review by Camfferman et al.22 (5 studies) represented no correlation between CBFV and PVL (Fig. 10). We need further evaluation.
Figs 10A and B: Doppler study in a 1-month-old 27-week premature neonate with periventricular leukomalacia (PVL): (A) Parasagittal view: multiple cysts (3–4 mm) in frontal and parietal periventricular regions. The PVL was assessed as grade 3 with ventricular prominence; (B) Sagittal view PWD in ACA (red flow) showing increased RI: 0.9, decreased diastolic flow
ACA, anterior cerebral artery; RI, resistive index PWD; pulsed wave Doppler
Perinatal Asphyxia
In perinatal asphyxia, there is an initial adaptive vasodilation to maintain oxygen delivery to the brain tissue. This leads to increased diastolic flow and a low RI (Fig. 11) indicating low vessel resistance and higher CBFV that is a marker of reperfusion injury. In severe asphyxia, the cerebral autoregulation may get impaired, leading to high RI (Fig. 11), and leads to increased vascular resistance. Natique et al.27 noted an inverse correlation of RI in the MCA measured shortly after birth and the severity of encephalopathy. Neonates with mild HIE have been noted to show abnormal mean RIs, congruity-abnormal amplitude electroencephalography (45%), and abnormal brain magnetic resonance imaging (45%) and head ultrasound (44%).
Figs 11A to D: Term infant with a history of severe perinatal asphyxia. Ultrasound examination performed on day 1 showed: (A) Coronal view: prominent cerebral edema with obliterated ventricles; (B) Sagittal view PWD in ACA showing increased EDV and decreased RI (0.5) in early asphyxia; (C) Second case-term baby with asphyxia ultrasound examination performed on day 3, coronal view: prominent cerebral edema with obliterated ventricle; (D) Sagittal view PWD of ACA showing decreased EDV and increased RI (0.85)
ACA, anterior cerebral artery; EDV, end diastolic velocity; PWD, pulse wave Doppler; RI, resistive index
Cerebral Doppler has been evaluated as a marker of adverse outcomes in cases of perinatal asphyxia now for several decades. In the late 1980s, Archer et al.28 noted that abnormal Doppler (RI in ACA <0.55) can predict adverse outcomes (death or handicap) with 86% accuracy (100% sensitivity, 81% specificity). In another study, Liu et al.29 classified the severity of asphyxiated brain injury based on cerebral Doppler parameters. Mild HIE was typically associated with an RI < 0.55 with significantly decreased blood flow velocity suggesting hypoperfusion. Some infants with moderate-to-severe HIE showed RI < 0.55 but had increased blood flow velocity (>2 SD), suggesting hyper-perfusion. Overall, low RIs were associated with severe HIE.
Elevated RI with decreased cerebral blood flow velocities, especially EDV, consistently indicates the diagnosis of HIE, with RI > 0.9 to be usually associated with severe encephalopathy. High RIs with the absence of blood flow during diastolic phases denote severe HIE. In cases with most severe HIE, there may be high RI with reversed diastolic flow. This inverse perfusion in cerebral tissues during diastolic phases indicates brain death (Fig. 12).
Fig. 12: Term infant with a history of severe perinatal asphyxia on postnatal day 4. PWD of ACA in sagittal view showed short systolic spikes and retrograde diastolic flow evolving to a brain death pattern
ACA, anterior cerebral artery; PSV, peak systolic velocity; PWD, pulsed wave Doppler
Rath et al.30 systematically reviewed 26 studies and evaluated the importance of Doppler parameters in predicting long-term outcomes following perinatal asphyxia. They separately analyzed studies from the precooling and cooling eras. From the pretherapeutic era, pooled sensitivity and specificity, area under the receiver-operating characteristic curve, and diagnostic odds ratio of RI or CBFV for predicting “death or severe disability” were 0.83 [95% confidence interval (CI) 0.45–0.97] and 0.92 [95% CI 0.74–0.98], 0.94 [95% CI 0.92–0.96], and 54 [95% CI 7–391], respectively. Measurements from the therapeutic hypothermia era were 0.62 [95% CI 0.41–0.80] and 0.96 [95% CI 0.88–0.99], 0.93 [95% CI 0.89–0.94], and 23 [95% CI 6–91]. These measurements were taken before cooling was initiated. Studies measuring cerebral velocities during and after cooling represented the following outcomes, respectively: 0.51 [95% CI 0.24–0.78] and 0.83 [95% CI 0.73–0.90], 0.81 [95% CI 0.78–0.85], and 5 [95% CI 2–13]. Hence, cerebral Doppler may be useful in predicting death or disability in infants with HIE who are not cooled or if performed prior to cooling. However, the tests might not be valid if performed during or after cooling.
Sepsis
The data on the effects of sepsis on CBF show considerable variability. Some studies showed increased flow correlating to vasodilatation,31,32 whereas others illustrated increased PI as representing decreased CBF.33,34 These alterations in cerebral hemodynamics have been attributed to impaired blood–brain barrier secondary to the systemic inflammatory response via cytokines and endotoxins affecting cerebral circulation. Cerebral dysfunction may also be affected both due to cardiac dysfunction and because of microthrombi altering the autoregulatory mechanisms in the microcirculation. Increased CBF could well begin in utero prior to postnatal inflammatory changes. Hence, cerebral Doppler could serve as a surrogate diagnostic marker of early-onset sepsis (EONS). The MCA, ICA, and vertebral artery (VA) have been studied; one study has shown nearly 100% sensitivity and diagnostic accuracy of measuring PI in VA.2 Also, higher PSV has also been observed in these major vessels.31
Late-onset sepsis (LONS): Only a single study has specifically evaluated the effect of CBF in cases with LONS, demonstrating an increased incidence of RI (>0.82) in ACA in culture-proven sepsis, suggesting decreased flow.35
The variability in CBF data in LONS and EONS might be due to the extent of adversely disturbed autoregulatory cerebral circulation, where a critical drop of blood pressure in sepsis may have been transmitted directly to the cerebral vascular bed, leading to cerebral hypoperfusion.36,37
Shock
Abrupt changes in cardiac output and blood pressure can affect cerebral circulation with changes that are tenfold greater than in the systemic blood vessels.38 Cerebral blood flow also falls with lower systemic blood pressure. In preterm infants with severe shock (MAP <10th centile), changes are clearly evident in MCA flow as low end-diastolic velocity and peak-systolic velocity.6 This is further reaffirmed by the return of the cerebral blood flow velocity (CBFV) near to normal range on regaining systemic perfusion. In fact, marked beat-to-beat fluctuations and reversal of arterial flow in ACA represent troublesome findings and may precede IVH in preterm neonates.7 With every 8 mL change in cardiac output (outside the range of 190–440 mL/kg/min), peak-systolic velocity changes by 1 cm, whereas this change is 1.5 cm with every mm Hg change in blood pressure (outside the range of 30–40 mm Hg) and changes in mean velocity by 0.15 cm/mm Hg.39
HsPDA
Altered CBFV secondary to HsPDA serves as a surrogate maker with both diagnostic and prognostic significance. An association between HsPDA with higher RI and lower MV in the ACA, MCA, and ICA has been observed in various clinical studies with a wide variability of RI ranging from 0.78 to 1.2 in cases with HsPDA to RI of 0.61–0.81 in preterm infants without a significant PDA representing an overlapping range.13,37,40–42 These changes in CBF are attributed to the ductal steal phenomenon. Unaltered RI even in the presence of HsPDA could primarily be a result of unaltered autoregulation. Second, this might indicate that RI may not change when both diastolic and systolic flows are equally affected.
Bravo et al.43 concluded that an RI of ≥0.74 in MCA serves as the best biomarker of moderate-to-large PDA (sensitivity 82%, specificity 72%, positive predictive value 50%, and negative predictive value 92%) when assessed 24 hours after termination of the ibuprofen course. In general, a Doppler assessment of the ACA showing a retrograde flow during diastole would suggest a significant ductal shunt (Fig. 13).
Figs 13A and B: 2D-Echo in a ductal view showing patent ductus arteriosus (red flow) with a cranial sagittal view pulsed-wave Doppler in the anterior cerebral artery showing increased RI with absent diastolic flow indicating HsPDA requiring treatment (HsPDA, hemodynamically significant patent ductus arteriosus)
Hydrocephalous
Correctly diagnosing hemodynamic alterations in progressive hydrocephalus could assist in determining the need for drainage, especially in cases of slowly progressive hydrocephalus. Baseline velocities and indices are usually normal in such cases. Hence, RI measured pre and post compression (delta RI = 1–19%) could represent disturbed cerebral compliance and need for shunting. Postsurgical blockage of a shunt could also be detected by the compression technique showing decreased or absent flow in cases of shunt occlusion (Fig. 14).20
Fig. 14: Post-hemorrhagic hydrocephalus in a 1-month-old, premature infant born at a gestational age of 30 weeks. Coronal view showing posthemorrhagic hydrocephalus, PWD of ACA on sagittal view showing increased RI
ACA, anterior cerebral artery; PWD, pulse wave Doppler; RI, resistive index
Assessment of Cerebral Vasculature, as in Arterial stroke, Cerebral Sino-venous Thrombosis (CSVT) Vascular Anomalies
Cerebral veins can be visualized in parasagittal planes through the anterior fontanelle with conventional pulsed-wave Doppler sample volume placed at a point midway along the length of the vein of Galen (mean velocity 5.5 ± 1.5 cm/s ± SD), along the straight sinus (behind the cerebellum), in the internal cerebral vein ([8.8 ± 3 cm/s ± SD] behind the 3rd ventricle), and superior sagittal sinus (16.5 ± 5 cm/s ± SD) (Fig. 15).
Fig. 15: Cerebral veins and sinuses seen through anterior fontanelle midsagittal view: (A) Inferior sagittal sinus (ISS), internal cerebral vein (ICV), vein of Galen (VOG), straight sinus (SS); (B) Superior sagittal sinus (SSS)
In a stable newborn, the cerebral venous pattern is typically characterized by continuous low-velocity flow. The four main venous flow patterns are band-like, sinusoid, intermittent, and reverse flow (Fig. 9). The first two patterns are seen in healthy neonates, and the last two prognosticate adverse outcomes in sick premature neonates, indicating reduced venous flow.
Doppler ultrasound can demonstrate partial or a total absence of flow in combination with partial or complete occlusion of the affected sinus(es) or vessel. Furthermore, it can depict associated brain lesions in the form of (late-onset) IVH and white matter injury. Previous retrospective studies reported only a moderate sensitivity of cranial ultrasound for the detection of CSVT. In the study by Berfelo et al., 37% of cases were diagnosed with cUS and 63% solely on MRI, and in another study, approximately half of CSVT was detected with cUS.44,45
In ultrasound evaluation, ischemic stroke appears as a wedge-shaped focal increase in echogenicity in the supply region of an artery, typically in the MCA. Doppler can be used to differentiate between complete occlusion and severe stenosis and the success of therapeutic measures can also be determined in the further course on the basis of the recanalization of vessels and the morphological consequences of stroke (cyst formation due to liquefactive necrosis).46
Vascular malformations such as the vein of Galen malformation, if untreated, showed pathologic high systolic (up to >1.0 m/s), very high diastolic velocities (up to >0.5 m/s), and low RI (<0.6) with statistically significant differences between the pre- and the post-embolization RI with pathologic low RI before and nearly normal RI after successful shunt reduction.47
Effect of Kangaroo Mother Care (KMC) on Cerebral Doppler
Kangaroo mother care is a multisensory stimulation strategy that is postulated to optimize CBF. Cerebral blood flow has shown a significantly sustained improvement after KMC in decreasing RI and increasing EDV and MV in MCA. This plausible improvement is attributed to the activation of slow-conducting unmyelinated afferents by tactile stimulation that activates the release of vasodilatory mediators in the cortex. The residual effects of KMC on the cerebral Doppler might provide an explanation of KMC on long-term neurodevelopment.48,49
Intrauterine Growth Restriction (IUGR)
Basu et al.50 observed decreased PSV and higher RI in all cerebral vessels in IUGR neonates as compared with their appropriately grown counterparts and attributed it to higher venous hematocrit and lower CBFV. Cerebral Doppler in IUGR is a niche area of research that requires more rigorous evaluation; the results could help predict long-term neurodevelopment outcomes.
Brain Death
Transcranial Doppler examination may not be a consistently reliable marker of brain death and should not be used as a single modality for making these determinations. A reduced systolic antegrade flow followed by a diastolic retrograde flow and with the subsequent appearance of the characteristic short systolic spikes in ACA is reported in cases of brain death.51
Neurological Outcome
Low mean CBFV52 and higher RI53 reported in the first few days after birth in ACA are found to be associated with lower Griffith’s score at 1–2 years of corrected age. Low CBFV is proposed to be a consequence, not a cause of brain injury, as the damaged brain does not grow and may require less blood flow.
LIMITATIONS
Being a nonhazardous low-cost, noninvasive modality, cranial Doppler has evoked interest. However, there are limitations as this is an operator-dependent tool with a learning curve; there is a need for expertise to derive a stable long-term signal to measure blood flow velocities. Inadequate acoustic windows in cases with overriding sutures and craniosynostosis can limit these evaluations. We need predictive tools that could combine CBF parameters with clinical parameters or validated clinical scores and can be used to postulate long-term neurological outcomes.
CONCLUSION
Doppler parameters can help in the near-accurate prediction of CBF, even though a single parameter might not be sufficient. Resistive index is the most user-friendly index that has a minimum inter-observer variability with no dependence on the angle of insonation. Elevated RI in the ACA and MCA can help assess a HsPDA. Doppler may also predict disability in infants with hypoxic brain damage before cooling. Further research is needed to assess its value in measuring vascular tone and/or shunts. A systematically conducted, adequately powered study is needed to evaluate the correlation of Doppler parameters to long-term neurodevelopment outcomes.
ORCID
Jyoti Patodia https://orcid.org/0000-0002-1722-409X
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