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Transcranial color Doppler sonography on healthy pre-school children: Flow velocities and total cerebral blood flow volume
Brain & Development 29 (2007) 64–68 www.elsevier.com/locate/braindev
Transcranial color Doppler sonography on healthy pre-school children: Flow velocities and total cerebral blood flow volume Kuang-Lin Lin, Kuo-Shin Chen, Meng-Ying Hsieh, Huei-Shyong Wang
*
From Division of Pediatric Neurology, Chang Gung Children’s Hospital, Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan Received 7 December 2005; received in revised form 6 June 2006; accepted 16 June 2006
Abstract Transcranial color Doppler sonography (TCCD) is a useful tool for intracranial investigation. Using TCCD to calculate total cerebral blood flow volume (TCBFV) can be a useful indicator for intracranial hemodynamic status. We performed a series study of TCCD on 60 healthy kindergarten students. Peak-systolic, end-diastolic, and mean blood velocities of major cerebral arteries, and depth of flow waves were measured. We also collected Gosling pulsatile index (PI) and Pourcelot resistance index (RI) of the arteries. TCBFV was calculated from the mean blood flood velocity and vessel chamber size of the internal carotid artery (ICA) and basilar artery (BA). Fifty children completed the examinations. The TCBFV was 1538 ± 416 ml/min with mean cerebral blood flow volume of 571 ± 241 ml/min for the ICA system and 983 ± 343 ml/min for the BA system. PI, RI, and the velocities of A1, A2, M1, M2, BA, ICA, and TCBFV were not significantly different between girls and boys in this age group. In this study, we used TCCD to determine the normal data of main cerebral arteries and TCBFV of pre-school children in Taiwan. The reference data of velocities and other parameters of main cerebral arteries from our study may serve as a guide for additional pediatric cerebral hemodynamic studies. Ó 2007 Published by Elsevier B.V. Keywords: Transcranial color Doppler sonography; Total cerebral blood flow volume; Cerebral hemodynamic
1. Introduction Transcranial color Doppler sonography (TCCD) is a useful tool for intracranial investigation. It provides direct sonographic imaging of intracranial vessels and brain parenchyma. It is also a noninvasive, reproducible and bedside mobile device for evaluating the cerebral hemodynamics, including blood flow direction, flow velocities, and other abnormal vascular lesions [1]. Some reference data, focusing on pediatric patients, have been reported by several investigators [2–5]. Nevertheless, it is still a technical issue concerning the poor cooperation of *
Corresponding author. Tel.: +886 3 3281200x8200; fax: +886 3 3288957. E-mail address: [email protected] (H.-S. Wang). 0387-7604/$ - see front matter Ó 2007 Published by Elsevier B.V. doi:10.1016/j.braindev.2006.06.003
pre-school children in clinical practice without sedation of the children. It might be the reason that no normal data of this age group are available in Taiwan. Total cerebral blood flow volume (TCBFV) is an important yet largely unknown factor in the treatment of neurologically intensive care patients suffering, for example, from cerebrovascular disorders and/or intracranial hypertension. Until now, the quantitative measurement of TCBFV has been possible by exposing patients to invasive or to radionucleotide technique [6–9]. Apply TCCD on calculating TCBFV can be a noninvasive and useful elucidation of intracranial hemodynamic status [6]. The goal of this study was to record normal data of flow velocities and waveform parameters of basal cerebral arteries and to measure TCBFV via TCCD in healthy pre-school children.
K.-L. Lin et al. / Brain & Development 29 (2007) 64–68
2. Materials and methods We performed studies of TCCD on 60 healthy kindergarten students, aged from 4 to 6 years old (30 females, 30 males), without headache or systemic disease. The volunteers were recruited from the kindergarten in Chang Gung Medical Village. Written informed consent was obtained before the examination from parents of all the children receiving procedure. We performed the sonographic examinations in the pediatric neurosonographic exam room in Chang Gung Children’s Hospital. It took 45 min to complete the whole procedure in each subject, including 15 min for environment adaptation and 30 min for sonographic procedure. A computed sonography system (128XP; Acuson, a Siemen Company, Mountain View, CA) with a 2.0MHz transducer (for intracranial arteries) and a 7.0MHz linear transducer (for extracranial arteries) were used for the examination. Before the examination, we played with the children for 15 min. The room was rich in kid songs, colorful pictures and interesting toys in order to increase compliance of the subjects. The examination began after 5 min of rest in a supine position with the parents by the child’s beside (for consolation). The probe was applied to the transtemporal window, supraorbital window [10], and carotid area (for internal carotid artery, ICA) when the volunteer was supine, and the suboccipital window (for basilar artery, BA) when in the left decubitus position. We studied in B-mode first and then in color Doppler mode to present the course of arteries. The color Doppler of blood flow toward the transducer was shown in red and flow away from the transducer was shown in blue. We surveyed the M1- and M2-segments of the middle cerebral artery (MCA) and the A1-segment of the anterior cerebral artery (ACA) through the transtemporal window, the A2-segment of the ACA through the supraorbital window. We surveyed the BA 1.5 cm distal to the junction of the vertebrobasilar system through the suboccipital window with mild head bending posture, and the ICA 1.5 cm distal to the common carotid artery through the carotid window. The site of measurement was set 1.5 cm distal to the junction to ascertain the circular lumen. We paid special attention to prevent turbulent flow at the site of Doppler recordings. We collected data on age, sex, body weight (BW), body length (BL), and systolic and diastolic blood pressures (BP) before the examination. We measured peaksystolic (PS), end-diastolic (ED), and mean blood velocities of the right and left ACA-A1, A2; MCA-M1, M2; ICA; and BA, and depth of flow detected. Color Doppler measurements were taken only when the signal was stable for at least 5 s. We also collected Gosling pulsatile index (PI) and Pourcelot resistance index (RI) of the above arteries [11], and the diameters of the right and left ICA and BA so we could calculate TCBFV from
65
the mean blood flow velocity and vessel chamber size. We searched the vessels by color Doppler mode. The diameters of vessels were calculated by real-time B-mode sonography without Doppler coded. The diameters were calculated at systolic phase. We calculated the intravascular flow volume as the product of time-averaged mean flow velocities and the cross-sectional area of the vessel. We defined TCBFV as the blood flow through the right and left ICA and BA. We used the Student’s t-test and analysis of variance (ANOVA) with post hoc test for statistical analysis with a significant p-value less than 0.05 for all parameters.
3. Results Ten children did not complete the sonographic procedure because of irritability and emotional intolerance. Thus, a total of 50 healthy children (8 – 4-year-old, 19 – 5-year-old, and 23 – 6-year-old children) was included in this study, including 25 girls and 25 boys. Their mean BP was 103.1 ± 12.0 over 62.3 ± 10.1 mm Hg. Their mean BW and mean BL were 21.3 ± 5.0 kg and 114.5 ± 7.3 cm, respectively (Table 1). There was no significant difference between the girls and boys in age, BW, or BP, either systolic or diastolic. All parameters of the main cerebral arteries by TCCD recording are summarized in Table 2. There was no significant difference between the right- and left-sided study in PS, ED, or mean of PI, RI of A1, M1, and M2 groups (t-test; p > 0.05). There was also no significant difference in the cerebral blood flow velocities between the boys and girls (Fig. 1). No significant difference was found between the right and left ICA in either PS, ED, mean velocity, PI, or RI, but a significant difference was detected in depth (t-test; p = 0.004). No statistically significant difference distinguished the group of age 4 from age 6 children in PS, ED, and mean velocities (ANOVA with post hoc test; p > 0.05). Neither did PI and RI of the main cerebral arteries differ significantly among Table 1 The profiles of 50 children receiving transcranial Doppler sonography Age (years) 4 year, n 5 year, n 6 year, n
8 19 23
Sex Male:Female
25:25
Blood pressure (mm Hg) Diastolic pressure Systolic pressure
62.3 ± 10.1 103.1 ± 12.0
Body height (mean ± SD, cm)
114.5 ± 7.3
Body weight (mean ± SD, kg)
21.3 ± 5.0
SD, standard deviation.
0.74 ± 0.08 1.59 ± 0.37 20 ± 8 11 ± 6 17 ± 3 983 ± 343 308 ± 177
0.56 ± 0.06 0.58 ± 0.07 0.56 ± 0.06 0.74 ± 0.08 0.83 ± 0.14 0.89 ± 0.19 0.80 ± 0.13 1.57 ± 0.41 91 ± 36 79 ± 34 60 ± 14 22 ± 12 135 ± 50 118 ± 50 86 ± 19 43 ± 20 59 ± 5 44 ± 4 62 ± 6 19 ± 3
59 ± 23 49 ± 21 38 ± 10 11 ± 6
0.55 ± 0.07 0.81 ± 0.17 85 ± 34 54 ± 24 126 ± 42 63 ± 7
ACA-A1 ACA-A2 MCA-M1 MCA-M2 BAb ICA
RI PI Mean (cm/s) ED (cm/s) PS (cm/s)
44 ± 21
0.82 ± 0.21 0.78 ± 0.20 0.85 ± 0.17 0.86 ± 0.18 73 ± 31 63 ± 21 87 ± 35 68 ± 25 62 ± 6 46 ± 5 59 ± 6 44 ± 5
107 ± 47 89 ± 29 128 ± 52 102 ± 37
48 ± 22 42 ± 15 55 ± 23 44 ± 18
0.55 ± 0.07 0.53 ± 0.06 0.57 ± 0.07 0.56 ± 0.07
CBFV (ml/min) RI PI Mean (cm/s) ED (cm/s) Depth (mm)
PS (cm/s)
Left hemisphere
Depth (mm)
CBFV (ml/min) Right hemisphere Vessela
Table 2 Normal reference values of blood flow velocities of basal cerebral arteries in 50 healthy pre-school children
ACA, anterior cerebral artery; A1, A1 segment of ACA; A2, A2 segment of ACA (We record left A2 only); MCA, middle cerebral artery; M1, M1 segment of MCA; M2, M2 segment of MCA; BA, basilar artery; ICA, internal carotid artery; PS, peak-systolic blood flow velocity; ED, end-diastolic blood flow velocity; PI (Gosling pulsatile index), (PS–ED)/M; RI (Pourcelot resistance index), (PS–ED)/PS CBFV, cerebral blood flow volume. a All data were presented as ‘‘mean ± 1SD’’. b Basilar artery is located at the midline of brain.
K.-L. Lin et al. / Brain & Development 29 (2007) 64–68
263 ± 107
66
various age groups (ANOVA with post hoc test; p > 0.05; Fig. 2A and B). The mean diameter of the BA was 5.9 ± 0.7 mm. The diameter of the right and left ICA were 5.4 ± 0.6 and 5.3 ± 0.7 mm, respectively. The mean cerebral blood flow volume was 571 ± 241 ml/min for the ICA system and 983 ± 343 ml/min for the BA system. The mean TCBFV was 1538 ± 416 ml/min. The carotid and basilar systems accounted for 37% and 63% of TCBFV, respectively. There was a significant difference between the blood flow from the carotid and basilar systems (t-test; p < 0.01). For TCBFV, there was no marked difference between the girls and boys, neither did it differ between the age 4 group and 6 group (ANOVA with post hoc test; p > 0.05; Fig. 3A and B).
4. Discussion Using color Doppler sonography to estimate TCBFV was first described by Scho¨ning et al. in a group of young and middle-aged healthy adults [12]. Since then, there have been rare reports of TCBFV surveyed with the tool of TCCD in this age group [6,12–14]. Furthermore, to date, there have been few reference data of TCCD focusing on healthy pre-school children, and none in Taiwan. This may be due to inattention and poor compliance of young children. In this study, we tried our best to offer the children a comfortable environment in order for us to obtain good results from the examination. There was no statistically significant difference between the pre-school girls and boys in blood flow parameters of the main cerebral arteries, including velocities, PI, and RI. In the study of Brouwers et al., girls of 10 years of age or older showed a tendency of higher mean flow velocity values than boys of the same age [3]. They suggest that females in their reproductive years have higher maximal mean flow velocity values than males, which makes speculating the hormonal influence on mean flow velocity become tempting [3]. Nonetheless, in our study, the hormone effect is excluded because all the subjects are pre-school children. The results of TCBFV in this study also showed no difference between the girls and boys. These findings are in accordance with those of Scheel et al. and Buijs et al. [6,15]. On the contrary, it is well known that brain weight from the first year of life is in average 10% higher in men than in woman of the same age [16]. Rodriguez et al. reported that global CBF (per 100 g brain weight) is 11% higher in woman than in men [17]. These opposing trends may explain why there is no difference in TCBFV between boys and girls [6]. As a matter of fact, the factors that influence values of TCBFV are blood flow velocities and vessels diameters. In our study, there is no difference of cerebral flow velocities between the boys and girls. If the brain weights of boys are higher than
K.-L. Lin et al. / Brain & Development 29 (2007) 64–68
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Fig. 1. There was no significant difference of cerebral blood flow velocities between boys and girls. Data are presented as mean ± SD, p > 0.05 in each cerebral blood vessel.
Fig. 2. The (A) Gosling pulsatile index (PI) and (B) Pourcelot resistance index (RI) of main cerebral arteries were not significantly different among various age groups. Data are presented as mean ± SD, p > 0.05 in each cerebral vessel.
Fig. 3. Total cerebral blood flow volume (TCBFV) was estimated by the total blood flow through right and left ICA and BA. There was not significant difference between girls and boys (A), and no significant difference between age groups of 4- and 6-year-old (B). Data are presented as mean ± SD, p > 0.05 in each cerebral vessel.
those of girls, the only change is the value of global CBF (per 100 g brain weight). The maximal values of cerebral blood flow velocities were recorded at the age of 5–6 years in the study of Bode et al. [2]. After that the velocities decreased linearly to 70% of their maximum at the age of 18 years. In this study, the blood flow velocities of ACA and MCA were compatible with the data shown in previous literatures [12–14]. The right and left ICA blood flow parameters were not significantly different, but there was a significant difference in the depth of bilateral ICA. This was probably due to the operator sitting by one side of the volunteer, so a different degree of neck compression occurred. Measurement of cerebral blood flow volume is required for identification and quantification of focal or generalized perfusion disturbances in the course of traumatic, infectious, or neurodegenerative disorders [18]. We choose ICA and BA for the TCBFV calculation. That can include all the blood flow into the brain and represent the general perfusion status of brain. In our study, the TCBFV for the healthy pre-school children was 1538 ± 416 ml/min. This is much higher when compared to older age groups, such as the Scho¨ning group (mean 35 ± 12 years old, TCBFV = 701 ± 104 ml/min) [12], the Do¨rfler group (20–30 years old, TCBFV = 668 ± 84 ml/min) [18]. Also, it is higher than the same age group reported by Scho¨ning et al (3 to 6.5 years old, 687 ± 85 to 896 ± 110 ml/min) [14]. In our study, the main reason for the higher TCBFV than the previous study is the high CBFV of posterior brain circulation. We surveyed the BA 1.5 cm distal to the junction of the vertebrobasilar system through the suboccipital window with mild head bending posture. In this posture, we do not need angle correction for blood flow detection. But, we do not know if this posture makes any disturbance on posterior brain circulation. Two possible errors in this study that made the higher posterior circulation were as follows: first, falselarger diameters of the basilar arteries were measured by the operators; second, neck bending postures might
68
K.-L. Lin et al. / Brain & Development 29 (2007) 64–68
cause abnormal carotid arteries compression. To sum up, the possible factors that result in higher TCBFV in this study than the previous ones include different races, different target vessels (basilar artery vs. vertebrae artery), necessity of angle correction, different postures and possible errors of vessel diameters detection. Nevertheless, we have presented a different method to estimate TCBFV. According to the study of Scho¨ning et al., TCBFV increased significantly from 3 to 6.5 years of age. The TCBFV of pre-school age group is the summit of life [14]. Age dependence of flow velocity was demonstrated by Scho¨ning et al. in the MCA, ACA, posterior cerebral artery, and BA from 3 years of age to the sixth decade of life, in linear reduction [5]. Krejza et al. demonstrated mean PI and RI increased with advancing age, especially in subjects more than 40 years of age [19]. In our study, there was no statistically significant difference among age groups of 4- to 6-year-old children in the cerebral blood velocity, PI, RI, and TCBFV. The reasons might be the small numbers of subjects and the narrow age differences (4–6 years). A larger number of cases may be needed to evaluate the age-dependent relationship for these parameters. In summary, TCCD is a useful tool to evaluate flow velocity of the main cerebral arteries. TCCD can survey the TCBFV and investigate the physiology and pathophysiology of the cerebral circulation. The reference data of velocities and other parameters of main cerebral arteries from our study may serve as a guide for additional pediatric cerebral hemodynamic studies.
[5]
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References [1] Lin SK, Ryu SJ, Lee ST, Wang HS. Transcranial color-coded sonography in normal Chinese adults and its clinical applications. Chang Gung Med J 1995;18:201–8. [2] Bode H, Wais U. Age dependence of flow velocities in basal cerebral arteries. Arch Dis Child 1988;63:606–11. [3] Brouwers PJ, Vriens EM, Musbach M, Wieneke GH, vanHuffelen AC. Transcranial pulsed Doppler measurements of blood flow velocity in the middle cerebral artery: reference values at rest and during hyperventilation in healthy children and adolescents in relation to age and sex. Ultarsound Med Biol 1990;16:1–8. [4] Scho¨ning M, Staab M, Walter J, Niemann G. Transcranial color duplex sonography in childhood and adolescence. Age
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[19]
dependence of flow velocities and waveform parameters. Stroke 1993;24:1305–9. Scho¨ning M, Niemann G, Hartig B. Transcranial color duplex sonography of basal cerebral arteries: reference data of flow velocities from childhood to adulthood. Neuropediatrics 1996;27:249–55. Scheel P, Ruge C, Petruch UR, Scho¨ning M. Color duplex measurement of cerebral blood flow volume in healthy adults. Stroke 2000;31:147–50. Kety SS, Schmidt CF. The nitrous oxide method for quantitative determination of cerebral blood flow in man: theory, procedure, and normal values. J Clin Invest 1948;27:476–83. Waldemar G, Hasselbalch SG, Andersen AR, Delecluse F, Petersen P, Johnsen A, Paulson OB. 99mTc-d, 1-HMPAO and SPECT of the brain in normal aging. J Cere Blood Flow Metab 1991;11:508–21. Frackowiak RSJ, Lenzi GL, Jones T, Heather JD. Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values. J Comput Assist Tomogr 1980;4:727–36. Wang HS, Kuo MF. Supraorbital approach of the anterior cerebral artery: a new window for transcranial Doppler sonography. J Ultrasound Med 1995;14:259–61. Dayeel G, Robert AM. Intracranial pressure and cerebral arterial flow velocity in childhood hydrocephalus: current review. Child’s Nerv Syst 1995;11:392–6. Scho¨ning M, Walter J, Scheel P. Estimation of cerebral blood flow through color duplex sonography of the carotid and vertebrae arteries in healthy adults. Stroke 1994;25:17–22. Scho¨ning M, Scheel P. Color duplex measurement of cerebral blood flow volume: intra- and interobserver reproducibility and habituation to serial measurements in normal subjects. J Cereb Blood Flow Metab 1996;16:523–31. Scho¨ning M, Hartig B. Age dependence of total cerebral blood flow volume from childhood to adulthood. J Cereb Blood Flow Metab 1996;16:827–33. Buijs PC, Krabbe Hartkamp MJ, Bakker CJ, de Lange EE, Ramos LM, Breteler MM, Mali WP. Effect of age on cerebral blood flow: measurement with ungated two-dimensional phasecontrast MR angiography in 250 adults. Radiology 1998;209:667–74. Dekaban AS, Sadowsky D. Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol 1978;4:345–56. Rodriguez G, Warkentin S, Risberg J, Rosadini G. Sex differences in regional cerebral blood flow. J Cereb Blood Flow Metab 1988;8:783–9. Do¨rfler P, Puls I, Schließer M, Ma¨urer M, Becker G. Measurement of cerebral blood flow volume by extracranial sonography. J Cereb Blood Flow Metab 2000;20:269–71. Krejza J, Mariak Z, Walecki J, Szydlik P, Lewko J, Ustymowicz A. Transcranial color Doppler sonography of basal cerebral arteries in 182 healthy subjects: age and sex variability and normal reference values for blood flow parameters. AJR 1999;172:213–8.
Transcranial color Doppler sonography on healthy pre-school children: Flow velocities and total cerebral blood flow volume Kuang-Lin Lin, Kuo-Shin Chen, Meng-Ying Hsieh, Huei-Shyong Wang
*
From Division of Pediatric Neurology, Chang Gung Children’s Hospital, Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan Received 7 December 2005; received in revised form 6 June 2006; accepted 16 June 2006
Abstract Transcranial color Doppler sonography (TCCD) is a useful tool for intracranial investigation. Using TCCD to calculate total cerebral blood flow volume (TCBFV) can be a useful indicator for intracranial hemodynamic status. We performed a series study of TCCD on 60 healthy kindergarten students. Peak-systolic, end-diastolic, and mean blood velocities of major cerebral arteries, and depth of flow waves were measured. We also collected Gosling pulsatile index (PI) and Pourcelot resistance index (RI) of the arteries. TCBFV was calculated from the mean blood flood velocity and vessel chamber size of the internal carotid artery (ICA) and basilar artery (BA). Fifty children completed the examinations. The TCBFV was 1538 ± 416 ml/min with mean cerebral blood flow volume of 571 ± 241 ml/min for the ICA system and 983 ± 343 ml/min for the BA system. PI, RI, and the velocities of A1, A2, M1, M2, BA, ICA, and TCBFV were not significantly different between girls and boys in this age group. In this study, we used TCCD to determine the normal data of main cerebral arteries and TCBFV of pre-school children in Taiwan. The reference data of velocities and other parameters of main cerebral arteries from our study may serve as a guide for additional pediatric cerebral hemodynamic studies. Ó 2007 Published by Elsevier B.V. Keywords: Transcranial color Doppler sonography; Total cerebral blood flow volume; Cerebral hemodynamic
1. Introduction Transcranial color Doppler sonography (TCCD) is a useful tool for intracranial investigation. It provides direct sonographic imaging of intracranial vessels and brain parenchyma. It is also a noninvasive, reproducible and bedside mobile device for evaluating the cerebral hemodynamics, including blood flow direction, flow velocities, and other abnormal vascular lesions [1]. Some reference data, focusing on pediatric patients, have been reported by several investigators [2–5]. Nevertheless, it is still a technical issue concerning the poor cooperation of *
Corresponding author. Tel.: +886 3 3281200x8200; fax: +886 3 3288957. E-mail address: [email protected] (H.-S. Wang). 0387-7604/$ - see front matter Ó 2007 Published by Elsevier B.V. doi:10.1016/j.braindev.2006.06.003
pre-school children in clinical practice without sedation of the children. It might be the reason that no normal data of this age group are available in Taiwan. Total cerebral blood flow volume (TCBFV) is an important yet largely unknown factor in the treatment of neurologically intensive care patients suffering, for example, from cerebrovascular disorders and/or intracranial hypertension. Until now, the quantitative measurement of TCBFV has been possible by exposing patients to invasive or to radionucleotide technique [6–9]. Apply TCCD on calculating TCBFV can be a noninvasive and useful elucidation of intracranial hemodynamic status [6]. The goal of this study was to record normal data of flow velocities and waveform parameters of basal cerebral arteries and to measure TCBFV via TCCD in healthy pre-school children.
K.-L. Lin et al. / Brain & Development 29 (2007) 64–68
2. Materials and methods We performed studies of TCCD on 60 healthy kindergarten students, aged from 4 to 6 years old (30 females, 30 males), without headache or systemic disease. The volunteers were recruited from the kindergarten in Chang Gung Medical Village. Written informed consent was obtained before the examination from parents of all the children receiving procedure. We performed the sonographic examinations in the pediatric neurosonographic exam room in Chang Gung Children’s Hospital. It took 45 min to complete the whole procedure in each subject, including 15 min for environment adaptation and 30 min for sonographic procedure. A computed sonography system (128XP; Acuson, a Siemen Company, Mountain View, CA) with a 2.0MHz transducer (for intracranial arteries) and a 7.0MHz linear transducer (for extracranial arteries) were used for the examination. Before the examination, we played with the children for 15 min. The room was rich in kid songs, colorful pictures and interesting toys in order to increase compliance of the subjects. The examination began after 5 min of rest in a supine position with the parents by the child’s beside (for consolation). The probe was applied to the transtemporal window, supraorbital window [10], and carotid area (for internal carotid artery, ICA) when the volunteer was supine, and the suboccipital window (for basilar artery, BA) when in the left decubitus position. We studied in B-mode first and then in color Doppler mode to present the course of arteries. The color Doppler of blood flow toward the transducer was shown in red and flow away from the transducer was shown in blue. We surveyed the M1- and M2-segments of the middle cerebral artery (MCA) and the A1-segment of the anterior cerebral artery (ACA) through the transtemporal window, the A2-segment of the ACA through the supraorbital window. We surveyed the BA 1.5 cm distal to the junction of the vertebrobasilar system through the suboccipital window with mild head bending posture, and the ICA 1.5 cm distal to the common carotid artery through the carotid window. The site of measurement was set 1.5 cm distal to the junction to ascertain the circular lumen. We paid special attention to prevent turbulent flow at the site of Doppler recordings. We collected data on age, sex, body weight (BW), body length (BL), and systolic and diastolic blood pressures (BP) before the examination. We measured peaksystolic (PS), end-diastolic (ED), and mean blood velocities of the right and left ACA-A1, A2; MCA-M1, M2; ICA; and BA, and depth of flow detected. Color Doppler measurements were taken only when the signal was stable for at least 5 s. We also collected Gosling pulsatile index (PI) and Pourcelot resistance index (RI) of the above arteries [11], and the diameters of the right and left ICA and BA so we could calculate TCBFV from
65
the mean blood flow velocity and vessel chamber size. We searched the vessels by color Doppler mode. The diameters of vessels were calculated by real-time B-mode sonography without Doppler coded. The diameters were calculated at systolic phase. We calculated the intravascular flow volume as the product of time-averaged mean flow velocities and the cross-sectional area of the vessel. We defined TCBFV as the blood flow through the right and left ICA and BA. We used the Student’s t-test and analysis of variance (ANOVA) with post hoc test for statistical analysis with a significant p-value less than 0.05 for all parameters.
3. Results Ten children did not complete the sonographic procedure because of irritability and emotional intolerance. Thus, a total of 50 healthy children (8 – 4-year-old, 19 – 5-year-old, and 23 – 6-year-old children) was included in this study, including 25 girls and 25 boys. Their mean BP was 103.1 ± 12.0 over 62.3 ± 10.1 mm Hg. Their mean BW and mean BL were 21.3 ± 5.0 kg and 114.5 ± 7.3 cm, respectively (Table 1). There was no significant difference between the girls and boys in age, BW, or BP, either systolic or diastolic. All parameters of the main cerebral arteries by TCCD recording are summarized in Table 2. There was no significant difference between the right- and left-sided study in PS, ED, or mean of PI, RI of A1, M1, and M2 groups (t-test; p > 0.05). There was also no significant difference in the cerebral blood flow velocities between the boys and girls (Fig. 1). No significant difference was found between the right and left ICA in either PS, ED, mean velocity, PI, or RI, but a significant difference was detected in depth (t-test; p = 0.004). No statistically significant difference distinguished the group of age 4 from age 6 children in PS, ED, and mean velocities (ANOVA with post hoc test; p > 0.05). Neither did PI and RI of the main cerebral arteries differ significantly among Table 1 The profiles of 50 children receiving transcranial Doppler sonography Age (years) 4 year, n 5 year, n 6 year, n
8 19 23
Sex Male:Female
25:25
Blood pressure (mm Hg) Diastolic pressure Systolic pressure
62.3 ± 10.1 103.1 ± 12.0
Body height (mean ± SD, cm)
114.5 ± 7.3
Body weight (mean ± SD, kg)
21.3 ± 5.0
SD, standard deviation.
0.74 ± 0.08 1.59 ± 0.37 20 ± 8 11 ± 6 17 ± 3 983 ± 343 308 ± 177
0.56 ± 0.06 0.58 ± 0.07 0.56 ± 0.06 0.74 ± 0.08 0.83 ± 0.14 0.89 ± 0.19 0.80 ± 0.13 1.57 ± 0.41 91 ± 36 79 ± 34 60 ± 14 22 ± 12 135 ± 50 118 ± 50 86 ± 19 43 ± 20 59 ± 5 44 ± 4 62 ± 6 19 ± 3
59 ± 23 49 ± 21 38 ± 10 11 ± 6
0.55 ± 0.07 0.81 ± 0.17 85 ± 34 54 ± 24 126 ± 42 63 ± 7
ACA-A1 ACA-A2 MCA-M1 MCA-M2 BAb ICA
RI PI Mean (cm/s) ED (cm/s) PS (cm/s)
44 ± 21
0.82 ± 0.21 0.78 ± 0.20 0.85 ± 0.17 0.86 ± 0.18 73 ± 31 63 ± 21 87 ± 35 68 ± 25 62 ± 6 46 ± 5 59 ± 6 44 ± 5
107 ± 47 89 ± 29 128 ± 52 102 ± 37
48 ± 22 42 ± 15 55 ± 23 44 ± 18
0.55 ± 0.07 0.53 ± 0.06 0.57 ± 0.07 0.56 ± 0.07
CBFV (ml/min) RI PI Mean (cm/s) ED (cm/s) Depth (mm)
PS (cm/s)
Left hemisphere
Depth (mm)
CBFV (ml/min) Right hemisphere Vessela
Table 2 Normal reference values of blood flow velocities of basal cerebral arteries in 50 healthy pre-school children
ACA, anterior cerebral artery; A1, A1 segment of ACA; A2, A2 segment of ACA (We record left A2 only); MCA, middle cerebral artery; M1, M1 segment of MCA; M2, M2 segment of MCA; BA, basilar artery; ICA, internal carotid artery; PS, peak-systolic blood flow velocity; ED, end-diastolic blood flow velocity; PI (Gosling pulsatile index), (PS–ED)/M; RI (Pourcelot resistance index), (PS–ED)/PS CBFV, cerebral blood flow volume. a All data were presented as ‘‘mean ± 1SD’’. b Basilar artery is located at the midline of brain.
K.-L. Lin et al. / Brain & Development 29 (2007) 64–68
263 ± 107
66
various age groups (ANOVA with post hoc test; p > 0.05; Fig. 2A and B). The mean diameter of the BA was 5.9 ± 0.7 mm. The diameter of the right and left ICA were 5.4 ± 0.6 and 5.3 ± 0.7 mm, respectively. The mean cerebral blood flow volume was 571 ± 241 ml/min for the ICA system and 983 ± 343 ml/min for the BA system. The mean TCBFV was 1538 ± 416 ml/min. The carotid and basilar systems accounted for 37% and 63% of TCBFV, respectively. There was a significant difference between the blood flow from the carotid and basilar systems (t-test; p < 0.01). For TCBFV, there was no marked difference between the girls and boys, neither did it differ between the age 4 group and 6 group (ANOVA with post hoc test; p > 0.05; Fig. 3A and B).
4. Discussion Using color Doppler sonography to estimate TCBFV was first described by Scho¨ning et al. in a group of young and middle-aged healthy adults [12]. Since then, there have been rare reports of TCBFV surveyed with the tool of TCCD in this age group [6,12–14]. Furthermore, to date, there have been few reference data of TCCD focusing on healthy pre-school children, and none in Taiwan. This may be due to inattention and poor compliance of young children. In this study, we tried our best to offer the children a comfortable environment in order for us to obtain good results from the examination. There was no statistically significant difference between the pre-school girls and boys in blood flow parameters of the main cerebral arteries, including velocities, PI, and RI. In the study of Brouwers et al., girls of 10 years of age or older showed a tendency of higher mean flow velocity values than boys of the same age [3]. They suggest that females in their reproductive years have higher maximal mean flow velocity values than males, which makes speculating the hormonal influence on mean flow velocity become tempting [3]. Nonetheless, in our study, the hormone effect is excluded because all the subjects are pre-school children. The results of TCBFV in this study also showed no difference between the girls and boys. These findings are in accordance with those of Scheel et al. and Buijs et al. [6,15]. On the contrary, it is well known that brain weight from the first year of life is in average 10% higher in men than in woman of the same age [16]. Rodriguez et al. reported that global CBF (per 100 g brain weight) is 11% higher in woman than in men [17]. These opposing trends may explain why there is no difference in TCBFV between boys and girls [6]. As a matter of fact, the factors that influence values of TCBFV are blood flow velocities and vessels diameters. In our study, there is no difference of cerebral flow velocities between the boys and girls. If the brain weights of boys are higher than
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Fig. 1. There was no significant difference of cerebral blood flow velocities between boys and girls. Data are presented as mean ± SD, p > 0.05 in each cerebral blood vessel.
Fig. 2. The (A) Gosling pulsatile index (PI) and (B) Pourcelot resistance index (RI) of main cerebral arteries were not significantly different among various age groups. Data are presented as mean ± SD, p > 0.05 in each cerebral vessel.
Fig. 3. Total cerebral blood flow volume (TCBFV) was estimated by the total blood flow through right and left ICA and BA. There was not significant difference between girls and boys (A), and no significant difference between age groups of 4- and 6-year-old (B). Data are presented as mean ± SD, p > 0.05 in each cerebral vessel.
those of girls, the only change is the value of global CBF (per 100 g brain weight). The maximal values of cerebral blood flow velocities were recorded at the age of 5–6 years in the study of Bode et al. [2]. After that the velocities decreased linearly to 70% of their maximum at the age of 18 years. In this study, the blood flow velocities of ACA and MCA were compatible with the data shown in previous literatures [12–14]. The right and left ICA blood flow parameters were not significantly different, but there was a significant difference in the depth of bilateral ICA. This was probably due to the operator sitting by one side of the volunteer, so a different degree of neck compression occurred. Measurement of cerebral blood flow volume is required for identification and quantification of focal or generalized perfusion disturbances in the course of traumatic, infectious, or neurodegenerative disorders [18]. We choose ICA and BA for the TCBFV calculation. That can include all the blood flow into the brain and represent the general perfusion status of brain. In our study, the TCBFV for the healthy pre-school children was 1538 ± 416 ml/min. This is much higher when compared to older age groups, such as the Scho¨ning group (mean 35 ± 12 years old, TCBFV = 701 ± 104 ml/min) [12], the Do¨rfler group (20–30 years old, TCBFV = 668 ± 84 ml/min) [18]. Also, it is higher than the same age group reported by Scho¨ning et al (3 to 6.5 years old, 687 ± 85 to 896 ± 110 ml/min) [14]. In our study, the main reason for the higher TCBFV than the previous study is the high CBFV of posterior brain circulation. We surveyed the BA 1.5 cm distal to the junction of the vertebrobasilar system through the suboccipital window with mild head bending posture. In this posture, we do not need angle correction for blood flow detection. But, we do not know if this posture makes any disturbance on posterior brain circulation. Two possible errors in this study that made the higher posterior circulation were as follows: first, falselarger diameters of the basilar arteries were measured by the operators; second, neck bending postures might
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cause abnormal carotid arteries compression. To sum up, the possible factors that result in higher TCBFV in this study than the previous ones include different races, different target vessels (basilar artery vs. vertebrae artery), necessity of angle correction, different postures and possible errors of vessel diameters detection. Nevertheless, we have presented a different method to estimate TCBFV. According to the study of Scho¨ning et al., TCBFV increased significantly from 3 to 6.5 years of age. The TCBFV of pre-school age group is the summit of life [14]. Age dependence of flow velocity was demonstrated by Scho¨ning et al. in the MCA, ACA, posterior cerebral artery, and BA from 3 years of age to the sixth decade of life, in linear reduction [5]. Krejza et al. demonstrated mean PI and RI increased with advancing age, especially in subjects more than 40 years of age [19]. In our study, there was no statistically significant difference among age groups of 4- to 6-year-old children in the cerebral blood velocity, PI, RI, and TCBFV. The reasons might be the small numbers of subjects and the narrow age differences (4–6 years). A larger number of cases may be needed to evaluate the age-dependent relationship for these parameters. In summary, TCCD is a useful tool to evaluate flow velocity of the main cerebral arteries. TCCD can survey the TCBFV and investigate the physiology and pathophysiology of the cerebral circulation. The reference data of velocities and other parameters of main cerebral arteries from our study may serve as a guide for additional pediatric cerebral hemodynamic studies.
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