-course changes in cerebral blood volume in preterm infants during the first 3 days of life using a portable near

Assessment of time ^- course changes in cerebral blood volume in preterm infants during the first 3 days of life using a portable near ^- infrared

time ^- resolved spectroscopy system

Tao FUJIOKA, Takeshi TAKAMI, Hiroki ISHII, Yuusuke SUGANAMI, Norio MIZUKAKI, Atsushi KONDO,

Daisuke SUNOHARA and Akinori HOSHIKA

Department of Pediatrics, Tokyo Medical University

Abstract

  Objective

: The aim of this study was to evaluate, using a portable 3

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wavelength near

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infrared time

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resolved spectroscopy (NIR

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TRS) system, chronological changes in cerebral blood volume (CBV) and to clarify their asso- ciation with cerebral oxygen metabolism, PCO 2 , mean arterial blood pressure (MABP) and hematocrit (Ht) levels during the first 3 postnatal days of preterm infants.

  Study Design

: CBV, cerebral oxygen saturation (cSO 2 ) and cerebral fractional tissue oxygen extraction (FTOE) among 31 preterm infants of 28

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35 weeks gestation were monitored using NIR

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TRS at 3

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6, 12, 24, 48 and 72 hours after birth with the optode placed on the front head. MABP, PCO 2 and Ht levels were measured simultaneously with the NIR

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TRS measurement.

  Results

: CBV and cSO 2 transiently decreased 12 hours after birth and subsequently significantly increased (P<0.01) 72 hours after birth. Conversely, FTOE increased steadily until 12 hours after birth and then signifi- cantly decreased (P<0.01). CBV correlated with cSO 2 3

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6 hours (P<0.05, r=0.38), 12 hours (P<0.01, r=0.62) and 24 hours (P<0.05, r=0.36) after birth, with FTOE 12 hours (P<0.01, r=−0.58) after birth, and with Ht 3

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6 hours (P<0.01, r=−0.49), 48 hours (P<0.01, r=−0.51) and 72 hours (P<0.05, r=−0.38) after birth. There were no correlations among CBV, PCO 2 or MABP.

  Conclusion

: This study indicates that changes in CBV may be related to those in the cerebral oxygen utili- zation and Ht level during the first 3 days of life in preterm infants.

Received November 4, 2011, Accepted December 19, 2011

Key words : Cerebral blood volume, Cerebral oxygen saturation, Cerebral fractional tissue oxygen extraction, Near

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infrared time

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re- solved spectroscopy, Preterm infant

Corresponding author : Tao Fujioka, MD., Department of Pediatrics, Tokyo Medical University, 6

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7

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1 Nishishinjuku, Shinjuku

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ku, Tokyo 160

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0023, Japan

TEL : +81

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(0)3

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3342

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6111 FAX : +81

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(0)3

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3344

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0643 E

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mail : [email protected] Introduction

Drastic hemodynamic changes in adaptation during the transition from fetal to extrauterine life lead to cardiac insufficiency and cerebral complications, including intra- ventricular hemorrhage (IVH) and hypoxic ischemic encephalopathy (HIE) in newborn infants during the postnatal period ¹⁾ . Furthermore, preterm infants are at

greater risk of these cerebral injuries due to their imma- turity. Cerebral complications are major problems that can cause long

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term neurological sequelae, and therefore it is essential to evaluate cerebral perfusion during the immediate postnatal period. To date, changes in cere- bral perfusion have not yet been fully elucidated.

Near

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infrared spectroscopy (NIRS) can noninvasively

investigate cerebral oxygenation and metabolism. Sev-

J. Tokyo Med. Univ., 70 （1） : 26

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33, 2012

eral kinds of NIRS instruments have been developed and widely applied to evaluate cerebral perfusion in different neonatal fields. Although there have been several reports on the quantification of cerebral blood flow (CBF) or cerebral blood volume (CBV) using NIRS in conjunc- tion with the intravenous ¹³³ Xenon clearance technique ²⁾ , rapid changes in arterial oxygen saturation ³

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⁷⁾ and injec- tion of indocyanine green (ICG) ⁸⁾ , these procedures may be harmful in immature neonates, and it is difficult to obtain measurements in sick infants.

By using a recently developed near

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infrared time

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resolved spectroscopy (NIR

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TRS) system, the distribu- tion of the optical path length is directly measured using a time

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correlated single photon counting (TCSPC) method ⁹⁾¹⁰⁾ . Furthermore, by using a photon diffusion equation, we can measure absolute the light absorption coefficient (μ a ), light

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reduced scattering coefficient μ’ s , oxyHb and deoxyHb using a photon diffusion theory at the bedside, and also calculate CBV without performing any invasive procedures ¹¹⁾ .

In this study, we evaluated the time

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course changes in the CBV of preterm infants using a portable NIR

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TRS system and clarified their association with cerebral oxy- gen metabolism, PCO 2 , mean arterial blood pressure (MABP) and hematocrit (Ht) levels during the first 3 postnatal days.

Materials and Methods   Study participants

We studied 31 preterm infants admitted to the neonatal intensive care unit of Tokyo medical university hospital from November 1, 2009 to February 28, 2011. The inclusion criteria of the study were as follows : 1) sub- jects without anomalies and who were not small for their gestational age ; 2) subjects who had not undergone a cranial ultrasound scan during the study ; 3) subjects who did not show severe electrolyte abnormalities or metabolic acidosis during the study ; 4) subjects who were maintained in a stable respiratory condition with or without mechanical ventilation (SpO 2 ≥ 90% and PCO 2

range=30

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60 mm Hg during the study period) ; 5) sub- jects with an Apgar score of greater than 7 at 5 min- utes. This study was approved by the Research Ethics Committee of Tokyo Medical University, and written informed consent was obtained from the parents of all infants.

  NIR-TRS system and analysis

Measurements were obtained using a portable NIR

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TRS system (TRS

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20, Hamamatsu Photonics K.K., Shi- zuoka, Japan) employing the TCSPC method to obtain a temporal profile of the detected photons. This system features improved optical sensitivity compared with the TRS

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10 system ⁹⁾¹⁰⁾ employing a GaAs photocathode pho- tomultiplier tube (H7422P

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50MOD, Hamamatsu Photon-

ics K.K.), with a quantum efficiency above 12% at approximately 800 nm. The TRS

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20 is computer

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con- trolled through a digital input/output (I/O) interface, con- sisting of a 3

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wavelength (761, 801 and 834 nm) pico- second light pulser (PLP, Hamamatsu Photonics K.K.) as the light source, a photon

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counting head (composed of a fast

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response, highly sensitive photomultiplier tube and high speed amplifier) with a 9

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step optical attenuator for single photon detection, and signal processing circuits (which consisted of a constant fraction discriminator, time

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to

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amplitude converter, analog/digital (A/D) con- verter and histogram memory) for time

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resolved mea- surement. The PLP generates a light pulse with a pulse width of 100 ps, a pulse rate of 5 MHz and an average power of approximately 80 µW. Three PLPs emit light pulses sequentially, and the 3

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wavelength light pulses are guided into 1 illuminating optical fiber by a fiber coupler (NTT Advanced Technology Corporation, Tokyo, Japan). A grated index (GI)

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type single optical fiber with a numerical aperture (NA) of 0.25 and a core diam- eter of 200 µm was used for tissue irradiation. An opti- cal bundle fiber (Moritex Corporation, Tokyo, Japan) with an NA of 0.26 and a bundle diameter of 3 mm was used to collect diffuse light from the tissue ¹²⁾ for light detection.

To calculate the values of µ a , and μ’ s for the 3 wave- lengths, the re

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emission profiles observed at each mea- surement point were fitted into the photon diffusion equation proposed by Patterson et al ¹³⁾ using the non

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lin- ear least squares fitting method. Then, oxyHb and deoxyHb levels were calculated from the µ a of the 3 wavelengths (761, 801 and 834 nm) using the following equations :

µ a 761 nm =ε oxyHb 761 nm C oxyHb +ε deoxyHb 761 nm C deoxyHb +ε H2O 761 nm C H2O

µ a 801 nm =ε oxyHb 801 nm C oxyHb +ε deoxyHb 801 nm C deoxyHb +ε H2O 801

nm C H2O

µ a 834 nm =ε oxyHb 834 nm C oxyHb +ε deoxyHb 834 nm C deoxyHb +ε H2O 834 nm C H2O

where ε m λ nm is the molar extinction coefficient of the sub- stance m at wavelength λ, and C m is the concentration of the substance m. On the assumption that in the living body, light absorption in this wavelength occurs in oxyHb, deoxyHb and water, and that there is no other background absorption in the living body, we determined the TRS values for TRS HbO 2 and TRS deoxyHb with a tissue water concentration of 85% ¹⁴⁾¹⁵⁾ .

Cerebral total Hb (tHb) level, cerebral oxygen satura- tion (cSO 2 ), CBV and cerebral fractional tissue oxygen extraction (FTOE) were obtained using the following equations ¹¹⁾¹⁶⁾ .

[tHb] (μM)=[oxyHb]+[deoxyHb]

cSO 2 (%)=[oxyHb]/[tHb]×100

CBV (mL/100 g)=[tHb]×MW Hb ×10

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⁶ /(tHb×10

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² ×Dt

×10) FTOE=(SpO 2 – cSO 2 )/SpO 2

where [ ] indicates the Hb level (µM), MW Hb is the molecular weight of Hb (64,500), tHb is the blood Hb level (g/dL), and Dt is the brain tissue density (1.05 g/

mL). The TRS

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20 was switched on for more than 20 min- utes before measurements were taken to stabilize the sys- tem. The optode with a distance of 30 mm between the irradiation fiber and the detection fiber was placed on the front head, and was covered with an opaque cloth to pre- vent stray light from reaching the detector. Measure- ments were taken in the reflectance mode 3

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6, 12, 24, 48 and 72 hours after birth. The conditions of infants were stable, and each measurement session lasted for more than 1 minute. If the measurement was affected by movement artifact or stray light, we took repeated mea- surements until we obtained reproducible data.

Measurements of other variables

Heart rate (HR), MABP and SpO 2 were monitored and recorded simultaneously with the NIRS measurement by a neonatal monitoring system (BSM

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2300 ; Nihon Kohden Corporation, Tokyo, Japan). MABP was mea- sured either directly with arterial lines or indirectly (oscillometric technique with an inflatable cuff : BSN

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2303 ; Nihon Kohden Corporation). HR and SpO 2

were continuously measured using a pulse oximeter (Nellcor Pulse Oximeter N

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200 ; Tyco Healthcare Japan, Tokyo, Japan). Blood gas (PCO 2 , blood Hb and Ht) levels were collected by a heel lance immediately after TRS

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20 measurements (ABL835 ; Radiometer K.K., Tokyo, Japan). The data were stored in a personal com- puter, and we calculated the median values over the mea- surement period.

Statistical analysis

Statistical analyses were performed using the computer package SPSS II for Windows (SPSS Japan, Tokyo, Japan). The gestational age (GA) and birth weight were expressed as means±standard deviation (SD). Serial data obtained using NIR

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TRS and physical examination at different time points were compared using repeated

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measures one

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way ANOVA, followed by Bonferroni multiple comparison tests. The Pearson correlation coefficient and simple linear regression analysis were used to determine the relationships among CBV, cSO 2 , MABP, PCO 2 and Ht level at each measurement point. A P value of less than 0.05 was considered to indicate a statistically significant difference.

Results

Cerebral complications were not diagnosed by cranial ultrasound examinations during the study period. Peri- ventricular leukomalacia diagnosed by magnetic reso- nance imaging developed in 1 infant before dis- charge. The clinical variables of the infants are shown in Table 1.

The mean CBV was 1.67±0.28 (standard deviation (SD)) mL/100 g during the study period. The mean cSO 2 was 71.1%±4.2% (SD) during the study period. 

Changes in CBV, cSO 2 , FTOE, MABP, HR, SpO 2 , PCO 2 , and blood Hb and Ht levels are shown in Table 2. CBV steadily decreased until 12 hours after birth and then gradually increased. There was a marked increase in CBV between 12 hours and 48, and 72 hours after birth. Similarly, cSO 2 decreased steadily until 12 hours after birth, followed by a gradual increase. The cSO 2

increased significantly between 3 to 6 hours and 48, and 72 hours, between 12 hours and 48, and 72 hours, between 24 hours and 48, and 72 hours after birth. 

Converse to CBV and cSO 2, FTOE increased steadily until 12 hours after birth, followed by a gradual decrease. 

There was a marked decrease in FTOE between 3 to 6 hours and 48, and 72 hours, between 12 hours and 48, and 72 hours, and between 24 hours and 48 hours after birth. There were marked changes in MABP, HR, SpO 2 , and blood Hb and Ht levels.

The MABP increased significantly between 3 to 6 hours and 48, and 72 hours after birth. The HR decreased significantly between 3 to 6 hours and 24, 48, and 72 hours after birth. SpO 2 showed a marked decrease between 12 hours and 48 hours after birth. 

There were marked decreases in blood Hb levels between

Table 1 Clinical data of 31 infant subjects Variable

Gestational age (w) 32±2 (28

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35)

Birth weight (g) 1695±427 (914

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2406)

Blood pH at birth 7.32±0.1

Male/female 13/18

Mechanical ventilation 17

Indomethacin 4

Mode of delivery (TV/CS) 10/21

  Values are presented as means (standard deviation [SD]) of number of cases

  VD, vaginal delivery ; CD, cesarean delivery

3 to 6 hours and 48, and 72 hours, and between 12 hours and 48, and 72 hours after birth. There were significant decreases in Ht level between 3 to 6 hours and 48, and 72 hours, between 12 hours and 48, and 72 hours after birth. There was no significant change in PCO 2 .

The correlations between CBV and other variables are shown in Table 3. There were significant correlations between CBV and cSO 2 3

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6 hours (P<0.05, r=0.38), 12 hours (P<0.01, r=0.62) and 24 hours (P<0.05, r=0.36) after birth. There was a significant inverse correlation between CBV and FTOE 12 hours (P<0.01, r=−0.58) after birth. Analysis of the correlation between cSO 2

and FTOE was not appropriate as FTOE was derived from cSO 2 . There was a significant inverse correlation between CBV and Ht 3

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6 hours (P<0.01, r=−0.49), 48 hours (P<0.01, r=−0.51) and 72 hours (P<0.05, r=

−0.38) after birth. Analysis of correlations among CBV and [tHb] and blood Hb levels was not appropriate as CBV was derived from [tHb] and blood Hb lev- els. There were no correlations between CBV and PCO 2 , or between CBV and MABP.

Discussion

We set out to evaluate the time course changes in CBV

of preterm infants by NIR

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TRS and clarified their associ- ation with cerebral oxygen metabolism, PCO 2 , MABP and Ht levels during the first 3 postnatal days. There have been several studies of CBV in neonates by NIRS using oxyHb ³⁾⁴⁾ or ICG ⁸⁾ as a tracer. The estimated CBVs were 2.22±0.4 and 3.7 mL/100 g using the modi- fied Beer

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Lambert law, with changes in arterial satura- tion ³⁾ and PCO 2 4) , respectively. Leung et al ⁸⁾ reported an estimated CBV of 1.72±0.76 mL/100 g as determined by NIR

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SRS with ICG. Ijichi et al ¹¹⁾ reported an absolute CBV of 2.31±0.56 mL/100 g as determined by NIR

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TRS in neonates (mean GA : 36.8±3.1 (SD) wks, mean BW : 2,365±791 g (SD)). These results were higher than those of the present study (1.67±0.28 (SD) mL/100 g). It has been reported that CBV increases with postcon- ceptional age, and that the relationship between these variables was based on the results of anatomic studies of the development of cerebral blood vessels ¹¹⁾¹⁷⁾ . Further- more, it has been reported that the CBV in human adults was 4.81±0.37 mL/100 g using single

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photon emission computed tomography ¹⁸⁾ , and 4.7±1.1 mL/100 g using positron emission tomography ¹⁹⁾ , which were higher than those in neonates. Wyatt et al ³⁾ speculated that regional Table 2 Measurement results

3

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6 h 12 h 24 h 48 h 72 h P value

CBV (ml/100 g) 1.61±0.30 1.54±0.27 1.62±0.25 1.78±0.22 1.80±0.26 < 0.01

cSO

2

(%) 70.1±4.1 70.0±5.3 69.9±3.4 73.4±2.9 73.0±2.9 < 0.01

FTOE 0.28±0.05 0.30±0.06 0.28±0.04 0.24±0.03 0.25±0.03 < 0.01

MABP (mmHg) 38.4±6.3 40.1±5.1 39.8±7.8 43.0±6 43.3±6.3 < 0.01

HR (/min) 142±16 136±12 132±11 132±10 133±12 < 0.01

SpO

2

(%) 98 (98

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99) 98 (97

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100) 98 (96

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99) 97 (95

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99) 98 (97

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98) 0.03

PCO

2

(mm Hg) 41.3±10.2 39.7±8.3 36.8±6.9 40.1±5.3 41.6±5.2 0.09

Hb (g/dl) 18.2±1.7 18.4±2.0 17.5±2.0 16.6±1.9 16.6±1.8 < 0.01

Ht (%) 55.4±5.1 56.1±6.0 53.4±6.1 50.7±5.8 50.8±5.3 < 0.01

Values are presented as means±standard deviation [SD]. Data for SpO

2

are presented as medians (interquartile range [IQR]).

CBV : cerebral blood volume ; cSO

2

: cerebral oxygen saturation ; FTOE : fractional regional cerebral oxygen extraction ; MABP : mean arterial blood pressure ; HR : heart rate ; Hb : blood hemoglobin ; Ht : hematocrit

Statistical values were generated by one

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factor repeated measures ANOVA. Details of analyses performed using the Bonferroni multiple comparison test are described in the text.

Table 3 Correlations between CBV and other variables

V ariable 3

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6 h 12 h 24 h 48 h 72 h

MABP P > 0.05 P > 0.05 P > 0.05 P > 0.05 P > 0.05 PCO

2

P > 0.05 P > 0.05 P > 0.05 P > 0.05 P > 0.05

Ht P < 0.01

r = −0.49 P > 0.05 P > 0.05 P < 0.01

r = −0.51 P < 0.05 r = −0.38 FTOE P > 0.05 P < 0.01

r = −0.58 P > 0.05 P > 0.05 P > 0.05 cSO

2

P < 0.05

r = 0.38 P < 0.01

r = 0.62 P < 0.05

r = 0.36 P > 0.05 P > 0.05

  r = Pearson correlation coefficient

CBV was lower in the white matter than in the gray cere- bral matter, and the relatively low mean CBVs in infants may reflect a relative preponderance of the white matter compared with the adult brain. These hypotheses sup- port the current results, as the mean GA in this study (32 wks) was shorter than that of a study using NIR

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TRS (36.8 wks) ¹¹⁾ . The different time window of measure- ments may also have influenced these results, because CBV measurements by NIRS using oxyHb ³⁾⁴⁾ and ICG ⁸⁾ as a tracer were higher than the current results, despite the immaturities noted (mean GA : 29 wks ³⁾⁴⁾ and 28 wks ⁸⁾ ).

Changes in CBV mainly represent alterations in cere- bral Hb levels, which may be influenced by CBF. In this study, CBV gradually decreased until 12 hours from birth. We previously reported a relationship between systemic circulation and cerebral circulation by echocar- diography and NIR

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SRS in extremely low birth weight (ELBW) infants during the first 3 days after birth ²⁰⁾ which demonstrated that the tissue oxygenation index (TOI) values that represented CBF with stable blood Hb and SpO 2 levels ²¹⁾²²⁾ decreased until 12 hours and then increased gradually. The changing pattern of the CBV in the present study was similar to that of the TOI in our previous study. We also demonstrated in our previous report that the changing pattern of TOI was similar to that of systemic perfusion in terms of left ventricle car- diac output and superior vena cava flow. We proposed that the changes in cerebral oxygenation and blood flow immediately after birth were likely to reflect low cardiac output because of the limited capacity of the immature myocardium to adapt to perinatal circulatory change.

It has been said that PCO 2 is important factors that affect CBF. Cerebrovascular resistance decreases with an increase in PCO 2 23)

. CBF measurements using the Xenon clearance technique have indicated that an increase in postnatal age correlates with changes in PCO 2 2) . However, several other reports have failed to demonstrate a relation between CBF and PCO 2 5)7) . In the present study, there was no correlation between CBV and PCO 2 . While a report by Pryds and Greisen ²⁾ showed a correlation between CBV and PCO 2 , the mean PCO 2 levels were (4.0 (30), 4.6 (34.5) and 4.4 (33) kPa (mm Hg) on days 1, 2 and 3, respectively), which were lower than the present results (mean : 39.9±7.5 (SD) mm Hg). This may explain why PCO 2 did not affect cerebrovascular resistance at approximately 40 mm Hg in the present study.

The Ht level increased until 12 hours after birth, and then gradually decreased. This changing pattern of Ht was inversely correlated to that of CBV, and we found significant inverse correlations between these vari- ables. The current results are supported by a study which demonstrated a significant inverse correlation

between CBF and arterial blood Hb concentration ²⁾ , or Ht level ²⁴⁾ using the Xenon clearance technique. Although both arterial oxygen content and blood viscosity have been reportedly related to CBF ²⁵⁾ , it has been suggested that CBF increased mainly as a compensatory mecha- nism for the lower oxygen

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carrying capacity to maintain constant oxygen delivery ^2)24)26) .

In the present study, we showed an inversely changing pattern in CBV and FTOE, and found a significant nega- tive correlation between these variables 12 hours after birth.

Cerebral fractional oxygen extraction (FOE) is a use- ful measurement variable which represents the ratio of cerebral oxygen consumption to cerebral oxygen deliv- ery ²⁷⁾ . Naulaes et al ¹⁶⁾ showed a close correlation between the FTOE measured by NIRS and the actual FOE in piglets and concluded that FTOE is likely to pro- vide important information on the oxygenation status of the brain. An increase in FTOE reflects an increase in oxygen extraction by brain tissue, suggesting a higher consumption of oxygen than delivery and a decrease in FTOE indicates less utilization of oxygen by brain tissue compared with oxygen supply. There have been several reports of a relationship between blood Hb level and FTOE. Van Hoften et al ²⁸⁾ found that blood transfusion led to a decrease in FTOE, which indicated that if the blood Hb level decreased, FTOE would increase as a compensatory mechanism to maintain cerebral tissue oxygenation. However, in the present report, although the blood Hb level decreased, FTOE continued to decrease concurrently with an increase in CBV after birth. These results suggest that any increase in CBV which occurs as a result of an increase in CBF depends not only on a change in Ht level as described above, but also on other variable changes as adaptations from fetal to extrauterine life. Meek et al ⁵⁾ and Kissack et al ⁶⁾⁷⁾ showed an increase in CBF during the first 3 days of life of ELBW infants, and proposed that this change may be a normal adaptive response of the cerebral circulation to postnatal life. We speculate that an increase in oxygen delivery via increased CBF as an adaptive response exceeds a decrease in oxygen delivery via decreased blood Hb level. As a result of increased CBF, sufficient oxygen is delivered to the brain, possibly causing FTOE to decrease.

The relationship between cerebral perfusion and arte-

rial blood pressure is controversial. Tsuji et al ²⁹⁾

reported that in preterm neonates, blood pressure and

cerebral oxygenation index (oxyHb level

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deoxyHb

level), which possibly reflects CBF, have a significant

association, which indicates an absence of cerebral auto-

regulation in some preterm infants. In this study, we

found no correlation between CBV and MABP. This

result suggests that the autoregulation of cerebral circula-

tion was intact in the subjects in our cohort. However, as the number of patients was small, the results should be interpreted cautiously, and further studies are required.

The change in cSO 2 is determined mainly by changes in blood Hb level, SpO 2, CBF, the cerebral metabolic rate of oxygen utilization and the arterial and venous anatom- ical ratio. For this reason, it has been considered that a change in cSO 2 may reflect a change in CBF among infants with stable blood Hb and SpO 2 levels ²¹⁾²²⁾ . How- ever, in the present study, although we demonstrated similar changing patterns in CBV and cSO 2, a significant correlation between these variables was not shown 48 hours after birth. This may be because the drastic changes in FTOE and blood Hb levels, which influence cerebral hemodynamics during the immediate postnatal period, affected these relationships.

There were some limitations in this study. The num- ber of patients of this cohort was small, and there were patients with various circulatory conditions. It has been considered that respiratory distress syndrome, surfactant therapy and mechanical ventilation influence cerebral hemodynamics ³⁰⁾³¹⁾ . However, these conditions were not investigated in the present study. Furthermore, although the sensitivity and the reliability of this NIR

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TRS system have previously been assessed using a piglet hypoxia model ³²⁾ , there have been few reports regarding the cerebral perfusion of human neonates, and further studies are required.

In conclusion, we evaluated changes in cerebral perfu- sion in preterm infants during the immediate postnatal period using a newly developed portable NIR

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TRS sys- tem without any invasive procedures. CBV showed a significant increase, and CBV changes may be related to changes in CBF, the cerebral metabolic rate of oxygen utilization, and Ht level. Serial measurements of these parameters at bedside using a portable NIR

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TRS system may be useful for evaluating postnatal changes in CBV and the cerebral metabolism of preterm infants in an intensive care unit.

Acknowledgments

We would like to thank Motoki Oda (Central Research Laboratory, Hamamatsu Photonics K.K.) for his techni- cal assistance, and the nursing staff in the NICU of Tokyo Medical University Hospital for their coopera- tion. We are also indebted to Mr. Roderick J. Turner, Assistant Professor Edward F. Barroga and Professor J.

Patrick Barron, Chairman of the Department of Interna- tional Medical Communications at Tokyo Medical Uni- versity, for their editorial review of the English manu- script.

Conflict of interest

 All authors declare no conflicts of interest associated

with this study. There was no external financial support received for this study.

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近赤外時間分解分光装置を用いた早産児における生後 3 日間の 脳血液量の経時的評価

藤　岡　泰　生　　　高　見　　　剛　　　石　井　宏　樹 菅　波　佑　介　　　水　書　教　雄　　　近　藤　　　敦

春　原　大　介　　　星　加　明　德

東京医科大学小児科学講座

 【目的】 移動式

3

波長近赤外時間分解分光法システム （NIR^-

TRS ; near

^-

infrared time

^-

resolved spectroscopy）

を用い た、早産児における生後

3

日間の脳血液量 （CBV

; cerebral blood volume）

の経時的変化の評価及び、CBVと脳組織 酸素代謝、血中二酸化炭素分圧 （PCO

2

）、平均血圧との関連性の検討を目的とした。【対象および方法】 対象は在胎 週数

28

^-

35

週の早産児

31

例。NIR^-

TRS

のオプトードを前額部に設置し、生後

3

^-

6、12、24、48、72

時間において

CBV、脳組織ヘモグロビン酸素飽和度

（cSO

2

）、脳組織

fractional tissue oxygen extraction

（FTOE）を計測した。NIR^-

TRS

計測と同時に、平均血圧、PCO

2

、ヘマトクリット （Ht）を測定した。【結果】 CBVと

cSO 2

は生後

12

時間に一 過性に低下し、その後、72時間にかけ有意な上昇を示した （P < 0.01）

のに対し、FTOE

は生後

12

時間に一過性に上 昇し、その後、有意な低下 （P < 0.01）

を示した。CBV

と

cSO 2

の間に生後

3

^-

6

時間 （P < 0.05、r=0.38）、12時間 （P

< 0.01、 r=0.62）、 24

時間 （P < 0.05、

r=0.36）において有意な正の相関を認めた。CBV

と

FTOE

の間に生後

12

時間 （P

< 0.01、r=−0.58）において有意な負の相関を認めた。CBV

と

Ht

の間に生後

3

^-

6

時間 （P < 0.01、r=−0.49）、48時 間 （P < 0.01、r=−0.51）、72時間 （P < 0.01、r=−0.38）

において有意な負の相関を認めた。CBV

と

PCO 2

、平均血圧 の間に有意な相関は認めなかった。【結語】 本研究により早産児における生後

3

日間の

CBV

の変化は脳における酸 素摂取率や血中

Ht

に影響を受ける可能性が示唆された。

〈キーワード〉 脳血液量 （CBV）、脳組織ヘモグロビン酸素飽和度 （cSO

2

）、

FTOE、近赤外時間分解分光法

（NIR^-

TRS）、

早産児