Research Papers: Sensing

Examiner’s finger-mounted fetal tissue oximetry

[+] Author Affiliations
Naohiro Kanayama

Hamamatsu University School of Medicine, Department of Obstetrics and Gynecology, Hamamatsu 431-3192 Japan

Masatsugu Niwayama

Shizuoka University, Department of Electrical and Electronics Engineering, Hamamatsu 431-3192 Japan

Shizuoka University, Research Institute of Electronics, Hamamatsu 431-3192 Japan

J. Biomed. Opt. 19(6), 067008 (Jun 24, 2014). doi:10.1117/1.JBO.19.6.067008
History: Received November 5, 2013; Revised May 13, 2014; Accepted May 16, 2014
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Abstract.  The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor’s finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO2) with the new tissue oximeter. Neonatal StO2 was measured at any position of the head regardless of amount of hair. Neonatal StO2 was found to be around 77%. Fetal StO2 was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO2 without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO2 in any condition of the fetus.

Figures in this Article

Fetal heart rate (FHR) monitoring is a popular worldwide method to evaluate the condition of the fetus. The best approach to diagnose the fetal condition is to measure the fetal blood pressure and oxygen status, which at the moment, cannot be achieved noninvasively. The FHR is the gold standard in evaluating the fetal condition, however, the FHR monitoring has shown low false-negative and high-false positive rates. Thus, obstetricians have attempted to measure the fetal oxygen status instead of or in addition to the FHR monitoring. As a result, there have been many reports on the development and clinical trials of the fetal pulse oximetry.

The pulse oximetry enables us to determine the degree of oxygen saturation both noninvasively and continuously by measuring pulsating wave absorbance in the peripheral tissues, such as fingertips. Some researchers have reported that the oxygen dynamics can be measured over the course of delivery using a pulse oximetry probe applied transvaginally to the fetal head.13 Moreover, the intravaginal optical probe for tissue oximetry using the near-infrared spectroscopy (NIRS) has been developed.4,5 However, the sensor volume of 4cm3 (diameter 1 cm, length 5 cm) was too large to apply during delivery. The dimensions of the commercially available small optical probes for the brain (NIRO-200NX, Hamamatsu Photonics, Hamamatsu, Japan) and the muscle (Hb-14, ASTEM, Kawasaki, Japan) were 1×3×0.5cm (width, length, and thickness). The sensors’ volume of 1.5cm3 was too large for monitoring the fetus directly. Additionally, the significantly low data capturing rate is one of the biggest drawbacks to these procedures. East et al. have reported that during the active phase of labor, every method has a significant rate of signal loss and the loss of sensor contact occurred up to 64% of time with oximetry.6 Another drawback of this transvaginal procedure is that the probe often moves away from the fetal head during delivery, which may lead to an intrauterine infection caused by rupture of the gestational sac. Furthermore, these methods are essentially invasive, as the probe is inserted into the uterine cervix only after the rupture of the gestational sac. In addition to these problems, many patients feel discomforted by the intravaginal sensor. Obstetricians also feel that there is interference with the cervical examination by the sensor. Although many clinical trials of the fetal pulse oximetry have been performed, its clinical usefulness has been controversial. Thus, there are no established methods for detecting the fetal hypoxia during parturition yet. At present, many obstetricians look forward to further improvement of oximetry and a better understanding of clinical management.

We changed the conventional placement of sensors to overcome those problems. We proposed an idea of moving the sensor attachment from the fetus to the examiner. Namely, we attached an NIRS probe to the doctor’s finger, instead of the fetal head or cheek. The obstetricians and midwives need to perform a cervical examination to understand the progress of delivery. They need to touch the fetal head to detect any cervical dilatation and the fetal position during delivery. Therefore, we hypothesized that if an NIRS probe was placed on the examiner’s finger pulp and the appropriate calculation algorithms on the near field of the light source were developed, we could obtain the fetal oxygen status noninvasively. With this concept, we succeeded in attaching an NIRS probe to the examiner’s finger pulp. Here, we report our intruments and preliminary clinical data.

An NIRS probe consists of near-infrared light emitting diodes (LEDs) and photodiodes. The source-detector distance was 4.0 cm in accordance with the Nelcore’s fetal pulse oximetry (Nellcor N-400 system), which has been used in many clinical trials. We considered that if the distance could be shortened to around 1 cm, it would be possible to place the sensor on the examiner’s finger. Our previous study showed that the strong signals of the arteries in the fetal scalp and brain surface were obtained at the point of 10 mm of the source-detector separation.7 Therefore, we thought that the miniaturized sensor would detect a fetal oxygenation signal by (1) deriving the calculation algorithm of the hemoglobin concentration satisfied in the near field of the light source, (2) blocking light propagation to the examiner’s finger to prevent it from mixing with the unwanted finger oxygenation, and (3) manufacturing an ultrathin optical probe which fits to the finger pulp. Fortunately, we successfully developed a new small volume sensor with a polyimide-based flexible substrate. The wavelengths of the light sources were 770 and 810 nm, and sensitivity of the photodiodes (PD2501, Kyoto, Epitex) was high in the near-infrared band. The bare chips of the LEDs and photodiodes were mounted on the substrate with a wire bonding. The detectors were located 6 and 8 mm away from the LEDs in order to determine an absolute value of the hemoglobin concentration using the spatially resolved NIRS [Fig 1(a)], which was created based on a laboratory-made low noise instrument.

Graphic Jump LocationF1 :

Scheme (a) and photograph (b) of the oximeter probe attached to the examiner’s finger pulp. Flexible substrate mounted two LEDs and two photodiodes are adhered to a black rubber sheet.

We placed a 1-mm thick black rubber sheet between the optical probe and finger pulp to block the light scattered through the examiner’s finger. Then, the probe was fixed with an adhesive sheet on the black-colored finger sac. The optical elements integrated with a flexible cable (80-μm thick, 100-mm long) were connected to a soft shield cable on the examiner’s palm. A 1.5-m long shield line was connected to the microcomputer unit in the examiner’s breast pocket. In order to reduce external noise, the unit was battery powered and had a 2.4 GHz wireless module. The measured data were wirelessly transmitted into the computer. The trend of the hemoglobin concentration processed8 and calculated by the computer was shown on the screen in real time.

We prepared transparent vinyl gloves in collaboration with Utsunomiya Seisaku Co., Ltd. (Higashi Osaka-shi, Japan). The same amount of scattered light as without gloves was detected with the gloves. Figure 1(b) shows the examiner’s finger with the developed optical probe.

We examined the light propagation in the fetal head model. The simulation model consists of the fetal scalp, skull, cerebrospinal fluid (CSF), brain, optical block, and examiner’s finger. Table 1 shows the scattering coefficient, absorption coefficient, and thickness, which were set based on the literature data.911

Table Grahic Jump Location
Table 1Optical properties and thickness of each layer for Monte Carlo analysis.

The anisotropic factors for each layer were 0.95.12 The propagation of photons in the simulation was based on the transport theory with the Monte Carlo method. The model was divided into small cubes, and the optical path lengths in each cube were calculated to examine the measurement sensitivity. Figure 2 presents the sensitivity distribution obtained from the simulation results.

Graphic Jump LocationF2 :

Model for the Monte Carlo analysis and the sensitivity distribution obtained by the simulation.

The results suggest that the light propagated to the finger does not contribute to the detected light intensity. In the simulation, the absorption coefficient of the optical block attached to the finger was 10mm1. The optical absorber of the actual probe was easily realized because a typical colored adhesive tape has an absorption coefficient from 1 to 20mm1. The changes in spatial intensity slope were examined to reveal the measurement sensitivity for the brain and the scalp. The slope values of S0, Sbrain, and Sscalp represent an initial state (μa_brain=0.02mm1, μa_scalp=0.02mm1), a state where only the brain has changed (μa_brain=0.025mm1, μa_scalp=0.02mm1), and a state where only the scalp has changed (μa_brain=0.02mm1, μa_scalp=0.025mm1), respectively. The changes in slope were calculated as follows: ΔSbrain=SbrainS0 and ΔSscalp=SscalpS0. The sensitivity ratio was defined as ΔSbrain/ΔSscalp. The ratio became high due to an increase in the source-detector distance, as shown in Fig. 3. When the detectors were located 6 and 8 mm from the light source, the sensitivities for the brain and the scalp were comparable. If the hemoglobin concentration of the brain is higher than that of the scalp, the values of the oxygen saturation and blood volume would contain more information about the brain than the scalp. Although the long source-detector distance was preferable in order to focus on measuring the cerebral tissue, we adopted the length of the 6 and 8 mm pair, considering convenience due to the size reduction.

Graphic Jump LocationF3 :

Relationship between the brain-scalp sensitivity ratio and the pair of source-detector distances.

In this study, the hemoglobin concentrations of both brain and scalp were measured. Therefore, we simultaneously varied the values of μa_brain and μa_scalp from 0.00 to 0.05mm1. Then, we made a lookup table of the relationship between the value of μa and the spatial slope. In the measurement, the value of μa was calculated from the spatial slope of the measured light intensity using the lookup table. The following equations were used to calculate the concentrations of oxyhemoglobin [O2Hb] and deoxyhemoglobin [HHb]: Display Formula

[O2Hb]=εHbλ2μaλ1εHbλ1μaλ2εHbO2λ1εHbλ2εHbO2λ2εHbλ1,(1)
Display Formula
[HHb]=εHbO2λ2μaλ1εHbO2λ1μaλ2εHbO2λ1εHbλ2εHbO2λ2εHbλ1,(2)
where εHHbλ1,2 and εO2Hbλ1,2 are the extinction coefficients of HHb and O2Hb, respectively, at the wavelengths λ1 and λ2.13 Tissue oxygen saturation StO2 was calculated by [O2Hb]/([O2Hb]+[HHb]).

To determine whether our tissue oximetry obtained the fetal oxygenation, we measured StO2 of three just delivered newborns at first. All the neonates were born in spontaneous vaginal delivery from 39 to 40 weeks of gestation. The FHR monitored during labor showed a reassuring fetal status pattern in all cases. The Apgar scores of the neonates were 9, 9, 10 at 1 min and 10, 10, 10 at 5 min. We attached the probe on the front hair, parietal, and occiput of head just after delivery. Each measurement lasted at least 10 s.

Second, we measured fetal StO2 during labor, as shown in Fig. 4. We measured StO2 for one parturient at the first and the second stages of labor after the rupture of membranes. The parturient was in her 39th week of pregnancy. The course of delivery was normal. The probe was attached to the fetus head during delivery. We examined the results for 2 min during the first and second stages of labor. We continued the measurement for 10 min after delivery. Informed consent was obtained from the subjects, and all measurements were approved by the ethical committee of Hamamatsu University School of Medicine.

Graphic Jump LocationF4 :

Outlook of the measurement with an oximeter attached to the examiner’s finger during labor.

The StO2 values of the parietal region in the three newborns were 78.5±2.6%, 78.4±3.2%, and 75.8±2.3%, respectively. The values of front and occiput were similar to those of the parietal region in each newborn (data not shown). We could obtain the StO2 easily in any condition of the neonate head, such as wetness or color of the hair.

The intrapartum fetal StO2 was detected through the whole delivery (Fig. 5).

Graphic Jump LocationF5 :

The actual chart of the fetal StO2 during labor. Left and right parts correspond to the first and the second stages of labor, respectively. UC denotes uterine contraction.

The fetal StO2 was detected even during labor pains and the bearing down effort. We obtained the StO2 data smoothly and quickly. The doctor got the fetal StO2 as well as the cervical findings at the same time. Furthermore, the patient felt neither pain nor discomfort during the measurement. The fetal StO2 in the first stage of labor was about 70% without labor pains and about 60% in a presence of labor pains. In the second stage of labor, the fetal SpO2 was 60% without labor pains, and it decreased during labor pains and the bearing down effort. The lowest level of the fetal StO2 was around 30%. After delivery, the neonate StO2 increased rapidly up to 70%.

All previous oximeter sensors were attached to the fetus. We have recognized the accidental possibility of the movement of the sensor and its slip during labor. Poor data capture was observed in some pregnant women due to the detachment of the sensor caused by frequent changes of the body position during labor.

Our oximetry system is able to detect the fetal StO2 in the first and the second stages of labor very precisely regardless of the presence of labor pains. As the examiner can touch suitable sites during the internal examination, it is possible to measure the fetal StO2 very naturally. Our fetal StO2 measurements can be performed at the same time and in the same manner as obstetrical examinations during delivery. We recognized the fetal head promptly and obtained the fetal StO2 precisely, because the pressure for an ultrathin probe propagated to the finger and the finger pulp was very sensitive. Furthermore, our sensor never touches the fetus directly because the sensor is inside the transparent sterilized gloves. We think that our measurement system is safer and more noninvasive than the previous one. Moreover, the parturient does not feel discomfort during the measurement.

As for the clinical analysis, the fetal StO2 in the first stage of labor was about 70% without labor pains and about 60% in the presence of labor pains. The fetal oxygen saturation SpO2 with a pulse oximeter is 59±10% in the first stage of labor, and 53±10% in the second stage.2 The measurements of low saturation were estimated at 33% as two standard deviations below the mean. Since the decrease in arterial oxygenation rapidly results in low tissue oxygenation, the value of StO2 would be correlated to SpO2 strongly. Chipchase et al. have reported that the cerebral StO2 for a fetus was 59±12% using an optical fiber-based NIRS instrument.14 The oxygen saturation values in this study were the same or slightly higher compared to the previous studies. One of the reasons would be that the value of StO2 was a mixed measurement of the scalp and the brain. If the sensitivity of the scalp was suppressed by using a long separation probe, the values may be close to the cerebral oxygen saturation values previously reported. The comparison of results suggests that our new concept of oximetry could be applicable to clinical practice.

In this study, there was no caput succedaneum in the fetal head. When the thickness of the caput succedaneum layer is thick, the cerebral sensitivity (the ratio of ΔSbrain/ΔSscalp) would decrease. In the future, we may solve the problem of the swelling layer by squeezing the subcutaneous fluid and by measuring the surface layer thickness with an ultrasound apparatus.

As for neonatal monitoring, the values of cerebral StO2 for a child and a neonate have been reported to range from 65% to 85%15 and from 67% to 80%,16,17 respectively. The oxygen saturation values in this study (75%–78%) were similar to that reported in the literature.

Fouzas et al. described that SpO2 with a pulse oximeter might not be measured or might be inaccurate in low-perfusion states, such as low cardiac output, shock, hypothermia, vasoconstriction, and arterial occlusion.18 They also stated that a continuous oxygen saturation monitoring is essentially needed for the safety of the newborn. Rapid measurements of several sites of StO2 are needed in the case of neonatal asphyxia. But the commercially available sensor is set on one site of the skin of the neonate. Our sensor can be set on any site of the newborn where doctors want to measure. In addition, the spatially resolved NIRS system can detect the tissue oxygenation in a low-perfusion condition, because the StO2 measurements require only the spatial intensity slope and do not require the weak pulsation signals on a pulse oximetry. Our system could be useful in practice for such cases. To assure the usefulness of this oximetry, we must accumulate more data. At the moment, we are planning a multicenter study to confirm the usefulness of our system.

In conclusion, we developed an oximeter with the sensors attached to the fingers of an obstetrician or a midwife, in contrast to conventional oximeters whose sensors were attached to the fetus. We successfully detected the fetal oxygenation smoothly and certainly. We are sure that our system could become a new fetal monitoring approach.

We would like to thank Mr. Hikaru Suzuki, CEO of ASTEM Co., Ltd. (Kawasaki, Japan) for general advice in development of the instruments.

van Oudgaarden  E., Johnson  N., “Clinical value of antenatal fetal pulse oximetry,” J. Perinat. Med.. 22, (4 ), 295 –300 (1994). 0300-5577 CrossRef
Dildy  G. A. et al., “Intrapartum fetal pulse oximetry: fetal oxygen saturation trends during labor and relation to delivery outcome,” Am. J. Obstet. Gynecol.. 171, (3 ), 679 –684 (1994). 0002-9378 CrossRef
Dildy  G. A., “Fetal pulse oximetry,” Clin. Obstet. Gynecol.. 54, (1 ), 66 –73 (2011). 0009-9201 CrossRef
Aldrich  C. J. et al., “Fetal cerebral oxygenation measured by near-infrared spectroscopy shortly before birth and acid-base status at birth,” Obstet. Gynecol.. 84, (5 ), 861 –866 (1994). 0029-7844 
Schmidt  S., “Laserspectroscopy in the fetus during labour,” Eur. J. Obstet. Gynecol. Reprod. Biol.. 110, (Suppl 1 ), S127 –S131 (2003). 0301-2115 CrossRef
East  C. E. et al., “Fetal pulse oximetry for fetal assessment in labour,” Cochrane. Database Syst. Rev.. 2, , CD004075  (2007). 1469-493X 
Stuban  N., Niwayama  M., Santha  H., “Phantom with pulsatile arteries to investigate the influence of blood vessel depth on pulse oximeter signal strength,” Sensors (Basel). 12, (12 ), 895 –904 (2012). 1424-8220 CrossRef
Niwayama  M. et al., “Noncontact measurement of deep tissue absorption coefficient using spatially resolved near-infrared spectroscopy,” IEEJ T. Electr. Electron. Eng.. 2, (4 ), 485 –487 (2007). 1931-4973 CrossRef
Simpson  C. R. et al., “Near-infrared optical properties of ex vivo human skin and subcutaneous tissues measured using the Monte Carlo inversion technique,” Phys. Med. Biol.. 43, (9 ), 2465 –2478 (1998). 0031-9155 CrossRef
Firbank  M. et al., “Measurement of the optical properties of the skull in the wavelength range 650–950 nm,” Phys. Med. Biol.. 38, (4 ), 503 –510 (1993). 0031-9155 CrossRef
Yaroslavsky  A. N. et al., “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.. 47, (12 ), 2059 –2073 (2002). 0031-9155 CrossRef
Cheong  W. F., Prahl  S. A., Welch  A. J., “A review of the optical-properties of biological tissues,” IEEE J. Quant. Electron.. 26, (12 ), 2166 –2185 (1990). 0018-9197 CrossRef
Matcher  S. J. et al., “Performance comparison of several published tissue near-infrared spectroscopy algorithms,” Anal. Biochem.. 227, (1 ), 54 –68 (1995). 0003-2697 CrossRef
Chipchase  J. et al., “Cerebral hemoglobin concentration and oxygen saturation measured by intensity modulated optical spectroscopy in the human fetus during labor,” J. Perinat. Med.. 30, (6 ), 502 –509 (2002). 0300-5577 CrossRef
Quaresima  V. et al., “Noninvasive measurement of cerebral hemoglobin oxygen saturation using two near infrared spectroscopy approaches,” J. Biomed. Opt.. 5, (2 ), 201 –205 (2000). 1083-3668 CrossRef
Naulaers  G. et al., “Cerebral tissue oxygenation index in very premature infants,” Arch. Dis. Child Fetal Neonatal Ed.. 87, (3 ), F189 –F192 (2002). 1359-2998 CrossRef
Pichler  G. et al., “Reference ranges for regional cerebral tissue oxygen saturation and fractional oxygen extraction in neonates during immediate transition after birth,” J. Pediatr.. 163, (6 ), 1558 –1563 (2013). 0044-2917 CrossRef
Fouzas  S., Priftis  K. N., Anthoracopoulos  M. B., “Pulse oximetry in pediatric practice,” Pediatrics. 128, (4 ), 740 –752 (2011). 0031-4005 CrossRef

Naohiro Kanayama received his PhD degree from Hamamatsu University School of Medicine in 1980 and he has been a professor (chairman) of the Department of Obstetrics and Gynecology in Hamamatsu University School of Medicine since 1999. His major research interests include obstetrical disseminated intravascular coagulation (DIC), preterm delivery, mechanism of cervical maturation, infrared spectroscopy for fetal monitoring, and photodynamic therapy.

Masatsugu Niwayama received the PhD degree in biomedical engineering from Hokkaido University, Sapporo, Japan, in 2001. He is currently an associate professor in the Department of Electrical and Electronic Engineering, Shizuoka University, Hamamatsu, Japan. His current research interests include development of accurate and convenient NIRS systems.

© The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Citation

Naohiro Kanayama and Masatsugu Niwayama
"Examiner’s finger-mounted fetal tissue oximetry", J. Biomed. Opt. 19(6), 067008 (Jun 24, 2014). ; http://dx.doi.org/10.1117/1.JBO.19.6.067008


Figures

Graphic Jump LocationF1 :

Scheme (a) and photograph (b) of the oximeter probe attached to the examiner’s finger pulp. Flexible substrate mounted two LEDs and two photodiodes are adhered to a black rubber sheet.

Graphic Jump LocationF2 :

Model for the Monte Carlo analysis and the sensitivity distribution obtained by the simulation.

Graphic Jump LocationF3 :

Relationship between the brain-scalp sensitivity ratio and the pair of source-detector distances.

Graphic Jump LocationF4 :

Outlook of the measurement with an oximeter attached to the examiner’s finger during labor.

Graphic Jump LocationF5 :

The actual chart of the fetal StO2 during labor. Left and right parts correspond to the first and the second stages of labor, respectively. UC denotes uterine contraction.

Tables

Table Grahic Jump Location
Table 1Optical properties and thickness of each layer for Monte Carlo analysis.

References

van Oudgaarden  E., Johnson  N., “Clinical value of antenatal fetal pulse oximetry,” J. Perinat. Med.. 22, (4 ), 295 –300 (1994). 0300-5577 CrossRef
Dildy  G. A. et al., “Intrapartum fetal pulse oximetry: fetal oxygen saturation trends during labor and relation to delivery outcome,” Am. J. Obstet. Gynecol.. 171, (3 ), 679 –684 (1994). 0002-9378 CrossRef
Dildy  G. A., “Fetal pulse oximetry,” Clin. Obstet. Gynecol.. 54, (1 ), 66 –73 (2011). 0009-9201 CrossRef
Aldrich  C. J. et al., “Fetal cerebral oxygenation measured by near-infrared spectroscopy shortly before birth and acid-base status at birth,” Obstet. Gynecol.. 84, (5 ), 861 –866 (1994). 0029-7844 
Schmidt  S., “Laserspectroscopy in the fetus during labour,” Eur. J. Obstet. Gynecol. Reprod. Biol.. 110, (Suppl 1 ), S127 –S131 (2003). 0301-2115 CrossRef
East  C. E. et al., “Fetal pulse oximetry for fetal assessment in labour,” Cochrane. Database Syst. Rev.. 2, , CD004075  (2007). 1469-493X 
Stuban  N., Niwayama  M., Santha  H., “Phantom with pulsatile arteries to investigate the influence of blood vessel depth on pulse oximeter signal strength,” Sensors (Basel). 12, (12 ), 895 –904 (2012). 1424-8220 CrossRef
Niwayama  M. et al., “Noncontact measurement of deep tissue absorption coefficient using spatially resolved near-infrared spectroscopy,” IEEJ T. Electr. Electron. Eng.. 2, (4 ), 485 –487 (2007). 1931-4973 CrossRef
Simpson  C. R. et al., “Near-infrared optical properties of ex vivo human skin and subcutaneous tissues measured using the Monte Carlo inversion technique,” Phys. Med. Biol.. 43, (9 ), 2465 –2478 (1998). 0031-9155 CrossRef
Firbank  M. et al., “Measurement of the optical properties of the skull in the wavelength range 650–950 nm,” Phys. Med. Biol.. 38, (4 ), 503 –510 (1993). 0031-9155 CrossRef
Yaroslavsky  A. N. et al., “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.. 47, (12 ), 2059 –2073 (2002). 0031-9155 CrossRef
Cheong  W. F., Prahl  S. A., Welch  A. J., “A review of the optical-properties of biological tissues,” IEEE J. Quant. Electron.. 26, (12 ), 2166 –2185 (1990). 0018-9197 CrossRef
Matcher  S. J. et al., “Performance comparison of several published tissue near-infrared spectroscopy algorithms,” Anal. Biochem.. 227, (1 ), 54 –68 (1995). 0003-2697 CrossRef
Chipchase  J. et al., “Cerebral hemoglobin concentration and oxygen saturation measured by intensity modulated optical spectroscopy in the human fetus during labor,” J. Perinat. Med.. 30, (6 ), 502 –509 (2002). 0300-5577 CrossRef
Quaresima  V. et al., “Noninvasive measurement of cerebral hemoglobin oxygen saturation using two near infrared spectroscopy approaches,” J. Biomed. Opt.. 5, (2 ), 201 –205 (2000). 1083-3668 CrossRef
Naulaers  G. et al., “Cerebral tissue oxygenation index in very premature infants,” Arch. Dis. Child Fetal Neonatal Ed.. 87, (3 ), F189 –F192 (2002). 1359-2998 CrossRef
Pichler  G. et al., “Reference ranges for regional cerebral tissue oxygen saturation and fractional oxygen extraction in neonates during immediate transition after birth,” J. Pediatr.. 163, (6 ), 1558 –1563 (2013). 0044-2917 CrossRef
Fouzas  S., Priftis  K. N., Anthoracopoulos  M. B., “Pulse oximetry in pediatric practice,” Pediatrics. 128, (4 ), 740 –752 (2011). 0031-4005 CrossRef

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