Laser spectrophotometry in the fetus

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Schmidt et al, Laser spectrophotometry in the fetus

Short communications

J. Perinat. Med. 17 (1989) 57

Laser spectrophotometry in the fetus Stephan Schmidt1, Allmuth Lenz1, Helge Eilers1, Niels Helledie2, and Dieter Krebs1 Women's Hospital University of Bonn, Bonn, West Germany, and 2Radiometer, Copenhagen, Danmark

1 Introduction While cardiotocography is widely accepted as the basic method of fetal monitoring, it has obvious shortcomings by giving false positive indications of fetal distress in cases where by the fetus blood sampling (FBA) unnecessary operative deliveries are avoided. This technique has the disadvantage of being a single point test and therefore it often has to be repeated at short intervals. It is judged to be too cumbersome for clinical routine [7]. Thus a continous record of a biochemical indicator of fetal distress is preferable. While a number of techniques for such measurements (TpH, tcPo2, tcPco2) have been proposed, the newly developed monitor for laser spectrophotometry in the fetus is of special interest as it provides information about biochemical parameters in a noninvasive and approximatively continuous way [2, 4, 6]. In this article we report on laserspectrophotometry in the near-infrared range [5]. The configuration of the measuring system aimes at the calculation of both the intracellular redoxstate and relative changes of blood volume. Observations during application of the system on a fetus give a first impression of the method's potential. 2 Method The Radiometer prototype that was used comprises a Hewlett Packard personal computer interconnected with a near-infrared data collection unit (NIRDCU). The NIRDCU includes a transmitter board with four laser diodes, wavelengths 775 nm, 805 nm, 845 nm and 904 nm as well as a microcomputer board with power supply. Additionally a receiver module with an optical receiver, an amplifier and a converter is installed (figure 1). 1989 by Walter de Gruyter & Co. Berlin · New York

Figure 1. The near infrared measuring system for laser spectrophotometry in the fetus. 1 = fibrebundle for the conduction of laserlight intermittantly emitted by the laserdiodes (wavelength 775, 805, 845, 904 nm) 2 = fibrebundle for the conduction of reflected light as received by the fetal sensor 3 = near-infrared data collection unit (NIRDCU) 4 = interconnected personal computer for data processing The system is constructed in accordance with the research published by Rea and coworkers [5]. The light of the laser diodes is conducted by means of optical fiberbundles to a prisma located in the sensor (figure 2). The reflected light is collected in a sensor and registered in the NIRDCU by means of photodiodes. Changes of the optical density in relation to the time are displayed on the monitor, while data are also stored for graphical processing. The first application of a near-infrared laser sensor was performed in a 20 year old I gravida 0 para. Informed consent was obtained during the first stage of labor a suspect heart rate pattern (variable decelerations) was recorded while the pH values

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Schmidt et al, Laser spectrophotometry in the fetus of fetal blood samples were in the normal range [6]. When at a dilatation of the cervix of 5 cm no further progress of labor occured, a caesarean section was indicated. The laser sensor was applied during the first stage of labor on the fetal head. The angle between the main beam of the laser light and the prisma of the photodiodes was adjusted during the measurement in order to achieve an optimal signal to noise ratio. 3 Results

Figure 2. Sensor for laser spectrophotometry in the fetus 1 = laserlight-conducting fibrebundle 2 = housing of the sensor incorporating on optical prisma 3 = optical window for the emission of laserlight

After application and adjustment of the laser sensor on the fetal head, we obtained optical signals adequate for calculating relative changes of saturated hemoglobin, reduced hemoglobin and exydized cytochrome aa3. Additionally -changes in blood volume were detected by changes of total hemoglobin. Figures 3 to 6 demonstrate the potential of spectrophotometry in the fetus as well as the remaining difficulties. As can be seen in all

FETUS Ox Cytochrome aa3 l.OOOE+01

-l.OOE+01

Time (min)

0

C:

10.0

Ox Cytaa3

Figure 3. Tracing of the cytochrome aa3 signal from the fetal head fetus. The arrow indicates readjustment of the sensor on the fetal head. J. Perinat. Med. 17 (1989)


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the NIRDCU curves adequate recordings are only achievable when the position of the sensor is optimal. Only after its readjustment are biochemical parameters detected with sufficient accuracy. The redox state of the fetal cells is indicated to be stable, shown by the curve of cytochrome aa3 (figure 3). On the other hand changes of hemoglobin concentrations are obvious (figure 4 and 5). Such alterations in the biologic sample seemed to be caused by relative changes of blood volume (figure 6).

4 Discussion

While the recording of photometric spectra in the fetus during labor may provide new information, the interpretation of such data should be based on an understanding of both the physical background of the measuring system and the background of the biological parameters [1], The basic aim of fetal monitoring during labor is to detect an intrauterine complication early enough to prevent serious depressions in cellular

function [3, 8]. Of special interest are irreversible changes of brain tissue that are highly dependent on adequate oxygen content [1]. Critical changes in cell metabolism of such cells can be detected by the redox state because 99% of energy production in neurocyts is mediated by cytochromes of the respiratory chain [2, 3]. The cytochromes are hemo-proteins in respiratory chain [2, 3]. The cytochromes are hemo-Proteins in which reversible Fe2+ - Fe3+ transitions occur. They are classified according to their absorbance spectra in the visible region of the spectrum. Cytochrome a, Ci, c and aa3 in the reduced condition have maximal absorbance at 563, 554, 550 and 605 nm; whereas in the oxidized condition their absorbance at these wavelengths is much less. It is possible to determine the redox state of any one of the cytochromes, expressed by the proportion reduced oxydized enzyme. This is achieved by measuring the absorbance of the sample at a wavelength corresponding to the absorbance maximum of the reduced form of the cytochrome concerned. In a mixture of cytochromes the redox state of one can be distinguished frpm those of the others by making measurements at several wavelengths [5].

FETUS Hb02 b l.OOOE+01

-l.OOE+01

0 A:

Time (min) Hb02

Figure 4. Tracing of saturated hemoglobin as detected by means of laserspectrophotometry. J. Perinat. Med. 17 (1989)

10.0

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Schmidt et al, Laser spectrophotometry in the fetus FETUS HbR b

l.OOOE+01

-l.OOE+01

0 D:

Time (min)

10.0

HbR

Figure 5. Tracing of reduced hemoglobin as detected by means of laserspectrophotometry. FETUS relative bloodvolume b l.OOOE+01

-l.OOE+01

0 B:

Time (min)

10.0

• r e l . bloodvol.

Figure 6. Relative changes of blood volume in the fetal head during laserspectrophotometry. Blood volume changes are calculated from data achieved at the isobestic point of hemoglobin. J. Perinat. Med. 17 (1989)

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Cytochrome aa3 by possessing copper centers absorbs light in the near-infrared range with a maximum at 830—845 nm. Relative changes in the concentration of oxydized cytochrome aa3 can be traced by means of laser spectrophotometry using a laser beam at 845 nm [5]. Blood volume alterations can be determined by near-infrared laser spectrophotometry at 805 nm which represents the isobestic wavelength for hemoglobin and is the basis for calculation of changes of total hemoglobin. The tracing of this parameter is of special interest for the perinatal period as changes in blood volume in the brain are supposed to be one major cause of cerebral hemorrhage. It should be pointed out, that as a result of our measurements we achieved only a detection of relative changes of the biological parameters. According to the Lambert-Beer equation it is a precondition of a quantitative analysis to know the length of a beam in the tissue. Theoretically a

mathematical model may provide an estimation. This may become a basis to calculate absolut values of biochemical concentrations in the tissue during measurements. Artefacts due to fetal and maternal movements may in the future have only minor effect on laser spectroscopic tracings when fetal application is optimized by means of specially designed sensors. Of special interest when a new technique is applied, is the accurrence of side effects of a given method. Laser diodes which have a relative high output power of 10 W are not used in a continouswave mode. Laser pulses with a maximum length of 200 ns with a repetition frequency of 500 Hz lead to a low optical output power of less than 4 mW. Additionally according to the Planck-Einstein relation, the photon energy in the near-infrared range is supposed to be low. In conclusion we might say that laser spectrophotometric monitors have the potential to become safe, low coast, and portable instruments for the noninvasive assessment of biochemical status of the fetus.

Summary

Laser spectrophotometry with near-infrared light is newly available for clinical application. The equipment consists of a near-infrared datacollection unit (NIRDCU) and apersonal computer. Emission of laser light at wavelengths of 775, 805, 845 and 904 nm is provided by the four laserdiodes of the NIRDCU. By analyzing changes of optical density during laser radiation, information is achieved about the intracellular redoxstate and relative changes of blood volume. During measurement with the system on fetal head we were able

to get a first impression of the methods potential. While the application of the laser sensors is still cumbersome, signals providing information of the relative changes of hemoglobine concentrations, relative changes of blood volume and cytochrome aa3 seem achievable. Laser spectrophotometric monitors may become save, low cost and portable instruments for the noninvasive assessment of the biochemical and biophysical status in the fetus.

Keywords: Acid base balance, fetal monitoring, laser spectrophotometry, near-infrared light (NIR).

Laserspektrophotometrie beim Feten

Die ersten Geräte zum klinischen Einsatz der Laserspektrophotometrie stehen jetzt zur Verfügung. Das von uns verwendete Gerät besteht aus einer Datenerfassungseinheit von Licht im nahinfraroten Bereich (NIRDCU) und einem Personal Computer. Die 4 Laserdioden der NIRDCU emittieren Licht der Wellenlängen 775, 805, 845 und 904 nm. Durch die Messung von Veränderungen in der optischen Dichte während der Lasereinstrahlung erhält man Informationen über den intrazellulären Redoxstatus und relative Blutvolumenschwankungen. Die ersten Eindrücke über die Möglichkeiten dieser Methode

erhielten wir durch die Messung auf dem Kopf eines Feten sub partu. Während die Handhabung der Lasersensoren noch problematisch ist, konnten Daten über Veränderungen der relativen Hämoglobinkonzentration, des relativen Blutvolumens und des Cytochrom aa3 gesammelt werden. Geräte zur Laserspektrophotometrie könnten sichere, kostengünstige und leicht zu transportierende Meßsysteme für die nichtinvasive Beurteilung des biochemischen und biophysikalischen Zustandes des Feten werden.

Schlüsselwörter: Fetale Überwachung, Laserspektrophotometrie, Nahinfrarotes Licht (NIR), Säure-Basen-Haushalt. J. Perinat. Med. 17 (1989)

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Resume Spectrophotometrie laser chez le foetus

La spectophotometrie laser par lumiere proche de 1'infrarouge est depuis peu utilisable en application clinique. L'equipement comprend une unite de traitement de lumiere proche de Pinfra-rouge (NIRDCU) et un ordinateur individuel. Les 4 diodes laser du NIRDCU assurent remission du rayons lasers de longeurs d'onde de 775, 805, 845 et de 904 nm. On obtient des informatiens sur Fequilibre redox intracellulaire et sur les modifications relatives du volume sanguin en analysant les modifications de densite optique au cours du rayonnement laser. Nous avons pü obtenir une premiere impression du

potentiel de la methode par des mesures en utilisant le Systeme au niveau de la tete foetale. Bien que Papplication de recepteurs lasers soit encore encombrante, il semble que soient atteignables des signaux fouraissant des informations sur les modifications relatives des concentrations d'hemoglobine, les changements du volume sanguin et du cytochrome aa3. Les apparails de Spectrophotometrie laser deviendront sürs, peu couteux et portables, ils permettront 1'exploration non invasible de l'etat biochimique et biophysique du foetus.

Mots-cles: Equilibre acido-basique, lumiere proche de l'infra-rouge (NIR), Spectrophotometrie laser, surveillance foetale.

References

[1] CHANCE B, GR WILLIAMS: Respiratory enzymes in oxidative phosphorylation. J of Biol Chem 217 (1955) 409 [2] JOBSIS FF: Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198 (1977) 1264 [3] JOBSIS FF: Oxidative metabolic efects of cerebral hypoxia. Adv Neurol 26 (1979) 299 [4] HUGH A, R HUGH, H SCHNEIDER, J PEABODY: Experience with transcutaneous Po2 monitoring of mother, fetus and newborn. J Perinat Med 8 (1980) 51 [5] REA PA, J CROWE, WICKRAMASINGHE, P ROLFE: Noninvasive optical methods for the study of cerebral metabolism in the human newborn: a technique for the future? J Med Eng Technol 9 (1985) 160

[6] SALING E: Pathophysiology, clinical relevance of continous measurement of pH and, or CO2 in the fetus. J Perinat Med 12 (1984) 234 [7] SCHMIDT S, E SALING: The continous measurement of transcutaneous carbondioxide (tcPco2), an atraumatic tool to verify fetal acidosis? Brit J Obstet Gynec 94 (1987) 963 [8] WEBER T: The validity of discontinous pH measurements on fetal blood and of CTG in predicting neonatal APGAR score. Dan Med Bull 26 (1979) 186 Received October 14, 1988. Accepted October 14, 1988. Prof. Dr. Stephan Schmidt Women's Hospital, University of Bonn Sigmund-Freud-Straße 25 D-5300 Bonn 1, West-Germany

J. Perinat. Med. 17 (1989)

Kirkinen et al, Paradoxical umbilical blood supply of an acardiac twin

J. Perinat. Med. 17 (1989) 63

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Documentation of paradoxical umbilical blood supply of an acardiac twin in the antepartum state Pertti Kirkinen, Riitta Herva, Juha Räsänen, Juhani Airaksinen, and Markken Ikäheimo

Departments of Obstetrics and Gynaecology, Pathology and Internal Medicine, University of Oulu, Finland

The clinical features and autopsy findings in acardiac twins have been extensively evaluated in numerous case reports [3]. This bizarre and fatal abnormality can be diagnosed antepartally by ultrasound [2]. An abnormal circulatory system is one central affection of this anomaly. Up to now, only indirect evidence, mostly based on the postnatal autopsy findings, has been available regarding the functional circulatory condition of an acardiac twin. We report here in the antepartum state, findings in the circulatory system in this congenital abnormality as well as the corresponding anatomic structures at autopsy.

waveforms from the umbilical artery and vein when measured at the fetal attachment of the cord, and also normal fetal aortic flow velocity waveforms. The relative size of the heart and the contractility of the myocardium of this fetus, evaluated by echocardiographic measurements of the biventricular end-diastolic transversal diameter and biventricular fractional shortening, were in

Case history: A routine ultrasound screening examination of the pregnancy of an 23 year para 4 was made during the 22nd gestational week. This revealed a twin pregnancy, with appropriate-forgestational age dimensions and anatomy for fetus A, but severely abnormal structures for fetus B. Anencephaly, absent upper extremities, absent left lower limb and absent cardiac structures were noted (figure 1). The subcutaneous tissue of the fetus was severly hydropic. The fetus was moving only passively in connection with the movements of the healthy fetus. Polyhydramnios was present and the large placenta was attached to the anterior uterine wall. No membranes could be seen between the fetuses. At repeat examination 2 weeks later, both fetuses had grown proportionally for the gestational age. Circulatory conditions of these fetuses were examined by pulsed Doppler examinations and by color Doppler imaging (HEWLET-PACKARD 2-D ultrasound system 77020 A, 5 MHz probe). The healthy fetus demonstrated normal blood velocity 1989 by Walter de Gruyter & Co. Berlin · New York

Figure 1. Transversal ultrasound image of the acardiac twin. Sp = spine H = hydrops A = ascites UV = umbilical vessel.

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Kirkinen et al, Paradoxical umbilical blood supply of an acardiac twin

normal ranges [5, 6]. In contrast, when the Doppler examinations were made at the attachment of the cord to the acardiac twin, a pulsatile flow was recorded in the larger vessel of the cord (figure 2). Color Doppler imaging gave evidence that this pulsatile flow was directed from the placenta towards the acardiac fetus. The pulse rate in this vessel was identical to that of the healthy twin. In the other vessel of the cord of the acardiac twin, the flow profile was of a venous type and directed away from the fetus towards the placenta.

The placenta was monochorionic diamniotic, within each sac there was a single umbilical cord. The cord of fetus A was 34 cm, it was attached at the equator and had three vessels. The cord of the acardiac twin was only 4cm, with two vessels. When the vein of the placenta! end of the cord of fetus A was injected with 30% urografin, the contrast medium was found to appear in the cordal vein and the circulatory system of the acardiac twin (figure 3).

Figure 2. Velocity waveforms measured at the attachment of the cord of the acardiac twin. The pulsating flow is directed to the fetus.

Figure 3. Postnatal x-ray contrast medium angiography of the placental side of the umbilical circulation of the twins. Vascular anastamose is demonstrated (arrow). A = acradiac twin.

Spontaneous labor began with rupture of the membranes in the 25th gestational week. The birthweight of fetus A was 685 g and Apgar scores 1/1. She died at 37 minutes. The autopsy revealed no structural malformations; the liver was large in relation to body weight, 49.3 g (normal approximately 39 g). The weight of the heart was normal.

Discussion

Fetus B was stillborn with a birth weight of 414 g and length 16.5 cm. The normal form was lost. The head and right arm were absent. The left arm and left leg were rudimentary and the right^leg reduced. There was marked generalized eddfea. Autopsy revealed one cavity inside the fetus. The heart, lungs, liver and spleen were absent. A single aorta, great arteries, one kidney, two adrenals, atretic intestine, pancreas and an ovary were identified.

Examinations of pregnancies complicated by an acardiac twin have revealed extensive artery-toartery and vein-to-vein anastamoses in the placentas of the twins [6, 7]. Similarly, anastamoses were present in our case, which was a typical example of this congenital abnormality. The Doppler examinations demonstrated paradoxical blood supply, with pulsatile flow in the vessel going to the fetus and venous flow profile in the vessel going to the placenta. This was supplied by the cardiac contractions of the second healthy fetus. Our postmortem radiographic examination revealed vascular anastamoses of the venous sides of the umbilical circulations. Most probably the corresponding anastamoses existed also in the arterial sides, and retrograde pulsative flow was present in the umbilical artery of the acardiac twin. The J. Perinat. Med. 17 (1989)

Kirkinen et al, Paradoxical umbilical blood supply of an acardiac twin velocity waveform in the vessel supplying the acardiac twin was very similar to that of the normal umbilical artery. This reflects the great functional reserves of the heart of the healthy twin, which had a double circulatory load when supporting the circulation of the both fetuses. In our case, both the relative size of the heart and the contractility of the myocardium were normal at the end of the second trimester. Some case reports have shown that this condition can later, during the last trimester, result in cardiac insufficiency in the other fetus [6]. Platt et al. have speculated on the possible therapeutic importance of intrauterine clipping of the umbilical cord of the acardiac twin [4]. Our experience supports their opinion, when

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demonstrating the existence in vivo of retrograde umbilical circulation to the acardiac twin during the second trimester. The pathophysiological mechanisms behind the polyhydramnios and fetal hydrops, which are typically associated with this abnormality, are difficult to understand. In our case the rapidly progressing polyhydramnios was associated with placental vascular anastamoses and retrograde umbilical circulation in the second twin. Correspondingly, it can be speculated that acute polyhydramnios, which can develope in multiple pregnancies with anatomically normal fetuses, is probably pathophysiologically associated with similar twin-to-twin circulatory changes as was demonstrated by our acardiac twin pregnancy.

Abstract In a case with one acardiac twin, color Doppler examination revealed retrograde umbilical circulation to this fetus. This pulsatile flow in the umbilical vessel of the

acardiac fetus was supported by the cardiac function of the co-existing healthy twin.

Keywords: Acardie, Doppler, umbilical circulation. Zusammenfassung Antepartal dokumentierte, paradoxe umbilikale Blutversorgung eines Acardiacus

Wir berichten über den Fall eines Acardiacus, in dem farbige Doppier-Untersuchungen die retrograde Zirku-

lation in der Nabelschnur dieses Feten aufdeckten. Der pulsierende Flow in dem Nabelschnurgefaß des Acardiacus wurde durch die cardiale Funktion des koexistenten gesunden Zwillings unterhalten.

Schlüsselwörter: Acardiacus, Doppler, Nabelschnurzirkulation. Resume Suppleance sanguine ombilicale paradoxale d'un jumeau acardiaque, une observation antepartum documentee.

Le Doppler Couleur a revele une circulation ombilicale retrograde chez un monstre acardiaque.

C'est la fonction cardiaque du jumeau co-existant en bonne sante qui supportait ce flux pulsatif dans les vaisseaux ombilicaux.

Mots-cles: Circulation ombilicale, Doppler, Monstre acardiaque. References

[1] BIEBER F, W NANCE, C MORTON: Genetic studies of an acradiac monster: evidence of polar body twinning in man. Science 213 (1981) 775 [2] MACH LA, M GRAVETT, C RUMACK: Antenatal ultrasonic evaluation of acardiac monsters. J Ultrasound Med 1 (1982) 13 [3] NAPOLITANI FD, J SCHREIBER: The acardiac monster: A review of the world's literature and presentation of 2 cases. Am J Obstet Gynecol 80 (1960) 582 [4] PLATT L, G DEVÖRE, A BIENIARZ: Antenatal diagnosis of acephalus acardia: A proposed management scheme. Am J Obstet Gynecol 146 (1983) 857 [5] RÄSÄNEN J, P KIRKINEN: Growth and function of human fetal heart in normal, hypertensive and diabetic pregnancy. Acta Obstet Gynecol Scand 66 (1987) 349 J. Perinat. Med. 17 (1989)

[6] RÄSÄNEN J, P KIRKINEN, P JOUPPILA: Fetal aortic blood flow and echocardiographic findings in human pregnancy. Eur J Obstet Gynecol Reprod Biol 27 (1988) 115 [7] VAN ALLEN MI, D SMITH, J SHEPARD: Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Sem Perinatol 7 (1983) 285 Received October 18,1988. Accepted November 14, 1988. Pertti Kirkinen, M. D. Department of Obstetrics and Gynecology University of Oulu 90220 Oulu 22 Finland