Kazunori Baba

Development of an ultrasonic system for three-dimensional reconstruction of the fetus

The ultrasonic diagnostic devices available at present can only represent one section of the fetus. We have developed a system for three-dimensional reconstruction of the ultrasonic fetal image in order to facilitate the understanding of the 3-D structure of the fetus and also to make 3-D recordings of this image. Either a real-time linear array probe or a convex array probe of the ultrasonic scanner was mounted on a position sensing arm of a manual compound scanner in order to detect the position of the probe. A microcomputer was used to convert the positional information to a recording of a visual image of videotape. This image was superimposed onto the ultrasonic tomographic image simultaneously using a superimposer and was recorded on the video tape, thereafter, being recalled by the image processing minicomputer. The minicomputer VAX11/780 (DEC) system was used for 3-D reconstruction and 3-D display. In the memory system the image of the anterior uterine wall was identified and subsequently excluded in order to visualise the fetus more clearly. The threshold of brightness was set to a high level so that the fetus could be separated from the amniotic fluid. The fetus was displayed three-dimensionally using computer graphics. Using this system, we have made it possible to observe the whole image of the fetus in utero non-invasively. This system offers a method for easier understanding of the 3-D structure of the fetus in utero and also makes 3-D recording possible. In the future, we confidently expect that this system will be used for screening for fetal anomalies and abnormalities of fetal growth.

Early axonal and glial pathology in fetal sheep brains with leukomalacia induced by repeated umbilical cord occlusion

We conducted a chronic preparation experiment involving near term fetal sheep to evaluate the contribution of umbilical cord occlusion to fetal brain injury. In experimental groups (n = 11), complete cord occlusion for 3 min followed by 5 min release, repeated 5 times were performed at 3 days after initial surgery. Instrumental cases without cord occlusion (n = 3) and uninstrumental twins (n = 6) were also examined as controls. Multiple necrotic foci predominantly in the periventricular white matter were found in the fetal brains examined at 1-3 days after cord occlusion. To estimate the contribution of early axonal and glial reaction to brain injury the following immunohistochemical study was performed. In the lesions, coagulation necrosis, axonal swelling and microglial activation were demonstrated with amyloid precursor protein or ionized calcium binding adapter molecule 1 immunohistochemistry. The induction of tumor necrosis factor alpha and inducible nitric oxide synthase were also detected immunohistochemically in the microglia at 1 and 3 days after cord occlusion. In contrast, the reaction of glial fibrillary acidic protein positive astrocytes was faint at 1 day after occlusion, but the induction of cyclooxygenase-2 was observed. These findings suggest the glial reaction of cytokines and free radicals induced by fetal hypoxia may contribute to the occurrence of brain injury.

Generation of Periventricular Leukomalacia by Repeated Umbilical Cord Occlusion in Near-Term Fetal Sheep and Its Possible Pathogenetical Mechanisms

Periventricular leukomalacia (PVL) is a major cause of cerebral palsy. However, pathogenetic mechanisms of PVL have not been fully understood. Although it has been postulated that umbilical cord compression is related to the development of PVL, no animal experiments clearly demonstrated an association of umbilical cord occlusion with ‘periventricular’ white matter lesions. The purpose of this study is to determine whether umbilical cord occlusions could produce periventricular white matter lesions in fetal sheep and to examine how changes in fetal cardiovascular and metabolic variables are related to the induction of brain damage. Fourteen near-term fetal sheep underwent umbilical cord occlusion (3-min total cord occlusions 5 times at 5-min intervals). Dissections performed 24 h after cord occlusion revealed that periventricular white matter lesions were produced in 7 out of 14 sheep fetuses. According to the pattern of brain damage, we classified the fetal sheep into three groups: 5 fetuses with dominant lesions in the periventricular white matter (group I), 4 fetuses with brain lesions in the cerebral cortex and thalamus (group II) and 5 fetuses with no or minimal brain lesions (group III). Group I showed higher blood pressure and higher plasma lipid peroxide levels before cord occlusion compared to the other groups, while group II showed systemic hypotension during cord occlusion. No significant differences in changes in pH, PaCO2, PaO2 and heart rate were found between the three groups. It is speculated that PVL might be produced by an association of preexisting chronic circulatory instability with an acute episode of severe repetitive cord occlusion.

Real-time processable three-dimensional fetal ultrasound

SIR—Three-dimensional ultrasound (3DUS) provides threedimensional fetal images. However, it has found only limited use because many fetal abnormalities can be diagnosed by two-dimensional ultrasonography and the procedure is complex and time consuming. If the ultrasound beam is regarded as a projection ray in volume rendering, and ray tracing is conducted in real time, the procedure would not be as complex and images could be obtained immediately. 66 normal fetuses (12–40 weeks gestation) were scanned with an experimental 3DUS machine (Aloka Co Ltd, Tokyo, Japan) consisting of an ultrasound scanner SSD-1700 (Aloka Co Ltd) specially designed for ray tracing and a transabdominal 3D probe. The 3D probe scans an area of 7 7 cm, with a 60o angle of divergence in 5·5 s. Informed consent was obtained in all cases. A 5·5 s scan immediately produced a 3D fetal image (figure). Images of overlying maternal abdominal wall and anterior uterine wall were removed by setting a depth for ray tracing greater than either. The most appropriate gestational age range was from 28 to 35 weeks, within which 3D surfaceimage quality of upper and lower limbs was satisfactory in 25 of 26 (96%), and 3D facial images sufficiently clear in 13 of 26 cases (50%). After 35 weeks’ gestation, the images became increasingly less satisfactory owing to decrease in amniotic fluid relative to fetal size. From 12 to 27 weeks’ gestation, fetal 3D images were less satisfactory than from 28 to 35 weeks’ gestation. At less than 24 weeks, no facial images were satisfactory. Scan repetition was possible every 8 s, providing a sequence of 3D fetal images. Rapid fetal movement during the 5·5 s period of scanning led to 3D image distortion, but slow yawn-like openings of the mouth and opening and shutting the hands appeared quite clearly in the sequence of images. This is not possible by conventional 3DUS when images are generally analysed from 3D data sets obtained in a steady state. The new 3DUS would not be applicable to all fetuses mainly on account of limited viewing direction, but it is possible to obtain fetal 3D images by procedures far simpler than conventional 3DUS.

Over 500 Days’ Survival of a Goat with a Total Artificial Heart with 1/R Control

The 1/R control was developed to provide control over the output of a total artificial heart (TAH) by the central nervous system by using the peripheral vascular conductance (1/R) the vasodilatation in for the control signal. The physiologic stability of the 1/R control algorithm was tested by using goats with TAH. To apply the 1/R control equation to TAH in goats, real-time and continuous measurements of cardiac output, aortic pressure, and right atrial pressure were performed throughout the survival period. Left atrial pressure was also measured, to prevent lung edema. Under the 1/R control, 532 days’ survival was obtained in a goat with a TAH. Findings over the course of the experiment showed no hemodynamic or metabolic abnormality. Autopsy findings showed macroscopically no congestion in the liver. The experiment demonstrated the physiologic stability of the 1/R control algorithm for an extended period. Improvement of methods for measurement, such as the development of feasible techniques for the noninvasive measurement of the required hemodynamic parameters, will make it possible to use 1/R control in practice, especially for a totally implantable TAH system.

Goat Fetuses Disconnected from the Placenta, but Reconnected to an Artificial Placenta, Display Intermittent Breathing Movements

To investigate whether placental factors are involved in the intermittent breathing movements in goat fetuses, we assessed electrocortical activity (ECoA) and tracheal pressure in 5 fetuses (124–135 days) separated from the placenta and connected for 48 h to an extrauterine fetal incubation system that provided umbilical arteriovenous extracorporeal membrane oxygenation. The fetal physiological condition on this system was almost the same as that in utero for at least 48 h after the preparation. All fetuses showed intermittent low-voltage ECoA and breathing movements. The breathing movements occurred almost exclusively during periods of low- voltage ECoA. The proportions of time spent in low-voltage ECoA and breathing movements were 48–57% and 46–56%, respectively. In conclusion, breathing movements of fetuses on the extrauterine incubation system were episodic, suggesting that intermittent breathing movements are intrinsic to fetuses, independent of placenta-derived factors.

Herbal medicines, Sairei-to and Tokishakuyaku-san, differently modulate the release of cytokines from decidual versus peripheral blood mononuclear cells.

PROBLEM AND METHOD OF STUDY: We have shown that Tokishakuyaku‐san (Toki) and Sairei‐to (Sai) enhance T helper‐1 (Th1) cytokine release from peripheral blood mononuclear cells (PBMCs); thereby, they could be a therapeutic means in the treatment of autoimmunity related recurrent abortion in which T helper‐2 (Th2) polarization is exaggerated, the condition purported to benefit from these herbal medicines. However, an open question is whether these medicines might enhance Th1 cytokine release in decidual tissues and thereby stimulate the killer activity, thus, working counterproductively by accelerating maternal alloimmune reactions toward fetal tissues. To address this, we examined the effects of these medicines on the release of cytokines from decidual mononuclear cells (DMCs) in comparison with PBMCs on the assumption that they might act differently on these cell types. The effects of these medicines were investigated as related to human leukocyte antigen (HLA)‐G, a nonclassical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay.
 RESULTS: Regarding Th1 cytokines, Toki marginally increased the release of tumor necrosis factor (TNF)‐α, but not interferon (IFN)‐γ from DMCs while Sai did not affect the release of both. Both Toki and Sai were without effect in modulating the release of interleukin (IL)‐4, a member of Th2 cytokines. Interestingly, the presence of HLA‐G reduced the release of Th1 cytokines from DMCs regardless of the addition of Toki, Sai or none. These findings are in sharp contrast with PBMCs on which these medicines seem to act so as to enhance Th1 polarization and attenuate Th2 polarization.
 CONCLUSION: Differential effects of Toki and Sai on the release of Th1/Th2 cytokines between DMCs and PBMCs may afford the rationale of these medicines in the treatment of autoimmunity‐related recurrent abortion.

Extended field-of-view ultrasound imaging in obstetrics and gynecology: preliminary experience.

In obstetric and gynecological ultrasonography, real-time ultrasound scanners are now being used in place of static B-mode scanners: compound B-mode scanners and the octoson. Real-time ultrasound scanners have the disadvantage of a small field-of-view (FOV) and are not capable of indicating large abnormalities in image form, as is possible with static B-mode ultrasound scanners. Extended-FOV imaging technology (SieScape; Siemens Medical Engineering Group, Iselin, USA) developed recently makes possible panoramic images such as those obtainable with static B-mode ultrasound scanners, by moving a real-time ultrasound probe manually in the direction of the transducer array. This image processing technology estimates translation and rotation of the probe by comparing successive images during probe movement, and no probe position-sensing mechanism is necessary. The images transformed geometrically according to the estimated probe motion are put into the extended-FOV image buffer and combined with previous images to produce an extendedFOV image. This paper presents preliminary findings on the use of extended-FOV imaging in obstetrics and gynecology.

A step forward for the undulation pump total artificial heart

In the University of Tokyo, various types of total artificial heart (TAH) have been studied. Based on the experiences of TAH research, the development of the undulation pump total artifical heart (UPTAH) started in 1994. The undulation pump is a small-size, continuous-flow, displacement-type blood pump, and the UPTAH is a unique implantable total artificial heart that uses the undulation pump. To date, three models of UPTAH have been developed. The first model, UPTAH1, was developed to investigate the possibility of reducing the size of the device so it could be implanted in small adults, such as Japanese patients, in 1994. The second model, UPTAH2, which was the prototype of the animal experimental model, was developed in 1996 to investigate the possibility of survival with the UPTAH. The third model, UPTAH3, which is the present model, was developed in 1998 to enable long-term survival in animal experiments and to investigate the pathophysiology of the UPTAH. From July 1996 to October 1999, 22 implantations of UPTAH2 or UPTAH3 were performed in goats. In spite of the limitation of their small chest cavity, the UPTAH could be implanted into the chest of all goats. Using UPTAH3, survival of 31 days could be obtained. The research and development of UPTAH are ongoing.

Calcification and Thrombus Formation on Polymer Surfaces of an Artificial Heart

Calcification and thrombus formation are still important problems in artificial heart research. The calcification and thrombus formation generated in artificial heart blood pumps, driven without anticoagulant for 312 days as the left side and 414 days as the right side, were analyzed in this study. A thrombus was observed at the circumference of the sac in the 312-day pump, but it was not associated with calcification. Several phenomena were observed on the polymer membrane valves (jellyfish valves) incorporated into the blood pump: plastic deformation of the valve membrane by creep fatigue; no calcification of stationary parts such as spokes and the center of the membrane; calcification of the particular portion which received repeated stretching stress; and no association of calcification with thrombus. The calcification of the valve area which received repeated stretching force might be explained as follows. Repeated stretching forces extend the polymer membrane, causing some loosening between polymer molecules and generating microgaps. Blood proteins and phospholipids invade these microgaps, which then attract Ca2+ ions followed by phosphate ions(PO4 2-) leading to the formation of calcium phosphate complexes.