A transmission line model of the human foetal circulatory system

Background: Fetal growth restriction (FGR) is a major contributor to perinatal morbidity and mortality, frequently resulting from placental insufficiency. Doppler ultrasonography of the umbilical artery (UA) and middle cerebral artery (MCA) provides valuable insights into placental resistance and fetal adaptation. Aim: To evaluate and compare the role of umbilical and cerebral artery Doppler in pregnancies with FGR and in normal fetuses. Methods: This prospective cross-sectional study was conducted over 18 months (June 2023 – Dec 2024) in the Department of Obstetrics and Gynaecology, Adichunchanagiri Institute of Medical Sciences and Research Centre, Karnataka. Singleton pregnancies between 32–36 weeks were included. Women underwent ultrasound and color Doppler evaluation . UA and MCA pulsatility indices (PI), systolic/diastolic ratios (S/D), and cerebroplacental ratio (CPR) were measured. Estimated fetal weight was classified as appropriate for gestational age (AGA) or small for gestational age (SGA). Doppler findings were correlated with gestational age, fetal growth, and perinatal outcomes. Results: Abnormal Doppler indices were significantly more common in FGR pregnancies compared to normal pregnancies. Elevated UA PI and S/D ratio indicated increased placental resistance, while reduced MCA PI demonstrated the “brain-sparing effect.” Low CPR was strongly associated with adverse perinatal outcomes, including low birth weight, low APGAR scores, and NICU admission. In contrast, normal pregnancies exhibited progressively declining UA resistance and stable MCA PI with advancing gestation. Conclusion: Combined assessment of UA and MCA Doppler, particularly CPR, is a reliable, non-invasive tool for differentiating constitutionally small from growth-restricted fetuses. Incorporating these Doppler parameters into routine antenatal surveillance enables early detection of fetal compromise and aids in optimizing delivery timing, thereby improving perinatal outcomes.

Likelihood, privileges and obligations*

Human tolerance to hypergravity is of increasing importance given the rising number of spaceflight participants. In this paper, we present a mathematical model of the human circulatory system that can predict an individual’s tolerance to hypergravity. We adopt a steady-state approach, where simplicity enables us to predict an individual’s tolerance to high gravitational acceleration (G-tolerance) with lower computational cost. Moreover, while our parameter set can be personalized to individual parameters, the model only requires cardiac output, three anthropometric measurements, vital signs, and sex to make a satisfactory prediction. Key features of the model include compartmentalization of the upper and lower circulation to allow for gravitational acceleration in the vertical direction to be varied, a model of venous collapse of the systemic veins, and feedback control to simulate regulation of heart rate and reserve volume. We also provide a case study of parameter calibration to predict G-tolerance for a single subject based on physiologic measurements before and during centrifuge-induced hypergravity. Simulation results were consistent with physiological expectations and subject report of G-related symptoms. These findings suggest that our model of the circulatory system has the potential to predict G-tolerance and serve as a clinical decision support tool to risk stratify subjects prior to spaceflight.

Objective: The aim of the study is to assess the relationship between uteroplacental Doppler sonography findings and cerebral diffusion measured by diffusion-weighted magnetic resonance imaging (DWI) in fetuses with early-onset intrauterine growth restriction (IUGR).Materials and methods: The study included 54 pregnant women with fetal IUGR and 15 healthy controls (n: 15). Fetuses with IUGR were classified into four groups based on Doppler findings: group 1 (n = 12), umbilical artery (UA) pulsatility index (PI) > 95pc; group 2 (n = 11), UA PI >95 pc and middle cerebral artery PI < 5pc; group 3 (n = 21), absent end-diastolic (A-EDF) in UA; group 4 (n = 10), reversed EDF in UA. After Doppler evaluation, DWI was performed in all patients within hours. The groups were compared with respect to apparent diffusion coefficient (ADC) levels.Findings: In cases with fetal IUGR, significant decreases were detected in ADC values of periatrial white matter (PAWM) (p = .01), frontal white matter (FWM) (p = .038), thalamus (p = .004), and basal ganglia (p = .013) compared to controls. In Doppler subgroup analysis adjusted for gestational age, ADC values of FWM, thalami, and pons were significantly lower in group 4 than control group (p = .02, p = .02, and p = .037, respectively). In PAWM, ADC values were significantly lower in group 4 than control and Group 1 (p = .004). No significant differences with regard to ADC values in basal ganglia, cerebellum was found between Doppler groups and control.Conclusions: In fetuses with IUGR, ADC values as measured by DWI decreases. The critical Doppler finding that is associated with reduced diffusion in some brain areas (FWM, PAWM, thalami, pons) is reverse end-diastolic flow in umbilical artery. Further prospective studies with larger sample size are needed to introduce cerebral ADC values in the management of IUGR

Application of a PExSim for modeling a POLVAD artificial heart and the human circulatory system with left ventricle assistance This paper presents a model of the human circulatory system with the possible addition of a parallel assist device, which was developed for the purpose of artificial heart monitoring. Information about an identification experiment of an extracorporeal ventricle assist device POLVAD is included. The modelling methods applied and the corresponding functional blocks in a PExSim package are presented. The results of the simulation for physiological conditions, left ventricle failure and pathological conditions with parallel assistance are included.

A single umbilical artery (SUA) is an independent risk factor for perinatal morbidity and mortality in healthy fetuses. The aims of the study were (1) to determine middle cerebral artery (MCA) blood flow velocimetric values among fetuses without structural or chromosomal anomalies with an SUA and to compare them with nomograms of patients with a 3-vessel cord and (2) to measure the pulsatility index (PI) of the umbilical artery among these patients. The PI values of the MCA and umbilical arteries were determined prospectively among 98 healthy fetuses with an SUA. The PI values were compared with nomograms of patients with a 3-vessel umbilical cord. For the MCA, peak systolic velocity (PSV) was also measured. Patients carrying fetuses with intrauterine growth restriction or congenital anomalies were excluded from the study. Middle cerebral artery PI values below the fifth percentile and PSV values above the 95th percentile adjusted for gestational age were considered abnormal. Gestational age ranged between 22 and 37.9 weeks (median, 30.3 weeks). After adjusting for gestational age, no alterations in the MCA PI and umbilical PI were found in comparison with the normal range for a 3-vessel cord known in the literature. Middle cerebral artery PSV values were also within the normal range for gestational age in all patients. The MCA PI and PSV values among healthy fetuses with an isolated SUA were similar to nomograms for fetuses with a 3-vessel umbilical cord. Therefore, abnormal MCA PI and PSV values among fetuses with an SUA should be treated the same as in patients with a 3-vessel umbilical cord.

Chronic Periaortitis

To evaluate the utility of cerebroplacental ratio (CPR) for prediction of subsequent fetal demise (FD) after fetoscopic laser photocoagulation of placental communication (FLP) in cases with Twin–twin transfusion (TTTS) or selective intrauterine growth restriction (sIUGR), complicated with absent end-diastolic flow in umbilical artery (UA-AEDF). FLP were performed from 2015 to 2017. CPR (MCA-PI/UA-PI) was recorded within 24 hours before FLP and postoperative 1, 4-7 or 9-15 days. All patient was followed until neonatal period. Relation between the perinatal outcome, especially FD of smaller twin, and values of CPR were analysed. Three cases of TTTS stage 3 and 10 cases of sIUGR were treated with FLP. Median gestational age at FLP was 19.3 (16.0-23.1). Eight case (62%) showed two neonatal survivals and other 5 twins (38%) were complicated with FD of donor or smaller twin at 31, 39, 80, 84 and 105 days after FLP, respectively. All recipient or larger twins survived after FLP. Preoperative CPR showed no significant difference between two groups with or without FD of donor or smaller twin. CPR of 8 survived donor or smaller twin showed marked increases after FLP, in which all CPR values increased at least more than 0.57 at the point of around 2 weeks after FLP. On the other hand, all 5 twins resulted in FD showed low CRP value, which remained less than 0.57 until 2 weeks after FLP. In compromised monochorionic twins showing UA-AEDF in donor or smaller twin, continuation of lower CPR in donor or smaller twin after laser surgery can predict the subsequent fetal demise. Such low CPR value might reflect severe insufficient placental function of remained placental territory in donor or smaller twins.

To evaluate neonatal mortality and brain damage in a group born prior to 32 weeks' gestation. The last prenatal feto-maternal Doppler evaluation was considered for the analysis. The absence (AEDV) or reversal (REDV) and the presence (PEDV) of end-diastolic velocity in UA were recorded. In PEDV fetuses a pulsatility index at the level of the MCA lower or equal-higher than the 10th percentile defined the “Brain spared fetuses” (BSF) and the “Non brain” (non BSF). AREDV and PEDV fetuses differed in birthweight and in the rate of SGA; no differences were found as to neonatal mortality and the prevalence of IVH, RDS, NEC and sepsis. The only case of periventricular leukomalacia occurred in the PEDV group. REDV fetuses were characterized by a low birthweight and a high prevalence of mortality. Non BSF fetuses were characterized by a similar rate of neonatal mortality and IVH when compared to REDV fetuses. The prevalence of preeclampsia in non BSF fetuses was 87%. In very preterm fetuses AEDV condition, if compared to PEDV, is not a major risk factor in predicting perinatal mortality and neurological complications, while REDV appears to be a relevant Doppler feature for neonatal mortality. Fetuses born prior to 32 weeks because of preeclampsia, characterized by positive end-diastolic flow in umbilical artery and no vasodilation in the middle cerebral artery, resulted to be a high risk group. Surprisingly, the neonatal mortality and neurological morbidity of these fetuses was similar to those of REDV ones.

A concentrated parameter model for the human cardiovascular system including heart valve dynamics and atrioventricular interaction

Fetal heart rate (FHR) is commonly used to assess fetal well-being. The aim was to establish normal ranges of FHR during pregnancy by umbilical artery (UMB-A) Doppler analysis in a healthy Polish population. The study was conducted in a tertiary center for fetal cardiology. Data on gestational age (GA), FHR measured on UMB-A, cardiac problems, and extracardiac problems were collected. All fetuses underwent echocardiographic examination. The inclusion criteria comprised normal fetal biometry and biophysical profile, labels of "normal heart anatomy and normal heart function", "no extracardiac malformations", and no "extracardiac anomalies". Based on the data from 258 healthy fetuses, a scatter graph with regression line giving a prognosis of normal values for FHR during pregnancy was prepared (95% confidence interval). The regression equation for FHR, as function of GA in weeks, was found to be: FHR (beats/minute) = 149 - GA according to biometry (weeks) × 0.22; (r = -0.1032; P = 0.098); FHR (beats/minute) = 148 - GA according to the last menstrual period (weeks) × 0.16; (r = -0.0722; P = 0.253). The 5th, 50th, 95th percentiles, mean and standard deviation of FHR between weeks 18 and 29 of gestation were calculated. We present the normal ranges for FHR measured on UMB-A for weeks 18 to 29 of gestation in healthy fetuses with normal heart function and anatomy. The obtained values may be of value to departments of obstetrics and should be considered important elements of the basic fetal ultrasound report.

Sonographic morphology and hyaluronan content of umbilical cords of healthy and down syndrome fetuses in early gestation

To investigate the effects of maternal dexamethasone administration on umbilical and fetal cerebral artery flow velocity waveforms. Cross-sectional study. Department of Obstetrics and Gynaecology, Robert Ballanger Hospital, Aulnay-sous-Bois, France. Twenty-six pregnant women with singleton pregnancies considered at risk for preterm delivery. At baseline, all pregnancies had normal fetoplacental vascular resistance. These women were given weekly six intravenous doses of 4 mg of dexamethasone eight hours apart. Doppler studies were performed from both umbilical artery (UA) and fetal middle cerebral artery (MCA) before (day 0), during (day 2), immediately after (day 4) and shortly after (day 7) every steroid course. No significant variation was noted in both umbilical artery pulsatility index (PI) and fetal heart rate through dexamethasone therapy. Compared with mean initial values, we found on day 4 a significant decrease in MCA PI of 0.28 (F = 7.17, P < 0.001) and a significant increase in UA:MCA PI ratio of 0.08 (F = 3.85, P = 0.013); in contrast no significant change was documented on days 2 and 7 in both MCA pulsatility index and UA:MCA PI ratio. After multiple regression analysis, only the decrease in fetal middle cerebral artery pulsatility index on day 4 remained significant (F= 5.84, P= 0.001). The current study finds in healthy fetuses a transient, significant and unexplained decrease in fetal middle cerebral artery impedance on the fourth day following maternal dexamethasone administration. Further basic research and clinical studies including larger sample sizes or pregnancies with fetoplacental dysfunction are needed.

Blood flow velocity waveforms in the middle cerebral, renal and femoral arteries of human fetuses

Chronic periaortitis (CP) is a rare disease characterized by fibro-inflammatory tissue surrounding the abdominal aorta and the iliac arteries. Anecdotal reports have shown that CP may also involve other vascular districts, particularly the thoracic aorta. The aim of this study was to investigate the thoracic aorta and epiaortic artery involvement in CP. Patients were eligible if they had undergone imaging studies assessing inflammatory involvement of the thoracic aorta and its major branches (e.g. contrast CT, MRI or PET-CT). We explored the patterns of thoracic vessel involvement and compared the clinical characteristics of patients with and without thoracic disease. Where available, we also reviewed the thoracic vascular/perivascular tissue biopsies. Of 153 CP patients seen between 1999 and 2012, 77 were eligible. Of these, 28 (36%) had thoracic involvement: 15 (54%) had thoracic periaortitis, with 7 also showing epiaortic artery involvement; 6 (21%) had periaortitis surrounding a thoracic aortic aneurysm, 2 of them with epiaortic artery involvement; 7 (25%) had a thoracic aortic aneurysm without periaortitis. Patients with thoracic disease were more frequently female (P = 0.01), were older (P = 0.001) and had a higher frequency of pain and constitutional symptoms (P = 0.02). Thoracic (peri)vascular biopsies revealed adventitial and peri-adventitial fibro-inflammatory patterns similar to those observed in abdominal CP. In about one-third of patients, CP also involves the thoracic aorta and the epiaortic arteries, which supports the hypothesis of a systemic inflammatory disease of the large arteries.