13:00   Abdominal On the use of digital twin technology Arielle for the development of new generation perinatal life support systems Bettine van Willigen, Beatrijs van der Hout-van der Jagt, Frans van de Vosse Abstract: The Perinatal Life Support (PLS) consortium is developing a liquid-based environment (PLS system) to increase chance of survival of extremely preterm infants (< 28 weeks of gestational age). To develop such a complex device, knowledge from multidisciplinary fields must integrate into one single system. Mathematical models are used to support this integration by composing a digital twin Arielle of the PLS system and the preterm infant to allow computer simulations of the interaction with the device. In addition, these models are connected with a manikin to support clinical implementation. Since there is more available information and clinical data of full-term fetuses, the development of Arielle starts with the mathematical implementation of a cardiovascular system of a healthy full-term fetus. This closed-loop fetal cardiovascular mathematical model consists of seven parts: 1) A four chamber cardiac model based on the left ventricular one-fiber model of (Bovendeerd et al., 2006). 2) A valve model to describes the dynamic motion of cardiac valves (Mynard et al., 2012). 3) A 1D model to describe the blood flow and pressure wave propagation inside larger vessels. 4) A lumped parameter model to mimic the microcirculation of organs. 5) A coronary microcirculation model based on (van der Horst et al., 2013) to simulate the effect of intramyocardial pressure on the pressure and flow inside the coronary vessels. 6) A liver circulation model that allows connection of the umbilical vein via the portal veins to right atrium (Mynard, 2011). 7) Junction elements that considers pressure loss in bifurcations (Boom et al., 2018). The model provides a left and right cardiac output of 0.64 and 0.87 L/min, respectively, which corresponds with the empirical results of (Mielke and Benda, 2001). Furthermore, it simulates the clinical relevant pulsatility index of the umbilical arteries realistically with a value of 0.8 (Acharya et al., 2005). A cardiovascular model of a healthy full-term fetus is implemented successfully. In order to support development of the PLS system and its clinical implementation, next steps include the addition of modules to simulate fetal growth, maternal-fetal gas exchange, baro- and chemoreceptor reflexes, and metabolism. References Acharya, G., Wilsgaard, T., Berntsen, G.K.R., Maltau, J.M., and Kiserud, T. (2005). Reference ranges for serial measurements of umbilical artery Doppler indices in the second half of pregnancy. Am. J. Obstet. Gynecol. 192, 937–944. Boom, T. van den, Stevens, R., Delhaas, T., Vosse, F. van de, and Huberts, W. (2018). Zero-dimensional lumped approach to incorporate the dynamic part of the pressure at vessel junctions in a 1D wave propagation model. Int. J. Numer. Methods Biomed. Eng. 34, e3116. Bovendeerd, P.H.M., Borsje, P., Arts, T., and van De Vosse, F.N. (2006). Dependence of Intramyocardial Pressure and Coronary Flow on Ventricular Loading and Contractility: A Model Study. Ann. Biomed. Eng. 34, 1833–1845. van der Horst, A., Boogaard, F.L., van’t Veer, M., Rutten, M.C.M., Pijls, N.H.J., and van de Vosse, F.N. (2013). Towards Patient-Specific Modeling of Coronary Hemodynamics in Healthy and Diseased State. Comput. Math. Methods Med. 2013, e393792. Mielke Gunther and Benda Norbert (2001). Cardiac Output and Central Distribution of Blood Flow in the Human Fetus. Circulation 103, 1662–1668. Mynard, J.P. (2011). Computer modelling and wave intensity analysis of perinatal cardiovascular function and dysfunction. University of Melbourne. Mynard, J.P., Davidson, M.R., Penny, D.J., and Smolich, J.J. (2012). A simple, versatile valve model for use in lumped parameter and one-dimensional cardiovascular models. Int. J. Numer. Methods Biomed. Eng. 28, 626–641. The effects of advancing gestation on maternal autonomic response Maretha Bester, Rohan Joshi, Massimo Mishi, Judith van Laar, Rik Vullings Abstract: Background: Maternal autonomic adaptation is essential in facilitating the physiological changes that pregnancy necessitates. Insufficient adaptation is linked to complications such as hypertensive diseases of pregnancy. Consequently, tracking autonomic modulation throughout pregnancy could allow for the early detection of emerging deteriorations in maternal health. Autonomic modulation can be longitudinally monitored by assessing heart rate variability (HRV). Yet, changes in maternal HRV corresponding to normally progressing pregnancy remain poorly understood. Current literature focuses on standard HRV features that inform on the activity of the two autonomic branches, often showing conflicting results. Investigating further characteristics of autonomic regulation may offer clarity on autonomic changes during normal pregnancy. One such characteristic is the responsivity of HR to stimuli, which has been shown to be elevated in complicated pregnancies. Subsequently, we investigate whether the increasing stress of healthily advancing gestation alters the maternal autonomic response. Methods: Multiple ECG measurements (≈45 minutes) were obtained longitudinally from 29 healthy pregnant women (range 14-41 weeks of gestation). Maternal autonomic response was assessed with phase rectified signal averaging (PRSA), which graphically shows the rate and magnitude of HR responsivity. Deceleration capacity (DC), which quantifies the response observed in PRSA, was calculated correspondingly. Results were grouped into three gestational age ranges (i.e. under 23 weeks (GA₁), 23 to 32 weeks (GA₂), and over 32 weeks (GA₃)). Friedman’s test, with a Dunn’s post hoc test and Bonferroni correction, and Cohen’s U₁ were performed to determine the significance and effect sizes of differences between groups, respectively. Results: The median and interquartile ranges of the DC were 11.7 (8.3 – 14.9) for GA₁; 9.5 (5.8 – 12.8) for GA₂, and 8.4 (6.2 – 11.7) for GA₃. Changes across groups were significant (p = 0.002), yet the effect sizes were small (U₁ = 0.05, 0.02 and 0.04, respectively). Conclusion: Autonomic responsiveness dampens under the increasing stress of advancing gestation. This downward trend starts before 20 weeks of gestation, i.e. before the timepoint after which complications are typically diagnosed. Subsequently, longitudinally tracking maternal autonomic response with PRSA may aid in the early detection of complications. An ultrasound reconstruction algorithm correcting for local speed-of-sound deviations in abdominal imaging Vera van Hal, Jan-Willem Muller, Hans-Martin Schwab, Richard Lopata Abstract: Abdominal ultrasound imaging is used to monitor rupture risk of abdominal aortic aneurysms. In our previous study, we showed that a more complete understanding of aneurysm geometry and wall motion can be retrieved using two transducers, and an ultrafast dual-receive acquisition scheme. In-vivo, multi-perspective image fusion and coherent compounding is hampered by wavefront aberrations, caused by the strong speed-of-sound variations between muscle and fat in the abdominal wall. This significantly limits abdominal ultrasound image quality, by introducing geometric distortions of the imaged structures, and general blurring of the ultrasound image, especially at deep imaging locations like the aorta. In multi-perspective ultrasound, these aberrations can be even more severe, as a rigid registration of images from different probes is infeasible. In this study, a generic algorithm for aberration correction in delay-and-sum (DAS) beamforming is developed to improve image quality for both single-perspective and multi-perspective ultrasound. The method employs aberration corrected wavefront arrival times based on a speed-of-sound estimate derived from the image data. Two wavefront models are compared. The first model is based on a straight ray (SR) approximation, and the second model on the Eikonal equation, which is solved by a multi-stencils fast marching (MSFM) method. Their accuracy for abdominal imaging was evaluated in acoustic simulations and phantom experiments involving tissue-mimicking and porcine material that were placed on top of a commercial CIRS phantom. In the ultrasound simulations, a medium was designed to mimic the abdominal wall, and an aorta was implemented at a depth of 9 cm. Standard DAS beamforming resulted in a duplication of the aorta, because of refraction (‘double aorta syndrome’). Using aberration correction in DAS, this was completely resolved. The lateral resolution was improved by up to 90% in simulations and up to 65% in experiments compared to standard DAS, in which MSFM-DAS outperformed SR-DAS. Moreover, successful multi-perspective image fusion in the presence of aberration was shown. In conclusion, aberration correction by modelling arrival times in DAS is feasible in-vivo, which can significantly improve image quality by resolving blurring effects, and allow for multi-perspective image fusion, by correction of geometric distortions. Accuracy of vital parameters measured by a wearable following major abdominal cancer surgery Jonna van der Stam, Eveline Mestrom, Jai Scheerhoorn, Fleur Jacobs, Ignace de Hingh, Natal van Riel, Arjen-Kars Boer, Volkher Scharnhorst, Simon Nienhuijs, Arthur Bouwman Abstract: Background The recovery of patients undergoing major surgery is frequently affected by complications. Up to 25% of the patients suffers from major adverse events such as pneumonia, anastomotic leakage, abscesses or bleeding[1]. Clinical deterioration is often preceded by a substantial disturbance in vital parameters [2–6]. When these disturbed vital parameters can be accurately captured by a wearable sensor, prediction or recognition of the deteriorating patient may be improved. Recent advances in wearable technology allow for the development of wireless sensors to continuously measure vital parameters in the general ward or even at home. Purpose The present study assesses the accuracy of a wearable patch (Healthdot) for continuous monitoring of heartrate (HR) and respiration rate (RR) in postoperative major abdominal surgery patients. Method The Healthdot, a wearable patch that performs measurements using chest accelerometry, was evaluated for accuracy of measurement of both HR and RR in a postoperative population following major abdominal oncological surgery. The analysis focused on the agreement between HR and RR measured by the Healthdot and the gold standard patient monitor in the intensive and post-anesthesia care unit. Bland-Altman and Clarke error grid analysis are performed to determine agreement and clinical accuracy. Results For HR, a total of 112 hours of measurements was collected in 26 patients. For RR, a total of 102 hours of measurements was collected in 21 patients. On second to second analysis, 97% of the HR and 87% of the RR measurements were within 5 bpm and 3 rpm of the reference monitor. Assessment of 5-minute averaged data resulted in 96% of the HR and 95% of the RR measurements within 5 bpm and 3 rpm of the reference monitor. A Clarke error grid analysis showed that 100% of the HR and 99.4% of the 5-minute averaged data was clinically acceptable. Conclusions The wireless wearable accelerometry patch (Healthdot) accurately measured HR and RR in a cohort of patients recovering from major abdominal surgery, provided that good quality data was obtained. These results push the Healthdot forward as a clinically acceptable tool in low acuity settings for unobtrusive, automatic, wireless and continuous monitoring. Hyperspectral imaging to discriminate ovarian cancer tissues after surgery: a pilot study Sharline M. van Vliet - Pérez, Nick J. van de Berg, Francesca Manni, Marco Lai, L. Lucia Rijstenberg, Benno H. W. Hendriks, Jenny Dankelman, Patricia C. Ewing-Graham, Gatske M. Nieuwenhuyzen-de Boer, Heleen J. van Beekhuizen Abstract: The completeness of cytoreductive surgery (CRS) is the most important prognostic factor for the survival of advanced-stage epithelial ovarian cancer (EOC) patients. An intraoperative technique to detect microscopic tumours would therefore be of great value to prevent over and under-treatment. In this pilot study we aim to assess the use of near infrared (NIR) hyperspectral imaging (HSI) for the detection of malignant ovarian cancer. To this end, 10 patients with proven or suspected ovarian cancer provided informed consent and were enrolled. After CRS, this resulted in 26 tissue samples that were photographed ex-vivo at the pathology department. Included tissues originated from the ovaries, fallopian tubes, uterus, omentum and/or part of the intestines. Each hyperspectral image had 25 spectral bands in the wavelength range of 665-975 nm. The HSI data were processed by image calibration, min-max normalisation and glare removal. Subsequently, based on histological findings, image masks were created to separate spectra belonging to tumorous regions (>50% tumour cells) and non-tumorous regions. Spectrum features were selected and used for linear support vector machine (SVM) classifier training. The spectra belonging to in-between regions (<50% tumour cells) were not used for training. This way, a total of 26.446 data points were matched to the histological results. Finally, the performance of the classification was assessed by leave-one-out cross-validation. The HSI data and SVM classifier combined enabled the discrimination of tumour tissue and non-tumour tissue with a sensitivity of 0.81, specificity of 0.75, area under the curve of 0.83, and Matthew’s correlation coefficient of 0.41. To conclude, HSI is a suitable approach for intra-operative guidance during CRS as it can scan tissue surfaces in a fast and non-contact manner. In this pilot study we have shown that HSI is a promising technique in EOC management, as it can be used to discriminate ovarian carcinomas from healthy tissues.

end %-->