Table_1_A review study of fetal circulatory models to develop a digital twin of a fetus in a perinatal life support system.pdf

BackgroundPreterm birth is the main cause of neonatal deaths with increasing mortality and morbidity rates with decreasing GA at time of birth. Currently, premature infants are treated in neonatal intensive care units to support further development. However, the organs of, especially, extremely premature infants (born before 28 weeks of GA) are not mature enough to function optimally outside the womb. This is seen as the main cause of the high morbidity and mortality rates in this group. A liquid-filled incubator, a so-called PLS system, could potentially improve these numbers for extremely premature infants, since this system is designed to mimic the environment of the natural womb. To support the development and implementation of such a complex system and to interpret vital signals of the fetus during a PLS system operation, a digital twin is proposed. This mathematical model is connected with a manikin representing the digital and physical twin of the real-life PLS system. Before developing a digital twin of a fetus in a PLS system, its functional and technical requirements are defined and existing mathematical models are evaluated.Method and resultsThis review summarizes existing 0D and 1D fetal circulatory models that potentially could be (partly) adopted for integration in a digital twin of a fetus in a PLS system based on predefined requirements. The 0D models typically describe hemodynamics and/or oxygen transport during specific events, such as the transition from fetus to neonate. Furthermore, these models can be used to find hemodynamic differences between healthy and pathological physiological states. Rather than giving a global description of an entire cardiovascular system, some studies focus on specific organs or vessels. In order to analyze pressure and flow wave profiles in the cardiovascular system, transmission line or 1D models are used. As for now, these models do not include oxygen transport.ConclusionThis study shows that none of the models identified in literature meet all the requirements relevant for a digital twin of a fetus in a PLS system. Nevertheless, it does show the potential to develop this digital twin by integrating (parts) of models into a single model.</p

アイヌ遺骨問題に関する関係者インタビュー

北海道には先住民族であるアイヌ民族が住んでいます。独自の文化と言語を持つ彼らに対して、開拓の名のもとに同化政策を押し進められたのが約150 年前です。また、世界的に形質人類学がもてはやされた時期からは、盗掘ともとれる大々的な収集が組織的に行われました。そして、それは主に各地の大学機関によって行われ、北海道大学が一番多くアイヌの遺骨を保管していました（2019年11月に慰霊施設に集約されました）。1980 年代からアイヌ民族による遺骨返還の請求があり、ごく一部の遺骨に関しては返還できたものの、それ以降2010年代は裁判の和解による返還しか実現できていません。 多くの科学技術や研究開発が人々の幸福を望んで行われていることは間違いないと思います。しかし、その結果が研究者の意図に反して社会との軋轢を生じる場合もあります。その一例がアイヌ遺骨の収集の歴史と現在だと思います。本調査では、北海道大学が研究のために収集・保管しているアイヌの遺骨、副葬品など、過去の研究が現在にもたらした「負の側面」に注視し、ステークホルダーへのインタビューを敢行します。過去の研究がもたらした結果に、それぞれの立場で、どのように向き合っているのかを、わずかでも浮き彫りにできればと思います

Examples of patients in the non-overlapping group, who experienced thrombosis.

<p>The left pane shows orthogonal views on the site of interest, while the right pane displays an overlay between blood vessel segmentation (red) and a maximum intensity projection of the original data. (a). Patient #1, who had a mild narrowing (25%, see arrows) in a 5 cm long section of the blood vessel. The radius profile between start and end is given as well, including the start and end marks of the narrowing. (b). Patient #25, showing a 3.5 cm long severe (75%) stenosis, indicated by the white arrows. The yellow arrows indicate locations where no valid diameter measurement could be retrieved. These are also indicated in the graph of the radius. Begin and end of the stenosis region are shown in the radius plot as well.</p

Overview of the computer model geometry and element types.

<p>Left: Schematic overview of the upper and lower arm generic geometries, divided into elements for the computer model. Inflow to the circulation was defined by a characteristic flow curve with an average flow of 5100 ml/min. At the end of the venous system (subclavian vein) a pressure of 10 mmHg was prescribed. The right panel shows a legend of the element types in the computer model and their (geometrical) parameters: radius (), wall thickness (), Young's modulus (), area (), length (), windkessel impedance (, calculated from radius), compliance (), and peripheral resistance (). The stenosis element was only used for the cases when the NCE-MRA was studied in detail and a stenosis was present.</p

Comparison of postoperative flow measurements (green) with computer model predictions based on geometric uncertainty analysis (orange) and full uncertainty analysis (red, data from Bode et al.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053615#pone.0053615-Bode1" target="_blank">[<b>10</b>]</a><b>).</b> The error bars of the computer model indicate the 25th–75th percentile interval, while the error bars for the US flow measurements indicate the flow range that results from assuming a parabolic (lower value) or flat (upper value) velocity profile. Patients #8 and #24 were not simulated, because a non-standard surgical method was used. Patient #15 received a prosthetic PTFE graft, which could not be simulated, and patient #21 experienced thrombosis during surgery, which made postoperative flow results unavailable. Cases for which no overlap exists between the geometric uncertainty intervals of the computer model and postoperative flows are indicated with red circles (6/21). These were used for identification of geometry-related sources of error. (a). Patient #23 with thrombosis reported at one week post-surgery. A relevant section of the upper basilic vein is displayed with a significant (75%) stenosis, indicated by the arrows. (b). Patient #21, who experienced thrombosis during surgery. A relevant section of the lower arm artery (radial) is displayed. Average radius in this section was 0.71 mm, while US reported 1.12 mm. The surgical threshold for lower arm VA creation is at a radius of 1 mm <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053615#pone.0053615-Tordoir4" target="_blank">[37]</a>.</p

Extraction of subclavian/axillary and brachial artery radius from the original data by three-phase line regression.

<p>The blue stars show the original radius values. Variable is the normalized position along the curve. The governing equations and the constants to be fitted (parameters: , , , and , transition points: and ) are shown as well. The red line demonstrates the result of the three-phase fitting, while the black circles indicate the fitted values at the vessel mapping locations of the US protocol.</p

Updated computer model results (in blue) for the three cases identified with stenosis.

<p>For comparison the results of the geometric uncertainty analysis without stenosis, and the results of Bode et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053615#pone.0053615-Bode1" target="_blank">[10]</a> are shown as well. The postoperative US flows are shown in green.</p

Patient-specific measurements performed in the context of the study.

<p>Patient-specific measurements performed in the context of the study.</p

Left arm vasculature divided into arterial, venous and anastomosis segments (middle).

<p>These segments locally describe the relation between pressure <i>p</i> and flow <i>q</i> via a lumped parameter approach (right), and consists of a resistor <i>R</i> (viscous resistance to blood flow), a resistor <i>R_L</i> (viscous resistance of blood flow to small side-branches), an inductor L (blood inertia) and a capacitor <i>C</i> (vascular compliance). The anastomosis is modeled with two nonlinear resistors <i>R_v</i> and <i>R_d</i>. The windkessels consist of two resistors, <i>Z_wk and R_wk</i> (together the peripheral resistance) and a capacitor C_wk (peripheral compliance). This figure is adapted from Huberts et al.</p

The names of all vessels included in the computational domains.

<p>The names of all vessels included in the computational domains.</p