Mathematical simulations towards preventing cerebral hemorrhage in premature infants

One of the most frequent complications during the postnatal development of premature infants is intraventricular hemorrhage, which may lead to permanent disabilities. Infants born before 30 weeks of gestation or those with a birth weight below 1500 g are at risk of hemorrhage with an overall incidence of 20% to 25%. Intraventricular hemorrhage originates mostly in the subependymal germinal matrix (GM), a specific area of the developing brain that consists of highly vascularized neuroepithelial cells and a fragile capillary network. The pathogenesis of intraventricular hemorrhage is multifactorial. One of the most important factors is strong fluctuations of cerebral blood flow (CBF) caused by impaired cerebral autoregulation, which plays an important role in maintaining the required level of cerebral perfusion. The aim of the current project is the development of numerical methods for the simulation of the blood vessel system and CBF in immature brain. The cerebrovascular system of the adult brain has been the object of mathematical studies over the past 20 years. However, despite significant progress in understanding the cerebral regulatory mechanism, there is a lack of knowledge about impaired cerebral circulation in premature newborns. Therefore, creating an appropriate mathematical description of the cerebral circulation that simulates the peculiarities of the immature brain is a challenging task. We develop a mathematical model which takes into account the morphological characteristics of the blood vessels according to gestational and postnatal age. In addition, the cerebral autoregulation and dependence of CBF on variations in blood pressure, pCO2, pO2 and hematocrit is modeled by corresponding vascular reactivity (i.e., vasoconstrition and vasodilation). The calculated CBF will then be added to the multivariate statistical analysis as an additional independent variable to enhance the prognostic accuracy of early detection of premature infants at increased risk of hemorrhage.

This project is funded by the Klaus Tschira Foundation (Heidelberg, Germany).

The project is a joint collaboration of  Renée Lampe (Head of the Research Unit of the Buhl-Strohmaier Foundation for Cerebral Palsy and Paediatric Neuroorthopaedics at Technical University of Munich, School of Medicine, Klinikum rechts der Isar in Munich, Germany and holder of the Markus Würth endowed professorship) and Johannes Zimmer (Chair for Analysis and Modelling, School of Computation, Information and Technology)

Team members: Andrey Kovtanyuk (School of Computation, Information and Technology) and Irina Sidorenko (Klinikum rechts der Isar)