Analysis of dynamic system compliance for the therapy of Normal Pressure Hydrocephalus

常压性脑积水（NPH）是一种脑脊液（CSF）内腔的病理性增大而不伴有压力升高，近年来患者数量有所增加。目前病理生理尚不完全清楚，但已知颅内顺应性降低在发病机制中起重要作用。因此，本研究项目旨在研究颅内顺应性，特别是其动力学，其与NPH的关系分析不足，并为该疾病开发新的治疗和诊断方案。为了更好地了解导致颅内依从性降低的潜在机制，本项目最初侧重于对迄今尚未研究的参数进行建模，以进行敏感性分析。由于现有模型对动态顺应性的再现不够充分，简化了脑脊液的重吸收和脉冲波的形成，导致整个系统的动力学失真。在此背景下，将创建一个新的模型，该模型将颅脊髓系统与形态学和功能上合理的动态顺应性进行映射。在有限元模型中，将基于结缔组织不同动脉壁层的结构力学行为，模拟大颅动脉与脑脊液的动脉脉冲波耦合，并在模拟中分析结缔组织年龄相关变化的影响。参数研究应揭示各种因素对顺应性的影响，对组织损伤的动态载荷对实质的影响，从而对NPH形成的影响。根据这些参数研究的结果，将对现有的实时功能模型进行相应的调整，该模型具有集中的颅脊髓系统参数，包括自动调节和动态脊柱顺应性。在这个模型中，特别要考虑到年龄相关或病理改变的脊髓重吸收部位的流出阻力，这是由年龄相关的脊髓缩短和其他影响引起的。基于对影响参数的更好理解和相应扩展的建模，将开发一种旨在改进治疗的人工顺应性和生物阻抗测量导管。实时模型用于配置人工顺应性，新开发的有限元模型用于设计生物阻抗导管。利用生物阻抗测量心室大小和大小变化可以得出总体顺应性的结论，随后可以在必要时用于控制现有的引流系统。在研究的同时，将开发一个模块化的假体模型，以验证生物电和生物力学模拟中显示的相关性，并测试人工顺应性和生物阻抗导管。

The number of patients suffering from Normal Pressure Hydrocephalus (NPH), a pathological enlargement of the inner cerebrospinal fluid (CSF) spaces without accompanying pressure rise, has increased in recent years. Currently the pathophysiology is not completely understood, but it is known that reduced intracranial compliance plays an important role in the pathogenesis. Therefore, this research project aims to investigate the intracranial compliance especially concerning its dynamics, which has only been insufficiently analyzed in its relation to NPH, and to develop new therapeutic and diagnostic options for this disease. In order to understand the underlying mechanism leading to a reduced intracranial compliance better, this project initially focuses on the modeling of parameters so far not investigated to perform a sensitivity analysis. Since existing models reproduce the dynamic compliance insufficiently and simplify the reabsorption of cerebrospinal fluid and the formation of the pulse wave, the dynamics of the entire system are distorted. Against this background, a new model will be created, which maps the craniospinal system with a morphologically and functionally justified dynamic compliance. In a finite element model the coupling of the arterial pulse wave over large cranial arteries to the CSF will be modeled, based on the structural mechanical behavior of the different arterial wall layers of connective tissue, and the influence of age-related changes of connective tissue will be analyzed in simulation. Parameter studies should shed light on the influence of various factors on the compliance, on tissue-damaging dynamic loads on the parenchyma and thus on the formation of NPH. On the basis of these findings from the parameter studies an existing real-time capable model with concentrated parameters of the craniospinal system including autoregulation and dynamic spinal compliance will be adapted accordingly. In this model in particular age-related or pathologically altered outflow resistance at the spinal reabsorption sites caused by an age-related shortening of the spinal cord and other effects will be taken into account. Based on an improved understanding of the influencing parameters and a correspondingly extended modeling an artificial compliance and a bioimpedance measuring catheter aiming at an improved therapy will be developed. The real-time model serves to configure the artificial compliance, the newly developed finite element model to design the bioimpedance catheter. Using bioimpedance to measure the ventricular size and the change in size conclusions can be drawn on the overall compliance, which subsequently can be used to control the existing drainage system when necessary. Parallel to the investigation, a modular phantom model will be developed in order to validate the correlations shown in bioelectrical and biomechanical simulation as well as to test both the artificial compliance and the bioimpedance catheter.