论文标题

伪层模式形成的数据驱动建模

Data Driven Modeling of Pseudopalisade Pattern Formation

论文作者

Hiremath, Sandesh Athni, Surulescu, Christina

论文摘要

在本文中,我们提出了一种数据驱动的方法,以深入了解不同类型的假时结构的形成。为此,我们从用于GBM动力学的最先进的宏观模型开始,该模型与细胞外pH的动力学结合,并制定终端值最佳控制问题。因此,鉴于特定的,观察到的伪层模式,我们确定了对其出现负责的参数(生物力学)的演变。选择表现出伪层状结构的随机组织学图像作为目标模式。在确定了生成指定目标模式的最佳模型参数之后,我们制定了两种不同类型的模式来抵消Ansatzes,以确定可能损害或阻碍假时形成过程的可能方法。这为设计恶性GBM的主动或实时控制提供了基础。此外,我们还提供了一种简单但有见地的机制,通过线性组合负责生成不同已知目标模式的最佳模型参数来综合新的假时模式。这尤其提供了一个暗示,即可以通过负责生成简单模式的参数的线性组合来综合复杂的伪层模式。进一步,我们问自己,是否可以通过线性组合来构想复杂的治疗方法,从而能够逆转或破坏简单的假层状模式,然后在数值模拟的帮助下积极回答。

In this paper we propose a data-driven methodology to gain insight into the formation of different types of pseudopalisade structures. To this end, we start from a state of the art macroscopic model for the dynamics of GBM, that is coupled with the dynamics of extracellular pH, and formulate a terminal value optimal control problem. Thus, given a specific, observed pseudopalisade pattern, we determine the evolution of parameters (bio-mechanisms) that are responsible for its emergence. Random histological images exhibiting pseudopalisade-like structures are chosen to serve as target pattern. Having identified the optimal model parameters that generate the specified target pattern, we then formulate two different types of pattern counteracting ansatzes in order to determine possible ways to impair or obstruct the process of pseudopalisade formation. This provides the basis for designing active or live control of malignant GBM. Furthermore, we also provide a simple, yet insightful, mechanism to synthesize new pseudopalisade patterns by linearly combining the optimal model parameters responsible for generating different known target patterns. This particularly provides a hint that complex pseudopalisade patterns could be synthesized by a linear combination of parameters responsible for generating simple patterns. Going even further, we ask ourselves if complex therapy approaches can be conceived by linearly combining such that are able to reverse or disrupt simple pseudopalisade patterns, which is then positively answered with the help of numerical simulations.

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