Name
Title | ||
|---|---|---|
Bridging Cell-Scale Simulations And Radiologic Images To Explain Short-Time Intratumoral Oxygen Fluctuations |
Abstract | ||
|---|---|---|
Radiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a macroscopic scale (average value per voxel) and are not able to capture microscopic scale (cell-level) phenomena. Nevertheless, to examine the causes of frequent fast fluctuations in tissue oxygenation, models simulating individual cells' behavior are needed. Here, we provide a link between the average data values recorded for radiologic images and the cellular and vascular architecture of the corresponding tissues. Using hybrid agent-based modeling, we generate a set of tissue morphologies capable of reproducing oxygenation levels observed in radiologic images. We then use these in silico tissues to investigate whether oxygen fluctuations can be explained by changes in vascular oxygen supply or by modulations in cellular oxygen absorption. Our studies show that intravascular changes in oxygen supply reproduce the observed fluctuations in tissue oxygenation in all considered regions of interest. However, larger-magnitude fluctuations cannot be recreated by modifications in cellular absorption of oxygen in a biologically feasible manner. Additionally, we develop a procedure to identify plausible tissue morphologies for a given temporal series of average data from radiology images. In future applications, this approach can be used to generate a set of tissues comparable with radiology images and to simulate tumor responses to various anti-cancer treatments at the tissue-scale level.Author summary Low levels of oxygen, called hypoxia, are observable in many solid tumors. They are associated with more aggressive malignant cells that are resistant to chemo-, radio-, and immunotherapies. Recently developed imaging techniques provide a way to measure the magnitude of frequent short-term oxygen fluctuations, but they operate on a macro-scale voxel level. To examine the possible causes of rapid oxygen fluctuations at the cell level, we developed a hybrid agent-based mathematical model. We tested two different mechanisms that may be responsible for these cyclic effects on tissue oxygenation: temporal variations in vascular influx of oxygen and modulations in cellular oxygen absorption. Additionally, we developed a procedure to identify plausible tissue morphologies from data collected from radiological images. This can provide a bridge between the micro-scale simulations with individual cells and the longitudinal medical images containing average values. In future applications, this approach can be used to generate a set of tissues compatible with radiology images and to simulate tumor responses to various anticancer treatments at the cell-scale level. |
Year | DOI | Venue |
|---|---|---|
2021 | 10.1371/journal.pcbi.1009206 | PLOS COMPUTATIONAL BIOLOGY |
DocType | Volume | Issue |
Journal | 17 | 7 |
ISSN | Citations | PageRank |
1553-734X | 0 | 0.34 |
References | Authors | |
0 | 4 | |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Jessica L Kingsley | 1 | 0 | 0.34 |
| James R Costello | 2 | 0 | 0.34 |
| Natarajan Raghunand | 3 | 0 | 0.34 |
| Katarzyna A. Rejniak | 4 | 3 | 0.84 |