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Dynamic Model for Late Radiation Injury of Spinal Cord

J Li*, C Shi , M Chan , Memorial Sloan-Kettering Cancer Center, Basking Ridge, NJ


(Sunday, 7/29/2018) 3:00 PM - 6:00 PM

Room: Exhibit Hall

Purpose: Experimental studies revealed that the response of spinal cord to radiation is a continuously interactive process. The outcome of dynamic cellular interactions in spinal cord microenvironment is the determining factor of its late radiation injury. This work is to develop a dynamic model that studies the relationship between the initial radiation dose and latency of radiation myelopathy.

Methods: The model is based on mass-action kinetics and consists of three ordinary equations that describe three components of biological process: an initial injury that can deteriorate or be repaired by inflammatory or remyelination mechanism; an inflammatory mediator that is activated by radiation injury and can be transformed from beneficial to harmful effects based on its intensity; and finally, a remyelination agent that is recruited by inflammatory response and radiation injury through a sigmoidal coupling function once inflammation subsides. Model parameters were chosen to simulate experimental data. The latent period is defined by the time when injury increases to a saturation level.

Results: The model generates results similar to experimental observations: at low initial radiation dose, combinational process of inflammatory reactions and remyelination repairs the initial damage. On the other hand, when the initial radiation dose is high, the inflammatory responses cannot be suppressed and maintained at elevated levels and eventually inflict more harm than benefit to the initial injury. The experimental relationship between initial radiation dose and latent period is reproduced: a linear relationship shown at the higher dose region vs. a non-linear response at low dose region.

Conclusion: A three-dimensional ordinary differential equation model is developed to represent late radiation injury to the spinal cord. The model reproduces important features observed in experimental studies. Further validation through experimental data will lead to better a understanding of important cellular interaction processes that determine the late radiation injury to the spinal cord.


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