The volume effect of normal tissues and organs is an important factor for
predicting normal tissue complication probability (NTCP) following partial,
heterogeneous irradiation of organs at risk, and reducing the late sequela by
conformal radiation therapy. We have previously developed a reliability model for
calculation of NTCP, assuming a parallel architecture of functional subunits
(FSU), where a critical number (k) out of the total number of FSUs (N) must be
intact for the organ to maintain its function. Published data on
radiation-induced lethal pneumonitis and altered breathing rate following partial
volume irradiation of the mouse lung were analysed, and critical fraction and
corresponding spatial density distribution of FSUs were estimated using this
model. The critical fraction (k/N) seemed to be similar for the two endpoints,
and a value of 0.7 was found to provide good fit to the experimental data. The
critical fraction did not vary throughout the lung, and variation in volume
effect cannot therefore be attributed to heterogeneous tissue architecture. On
the other hand, our analysis revealed that the observed variation in volume
effect of mouse lung may be attributed to heterogeneous spatial distribution in
FSU density or also the spatial variation in inactivation probability of the
FSUs.