# Neural Network Ensemble to Detect Dicentric Chromosomes in Metaphase Images
## 1 Introduction
Since most deterministic effects increase as a function of radiation dose, absorbed dose estimation will help in choosing the appropriate medical countermeasures to mitigate or alleviate the severity of IR-induced radiation injuries or sickness. The DCA is universally accepted as the gold standard for absorbed radiation dose estimation [14] due to several salient features: (I) the low baseline frequency of dicentric chromosomes (1 dicentric chromosome in 1000 T-lymphocytes, 0.001/cell), (II) baseline frequency is not modulated by age and gender, (III) it is fairly specific to radiation exposure, (IV) it has a radiation dose-dependent formation and (V) the detection range is from 0.05 to 5 Gy. The upper limit of detection can be extended to >20 Gy using a technique known as prematurely condensed chromosomes (PCCs), performed by cell fusion in the G0/G1 phase and by Calyculin-A in the G2 phase of the cell cycle. Since the centromic regions of the PCCs are not clearly detectable in Giemsa-stained preparations, fluorescence in situ hybridization (FISH) with a pan-centromeric DNA probe is needed to detect dicentric chromosomes. Dicentric chromosomes are formed due to the mis-rejoining of two broken chromosomes with intact centromeres. Dicentric chromosomes, in most cases, are accompanied by acentric fragments resulting from the two broken chromosomes. Since the number of dicentric chromosomes increases as a function of radiation dose, absorbed radiation dose can be easily estimated from the frequency of dicentric chromosomes using several currently available algorithms (Dose Estimate, CABAS and BioDose) with an ex vivo generated dose-response curve, using either X-rays or gamma rays. DCA is labor-intensive and the turnaround time for dose estimation varies from 72 to 96 h. Manual scoring of dicentric chromosomes creates one of the bottlenecks for large-scale incidents or accidents where absorbed dose estimation is needed for hundreds of thousands of exposed individuals. Developing an efficient automated detection system for dicentric chromosomes would considerably shorten the manual scoring time and help in biodose estimation for medical intervention, particularly for those who received high-dose exposures (>2 Gy). To accelerate the speed of dicentric chromosome detection/counting in the metaphase images of lymphocytes, an AI-based approach was undertaken in this study. Studies have shown that there is a relationship between the frequency of dicentric chromosomes and radiation exposure dose [15; 16; 17]. The frequency officentrics is dependent on the absorbed dose. The linear quadratic equation for the yield of dicentrics is as follows:  
\[Y=\alpha D+\beta D^{2}+c\]  
where \(Y\) corresponds to the frequency of dicentrics, \(D\) to the radiation dose and \(c\) to the frequency of dicentrics prior to exposure. \(\alpha\) and \(\beta\) are coefficients obtained from statistical analysis. Owing to a low base line frequency of dicentric chromosomes in healthy individuals (1 dicentric chromosomes in 1000 lymphocytes 0.001/cell), the \(c\) value is usually negligible [18]. On the other hand, the coefficient \(\beta\) usually tends toward 0 for particularly high LET radiation such as neutrons. Hence, in this way, the dose effect relationship is linear for dicentrics:  
\[Y=\alpha D\]  
Therefore, the absorbed radiation dose can be easily estimated from the yield of dicentric chromosomes, and thus the prognosis of the patient can be established: an individual who has received an absorbed dose less than 2 Gy has a high chance of survival; if the absorbed dose ranges between 2 and 6 Gy, there is a chance of survival if the individual receives adequate medical countermeasures; and if the absorbed dose is higher than 6 Gy, chance of survival will be minimal, and therefore palliative treatment should be given.