Optimization and validation of automated dicentric chromosome analysis for radiological/nuclear triage applications

Ryan, Terri L.; Escalona, Maria; Smith, Tammy L.; Albanese, Joseph; Iddins, Carol J.; Balajee, Adayabalam S.

doi:10.1016/j.mrgentox.2019.503087

Cited by 20 publications

(17 citation statements)

References 21 publications

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“…dicentric chromosome assay (DCA) [22] was used successfully for dose assessment in incidents like Chernobyl, Goiania, and Fukushima [31][32][33]. However, the DCA technique needs well-trained manpower and is time-consuming which has proved to be the main hindrance in its application [22][23][24]. In the case of MN, the analysis is in uenced by various factors and induced by several agents, thus not radiation speci c [34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…The dicentric chromosome assay (DCA) was initially designed in 1962 and is now considered as a "gold standard" of radiation biodosimetry due to its high speci city and being neutral of gender, age, or region [21][22]. However, it is necessary to take note that the DCA technique needs well-trained manpower and is time-consuming [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Linear Dose Response of Acrocentric Chromosome Associations (Aca) To Gamma Irradiation In Human Lymphocytes

Samarth¹,

Gandhi²,

Chaudhury³

2021

Preprint

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Purpose: The frequency of acrocentric chromosome associations (ACA) was studied to determine the possible dose-response relation with low doses of gamma irradiation in lymphocytes. Methods: Peripheral blood collected from three healthy donors were irradiated with 0, 0.1, 0.25, 0.5, 0.75, and 1 Gy gamma radiation. Chromosomal preparations were made after 48 hrs culture as per the standard guidelines. Results: The average number of ACA and ACA % were increased significantly with an increase in a dose. The D-G and D-D type of association was most prominent and showed a dose-dependent increase. The ACA frequency in irradiated lymphocytes showed an increase concerning the dose. The fitted regression equation was y=0.4759x+0.1663 (R2=0.9635; p=0.0005). An assessment of dicentric chromosomes (DC) was carried for the same slides. The correlation curve was prepared for ACA frequencies versus DC frequencies, resulting in a regression equation as y=8.659x+0.2.37 (R2=0.8275; p=0.0119). Conclusion: Our results showed an increase in frequencies of ACA in irradiated lymphocytes with an increase in radiation dose and followed a similar linear trend with DC frequency, thus, ACA may serve as a candidate cytogenetic biomarker for radiation biodosimetry especially for low radiation doses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Linear Dose Response of Acrocentric Chromosome Associations (Aca) To Gamma Irradiation In Human Lymphocytes

Samarth¹,

Gandhi²,

Chaudhury³

2021

Preprint

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“…Hence, many image training classifiers were created to improve the specificity of automated DC analysis algorithm. However, accuracy and efficiency of the automated (unsupervised) DC scoring are still requiring more optimization for accurate dose estimation (41). In this study, we have used the embedded Metafer DCScore algorithm to evaluate the usefulness of the automated DC score.…”

Section: Discussionmentioning

confidence: 99%

“…The actual dose threshold level may vary with the associated trauma and the capacity of the healthcare system. The automated triage mode can provide valuable preliminary diagnostic evidence to segregate between these various categories of risk groups (41). Of particular significance, the automated mode can provide dose estimations that are close to those calculated by the assisted mode in the critical dose exposure range of 2 Gy, which can rapidly identify low risk victims (<2 Gy), who do not require urgent medical attention and high-risk victims (>2 Gy), requiring immediate medical countermeasures and potential therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Establishing a Reference Dose–Response Calibration Curve for Dicentric Chromosome Aberrations to Assess Accidental Radiation Exposure in Saudi Arabia

Al-Hadyan

Al-Harbi

Judia

et al. 2020

Front. Public Health

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In cases of nuclear and radiological accidents, public health and emergency response need to assess the magnitude of radiation exposure regardless of whether they arise from disaster, negligence, or deliberate act. Here we report the establishment of a national reference dose–response calibration curve (DRCC) for dicentric chromosome (DC), prerequisite to assess radiation doses received in accidental exposures. Peripheral blood samples were collected from 10 volunteers (aged 20–40 years, median = 29 years) of both sexes (three females and seven males). Blood samples, cytogenetic preparation, and analysis followed the International Atomic Energy Agency EPR-Biodosimetry 2011 report. Irradiations were performed using 320 kVp X-rays. Metafer system was used for automated and assisted (elimination of false-positives and inclusion of true-positives) metaphases findings and DC scoring. DC yields were fit to a linear–quadratic model. Results of the assisted DRCC showed some variations among individuals that were not statistically significant (homogeneity test, P = 0.66). There was no effect of age or sex (P > 0.05). To obtain representative national DRCC, data of all volunteers were pooled together and analyzed. The fitted parameters of the radiation-induced DC curve were as follows: Y = 0.0020 (±0.0002) + 0.0369 (±0.0019) *D + 0.0689 (±0.0009) *D2. The high significance of the fitted coefficients (z-test, P < 0.0001), along with the close to 1.0 p-value of the Poisson-based goodness of fit (χ2 = 3.51, degrees of freedom = 7, P = 0.83), indicated excellent fitting with no trend toward lack of fit. The curve was in the middle range of DRCCs published in other populations. The automated DRCC over and under estimated DCs at low (<1 Gy) and high (>2 Gy) doses, respectively, with a significant lack of goodness of fit (P < 0.0001). In conclusion, we have established the reference DRCC for DCs induced by 320 kVp X-rays. There was no effect of age or sex in this cohort of 10 young adults. Although the calibration curve obtained by the automated (unsupervised) scoring misrepresented dicentric yields at low and high doses, it can potentially be useful for triage mode to segregate between false-positive and near 2-Gy exposures from seriously irradiated individuals who require hospitalization.

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“…Development of these techniques continues throughout the world 23 – 25 . High-throughput automated approaches using scanning and imaging software are available to implement these assays 26 – 28 .…”

Section: Introductionmentioning

confidence: 99%

Machine learning methodology for high throughput personalized neutron dose reconstruction in mixed neutron + photon exposures

Shuryak

Turner

Pujol-Canadell

et al. 2021

Sci Rep

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We implemented machine learning in the radiation biodosimetry field to quantitatively reconstruct neutron doses in mixed neutron + photon exposures, which are expected in improvised nuclear device detonations. Such individualized reconstructions are crucial for triage and treatment because neutrons are more biologically damaging than photons. We used a high-throughput micronucleus assay with automated scanning/imaging on lymphocytes from human blood ex-vivo irradiated with 44 different combinations of 0–4 Gy neutrons and 0–15 Gy photons (542 blood samples), which include reanalysis of past experiments. We developed several metrics that describe micronuclei/cell probability distributions in binucleated cells, and used them as predictors in random forest (RF) and XGboost machine learning analyses to reconstruct the neutron dose in each sample. The probability of “overfitting” was minimized by training both algorithms with repeated cross-validation on a randomly-selected subset of the data, and measuring performance on the rest. RF achieved the best performance. Mean R2 for actual vs. reconstructed neutron doses over 300 random training/testing splits was 0.869 (range 0.761 to 0.919) and root mean squared error was 0.239 (0.195 to 0.351) Gy. These results demonstrate the promising potential of machine learning to reconstruct the neutron dose component in clinically-relevant complex radiation exposure scenarios.

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Optimization and validation of automated dicentric chromosome analysis for radiological/nuclear triage applications

Cited by 20 publications

References 21 publications

Linear Dose Response of Acrocentric Chromosome Associations (Aca) To Gamma Irradiation In Human Lymphocytes

Linear Dose Response of Acrocentric Chromosome Associations (Aca) To Gamma Irradiation In Human Lymphocytes

Establishing a Reference Dose–Response Calibration Curve for Dicentric Chromosome Aberrations to Assess Accidental Radiation Exposure in Saudi Arabia

Machine learning methodology for high throughput personalized neutron dose reconstruction in mixed neutron + photon exposures

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