Australian Clinical Guidelines for Radiological Emergencies - September 2012

Radiation Dose Assessment

Page last updated: 07 December 2012

The health effects of ionising radiation exposure to individuals, through external exposure or internal contamination, are dependent on the dose received as well as individual prior disease state. In the investigation of accidental radiation exposure, an estimation of the absorbed dose is needed. Estimates may be used for treatment planning, prognostic advice, epidemiological investigation and reassurance of affected persons, as well as for the management of occupational health and safety.

Methods available to estimate absorbed dose include:

  • Dosimetry readings, if available
  • Physical reconstruction of events to enable dose estimation on the basis of time and proximity to the source
  • Clinical symptoms and signs
  • Lymphocyte depletion kinetics
  • Measurement of radionuclides distributed to specific tissues and contained in excretions
  • Measures of chromosomal aberration in peripheral lymphocytes
  • Measurement of the effects of radiation on tissues such as teeth and nails
  • Analysis of selected materials in the vicinity of the event or carried by the affected person
  • Measurement of sodium activation in humans exposed to a neutron source
Biodosimetry is the direct measurement of radiation induced biological or physical effects within the body to assess the radiation dose to an individual. Such measurements include certain blood tests, urine and faecal radionuclide assays, and whole body and specific organ counts.

Multiple assay techniques are required to refine dose estimates and to address various scenarios and casualty numbers.

Physical Dosimetry

Dosimeter Readings

The availability of personal dosimeter readings provides the best measure of cumulative exposure, assuming whole body exposure from an external source. Limitations of personal dosimetry relate to:
  • awareness of potential exposure and proper wearing of the device
  • the device type. Film badges and thermoluminescent badges must be analysed in a laboratory, delaying the availability of results. However, immediate results can be obtained from electronic personal dosimeters.
  • partial body exposures due to proximity to the source (handling a source, for instance, must result in a localised exposure), or shielding
  • exposure from internal contamination is not effectively measured by personal dosimetry
  • does not account for biological differences in susceptibility to the DNA damaging effect of radiation, which is the fundamental cause of the resulting morbidity and heightened cancer risk.

Physical reconstruction of events

Following identification of the source and its location, health physicists can reconstruct the field intensity and calculate the likely dose received by individuals in that environment adjusted for their proximity to the source and duration of exposure.

The time taken to perform a reconstruction of events is dependent on:
  • recognition of an illness as possibly due to radiological exposure
  • determination of the likely exposure history
  • the search for the source and establishment of radiological safety
  • identification of the properties of the source
  • evaluation of the physical environment in which the exposure took place
  • measurement or calculation of the field intensity, and
  • calculations based on individual movements around the environment.
Dose calculations need to be repeated for each person or similarly-behaved group exposed in that environment.

Biological dosimetry

Clinical Symptoms and Signs

Whilst the symptoms and signs of radiation exposure are non-specific, the timing, severity and pattern characterise the dose received. The main disadvantage is the time required for symptoms and signs to develop.

For known exposures to total body irradiation, the likely severity and timing of the manifest illness can be predicted, particularly from the time of onset of nausea and vomiting. Onset of vomiting less than 4 hours after exposure is consistent with progression to haematopoietic syndrome. Onset of vomiting within 1 hour is characteristic of lethal exposures. Other causes of vomiting, e.g. psychogenic, need to be excluded.

The time to onset of vomiting is the most sensitive clinical sign corresponding to absorbed radiation dose. Importantly, this and the absolute lymphocyte count may be the only means to predict the absorbed dose for affected individuals during the initial days following exposure.

Figure 10.1 Time to onset of vomiting and dose

This graph represents the correspondence between time to onset of vomiting and doseD

Adapted from the Medical Effects of Ionising Radiation Course, presented by the U.S Armed Forces Radiobiology Research Institute.

Table 10.1 Symptom characteristics and timing for various doses of absorbed radiation to the whole body.

Acute Radiation Syndrome
Phase of syndromeFeatureFeatureEffects of whole body irradiation by dose range (Gy)

0-1
Effects of whole body irradiation by dose range (Gy)

1-2
Effects of whole body irradiation by dose range (Gy)

2-4
Effects of whole body irradiation by dose range (Gy)

4-6
Effects of whole body irradiation by dose range (Gy)

6-8
Effects of whole body irradiation by dose range (Gy)

8-30
Effects of whole body irradiation by dose range (Gy)

>30
ProdromalNausea, vomitingAffected personsNone5-50%50-100%50-100%75-100%90-100%100%
ProdromalNausea, vomitingTime of onset3-6 hr2-4 hr2-4 hr1-2 hr< 1 hrMinutes
ProdromalNausea, vomitingDuration< 24 hr2-4 hr2-4 hr< 48 hr< 48 hrN/A
ProdromalDiarrhoeaAffected persons< 10%> 10%100%100%
ProdromalDiarrhoeaTime of onset3-8 hr1-3 hr< 1 hr< 1 hr
ProdromalDiarrhoeaSeverity4-6 stools/d, occasional blood, severe cramping7-8 stools/d, persistent blood, severe cramping> 10 watery, bloody stools/d, excruciating pain> 10 watery, bloody stools/d, excruciating pain
ProdromalHeadacheAffected persons50%80%80-90%80-90%
ProdromalHeadacheTime of onset4-24 hr3-4 hr1-2 hr1-2 hr
ProdromalHeadacheSeverityslightmildmoderatesevereseveresevere
ProdromalTemperatureAffected persons10-80%80-100%100%100%100%
ProdromalTemperatureTime of onset1-3 hr1-2 hr< 1 hr< 1 hr< 1 hr
ProdromalTemperatureSeverity< 38C38-40C> 40C for < 24 hr> 40C for > 24 hr> 40C for > 24 hr
ProdromalConscious
state
SeverityNo impairmentNo impairmentRoutine task performance. Cognitive impairment for 6-20 hrRoutine task performance. Cognitive impairment for 6-20 hrSimple task performance. Cognitive impairment for > 20 hrRapid incapacitation. May have a lucid period of several hoursRapid incapacitation. May have a lucid period of several hours
LatentNo symptoms> 2 wk7-15 d0-7 d0-7 d0-2 dNoneNone
Manifest illnessSymptoms, signsNoneModerate leucopaeniaSevere leucopaenia, purpura, haemorrhage, pneumonia. Hair loss > 3 GySevere leucopaenia, purpura, haemorrhage, pneumonia. Hair loss > 3 GySevere leucopaenia, purpura, haemorrhage, pneumonia. Hair loss > 3 GyDiarrhoea, fever, electrolyte disturbanceConvulsions, ataxia, tremor, lethargy
Manifest illnessOrgan systemNoneHaemopoietic, respiratory mucosaHaemopoietic, respiratory mucosaHaemopoietic, respiratory mucosaGastrointestinalCNS, CVS
Manifest illnessTime of onset> 2 wk2 d to 2 wk2 d to 2 wk2 d to 2 wk1-3 d1-3 d

Adapted from AFRRI. Medical management of radiological casualties handbook. 2nd ed. 2003.


Localised radiation exposures may result in cutaneous injury. The characteristic symptoms and signs are described in Table 10.2. Photographs are useful to document the progress of the injury.

Table 10.2 Symptom characteristics and timing for various doses of absorbed radiation to the skin

Cutaneous Radiation Syndrome
Phase of syndromeFeatureTime of onset for effects of local irradiation by dose range (Gy)

< 3
Time of onset for effects of local irradiation by dose range (Gy)

3-6
Time of onset for effects of local irradiation by dose range (Gy)

6-10
Time of onset for effects of local irradiation by dose range (Gy)

10-15
Time of onset for effects of local irradiation by dose range (Gy)

15-30
Time of onset for effects of local irradiation by dose range (Gy)

> 30
Time of onset for effects of local irradiation by dose range (Gy)

> 50
ProdromalTransient erythema or abnormal sensation (pruritis or pain)NoneNone12-24 hr8-15 hr3-6 hr3-6 hr
ProdromalOedema3-6 hr3-6 hr
LatentDuration2-5 w1-3 w0-2 w
Manifest illnessEpilation14-21 d
Manifest illnessErythema 20-30 d14-21 d20-24 d15-20 d8-14 d4-6 d
Manifest illnessDry desquamation6-7 w14-21 d
Manifest illnessBlisters20-25 d10-18 d6-8 d
Manifest illnessMoist desquamation2-3 w10-18 d6-8 d
Manifest illnessUlceration20-30 d
Manifest illnessOvert radionecrosis > 90 d> 4 w

Adapted from IAEA. Diagnosis and treatment of radiation injuries. 1997

Lymphocyte Depletion Kinetics

Lymphocytes are the most radiation-sensitive haemopoietic element. Predictable decline in lymphocytes occurs following exposure to radiation. The absolute lymphocyte count should be measured 6 hourly for the initial 48 hours and periodically thereafter.

A fall of 50% in the first 24 hours is suggestive of a potentially lethal radiation exposure.

Table 10.3 Biodosimetry based on acute photon equivalent exposures
Dose

Gy
Lymphocyte count (x109/L) at day

0.5
Lymphocyte count (x109/L) at day

1
Lymphocyte count (x109/L) at day

2
Lymphocyte count (x109/L) at day

4
Lymphocyte count (x109/L) at day

6
Lymphocyte count (x109/L) at day

8
Lymphocyte depletion rate

Rate constant
0
2.45*
2.45
2.45
2.45
2.45
2.45
-
1
2.30
2.16
1.90
1.48
1.15
0.89
0.126
2
2.16
1.90
1.48
0.89
0.54
0.33
0.252
3
2.03
1.68
1.15
0.54
0.25
0.12
0.378
4
1.90
1.48
0.89
0.33
0.12
.044
0.504
5
1.79
1.31
0.69
0.20
0.06
.020
0.63
6
1.68
1.15
0.54
0.12
0.03
.006
0.756
7
1.58
1.01
0.42
.072
.012
.002
0.881
8
1.48
0.89
0.33
.044
.006
<.001
1.01
9
1.39
0.79
0.25
.030
.003
<.001
1.13

The normal range for lymphocytes in human blood is between 1.4 and 3.5 x 109 per litre

Adapted from the Medical Effects of Ionising Radiation Course, presented by the U.S Armed Forces Radiobiology Research Institute.

Measurement of specific radionuclides

In addition to the techniques discussed in this chapter, in circumstances of internal radiological contamination, dose may be assessed by:
  • contamination survey (including nasal swabs and wound dressings)
  • whole body and specific organ counts, and
  • bioassay of bodily fluids (urine, faeces, pulmonary lavage washings)
The principles of dose assessment following internal contamination are discussed in detail from page 91.

Cytogenetics

Cytogenetics is indicated when:
  • time to emesis is less than 2 hours after exposure
  • lymphocyte counts are depleted to less than 50% within 12 hours of exposure
  • geographical location-based physical dosimetry indicates a dose of > 3 Gy
  • there are multiple clinical symptoms indicative of acute radiation syndrome.
Cytogenetics may also be used in evaluating asymptomatic exposed persons in an epidemiological evaluation of an incident, for prognostic advice and to plan longer-term surveillance.

Dicentric Assay

Chromosomal dicentrics and ring forms are formed during cell division in cells affected by radiation. These can be identified during metaphase. The frequency of formation corresponds to the absorbed dose of radiation.

Figure 10.2 Dicentric and fragment
This image shows dicentric and ring chromosomes in a slide preparation of activated lymphocytes arrested in metaphase. The dicentric and ring chromosomes are circled in redD

This assay is the most specific and sensitive method for determining absorbed doses from recent (from within days up to six months) exposures to ionising radiation. Dicentric and ring chromosomes are identified from slide preparations of activated lymphocytes arrested in metaphase. From 500 to 1000 cells may require scoring, requiring 2 – 3 person-days at the microscope. At least 100 dicentrics should be identified. The dose is estimated from calibration curves developed by irradiating in vitro samples of blood. The range of absorbed dose detectable using this technique is 0.2 to 5.0 Gy.

The usefulness of dicentric analysis is limited to exposures occurring in the previous six months because of the half-life of the cells containing the chromosomal aberrations. As lymphocyte activation requires cell culture and mitosis, the result is not especially timely, taking 4 to 5 days to complete, and up to 2 weeks for results to become available if the sample is sent overseas. Capacity is also limited with cytogenetics laboratories able to process a maximum of 50 to 200 samples per week.

Dicentric analysis is a labour intensive technique that can be adapted for application to mass casualties. The technique can be modified, by reducing the number of metaphases scored to 50, in order to increase throughput of samples. Reporting of this sample triage provides a likely absorbed dose range useful for identification of individuals requiring medical intervention. These individuals can have repeat dicentric assays to more precisely determine their absorbed dose.

It is expected that the reporting format for dicentric analysis sample triage would be expressed as a range. For example:
  • < 1.0 Gy
  • 1.0 – 3.5 Gy
  • 3.5 – 5.0 Gy
  • > 5.0 Gy

Table 10.4 Comparison of dicentric assay techniques for dose assessment
Dose estimate (Gy)
Dicentrics in human peripheral blood lymphocytes

Per 50 cells (sample triage)
Dicentrics in human peripheral blood lymphocytes

Per 1000 cells (dicentric assay)
0
0.05-0.10
1-2
1
4
88
2
12
234
3
22
439
4
35
703
5
51
1024

Adapted from Wasalenko JK, et al. Ann Int Med. 2004; 140: 1037-1051.

Present arrangements for dicentric assay require specimens to be transported overseas. Under the International Health Regulations, the World Health Organisation is developing a global biodosimetry network of reference and supporting laboratories. This network will facilitate common standard operating procedures and surge capacity arrangements.

Dicentric assay is available within Australia at the CSIRO DNA Damage Diagnostics Laboratory in Adelaide and will soon be made available for radiation biodosimetry purposes. This laboratory is participating in the WHO Biodose network to comply with the standard protocol with a view to being established as a reference laboratory in the network. The test is expected to be made available for radiation biological dosimetry purposes by mid-2010.

There are other Australian clinical cytogenetics laboratories performing assays for prenatal screening, developmental delay and cancer investigation. These laboratories may be able to assist under protocols for mass screening.

Laboratories performing dicentric assay should meet the International Organisation for Standardisation (ISO) standard – Performance criteria for service laboratories performing biological dosimetry by cytogenetics (ISO 19238).

Cytokinesis block micronucleus (CBMN) assay

Micronuclei are formed when acentric chromosomal fragments caused by exposure to ionising radiation do not integrate into the nuclei of daughter cells during ex vivo division in cultured lymphocytes from peripheral blood. In this assay it is also possible to measure nucleoplasmic bridges that are formed from dicentric chromosomes induced by ionising radiation.

This technique requires less skill and time than dicentric assay, and is suitable for automated imaging of binucleated cells. Dose estimation correlates well to dicentric assay using appropriate calibration curves.

The sensitivity of this technique is limited to thresholds of 0.3 Gy, due to the presence of background micronuclei from other environmental causes. This is still sufficiently sensitive to identify persons needing medical intervention from those requiring continued surveillance.

This assay is available in Australia at the DNA Damage Diagnostics Laboratory led by Prof. Michael Fenech at CSIRO Human Nutrition in Adelaide using both visual and automated scoring.

Figure 10.3 (A) Bi-nucleated lymphocyte containing a micronucleus (MN); (B) Bi-nucleated cell containing a nucleoplasmic bridge (NPB) and a micronucleus (MN).


Figure 10.3 (A) Bi-nucleated lymphocyte containing a micronucleus (MN); (B) Bi-nucleated cell containing a nucleoplasmic bridge (NPB) and a micronucleus (MN) - This image shows cultured lymphocytes at cell division with the formation of a separate micronuD


This photomicrograph was kindly provided by Prof. Michael Fenech from the Genome Damage Diagnostics Laboratory at CSIRO Human Nutrition, Adelaide, South Australia

Fluorescence in situ hybridisation (FISH) assay

Stable chromosomal translocations caused by radiation can persist over decades, unlike dicentrics. These can be identified using fluorescent microscopy using chromosome-specific fluorescently-labelled DNA probes. This research tool is limited by availability, turnaround time, and cost. Additionally, translocations may occur due to other environmental factors, limiting accuracy without pre-event samples.

Figure 10.4 Fluorescent labelling of chromosomal translocations
Image displays Figure 10.4 Fluorescent labelling of chromosomal translocationsD


This image from Sykes P, and Bain S; Laboratory capacity for cytogenetic analysis in Australia. Presented at the National Workshop on Biodosimetry Assessment, Yallambie, Victoria, August 2008

Premature chromosome condensation (PCC) assay

At radiation doses > 5 Gy, cells may never progress to mitosis because of the extent of damage. This may result in an underestimate of the absorbed dose at higher exposures where lymphocyte activation is a step in the assay.
Fusion of human lymphocytes with Chinese hamster ovary mitotic cells allows the identification of chromosomal aberration without lymphocyte activation.

Electron paramagnetic resonance (EPR) / Electron spin resonance (ESR)

When radiation causes ionisation of materials, most electrons recombine. However in relatively non-aqueous materials, some become trapped. In a magnetic field, the trapped electrons can be induced to provide a resonance spectrum.

This technique can be applied to relatively dry materials, such as teeth, bones and fingernail clippings. This is a validated technique with application in palaeontology. It has also been used in studies of atomic bomb survivors, Chernobyl victims and investigation of radiological over-exposures.

Radiation-induced changes in teeth are extremely stable, enabling measurement at any time after exposure. Naturally exfoliated teeth have been utilised in retrospective studies. Dental biopsies can also be used. However, rapid techniques have been developed for examination of teeth in situ, although this is not widely available. Molar teeth are preferred as they are not subject to UV radiation exposure. Dental disease may also alter the mineralisation of teeth, affecting measurements.

The dose range that can be detected using EPR on teeth is 0.1 Gy to several thousand Gy.

Bone has been used in retrospective analysis of amputated limbs in circumstances of localised radiation injury. Fingernail clippings are readily available, although children’s nails may have insufficient volume for this technique. Fingernail clippings need to be collected within 30 days.

The measurement obtained is the dose received by those specific tissues (teeth, bone or fingernails). If the exposure to the individual was not homogeneous, or occurred from internal contamination, this may not reflect the total dose received.

EPR on dental biopsies may be used to verify dose when considering heroic treatment measures for life-threatening exposures.

Luminescence

Luminescence is a technique that can apply to event reconstruction, as well as direct and indirect biodosimetry.

When radiation causes ionisation of materials, most electrons recombine. However some become trapped and will recombine only under an appropriate light or thermal stimulus. On recombining, a photon is released. The quantity of photons (luminescence) produced is equivalent to the number of trapped electrons, which is proportional to the absorbed radiation dose.

It is applicable to materials such as quartz, feldspar, mortar, concrete, gypsum, brick, ceramics, salt and many others. This is a validated technique with extensive applications in palaeontology, art authentication, soil science and UN nuclear weapons inspections.

Research is underway to validate the forensic application of this technique for examination of sites used to construct or store radiological and nuclear material, even when there is no residual radioactive contamination. It could be applied to retrospective examination of a location where a population was exposed to a covert source, identifying and quantifying the extent of exposure by an examination of the building materials. It enhances modelling of the field intensity of a removed source, by determining how long the source was in situ, and therefore the duration of exposure of affected persons.

There is potential for luminescence to be used to examine materials carried by people, such as credit cards, glass (in spectacles and watch covers), and jewellery to provide indirect biodosimetry.

Luminescence can also be applied to tooth enamel, bone and fingernail clippings to provide direct biodosimetry.

The objective of the Australian research program is the extension of protocols to new materials and the development of standard operating procedures to enable analysis to occur rapidly and flexibly.

Comparison of laboratory techniques for biodosimetry

The selection of appropriate laboratory tests to support dose estimation relates to a number of factors, summarised in Table 10.5. In a mass exposure event, the most suitable techniques for mass screening are clinical evaluation, lymphocyte depletion kinetics, dicentric assay sample triage, and automated cytokinesis block micronucleus assay.

Table 10.5 Comparison of laboratory techniques for biodosimetry

TechniqueDose range detectable (Gy)Measurement periodSpecimenPurposeAvailable in AustraliaTurnaround timeSample capacity per week
Dicentric assay0.2 to 5.01st six months after exposureWhole bloodDefinitive testFrom mid-20102 weeks50 - 200
CBMN assay0.3 to 5.01st six months after exposureWhole bloodTriage cytogenetics, definitive testYes2 – 3 days80*
300#
FISHDecadesWhole bloodRetrospective cytogeneticsResearch or special interest only
PCC1st six months after exposureWhole bloodConfirmation of doses > 5.0 Gy
EPR / ESR0.1 to 1000sTeeth indefinite;
Fingernails < 30 days (or clipped and stored at low temperature)
Teeth, fingernail clippingsConfirmation of doses > 5.0 GyYes, in vitro onlyIn situ dental readings < 5 minutes
Luminescence0.1 to 1000Building materials, etcEvent reconstructionForensic protocols in development

* Visual scoring. # Automated scoring.

Neutron activation

Where there is exposure to a neutron source, such as a reactor or critical assembly or selected industrial radiography sources, sodium activation may occur. Briefly holding a gamma survey instrument against the umbilicus to measure sodium activation is a straightforward indicator of the severity of the exposure and a useful screening tool. More precise measurement can be obtained with a whole-body counter, subsequently.

Biodosimetry Assessment Tool (BAT)


This image is of the Biodosimetry Assessment Tool (BAT) logo.

The U.S. Armed Forces Radiobiology Research Institute (AFRRI) has developed a software tool to assist in the dynamic recording of clinical and other data, interpret key parameters for estimation of dose, and summarise diagnostic and therapeutic information.

The tool is structured around sets of information pertaining to physical dosimetry, anatomical distribution of contamination, wound type, skin changes, prodromal symptoms, haematological indicators, and signs of manifest illness. The dose estimation is based on the available patient data compared with documented radiation dose responses, and revised as additional information is entered.

The software application can be accessed at Armed Forces Radiobiology Research Institute. The software is also available on cd-rom. A series of templates can be downloaded to assist in documenting relevant information.

Summary

Unavailable or inaccurate initial absorbed dose estimates can result in suboptimal medical intervention.

In instances of suspected radiological exposure, a number of indicators and measures may be used to determine the likely absorbed dose of ionising radiation. Each provides an estimation of dose range with recognised limitations in sensitivity, specificity and accuracy. Collectively the multi-parameter approach is used to create the best statistical evaluation of dose.

Where overexposure is suspected:
  • obtain a clinical and a location history
  • observe and document all prodromal symptoms and signs, including erythema. Photograph cutaneous injuries
  • obtain a full blood examination and differential cell count with absolute lymphocyte count immediately. Repeat every 6 hours for the first 48 hours, and 12 hourly for the subsequent 2 days
  • perform measurement and bioassay, if appropriate, for internal contamination
  • contact a qualified laboratory for dicentric assay. Seek guidance from the state or territory radiation safety unit with regard to assistance in arranging this.
  • consider other opportunistic dosimetry approaches as available
  • consider data entry into the Biodosimetry Assessment Tool
Dose assessments contribute, but should not be used alone to dictate life-saving medical treatment decisions. Factors such as dose rate and radiation quality can profoundly influence clinical outcome.

References

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