Measurement of Local Activity in the Wound

Direct measurement of the activity in the wound site is required for the estimation of the activity retained in the wound. If surgical removal of tissues is involved, measurement of the wound site before and after the tissue excision and measurements of excised tissue is required.

Monitoring procedures include the scan of the wound area to identify the activity level, define the diameter of the contaminated region, and determine the wound depth.

Wound measurements allow the identification and quantification of x-ray and gamma emitting radionuclides deposited in the wound site. The determination of the wound contamination of alpha emitters emitting low energy photons is especially challenging. The sensitivity of the measurement to wound-to-detector geometry and to wound depth should be taken into consideration. In case of alpha or beta wound contamination, a standard contamination survey instrument may be used for wound monitoring.

Successive measurements of the wound site allow the determination of the retention of the activity of radionuclides as a function of time. Methods for the calibration of detection systems should be established by defining proper counting geometry and using appropriate calibration sources that simulate wound contamination. The use of wound phantoms allows for the efficient calibration of detection systems. Wound-depth calibration is especially challenging. An alternative assessment of local activity can be achieved using Monte Carlo simulations of the wound measurement.Reference Broggio, Zhang and de Carlan^4, Reference Nadar, Patni and Akar⁵

No standard reference wound phantoms are available so far. The IRSN in France has fabricated a wound phantom using tissue substitute EVA (ethylvinylacetate) foam of circular shape (red in Figure 1). Partially contaminated cellulose filter and a drop of radioactive material (1 cm²) (blue plate in Figure 1) allow for the simulation of puncture-wound contamination. Tissue equivalent PMMA (polymethyl methacrylate) blank plates with a diameter of 10 cm and a thickness of 0.2 cm are used to simulate different depths of contamination. The plate of the source can be placed between the standard blank plates (Figure 1).

Figure 1. IRSN (left and centre) and SÚRO (right) wound calibration phantoms (dimensions in mm).

SÚRO (Czech Republic) has developed a wound-depth calibration phantom for ²⁴¹Am matrices or americium-containing Pu matrices⁶ (Figure 1). The phantom consists of an absorber made of PMMA with a tiny radionuclide source (an ion-exchange resin bead of a diameter 0.7–0.8 mm, with an average weight 0.4 mg and a volume of 0.18 mm³ for 0.8 mm diameter, containing ²⁴¹Am bound) simulating a puncture-wound and containing a metrologically measured activity to carry out calibration procedures. The PMMA absorbers consist of (1) a cast PMMA block (20 mm thick) with a borehole (ø 1 mm) for inserting radionuclide sources and (2) PMMA plates of various thicknesses to simulating additional tissue layers when placed over the absorber. Fifty beads were selected and used for sorption of ²⁴¹Am from a standard solution. Three types of phantoms were manufactured with different radionuclide source patterns: a single ion-exchange resin bead forming a point source for detector calibration purposes, 7 beads in a line forming a cca 6 mm-long line source for demonstration of the measurement uncertainty, and a 2-point source formed by 2 single beads placed in a 10 mm mutual distance for testing the spatial resolution of a detector. It is important to mention the limitations of phantom materials (EVA and PMMA) simulating radiation interactions with body tissues.

In Vivo/In Vitro Bioassay to Determine Systemic Contamination

The in vivo and in vitro monitoring methods to be applied are like those used in routine monitoring.

Whole body counting (shielding the wound site) serves to obtain the radionuclide activity retained in the total body (in case of x-ray and gamma emitters) after absorption from the wound entry. Radionuclides entering the bloodstream can also be retained in certain organs and tissues according to their biokinetics and can be measured by in vivo monitoring methods, if feasible.

In vitro bioassays allow for obtaining the activity excreted in urine/feces for alpha, beta, and gamma emitters, and should start as soon as possible. A 24-hour collection of urine samples is recommended, and 24-hour or 72-hour fecal samples are common practice. In case of chelation therapy, measurements of excreta samples are recommended before and after DTPA administration (this decorporation therapy is only considered for transuranium elements), permitting evaluation of its effectiveness.

Interpretation of Monitoring Data for Dose Assessments

There have been many ad hoc approaches for the interpretation of bioassay data after wound contamination. In some cases, bioassay data collected after a wound incident have been analyzed assuming injection. This simple approach may help explain bioassay data, particularly for contaminants dominated by highly-soluble materials.

Application of the NCRP 156 Wound Models

No consensus biokinetic model for the translocation of radioactive materials via wounds existed until the publication of NCRP Report 156.⁷ The NCRP Report 156 describes a multi-compartmental wound model based on biochemical principles. The model consists of 5 compartments – soluble; colloidal and intermediate states (CIS); particle, aggregates and bound states (PABS); trapped particles and aggregates (TPA); and fragments – that lead to uptake into the blood or clearance into the lymph nodes (Figure 2). The compartments describe the behavior of different physicochemical forms of the radioactive materials regardless of the initial physical and chemical state. The default categories of the radioactive materials defined in the report are: soluble, colloid, particulate, and fragment. Materials introduced into the wound initially in a soluble form enter the soluble compartment, from where a fraction is absorbed into the blood and the remainder into the CIS compartment. Material in the CIS and PABS compartments solubilize and transfer back into the soluble compartments. A fraction of the activity in the CIS and PABS compartments is transferred to the lymph nodes. The “soluble” material is divided into the retention classes of weak, moderate, strong, and avid categories depending on the solubility of the contaminant. Several radionuclides are assigned to 1 of these categories as judged by the patterns of retention of the injected radioactive material retained at the wound site after an intramuscular injection. Table 1 lists the nuclides (ions) in each category.

Figure 2. General compartmental model of the biokinetics of radioactive materials in wound (with permission of the National Council on Radiation Protection and Measurements, http://NCRPonline.org).

Table 1. Radionuclides in different NCRP 156 default retention categories

Particulate radionuclides are grouped into categories of colloids, particles, and fragments. The colloids, particles, and fragments are introduced into the wound by direct injection into the CIS, PABS, and fragment compartments, respectively.

Particles and fragments include solid materials, such as mixed oxides or metal alloys. The major difference between the particles and fragments is that the latter are too large (>20 μm) to be phagocytized and, thus, have potential to cause foreign body reactions to the tissue.

The transfer among the compartments is described by first-order kinetics or multi-exponential equations to represent the average retention behavior of different categories of materials.

The NCRP 156 wound models describe the translocation of material within the wound and clearance to the blood and to the lymph nodes. The models can be combined with a systemic model and an alimentary tract model to describe the complete behavior of radioactive material after a wound intake. The latest systemic models for different radionuclides are given in a series of publications by the International Commission on Radiological Protection (ICRP).^8–11

The system of the models can be “solved” to obtain time-dependent retention and excretion of radioactive materials after wound contamination. One can also obtain a rough estimate of intake from measurements of activity in the wound site. This is particularly true for particles and fragments, which are retained more strongly in the wound. Wound counts, along with urine and/or fecal measurements, provide important inferences regarding the solubility of the material.Reference Poudel, Guilmette and Klumpp^12, Reference Poudel, Klumpp and Bertelli¹³ While wound counts can be useful, one needs to consider many factors before using wound counts to estimate an intake. For example, for soluble and colloidal contaminants, it is important to consider the fraction of the intake that is already absorbed into the blood.

The NCRP 156 wound models were heavily based on data from animal experiments, and the authors of the models acknowledged this limitation and encouraged application of the model to human wound cases for validation and improvement.Reference Guilmette and Durbin¹⁴ Poudel et al.Reference Poudel, Klumpp and Waters¹⁵ reviewed applications of the NCRP 156 wound models to a limited number of plutonium- and americium-contaminated wounds. In many cases, some modifications to the parameters of the NCRP 156 wound models were needed to accurately describe the bioassay data.

Often, a combination of the wound models – rather than a single model – have been used to describe the bioassay data after wound contamination. For example, Poudel et al.Reference Poudel, Guilmette and Klumpp¹² applied a combination of the wound models to successfully explain both the urinary excretion data and wound retention data in 3 of the 4 cases from the Rocky Flats Plant.Reference Falk, Daugherty and Aldrich¹⁶

In another case, a Bayesian Markov-chain Monte Carlo codeReference Miller, Inkret and Martz^17–Reference Poudel, Miller and Klumpp¹⁹ used 7 biokinetic models: 4 NCRP 156 wound models, 2 specific wound models, and 1 injection model – to estimate intakes and doses from contaminated wounds. This method assigns equal probability to these biokinetic models (which constitute the priors) and computes the expected values of the intake and committed effective doses, as well as the posterior probability for each type of model.

It is important to note that modelling of biokinetics after contaminated wounds is particularly difficult, because contaminated wounds, by nature, have a large array of characteristics. The characteristics of the contaminant, e.g., the solubility, chemistry, particle size, and mass, greatly influence its behavior in the wound. In addition, the type of the wound and the degree of the tissue injury – i.e., whether the injury is a burn, abrasion, laceration, or a puncture – can also affect the biokinetics of the contaminant. IlyinReference Ilyin, Gusev, Guskova and Mettler²⁰ concluded that absorption of radionuclides from stab wounds (modelled by intramuscular injection) is higher compared with cutaneous and muscle wounds and lacerated wounds. Moreover, the pathophysiological response of the tissue, such as inflammation, edema, fibrosis, or encapsulation, also complicates the behavior of the radioactive material in the wound. Regardless, experience with human data has shown that the default recommendations in the NCRP 156 wound models can be used as a starting point.

Dosimetric Models

Dose coefficients for inhalation and ingestion have been available and in use for decades; however, because of the lack of a standard wound model until the publication of the NCRP Report 156, dose coefficients for intakes via wound were unavailable. After the publication of the NCRP Report, systemic dose coefficients can be calculated by coupling the wound models with an element-specific systemic model. The NCRP Report provides systemic dose coefficients for wound intakes of uranium of different forms but does not do so for other radionuclides. Instead, the report provides only the upper limits of the dose coefficients for several radionuclides. It is important to note that these upper limits are based on an assumption that all the activity deposited in the wound site becomes systemic. While these dose coefficients may be very close to the actual dose coefficients for intakes of soluble radionuclides, they may significantly overestimate the doses due to wound intake of radionuclides in particle or fragment forms.

Recognizing the lack of dose coefficients for wound intakes, Toohey et al.Reference Toohey, Bertelli and Sugarman^21, Reference Toohey, Bertelli and Sugarman²² computed the committed effective dose coefficients and equivalent dose coefficients for intakes via contaminated wounds for several radionuclides. These coefficients were obtained by coupling the older systemic models; one can do the same with the new systemic models. Bertelli et al.Reference Bertelli, Reis and Klumpp²³ (2025) provided dose coefficients obtained by combining the NCRP 156 wound models with the ICRP OIR (Occupational Intake of Radionuclides) series of systemic models^8–11 and using the new dosimetric methodology.²⁴

Galipeau et al.Reference Galipeau, Sugarman and Waller²⁵ calculated the local dose coefficients for different geometries of wounds contaminated with 38 commonly encountered radionuclides. The local dose coefficients were then used to create a suggested activity limit above which clinically significant effects may occur.

Software Tools for Dose Assessment

Several computer codes have been developed to assist in dose assessment after intakes of radionuclides. Examples of tools that allow users to evaluate intakes via contaminated wounds and to calculate whole-body or specific organs are discussed below.

VARSKIN

The VARSKIN code, sponsored by the US Nuclear Regulatory Program (USNRC), is widely used to calculate occupational dose to the skin. The latest version of the code, referred to as VARSKIN+,Reference Hamby, Mangini and Luitjens³¹ is distributed through the Radiation Protection Computer Code Analysis and Maintenance Program (RAMP). In this version, nuclide libraries from both the ICRP Publication 38³² and 107²⁴ are available. VARSKIN+ Version 1.0 includes a module for wound dosimetry.

“WoundDose” module (Figure 3) implements the recommendations of the NCRP Report 156 to calculate (1) shallow dose, determined at a basal-layer depth of 70 μm beneath the surface of the skin, (2) local dose to tissues surrounding the injured skin, and (3) committed organ/effective dose from contaminated wounds due to industrial or medical events.Reference Klumpp, Poudel and Dumit³⁰ For systemic dosimetry, the “WoundDose” module implements all 7 NCRP 156 solubility categories, by using dose coefficients calculated based on the NCRP wound model.Reference Ilyin, Gusev, Guskova and Mettler^20, Reference Toohey, Bertelli and Sugarman²² The code also allows for entering the user-defined biological half-life for wound retention.

Figure 3. VARSKIN+ user interface for the “WoundDose” module.

IMBA

The IMBA^TM software was jointly developed by the National Radiological Protection Board (now incorporated into the UK Health Security Agency), British Nuclear Fuels Ltd, and the Westlakes Research Institute.Reference Birchall, Jarvis and Peace³³ NRPB and ACJ & Associates, Inc. (USA) incorporated these code modules into the IMBA^TM Expert and Professional Plus series of customized bioassay and internal dosimetry software applications.Reference Birchall, Puncher and James^34, Reference Birchall, Puncher and Marsh³⁵

Currently, the code is available in 3 standard versions - IMBA^Lite, IMBA^Plus, and IMBA^Pro, distributed by the USNRC through the RAMP program or by UKHSA for Europe.

The advanced feature of both the IMBA^Plus and IMBA^Pro versions is the ability to deal with intakes from contaminated wounds (Figure 4). Users can choose 1 of the default wound retention categories defined in the NCRP Report 156 or enter their own values for the retention function as a sum of exponentials. The default retention functions implemented in IMBA^TM have been calculated by solving the compartmental wound model for each wound retention category. Therefore, the IMBA^TM retention functions are slightly different from those published by the NCRP⁷, which represent the retention in the wound only.

Figure 4. Interface of the wound retention model implemented in IMBA^TM.

Taurus

A new internal dosimetry software application called “Taurus” is under development by UKHSA; it is the successor to IMBA^TM, and implements the biokinetic and dosimetric methodology that underpins the ICRP OIR series of publications. Taurus combines the prospective calculation functionality from UKHSA’s PLEIADES codeReference Fell, Phipps and Smith³⁶, used to produce reference bioassay and dose data for ICRP publications, with an updated fitting module, based on the one in IMBA^TM, for retrospective calculation of intakes and doses from bioassay measurements.

A version of Taurus with wound dosimetry functionality, using the NCRP 156 wound model in conjunction with OIR methodology, is already available. Calculations can be conducted for wounds containing a mixture of 2 or more NCRP 156 material retention types; the “Linked” intake regime functionality in the software permits the fraction of each type to be fixed for data-fitting purposes, if required (Figure 5).

Figure 5. Taurus and DPlot output showing results for a simultaneous fit to wound and urine measurement data for a wound involving 2 NCRP wound model retention parameter types, Soluble “Strong” (WS) and “Fragment” (WF).

IDode

The IDode software packageReference Dumit, Bertelli and Klumpp^27, Reference Miller, Bertelli and Klare³⁸ is a state-of-the-art code that can handle unique, complex problems, and is able to perform powerful statistical analysis, which are indispensable for chelation modelling studies and internal dosimetry (Figure 6). IDode can solve second-order kinetics and allows for the construction of a pharmacokinetic front-end for biokinetic models.

Figure 6. IDode interface showing the plot.

IDode software has been used in numerous studies and has showed to be a crucial modelling tool for building not only chelation models but also a variety of biokinetic models: wound models and systemic models, for example. The program will be freely shared with other researchers by request to IDodeSoftware@gmail.com.

MIODOSE

The MIODOSE software allows the estimation of internal dose from bioassay measurements.Reference Davesne, Blanchardon and Bohand^39, Reference Bodin and Menetrier⁴⁰ MIODOSE offers the functionality of managing intakes through different pathways (inhalation, ingestion, injection, and wound).

MIODOSE solves the ICRP biokinetic models: the OIR series are implemented as well as the former ICRP models. Effective doses and organ doses are also calculated according to ICRP methodology. MIODOSE has been extensively benchmarked against data provided by the ICRP OIR Data Viewer. The NCRP Report 156 wound model linked to the ICRP systemic models is also implemented and includes all 7 default retention categories. Moreover, because biokinetic models are solved in MIODOSE, one could define other wound models or modify transfer rates of the NCRP model if needed. Figure 7 shows bioassay data fitting and dose assessment for a wound case. This case involves plutonium and americium, and chelation therapy by DTPA injections for several days; the case is taken from example 4 of EC Report 188.⁴¹

Figure 7. Urine data fitting and dose assessment with MIODOSE for a wound case.