RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

The 2019-2020 EURADOS WG10 and RENEB Field Test of Retrospective Dosimetry Methods in a Small-Scale Incident Involving Ionizing Radiation.

With the use of ionizing radiation comes the risk of accidents and malevolent misuse. When unplanned exposures occur, there are several methods which can be used to retrospectively reconstruct individual radiation exposures; biological methods include analysis of aberrations and damage of chromosomes and DNA, while physical methods rely on luminescence (TL/OSL) or EPR signals. To ensure the quality and dependability of these methods, they should be evaluated under realistic exposure conditions. In 2019, EURADOS Working Group 10 and RENEB organized a field test with the purpose of evaluating retrospective dosimetry methods as carried out in potential real-life exposure scenarios. A 1.36 TBq 192Ir source was used to irradiate anthropomorphic phantoms in different geometries at doses of several Gy in an outdoor open-air geometry. Materials intended for accident dosimetry (including mobile phones and blood) were placed on the phantoms together with reference dosimeters (LiF, NaCl, glass). The objective was to estimate radiation exposures received by individuals as measured using blood and fortuitous materials, and to evaluate these methods by comparing the estimated doses to reference measurements and Monte Carlo simulations. Herein we describe the overall planning, goals, execution and preliminary outcomes of the 2019 field test. Such field tests are essential for the development of new and existing methods. The outputs from this field test include useful experience in terms of planning and execution of future exercises, with respect to time management, radiation protection, and reference dosimetry to be considered to obtain relevant data for analysis.

Task-dependent modulation of short- and long-latency electromyographic responses in upper limb muscles.

Records were made of electromyographic (EMG) responses of both upper limb muscles and the corresponding elbow joint movements following sinusoidal (0.3 Hz) isometric displacement of the elbow joint itself. Two motor conditions were tested. Firstly, the subjects had to control elbow position and secondly control joint torque. Randomly timed, flexing or extending ramp impulses were induced at different displacement velocities and amplitudes. Following long duration displacements (> 100 msec) the recorded EMG responses could clearly be separated into 3 different components (M1-M3). The M1 component was of constant duration but M3 corresponded to the duration of the ramp displacement. It is proposed that the M1 component is "coded" by the acceleration signal and the M3 component by the velocity signal. Only the shape of the M2 component was dependent upon the actual motor condition. With the subjects controlling the elbow joint angle the M2 components in the arm flexor and extensor EMG responses exhibited a peak whose rate of rise was dependent on displacement velocity. However, when elbow torque was controlled by the subjects the M2 component exhibited a plateau whose amplitude was dependent on displacement velocity. The amplitude of the M2 component was significantly larger during position-control than during torque-control. We propose that the difference in the behaviour of the EMG responses may be achieved by the appropriate central regulation of gamma-motoneurone activity or, alternatively, by selective modulation of different receptor inputs between the two tasks.

Influence of subjects' height on the stabilization of posture.

In order to investigate the influence of subjects' height in stabilization of body sway, postural EMG reactions were analysed following perturbation of posture during stance on a force measuring platform. Perturbing momenta of different strengths were unexpectedly applied at the back (level of the center of gravity) after being matched to the body weight of each subject. EMG activity of the antagonistic leg muscles and head, hip and ankle joint movements were recorded. There was a close correlation between displacement amplitude at the ankle joint and height of the subject, with the largest displacements in small subjects. The consequence of this relationship was that 1) The compensatory reactions consisted of larger gastrocnemius responses and a stronger coactivation of the tibialis anterior; 2) Momenta of increasing strength resulted in a larger increment of both ankle joint displacement and gastrocnemius EMG responses in small compared to larger subjects. In analogy to tip-toeing movements, it is concluded that the coactivation pattern is typical for stance conditions with a restricted area of support in order to reduce body sway. On the basis of latency measurements it is suggested that the response pattern is induced by proprioceptive information from the impact site of the momentum.

Developmental aspects of stance regulation, compensation and adaptation.

Recordings of electromyographic (EMG) leg muscle activity, head and joint movements and platform torque were taken in healthy subjects within three age groups (approximately 6, 10 and greater than 22 years) standing upright upon a sinusoidally moving treadmill. The sinusoidal frequency was randomly changed between 0.5, 0.33 and 0.25 Hz, while the amplitude of the deflection was constant (+/- 12 cm). During an adapted sinus, forward inclination of the body at the posterior turning point was associated with a slowly increasing tibialis anterior and decreasing gastrocnemius activity, while straightening of the body at the anterior turning point was associated with a sharply increasing gastrocnemius and decreasing tibialis anterior activity. The angle of forward inclination was greatest in the groups of children and was dependent upon both the sinus frequency and the child's height. The presumed programmed adjustment of the body inclination was such that the net effect of both inertial and gravitational forces acting on the body coincided approximately with the axis of the body at the posterior turning point. Changes of sinusoidal frequency were followed by compensatory responses, the amplitude of which depended upon the velocity of the body's displacement and the height of the subjects. In all three subject groups the response latencies were significantly shorter at the posterior turning point for the gastrocnemius response to a change from 0.5 to 0.25 Hz (105 ms for children and 119 ms for adults) than for the tibialis anterior response to a change from 0.25 to 0.5 Hz for which the values were 162 and 169 ms, respectively. This difference could be attributed to the forward inclination of the body at the posterior turning point which requires an earlier onset of compensatory extensor activity in order to maintain equilibrium. Adaptation to a new sinusoidal frequency occurred within 4 cycles following a change in sinus frequency. The phase shifts between treadmill position and the biomechanical and EMG signals that occurred during the adaptational process suggest that the position of the body's centre of gravity is the variable controlled by the programmed leg muscle activation. In young children the phase shifts during adaptation were absent, which may contribute to their greater instability. It is concluded that posture is continually adjusted in such a way that the resulting torque acting on the body during the treadmill movement becomes minimized. For this regulation load receptors in addition to the classical afferent impulses from visual, vestibular and muscle stretch receptors could play a major role.

Compensation of human stance perturbations: selection of the appropriate electromyographic pattern.

Perturbations of stance evoke purposive EMG patterns which are directed to hold the body's centre of gravity over the feet. Dorsiflexing rotation of the feet is followed by a monosynaptic stretch reflex response in the gastrocnemius muscle, succeeded by a late compensatory tibialis anterior activation. Backward translation of the feet elicits only a compensatory polysynaptic EMG response in the gastrocnemius muscle, while an early gastrocnemius response is absent. The amplitude modulation of the gastrocnemius H-reflex has been investigated during the early part of the two modes of perturbation. Only during translational perturbation a progressive decrease in gastrocnemius H-reflex amplitude started within 5 ms after onset of displacement. The degree of the reduction in amplitude in the former perturbation was dependent on the displacement velocity. Only the contact forces (torques) differed between the two modes of perturbations within the first 10 ms after onset of perturbations. It is suggested that signals from pressure receptors within the body are responsible for the early change in H-reflex amplitude during translational perturbations and it is concluded that the simplest spinal reflex is under very rapid and powerful moment-to-moment control by changes in peripheral feedback. In view of a strong reciprocal modulation of monosynaptic and polysynaptic reflex responses, the later purposive EMG responses may be determined by early changes in presynaptic inhibition of group I afferents.

Amplitude modulation of the human quadriceps tendon jerk reflex during gait.

Amplitude modulation of the quadriceps tendon jerk reflex was investigated during the step cycle in normal human subjects. Reflex amplitude was compared with that obtained during a control stance condition, with "equivalent" levels of EMG activity and limb position. During gait there was a progressive decrease in the reflex amplitude early in the stance phase, i.e. during yielding of the knee, and it remained reduced throughout the step cycle. This pattern of changes in reflex amplitude correlated with neither the quadriceps EMG activity nor with the knee joint movements. The behavior of the tendon reflex was similar to that described for the modulation of the quadriceps H-reflex during the early stages of the stance phase of gait. In the latter study it was argued that changes in presynaptic inhibition of quadriceps la terminals could account for the amplitude modulation. We conclude that there is no dramatic change in the gamma drive to quadriceps muscle spindles: tendon reflexes are modulated during the step cycle in much the same way as H-reflexes, in spite of the peripheral and central differences between them. Similar behavior has been described for the soleus H-reflex and Achilles tendon reflex during gait although the modulation of these reflexes followed a different pattern than that seen in the quadriceps.