Use of the GATE Monte Carlo package for dosimetry applications

6 pages, 3 figures - submitted to NIM A, presented by D. VisvikisInternational audienceOne of the roles for MC simulation studies is in the area of dosimetry. A number of different codes dedicated to dosimetry applications are available and widely used today, such as MCNP, EGSnrc and PTRAN. However, such codes do not easily facilitate the description of complicated 3D sources or emission tomography systems and associated data flow, which may be useful in different dosimetry application domains. Such problems can be overcome by the use of specific MC codes such as GATE, which is based on Geant4 libraries, providing a scripting interface with a number of advantages for the simulation of SPECT and PET systems. Despite this potential, its major disadvantage is in terms of efficiency involving long execution times for applications such as dosimetry. The strong points and disadvantages of GATE in comparison to other dosimetry specific codes are discussed and illustrated in terms of accuracy, efficiency and flexibility. A number of features, such as the use of voxelised and moving sources, as well as developments such as advanced visualisation tools and the development of dose estimation maps allowing GATE to be used for dosimetry applications are presented. In addition, different examples from dosimetry applications with GATE are given. Finally, future directions with respect to the use of GATE for dosimetry applications are outlined

Setting up a quantitative SPECT imaging network for a European multi-centre dosimetry study of radioiodine treatment for thyroid cancer as part of the MEDIRAD project

Background: Differentiated thyroid cancer has been treated with radioiodine for almost 80 years, although controversial questions regarding radiation-related risks and the optimisation of treatment regimens remain unresolved. Multi-centre clinical studies are required to ensure recruitment of sufficient patients to achieve the statistical significance required to address these issues. Optimisation and standardisation of data acquisition and processing are necessary to ensure quantitative imaging and patient-specific dosimetry. Material and methods: A European network of centres able to perform standardised quantitative imaging of radioiodine therapy of thyroid cancer patients was set-up within the EU consortium MEDIRAD. This network will support a concurrent series of clinical studies to determine accurately absorbed doses for thyroid cancer patients treated with radioiodine. Five SPECT(/CT) systems at four European centres were characterised with respect to their system volume sensitivity, recovery coefficients and dead time. Results: System volume sensitivities of the Siemens Intevo systems (crystal thickness 3/8″) ranged from 62.1 to 73.5 cps/MBq. For a GE Discovery 670 (crystal thickness 5/8″) a system volume sensitivity of 92.2 cps/MBq was measured. Recovery coefficients measured on three Siemens Intevo systems show good agreement. For volumes larger than 10 ml, the maximum observed difference between recovery coefficients was found to be ± 0.02. Furthermore, dead-time coefficients measured on two Siemens Intevo systems agreed well with previously published dead-time values. Conclusions: Results presented here provide additional support for the proposal to use global calibration parameters for cameras of the same make and model. This could potentially facilitate the extension of the imaging network for further dosimetry-based studies

Do production patterns influence the processing of speech in prelinguistic infants?

The headturn preference procedure was used to test 18 infants on their response to three different passages chosen to reflect their individual production patterns. The passages contained nonwords with consonants in one of three categories: (a) often produced by that infant (‘own’), (b) rarely produced by that infant but common at that age (‘other’), and (c) not generally produced by infants. Infants who had a single ‘own’ consonant showed no significant preference for either ‘own’ (a) or ‘other’ (b) passages. In contrast, infants’ with two ‘own’ consonants exhibited greater attention to ‘other’ passages (b). Both groups attended equally to the passage featuring consonants rarely produced by infants of that age (c). An analysis of a sample of the infant-directed speech ruled out the mothers’ speech as a source of the infant preferences. The production-based shift to a focus on the ‘other’ passage suggests that nascent production abilities combine with emergent perceptual experience to facilitate word learning

Interactive Language Learning by Robots: The Transition from Babbling to Word Forms

The advent of humanoid robots has enabled a new approach to investigating the acquisition of language, and we report on the development of robots able to acquire rudimentary linguistic skills. Our work focuses on early stages analogous to some characteristics of a human child of about 6 to 14 months, the transition from babbling to first word forms. We investigate one mechanism among many that may contribute to this process, a key factor being the sensitivity of learners to the statistical distribution of linguistic elements. As well as being necessary for learning word meanings, the acquisition of anchor word forms facilitates the segmentation of an acoustic stream through other mechanisms. In our experiments some salient one-syllable word forms are learnt by a humanoid robot in real-time interactions with naive participants. Words emerge from random syllabic babble through a learning process based on a dialogue between the robot and the human participant, whose speech is perceived by the robot as a stream of phonemes. Numerous ways of representing the speech as syllabic segments are possible. Furthermore, the pronunciation of many words in spontaneous speech is variable. However, in line with research elsewhere, we observe that salient content words are more likely than function words to have consistent canonical representations; thus their relative frequency increases, as does their influence on the learner. Variable pronunciation may contribute to early word form acquisition. The importance of contingent interaction in real-time between teacher and learner is reflected by a reinforcement process, with variable success. The examination of individual cases may be more informative than group results. Nevertheless, word forms are usually produced by the robot after a few minutes of dialogue, employing a simple, real-time, frequency dependent mechanism. This work shows the potential of human-robot interaction systems in studies of the dynamics of early language acquisition

p53 Status and Tumor Cell Response to Radioimmunotherapy using 125I-mAbs

Introduction: While radioimmunotherapy (RIT) of non-Hodgkins B-cell lymphoma with Zevalin® and Bexxar ® (anti-CD20 labelled to 90Y or 131I) has demonstrated its efficiency. However, new strategies must be developed in order to treat solid tumours by RIT. In a previous study, we proposed to use the highly cytotoxic Auger electrons emitted by 125I to overcome the radioresistance of solid tumours. We showed that tumour killing achieved with non-internalizing labeled monoclonal antibodies (mAbs) is more significant than that of internalizing 125I-mAbs. This suggests that while the nucleus remains the main target of irradiation, the membrane is also a sensitive target. In the present study, we investigated the role of the nuclear p53 protein and that of ceramide, a major mediator of apoptosis, in the cellular response to 125I mAbs exposure. Material and Methods: Two carcinoma colic cell lines, H3E5 (p53 wt) and HCT116-KO (p53 deficient) expressing cell surface HER1 and CEA receptors were exposed for 2 days to increasing activities (04 MBq/mL) of either internalizing (anti-HER1) or non-internalizing (anti-CEA) 125I-mAbs. Survival was assessed by standard clonogenic assay and dosimetry was investigated using the MIRD scheme. For this purpose, uptake of radioactivity per cell was measured, and S-factors for 125I were specifically calculated for cell surface and cell cytoplasm localisation. Then, first experiments were carried out with alkaline comet assay to observe DNA damage from RIT. Results: For both cell lines, we confirmed that the toxicity due to 125I decays was greater with non-internalizing rather than with internalizing 125I-mAbs. Moreover, we showed that H3E5 cell line was more sensitive to X-ray external beam irradiation rather than HCT116-KO. By contrast, for both 125I localisations, preliminary experiment showed no significant difference on the survival between the two cell lines. These results would indicate that p53 status does not mediate the response to RIT with Auger electrons. A tentative explanation may involve the low dose rate induced by RIT. Under these conditions, no detectable DNA damage was measured by the alkaline comet assay. Conclusion: Our preliminary results seem to indicate that p53 status does not interfere with tumour cell response to RIT. Ongoing experiments are assessing the role of ceramide as a mediator of apoptosis, to explain membrane irradiation efficiency

Voxel-based dosimetry is superior to mean-absorbed dose approach for establishing dose-effect relationship in targeted radionuclide therapy

It is becoming evident that patient-individualized dosimetry in targeted radionuclide therapy (TRT) is a must and not a luxury in the era of precision medicine. It's often argued that patient-specific absorbed dose assessment should be the standard and become routine in TRT, similar to other forms of radiation therapy to improve the correlations between the administered activitiy and the clinical outcome and enable better understanding of the absorbed dose-response relationship