Patient-specific biokinetics and hybrid 2D/3D approach integration in OEDIPE software: Application to radioiodine therapy.

BACKGROUND: The progression of targeted radionuclide therapy requires the development of dosimetry software accounting for patient-specific biokinetics. New functionalities were thus developed in the OEDIPE software, to deal with multiple 3D images or multiple planar images and a SPECT image. MATERIEL & METHOD: Methods were implemented to recover patient biokinetics in volumes of interest. If several 3D SPECT images are available, they are registered to a reference CT scan. When several planar images and a single SPECT are available, the planar images are registered to the SPECT and counts of the planar images converted to activity. To validate these developments, six SPECT/CT and planar images of a Jaszczak phantom containing I-131 were acquired at different dates. Cumulated activity was estimated in each sphere using the SPECT/CT images only or the planar series associated to one SPECT/CT. Biokinetics and doses in lesions and in the lungs of a patient treated with I-131 for differentiated thyroid cancer were then estimated using four planar images and a SPECT/CT scan. Whole-body retention data were used to compare the biokinetics obtained from the planar and SPECT data. RESULTS: Activities and cumulated activities estimated using OEDIPE in the phantom spheres agreed well with the reference values for both approaches. Results obtained for the patient compared well with those derived from whole-body retention data. CONCLUSION: The implemented features allow automatic evaluation of patient-specific biokinetics from different series of patient images, enabling patient-specific dosimetry without the need for external software to estimate the cumulated activities in different VOIs.

Using radial distribution functions to calculate cellular cross-absorbed dose forßemitters: comparison with reference methods and application for18F-FDG cell labeling.

To further improve the understanding ofin vitrobiological effects of incorporated radionuclides, it is essential to accurately determine cellular absorbed doses. In the case ofßemitters, the cross-dose is a major contribution, and can involve up to millions of cells. Realistic and efficient computational models are needed for that purpose. Conventionally, distances between each cell are calculated and the related dose contributions are cumulated to get the total cross-dose (standard method). In this work, we developed a novel approach for the calculation of the cross-absorbed dose, based on the use of the radial distribution function (rdf)) that describes the spatial properties of the cellular model considered. The dynamic molecular tool LAMMPS was used to create 3D cellular models and computerdfsfor various conditions of cell density, volume size, and configuration type (lattice and randomized geometry). The novel method is suitable for any radionuclide of nuclear medicine. Here, the model was applied for the labeling of cells with18F-FDG used for PET imaging, and first validated by comparison with other reference methods. MeanScrossvalues calculated with the novel approach versus the standard method agreed very well (relative differences less that 0.1%). Implementation of therdf-based approach with LAMMPS allowed to achieved results considerably faster than with the standard method, the computing time decreasing from hours to seconds for 106cells. Therdf-based approach was also faster and easier to accommodate more complex cellular models than the standard and other published methods. Finally, a comparative study of the meanScrossfor different types of configuration was carried out, as a function of the cell density and the volume size, allowing to better understand the impact of the configuration on the cross-absorbed dose.

Optimisation of reconstruction, volumetry and dosimetry for 99mTc-SPECT and 90Y-PET images: Towards reliable dose-volume histograms for selective internal radiation therapy with 90Y-microspheres.

PURPOSE: In Selective Internal Radiation Therapy (SIRT), 99mTc-MAA SPECT images are commonly used to predict microspheres distribution but recent works used 90Y-microspheres PET images. Nevertheless, evaluation of the predictive power of 99mTc-MAA has been hampered by the lack of reliable comparisons between 99mTc-SPECT and 90Y-PET images. Our aim was to determine the "in situ" optimisation procedure in order to reliably compare 99mTc-SPECT and 90Y-PET images and achieve optimal personal dosimetry. METHODS: We acquired 99mTc-SPECT/CT and 90Y-PET/CT images of NEMA and Jaszczak phantoms. We found the best reconstruction parameters for quantification and for volume estimations. We determined adaptive threshold curves on the volumetric reconstruction. We copied the optimised volumes on the quantitative reconstruction, named here the "cross volumes" technique. Finally, we compared 99mTc-SPECT and 90Y-PET Dose Volume Histograms. RESULTS: Our "in situ" optimisation procedure decreased errors on volumes and quantification (from -44.2% and -15.8% to -3.4% and -3.28%, respectively, for the 26.5mL PET phantom sphere). Moreover, 99mTc-SPECT and 90Y-PET DVHs were equivalent only after the optimisation procedure (difference in mean dose <5% for the three biggest spheres). CONCLUSIONS: This work showed that a preliminary "in situ" phantom study was necessary to optimise volumes and quantification of 99mTc-SPECT and 90Y-PET images and allowed to achieve a reliable comparison between patient treatment planning and post implant dosimetry, notably by the use of the "cross volumes" technique. Methodology developed in this work will enable robust evaluations of the predictive power of 99mTc-SPECT, as well as dose-response relationship and side effects in SIRT treatments.

Application of rodes software to experimental biokinetic data for dose assessment in mice and rats.

H Miloudi, M Locatelli, G Autret, D Balvay, A Desbrée, E Blanchardon, J M Bertho: application of RODES software to experimental biokinetic data for dose assessment in mice and rats. In support of experimental studies of chronic, long-term contamination in rodents, voxel-based computer models were built representing adult mice and juvenile, adult and elderly rats of both sexes. RODES software was created to calculate absorbed radiation doses to organs with these specific anatomical models. Absorbed doses were then calculated starting from previously published biokinetic data. Whole body doses showed less than 5% differences between calculation with RODES and calculation with the ICRP Publication 108 model for long term exposure to 90Sr of mice. Similar results were obtained for long term exposure to 137Cs. Dose distribution for 90Sr internal contamination also showed that the dose to the skeleton is six fold more as compared to the whole body dose while radiation dose to other organs is less than the mean whole body dose. These results underline the importance of using specific anatomical models according to the age and the sex of experimental animals.

Dosimetry at the sub-cellular scale of Auger-electron emitter 99mTc in a mouse single thyroid follicle.

The Auger-electrons emitted by (99m)Tc have been recently associated with the induction of thyroid stunning in in vivo experiments in mice, making the dosimetry at the sub-cellular level of (99m)Tc a pertinent and pressing subject. The S-values for (99m)Tc were calculated using MCNP6, which was first validated for studies at the sub-cellular scale and for low energies electrons. The calculation was then performed for (99m)Tc within different cellular compartments in a single mouse thyroid follicle model, considering the radiative and non-radiative transitions of the (99m)Tc radiation spectrum. It was shown that the contribution of the (99m)Tc Auger and low energy electrons to the absorbed dose to the follicular cells' nucleus is important, being at least of the same order of magnitude compared to the emitted photons' contribution and cannot be neglected. The results suggest that Auger-electrons emitted by (99m)Tc play a significant role in the occurrence of the thyroid stunning effect in mice.

Liver Selective Internal Radiation Therapy with (90)Y resin microspheres: comparison between pre-treatment activity calculation methods.

Different methods to calculate (90)Y resin microspheres activity for Selective Internal Radiation Therapy (SIRT) were compared. Such comparison is not yet available and is needed in clinical practice to optimize patient specific treatment planning. 32 (99m)Tc-macroagregates (MAA) evaluations were performed, followed by 26 treatments. Four methods to calculate (90)Y-activity were applied retrospectively: three based on Body Surface Area and one based on MIRD formalism, partition model (PM). Relationships between calculated activities, lung breakthrough (LB), the activity concentration ratio between lesions and healthy liver (T/N) and tumour involvement were investigated, where lobar and whole liver treatments were analysed separately. Without attenuation correction, overestimation of LB was 65%. In any case, the estimated lungs' doses remained below 30 Gy. Thus, the maximal injectable activity (MIA) is not limited by lungs' irradiation. Moreover, LB was not significantly related to T/N, neither to tumour involvement nor radiochemical purity (RP). Differences in calculated activity with the four methods were extremely large, in particular they were greater between BSA-based and PM activities for lobar treatments (from -85% to 417%) compared to whole liver treatments (from -49% to 61%). Two values of T/N ratio were identified as thresholds: for BSA-based methods, healthy liver doses are much higher than 30 Gy when T/N < 3; for PM, tumour doses are higher than 120 Gy when T/N > 4. As PM accounts for uptake ratio between normal and tumour liver, this method should be employed over BSA-based methods.

Comparison of organs' shapes with geometric and Zernike 3D moments.

The morphological similarity of organs is studied with feature vectors based on geometric and Zernike 3D moments. It is particularly investigated if outliers and average models can be identified. For this purpose, the relative proximity to the mean feature vector is defined, principal coordinate and clustering analyses are also performed. To study the consistency and usefulness of this approach, 17 livers and 76 hearts voxel models from several sources are considered. In the liver case, models with similar morphological feature are identified. For the limited amount of studied cases, the liver of the ICRP male voxel model is identified as a better surrogate than the female one. For hearts, the clustering analysis shows that three heart shapes represent about 80% of the morphological variations. The relative proximity and clustering analysis rather consistently identify outliers and average models. For the two cases, identification of outliers and surrogate of average models is rather robust. However, deeper classification of morphological feature is subject to caution and can only be performed after cross analysis of at least two kinds of feature vectors. Finally, the Zernike moments contain all the information needed to re-construct the studied objects and thus appear as a promising tool to derive statistical organ shapes.

Microdosimetry of alpha particles for simple and 3D voxelised geometries using MCNPX and Geant4 Monte Carlo codes.

Microdosimetry using Monte Carlo simulation is a suitable technique to describe the stochastic nature of energy deposition by alpha particle at cellular level. Because of its short range, the energy imparted by this particle to the targets is highly non-uniform. Thus, to achieve accurate dosimetric results, the modelling of the geometry should be as realistic as possible. The objectives of the present study were to validate the use of the MCNPX and Geant4 Monte Carlo codes for microdosimetric studies using simple and three-dimensional voxelised geometry and to study their limit of validity in this last case. To that aim, the specific energy (z) deposited in the cell nucleus, the single-hit density of specific energy f(1)(z) and the mean-specific energy were calculated. Results show a good agreement when compared with the literature using simple geometry. The maximum percentage difference found is <6 %. For voxelised phantom, the study of the voxel size highlighted that the shape of the curve f(1)(z) obtained with MCNPX for <1 µm voxel size presents a significant difference with the shape of non-voxelised geometry. When using Geant4, little differences are observed whatever the voxel size is. Below 1 µm, the use of Geant4 is required. However, the calculation time is 10 times higher with Geant4 than MCNPX code in the same conditions.

Construction of an extended library of adult male 3D models: rationale and results.

In order to best cover the possible extent of heights and weights of male adults the construction of 25 whole body 3D models has been undertaken. Such a library is thought to be useful to specify the uncertainties and relevance of dosimetry calculations carried out with models representing individuals of average body heights and weights. Representative 3D models of Caucasian body types are selected in a commercial database according to their height and weight, and 3D models of the skeleton and internal organs are designed using another commercial dataset. A review of the literature enabled one to fix volume or mass target values for the skeleton, soft organs, skin and fat content of the selected individuals. The composition of the remainder tissue is fixed so that the weight of the voxel models equals the weight of the selected individuals. After mesh and NURBS modelling, volume adjustment of the selected body shapes and additional voxel-based work, 25 voxel models with 109 identified organs or tissue are obtained. Radiation transport calculations are carried out with some of the developed models to illustrate potential uses. The following points are discussed throughout this paper: justification of the fixed or obtained models' features regarding available and relevant literature data; workflow and strategy for major modelling steps; advantages and drawbacks of the obtained library as compared with other works. The construction hypotheses are explained and justified in detail since future calculation results obtained with this library will depend on them.

[EBV infection revealing a long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in a 3-year-old boy]. / Infection à EBV révélatrice à l'âge de 3 ans d'un déficit en 3-hydroxyacyl-CoA déshydrogénase des acides gras à chaîne longue (LCHAD).

OBSERVATION: We report on the case of a 3-year-old child from La Réunion island, who presented with hypoglycemic hypoketotic coma secondary to a primary Epstein-Barr virus (EBV) infection. The discovery of the G1528C homozygote mutation provided the diagnosis of long-chain-3-hydroxyacyl-CoA-dehydrogenase (LCHAD); an adapted dietary plan with prevention of fasting and L-carnitine supplementation was initiated. After 2 years, a pigmentary retinopathy appeared and muscle weakness increased. COMMENTS: Isolated LCHAD deficiency is an autosomal recessive disorder of fatty acid metabolism. Prevalence is about 1-9/100,000 and diagnosis is often made before the age of 2 years. The late age of revelation in our case is related to a spontaneous diet without animal fats (disgust for meat, diet based on white rice and skimmed milk) and nighttime breastfeeding until the age of 3 years. In an affected fetus, heterozygous mothers are susceptible to developing a hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome or an acute fatty liver pregnancy (AFLP) syndrome during the 3rd trimester of pregnancy, which motivated us to set up a systematic neonatal screening program and a specific monitoring of these newborns.

Application of the ICRP/ICRU reference computational phantoms to internal dosimetry: calculation of specific absorbed fractions of energy for photons and electrons.

The emission of radiation from a contaminated body region is connected with the dose received by radiosensitive tissue through the specific absorbed fractions (SAFs) of emitted energy, which is therefore an essential quantity for internal dose assessment. A set of SAFs were calculated using the new adult reference computational phantoms, released by the International Commission on Radiological Protection (ICRP) together with the International Commission on Radiation Units and Measurements (ICRU). Part of these results has been recently published in ICRP Publication 110 (2009 Adult reference computational phantoms (Oxford: Elsevier)). In this paper, we mainly discuss the results and also present them in numeric form. The emission of monoenergetic photons and electrons with energies ranging from 10 keV to 10 MeV was simulated for three source organs: lungs, thyroid and liver. SAFs were calculated for four target regions in the body: lungs, colon wall, breasts and stomach wall. For quality assurance purposes, the simulations were performed simultaneously at the Helmholtz Zentrum München (HMGU, Germany) and at the Institute for Radiological Protection and Nuclear Safety (IRSN, France), using the Monte Carlo transport codes EGSnrc and MCNPX, respectively. The comparison of results shows overall agreement for photons and high-energy electrons with differences lower than 8%. Nevertheless, significant differences were found for electrons at lower energy for distant source/target organ pairs. Finally, the results for photons were compared to the SAF values derived using mathematical phantoms. Significant variations that can amount to 200% were found. The main reason for these differences is the change of geometry in the more realistic voxel body models. For electrons, no SAFs have been computed with the mathematical phantoms; instead, approximate formulae have been used by both the Medical Internal Radiation Dose committee (MIRD) and the ICRP due to the limitations imposed by the computing power available at this time. These approximations are mainly based on the assumption that electrons are absorbed locally in the source organ itself. When electron SAFs are calculated explicitly, discrepancies with this simplifying assumption are notable, especially at high energies and for neighboring organs where the differences can reach the same order of magnitude as for photon SAFs.

Analytical and Monte Carlo assessment of activity and local dose after a wound contamination by activation products.

The activity and local dose following a right index finger wound contamination by activation products are assessed. Measurements with a high purity germanium detector and a four positions measurement protocol enabled a better localization of the contaminant source. From the source location and detector calibration, the remaining wound activity and local absorbed dose were deduced. An analytical model, based on a two dimensional simplification of the problem, is presented. It is shown to provide a fast and quite accurate activity assessment when the contaminants are described as a point source. The contaminants' location and activity were then more accurately assessed using Monte Carlo calculations based on the OEDIPE software and a voxelized phantom of the index finger. Describing the contaminant mixture as a point source resulted in an agreement of experimental and computed data around 6% for most of the radionuclides. The total activity, due to 11 radionuclides, was estimated to be (9.5 +/- 0.4) kBq at measurement day. Since the point source is found to be less than 1 mm under the skin, the equivalent skin dose is calculated and found to be around 680 mSv in the first year after the contamination, and this value decreases to 250 mSv in the second year. The relevance of equivalent skin dose as an estimate of the sanitary risk is discussed, and it is concluded that for this case it gives the upper end estimate of the risk.

Simultaneous in vivo magnetic resonance imaging and radioactive measurements with the beta-MicroProbe.

PURPOSE: Multimodal instrumentation is a new technical approach allowing simultaneous and complementary in vivo recordings of complementary biological parameters. To elucidate further the physiopathological mechanisms in intact small animal models, especially for brain studies, a challenging issue is the actual coupling of magnetic resonance imaging (MRI) techniques with positron emission tomography (PET): it has been shown that running the technology for radioactive imaging in a magnet alters the spatiotemporal performance of both modalities. Thus, we propose an alternative coupling of techniques that uses the beta-MicroProbe instead of PET for local measurements of radioactivity coupled with MRI. METHODS: We simultaneously recorded local radioactivity due to [(18)F]MPPF (a 5-HT(1A) receptor PET radiotracer) binding in the hippocampus with the beta-MicroProbe and carried out anatomical MRI in the same anaesthetised rat. RESULTS: The comparison of [(18)F]MPPF kinetics obtained from animals in a magnet with kinetics from a control group outside the magnet allowed us to determine the stability of tracer biokinetic measurements over time in the magnet. We were thus able to show that the beta-MicroProbe reliably measures radioactivity in rat brains under an intense magnetic field of 7 Tesla. CONCLUSION: The biological validation of a beta-MicroProbe/MRI dual system reported here opens up a wide range of future multimodal approaches for functional and pharmacological measurements by the probe combined with various magnetic resonance technologies, including anatomical MRI, functional MRI and MR spectroscopy.