Impact of scatter correction on personalized dosimetry in selective internal radiotherapy using 166Ho-PLLA: a single-center study including Monte-Carlo simulation, phantom and patient imaging.

BACKGROUND: Developments in transarterial radioembolization led to the conception of new microspheres loaded with holmium-166 (166Ho). However, due to the complexity of the scatter components in 166Ho single photon emission computed tomography (SPECT), questions about image quality and dosimetry are emerging. The aims of this work are to investigate the scatter components and correction methods to propose a suitable solution, and to evaluate the impact on image quality and dosimetry including Monte-Carlo (MC) simulations, phantom, and patient data. METHODS: Dual energy window (DEW) and triple energy window (TEW) methods were investigated for scatter correction purposes and compared using Contrast Recovery Coefficients (CRC) and Contrast to Noise Ratios (CNR). First, MC simulations were carried out to assess all the scatter components in the energy windows used, also to confirm the choice of the parameter needed for the DEW method. Then, MC simulations of acquisitions of a Jaszczak phantom were conducted with conditions mimicking an ideal scatter correction. These simulated projections can be reconstructed and compared with real acquisitions corrected by both methods and then reconstructed. Finally, both methods were applied on patient data and their impact on personalized dosimetry was evaluated. RESULTS: MC simulations confirmed the use of k = 1 for the DEW method. These simulations also confirmed the complexity of scatter components in the main energy window used with a high energy gamma rays component of about half of the total counts detected, together with a negligible X rays component and a negligible presence of fluorescence. CRC and CNR analyses, realized on simulated scatter-free projections of the phantom and on scatter corrected acquisitions of the same phantom, suggested an increased efficiency of the TEW method, even at the price of higher level of noise. Finally, these methods, applied on patient data, showed significant differences in terms of non-tumoral liver absorbed dose, non-tumoral liver fraction under 50 Gy, tumor absorbed dose, and tumor fraction above 150 Gy. CONCLUSIONS: This study demonstrated the impact of scatter correction on personalized dosimetry on patient data. The use of a TEW method is proposed for scatter correction in 166Ho SPECT imaging.

Monte Carlo as quality control tool of stereotactic body radiation therapy treatment plans.

PURPOSE/OBJECTIVE: The objective of this study was to verify the accuracy of treatment plans of stereotactic body radiation therapy (SBRT) and to verify the feasibility of the use of Monte Carlo (MC) as quality control (QC) on a daily basis. MATERIAL/METHODS: Using EGSnrc, a MC model of Agility™ linear accelerator was created. Various measurements (Percentage depth dose (PDD), Profiles and Output factors) were done for different fields sizes from 1x1 up to 40x40 (cm2). An iterative model optimization was performed to achieve adequate parameters of MC simulation. 40 SBRT patient's dosimetry plans were calculated by Monaco™ 3.1.1. CT images, RT-STRUCT and RT-PLAN files from Monaco™ being used as input for Moderato MC code. Finally, dose volume histogram (DVH) and paired t-tests for each contour were used for dosimetry comparison of the Monaco™ and MC. RESULTS: Validation of MC model was successful, as <2% difference comparing to measurements for all field's sizes. The main energy of electron source incident on the target was 5.8 MeV, and the full width at half maximum (FWHM) of Gaussian electron source were 0.09 and 0.2 (cm) in X and Y directions, respectively. For 40 treatment plan comparisons, the minimum absolute difference of mean dose of planning treatment planning (PTV) was 0.1% while the maximum was 6.3%. The minimum absolute difference of Max dose of PTV was 0.2% while the maximum was 8.1%. CONCLUSION: SBRT treatment plans of Monaco agreed with MC results. It possible to use MC for treatment plans verifications as independent QC tool.

Molecular Weapons Contribute to Intracellular Rhizobia Accommodation Within Legume Host Cell.

The interaction between legumes and bacteria of rhizobia type results in a beneficial symbiotic relationship characterized by the formation of new root organs, called nodules. Within these nodules the bacteria, released in plant cells, differentiate into bacteroids and fix atmospheric nitrogen through the nitrogenase activity. This mutualistic interaction has evolved sophisticated signaling networks to allow rhizobia entry, colonization, bacteroid differentiation and persistence in nodules. Nodule cysteine rich (NCR) peptides, reactive oxygen species (ROS), reactive nitrogen species (RNS), and toxin-antitoxin (TA) modules produced by the host plants or bacterial microsymbionts have a major role in the control of the symbiotic interaction. These molecules described as weapons in pathogenic interactions have evolved to participate to the intracellular bacteroid accommodation by escaping control of plant innate immunity and adapt the functioning of the nitrogen-fixation to environmental signalling cues.

3D Monte Carlo dosimetry of intraoperative electron radiation therapy (IOERT).

PURPOSE: This paper studies the feasibility of using Monte Carlo (MC) for treatment planning of intraoperative electron radiation therapy (IOERT) procedure to get 3D dose by using patient's CT images. METHODS: The IOERT treatment planning was performed using the following successive steps: I) The Mobetron 1000® machine was modelled with the EGSnrc MC codes. II) The MC model was validated with measurements of percentage depth doses and profiles for three energies (12, 9, 6) MeV. III) CT images were imported as DICOM files. IV) Contouring of the planning target volume (PTV) and the organs at risk was done by the radiation oncologist. V) The medical physicist with the radiation oncologist, had chosen the same parameters of IOERT procedures like energy, applicator (type, size) and using or not bolus. VI) Finally, dose calculation and analysis of 3D maps was carried out. RESULTS: The tuning process of the MC model provides good results, as the maximum value of the root mean square deviation (RMSD) was less than 3% between the MC simulated PDDs and the measured PDDs. The contouring and dose analysis review were easy to conduct for the classical treatment planning system. The radiation oncologist had many tools for dose analysis such as DVH and color wash for all the slides. Summation of the 3D dose of IOERT with other radiotherapy plans is possible and helpful for total dose estimation. Archiving and documentation is as good as treatment planning system (TPS). CONCLUSIONS: The method displayed in this paper provides a step forward for IOERT Dosimetry and allows to obtain accurate dosimetry of treated volumes.

Shielding disk position in intra-operative electron radiotherapy (IOERT): A Monte Carlo study.

PURPOSE: In IOERT breast treatments, a shielding disk is frequently used to protect the underlying healthy structures. The disk is usually composed of two materials, a low-Z material intended to be oriented towards the beam and a high-Z material. As tissues are repositioned around the shield before treatment, the disk is no longer visible and its correct alignment with respect to the beam is guaranteed. This paper studies the dosimetric characteristics of four possible clinical positioning scenarios of the shielding disk. A new alignment method for the shielding disk in the beam is introduced. Finally, it suggests a new design for the shielding disk. METHODS: As the first step, the IOERT machine "Mobetron 1000" was modeled by using Monte Carlo simulation, tuning the MC model until an excellent match with the measured PDDs and profiles was achieved. Four possible shielding disk positioning scenarios were considered, determining the dosimetric impact. Furthermore, in our center, to prevent beam misalignment, we have developed a shielding disk equipped with guiding rods. Having ascertained a correct alignment between the disk and the beam, we can propose a new internal design of the shielding disk that can improve the dose distribution with a better coverage of the treated area. RESULTS: All MC simulations were performed with a 12 MeV beam, the maximum energy of Mobetron 1000 and a 5.5 cm diameter flat tip applicator, this applicator being the most clinically used. The simulations were compared with measurements performed in a water phantom and showed good results within 2.2% of root mean square difference (RMSD). The misplacement positions of the shielding disk have dosimetric impacts in the treatment volume and a small translation could have a significant influence on healthy tissues. The D-scenario is the worst which could happens when the shielding disk is flipped upside down, giving up to 144% dose instead of 90% at the surface of the Pb/Al shielding disk. A new shielding design used, together with our alignment tool, is able to give a more homogeneous dose in the target area. CONCLUSIONS: The accuracy of shielding disk position can still be problematic in IOERT dosimetry. Any method that can ascertain the good alignment between the shielding disk and the beam is beneficial for the dose distribution and is a prerequisite for an optimized shield internal design that could improve the coverage of the treated area and the protection of healthy tissues.

Physiological and biochemical responses involved in water deficit tolerance of nitrogen-fixing Vicia faba.

Climate change is increasingly impacting the water deficit over the world. Because of drought and the high pressure of the rising human population, water is becoming a scarce and expensive commodity, especially in developing countries. The identification of crops presenting a higher acclimation to drought stress is thus an important objective in agriculture. The present investigation aimed to assess the adaptation of three Vicia faba genotypes, Aguadulce (AD), Luz d'Otonio (LO) and Reina Mora (RM) to water deficit. Multiple physiological and biochemical parameters were used to analyse the response of the three genotypes to two soil water contents (80% and 40% of field capacity). A significant lower decrease in shoot, root and nodule dry weight was observed for AD compared to LO and RM. The better growth performance of AD was correlated to higher carbon and nitrogen content than in LO and RM under water deficit. Leaf parameters such as relative water content, mass area, efficiency of photosystem II and chlorophyll and carotenoid content were significantly less affected in AD than in LO and RM. Significantly higher accumulation of proline was correlated to the higher performance of AD compared to LO and RM. Additionally, the better growth of AD genotype was related to an important mobilisation of antioxidant enzyme activities such as ascorbate peroxidase and catalase. Taken together, these results allow us to suggest that AD is a water deficit tolerant genotype compared to LO and RM. Our multiple physiological and biochemical analyses show that nitrogen content, leaf proline accumulation, reduced leaf hydrogen peroxide accumulation and leaf antioxidant enzymatic activities (ascorbate peroxidase, guaiacol peroxidase, catalase and polyphenol oxidase) are potential biological markers useful to screen for water deficit resistant Vicia faba genotypes.

Sulfenylated proteins in the Medicago truncatula-Sinorhizobium meliloti symbiosis.

Reactive oxygen species such as hydrogen peroxide (H(2)O(2)), play a crucial role as signaling molecules in the establishment and functioning of the nitrogen-fixing legume-Rhizobium symbiosis. The regulation of protein function through oxidative modification has emerged as an important molecular mechanism modulating various biological processes. Protein cysteine residues are known to be sensitive targets of H(2)O(2), in a posttranslational modification called sulfenylation. We trapped and identified sulfenylated proteins in the Medicago truncatula-Sinorhizobium meliloti symbiosis, by combining the use of chemical and genetic probes with mass spectrometry analysis. We identified 44 M. truncatula proteins sulfenylated in inoculated roots (two days post infection, 2dpi) and 65 such proteins in the functioning symbiotic organ, the nodule (four weeks post infection, 4wpi); 18 proteins were identified at both time points. However, the largest functional groups at 2dpi and 4wpi were different: redox state-linked proteins early in the interaction and proteins involved in amino-acid and carbohydrate metabolism in the nodule. Twenty proteins from S. meliloti, including some directly involved in nitrogen fixation, were also identified as sulfenylated. These results suggest that sulfenylation may regulate the activity of proteins playing major roles in the development and functioning of the symbiotic interaction.

(Homo)glutathione depletion modulates host gene expression during the symbiotic interaction between Medicago truncatula and Sinorhizobium meliloti.

Under nitrogen-limiting conditions, legumes interact with symbiotic rhizobia to produce nitrogen-fixing root nodules. We have previously shown that glutathione and homoglutathione [(h)GSH] deficiencies impaired Medicago truncatula symbiosis efficiency, showing the importance of the low M(r) thiols during the nodulation process in the model legume M. truncatula. In this study, the plant transcriptomic response to Sinorhizobium meliloti infection under (h)GSH depletion was investigated using cDNA-amplified fragment length polymorphism analysis. Among 6,149 expression tags monitored, 181 genes displayed significant differential expression between inoculated control and inoculated (h)GSH depleted roots. Quantitative reverse transcription polymerase chain reaction analysis confirmed the changes in mRNA levels. This transcriptomic analysis shows a down-regulation of genes involved in meristem formation and a modulation of the expression of stress-related genes in (h)GSH-depleted plants. Promoter-beta-glucuronidase histochemical analysis showed that the putative MtPIP2 aquaporin might be up-regulated during nodule meristem formation and that this up-regulation is inhibited under (h)GSH depletion. (h)GSH depletion enhances the expression of salicylic acid (SA)-regulated genes after S. meliloti infection and the expression of SA-regulated genes after exogenous SA treatment. Modification of water transport and SA signaling pathway observed under (h)GSH deficiency contribute to explain how (h)GSH depletion alters the proper development of the symbiotic interaction.

Reactive oxygen and nitrogen species and glutathione: key players in the legume-Rhizobium symbiosis.

Several reactive oxygen and nitrogen species (ROS/RNS) are continuously produced in plants as by-products of aerobic metabolism or in response to stresses. Depending on the nature of the ROS and RNS, some of them are highly toxic and rapidly detoxified by various cellular enzymatic and non-enzymatic mechanisms. Whereas plants have many mechanisms with which to combat increased ROS/RNS levels produced during stress conditions, under other circumstances plants appear to generate ROS/RNS as signalling molecules to control various processes encompassing the whole lifespan of the plant such as normal growth and development stages. This review aims to summarize recent studies highlighting the involvement of ROS/RNS, as well as the low molecular weight thiols, glutathione and homoglutathione, during the symbiosis between rhizobia and leguminous plants. This compatible interaction initiated by a molecular dialogue between the plant and bacterial partners, leads to the formation of a novel root organ capable of fixing atmospheric nitrogen under nitrogen-limiting conditions. On the one hand, ROS/RNS detection during the symbiotic process highlights the similarity of the early response to infection by pathogenic and symbiotic bacteria, addressing the question as to which mechanism rhizobia use to counteract the plant defence response. Moreover, there is increasing evidence that ROS are needed to establish the symbiosis fully. On the other hand, GSH synthesis appears to be essential for proper development of the root nodules during the symbiotic interaction. Elucidating the mechanisms that control ROS/RNS signalling during symbiosis could therefore contribute in defining a powerful strategy to enhance the efficiency of the symbiotic interaction.

Analysis and effects of cytosolic free calcium increases in response to elicitors in Nicotiana plumbaginifolia cells.

Cell suspensions obtained from Nicotiana plumbaginifolia plants stably expressing the apoaequorin gene were used to analyze changes in cytosolic free calcium concentrations ([Ca(2+)](cyt)) in response to elicitors of plant defenses, particularly cryptogein and oligogalacturonides. The calcium signatures differ in lag time, peak time, intensity, and duration. The intensities of both signatures depend on elicitor concentration and extracellular calcium concentration. Cryptogein signature is characterized by a long-sustained [Ca(2+)](cyt) increase that should be responsible for sustained mitogen-activated protein kinase activation, microtubule depolymerization, defense gene activation, and cell death. The [Ca(2+)](cyt) increase in elicitor-treated cells first results from a calcium influx, which in turns leads to calcium release from internal stores and additional Ca(2+) influx. H(2)O(2) resulting from the calcium-dependent activation of the NADPH oxidase also participates in [Ca(2+)](cyt) increase and may activate calcium channels from the plasma membrane. Competition assays with different elicitins demonstrate that [Ca(2+)](cyt) increase is mediated by cryptogein-receptor interaction.