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<jats:title>Abstract</jats:title> <jats:p>Electron applicator cutouts for radiation therapy electron beam shaping are typically cast from Low Melting Point Alloys (LMPA), such as cerrobend. In this work, we describe the Monte Carlo modelling of novel 3D printed cutouts based on tungsten carbide powder and the resulting dose profiles subject to Elekta Agility electron beams. Cerrobend cutouts were also modelled using the Monte Carlo code EGSnrc. Cerrobend and tungsten carbide cutouts were found to have the same dose profiles within model variance. Computed profiles and percentage depth dose (PDDs) curves of the Elekta Agility accelerator model using standard cutouts in water were found to agree with water tank measurements using gamma criteria of 2%/2mm. The Monte Carlo computed dose profiles of the tungsten carbide cutouts in a polystyrene phantom were also found to agree with liquid-filled ionization chamber array measurements using gamma criteria of 2%/2mm. We conclude that the tungsten carbide cutouts are clinically equivalent to LMPA cutouts.</jats:p>

<jats:title>Abstract</jats:title> <jats:p>Small-angle x-ray scattering (SAXS) imaging may have the potential to image <jats:italic>β</jats:italic>-amyloid plaques <jats:italic>in vivo</jats:italic> in the brain without tracers for assessment of Alzheimer’s disease (AD). We use a laboratory SAXS system for planar imaging of AD model and control mouse brains slices to detect regions with high density of amyloid plaques. These regions were validated with histology methods. Using Monte Carlo techniques, we simulate SAXS computed tomography (SAXS-CT) system to study the potential of selectively differentiating amyloid targets in mouse and human head phantoms with detailed anatomy. We found contrast between amyloid and brain tissue at small <jats:italic>q</jats:italic> (below 0.8 nm<jats:sup>−1</jats:sup>) in the neocortex region of the transgenic brain slices as supported by histology. We observed similar behavior through planar SAXS imaging of an amyloid-like fibril deposit with a 0.8 mm diameter at a known location on a wild type mouse brain. In our SAXS-CT simulations, we found that 33-keV x rays provide increase plaque visibility in the mouse head for targets of at least 0.1 mm in diameter, while in the human head, 70-keV x rays were capable of detecting plaques as small as 2 mm. To increase radiation efficiency, we used a weighted-sum image visualization approach allowing the dose deposited by 70-keV x rays per SAXS-CT slice of the human head to be reduced by a factor of 10 to 71 mGy for gray matter and 63 mGy for white matter. The findings suggest that a dedicated SAXS-CT system for <jats:italic>in vivo</jats:italic> amyloid imaging in small animals and humans can be successfully developed with further system optimization to detect regions with amyloid plaques in the brain with a safe level of radiation dose.</jats:p>

<jats:title>Abstract</jats:title> <jats:p> <jats:italic>Background:</jats:italic> Spine injury risk due to military conflict is an ongoing concern among defense organizations throughout the world. A better understanding of spine biomechanics could assist in developing protection devices to reduce injuries caused by caudocephalad acceleration (+Gz) in under-body blasts (UBB). Although some finite element (FE) human models have demonstrated reasonable lumbar spine biofidelity, they were either partial spine models or not validated for UBB-type loading modes at the lumbar functional spinal unit (FSU) level, thus limiting their ability to analyze UBB-associated occupant kinematics. <jats:italic>Methods:</jats:italic> An FE functional representation of the human spine with simplified geometry was developed to study the lumbar spine responses under +Gz loading. Fifty-seven load curves obtained from post mortem human subject experiments were used to optimize the model. <jats:italic>Results:</jats:italic> The model was cumulatively validated for compression, flexion, extension, and anterior-, posterior-, and lateral-shears of the lumbar spine and flexion and extension of the cervical spine. The thoracic spine was optimized for flexion and compression. The cumulative CORrelation and Analysis (CORA) rating for the lumbar spine was 0.766 and the cervical spine was 0.818; both surpassed the 0.7 objective goal. The model’s element size was confirmed as converged. <jats:italic>Conclusions:</jats:italic> An FE functional representation of the human spine was developed for +Gz lumbar load analysis. The lumbar and cervical spines were demonstrated to be quantitatively biofidelic to the FSU level for multi-directional loading and bending typically experienced in +Gz loading, filling the capability gap in current models.</jats:p>

<jats:title>Abstract</jats:title> <jats:p> <jats:italic>Purpose:</jats:italic> Trajectory log files are increasingly being utilized clinically for machine and patient specific QA. The process of converting the DICOM-RT plan to a deliverable trajectory by the linac control software introduces some uncertainty that is inherently incorporated into measurement-based patient specific QA but is not necessarily included for trajectory log file-based methods. Roughly half of prior studies have included this uncertainty in the analysis while the remaining studies have ignored it, and it has yet to be quantified in the literature. <jats:italic>Methods:</jats:italic> We collected DICOM-RT files from the treatment planning system and the trajectory log files from four TrueBeam linear accelerators for 25 IMRT and 10 VMAT plans. We quantified the DICOM-RT Conversion to Trajectory Residual (DCTR, difference between ‘planned’ MLC position from TPS DICOM-RT file and ‘expected’ MLC position (the deliverable MLC positions calculated by the linac control software) from trajectory log file) and compared it to the discrepancy between actual and expected machine parameters recorded in trajectory log files. <jats:italic>Results:</jats:italic> RMS of the DCTR was 0.0845 mm (range of RMS per field/arc: 0.0173–0.1825 mm) for 35 plans (114 fields/arcs) and was independent of treatment technique, with a maximum observed discrepancy at any control point of 0.7255 mm. DCTR was correlated with MLC velocity and was consistent over the course of treatment and over time, with a slight change in magnitude observed after a linac software upgrade. For comparison, the RMS of trajectory log file reported delivery error for moving MLCs was 0.0205 mm, thus DCTR is about four times the recorded delivery error in the trajectory log file. <jats:italic>Conclusion:</jats:italic> The uncertainty introduced from the conversion process by the linac control software from DICOM-RT plan to a deliverable trajectory is 3–4 times larger than the discrepancy between actual and expected machine parameters recorded in trajectory log files. This uncertainty should be incorporated into the analysis when using trajectory log file-based methods for analyzing MLC performance or patient-specific QA.</jats:p>

<jats:title>Abstract</jats:title> <jats:p>This study proposes that incorporating marker-based visibility constraints into the optimization of volumetric modulated arc therapy (VMAT) will generate treatment plans which not only ensure a higher chance of successfully applying real-time tumor tracking techniques, but also simultaneously satisfy dosimetric objectives. This was applied clinically and investigated for multiple disease sites (10 prostate, 5 liver, and 5 lung) using a radiotherapy optimization software (<jats:italic>MonArc</jats:italic>), where these new constraints were added to conventional dosimetric constraints. For all the investigated sites, three fiducial markers were located inside or around the planning target volume (PTV), and VMAT plans were created for each patient. We modified <jats:italic>MonArc</jats:italic> to analyze the multi-leaf collimator (MLC) beam’s-eye-view at all control points in the gantry arc, while including marker-based visibility constraints of type ‘hard’ (i.e. requiring 100% visibility of all markers, HC) and ‘soft’ (i.e. penalizes visibility for one marker [SC<jats:sub>I</jats:sub>] or two markers [SC<jats:sub>II</jats:sub>] only) in the optimization process. Dose distributions resulting from the constrained plans (HC, SC<jats:sub>I</jats:sub>, and SC<jats:sub>II</jats:sub>) were compared to the non-constrained plan (NC—plans optimized without visibility constraints) using several quantitative dose metrics including the conformity index, homogeneity index, doses to PTV and to organs-at-risk (OAR). Generally, the NC plan produced the best PTV dose conformity and the least OAR doses for the entire patient datasets, followed by the SC and then HC plans, with all the optimization approaches typically achieving acceptable dose metrics. Across the three disease sites, visibility of all three markers in MLC apertures increased from 32% to 100% of available control points as visibility constraints strengthened. Although dose metrics showed some deterioration for constrained plans (−6% for SC<jats:sub>I</jats:sub> up to −15% for HC using the PTV average index), the required dosimetric objectives were still satisfied in at least 90% of patients. In conclusion, we demonstrated that marker and tumour visibility constraints can be incorporated with dosimetric objectives to produce treatment plans satisfying both objectives, which should ensure greater success when applying real-time tracking for VMAT delivery.</jats:p>

<jats:title>Abstract</jats:title> <jats:p>The aim of this work is the dosimetric characterization of a plane parallel ionization chamber under defined beam setups at the CERN Linear Electron Accelerator for Research (CLEAR). A laser driven electron beam with energy of 200 MeV at two different field sizes of approximately 3.5 mm FWHM and approximately 7 mm FWHM were used at different pulse structures. Thereby the dose-per-pulse range varied between approximately 0.2 and 12 Gy per pulse. This range represents approximately conventional dose rate range beam conditions up to ultra-high dose rate (UHDR) beam conditions. The experiment was based on a water phantom which was integrated into the horizontal beamline and radiochromic films and an Advanced Markus ionization chamber was positioned in the water phantom. In addition, the experimental setup were modelled in the Monte Carlo simulation environment FLUKA. In a first step the radiochromic film measurements were used to verify the beamline setup. Depth dose distributions and dose profiles measured by radiochromic film were compared with Monte Carlo simulations to verify the experimental conditions. Second, the radiochromic films were used for reference dosimetry to characterize the ionization chamber. In particular, polarity effects and the ion collection efficiency of the ionization chamber were investigated for both field sizes and the complete dose rate range. As a result of the study, significant polarity effects and recombination loss of the ionization chamber were shown and characterized. However, the work shows that the behavior of the ionization chamber at the laser driven beam line at the CLEAR facility is comparable to classical high dose-per-pulse electron beams. This allows the use of ionization chambers on the CLEAR system and thus enables active dose measurement during the experiment. Compared to passive dose measurement with film, this is an important step forward in the experimental equipment of the facility.</jats:p>

<jats:title>Abstract</jats:title> <jats:p>This work uses a simple low-cost wearable device embedded with discrete thermal sensors to map the breast skin surface temperature. A methodology has been developed to estimate diameter, blood perfusion, metabolic heat generation and location in X, Y, Z coordinate of tumor from this discrete set of data. An interactive 3D thermal tomography was developed which provides a detailed 3D thermal view of the breast anatomy. Using this system, the user can interactively rotate and slice the 3D thermal image of the breast for a detailed study of the tumor. Finite element method (FEM) and an evolution-based inverse method were used for the parameter estimation. The method was first validated using phantom experiments and the results obtained were within an error of 10% (0.005 W cm<jats:sup>−3</jats:sup>) for heat generation and 15% (0.3 cm) for heater location. Further validation was carried out through clinical trials on 60 human subjects. Estimated blood perfusion rate and metabolic heat generation rate exhibit distinguishable difference between cancerous and non-cancerous breast. Estimated diameter and location of tumor in cancerous breast shows good agreement with the actual clinical reports. We have obtained a sensitivity of 82.78% and specificity of 87.09%. Proposed breast tumor parameter estimation methodology with interactive 3D thermal tomography is a good screening tool for breast cancer detection and also useful for clinicians to find out location including depth.</jats:p>

<jats:title>Abstract</jats:title> <jats:p>We propose a semi-automatic segmentation pipeline designed for longitudinal studies considering structures with large anatomical variability, where expert interactions are required for relevant segmentations. Our pipeline builds on the regularized Fast Marching (rFM) segmentation approach by Risser <jats:italic>et al</jats:italic> (2018). It consists in transporting baseline multi-label FM seeds on follow-up images, selecting the relevant ones and finally performing the rFM approach. It showed increased, robust and faster results compared to clinical manual segmentation. Our method was evaluated on 3D synthetic images and patients’ whole-body MRI. It allowed a robust and flexible handling of organs longitudinal deformations while considerably reducing manual interventions.</jats:p>

<jats:title>Abstract</jats:title> <jats:p> <jats:italic>Purpose</jats:italic> Dose coefficients from rituximab, tetulomab, cetuximab, and huA33 monoclonal antibodies labelled with the radionuclide <jats:sup>177</jats:sup>Lu were estimated for human organs and tumours via a theoretical simulation based on experimental results. <jats:italic>Methods</jats:italic> The real experimental results were obtained from radiopharmaceutical distribution in hairless mice. Using the Sparks and Aydogan method, the cumulated activity for humans was recalculated. The simulation was used to assess the behaviour of MAbs labelled with <jats:sup>177</jats:sup>Lu after injection into the human body. The average absorbed doses were calculated for the most exposed organs and tissues. <jats:italic>Results</jats:italic> The huA33 monoclonal antibodies (MAbs) labelled with 177Lu (Lu-rituximab, Lu-tetulomab, Lu-cetuximab, and Lu-huA33), presented the maximum nuclear transformation per Bq intake for the main organs (blood, kidneys, liver, lung, and spleen, as well as for a tumour) The absorbed dose in the liver is three times lower for Lu-huA33 compared to the other drugs. In the case of cetuximab, the spleen received the lowest dose compared to the other drugs. The dependencies on absorbed dose for the alveolar, bronchioles, bone surface, heart wall, kidneys, liver, lung, lymphatic nodes, and spleen, are presented. For tumours, the absorbed dose for each drug is calculated separately for a sphere of unit volume by using the information on the injected dose. <jats:italic>Conclusion</jats:italic>, The ratios of the dose coefficient for the tumour to each organ, indicate that lutetium-177 can be recommended for targeted radionuclide therapy since the dose per tumour is much greater than the dose per organ.</jats:p>

<jats:title>Abstract</jats:title> <jats:p> <jats:italic>Objective</jats:italic>: MR-linac machines are being developed for image-guided radiation therapy but the magnetic field of such machines could affect dose distributions. The purpose of this work was to evaluate the effect of a magnetic field on linac beam dosimetric parameters including penumbra for circular cones used in radiosurgery. <jats:italic>Methods</jats:italic>: Monte Carlo simulation was conducted for a linac machine with circular cones at 6 MV beam. A homogenous magnetic field of 1.5 T was applied transversely and parallel to the radiation beam. Percentage depth dose (PDD) and beam profiles in a water phantom with and without the magnetic field were calculated. <jats:italic>Results</jats:italic>: The results have shown that when the magnetic field is applied transversely, the PDDs in the water phantom differ in the buildup region and distant part of PDD curves. The beam profiles at three different depths are all significantly different from those without the magnetic field. The penumbra is greater when a magnetic field has been applied. <jats:italic>Conclusion</jats:italic>: Linear accelerator-based SRT and SRS use small circular cones. The beam penumbra for these cones can change in the presence of a magnetic field. The perturbation of dose distribution has been also observed in a patient plan due to the presence of a magnetic field. The results of this study show that dose distributions in the presence of a magnetic field must be considered for MR-guided radiotherapy treatments.</jats:p>