This work tackles the commissioning and validation of a novel combination of a synchrotron-based proton beam therapy system (Hitachi, Ltd.) for use with a Monte Carlo treatment planning system (TPS). Four crucial aspects in this configuration have been investigated: (1) Monte Carlo-based correction performed by the TPS to the measured integrated depth-dose curves (IDD), (2) circular spot modelling with a single Gaussian function to characterize the synchrotron physical spot, which is elliptical, (3) the modelling of the range shifter that enables using only one set of measurements in open beams, and (4) the Monte Carlo dose calculation model in small fields.Integrated depth-dose curves were measured with a PTW Bragg peak chamber and corrected, with a Monte Carlo model, to account for energy absorbed outside the detector. The elliptical spot was measured by IBA Lynx scintillator, EBT3 films and PTW microDiamond. The accuracy of the TPS (RayStation, RaySearch Laboratories) at spot modelling with a circular Gaussian function was assessed.The beam model was validated using spread-out Bragg peak (SOBP) fields. We took single-point doses at several depths through the central axis using a PTW Farmer chamber, for fields between 2 x 2cm and 30 x 30cm. We checked the range-shifter modelling from open-beam data. We tested clinical cases with film and an ioni-zation chamber array (IBA Matrix).Sigma differences for spots fitted using 2D images and 1D profiles to elliptical and circular Gaussian models were below 0.22 mm. Differences between SOBP measurements at single points and TPS calculations for all fields between 5 x 5 and 30 x 30cm were below 2.3%. Smaller fields had larger differences: up to 3.8% in the 2 x 2cm field. Mean differences at several depths along the central axis were generally below 1%. Differences in range -shifter doses were below 2.4%. Gamma test (3%, 3 mm) results for clinical cases were generally above 95% for Matrix and film.Approaches for modelling synchrotron proton beams have been validated. Dose values for open and range -shifter fields demonstrate accurate Monte Carlo correction for IDDs. Elliptical spots can be successfully modelled using a circular Gaussian, which is accurate for patient calculations and can be used for small fields. A double-Gaussian spot can improve small-field calculations. The range-shifter modelling approach, which reduces clinical commissioning time, is adequate.

Objective. Periodic respiratory motion and inter-fraction variations are sources of geometric uncertainty in stereotactic body radiation therapy (SBRT) of pulmonary lesions. This study extensively evaluates and validates the separate and combined dosimetric effect of both factors using 4D-CT and daily 4D-cone beam CT (CBCT) dose accumulation scenarios. Approach. A first cohort of twenty early stage or metastatic disease lung cancer patients were retrospectively selected to evaluate each scenario. The planned-dose (3D(Ref)) was optimized on a 3D mid-position CT. To estimate the dosimetric impact of respiratory motion (4D(Ref)), inter-fractional variations (3D(Acc)) and the combined effect of both factors (4D(Acc)), three dose accumulation scenarios based on 4D-CT, daily mid-cone beam CT (CBCT) position and 4D-CBCT were implemented via CT-CT/CT-CBCT deformable image registration (DIR) techniques. Each scenario was compared to 3D(Ref.) A separate cohort of ten lung SBRT patients was selected to validate DIR techniques. The distance discordance metric (DDM) was implemented per voxel and per patient for tumor and organs at risk (OARs), and the dosimetric impact for CT-CBCT DIR geometric errors was calculated. Main results. Median and interquartile range (IQR) of the dose difference per voxel were 0.05/2.69 Gy and -0.12/2.68 Gy for 3DAcc-3DRef 4DAcc-3DRef. 4DRef-3DRef

Background It is widely accepted that Monte Carlo dose calculations offers a higher precision that the commercially available dose calculation algorithms. This advantage may be especially relevant for lung Stereotactic Body Radiation Therapy (SBRT), as this is a precise technique applied to an area of big inhomogeneity. Purpose We conducted a comparative study to reveal the differences between the doses calculated using the Collapsed Cone Convolution algorithm and the GAMOS/Geant4 Monte Carlo calculation for lung cancer patients treated with Stereotactic Body Radiation Therapy on an Elekta Versa HD linac. Methods For this study a set of ten patient treatments carried out at the Clínica Universidad de Navarra was selected. Theanalysis is based on the comparison of several dosimetric quantities for the Gross Tumor Volume (GTV) and several OrgansAt Risk (OARs), and also a gamma index calculation with distance-to-agreement set to 2 mm and dose difference to 3%, as recommended by ICRU to assess clinical impact. In order to guarantee a small uncertainty in the Monte Carlo calculation of the dosimetric quantities, we studied in detail the validity of different methods that may be used to determine this uncertainty. To compensate for lung movements, a 4D-Cone-beam Computed Tomography (CBCT) was acquired before treatment, whichallowed us to identify eight respiratory phases using a temporal binning. Using commercial MIM software®, we performed a deformable image registration between the eight CT respiration phases to construct the 4D doses. The same procedure was applied for the Treatment Planning System (TPS) dose files and for the Monte Carlo dose files. Results The differences between the two algorithms reveal the known weaknesses of the Collapsed Cone Convolution (CCC) algorithm for the calculation of lateral doses and in regions of large density change. The comparison between the two algorithms for individual phase doses shows differences up to 5% of the GTV D95 or 3¿4 Gy in some OARs, which may have a clinical impact. Nevertheless these differences are reduced for the 4D dose in most quantities under study. Conclusions Comparing the dose calculated with a Collapsed Cone Convolution algorithm with GAMOS/Geant4 for ten patients and eight respiratory phases, we found some differences that could have a clinical impact. When combining the eight temporal phases into a 4D dose using the MIM Deformable Image Registration software, the differences diminished substantially. Our statistical analysis concludes that dose uncertainty in the voxels with a maximum dose below a given percentage guarantees uncertainty in the dosimetric quantities below that figure.

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction, intermittent hypoxemia, and recurrent awakenings during sleep. The most used treatment for this syndrome is a device that generates a positive airway pressure-Continuous Positive Airway Pressure (CPAP), but it works continuously, whether or not there is apnea. An alternative consists on systems that detect apnea episodes and produce a stimulus that eliminates them. Article focuses on the development of a simple and autonomous processing system for the detection of obstructive sleep apneas, using polysomnography (PSG) signals: electroencephalography (EEG), electromyography (EMG), respiratory effort (RE), respiratory flow (RF), and oxygen saturation (SO2). The system is evaluated using, as a gold standard, 20 PSG tests labeled by sleep experts and it performs two analyses. A first analysis detects awake/sleep stages and is based on the accumulated amplitude in a channel-dependent frequency range, according to the criteria of the American Academy of Sleep Medicine (AASM). The second analysis detects hypopneas and apneas, based on analysis of the breathing cycle and oxygen saturation. The results show a good estimation of sleep events, where for 75% of the cases of patients analyzed it is possible to determine the awake/asleep states with an effectiveness of >92% and apneas and hypopneas with an effectiveness of >55%, through a simple processing system that could be implemented in an electronic device to be used in possible OSA treatments.

The purpose of this study was to devise and evaluate a method to quantify the dosimetric uncertainty produced by the interplay between the movement of multileaf collimator (MLC) and respiratory motion in lung stereotactic body radiation therapy (SBRT). The method calculates the dose distribution for all control points from a dynamic treatment in all respiratory phases. The methodology includes some characteristics of a patient's irregular breathing patterns. It selects, for each control point, the phases with maximum and minimum mean dose over the tumor and their corresponding adjacent phases, whenever necessary. According to this selection, the dose matrices from each control point are summed up to obtain two dose distributions in each phase, which are accumulated in the reference phase subsequently by Deformable Image Registration (DIR). D95 and Dmin,0.035cc were calculated over those accumulated dose distributions for Gross Tumor Volume (GTV), Planning Target Volume (PTV) - based on Internal Target Volume (ITV) approach - and Evaluation Target Volume (ETV), a novel concept that applies to 4D dose accumulation. With the ETV, DIR and interplay uncertainties are separated. The methodology also evaluated how variations in the breathing rate and field size affects the mean dose received by the GTV. The method was applied retrospectively in five patients treated with intensity modulated radiotherapy (IMRT) - minimum area defined by the leaves configuration at any control point was at least 4cm2-. Uncertainties in tumor coverage were small (in most patients, changes on D95 and Dmin,0.035cc were below 2% for GTV and ETV) but significant over- and under- dosages near ETV, which can be accentuated by highly irregular breathing. Uncertainties in mean dose for GTV tended to decrease exponentially with increasing field size and were reduced by an increase of breathing rate. The implementation of this method would be helpful to assess treatment quality in patients with irregular breathing. Furthermore, it could be used to study interplay uncertainties when small field sizes are used.

Obstructive sleep apnoea-hypopnoea syndrome (OSA) is a respiratory disorder characterised by repetitive obstruction of the upper airway, leading to several interruptions during sleep. It is currently one of the main public health problems worldwide and one of the main cardiovascular risk factors in developed and intermediate developing countries, whose populations are increasing in rates of obesity and age. One of the common treatments for OSA is a continuous positive airway pressure (CPAP) device, which pumps air through a hose, reaches a mask that the patient has over his or her nose and travels the airway, keeping the upper airway open during sleep and avoiding episodes of airway collapse. The problem is that CPAP is not accepted by some patients due to a lack of adaptation, so alternative treatments may be needed. For some years, there have been explorations of treatments related to electrical stimulation of the muscles of the upper airway as therapy to reduce the number of episodes of apnoea (measured through the apnoea¿hypopnoea index) during the night, strengthening these muscles through stimulation. This is the protocol of the first clinical study of a rehabilitation device for home use that not only provides functional stimulation of the upper-airway dilator muscles but also provides sensory stimulation. This device works by strengthening the dilating muscles of the upper respiratory tract and improving the sensory capacity of the laryngo-pharyngeal tract and is based on existing publications on the effectiveness of functional and somatosensory neurostimulation through neuroplasticity in the recovery of neurological deficits.

Purpose: To measure the in vitro flow properties of the PRESERFLO implant for comparison with the theoretical resistance to flow. Methods: The PRESERFLO was designed to control the flow of aqueous humor according to the Hagen-Poiseuille (HP) equation. Scanning electron microscopy (SEM) was performed to analyze the ultrastructure, and flow measurements were carried out using a gravity-flow setup. Results: SEM images of the PRESERFLO showed luminal diameters of 67.73 x 65.95 mu m and 63.66 x 70.54 mu m. The total diameter was 337.2 mu m, and the wall was 154 mu m wide. The theoretical calculation of the resistance to flow (R) for an aqueous humor (AH) viscosity of 0.7185 centipoises (cP) was 1.3 mm Hg/(mu L/min). Hence, assuming a constant AH flow of 2 mu L/min, the pressure differential across the device (AP) was estimated to be 2.6 mm Hg. The gravity-flow experiment allowed us to measure the experimental resistance to flow, which was R-E = 1.301 mm Hg/(mu L/min), in agreement with the theoretical resistance to flow R given by the HP equation. Conclusions: The experimental and theoretical flow testing showed that the pressure drop across this device would not be large enough to avoid hypotony unless the resistance to outflow of the sub-Tenon space was sufficient to control the intraocular pressure in the early postoperative period. Translational Relevance: The fluid properties of glaucoma subconjunctival drainage devices determine their specific bleb-forming capacity and ability to avoid hypotony and therefore their safety and efficacy profile. Translational Relevance: The fluid properties of glaucoma subconjunctival drainage devices determine their specific bleb-forming capacity and ability to avoid hypotony and therefore their safety and efficacy profile.

Purpose To use four-dimensional (4D) dose accumulation based on deformable image registration (DIR) to assess dosimetric uncertainty in lung stereotactic body radiation therapy (SBRT) treatment planning. A novel concept, the Evaluation Target Volume (ETV), was introduced to achieve this goal. Methods The internal target volume (ITV) approach was used for treatment planning for 11 patients receiving lung SBRT. Retrospectively, 4D dose calculation was done in Pinnacle v9.10. Total dose was accumulated in the reference phase using DIR with MIM. DIR was validated using landmarks introduced by an expert radiation oncologist. The 4D and three-dimensional (3D) dose distributions were compared within the gross tumor volume (GTV) and the planning target volume (PTV) using the D-95 and D-min (calculated as D-min,D-0.035cc) metrics. For lung involvement, the mean dose and V-20, V-10, and V-5 were used in the 3D to 4D dose comparison, and D-max (D-0.1cc) was used for all other organs at risk (OAR). The new evaluation target volume (ETV) was calculated by expanding the GTV in the reference phase in order to include geometrical uncertainties of the DIR, interobserver variability in the definition of the tumor, and uncertainties of imaging and delivery systems. D-95 and D-min,D-0.035cc metrics were then calculated on the basis of the ETV for 4D accumulated dose distributions, and these metrics were compared with those calculated from the PTV for 3D planned dose distributions.

The cylindrical wall boundary layer of a closed cylinder split in two halves at the equator is studied experimentally. When these two parts rotate in exact corotation the internal flow is essentially in solid-body rotation at the angular velocity of both halves. When a slight difference between the rotation frequencies is established a secondary flow is created due to the differential rotation between both sides and restricted to the boundary layer. This behavior of the boundary layer is compared with theoretical and numerical results finding the ¿sandwich¿ structure of a Stewartson boundary layer. Time-dependent waves are observed near the cylindrical wall. Their behavior for different values of the control parameters are presented. Finally, a global recirculation mode is also found due to a symmetry-breaking induced between sides that appears because of a slight misalignment of the experimental setup, whose characteristics are compatible with the behavior of a precessing cylinder.

We present a novel method to characterize the morphology of semicircular canals of the inner ear. Previous experimental works have a common nexus, the human-operator subjectivity. Although these methods are mostly automatic, they rely on a human decision to determine some particular anatomical positions. We implement a systematic analysis where there is no human subjectivity. Our approach is based on a specific magnetic resonance study done in a group of 20 volunteers. From the raw data, the proposed method defines the centerline of all three semicircular canals through a skeletonization process and computes the angle of the functional pair and other geometrical parameters. This approach allows us to assess the inter-operator effect on other methods. From our results, we conclude that, although an average geometry can be defined, the inner ear anatomy cannot be reduced to a single geometry as seen in previous experimental works. We observed a relevant variability of the geometrical parameters in our cohort of volunteers that hinders this usual simplification.

Factors determining the variability of air-pulse pressure to determine the thresholds of laryngeal-pharyngeal reflexes, which are related to swallowing and airway protection, were explored. Potential factors affecting the reproducibility of air-pulses were experimentally evaluated and included in a multiple linear regression model. A novel device controlling these factors and minimizing variability was designed. Its reproducibility was assessed by the coefficient of variation (CV) of the pressures and duration of air-pulses, and its validity was assessed by comparing obtained pressures and durations with desired pressures and durations. Differences in the pressures of airpulse categories were assessed by a one-way ANOVA of repeated measures, a Tukey test and a box and whisker plot. The distance and angle between the exit of the tube conducting the pulses and the surface to be impacted, the diameter of the tube, the feeding pressure of the system, and the duration of air-pulses significantly affected the accuracy of air-pulses. The novel device incorporated electronic valves and a telemeter for use during the fiberoptic endoscopic evaluation of swallowing. The differences between the desired and obtained pressures and durations were below 3%. The CV of the air-pulse pressures of the novel device was 0.02. The CV of air-pulse duration was 0.05. The oneway ANOVA, Tukey test and box and whisker plot showed that the outlet pressures of air-pulse categories had statistically significant differences between them without overlap between categories, which helps to obtain an accurate threshold.