Th1- and Th17-Related Cytokines in Venous and Arterial Blood of Sclerodermic Patients with and without Digital Ulcers.

The earliest clinical manifestation of SSc is usually Raynaud's phenomenon, a small-arteries vasospasm driven by vascular tone dysregulation and microcirculatory abnormalities, resulting in digital ulcers (DU) in up to 50% of patients. Many cytokines as well as growth factors have been shown to play a role in promoting vascular smooth muscle cell proliferation and fibroblast activation, leading to ischemic damage as well as skin fibrosis. We aim to investigate a possible difference in venous and arterial blood levels of many cytokines (Th1- and Th17-related), GM-CSF, and endothelin-1 (ET1) in patients with and without DU. In the same patients, the correlations between capillary damage, evaluated by nailfold videocapillaroscopy (NVC), extension of skin fibrosis, calculated by modified Rodnan skin score (mRSS), and cytokines, ET-1, and GM-CSF levels were also measured. Patients with DU showed venous levels of IL-1ß (p=0.024), IL-6 (p=0.012), IL-22(p=0.006), and TGF-ß (p=0.046) significantly higher compared to arterial levels and arterial levels of GM-CSF and TNF-alpha significantly higher compared to venous levels (p < 0.001). NVC abnormalities were correlated with arterial TNFa and venous IL22, IL23, and IL17 levels and negatively correlated with venous ET-1 levels, whereas mRSS showed a negative correlation with IL-21(ρ = -0.427, p=0.050). The increased Th17-cytokine levels in venous compared to arterial blood of patients with DU suggest local cytokine production on ulcer site. The higher TNFa and GM-CSF levels in arterial blood of DU patients support the attempt to mitigate the hypoxic damage, and the correlation between Th17-cytokines, mRSS, NVC, and ET1 agrees with the potent profibrotic stimulus at the onset of the disease, which decreases as the SSc progresses.

Monte Carlo simulation tool for online treatment monitoring in hadrontherapy with in-beam PET: A patient study.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

Human thyroid-stimulating hormone synthesis in human embryonic kidney cells and related N-glycoprofiling analysis for carbohydrate composition determination.

A strain of embryonic human kidney cells (HEK293) was transiently co-transfected with the expression vectors coding for the α- and ß-subunits of human thyroid-stimulating hormone (hTSH), and, for the first time, a human cell-derived recombinant hTSH was synthesized and extensively characterized. The purification strategy involving two steps provided an overall yield of 55% and a purity level > 90%. The purified material (hTSH-HEK) was analyzed and compared to a CHO-derived recombinant preparation (hTSH-CHO) and to a pituitary-derived (hTSH-Pit) preparation. The three preparations showed an equivalent purity (> 95%) with a hTSH-HEK molecular mass 2.1% lower than that of hTSH-CHO and 2.7% higher than that of hTSH-Pit. Remarkable differences were found in the carbohydrate moiety, the lowest sialic acid content and highest fucose content being observed in hTSH-HEK. In vivo biological activity was confirmed for the three preparations, the hTSH-HEK bioactivity being 39 and 16% lower than those of hTSH-CHO and hTSH-Pit, respectively. The hTSH-HEK circulatory half-life (t 1/2) was also shorter than those of hTSH-CHO (1.5-fold) and hTSH-Pit (1.2-fold). According to these findings, HEK-293-derived hTSH can be considered to be useful for clinical applications, in view as well of its human origin and particular carbohydrate composition.

Neuromuscular taping enhances hand function in patients with systemic sclerosis: a pilot study.

Hand functioning is often impaired in patients with Systemic sclerosis. Neuromuscular Taping is a novel application of tape able to improve functioning. The aim of this study was to evaluate the possible role of this application in the hand functionality of patients with Systemic sclerosis. Women with a diagnosis of SSc has been recruited and evaluated using different scales before and immediately after NMT application and after one, three and six months. Fifty-three women has been evaluated and Cochin Hand Functional Disability scale, Hand Mobility in Sclerodermia, Modified Rodnan Skin Score and Dreiser Algo - Functional Index scores showed statistical significant differences during all the period; moreover a reduction of pain and Raynaud Phenomenon's and an improvement of finger flexion has been observed. Application of NMT in patients with Systemic sclerosis have showed beneficial effect and future studies are needed to confirm these results.

Efficient Non-Invasive Plasmid-DNA Administration into Tibialis Cranialis Muscle of "Little" Mice.

BACKGROUND: An alternative treatment for growth hormone deficiency based on hGH-DNA administration, followed by electro gene transfer, was investigated by injecting the plasmid into surgically exposed or non-exposed quadriceps or tibialis muscle of immunodeficient "little" mice. METHODS: An optimization of electrotransfer conditions via a new combination of high/low voltage pulses is presented. After 3 days, serum hGH was determined and in a 28-day assay, the relative growth parameters were compared. RESULTS: Both groups exhibited similar results: 5.0 ± 2.2 (SD) and 3.5 ± 0.9 ng hGH/ml (P>0.05; n=7) for the exposed quadriceps and non-exposed tibialis treatments, respectively. The final body weight increases were 16.1% for the quadriceps and 18.9% for the tibialis group. The tail and nose-to-tail length increases were 4.5% and 7.1% for the quadriceps and 4.8 and 4.6% for the tibialis group. The right and left femur length increases, obtained from radiographic measurements, were 16.9% and 12.7% for the quadriceps and 19.4% and 12.3% for the tibialis, respectively. A non-significant difference between exposed quadriceps and non-exposed tibialis treatments (P=0.48) was confirmed via a completely integrated statistical analysis. Circulating mIGF-1 levels were 126 ± 47, 106 ± 93 (P>0.05) and 38 ± 15 ng/ml for the quadriceps, tibialis and saline treatments, respectively. CONCLUSION: These results show that hGH-DNA administration into non-exposed tibialis muscle followed by the new HV/LV electrotransfer protocol was an equally efficient, less traumatic treatment, much more suitable for pre-clinical testing than administration into exposed quadriceps.

Full-beam performances of a PET detector with synchrotron therapeutic proton beams.

Treatment quality assessment is a crucial feature for both present and next-generation ion therapy facilities. Several approaches are being explored, based on prompt radiation emission or on PET signals by [Formula: see text]-decaying isotopes generated by beam interactions with the body. In-beam PET monitoring at synchrotron-based ion therapy facilities has already been performed, either based on inter-spill data only, to avoid the influence of the prompt radiation, or including both in-spill and inter-spill data. However, the PET images either suffer of poor statistics (inter-spill) or are more influenced by the background induced by prompt radiation (in-spill). Both those problems are expected to worsen for accelerators with improved duty cycle where the inter-spill interval is reduced to shorten the treatment time. With the aim of assessing the detector performance and developing techniques for background reduction, a test of an in-beam PET detector prototype was performed at the CNAO synchrotron-based ion therapy facility in full-beam acquisition modality. Data taken with proton beams impinging on PMMA phantoms showed the system acquisition capability and the resulting activity distribution, separately reconstructed for the in-spill and the inter-spill data. The coincidence time resolution for in-spill and inter-spill data shows a good agreement, with a slight deterioration during the spill. The data selection technique allows the identification and rejection of most of the background originated during the beam delivery. The activity range difference between two different proton beam energies (68 and 72 MeV) was measured and found to be in sub-millimeter agreement with the expected result. However, a slightly longer (2 mm) absolute profile length is obtained for in-spill data when compared to inter-spill data.

Th-17 cytokines and interstitial lung involvement in systemic sclerosis.

The two phenotypes of both limited and diffuse systemic sclerosis (SSc) have different forms of pulmonary involvement: pulmonary arterial hypertension (limited phenotype) or interstitial lung disease (ILD) (diffuse phenotype). We aimed to investigate whether Th17-related cytokines, as measured in exhaled breath condensate (EBC) and in serum were connected to ILD in diffuse SSc patients. We found that for both limited and diffuse SSc, the EBC levels of all cytokines and most of the cytokine serum levels were significantly higher in patients than in controls, while, the EBC levels of Th-17 cytokines and the serum levels of IL-10 and TNF-α were significantly higher in diffuse than in limited SSc. Moreover, the thoracic CT-scan score of ILD was significantly associated with the EBC levels of IL-1 beta and with the serum IL-23, TNF-α and IL-10 levels, whereas lung carbon monoxide diffusing capacity was negatively related to the EBC levels of IL-1 beta, IL-17 and serum IL-10. Serum IL-23 was also inversely correlated with vital capacity. In conclusion, in diffuse SSc patients our results show a clear link between Th-17 cytokines measured both in EBC and in serum with interstitial lung involvement. This highlights how important it is to target Th-17 cytokines when developing new treatments for lung fibrosis.

Large scale validation of the M5L lung CAD on heterogeneous CT datasets.

PURPOSE: M5L, a fully automated computer-aided detection (CAD) system for the detection and segmentation of lung nodules in thoracic computed tomography (CT), is presented and validated on several image datasets. METHODS: M5L is the combination of two independent subsystems, based on the Channeler Ant Model as a segmentation tool [lung channeler ant model (lungCAM)] and on the voxel-based neural approach. The lungCAM was upgraded with a scan equalization module and a new procedure to recover the nodules connected to other lung structures; its classification module, which makes use of a feed-forward neural network, is based of a small number of features (13), so as to minimize the risk of lacking generalization, which could be possible given the large difference between the size of the training and testing datasets, which contain 94 and 1019 CTs, respectively. The lungCAM (standalone) and M5L (combined) performance was extensively tested on 1043 CT scans from three independent datasets, including a detailed analysis of the full Lung Image Database Consortium/Image Database Resource Initiative database, which is not yet found in literature. RESULTS: The lungCAM and M5L performance is consistent across the databases, with a sensitivity of about 70% and 80%, respectively, at eight false positive findings per scan, despite the variable annotation criteria and acquisition and reconstruction conditions. A reduced sensitivity is found for subtle nodules and ground glass opacities (GGO) structures. A comparison with other CAD systems is also presented. CONCLUSIONS: The M5L performance on a large and heterogeneous dataset is stable and satisfactory, although the development of a dedicated module for GGOs detection could further improve it, as well as an iterative optimization of the training procedure. The main aim of the present study was accomplished: M5L results do not deteriorate when increasing the dataset size, making it a candidate for supporting radiologists on large scale screenings and clinical programs.

The CNAO dose delivery system for modulated scanning ion beam radiotherapy.

PURPOSE: This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy. METHODS: CNAO Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real-time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery. RESULTS: The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing comparable performances and are presently in use on the CNAO beam lines for clinical activity. CONCLUSIONS: The dose delivery system described in this paper is one among the few worldwide existing systems to operate ion beam for modulated scanning radiotherapy. At the time of writing, it has been used to treat more than 350 patients and it has proven to guide and control the therapeutic pencil beams reaching performances well above clinical requirements. In particular, in terms of dose accuracy and stability, daily quality assurance measurements have shown dose deviations always lower than the acceptance threshold of 5% and 2.5%, respectively.

Microbial bio-based plastics from olive-mill wastewater: Generation and properties of polyhydroxyalkanoates from mixed cultures in a two-stage pilot scale system.

The operational efficiency of a two stage pilot scale system for polyhydroxyalkanoates (PHAs) production from three phase olive oil mill wastewater (OMW) was investigated in this study. A mixed anaerobic, acidogenic culture derived from a municipal wastewater treatment plant, was used in the first stage, aiming to the acidification of OMW. The effluent of the first bioreactor that was operated in continuous mode, was collected in a sedimentation tank in which partial removal of the suspended solids was taking place, and was then forwarded to an aerobic reactor, operated in sequential batch mode under nutrient limitation. In the second stage an enriched culture of Pseudomonas sp. was used as initial inoculum for the production of PHAs from the acidified waste. Clarification of the acidified waste, using aluminium sulphate which causes flocculation and precipitation of solids, was also performed, and its effect on the composition of the acidified waste as well as on the yields and properties of PHAs was investigated. It was shown that clarification had no significant qualitative or quantitative effect on the primary carbon sources, i.e. short chain fatty acids and residual sugars, but only on the values of total suspended solids and total chemical oxygen demand of the acidified waste. The type and thermal characteristics of the produced PHAs were also similar for both types of feed. However the clarification of the waste seemed to have a positive impact on final PHAs yield, measured as gPHAs/100g of VSS, which reached up to 25%. Analysis of the final products via nuclear magnetic resonance spectroscopy revealed the existence of 3-hydroxybutyrate (3HB) and 3-hydroxyoctanoate (HO) units, leading to the conclusion that the polymer could be either a blend of P3HB and P3HO homopolymers or/and the 3HB-co-3HO co-polymer, an unusual polymer occurring in nature with advanced properties.

Efficacy of bosentan in the treatment of Raynaud's phenomenon in patients with systemic sclerosis never treated with prostanoids.

The objective of this study was to evaluate the efficacy of the endothelin receptor antagonist, bosentan, in patients with Raynaud's phenomenon secondary to systemic sclerosis never treated with prostanoids and without digital ulcers. The study design is a preliminary, prospective open label trial. The patients recruited took one 62.5 mg dose of bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 24 weeks. Of the 10 patients recruited, all completed the study. The reduction in Raynaud's phenomenon attacks at week 24 from the baseline was statistically significant (Δ-1.3, P=0.0126). The Raynaud's condition score showed a statistically significant improvement (Δ-1.4, P=0.0279), as did the visual analog pain scale (Δ-1.5, P=0.0016) at the 24th week. Bosentan appears to be effective and may be a valid alternative for the treatment of severe secondary Raynaud's phenomenon for patients where prostanoids therapy is contraindicated or refused.

SU-E-T-298: Evaluation of the CNAO Spot Scanning Technique Based on the First Clinical Deliveries.

PURPOSE: The first Italian hospital-based facility for hadrontherapy is the Centro Nazionale di Adroterapia Oncologica (CNAO) which started the clinical activity on September 2011 with protons beams. The control of the treatment is performed online by the Dose Delivery (DD) system which guides the whole treatment by measuring beam characteristics as number of delivered particles and beam position. The author will present the comparison between the required and delivered quantities. METHODS: The CNAO facility is based on a synchrotron designed to accelerate and deliver proton and carbon ion beams in the clinical ranges. Unlike most of the proton-therapy centres, the delivery technique adopted at CNAO is the "quasi-discrete" active scanning where dedicated magnets are used to drive a pencil beam through the target and the beam is normally not switched off during the transition between adjacent spots. These operations are performed by the DD system which, based on the treatment planning and the online analysis of dedicated beam monitor chambers, drives the scanning magnets. Spot by spot the DD records data which allow the comparison between the measured number of particles and position and the prescription. RESULTS: The data collected by the dose delivery during the treatments were analyzed in detail, each treatment consisting in more than 30 identical fractions. This allows checking the stability and the accuracy of the CNAO delivery over identical spot sequences. The comparison between the measured number of particles, the measured position of each spot, and the corresponding prescribed quantities will be presented in detail. Critical points will be discussed together with the proposed improvement of the system. CONCLUSIONS: The results confirm the good performance of the CNAO beam delivery obtained during the commissioning phase.

Analysis of the reliability of the local effect model for the use in carbon ion treatment planning systems.

In radiotherapy with carbon ions, biological effects of treatments have to be predicted. For this purpose, one of the most used models is the local effect model (LEM) developed at the Gesellschaft für Schwerionenforschung (GSI), Germany. At the Istituto Nazionale di Fisica Nucleare, Italy, the reliability of the last published version of LEM (LEM III) in reproducing radiobiological data has been checked under both monoenergetic and spread-out Bragg peak (SOBP) carbon-ion irradiation. The reproduction of the monoenergetic measurements with the LEM was rather successful for some cell lines, while it failed for the less-radioresistant ones. The SOBP experimental trend was predicted by the LEM, but a large shift between model curves and measured points was observed.

Online beam monitoring in the treatment of ocular pathologies at the INFN Laboratori Nazionali del Sud-Catania.

A detector (MOPI) has been developed for the online monitoring of the beam at the Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA), where shallow tumours of the ocular region are treated with 62 MeV protons. At CATANA the beam is passively spread to match the tumour shape. The uniformity of the delivered dose depends on beam geometrical quantities which are checked before each treatment. However, beam instabilities might develop during the irradiation affecting the dose distribution. This paper reports on the use of the MOPI detector to measure the stability of the beam profile during the irradiation in the clinical practice. The results obtained in the treatment of 54 patients are also presented.

Heuristic optimization of the scanning path of particle therapy beams.

Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

A treatment planning code for inverse planning and 3D optimization in hadrontherapy.

The therapeutic use of protons and ions, especially carbon ions, is a new technique and a challenge to conform the dose to the target due to the energy deposition characteristics of hadron beams. An appropriate treatment planning system (TPS) is strictly necessary to take full advantage. We developed a TPS software, ANCOD++, for the evaluation of the optimal conformal dose. ANCOD++ is an analytical code using the voxel-scan technique as an active method to deliver the dose to the patient, and provides treatment plans with both proton and carbon ion beams. The iterative algorithm, coded in C++ and running on Unix/Linux platform, allows the determination of the best fluences of the individual beams to obtain an optimal physical dose distribution, delivering a maximum dose to the target volume and a minimum dose to critical structures. The TPS is supported by Monte Carlo simulations with the package GEANT3 to provide the necessary physical lookup tables and verify the optimized treatment plans. Dose verifications done by means of full Monte Carlo simulations show an overall good agreement with the treatment planning calculations. We stress the fact that the purpose of this work is the verification of the physical dose and a next work will be dedicated to the radiobiological evaluation of the equivalent biological dose.

A method for the inter-calibration of a matrix of sensors.

We present a quick and easy method for the calibration of a matrix of sensors. The algorithm is based on a three-step irradiation procedure which relies only on the constancy of the delivered fluence at each step. With this method the gain of each sensor is derived relative to a reference detector. The algorithm has been applied to a matrix of (32 x 32) ionization chambers. After the calibration coefficients have been applied, by comparing the response of the matrix of chambers to a reference detector over a large field, we determined that the fluence measurement of individual chambers is better than 0.7%. The algorithm solves the cumbersome problem of the relative gain calibration of a matrix of a large number of sensors.

D-IMRT verification with a 2D pixel ionization chamber: dosimetric and clinical results in head and neck cancer.

Dynamic intensity-modulated radiotherapy (D-IMRT) using the sliding-window technique is currently applied for selected treatments of head and neck cancer at Institute for Cancer Research and Treatment of Candiolo (Turin, Italy). In the present work, a PiXel-segmented ionization Chamber (PXC) has been used for the verification of 19 fields used for four different head and neck cancers. The device consists of a 32x32 matrix of 1024 parallel-plate ionization chambers arranged in a square of 24x24 cm2 area. Each chamber has 0.4 cm diameter and 0.55 cm height; a distance of 0.75 cm separates the centre of adjacent chambers. The sensitive volume of each single ionization chamber is 0.07 cm3. Each of the 1024 independent ionization chambers is read out with a custom microelectronics chip.The output factors in water obtained with the PXC at a depth of 10 cm were compared to other detectors and the maximum difference was 1.9% for field sizes down to 3x3 cm2. Beam profiles for different field dimensions were measured with the PXC and two other types of ionization chambers; the maximum distance to agreement (DTA) in the 20-80% penumbra region of a 3x3 cm2 field was 0.09 cm. The leaf speed of the multileaf collimator was varied between 0.07 and 2 cm s-1 and the detector response was constant to better than 0.6%. The behaviour of the PXC was measured while varying the dose rate between 0.21 and 1.21 Gy min-1; the mean difference was 0.50% and the maximum difference was 0.96%. Using fields obtained with an enhanced dynamic wedge and a staircase-like (step) IMRT field, the PXC has been tested for simple 1D modulated beams; comparison with film gave a maximum DTA of 0.12 cm. The PXC was then used to check four different IMRT plans for head and neck cancer treatment: cervical chordoma, parotid, ethmoid and skull base. In the comparison of the PXC versus film and PXC versus treatment planning system, the number of pixels with gamma parameter

Two-dimensional and quasi-three-dimensional dosimetry of hadron and photon beams with the Magic Cube and the Pixel Ionization Chamber.

Two detectors for fast two-dimensional (2D) and quasi-three-dimensional (quasi-3D) verification of the dose delivered by radiotherapy beams have been developed at University and Istituto Nazionale di Fisica Nucleare (INFN) of Torino. The Magic Cube is a stack of strip-segmented ionization chambers interleaved with water-equivalent slabs. The parallel plate ionization chambers have a sensitive area of 24 x 24 cm2, and consist of 0.375 cm wide and 24 cm long strips. There are a total of 64 strips per chamber. The Magic Cube has been tested with the clinical proton beam at Loma Linda University Medical Centre (LLUMC), and was shown to be capable of fast and precise quasi-3D dose verification. The Pixel Ionization Chamber (PXC) is a detector with pixel anode segmentation. It is a 32 x 32 matrix of 1024 cylindrical ionization cells arranged in a square 24 x 24 cm2 area. Each cell has 0.4 cm diameter and 0.55 cm height, at a pitch of 0.75 cm separates the centre of adjacent cells. The sensitive volume of each single ionization cell is 0.07 cm3. The detectors are read out using custom designed front-end microelectronics and a personal computer-based data acquisition system. The PXC has been used to verify dynamic intensity-modulated radiotherapy for head-and-neck and breast cancers.

Dosimetric characterization of a large area pixel-segmented ionization chamber.

A pixel-segmented ionization chamber has been designed and built by Torino University and INFN. The detector features a 24 x 24 cm2 active area divided in 1024 independent cylindrical ionization chambers and can be read out in 500 micros without introducing dead time; the digital charge quantum can be adjusted between 100 fC and 800 fC. The sensitive volume of each single ionization chamber is 0.07 cm3. The purpose of the detector is to ease the two-dimensional (2D) verifications of fields with complex shapes and large gradients. The detector was characterized in a PMMA phantom using 60Co and 6 MV x-ray photon beams. It has shown good signal linearity with respect to dose and dose rate to water. The average sensitivity of a single ionization chamber was 2.1 nC/Gy, constant within 0.5% over one month of daily measurements. Charge collection efficiency was 0.985 at the operating polarization voltage of 400 V and 3.5 Gy/min dose rate. Tissue maximum ratio and output factor have been compared with a Farmer ionization chamber and were found in good agreement. The dose profiles have been compared with the ones obtained with an ionization chamber in water phantom for the field sizes supplied by a 3D-Line dynamic multileaf collimator. These results show that this detector can be used for 2D dosimetry of x-ray photon beams, supplying a good spatial resolution and sensibly reducing the time spent in dosimetric verification of complex radiation fields.