On the role of 4-hydroxynonenal in health and disease

AbstractPolyunsaturated fatty acids are susceptible to peroxidation and they yield various degradation products, including the main α,β-unsaturated hydroxyalkenal, 4-hydroxy-2,3-trans-nonenal (HNE) in oxidative stress. Due to its high reactivity, HNE interacts with various macromolecules of the cell, and this general toxicity clearly contributes to a wide variety of pathological conditions. In addition, growing evidence suggests a more specific function of HNE in electrophilic signaling as a second messenger of oxidative/electrophilic stress. It can induce antioxidant defense mechanisms to restrain its own production and to enhance the cellular protection against oxidative stress. Moreover, HNE-mediated signaling can largely influence the fate of the cell through modulating major cellular processes, such as autophagy, proliferation and apoptosis. This review focuses on the molecular mechanisms underlying the signaling and regulatory functions of HNE. The role of HNE in the pathophysiology of cancer, cardiovascular and neurodegenerative diseases is also discussed

Design of a solid-state array detector prototype for small-field dosimetry in megavoltage photon beams

Recent developments in imaging techniques, medical linear accelerator (linac) design and treatment modalities in megavoltage photon-beam radiotherapy have been aimed at optimizing the delivery of highly conformal dose distributions, leading to an escalation in the use of small radiation fields. Modern radiotherapy delivered with small fields has more stringent requirements, in terms of quality assurance (QA), than conventional radiotherapy with broad fields. Additionally, accurate dosimetry, paramount for the safe and efficient use of radiation, becomes challenging in this context. Accidents, near misses and discrepancies between the results of different investigators confirm that dosimetry in small fields is complex. The factors contributing to this are broadly summarized as an absorbed dose distribution characterized by a lack of charged particle equilibrium (CPE) over most of the treatment target, partial source occlusion by the collimation system of the linac, and a measurement of absorbed dose which is highly dependent on radiation detector design and the perturbations it introduces to particles fluence. Starting from the currently available knowledge on the physics of small radiation fields, the aim of the research in the present dissertation was the design and test of a novel radiation detector prototype with the potential to address the shortcomings of currently available dosimeters

On monolithic silicon array detectors for small-field photon beam dosimetry

Contemporary x-ray radiotherapy employs small radiation fields to deliver highly conformal dose distributions. Submillimeter accuracy in the measurement of the delivered dose map is a crucial requirement of detectors proposed for quality assurance applications. 2D monolithic silicon array detectors can provide high spatial-resolution by optimizing small sensitive volumes (SVs) in a large active area. They offer a stable and near energy-independent response in megavoltage photon beams, good dose linearity and real-time read-out. The SVs are ion-implanted on a silicon wafer whose geometry and physical characteristics, such as resistivity and defects concentration, dramatically affect the detector performance. The Octa is a novel 2D monolithic silicon array detector dedicated to small-field dosimetry. Its 512 diode-SVs are arranged with a sub-millimeter pitch along 4 intersecting orthogonal linear arrays. We report on the experimental and numerical characterization (performed with Sentaurus Workbench within the Synopsys framework) of two Octa detectors, manufactured respectively on a bulk and on an epitaxial silicon substrate. The effects of resistivity and defects concentration profiles across their large-area monolithic silicon wafers is compared and discussed in terms of the response linearity with dose, response uniformity, charge-collection efficiency and clinical performance in the case of a small radiation field delivered with a flattening filter free beam

Today\u27s monolithic silicon array detector for small field dosimetry: The Octa

The dosimetry of small photon beams is challenging due to detector position uncertainties, dose averaging and lack of electronic equilibrium. Currently only few, single detectors are suitable for measurements in this context, and none is ideal. This study reports on the dosimetric characterization of small fields collimated by fixed cones, performed by a novel 2D monolithic silicon array detector, the Octa

A novel high-resolution 2D silicon array detector for small field dosimetry with FFF photon beams

Purpose: Flattening filter free (FFF) beams are increasingly being considered for stereotactic radiotherapy (SRT). For the first time, the performance of a monolithic silicon array detector under 6 and 10 MV FFF beams was evaluated. The dosimeter, named Octa and designed by the Centre for Medical Radiation Physics (CMRP), was tested also under flattened beams for comparison. Methods: Output factors (OFs), percentage depth-dose (PDD), dose profiles (DPs) and dose per pulse (DPP) dependence were investigated. Results were benchmarked against commercially available detectors for small field dosimetry. Results: The dosimeter was shown to be a \u27correction-free\u27 silicon array detector for OFs and PDD measurements for all the beam qualities investigated. Measured OFs were accurate within 3% and PDD values within 2% compared against the benchmarks. Cross-plane, in-plane and diagonal DPs were measured simultaneously with high spatial resolution (0.3 mm) and real time read-out. A DPP dependence (24% at 0.021 mGy/pulse relative to 0.278 mGy/pulse) was found and could be easily corrected for in the case of machine specific quality assurance applications. Conclusions: Results were consistent with those for monolithic silicon array detectors designed by the CMRP and previously characterized under flattened beams only, supporting the robustn ess of this technology for relative dosimetry for a wide range of beam qualities and dose per pulses. In contrast to its predecessors, the design of the Octa offers an exhaustive high-resolution 2D dose map characterization, making it a unique real-time radiation detector for small field dosimetry for field sizes up to 3 cm side

The effect of an air gap on a 2D monolithic silicon detector for relative dosimetry

Purpose: To evaluate the impact of an air gap on the Magic Plate (MP512) response and optimize this gap for relative dosimetry in photon and electron beams. Materials and methods: MP512 is a 2D monolithic silicon detector manufactured on a p-Type substrate. The array consists of 512 pixels with 0.5 x 0.5 mm2 size and 2 mm pitch with an overall dimension of 52 x 52 mm2. The signal ratio (SR) as a function of beam size and the percentage were measured with MP512 in 6 MV and 10 MV photon beams. The enhanced dynamic wedge (EDW) beam profile measurements were performed for 6 MV photon beams. In this work the signal ratio is defined as the ratio of central axis MP512 reading for field sizes ranging from 0.5 x 0.5 cm2 to 10 x 10 cm2 and for the reference square field of side 10 cm at a depth of 10 cm in solid water phantom. The measurements were performed with an air gap immediately above the detector array of 0.5, 1.0, 1.2, 2.0 and 2.6 mm, respectively. The PDD was measured for field sizes 2x 2 cm2, 5x 5 cm2 and 10x 10 cm2 by scanning the MP512 from the depth of 0.5 cm to 10 cm. The beam profiles were measured for Varian linac enhanced dynamic wedge (EDW) angles of 15, 45 and 60 for field size 5x 5 cm2. The PDD for 6, 12 and 20 MeV electron beams were performed for a standard applicator providing 10x 10 cm2 field size. Results: The signal ratio measured with MP512 reduces with increasing air gap above the detector. The strongest effect of the air gap size was observed for small fields of 0.5x 0.5 cm2 and 1x 1 cm2 while the effect was negligible within ± 2% (1 standard deviation) for field sizes larger than 4x 4 cm2. The signal ratio measured with MP512 with air gaps of 0.5 mm and 1.2 mm showed a good agreement with signal ratio measured with the EBT3 film (within ± 2%) and MOSkinTM for 6 MV and 10 MV, respectively. Similar results were observed for the PDD measurement for field size 5x 5 cm2 and 10x 10 cm2. The PDD measured with M512 was in good agreement with Markus Ionization chamber (IC) within ± 1.6% (1 standard deviation) for 6 MV and ± 1.5% (1 standard deviation) for 10 MV. The PDD discrepancy for 2x 2 cm2 was within ± 3% of the EBT3 for both photon energies. The EDW dose profile matched well with the EBT3 for the air gap of 0.5 mm within ± 2% (1 standard deviation) for all wedge angles. The PDD measured by electron beams demonstrated no significant effect of the air gap size above MP512 for all energies. The results showed similar variations (within ± 3%) compared to Markus IC for both 0.5 mm and 2.6 mm gap. Conclusion: The MP512 diode array was demonstrated to be suitable as an in-phantom dosimeter for QA in small radiation treatment fields. The study shows that air gap size has a significant effect on small field photon beam dosimetry due to a loss of electronic equilibrium. The small air gaps of 0.5 mm and 1.2 mm were the best air gaps for 6 MV and 10 MV, respectively. The effect of the air gap in electron beam fields is not significant due to the fact that an electronic equilibrium is fully established