Scan path optimization with/without clustering for active beam delivery in charged particle therapy

PurposeTo compare different algorithms to optimize the scanning path in charged particle therapy with quasidiscrete scanning. We implemented a Hybrid Genetic Algorithm with Heuristics (HyGA) and combined it with clustering techniques. The performance was compared to Simulated Annealing (SA) and to commercially available treatment planning system (TPS).MethodsPerformance and clinical implications were assessed using data from 10 patients treated at CNAO (Centro Nazionale di Adroterapia Oncologica). Clinical treatments are performed relying on beam deflection, avoiding irradiation for transitions between adjacent spots larger than 2 cm. A clustering method was implemented with HyGA (HyGA_Cl), which assumes beam deflection during transition between clusters. Clinical performance was determined as the total number of particles delivered during spot transitions and the number of particles wasted due to beam deflection. Results were compared to scan paths obtained with CNAO TPS.ResultsSA and HyGA produced on average shorter paths compared to the currently available TPS. This did not result in a reduction of transit particles, due to the concomitant effect of beam deflection out of the extraction line. HyGA_Cl achieved 2% average reduction in transit particles when compared to CNAO TPS. As a drawback, wasted particles increased, due to more frequent use of beam deflection. Both the SA and HyGA algorithms reduced the number of wasted particles.ConclusionSA and HyGA proved to be the most cost-effective methods in reducing wasted particles, with benefits in terms of shorter scan paths. A decrease in transit particles delivered with beam deflection can be achieved using HyGA_Cl.     

Noninvasive diagnosis of a single cell with a probe beam

It is important to distinguish a living/dead cell in cell culture, especially in the regenerate medicine field including cell therapy, since those cells are usually in short supply and consequently the ex vivo culture process should be operated strictly. Conventional methods for distinguishing a living from a dead cell usually require labeling with a dye, which spoils the culture of the cell. Here we show a simple noninvasive method for diagnosing a dead or alive cell with a probe beam. If a cell is alive, the active transport of materials across the cell membrane causes a change of concentration gradients, and this change further induces a change of deflection of a probe beam passing through a vicinity of the cell membrane. If a cell is dead, no or little change in deflection of the probe beam is induced because no or little active materials movement across the cell membrane exists. The deflection of the probe beam is monitored, and judgment on whether a cell is dead or alive from the deflection signal agreed with the conventional decision.     

Application of Near-Infrared Spectroscopy in Real-Time Monitoring of Product Attributes of Ribbed Roller Compacted Flakes

This study assessed the utility of near-infrared (NIR) spectroscopy for the real-time monitoring of content uniformity and critical quality attributes (tensile strength, Young’s modulus, and relative density) of ribbed roller compacted flakes made by axially corrugated or ribbed rolls. A custom-built setup was used to capture off-line NIR spectra from the flakes containing micronized chlorpheniramine maleate, microcrystalline cellulose, lactose, and magnesium stearate. The partial least square regression method was employed to build calibration models from these off-line NIR spectra using experimental design and validated using test set validation. During calibration model development, various factors, such as spectral acquisition mode, probe positioning, spectral preprocessing method, and beam size, were investigated to improve the prediction ability of the models. The statistical results obtained for calibration models and their validation revealed that dynamic spectral acquisition and proper probe positioning were very crucial to minimize the incorporation of variability in NIR spectra resulting from the flake’s undulation. Calibration and validation statistics also suggested the importance of selecting appropriate spectral preprocessing method and beam size. In this study, best calibration models resulted from standard normal variate followed by first derivative preprocessed dynamic spectra captured using beam size ~1.2 mm. Best calibration models constructed from off-line NIR spectra were used in real-time analysis of flake attributes. Finally, adequacy of best calibration models was established from real-time prediction results. Overall, with the proposed setup, it was possible to monitor the roller compaction process in real time for various properties associated with the ribbed flakes in a rapid, efficient, and nondestructive manner.     

Photothermal beam deflection: a new method for in vivo measurements of thermal energy dissipation and photochemical energy conversion in intact leaves

A novel photosynthetic technique, photothermal deflection spectroscopy, is presented which is based on the mirage effect and allows the rapid measurement of thermal deactivation of excited pigments in leaf samples placed in an open cell. Modulated heat emission from leaves illuminated with intensity-modulated light was measured via the detection of the periodic deflection of a laser beam parallel to the sample surface. Photothermal deflection signals can be monitored in vivo in leaves placed in various, liquid or gaseous, environments with a satisfactory signal-to-noise ratio close to 60–80 (in distilled water) at low modulation frequencies (below 50 Hz). Using this new and simple photothermal method, it was possible to easily obtain useful information on the leaf photochemical activity and its light-saturation characteristics under normal or stress conditions, suggesting that in vivo deflection signals could be used for assaying the photosynthetic state of health of crop plants. The beam deflection method presented in this paper appears to be a potentially useful photosynthetic tool complementary to the related photoacoustic technique.Abbreviations DCMU dichlorophenyldimethylurea - PD photothermal deflection - PL photochemical energy storage - S/N ratio signal-to-noise ratio     

Beam Manipulating via an Array of Nanoslits Modified by Perpendicular Cuts and Bumps

We report the observation of focusing and deflection phenomena by employing a novel technique to perform phase front profile design in nanoslit-based planar plasmonic lenses and beam deflectors. Introducing perpendicular cuts and bumps to the perforated nanoslits on a thin metallic film is utilized to change the effective depth of the nanoslits which provide the possibility of manipulating the phase front profile based on the propagation property of the surface plasmon polaritons in the metal–insulator–metal waveguides. Using the dispersive finite-difference time-domain numerical method, simulations are conducted to explore the beam focusing and deflection phenomena, and the performance parameters of the lens and beam deflector include the focal length, full-width half-maximum, depth of focus, the efficiency of focusing, and the deflection angle. The whole structure is formed on a planar thin film which is convenient for miniaturization and high density integration besides that it can be fabricated by well-known techniques such as focused ion beam milling.     

Cantilever Arrays for Multiplexed Mechanical Analysis of Biomolecular Reactions

Microchips;ontaining arrays of cantilever beams have been used to mechanically detect and quantitatively analyze multiple reactions of DNA hybridization and antigen-antibody binding simultaneously. The reaction-induced deflection of a cantilever beam reflects the interplay between strain energy increase of the beam and the free energy reduction of a reaction, providing an ideal tool for investigating the connection between mechanics and chemistry of biomolecular reactions. Since free energy reduction is common for all reactions, the cantilever array forms a universal platform for label-free detection of various specific biomolecular reactions. A few such reactions and their implications in biology and biotechnology are discussed.     

Simulation of electron-beam irradiation of skin tissue model

Monte Carlo simulation of electrons stopping in liquid water was used to model the penetration and quality of electron-beam irradiation incident on the full-thickness EpiDerm? skin model (EpiDermFT? MatTek, Ashland, VA). This 3D tissue model has a fully developed basement membrane separating an epidermal layer of keratinocytes in various stages of differentiation from a dermal layer of fibroblasts embedded in collagen. The simulations were motivated by a desire to selectively expose the epidermal layer to low-linear energy transfer (LET) radiation in the presence of a nonirradiated dermal layer. The variable-energy electron microbeam at the Pacific Northwest National Laboratory (PNNL) was used as a model of device characteristics and irradiation geometry. At the highest beam energy available (90 keV), we estimate that no more than a few percent of the beam energy will be deposited in the dermal layer. Energy deposition spectra were calculated for 10-μm-thick layers near the 10th, 50th and 90th percentiles of penetration by the 90 keV electron beam. Bimodal spectra showed an increasing component of "stoppers" with increasing depth, which increases the probability of large energy deposition events. Nevertheless, screening by tissue above the layer of interest is the main factor determining energy deposited at a given depth.     

An application of beam theory to determine the stress and deformation of long bones

We present a generalized beam theory in which deformation and load are determined simultaneously, in order to analyze statically indeterminant problems involving long bones. We regard a long bone as a beam curved in three dimensions for which the cross-sectional properties vary continuously along its length. The theory is used to determine the force, moment, deflection and twist along the fifth metatarsal when it is subjected to both a pointwise and a distributed load.     

Beam quality and dose perturbation of 6 MV flattening-filter-free linac

The aim of this study is twofold: (a) determination of the spectral differences for flattening-filter-free (FFF) versus standard (STD) linac under various clinical conditions, (b) based on an extensive list of clinically important beam configurations, identification of clinical scenarios that lead to higher macroscopic dose perturbations due to the presence of high-Z material. The focus is on dose enhancement due to contrast agents including high-Z elements such as gold or gadolinium.EGSnrc was used to simulate clinical beams under various irradiation conditions: open/IMRT/spit-IMRT fields, in/out-off-field areas, different depths and field sizes. Spectra were calculated and analyzed for about 80 beams and for a total of 480 regions. Quantitative differential effects in beam quality were characterized using energy-dependent and cumulative dose perturbation metrics.Analysis of the spectral database showed that even though the general trends for both linacs (FFF/STD) were the same, there were crucial differences. In general, the relative changes between different conditions were smaller for FFF spectra. This was because of the higher component of low-energy photons of the FFF linac, which already lead to higher dose enhancement than for the STD linac (photon energies were more “uniformly” distributed for FFF spectra and henceforth their perturbation resulted in lesser relative changes). For out-of-field FFF spectra and split-IMRT fields the strongest enhancement were observed (∼25 and ∼5 respectively). Different spectral scenarios lead to different dose enhancements, however, they scale with the higher effective-Z of the materials and were directly related to the lower range of the spectra (<200 keV).     

Thermal and resonance neutrons generated by various electron and X-ray therapeutic beams from medical linacs installed in polish oncological centers

BackgroundHigh-energy photon and electron therapeutic beams generated in medical linear accelerators can cause the electronuclear and photonuclear reactions in which neutrons with a broad energy spectrum are produced. A low-energy component of this neutron radiation induces simple capture reactions from which various radioisotopes originate and in which the radioactivity of a linac head and various objects in the treatment room appear.AimThe aim of this paper is to present the results of the thermal/resonance neutron fluence measurements during therapeutic beam emission and exemplary spectra of gamma radiation emitted by medical linac components activated in neutron reactions for four X-ray beams and for four electron beams generated by various manufacturers’ accelerators installed in typical concrete bunkers in Polish oncological centers.Materials and methodsThe measurements of neutron fluence were performed with the use of the induced activity method, whereas the spectra of gamma radiation from decays of the resulting radioisotopes were measured by means of a portable high-purity germanium detector set for field spectroscopy.ResultsThe fluence of thermal neutrons as well as resonance neutrons connected with the emission of a 20 MV X-ray beam is ～10⁶ neutrons/cm² per 1 Gy of a dose in water at a reference depth. It is about one order of magnitude greater than that for the 15 MV X-ray beams and about two orders of magnitude greater than for the 18–22 MeV electron beams regardless of the type of an accelerator.ConclusionThe thermal as well as resonance neutron fluence depends strongly on the type and the nominal potential of a therapeutic beam. It is greater for X-ray beams than for electrons. The accelerator accessories and other large objects should not be stored in a treatment room during high-energy therapeutic beam emission to avoid their activation caused by thermal and resonance neutrons. Half-lives of the radioisotopes originating from the simple capture reaction (n,γ) (from minutes to hours) are long enough to accumulate radioactivity of components of the accelerator head. The radiation emitted by induced radioisotopes causes the additional doses to staff operating the accelerators.     

Energy distribution of runaway electrons generated by a nanosecond discharge in atmospheric-pressure air

The spectra of an ultrashort avalanche electron beam generated by a nanosecond discharge in atmospheric-pressure air were investigated. The temporal characteristics of the beam current pulses, gap voltage, and discharge current in a gas diode were measured with a time resolution of ～0.1 ns. A simple technique was developed for recovering electron spectra from the curves of beam attenuation by aluminum foils. The effect of the cathode design, electrode gap length, and generator parameters on the electron spectra were studied using seven setups. It is shown that generation of electrons with anomalously high energies requires the use of cathodes with increased curvature radius.     

Evaluation of energy deposition and secondary particle production in proton therapy of brain using a slab head phantom

AimEvaluation of energy deposition of protons in human brain and calculation of the secondary neutrons and photons produced by protons in proton therapy.BackgroundRadiation therapy is one of the main methods of treating localized cancer tumors. The use of high energy proton beam in radiotherapy was proposed almost 60 years ago. In recent years, there has been a revival of interest in this subject in the context of radiation therapy. High energy protons suffer little angular deflection and have a well-defined penetration range, with a sharp increase in the energy loss at the end of their trajectories, namely the Bragg peak.Materials and methodsA slab head phantom was used for the purpose of simulating proton therapy in brain tissue. In this study simulation was carried out using the Monte Carlo MCNPX code.ResultsBy using mono energetic proton pencil beams, energy depositions in tissues, especially inside the brain, as well as estimating the neutron and photon production as a result of proton interactions in the body, together with their energy spectra, were calculated or obtained. The amount of energy escaped from the head by secondary neutrons and photons was determined.ConclusionsIt was found that for high energy proton beams the amount of escaped energy by neutrons is almost 10 times larger than that by photons. We estimated that at 110 MeV beam energy, the overall proton energy “leaked” from the head by secondary photons and neutrons to be around 1%.     

In vivo measurement of spectroscopic and photochemical properties of intact leaves using the ‘mirage effect’

This paper describes a new, highly sensitive, method for in vivo studies of photosynthesis based on the ‘mirage effect’ in which thermal energy dissipation from intact leaves, illuminated with intensity-modulated light, is sensed through the periodic deflection of a laser beam propagating along the leaf surface. The photothermal deflection technique allows one to rapidly estimate the gross efficiency of photochemical energy storage by comparing the heat emission signal with and without an additional strong, photosynthetically saturating, non-modulated light. In pea leaves, the maximal storage efficiency at low light intensities was shown to approach 55%. The general utility of this simple photothermal method is illustrated by examining the variation of the deflection signal under different conditions. The spectral resolution of this new method is shown to be much higher than that of the photoacoustic method.     

Energetics and kinetics of photosynthetic water oxidation studied by photothermal beam deflection (PBD) experiments

Photosynthesis Research - Determination of thermodynamic parameters of water oxidation at the photosystem II (PSII) manganese complex is a major challenge. Photothermal beam deflection (PBD)...     

Dynamics of the primary cilium in shear flow

In this work, the equilibrium shape and dynamics of a primary cilium under flow are investigated by using both theoretical modeling and experiment. The cilium is modeled as an elastic beam that may undergo large deflection due to the hydrodynamic load. Equilibrium results show that the anchoring effects of the basal body on the cilium axoneme behave as a nonlinear rotational spring. Details of the rotational spring are elucidated by coupling the elastic beam with an elastic shell. We further study the dynamics of cilium under shear flow with the cilium base angle determined from the nonlinear rotational spring, and obtain good agreement in cilium bending and relaxing dynamics when comparing between modeling and experimental results. These results potentially shed light on the physics underlying the mechanosensitive ion channel transport through the ciliary membrane.     

In Vitro Validation of an Artefact Suppression Algorithm in X-Ray Phase-Contrast Computed Tomography

X-ray phase-contrast tomography can significantly increase the contrast-resolution of conventional attenuation-contrast imaging, especially for soft-tissue structures that have very similar attenuation. Just as in attenuation-based tomography, phase contrast tomography requires a linear dependence of aggregate beam direction on the incremental direction alteration caused by individual voxels along the path of the X-ray beam. Dense objects such as calcifications in biological specimens violate this condition. There are extensive beam deflection artefacts in the vicinity of such structures because they result in large distortion of wave front due to the large difference of refractive index; for such large changes in beam direction, the transmittance of the silicon analyzer crystal saturates and is no longer linearly dependent on the angle of refraction. This paper describes a method by which these effects can be overcome and excellent soft-tissue contrast of phase tomography can be preserved in the vicinity of such artefact-producing structures.     

Proportional counter dosimetry and microdosimetry for radiotherapy with multiple pion beams

At the Swiss Institute for Nuclear Research (SIN) cancer patients are irradiated with negatively charged pi mesons using a 60-beam medical pion generator, the Piotron. A low-pressure tissue-equivalent proportional counter was used to measure absorbed dose and microdosimetric spectra. A method was developed to allow discrimination of events from different beam components, i.e., beam contamination (electrons and muons), pions in flight, and stopping pions. Measurements were performed along the axis and at lateral distances off one of these identical pion beams. The marked changes of total microdosimetric spectra with depth in phantom detected in earlier measurements are mainly due to large variations in the dose contributions of the beam components and much less to changes in the shapes of the individual microdosimetric spectra. The single beam measurements were used to calculate three-dimensional distributions of absorbed dose and of dose mean lineal energy, yD, for dynamic patient irradiations. Within the whole target volume yD remains nearly constant when irradiated with all 60 beams, whereas considerable changes were found for irradiations with 31 beams coming from a semicircle. Both size and shape of target volumes influence yD, the maximum values ranging from 30 to 45 keV/micron.     

Measurement and validation of benchmark-quality thick-target tungsten X-ray spectra below 150 kVp

Pulse-height distributions of two constant potential X-ray tubes with fixed anode tungsten targets were measured and unfolded. The measurements employed quantitative alignment of the beam, the use of two different semiconductor detectors (high-purity germanium and cadmium-zinc-telluride), two different ion chamber systems with beam-specific calibration factors, and various filter and tube potential combinations. Monte Carlo response matrices were generated for each detector for unfolding the pulse-height distributions into spectra incident on the detectors. These response matrices were validated for the low error bars assigned to the data. A significant aspect of the validation of spectra, and a detailed characterization of the X-ray tubes, involved measuring filtered and unfiltered beams at multiple tube potentials (30-150 kVp). Full corrections to ion chamber readings were employed to convert normalized fluence spectra into absolute fluence spectra. The characterization of fixed anode pitting and its dominance over exit window plating and/or detector dead layer was determined. An Appendix of tabulated benchmark spectra with assigned error ranges was developed for future reference.     

Submillisecond Conformational Changes in Proteins Resolved by Photothermal Beam Deflection

Photothermal beam deflection together with photo-acoustic calorimetry and thermal grating belongs to the family of photothermal methods that monitor the time-profile volume and enthalpy changes of light induced conformational changes in proteins on microsecond to millisecond time-scales that are not accessible using traditional stop-flow instruments. In addition, since overall changes in volume and/or enthalpy are probed, these techniques can be applied to proteins and other biomacromolecules that lack a fluorophore and or a chromophore label. To monitor dynamics and energetics of structural changes associated with Ca²⁺ binding to calcium transducers, such neuronal calcium sensors, a caged calcium compound, DM-nitrophen, is employed to photo-trigger a fast (τ < 20 μsec) increase in free calcium concentration and the associated volume and enthalpy changes are probed using photothermal beam deflection technique.     

Coherent interaction of a relativistic electron beam with a plasma

Results are presented from experimental studies of the interaction of a modulated relativistic electron beam with a plasma. The electron energy spectra at the exit from the interaction chamber are measured for electron beams with energies of about 50 and 20 MeV. The coherent interaction of an electron beam with a microwave-driven plasma is studied. It is shown that, in strong electric fields that can be generated in the coherent interaction, the beam current is very sensitive to the phase of the microwave field.