Range verification in heavy-ion therapy using a hadron tumour marker.

Objective.A new method to estimate the range of an ion beam in a patient during heavy-ion therapy was investigated, which was previously verified for application in proton therapy.Approach.The method consists of placing a hadron tumour marker (HTM) close to the tumour. As the treatment beam impinges on the HTM, the marker undergoes nuclear reactions. When the HTM material is carefully chosen, the activation results in the emission of several delayed, characteristicγrays, whose intensities are correlated with the remaining range inside the patient. When not just one but two reaction channels are investigated, the ratio between these twoγray emissions can be measured, and the ratio is independent of any beam delivery uncertainties.Main results.A proof-of-principle experiment with an16O ion beam and Ag foils as HTM was successfully executed. The107Ag(16O,x)112Sb and the107Ag(16O,x)114Sb reaction channels were identified as suitable for the HTM technique. When only oneγ-ray emission is measured, the resulting range-uncertainty estimation is at the 0.5 mm scale. When both channels are considered, a theoretical limit on the range uncertainty of a clinical fiducal marker was found to be ±290µm.Significance.Range uncertainty of a heavy-ion beam limits the prescribed treatment plan for cancer patients, especially the direction of the ion beam in relation to any organ at risk. An easy to implement range-verification technique which can be utilized during clinical treatment would allow treatment plans to take full advantage of the sharp fall-off of the Bragg peak without the risk of depositing excessive dose into healthy tissue.

Improved sub-milimeter range-verification method for proton therapy using a composite hadron tumour marker (HTM).

Objective.The results of a follow-up experiment investigating a novel method for sub-milimetre range verification (RV) in proton therapy (PT) are presented.Approach.The method consists of implanting a hadron tumour marker (HTM) near the planned treatment volume, and measuring theγ-ray signals emitted as a result of activation by the proton beam. These signals are highly correlated with the energy of the beam impinging on the HTM and can provide an absolute measurement of the range of the beam relative to the position of the HTM, which is independent of any uncertainties in beam delivery.Main results.Three candidate HTM materials were identified and combined into a single composite HTM, which makes use of the strongest reaction in each material. The setup of the previous experiment was improved on by using high-purity germanium detectors to measure theγ-ray signal with a higher resolution than was previously achieved. A PMMA phantom was also used to simulate theγ-ray background from tissue activation. HTM RV using the data collected in this study yielded range measurements whose average deviation from the expected value was 0.13(22)mm.Significance.Range uncertainty in PT limits the prescribed treatment plan for cancer patients with large safety margins and constrains the direction of the proton beam in relation to any organ at risk. The sub-milimetre range uncertainty achieved in this study using HTM RV, if implemented clinically, would allow for a reduction in the size of safety margins, increasing the therapeutic window for PT.

Proton therapy range verification method via delayed γ-ray spectroscopy of a molybdenum tumour marker.

In this work, a new method of range verification for proton therapy (PT) is experimentally demonstrated for the first time. If a metal marker is implanted near the tumour site, its response to proton activation will result in the emission of characteristic γ rays. The relative intensity of γ rays originating from competing fusion-evaporation reaction channels provides a unique signature of the average proton energy at the marker, and by extension the beam's range, in vivo and in real time. The clinical feasibility of this method was investigated at the PT facility at TRIUMF with a proof-of-principle experiment which irradiated a naturally-abundant molybdenum foil at various proton beam energies. Delayed characteristic γ rays were measured with two Compton-shielded LaBr3 scintillators. The technique was successfully demonstrated by relating the relative intensity of two γ-ray peaks to the energy of the beam at the Mo target, opening the door to future clinical applications where the range of the beam can be verified in real time.

GEANT4 simulation of a range verification method using delayed γ spectroscopy of a 92Mo marker.

In this work, we propose a novel technique for in-vivo proton therapy range verification. This technique makes use of a molybdenum hadron tumour marker, implanted at a short distance from the clinical treatment volume. Signals emitted from the marker during treatment can provide a direct measurement of the proton beam energy at the marker's position. Fusion-evaporation reactions between the proton beam and marker nucleus result in the emission of delayed characteristic γ rays, which are detected off-beam for an improved signal-to-noise ratio. In order to determine the viability of this technique and to establish an experimental setup for future work, the Monte Carlo package GEANT4 was used in combination with ROOT to simulate a treatment scenario with the new method outlined in this work. These simulations show that the intensity of delayed γ rays produced from competing reactions yields a precise measurement of the range of the proton beam relative to the marker, with sub-millimetre uncertainty.

Follow-up monoclonal gammopathy of undetermined significance in kidney transplant.

OBJECTIVE: The aim of this work was to review the incidence of monoclonal gammopathy of undetermined significance (MGUS) and complications in kidney transplant (KT) patients at the Puerta del Mar Hospital in Cádiz, Spain. This diagnosis was not considered to be a contraindication for transplantation. METHODS: To estimate the incidence of MGUS in KT patients we used the database of our hospital, which included 1,016 patients who received a KT from 1992 to 2012 with a median follow-up of 30 months. The incidence of MGUS in non-transplant patients was estimated from the literature. RESULTS: Out of 1,016 KT patients, 16 developed MGUS; 10 (72.5%) were >50 years old. Two patients developed post-transplantation lymphoproliferative disorders. No cases of progression to multiple myeloma or amyloidosis were seen during immune suppression therapy or after. CONCLUSIONS: MGUS was >100 times more frequent in KT recipients than in the general population (P < .05). But in contrast to MGUS in general population, progression to plasma cell dyscrasia in these patients was absent and its incidence is unknown in KT patients.

A subnanosecond pulsed ion source for micrometer focused ion beams.

A new, compact design of an ion source delivers nanosecond pulsed ion beams with low emittance, which can be focused to micrometer size. By using a high-power, 25 fs laser pulse focused into a gas region of 10(-6) mbar, ions at very low temperatures are produced in the small laser focal volume of 5 mum diameter by 20 mum length through multiphoton ionization. These ions are created in a cold environment, not in a hot plasma, and, since the ionization process itself does not significantly heat them, have as a result essentially room temperature. The generated ion pulse, up to several thousand ions per pulse, is extracted from the source volume with ion optical elements that have been carefully designed by simulation calculations. Externally triggered, its subnanosecond duration and even smaller time jitter allow it to be superimposed with other pulsed particle or laser beams. It therefore can be combined with any type of collision experiment where the size and the time structure of the projectile beam crucially affect the achievable experimental resolution.

X-ray microprobe of orbital alignment in strong-field ionized atoms.

We have developed a synchrotron-based, time-resolved x-ray microprobe to investigate optical strong-field processes at intermediate intensities (10(14) - 10(15) W/cm2). This quantum-state specific probe has enabled the direct observation of orbital alignment in the residual ion produced by strong-field ionization of krypton atoms via resonant, polarized x-ray absorption. We found strong alignment to persist for a period long compared to the spin-orbit coupling time scale (6.2 fs). The observed degree of alignment can be explained by models that incorporate spin-orbit coupling. The methodology is applicable to a wide range of problems.

Triple coincidence (e,gamma2e) experiment for simultaneous electron impact ionization excitation of helium.

Simultaneous ionization and excitation of helium atoms by 500 eV electron impact is observed by a triple coincidence of an ionized slow electron, the recoiling He+ ion, and the radiated vacuum ultraviolet photon (lambda< or =30.4 nm). Kinematically complete differential cross sections are presented for the He+(2p)2P final ionic state, demonstrating the feasibility of a quantum mechanically complete experiment. The experimental data are compared to predictions from state-of-the-art numerical calculations. For large momentum transfers, a first-order treatment of the projectile-target interaction can reproduce the experimental angular dependence, but a second-order treatment is required to obtain consistent magnitudes.

Electron impact ionization in the presence of a laser field: a kinematically complete (ngammae,2e) experiment.

Single ionization of He by 1 keV electron impact in the presence of an intense (I=4 x 10(12) W/cm(2)) laser field (lambda=1064 nm) has been explored in a kinematically complete experiment using a reaction microscope. Distinct differences in the singly to fully differential cross sections compared to the field-free situation are observed which cannot be explained by a first-order quantum calculation. Major features, such as the number of photons exchanged and the modification of the energy spectrum of emitted electrons, can be understood qualitatively within a simple classical model.

Breakup of H2 in singly ionizing collisions with fast protons: channel-selective low-energy electron spectra.

Dissociative as well as nondissociative single ionization of H2 by 6 MeV proton impact has been studied in a kinematically complete experiment by measuring the momentum vectors of the electron and the H+ fragment or the H+2 target ion, respectively. For the two ionization pathways, the electron spectra reveal the role of autoionization of the doubly and singly excited states of H2. The latter explicitly involve the coupling between the electronic and the nuclear motion of the molecule. This is a clear manifestation of a breakdown of the Born-Oppenheimer approximation.

Projectile-charge sign dependence of four-particle dynamics in helium double ionization.

Double ionization of helium by 6 MeV proton impact has been explored in a kinematically complete experiment using a "reaction microscope." For the first time, fully differential cross sections for positively charged projectiles have been obtained and compared with data from 2 keV electron impact. The significant differences observed in the angular distribution of the ejected electrons are attributed to the charge sign of the projectile, resulting in different dynamics of the four-particle Coulomb system, which is not considered in the first Born approximation.

Coincident fragment detection in strong field photoionization and dissociation of H2.

Electron-ion momentum spectroscopy is used to investigate the correlated electronic and nuclear motion in fragmentation of H2 in 4 x 10(14) W/cm(2), 25 fs laser pulses at 795 nm. Reaction channel dependent photoelectron spectra indicate that besides the main, stepwise H2 ionization H2(+) dissociation mechanism resulting in the products H(1s) + H(+) + e(-) a second new mechanism has to be assumed. The momentum distribution of H(+) ions in the dissociation channels H(1s) + H(+) + e(-) and 2H(+) + 2e(-) is found to be independent of the kinetic energy of the photoelectrons.

Separation of recollision mechanisms in nonsequential strong field double ionization of Ar: the role of excitation tunneling.

Vector momentum distributions of two electrons created in double ionization of Ar by 25 fs, 0.25 PW/cm(2) laser pulses at 795 nm have been measured using a "reaction microscope." At this intensity, where nonsequential ionization dominates, distinct correlation patterns are observed in the two-electron momentum distributions. A kinematical analysis of these spectra within the classical "recollision model" revealed an (e,2e)-like process and excitation with subsequent tunneling of the second electron as two different ionization mechanisms. This allows a qualitative separation of the two mechanisms demonstrating that excitation-tunneling is the dominant contribution to the total double ionization yield.

Double ionization of helium by electron-impact: complete pictures of the four-body breakup dynamics.

The dynamics of He double ionization by 2 keV electron impact is studied experimentally for a momentum transfer of 0.6 a.u. at excess energies of 10 and 40 eV. Complete sets of fivefold differential cross sections are presented for all electron emission angles in coplanar geometry. Contributions beyond the first Born approximation are identified comparing experimental data with first order convergent close-coupling calculations which are in considerably better agreement with the present experiment than with the earlier measurement of Kheifets et al. [J. Phys. B 32, 5047 (1999)].

Non-sequential double ionization of Ne in intense laser pulses: a coincidence experiment.

The dynamics of Neon double ionization by 25 fs, 1.0 PW/cm 2 laser pulses at 795 nm has been studied in a many particle coincidence experiment. The momentum vectors of all ejected atomic fragments (electrons and ions) have been measured using combined electron and recoil-ion momentum spectroscopy. Electron emission spectra for double and single ionization will be discussed. In both processes the mean electron energies differ considerably and high energetic electrons with energies of more than 120 eV have been observed for double ionization. The experimental results are in qualitative agreement with the rescattering model.