Search

We report on a target system supporting automated positioning of nano-targets with a precision resolution of in three dimensions. It relies on a confocal distance sensor and a microscope. The system has been commissioned to position nanometer targets with 1Â Hz repetition rate. Integrating our prototype into the table-top ATLAS 300 TW-laser system at the Laboratory for Extreme Photonics in Garching, we demonstrate the operation of a 0.5Â Hz laser-driven proton source with a shot-to-shot variation of the maximum energy about 27% for a level of confidence of 0.95. The reason of laser shooting experiments operated at 0.5Â Hz rather than 1Â Hz is because the synchronization between the nano-foil target positioning system and the laser trigger needs to improve.

The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens' principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a refinement of the ionoacoustic approach. With its capability of completely monitoring a single, focused proton bunch with prompt readout and high repetition rate, I-BEAT is a promising approach to meet future requirements of experiments and applications in the field of laser-based ion acceleration. We demonstrate its functionality at two laser-driven ion sources for quantitative online determination of the kinetic energy distribution in the focus of single proton bunches.

A common approach for spectrum determination of polyenergetic proton bunches from laser-ion acceleration experiments is based on the time-of-flight (TOF) method. However, spectra obtained using this method are typically given in relative units or are estimated based on some prior assumptions on the energy distribution of the accelerated ions. In this work, we present a new approach using the TOF method that allows for an absolute energy spectrum reconstruction from a current signal acquired with a sub-nanosecond fast and 10 µ m thin silicon detector. The reconstruction is based on solving a linear least-squares problem, taking into account the response function of the detection system. The general principle of signal generation and spectrum reconstruction by setting up an appropriate system response matrix is presented. Proof-of-principle experiments at a 12 MV Tandem accelerator using different nanosecond-short (quasi-)monoenergetic and polyenergetic proton bunches at energies up to 20 MeV were successfully performed. Within the experimental uncertainties of 2.4% and 12.1% for energy and particle number, respectively, reconstructed energy distributions were found in excellent agreement with the spectra calculated using Monte Carlo simulations and measured by a magnetic spectrometer. This TOF method can hence be used for absolute online spectrometry of laser-accelerated particle bunches.

Proton ranges in water between 145 MeV to 227 MeV initial energy have been measured at a clinical superconducting synchrocyclotron using the acoustic signal induced by the ion dose deposition (ionoacoustic effect). Detection of ultrasound waves was performed by a very sensitive hydrophone and signals were stored in a digital oscilloscope triggered by secondary prompt gammas. The ionoacoustic range measurements were compared to existing range data from a calibrated range detector setup on-site and agreement of better than 1 mm was found at a Bragg peak dose of about 10 Gy for 220 MeV initial proton energy, compatible with the experimental errors. Ionoacoustics has thus the potential to measure the Bragg peak position with submillimeter accuracy during proton therapy, possibly correlated with ultrasound tissue imaging.

Ions provide a more advantageous dose distribution than photons for external beam radiotherapy, due to their so-called inverse depth dose deposition and, in particular a characteristic dose maximum at their end-of-range (Bragg peak). The favorable physical interaction properties enable selective treatment of tumors while sparing surrounding healthy tissue, but optimal clinical use requires accurate monitoring of Bragg peak positioning inside tissue. We introduce ionoacoustic tomography based on detection of ion induced ultrasound waves as a technique to provide feedback on the ion beam profile. We demonstrate for 20 MeV protons that ion range imaging is possible with submillimeter accuracy and can be combined with clinical ultrasound and optoacoustic tomography of similar precision. Our results indicate a simple and direct possibility to correlate, in-vivo and in real-time, the conventional ultrasound echo of the tumor region with ionoacoustic tomography. Combined with optoacoustic tomography it offers a well suited pre-clinical imaging system.

Nephronophthisis (NPH), a recessive cystic kidney disease, is the most frequent genetic cause for end-stage renal disease in the first two decades of life. Mutations in three genes (NPHP1, 2, and 3) were identified as causative. Extrarenal manifestations are known, such as retinitis pigmentosa (Senior-Loken syndrome, SLS) and ocular motor apraxia type Cogan. Recently, we identified a novel gene (NPHP4) as mutated in NPH. To date, a total of only 13 different NPHP4 mutations have been described. To determine the frequency of NPHP4 mutations, we performed mutational analysis by direct sequencing of all 30 NPHP4 exons in 250 different patients with isolated NPH, SLS, or Cogan syndrome ascertained worldwide over 14 years. We identified 23 novel NPHP4 sequence variants in 26/250 different patients (10%). Interestingly, we detected homozygous or compound heterozygous mutations of NPHP4 in only 6/250 different patients (2.4%), but only one heterozygous NPHP4 sequence variant in 20/250 different patients (8%). In the six patients with two NPHP4 mutations, 5/8 mutations (63%) were likely loss-of-function mutations, whereas in the 20 patients with only one sequence variant, only 1/20 (5%) was a likely loss-of-function (i.e., truncating) mutation. We conclude that: i) two recessive mutations in NPHP4 are a rare cause of nephronophthisis; ii) single heterozygous NPHP4 sequence variants are three times more prevalent than two recessive mutations; iii) there is no genotype/phenotype correlation; iv) there must exist further genes causing nephronophthisis, since in 224/250 (90%) patients, no sequence variants in either of the four NPH genes were detected.