Jean-François Germond

Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s

This study shows for the first time that normal brain tissue toxicities after WBI can be reduced with increased dose rate. Spatial memory is preserved after WBI with mean dose rates above 100Gy/s, whereas 10Gy WBI at a conventional radiotherapy dose rate (0.1Gy/s) totally impairs spatial memory.

High dose‐per‐pulse electron beam dosimetry – A model to correct for the ion recombination in the Advanced Markus ionization chamber

Purpose: The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose‐per‐pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two‐voltage‐analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Methods: Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source‐to‐surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose–response, in beams with varying dose rate/dose‐per‐pulse, with the chamber together with dose rate/dose‐per‐pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose‐per‐pulse (10−2 ≤ mean dose rate ≤ 103 Gy/s, 102 ≤ mean dose rate within pulse ≤ 107 Gy/s, 10−4 ≤ dose‐per‐pulse ≤ 101 Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. Results: The results demonstrate how the ion collection efficiency of the chamber decreased as the dose‐per‐pulse increased, and that the ion recombination was dependent on the dose‐per‐pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose‐per‐pulse range, but only for a low polarizing chamber voltage (50 V). However, the two‐voltage‐analysis method and the Burns & McEwen equation only agreed with the data at low dose‐per‐pulse values (≤ 10−2 and ≤ 10−1 Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. Conclusions: The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose‐per‐pulse. However, this chamber is still functional for dose measurements in beams with dose‐per‐pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less‐than‐accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose‐per‐pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8–4.0%, k = 1). The model depends on the dose‐per‐pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage.

High dose‐per‐pulse electron beam dosimetry: Usability and dose‐rate independence of EBT3 Gafchromic films

Purpose: The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose‐per‐pulse linear accelerator (linac), capable of delivering electron beams with a mean dose‐rate (Dm) ranging from 0.07 to 3000 Gy/s and a dose‐rate in pulse (Dp) of up to 8 × 106 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose‐rate dependence of their response. Material and methods: Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Dm dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Dm between 0.55 and 4.40 Gy/min, while Dp dependence was probed at the prototype machine for Dp ranging from 7 × 103 to 8 × 106 Gy/s. Dp dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo‐luminescent dosimeters (TLD) that have been reported as being dose‐rate independent up to such high dose‐rates. Results: We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Dm dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Dp range attainable at the prototype linac confirming the absence of any dose‐rate dependence within the investigated range (7 × 103 to 8 × 106 Gy/s). This aspect was further corroborated by the linear relationship between the dose‐per‐pulse (Dp) measured by films and the charge per pulse (Cp) measured at the prototype linac exit. Conclusion: Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose‐rate and energy independent.

Lung metastasis detection and visualization on CT images: a knowledge-based method

A solution to the problem of lung metastasis detection on computed tomography (CT) scans of the thorax is presented. A knowledge-based top-down approach for image interpretation is used. The method is inspired by the manner in which a radiologist and radiotherapist interpret CT images before radiotherapy is planned. A two-dimensional followed by a three-dimensional analysis is performed. The algorithm first detects the thorax contour, the lungs and the ribs, which further help the detection of metastases. Thus, two types of tumors are detected: nodules and metastases located at the lung extremities. A method to visualize the anatomical structures segmented is also presented. The system was tested on 20 patients (988 total images) from the Oncology Department of La Chaux-de-Fonds Hospital and the results show that the method is reliable as a computer-aided diagnostic tool for clinical purpose in an oncology department. Copyright

Impact of respiratory-correlated CT sorting algorithms on the choice of margin definition for free-breathing lung radiotherapy treatments.

BACKGROUND AND PURPOSE To investigate the impact of Toshiba phase- and amplitude-sorting algorithms on the margin strategies for free-breathing lung radiotherapy treatments in the presence of breathing variations. MATERIAL AND METHODS 4D CT of a sphere inside a dynamic thorax phantom was acquired. The 4D CT was reconstructed according to the phase- and amplitude-sorting algorithms. The phantom was moved by reproducing amplitude, frequency, and a mix of amplitude and frequency variations. Artefact analysis was performed for Mid-Ventilation and ITV-based strategies on the images reconstructed by phase- and amplitude-sorting algorithms. The target volume deviation was assessed by comparing the target volume acquired during irregular motion to the volume acquired during regular motion. RESULTS The amplitude-sorting algorithm shows reduced artefacts for only amplitude variations while the phase-sorting algorithm for only frequency variations. For amplitude and frequency variations, both algorithms perform similarly. Most of the artefacts are blurring and incomplete structures. We found larger artefacts and volume differences for the Mid-Ventilation with respect to the ITV strategy, resulting in a higher relative difference of the surface distortion value which ranges between maximum 14.6% and minimum 4.1%. CONCLUSIONS The amplitude- is superior to the phase-sorting algorithm in the reduction of motion artefacts for amplitude variations while phase-sorting for frequency variations. A proper choice of 4D CT sorting algorithm is important in order to reduce motion artefacts, especially if Mid-Ventilation strategy is used.

The advantage of Flash radiotherapy confirmed in mini-pig and cat-cancer patients

Purpose: Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Experimental Design: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called “FLASH-RT” and irradiation delivered at a conventional dose rate called “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Results: Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. Conclusions: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients. See related commentary by Harrington, p. 3

A computer aided diagnostic system for radiotherapy planning.

Planning for radiation therapy intervention implies the definition of treatment volumes as well as a clear delimitation of normal tissue. This paper presents a Computer Aided Diagnostic system for the automatic CT image analysis. Two important problems are solved: the spinal cord segmentation and the detection of lung metastases. Some subordinate problems are also solved: the detection of spinal canal, lamina, lungs, and ribs, as well as the identification of thorax contour. The developed methodologies use a knowledge-driven image processing based on Anatomical Structures Maps and task-oriented architecture. Experiments were performed on CT images from La Chaux de Fonds Hospital (Switzerland). Evaluations were performed using a visual inspection of the contours projected on the CT image slices. The radiologist decided whether each of the contours obtained with our system was acceptable or not. The accuracy of the method was defined as the fraction of CT slices in which the particular contour was correctly located. In the case of spinal cord segmentation, the procedure was tested on 23 patients (1051 images), resulting in an accuracy of 91%. In the case of lung tumors detection, the method showed an accuracy of > 90%, with testing performed on 20 patients for a total of 988 images. The experiments performed show that the method is reliable, with possible future application in an oncology department.

Determination of the effective dose delivered by image guided radiotherapy in head & neck and breast treatments

PURPOSE Image guided radiotherapy (IGRT) improves patient positioning for treatment delivery at the cost of an additional dose. This work aimed to calculate the effective dose (as an indicator of dose) for head & neck (H&N) and breast IGRT treatments by implementing dose calculation models to determine the dose distributions. METHODS The kV dose-models were created for the IGRT systems of Elekta Synergy (XVI) and Varian Clinac (OBI) linear accelerators within Philips Pinnacle TPS. Profiles and depth dose curves were measured in water. The models were validated in a CIRS thorax phantom. The IGRT dose distributions for five H&N and five breast patients were calculated. The effective dose was determined from the dose distributions following ICRP 103 recommendations. Moreover, time-saving approximations were studied in order to propose an alternative way of segmenting the tissues for a clinical implementation of the method. RESULTS AND CONCLUSION The effective dose specifically associated with IGRT varied from 1 to 10mSv depending on the protocol. The kV dose-model allowed us to calculate the dose distributions from IGRT for different configurations and patients, and to determine effective dose for IGRT protocols. The clinical implementation of the method was found to reduce time and to introduce a small enough increase of uncertainty in the results to be clinically usable.

PD-0577: Impact of respiratory-correlated reconstruction algorithms in the choice of margins in 4D IGRT

Purpose/Objective: 4D CT imaging based on respiratory-correlated algorithms incorporates organ motion which reduces motion artifacts and allows for an accurate determination of the tumor trajectory. However, breathing irregularities can cause considerable image distortions. Most of 4D CT images are reconstructed using a phasebased reconstruction method that is subject to image misalignments. The aim of this study is to investigate the impact of phaseand amplitude-based reconstruction algorithms in margins definition for lung cancer. These algorithms are studied in terms of image quality and dose distribution in presence of respiratory irregularities. Materials and Methods: 4D CT images of Dynamic Thorax Phantom are acquired in helical mode (pitch < 0.1) using a 16-slices Toshiba CT. The respiratory signal is tracked by the ANZAI belt. Two irregular breathings are simulated with amplitude and frequency variations. Artifacts are evaluated from the reconstructed images. Four VMAT plans (two simulated breathing models for the two reconstruction algorithms) delivered in two arcs are calculated in Monte-Carlo-based TPS in the exhale phase. The plans are evaluated for Dmin, Dmax, Dmean, homogeneity index (HI) and conformity index (CI).