Nuclear prompt gamma spectroscopy for range verification in ion-beam therapy

Proton and heavier ions have a characteristic energy deposition profile presenting the maximum at the end of range of the primary particles. This feature potentially allows delivering highly conformal radiation therapy, depositing most of the dose in the target volume and sparing the healthy tissue surrounding it. Despite its expanding clinical application, several limitations still affect this technique and there are great opportunities for further improvement. This thesis addresses the issue of range uncertainties. Many factors influence the range of the primary particles. Due to the sharp spatial gradients of the dose distribution, even a small shift can lead to severe changes in the treatment quality. Countermeasures are usually adopted in clinical practice to make the dose delivery robust to such shifts at the price of obtaining sub-optimal treatment plans. This thesis aims to develop a preclinical prototype to measure on-line and in-vivo the position of the dose deposition. The technique is based on nuclear prompt gamma spectroscopy. In this work, we first proposed the use of a novel detector type. Then, we optimized through simulations and experimentally characterized the detector system. Finally, we experimentally demonstrated the measurement of the particles range with millimetric precision in clinically relevant conditions

Degradation of proton and carbon Bragg peaks due to density inhomogeneities

Current analytical treatment planning of radiotherapy with protons and heavier ions neglect degradation of the sharp distal dose falloff (Bragg peak, BP) caused by inhomogeneous tissue. There is no appropriate model of this effect - which in turn allowed reduction of related dose deposition uncertainties. This thesis develops a comprehensive analytical model of the degradation resulting from static lung parenchyma. To do so, it adopts Monte Carlo (MC) simulations, validated by a series of transmission experiments on lung-like phantoms. Fluctuations in the water equivalent thickness (WET) were found the major degradation factor, contributing more than 75% (40%) to the distal falloff widening for a carbon (proton) BP - while energy and particle type were found to have no considerable impact. Also, it was found that the plateau of a clinical spread-out BP remains unaffected but the distal falloff is degraded and that the impact on the biological effect is driven by changes to the physical dose. The model was parametrized with respect to lung specific parametr (alveolar dimension and tissue density) and breathing state parameters (thickness traversed, air filling). Formulation of a Gaussian filter provided a unified, compact and complete description that can readily be implemented in a treatment planning system

Reduction of patient specific quality assurance through plan complexity metrics for VMAT plans with an open-source TPS script

PURPOSE Volumetric modulated arc therapy (VMAT) is a widespread technique for the delivery of normo-fractionated radiation therapy (NFRT) and stereotactic body radiation therapy (SBRT). It is associated with a significant hardware burden requiring dose rate modulation, collimator movement and gantry rotation synchronisation. Patient specific quality assurance (PSQA) guarantees that the linacs can precisely and accurately deliver the planned dose. However, PSQA requires a significant time allocation and class solutions to reduce this while guaranteeing the deliverability of the plans should be investigated. METHODS In this study, an in-house developed Eclipse Scripting API (ESAPI) script was used to extract five independent plan complexity metrics from N = 667 VMAT treatment fields. The correlation between metrics and portal dosimetry measurements was investigated with Pearson correlation, box plot analysis and receiver operating characteristic curves, which were used to defined the best performing metric and its threshold. RESULTS The incidence of fields failing the clinical PSQA criteria of 3%/2mm (NFRT) and 3%/1.5mm (SBRT) was low (N = 1). The mean MLC opening was the metric with the highest correlation with the portal dosimetry data and among the best in discriminating the requirement of PSQA. The thresholds of 16.12 mm (NFRT) and 7.96 mm (SBRT) corresponded to true positive rates higher than 90%. CONCLUSIONS This work presents a quantitative approach to reduce the time allocation for PSQA by identifying the most complex plans demanding a dedicated measurement. The proposed method requires PSQA for approximately 10% of the plans. The ESAPI script is distributed open-source to ease the investigation and implementation at other institutions

The Use of MR-Guided Radiation Therapy for Head and Neck Cancer and Recommended Reporting Guidance

Although magnetic resonance imaging (MRI) has become standard diagnostic workup for head and neck malignancies and is currently recommended by most radiological societies for pharyngeal and oral carcinomas, its utilization in radiotherapy has been heterogeneous during the last decades. However, few would argue that implementing MRI for annotation of target volumes and organs at risk provides several advantages, so that implementation of the modality for this purpose is widely accepted. Today, the term MR-guidance has received a much broader meaning, including MRI for adaptive treatments, MR-gating and tracking during radiotherapy application, MR-features as biomarkers and finally MR-only workflows. First studies on treatment of head and neck cancer on commercially available dedicated hybrid-platforms (MR-linacs), with distinct common features but also differences amongst them, have also been recently reported, as well as "biological adaptation" based on evaluation of early treatment response via functional MRI-sequences such as diffusion weighted ones. Yet, all of these approaches towards head and neck treatment remain at their infancy, especially when compared to other radiotherapy indications. Moreover, the lack of standardization for reporting MR-guided radiotherapy is a major obstacle both to further progress in the field and to conduct and compare clinical trials. Goals of this article is to present and explain all different aspects of MR-guidance for radiotherapy of head and neck cancer, summarize evidence, as well as possible advantages and challenges of the method and finally provide a comprehensive reporting guidance for use in clinical routine and trials

Multi-Analyte MS Based Investigation in Relation to the Illicit Treatment of Fish Products with Hydrogen Peroxide

Fishery products are perishable due to the action of many enzymes, both endogenous and exogenous. The latter are produced by bacteria that may contaminate the products. When fishes age, there is a massive bacteria growth that causes the appearance of off-flavor. In order to obtain “false” freshness of fishery products, an illicit treatment with hydrogen peroxide is reported to be used. Residues of hydrogen peroxide in food may be of toxicology concern. We developed two mass spectrometry based methodologies to identify and quantify molecules related to the treatment of fishes with hydrogen peroxide. With ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS) we evaluated the concentration of trimethylamine-N-oxide (TMAO), trimethylamine (TMA), dimethylamine (DMA), and cadaverine (CAD) in fish products. After evaluating LOQ, we measured and validated the lower limits of quantification (LLOQs as first levels of calibration curves) values of 50 (TMAO), 70 (TMA), 45 (DMA), and 40 (CAD) ng/mL. A high ratio between TMAO and TMA species indicated the freshness of the food. With a GC-MS method we confirmed the illicit treatment measuring the levels of H2O2 after an analytical reaction with anisole to give 2-hydroxyanisole as a marker. This latter product was detected in the headspace of the homogenized sample with simplification of the work-up. A LLOQ of 50 ng/mL was checked and validated. When fish products were whitened and refreshed with hydrogen peroxide, the detected amount of the product 2-hydroxyanisole could be very important, (larger than 100 mg/kg). The developed analytical methods were suitable to detect the illicit management of fishery products with hydrogen peroxide; they resulted as sensitive, selective, and robust

Adaptive fractionation at the MR-linac

Objective. Fractionated radiotherapy typically delivers the same dose in each fraction. Adaptive fractionation (AF) is an approach to exploit inter-fraction motion by increasing the dose on days when the distance of tumor and dose-limiting organs at risk (OAR) is large and decreasing the dose on unfavorable days. We develop an AF algorithm and evaluate the concept for patients with abdominal tumors previously treated at the MR-linac in 5 fractions.Approach. Given daily adapted treatment plans, inter-fractional changes are quantified by sparing factorsδ$_{t}$defined as the OAR-to-tumor dose ratio. The key problem of AF is to decide on the dose to deliver in fractiont, givenδ$_{t}$and the dose delivered in previous fractions, but not knowing futureδ$_{t}$s. Optimal doses that maximize the expected biologically effective dose in the tumor (BED$_{10}$) while staying below a maximum OAR BED$_{3}$constraint are computed using dynamic programming, assuming a normal distribution overδwith mean and variance estimated from previously observed patient-specificδ$_{t}$s. The algorithm is evaluated for 16 MR-linac patients in whom tumor dose was compromised due to proximity of bowel, stomach, or duodenum.Main Results. In 14 out of the 16 patients, AF increased the tumor BED$_{10}$compared to the reference treatment that delivers the same OAR dose in each fraction. However, in 11 of these 14 patients, the increase in BED$_{10}$was below 1 Gy. Two patients with large sparing factor variation had a benefit of more than 10 Gy BED$_{10}$increase. For one patient, AF led to a 5 Gy BED$_{10}$decrease due to an unfavorable order of sparing factors.Significance. On average, AF provided only a small increase in tumor BED. However, AF may yield substantial benefits for individual patients with large variations in the geometry

A Single-Particle Trigger for Time-of-Flight Measurements in Prompt-Gamma Imaging

[EN] Tracking of single particles accelerated by synchrotrons is a subject that crosses several physics fields. The high clinical intensities used in particle therapy that can exceed 10(9)p/s make this task very challenging. The tracking of the arrival time of single particles in the ion beam is fundamental for the verification of the particle range and dose delivered to the patient. We present a prototype made of scintillating fibers which has been used to provide time-of-flight (TOF) information for three beam species currently accelerated at the Heidelberg Ion-Beam Therapy Center (HIT). We have demonstrated a time-tracker for a prompt-gamma spectroscopy system that allows for a background TOF rejection with a sub-nanosecond time resolution.PM was supported by a research fellowship for postdoctoral researchers from the Alexander von Humboldt Foundation, Bonn, Germany. 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Physica Medica, 52, 11. doi:10.1016/j.ejmp.2018.06.099Mazzucconi, D., Agosteo, S., Ferrarini, M., Fontana, L., Lante, V., Pullia, M., & Savazzi, S. (2018). Mixed particle beam for simultaneous treatment and online range verification in carbon ion therapy: Proof‐of‐concept study. Medical Physics, 45(11), 5234-5243. doi:10.1002/mp.13219Scintillating Fiber Trackers: recent developments and applications204 BlancF 14th ICATPP Conference on Astroparticle, Particle, Space Physics and Detectors for Physics Applications2013JoramC UwerU LeveringtonBD KirnT BachmannS EkelhofRJ LHCb Scintillating Fibre Tracker Engineering Design Review Report: Fibres, Mats and Modules201