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NANO2021-Nanoteknologi og nye materiale

Neutron and gamma-ray imaging for real-time range verification and image guidance in particle therapy

Alternative title: Nøytron og fotonavbildning for rekkeviddeverifisering og bildeveiledning i partikkelterapi

Awarded: NOK 8.5 mill.

Radiotherapy using external energetic beams of photons is a standard radiotherapy modality used on a global basis to combat cancer tumours and increase the life span of cancer patients. A major disadvantage of photons is that the energy transferred to tissue falls exponentially. Thus, all tissue around the tumour including healthy tissue receive undesired radiation dose. Radiotherapy using charged particles, such as protons, has a potential to significantly reduce doses to healthy tissue. This is mainly due to their finite range in matter, including human tissue and the fact that maximum energy deposition occurs at the end of their range. By fine tuning their energy, charged particles can be made to stop exactly inside the tumorous region. This unique property of charged particles makes them a very effective cancer killing tool, given that one knows their range in tissue. Unfortunately, certain factors such as organ motion, anatomical changes and even millimetric positioning errors mean that the range is only known within a certain uncertainty. In practice, such uncertainties prevent benefiting fully from the finite range of particle beams. An ideal solution to mitigating these uncertainties would be to visualize the particle beams as they pass through the patient and "see" where the particles stop during treatment. Any undesired deviation could then be identified in real-time. The NOVO (Neutron and gamma-ray imaging for real-time range verification and image guidance in particle therapy) project aims to develop a novel camera that could "see" where incident particles stop in the patient. For the first time, the camera will detect secondary fast neutrons and prompt gamma-rays that are produced in the patient as by-products of interactions of charged particle interactions with tissue. The data collected by the camera will be used to produce a snapshot image of the particle beam and determine the particle range in the patient in real-time, or near real-time. The NOVO partners recently completed a feasibility study based on Monte Carlo radiation transport models of the NOVCoDA (The NOVO Compact Detector Array) along with realistic patient geometries and material compositions. The model data were also smeared out using experimentally determined detector resolutions. The results of the study, published in Nature Scientific Reports, indicated that range shifts of 1 mm can be identified at relatively low proton intensities around 2.23(13) x 107 protons/spot when imaging data from both fast neutrons and prompt gamma-ray are exploited simultaneously. Further analyses using machine learning and multivariate statistical analysis techniques have also been carried out to extract the most predictive features from reconstructed fast neutron and prompt gamma-ray distributions in the patient geometry. Most importantly, these analyses have revealed that combining data from both particle species and up to three predictive features significantly improve the range shift detection capabilities of the NOVCoDA. Moreover, the possibility of performing gamma-ray energy spectroscopy with the NOVCoDA has been explored. The preliminary model-based results show that energy spectroscopy performed in conjunction with advanced computational analysis techniques does provide a signal that correlates well with range shifts, a property that can also be exploited for range monitoring. The project partners will continue exploring these concepts, individually and in combination with each other. Future studies will be conducted using both computational models and experiments as the project partners are currently working on building a functional demonstrator prototype to be tested using radioisotope sources of gamma-rays and fast neutrons, in experimental fast neutron beams as well as therapeutic proton beams.

Particle therapy (PT) is an emerging radiation therapy modality offering highly conformal treatment plans as compared to conventional radiation therapy, contributing to spare healthy tissue during treatment. This is mainly due to the finite range of particles in tissue and the steep dose gradient toward the end of their range. An important challenge associated with PT is the considerable uncertainties in the particle ranges in tissue predicted by treatment planning systems in addition to those resulting from tissue heterogeneities, anatomical changes as well as inter- and intra-fractional organ motion. These uncertainties result in increased distal treatment margins in clinical protocols. Thus, it has not yet been possible to exploit the full potential of the finite range of protons in tissue, especially when tumors are located near organs at risk. There is therefore a consensus that it is of great importance to monitor the range of particles during treatment with high precision (~1-2mm). Range verification techniques will also allow on-line monitoring of the delivered dose to patient. We propose, for the first time, the development of a compact, high-efficiency single volume scatter camera (SVSC) based on optically segmented arrays of organic scintillators. The SVSC will be utilized for the detection and subsequent imaging of secondary neutrons and prompt gamma-rays (PGs) produced in nuclear interactions. The SVSC will be the first of its kind in PT offering "unification" of neutron and PG imaging in a single device with potentially revolutionizing improvements in achievable counting statistics to allow range and dose verification on a spot-by-spot basis, including weaker spots. To achieve the objective of the NOVO project, we will (1) perform a model-based design evaluation of the SVSC, (2) develop methods for optimal particle discrimination and (3) perform tests in clinically realistic conditions with a first functional prototype SVSC.

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NANO2021-Nanoteknologi og nye materiale