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Development of a Spatio-Temporal-Energetic Radiation Research Platform for Animals

Final Report Summary - STERRPA (Development of a Spatio-Temporal-Energetic Radiation Research Platform for Animals)

Final Report Summary-STERRPA (Development of a Spatio-Temporal-Energetic Radiation Research Platform for Animals) Summary description of the project objectives

i) Implementation of a prototype small animal irradiator and characterisation of x-ray beams
ii) Development of treatment planning software for small animal treatments
iii) Integration of an imaging panel for targeting accuracy
iv) Development of 3D cone beam imaging for verification imaging and Image-fusion capabilities
v) Development of accurate dose calculation models
vi) development of a dose verification procedure
remark: Obj v and vi were decided upon during the project, and replaced the original Obj v and vi. This was due to technological progress, and increased activities in the Obj i-iv.

Another main activity was that in March 2013 the first International Symposium on Precision Image-guided Small Animal Radiotherapy was organised by us in Maastricht, to consolidate research efforts in this new field. This conference was the first of its kind, was considered a success and has provided a boost to the field. We also embarked on a commercial spin-off of the STERRPA project by initiating the development of a fully versatile treatment planning system (TPS for small animals.

During the project, a first large animal trial was initiated to study the effectiveness of a new drug to counteract the effects of radiation-induced fibrosis in mouse lungs. If proven effective, this drug will move towards human trials, with the final aim to alleviate the deleterious effects of radiation damage to the healthy part of the lung in cancer patients. This would also allow giving a much higher dose to the lung tumor, almost certainly resulting in more patients cured. This is just one example of why we are investing much effort in this new field.

In another study started during STERRPA we explore imaging of small animals to discover their most active tumor regions, which we will then boost with an extra radiation dose. This is a concept that has been considered for many years, and that cant be implemented clinically without proper pre-clinical testing first.
These are just two examples of studies which are possible with the equipment and methods developed during STERRPA.

In an initial phase funding was acquired for the purchase of a prototype small animal precision irradiator/imager, through a Dutch ZonMW grant. The selected device was installed in april 2010. The device is known as SSmART (Smart Small Animal Radiation Therapy).

Since this research field is very new, we wrote a review paper (Verhaegen 2011). Several parts of the work were presented at various conferences. We are seen as one of the leaders in the newly developing field of preclinical small animal radiotherapy studies, especially since the first Symposium on precision image-guided small animal radiotherapy, Maastricht March 3.4.2013.

Since then, we have done much work on modeling the device, and developing procedures to operate it. Work was done on:
1) Assessment of the hardware for irradiation, and dosimetric measurements

The system was extensively tested, and to some extent redesigned. This involved optimising a new type of dosimeter (radiochromic film with 3-color readout). A tri-center comparison was done (Toronto, Amsterdam, Maastricht) of similar equipment, and a paper is being prepared now.
2) Development of treatment planning software
A Monte Carlo based TPS Smart-Plan was designed and version 1 was delivered, in collaboration with the leading company PXI. This is a unique TPS, which will be broadly applicable for many small animal radiation studies. Treatment planning software was developed which includes the following steps: convert animal CT scans into calculation phantoms, prescribe beam configuration and dose, perform Monte Carlo simulations in animal specimens, analyze dose. In 2013 we will publish a validation of Smart-Plan. It should be pointed out that the effort on this part of the project was much greater than originally planned. Originally we wanted to make a basic TPS for own use, but due to the international interest in our efforts, it was decided in 2012 to develop a fully versatile TPS, with commercial spinoff. External funding other than STERRPA was partially used to develop Smart-Plan.

Another aspect of this project is that we developed very detailed MC models of the irradiator, and also an approximative analytical source model, which was shown to be suitable for dose calculations with acceptable loss of accuracy but with significant gain of calculation speed. This will be published separately.
3) Assessment of imaging hardware and development of software

The onboard imager was thoroughly studied for use in different modes: static, fluoroscopic and cone beam CT. We studied the image quality and stability, as this is essential to use the imager to quantify e. g. radiation damage in small animals. The influence of photon scatter in the image quality was assessed. The CT images were made suitable for quantitative dose calculations, through corrections and calibrations. A start was made with exploring dual-energy CT and perfusion CT (not STERRPA objectives).
4) Procedure for dose reconstruction during irradiation. Not originally part of the proposal but identified as an opportunity during the project, was the reconstruction of the true received dose by the animal specimen. This work is based on our efforts to develop similar algorithms for human patients. A procedure was developed to calculate the expected image in the portal imager (on opposite side of the animal than the irradiator). This is then compared to the true acquired image during treatment. Differences indicate discrepancies between delivered and planned dose, which can then be identified. For this work, we used the calculation models described in the previous section.

The conclusion of this project is that precision image-guided small animal radiotherapy is feasible, provided the required technical developments in irradiation technology, imaging and treatment planning keep progressing at the current pace or better.

The socio-economic impact cannot yet be measured but is likely to come from improved and faster animal trials translating into more efficient human trials of new methods for radiotherapy possibly in synergy with other therapies.