Feriel Khellaf

Séminaires Jeunes docteurs du GDR du 12 avril 2021

Title: List-mode proton CT reconstruction

Abstract:

Proton therapy is used for cancer treatment to achieve better dose conformity by exploiting the energy-loss properties of protons. Proton treatment planning systems require knowledge of the stopping-power map of the patient’s anatomy to compute the absorbed dose. In clinical practice, this map is generated through a conversion from X-ray computed tomography (CT) Hounsfield units to proton stopping power relative to water (RSP). This calibration generates uncertainties as photon and proton physics are different, which leads to the use of safety margins and the reduction of dose conformity. In order to reduce uncertainties, proton CT (pCT) was proposed as a planning imaging modality since the reconstructed quantity is directly the RSP. In addition to energy loss, protons also undergo multiple Coulomb scattering (MCS) inducing non-linear paths, thus making the pCT reconstruction problem different from that of X-ray CT and degrading spatial resolution. The use of a most likely path (MLP) formalism for protons to account for the effects of MCS has improved the spatial resolution in pCT, although this formalism assumes a homogeneous medium.
The objective of this work was to improve image quality of pCT list-mode reconstruction.  First, we study the accuracy of the MLP formalism in heteregeneous media by comparing the theoretical MLP against Monte Carlo generated proton paths. Results in terms of spatial, angular, and energy distributions were analyzed to determine the maximum systematic error on the MLP and assess the impact on reconstruction.
The MLP formalism provides an additional information to the MLP estimate, which is the uncertainty envelope around the MLP. This information, included in a reconstruction algorithm, could help improve spatial resolution. In addition to MCS, the resolution of the trackers used to measure the protons' position and angle has also an impact on spatial resolution. We propose a deconvolution method using the uncertainty on the MLP estimate and the tracker resolution to improve the spatial resolution of pCT images. Results on simulated data show an improved spatial resolution in simple phantoms as well as anthropomorhpic phantoms.

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Floriane Poignant

Séminaire Jeunes Docteurs du GDR MI2B  du 12 avril 2021

Title: Physical, chemical and biological modelling for gold nanoparticle-enhanced radiation therapy: towards a better understanding and optimization of the radiosensitizing effect

Abstract:

In radiation therapy, high-Z nanoparticles such as gold nanoparticles (GNPs) have shown particularly promising radiosensitizing properties. At an early stage, an increase in dose deposition and free radical production throughout the tumor (photoelectric effect) and at sub-cellular scale (Auger cascade) might be responsible for part of the effect for low-energy X-rays. In this work, these early mechanisms are investigated with simulation tools to better quantify them and understand their impact on cell survival.

This work was based on Monte Carlo (MC) models developed to track electrons down to low energy both in water (meV) and gold (eV). In particular, the accuracy of electron transport in gold was assessed by comparing the MC predictions with experimental data in the literature.

Once validated, the MC simulation was used to quantify the energy deposited in nanotargets located near the GNP, which correlates with the probability to generate damages. These nanodosimetry results showed a significant increase of the probability of having an energy deposition in the nanotarget larger than a threshold, within 200 nm around the GNP. This suggests that GNPs may be particularly efficient at destroying biological nanotargets in its vicinity.

The MC simulation was then used to quantify chemical effects. At the macroscale, the increase of free radical production for a concentration of GNPs was calculated. Such increase correlated well with the increase of dose deposition at the macro-scale.

Finally, MC results were used together with the biophysical model NanOx to predict cell survival in presence of GNPs. NanOx was originally developed to calculate the biological dose in hadrontherapy. The Local Effect Model (LEM), currently the main biophysical model implemented for GNP-enhanced radiation therapy, was also used to calculate cell survival and to compare NanOx and LEM predictions. For a simple system where GNPs were homogeneously distributed in the cell, the increase of cell death with the biophysical model NanOx was purely due to the increase of the macroscopic dose. No increased biological effectiveness due to Auger electrons was obtained, which comes in contradiction with the LEM predictions.

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Sofia Ferreira

Séminaire Jeunes Docteurs du GDR MI2B  du 1er février 2021

Title: Inhibiting DNA repair with AsiDNA to radiosensitize pediatric brain tumors without added toxicity

Authors: Sofia Ferreira, Chloe Foray, Alberto Gatto, Magalie Larcher, Sophie Heinrich, Mihaela Lupu, Joel Mispelter, François D. Boussin, Célio Pouponnot and Marie Dutreix

Abstract: Medulloblastoma is a brain tumor of the cerebellum. It is an important cause of mortality and morbidity in pediatric oncology. Preclinical and clinical evidence showed that the DNA repair inhibitor AsiDNA improves treatments efficacy without added toxicity in adults. In our work, we investigated whether these properties of AsiDNA could be translated to medulloblastoma pediatric models, addressing a significant unmet clinical need in medulloblastoma care.
To evaluate the brain permeability of AsiDNA upon systemic delivery, we intraperitoneally injected a fluorescence form of AsiDNA in models harboring brain tumors and in models still in development. Studies evaluated toxicity associated with combination of AsiDNA with radiation in the treatment of young developing animals at subacute levels, related to growth and development, and at chronic levels, related to brain organization and cognitive skills. Efficacy of the combination of AsiDNA with radiation was tested in two different preclinical xenografted models of high-risk medulloblastoma and in a panel of medulloblastoma cell lines from different molecular subgroups and TP53 status. Role of TP53 on the AsiDNA-mediated radiosensitization was analyzed by RNA-sequencing, DNA repair recruitment, and cell death assays.
Capable of penetrating young brain tissues, AsiDNA showed no added toxicity to radiation. Combination of AsiDNA with radiotherapy improved the survival of animal models more efficiently than increasing radiation doses. Medulloblastoma radiosensitization by AsiDNA was not restricted to a specific molecular group or status of TP53. Molecular mechanisms of AsiDNA, previously observed in adult malignancies, were conserved in pediatric models and resembled dose increase when combined with irradiation.
Our results suggest that AsiDNA is an attractive candidate to improve radiotherapy in medulloblastoma, with no indication of additional toxicity in developing brain tissues.

Présentation (format video MP4)

Sébastien Curtoni:

Présentation au Séminaire Jeunes Docteurs du GDR MI2B le 1er février 2021

A diamond beam-tagging hodoscope for online ion verification in hadrontherapy by means of
time-of-flight enhanced Prompt-Gamma detection

Lien vers la présentation (format mp4)

Abstract:
Hadrontherapy could benefit from an online ion range monitoring system. First, it would allow to
reduce ion range specific security margins currently set in the treatment planning. It could also enable
to detect discrepancies between the planned and the actual ion range during a treatment session.
Several groups are currently developing online ion range verification techniques and many of them are
based on secondary particle detection. Among them, prompt-gamma photons (PG) emission results
from inelastic nuclear interactions occurring along the ion pathway and their emission profile is thus
spatially correlated to the ion range.
The CLaRyS national collaboration is developing such PG-based monitoring systems. The originality
in CLaRyS’ approach consists in adding a beam-tagging hodoscope to the detection system which
provides spatial and temporal information on incoming ions. Combining an overall 100 ps (σ)
resolution on the ion+PG time-of-flight and single ion regime, the efficiency and sensitivity of PGbased
verification systems could be notably improved. To fulfill these requirements, the hodoscope
should be fast, radiation-hard and sensitive to single ions. In this context, diamond-based hodoscope
demonstraters are currently under development.
As synthetic diamond is available in various crystalline qualities and sizes, this work was highly
focused on the characterization carried out on commercially available samples to highlight the best
hodoscope candidate. The presentation will review the different lab and beam tests done at lab and in
different particle beam configurations with Chemical Vapor Deposition (CVD) diamond samples. Their
single ion detection efficiency, time resolution and counting capabilities were measured. Their spatial
response was also assessed with a X-ray micro-beam. The first double-sided strip prototypes,
developed during this thesis, will also be introduced. The presentation will be concluded by a brief
presentation of larger area diamond hodoscope demonstrators which are currently under construction
with dedicated front-end electronics and acquisition system.