This note addresses an issue faced by every proton computed tomography (CT) reconstruction softwa... more This note addresses an issue faced by every proton computed tomography (CT) reconstruction software: the modelling and the parametrisation of the multiple Coulomb scattering power for the estimation of the most likely path of each proton. The conventional approach uses a polynomial model parameterised as a function of depth for a given initial beam energy. This makes it cumbersome to implement a software that works for proton CT data acquired with an arbitrary beam energy or with energy modulation during acquisition. We propose a simple way to parametrise the scattering power based on the measured proton CT list-mode data only and derive a compact expression for the most likely path (MLP) based on a conventional MLP model. Our MLP does not require any parameter. The method assumes the imaged object to be homogeneous, as most conventional MLPs, but requires no information about the material as opposed to most conventional MLP expressions which often assume water to infer energy loss. Instead, our MLP automatically adapts itself to the energy-loss which actually occurred in the object and which is one of the measurements required for proton CT reconstruction. We validate our MLP method numerically and find excellent agreement with conventional MLP methods.
HAL (Le Centre pour la Communication Scientifique Directe), Jan 10, 2022
Objective Proton computed tomography (CT) is similar to x-ray CT but relies on protons rather tha... more Objective Proton computed tomography (CT) is similar to x-ray CT but relies on protons rather than photons to form an image. In its most common operation mode, the measured quantity is the amount of energy that a proton has lost while traversing the imaged object from which a relative stopping power map can be obtained via tomographic reconstruction. To this end, a calorimeter which measures the energy deposited by protons downstream of the scanned object has been studied or implemented as energy detector in several proton CT prototypes. An alternative method is to measure the proton's residual velocity and thus its kinetic energy via the time of flight (TOF) between at least two sensor planes. In this work, we study the RSP resolution, seen as image noise, which can be expected from TOF proton CT systems. Approach We rely on physics models on the one hand and statistical models of the relevant uncertainties on the other to derive closed form expressions for the noise in projection images. The TOF measurement error scales with the distance between the TOF sensor planes and is reported as velocity error in ps/m. We use variance reconstruction to obtain noise maps of a water cylinder phantom given the scanner characteristics and additionally reconstruct noise maps for a calorimeter-based proton CT system as reference. We use Monte Carlo simulations to verify our model and to estimate the noise due to multiple Coulomb scattering inside the object. We also provide a comparison of TOF helium and proton CT. Main results We find that TOF proton CT with 30 ps/m velocity error reaches similar image noise as a calorimeter-based proton CT system with 1% energy error (1 sigma error). A TOF proton CT system with a 50 ps/m velocity error produces slightly less noise than a 2% calorimeter system. Noise in a reconstructed TOF proton CT image is spatially inhomogeneous with a marked increase towards the object periphery. Our modelled noise was consistent with Monte Carlo simulated images. TOF helium CT offers lower RSP noise at equal fluence, but is less advantageous at equal imaging dose. Significance This systematic study of image noise in TOF proton CT can serve as a guide for future developments of this alternative solution for estimating the residual energy of protons and helium ions after the scanned object.
Prompt-gamma imaging during ion therapy has proven its ability to control the ion range in real t... more Prompt-gamma imaging during ion therapy has proven its ability to control the ion range in real time. The achievable precision is of the order of the millimeter for a single spot in proton pencil beam scanning. Collimated gamma cameras have been developed, that are close to clinical application. The Compton cameras are also under development in various laboratories. Time of ight enables the reduction of the background due to other prompt radiations.
The CLaRyS collaboration focuses on the development of gamma detectors for medical applications, ... more The CLaRyS collaboration focuses on the development of gamma detectors for medical applications, in particular for what concerns the range monitoring in ion beam therapy. Part of the research program aims to implement two gamma-camera clinical prototypes, a multi-collimated camera and a Compton camera. A common absorber detector has been designed for the two prototypes, based on bismuth germanate (BGO) blocks, 3.5×3.8×3 cm 3 , assembled in various geometrical configurations to meet the application requirements. The surface of each block is streaked in a matrix of 8×8 pseudo pixels, which makes possible a position reconstruction via Anger logic from the signals collected by four read-out photo-multiplier tubes. The whole set of available blocks comes from a dismantled positron emission tomography system by Siemens, so that each single block must be tested and characterized in terms of space, time and energy response. We present in this work the implemented characterization method, which leads to a complete estimation of the block response via gamma source irradiations and data analysis devoted to a custom calibration for the imaging performance optimization of each detector module. A reference set of blocks has been completely characterized and showed very homogeneous responses: the average energy resolution is 25% FWHM at 511 keV and 20% FWHM at 1275 keV, the time resolution ranges between 3.9 and 5.3 ns FWHM and the spatial resolution has been verified to be limited to the pseudo-pixel size.
HAL (Le Centre pour la Communication Scientifique Directe), Oct 31, 2020
International audienceCompton cameras have the potential to become an emerging technology in Nucl... more International audienceCompton cameras have the potential to become an emerging technology in Nuclear Medicine. Previous studies have shown electronic collimation allows a gain in detection efficiency of 20 with respect to standard collimated cameras. In this work, we present ongoing simulation studies for further enhancing detection efficiency. To this end, we simulated with GATE/Geant4 a Compton camera made of a scatterer detector based on the prototype under development by CLaRyS collaboration consisting of double-sided silicon strip detectors and an ideal absorber covering all the sides of the scatterer except the entrance surface.We studied the performance of the camera by varying the number of scatterer layers in a range comprised between 5 and 25 layers separated by a distance of 10 mm between them. The energy resolution was set to 2.5% at 200 keV and the energy threshold was set to 5 keV. True coincidences sorted by event identification were analyzed. Detection efficiency was obtained as the fraction of events that produces a detected coincidence. For comparison purposes, ideal absorption was also considered inthe studied GE Healthcare Infinia collimated camera (HEGP and MEGP collimators). The detection efficiency was approximated by the geometrical efficiency of the collimator, neglecting septal penetration. Monochromatic gamma sources emitting in a range comprised between 140 keV and 511 keV were employed. The source was located at 100 mm from the first layer, in the center of the transverse surface. The same distance was considered from the source to the collimator surface. Preliminary results showed an increase of detection efficiency by a factor 80 (resp 95) compared to the HEGP (resp MEGP) collimator when the Compton camera based on 25 scatterer layers was considered. In the future, we plan to extend the work to the study of spatial resolution and to the comparison with innovative SPECT systems
The French collaboration ClaRyS is developing fast detectors for online ion range monitoring to r... more The French collaboration ClaRyS is developing fast detectors for online ion range monitoring to reduce treatment uncertainties in hadron therapy. Prompt gamma imaging (PGI), based on the detection of prompt gamma rays following nuclear reactions along the ion track, is a promising technique for the real time verification of ion range, especially when time of flight (TOF) is used to discriminate the prompt gamma rays issued from the patient from the large background of secondary radiation [1]. A Compton Camera prototype has been developed by CLaRyS for PGI. Using Compton kinematics, the photon emission point is reconstructed using either an iterative process, or, if the camera is used in conjunction with a beam-tagging hodoscope, an analytic process involving the intersection of a line and a cone. The iterative reconstruction yielded a precision of 2 mm in the measured range for a 160 MeV proton pencil beam incident on a PMMA phantom. Whilst much quicker than the iterative reconstruc...
This presentation will focus on two applications of diamond detectors in the field of innovative ... more This presentation will focus on two applications of diamond detectors in the field of innovative radiotherapies. The first one consists of a beam hodoscope for hadrontherapy (proton or carbon ion beams). This detector will be used for position and time stamp of the incident particle beam, in order to detect secondary particles (mainly prompt-gammas). Time of Flight is used to reduce background from massive particles, and select photons issued from the patient only. This detector will be made of a mosaic assembly of several diamond plates with double-side strip metallization. The electronic readout design will enable high count rate and high time resolution of the detector. Preliminary measurements were performed at ARRONAX with 68 MeV protons. Detection efficiency was measured with mono- and polycrystalline diamond detectors. For the latter, up to 95% efficiency (corrected from noise triggering) was obtained for single-proton detection. The time resolution was close to 100ps rms for...
Online ion range monitoring in hadron therapy can be performed via detection of secondary radiati... more Online ion range monitoring in hadron therapy can be performed via detection of secondary radiation, such as prompt γ-rays, emitted during treatment. The prompt γ emission profile is correlated with the ion depth-dose profile and can be reconstructed via Compton imaging. The line-cone reconstruction, using the intersection between the primary beam trajectory and the cone reconstructed via a Compton camera, requires negligible computation time compared to iterative algorithms. A recent report hypothesised that time of flight (TOF) based discrimination could improve the precision of the γ fall-off position measured via linecone reconstruction, where TOF comprises both the proton transit time from the phantom entrance until γ emission, and the flight time of the γ-ray to the detector. The aim of this study was to implement such a method and investigate the influence of temporal resolution on the precision of the fall-off position. Monte Carlo simulations of a 160 MeV proton beam incident on a homogeneous PMMA phantom were performed using GATE. The Compton camera consisted of a silicon-based scatterer and CeBr 3 scintillator absorber. The temporal resolution of the detection system (absorber + beam trigger) was varied between 0.1 and 1.3 ns RMS and a TOF-based discrimination method applied to eliminate unlikely solution(s) from the line-cone reconstruction. The fall-off position was obtained for varying temporal resolutions and its precision obtained from its shift across 100 independent γ emission profiles compared to a high statistics reference profile. The optimal temporal resolution for the given camera geometry and 10 8 primary protons was 0.2 ns where a precision of 2.30 ± 0.15 mm (1σ) on the fall-off position was found. This precision is comparable to current stateof-the-art Compton imaging using iterative reconstruction methods or 1D imaging with mechanically collimated devices, and satisfies the requirement of being smaller than the clinical safety margins.
A Monte Carlo (MC) variance reduction technique is developed for prompt-γ emitters calculations i... more A Monte Carlo (MC) variance reduction technique is developed for prompt-γ emitters calculations in proton therapy. Prompt-γ emitted through nuclear fragmentation reactions and exiting the patient during proton therapy could play an important role to help monitoring the treatment. However, the estimation of the number and the energy of emitted prompt-γ per primary proton with MC simulations is a slow process. In order to estimate the local distribution of prompt-γ emission in a volume of interest for a given proton beam of the treatment plan, a MC variance reduction technique based on a specific track length estimator (TLE) has been developed. First an elemental database of prompt-γ emission spectra is established in the clinical energy range of incident protons for all elements in the composition of human tissues. This database of the prompt-γ spectra is built offline with high statistics. Regarding the implementation of the prompt-γ TLE MC tally, each proton deposits along its track the expectation of the prompt-γ spectra from the database according to the proton kinetic energy and the local material composition. A detailed statistical study shows that the relative efficiency mainly depends on the geometrical distribution of the track length. Benchmarking of the proposed prompt-γ TLE MC technique with respect to an analogous MC technique is carried out. A large relative efficiency gain is reported, ca. 10(5).
Background: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and... more Background: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models: The aim was to identify of novel therapeutic target. Methods: The size of the heart was evaluated in CO-HO-RT patients by measurement of the Cardiac-Contact-Distance before and after radiotherapy (48 months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiationinduced cardiac damages were studied in mice and in rat neonatal cardiac cardiomyocyte. Results: In patients, time dependant enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the human radiation-induced pericarditis, activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals were measured. In irradiated mice, decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca 2+ transients were reported. Both hypertrophy and amyloid deposition were timely correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy's stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. Conclusion: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart.
ABSTRACT The quantification of the intrinsic performances of proton computed tomography (pCT) as ... more ABSTRACT The quantification of the intrinsic performances of proton computed tomography (pCT) as a modality for treatment planning in proton therapy. The performance of an ideal pCT scanner is studied as a function of various parameters. Using GATE/Geant4, we simulated an ideal pCT scanner and scans of several cylindrical phantoms with various tissue equivalent inserts of different sizes. Insert materials were selected in order to be of clinical relevance. Tomographic images were reconstructed using a filtered backprojection algorithm taking into account the scattering of protons into the phantom. To quantify the performance of the ideal pCT scanner, we study the precision and the accuracy with respect to the theoretical relative stopping power ratios (RSP) values for different beam energies, imaging doses, insert sizes and detector positions. The planning range uncertainty resulting from the reconstructed RSP is also assessed by comparison with the range of the protons in the analytically simulated phantoms. The results indicate that pCT can intrinsically achieve RSP resolution below 1%, for most examined tissues at beam energies below 300 MeV and for imaging doses around 1 mGy. RSP maps accuracy of less than 0.5 % is observed for most tissue types within the studied dose range (0.2-1.5 mGy). Finally, the uncertainty in the proton range due to the accuracy of the reconstructed RSP map is well below 1%. This work explores the intrinsic performance of pCT as an imaging modality for proton treatment planning. The obtained results show that under ideal conditions, 3D RSP maps can be reconstructed with an accuracy better than 1%. Hence, pCT is a promising candidate for reducing the range uncertainties introduced by the use of X-ray CT alongside with a semiempirical calibration to RSP.Supported by the DFG Cluster of Excellence Munich-Centre for Advanced Photonics (MAP).
This note addresses an issue faced by every proton computed tomography (CT) reconstruction softwa... more This note addresses an issue faced by every proton computed tomography (CT) reconstruction software: the modelling and the parametrisation of the multiple Coulomb scattering power for the estimation of the most likely path of each proton. The conventional approach uses a polynomial model parameterised as a function of depth for a given initial beam energy. This makes it cumbersome to implement a software that works for proton CT data acquired with an arbitrary beam energy or with energy modulation during acquisition. We propose a simple way to parametrise the scattering power based on the measured proton CT list-mode data only and derive a compact expression for the most likely path (MLP) based on a conventional MLP model. Our MLP does not require any parameter. The method assumes the imaged object to be homogeneous, as most conventional MLPs, but requires no information about the material as opposed to most conventional MLP expressions which often assume water to infer energy loss. Instead, our MLP automatically adapts itself to the energy-loss which actually occurred in the object and which is one of the measurements required for proton CT reconstruction. We validate our MLP method numerically and find excellent agreement with conventional MLP methods.
HAL (Le Centre pour la Communication Scientifique Directe), Jan 10, 2022
Objective Proton computed tomography (CT) is similar to x-ray CT but relies on protons rather tha... more Objective Proton computed tomography (CT) is similar to x-ray CT but relies on protons rather than photons to form an image. In its most common operation mode, the measured quantity is the amount of energy that a proton has lost while traversing the imaged object from which a relative stopping power map can be obtained via tomographic reconstruction. To this end, a calorimeter which measures the energy deposited by protons downstream of the scanned object has been studied or implemented as energy detector in several proton CT prototypes. An alternative method is to measure the proton's residual velocity and thus its kinetic energy via the time of flight (TOF) between at least two sensor planes. In this work, we study the RSP resolution, seen as image noise, which can be expected from TOF proton CT systems. Approach We rely on physics models on the one hand and statistical models of the relevant uncertainties on the other to derive closed form expressions for the noise in projection images. The TOF measurement error scales with the distance between the TOF sensor planes and is reported as velocity error in ps/m. We use variance reconstruction to obtain noise maps of a water cylinder phantom given the scanner characteristics and additionally reconstruct noise maps for a calorimeter-based proton CT system as reference. We use Monte Carlo simulations to verify our model and to estimate the noise due to multiple Coulomb scattering inside the object. We also provide a comparison of TOF helium and proton CT. Main results We find that TOF proton CT with 30 ps/m velocity error reaches similar image noise as a calorimeter-based proton CT system with 1% energy error (1 sigma error). A TOF proton CT system with a 50 ps/m velocity error produces slightly less noise than a 2% calorimeter system. Noise in a reconstructed TOF proton CT image is spatially inhomogeneous with a marked increase towards the object periphery. Our modelled noise was consistent with Monte Carlo simulated images. TOF helium CT offers lower RSP noise at equal fluence, but is less advantageous at equal imaging dose. Significance This systematic study of image noise in TOF proton CT can serve as a guide for future developments of this alternative solution for estimating the residual energy of protons and helium ions after the scanned object.
Prompt-gamma imaging during ion therapy has proven its ability to control the ion range in real t... more Prompt-gamma imaging during ion therapy has proven its ability to control the ion range in real time. The achievable precision is of the order of the millimeter for a single spot in proton pencil beam scanning. Collimated gamma cameras have been developed, that are close to clinical application. The Compton cameras are also under development in various laboratories. Time of ight enables the reduction of the background due to other prompt radiations.
The CLaRyS collaboration focuses on the development of gamma detectors for medical applications, ... more The CLaRyS collaboration focuses on the development of gamma detectors for medical applications, in particular for what concerns the range monitoring in ion beam therapy. Part of the research program aims to implement two gamma-camera clinical prototypes, a multi-collimated camera and a Compton camera. A common absorber detector has been designed for the two prototypes, based on bismuth germanate (BGO) blocks, 3.5×3.8×3 cm 3 , assembled in various geometrical configurations to meet the application requirements. The surface of each block is streaked in a matrix of 8×8 pseudo pixels, which makes possible a position reconstruction via Anger logic from the signals collected by four read-out photo-multiplier tubes. The whole set of available blocks comes from a dismantled positron emission tomography system by Siemens, so that each single block must be tested and characterized in terms of space, time and energy response. We present in this work the implemented characterization method, which leads to a complete estimation of the block response via gamma source irradiations and data analysis devoted to a custom calibration for the imaging performance optimization of each detector module. A reference set of blocks has been completely characterized and showed very homogeneous responses: the average energy resolution is 25% FWHM at 511 keV and 20% FWHM at 1275 keV, the time resolution ranges between 3.9 and 5.3 ns FWHM and the spatial resolution has been verified to be limited to the pseudo-pixel size.
HAL (Le Centre pour la Communication Scientifique Directe), Oct 31, 2020
International audienceCompton cameras have the potential to become an emerging technology in Nucl... more International audienceCompton cameras have the potential to become an emerging technology in Nuclear Medicine. Previous studies have shown electronic collimation allows a gain in detection efficiency of 20 with respect to standard collimated cameras. In this work, we present ongoing simulation studies for further enhancing detection efficiency. To this end, we simulated with GATE/Geant4 a Compton camera made of a scatterer detector based on the prototype under development by CLaRyS collaboration consisting of double-sided silicon strip detectors and an ideal absorber covering all the sides of the scatterer except the entrance surface.We studied the performance of the camera by varying the number of scatterer layers in a range comprised between 5 and 25 layers separated by a distance of 10 mm between them. The energy resolution was set to 2.5% at 200 keV and the energy threshold was set to 5 keV. True coincidences sorted by event identification were analyzed. Detection efficiency was obtained as the fraction of events that produces a detected coincidence. For comparison purposes, ideal absorption was also considered inthe studied GE Healthcare Infinia collimated camera (HEGP and MEGP collimators). The detection efficiency was approximated by the geometrical efficiency of the collimator, neglecting septal penetration. Monochromatic gamma sources emitting in a range comprised between 140 keV and 511 keV were employed. The source was located at 100 mm from the first layer, in the center of the transverse surface. The same distance was considered from the source to the collimator surface. Preliminary results showed an increase of detection efficiency by a factor 80 (resp 95) compared to the HEGP (resp MEGP) collimator when the Compton camera based on 25 scatterer layers was considered. In the future, we plan to extend the work to the study of spatial resolution and to the comparison with innovative SPECT systems
The French collaboration ClaRyS is developing fast detectors for online ion range monitoring to r... more The French collaboration ClaRyS is developing fast detectors for online ion range monitoring to reduce treatment uncertainties in hadron therapy. Prompt gamma imaging (PGI), based on the detection of prompt gamma rays following nuclear reactions along the ion track, is a promising technique for the real time verification of ion range, especially when time of flight (TOF) is used to discriminate the prompt gamma rays issued from the patient from the large background of secondary radiation [1]. A Compton Camera prototype has been developed by CLaRyS for PGI. Using Compton kinematics, the photon emission point is reconstructed using either an iterative process, or, if the camera is used in conjunction with a beam-tagging hodoscope, an analytic process involving the intersection of a line and a cone. The iterative reconstruction yielded a precision of 2 mm in the measured range for a 160 MeV proton pencil beam incident on a PMMA phantom. Whilst much quicker than the iterative reconstruc...
This presentation will focus on two applications of diamond detectors in the field of innovative ... more This presentation will focus on two applications of diamond detectors in the field of innovative radiotherapies. The first one consists of a beam hodoscope for hadrontherapy (proton or carbon ion beams). This detector will be used for position and time stamp of the incident particle beam, in order to detect secondary particles (mainly prompt-gammas). Time of Flight is used to reduce background from massive particles, and select photons issued from the patient only. This detector will be made of a mosaic assembly of several diamond plates with double-side strip metallization. The electronic readout design will enable high count rate and high time resolution of the detector. Preliminary measurements were performed at ARRONAX with 68 MeV protons. Detection efficiency was measured with mono- and polycrystalline diamond detectors. For the latter, up to 95% efficiency (corrected from noise triggering) was obtained for single-proton detection. The time resolution was close to 100ps rms for...
Online ion range monitoring in hadron therapy can be performed via detection of secondary radiati... more Online ion range monitoring in hadron therapy can be performed via detection of secondary radiation, such as prompt γ-rays, emitted during treatment. The prompt γ emission profile is correlated with the ion depth-dose profile and can be reconstructed via Compton imaging. The line-cone reconstruction, using the intersection between the primary beam trajectory and the cone reconstructed via a Compton camera, requires negligible computation time compared to iterative algorithms. A recent report hypothesised that time of flight (TOF) based discrimination could improve the precision of the γ fall-off position measured via linecone reconstruction, where TOF comprises both the proton transit time from the phantom entrance until γ emission, and the flight time of the γ-ray to the detector. The aim of this study was to implement such a method and investigate the influence of temporal resolution on the precision of the fall-off position. Monte Carlo simulations of a 160 MeV proton beam incident on a homogeneous PMMA phantom were performed using GATE. The Compton camera consisted of a silicon-based scatterer and CeBr 3 scintillator absorber. The temporal resolution of the detection system (absorber + beam trigger) was varied between 0.1 and 1.3 ns RMS and a TOF-based discrimination method applied to eliminate unlikely solution(s) from the line-cone reconstruction. The fall-off position was obtained for varying temporal resolutions and its precision obtained from its shift across 100 independent γ emission profiles compared to a high statistics reference profile. The optimal temporal resolution for the given camera geometry and 10 8 primary protons was 0.2 ns where a precision of 2.30 ± 0.15 mm (1σ) on the fall-off position was found. This precision is comparable to current stateof-the-art Compton imaging using iterative reconstruction methods or 1D imaging with mechanically collimated devices, and satisfies the requirement of being smaller than the clinical safety margins.
A Monte Carlo (MC) variance reduction technique is developed for prompt-γ emitters calculations i... more A Monte Carlo (MC) variance reduction technique is developed for prompt-γ emitters calculations in proton therapy. Prompt-γ emitted through nuclear fragmentation reactions and exiting the patient during proton therapy could play an important role to help monitoring the treatment. However, the estimation of the number and the energy of emitted prompt-γ per primary proton with MC simulations is a slow process. In order to estimate the local distribution of prompt-γ emission in a volume of interest for a given proton beam of the treatment plan, a MC variance reduction technique based on a specific track length estimator (TLE) has been developed. First an elemental database of prompt-γ emission spectra is established in the clinical energy range of incident protons for all elements in the composition of human tissues. This database of the prompt-γ spectra is built offline with high statistics. Regarding the implementation of the prompt-γ TLE MC tally, each proton deposits along its track the expectation of the prompt-γ spectra from the database according to the proton kinetic energy and the local material composition. A detailed statistical study shows that the relative efficiency mainly depends on the geometrical distribution of the track length. Benchmarking of the proposed prompt-γ TLE MC technique with respect to an analogous MC technique is carried out. A large relative efficiency gain is reported, ca. 10(5).
Background: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and... more Background: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models: The aim was to identify of novel therapeutic target. Methods: The size of the heart was evaluated in CO-HO-RT patients by measurement of the Cardiac-Contact-Distance before and after radiotherapy (48 months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiationinduced cardiac damages were studied in mice and in rat neonatal cardiac cardiomyocyte. Results: In patients, time dependant enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the human radiation-induced pericarditis, activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals were measured. In irradiated mice, decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca 2+ transients were reported. Both hypertrophy and amyloid deposition were timely correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy's stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. Conclusion: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart.
ABSTRACT The quantification of the intrinsic performances of proton computed tomography (pCT) as ... more ABSTRACT The quantification of the intrinsic performances of proton computed tomography (pCT) as a modality for treatment planning in proton therapy. The performance of an ideal pCT scanner is studied as a function of various parameters. Using GATE/Geant4, we simulated an ideal pCT scanner and scans of several cylindrical phantoms with various tissue equivalent inserts of different sizes. Insert materials were selected in order to be of clinical relevance. Tomographic images were reconstructed using a filtered backprojection algorithm taking into account the scattering of protons into the phantom. To quantify the performance of the ideal pCT scanner, we study the precision and the accuracy with respect to the theoretical relative stopping power ratios (RSP) values for different beam energies, imaging doses, insert sizes and detector positions. The planning range uncertainty resulting from the reconstructed RSP is also assessed by comparison with the range of the protons in the analytically simulated phantoms. The results indicate that pCT can intrinsically achieve RSP resolution below 1%, for most examined tissues at beam energies below 300 MeV and for imaging doses around 1 mGy. RSP maps accuracy of less than 0.5 % is observed for most tissue types within the studied dose range (0.2-1.5 mGy). Finally, the uncertainty in the proton range due to the accuracy of the reconstructed RSP map is well below 1%. This work explores the intrinsic performance of pCT as an imaging modality for proton treatment planning. The obtained results show that under ideal conditions, 3D RSP maps can be reconstructed with an accuracy better than 1%. Hence, pCT is a promising candidate for reducing the range uncertainties introduced by the use of X-ray CT alongside with a semiempirical calibration to RSP.Supported by the DFG Cluster of Excellence Munich-Centre for Advanced Photonics (MAP).
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Papers by Jean M Létang