Publications by authors named "Katia Parodi"

158 Publications

Radioactive Beams for Image-Guided Particle Therapy: The BARB Experiment at GSI.

Front Oncol 2021 19;11:737050. Epub 2021 Aug 19.

GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany.

Several techniques are under development for image-guidance in particle therapy. Positron (β) emission tomography (PET) is in use since many years, because accelerated ions generate positron-emitting isotopes by nuclear fragmentation in the human body. In heavy ion therapy, a major part of the PET signals is produced by β-emitters generated projectile fragmentation. A much higher intensity for the PET signal can be obtained using β-radioactive beams directly for treatment. This idea has always been hampered by the low intensity of the secondary beams, produced by fragmentation of the primary, stable beams. With the intensity upgrade of the SIS-18 synchrotron and the isotopic separation with the fragment separator FRS in the FAIR-phase-0 in Darmstadt, it is now possible to reach radioactive ion beams with sufficient intensity to treat a tumor in small animals. This was the motivation of the BARB (Biomedical Applications of Radioactive ion Beams) experiment that is ongoing at GSI in Darmstadt. This paper will present the plans and instruments developed by the BARB collaboration for testing the use of radioactive beams in cancer therapy.
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http://dx.doi.org/10.3389/fonc.2021.737050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422860PMC
August 2021

Investigating the accuracy of co-registered ionoacoustic and ultrasound images in pulsed proton beams.

Phys Med Biol 2021 Sep 9;66(18). Epub 2021 Sep 9.

Department of Medical Physics, Ludwig-Maximilians-Universität München, Garching b. München, Germany.

The sharp spatial and temporal dose gradients of pulsed ion beams result in an acoustic emission (ionoacoustics), which can be used to reconstruct the dose distribution from measurements at different positions. The accuracy of range verification from ionoacoustic images measured with an ultrasound linear array configuration is investigated both theoretically and experimentally for monoenergetic proton beams at energies relevant for pre-clinical studies (20 and 22 MeV). The influence of the linear sensor array arrangement (length up to 4 cm and number of elements from 5 to 200) and medium properties on the range estimation accuracy are assessed using time-reversal reconstruction. We show that for an ideal homogeneous case, the ionoacoustic images enable a range verification with a relative error lower than 0.1%, however, with limited lateral dose accuracy. Similar results were obtained experimentally by irradiating a water phantom and taking into account the spatial impulse response (geometry) of the acoustic detector during the reconstruction of pressures obtained by moving laterally a single-element transducer to mimic a linear array configuration. Finally, co-registered ionoacoustic and ultrasound images were investigated using silicone inserts immersed in the water phantom across the proton beam axis. By accounting for the sensor response and speed of sound variations (deduced from co-registration with ultrasound images) the accuracy is improved to a few tens of micrometers (relative error less than to 0.5%), confirming the promise of ongoing developments for ionoacoustic range verification in pre-clinical and clinical proton therapy applications.
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http://dx.doi.org/10.1088/1361-6560/ac215eDOI Listing
September 2021

Validation of proton dose calculation on scatter corrected 4D cone beam computed tomography using a porcine lung phantom.

Phys Med Biol 2021 08 30;66(17). Epub 2021 Aug 30.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Proton therapy treatment for lungs remains challenging as images enabling the detection of inter- and intra-fractional motion, which could be used for proton dose adaptation, are not readily available. 4D computed tomography (4DCT) provides high image quality but is rarely available in-room, while in-room 4D cone beam computed tomography (4DCBCT) suffers from image quality limitations stemming mostly from scatter detection. This study investigated the feasibility of using virtual 4D computed tomography (4DvCT) as a prior for a phase-per-phase scatter correction algorithm yielding a 4D scatter corrected cone beam computed tomography image (4DCBCT), which can be used for proton dose calculation. 4DCT and 4DCBCT scans of a porcine lung phantom, which generated reproducible ventilation, were acquired with matching breathing patterns. Diffeomorphic Morphons, a deformable image registration algorithm, was used to register the mid-position 4DCT to the mid-position 4DCBCT and yield a 4DvCT. The 4DCBCT was reconstructed using motion-aware reconstruction based on spatial and temporal regularization (MA-ROOSTER). Successively for each phase, digitally reconstructed radiographs of the 4DvCT, simulated without scatter, were exploited to correct scatter in the corresponding CBCT projections. The 4DCBCTwas then reconstructed with MA-ROOSTER using the corrected CBCT projections and the same settings and deformation vector fields as those already used for reconstructing the 4DCBCT. The 4DCBCTand the 4DvCT were evaluated phase-by-phase, performing proton dose calculations and comparison to those of a ground truth 4DCT by means of dose-volume-histograms (DVH) and gamma pass-rates (PR). For accumulated doses, DVH parameters deviated by at most 1.7% in the 4DvCT and 2.0% in the 4DCBCTcase. The gamma PR for a (2%, 2 mm) criterion with 10% threshold were at least 93.2% (4DvCT) and 94.2% (4DCBCT), respectively. The 4DCBCTtechnique enabled accurate proton dose calculation, which indicates the potential for applicability to clinical 4DCBCT scans.
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http://dx.doi.org/10.1088/1361-6560/ac16e9DOI Listing
August 2021

Proton range uncertainty reduction benefits for skull base tumors in terms of normal tissue complication probability (NTCP) and healthy tissue doses.

Med Phys 2021 Sep 29;48(9):5356-5366. Epub 2021 Jul 29.

Division of Radiation Biophysics, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Purpose: Proton therapy allows for more conformal dose distributions and lower organ at risk and healthy tissue doses than conventional photon-based radiotherapy, but uncertainties in the proton range currently prevent proton therapy from making full use of these advantages. Numerous developments therefore aim to reduce such range uncertainties. In this work, we quantify the benefits of reductions in range uncertainty for treatments of skull base tumors.

Methods: The study encompassed 10 skull base patients with clival tumors. For every patient, six treatment plans robust to setup errors of 2 mm and range errors from 0% to 5% were created. The determined metrics included the brainstem and optic chiasm normal tissue complication probability (NTCP) with the endpoints of necrosis and blindness, respectively, as well as the healthy tissue volume receiving at least 70% of the prescription dose.

Results: A range uncertainty reduction from the current level of 4% to a potentially achievable level of 1% reduced the probability of brainstem necrosis by up to 1.3 percentage points in the nominal scenario in which neither setup nor range errors occur and by up to 2.9 percentage points in the worst-case scenario. Such a range uncertainty reduction also reduced the optic chiasm NTCP with the endpoint of blindness by up to 0.9 percentage points in the nominal scenario and by up to 2.2 percentage points in the worst-case scenario. The decrease in the healthy tissue volume receiving at least 70% of the prescription dose ranged from -7.8 to 24.1 cc in the nominal scenario and from -3.4 to 38.4 cc in the worst-case scenario.

Conclusion: The benefits quantified as part of this study serve as a guideline of the OAR and healthy tissue dose benefits that range monitoring techniques may be able to achieve. Benefits were observed between all levels of range uncertainty. Even smaller range uncertainty reductions may therefore be beneficial.
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http://dx.doi.org/10.1002/mp.15097DOI Listing
September 2021

An empirical artifact correction for proton computed tomography.

Phys Med 2021 Jun 28;86:57-65. Epub 2021 May 28.

Department of Medical Physics, Fakultät für Physik, Ludwig-Maximilians-Universität München (LMU Munich), Am Coulombwall 1, Garching bei München, Germany. Electronic address:

Purpose: To reduce image artifacts of proton computed tomography (pCT) from a preclinical scanner, for imaging of the relative stopping power (RSP) needed for particle therapy treatment planning using a simple empirical artifact correction method.

Methods: We adapted and employed a correction method previously used for beam-hardening correction in x-ray CT which makes use of a single scan of a custom-built homogeneous phantom with known RSP. Exploiting the linearity of the filtered backprojection operation, a function was found which corrects water-equivalent path lengths (RSP line integrals) in experimental scans using a prototype pCT scanner. The correction function was applied to projection values of subsequent scans of a homogeneous water phantom, a sensitometric phantom with various inserts and an anthropomorphic head phantom. Data were acquired at two different incident proton energies to test the robustness of the method.

Results: Inaccuracies in the detection process caused an offset and known ring artifacts in the water phantom which were considerably reduced using the proposed method. The mean absolute percentage error (MAPE) of mean RSP values of all inserts of the sensitometric phantom and the water phantom was reduced from 0.87% to 0.44% and from 0.86% to 0.48% for the two incident energies respectively. In the head phantom a clear reduction of artifacts was observed.

Conclusions: Image artifacts of experimental pCT scans with a prototype scanner could substantially be reduced both in homogeneous, heterogeneous and anthropomorphic phantoms. RSP accuracy was also improved.
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http://dx.doi.org/10.1016/j.ejmp.2021.05.018DOI Listing
June 2021

Measurement-based range evaluation for quality assurance of CBCT-based dose calculations in adaptive proton therapy.

Med Phys 2021 Aug 29;48(8):4148-4159. Epub 2021 Jun 29.

Department of Radiation Oncology, University Hospital, LMU Munich, 81377, Munich, Germany.

Purpose: The implementation of volumetric in-room imaging for online adaptive radiotherapy makes extensive testing of this image data for treatment planning necessary. Especially for proton beams the higher sensitivity to stopping power properties of the tissue results in more stringent requirements. Current approaches mainly focus on recalculation of the plans on the new image data, lacking experimental verification, and ignoring the impact on the plan re-optimization process. The aim of this study was to use gel and film dosimetry coupled with a three-dimensional (3D) printed head phantom (based on the planning CT of the patient) for 3D range verification of intensity-corrected cone beam computed tomography (CBCT) image data for adaptive proton therapy.

Methods: Single field uniform dose pencil beam scanning proton plans were optimized for three different patients on the patients' planning CT (planCT) and the patients' intensity-corrected CBCT (scCBCT) for the same target volume using the same optimization constraints. The CBCTs were corrected on projection level using the planCT as a prior. The dose optimized on planCT and recalculated on scCBCT was compared in terms of proton range differences (80% distal fall-off, recalculation). Moreover, the dose distribution resulting from recalculation of the scCBCT-optimized plan on the planCT and the original planCT dose distribution were compared (simulation). Finally, the two plans of each patient were irradiated on the corresponding patient-specific 3D printed head phantom using gel dosimetry inserts for one patient and film dosimetry for all three patients. Range differences were extracted from the measured dose distributions. The measured and the simulated range differences were corrected for range differences originating from the initial plans and evaluated.

Results: The simulation approach showed high agreement with the standard recalculation approach. The median values of the range differences of these two methods agreed within 0.1 mm and the interquartile ranges (IQRs) within 0.3 mm for all three patients. The range differences of the film measurement were accurately matching with the simulation approach in the film plane. The median values of these range differences deviated less than 0.1 mm and the IQRs less than 0.4 mm. For the full 3D evaluation of the gel range differences, the median value and IQR matched those of the simulation approach within 0.7 and 0.5 mm, respectively. scCBCT- and planCT-based dose distributions were found to have a range agreement better than 3 mm (median and IQR) for all considered scenarios (recalculation, simulation, and measurement).

Conclusions: The results of this initial study indicate that an online adaptive proton workflow based on scatter-corrected CBCT image data for head irradiations is feasible. The novel presented measurement- and simulation-based method was shown to be equivalent to the standard literature recalculation approach. Additionally, it has the capability to catch effects of image differences on the treatment plan optimization. This makes the measurement-based approach particularly interesting for quality assurance of CBCT-based online adaptive proton therapy. The observed uncertainties could be kept within those of the registration and positioning. The proposed validation could also be applied for other alternative in-room images, e.g. for MR-based pseudoCTs.
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http://dx.doi.org/10.1002/mp.14995DOI Listing
August 2021

Assessment of the Sun Nuclear ArcCHECK to detect errors in 6MV FFF VMAT delivery of brain SABR using ROC analysis.

J Appl Clin Med Phys 2021 Jun 21;22(6):35-44. Epub 2021 May 21.

Irving K. Barber Faculty of Science, University of British Columbia, Okanagan Campus, Kelowna, BC, Canada.

Institutions use a range of different detector systems for patient-specific quality assurance (QA) measurements conducted to assure that the dose delivered by a patient's radiotherapy treatment plan matches the calculated dose distribution. However, the ability of different detectors to detect errors from different sources is often unreported. This study contains a systematic evaluation of Sun Nuclear's ArcCHECK in terms of the detectability of potential machine-related treatment errors. The five investigated sources of error were multileaf collimator (MLC) leaf positions, gantry angle, collimator angle, jaw positions, and dose output. The study encompassed the clinical treatment plans of 29 brain cancer patients who received stereotactic ablative radiotherapy (SABR). Six error magnitudes were investigated per source of error. In addition, the Eclipse AAA beam model dosimetric leaf gap (DLG) parameter was varied with four error magnitudes. Error detectability was determined based on the area under the receiver operating characteristic (ROC) curve (AUC). Detectability of DLG errors was good or excellent (AUC >0.8) at an error magnitude of at least ±0.4 mm, while MLC leaf position and gantry angle errors reached good or excellent detectability at error magnitudes of at least 1.0 mm and 0.6°, respectively. Ideal thresholds, that is, gamma passing rates, to maximize sensitivity and specificity ranged from 79.1% to 98.7%. The detectability of collimator angle, jaw position, and dose output errors was poor for all investigated error magnitudes, with an AUC between 0.5 and 0.6. The ArcCHECK device's ability to detect errors from treatment machine-related sources was evaluated, and ideal gamma passing rate thresholds were determined for each source of error. The ArcCHECK was able to detect errors in DLG value, MLC leaf positions, and gantry angle. The ArcCHECK was unable to detect the studied errors in collimator angle, jaw positions, and dose output.
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http://dx.doi.org/10.1002/acm2.13276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200516PMC
June 2021

Validation of the collapsed cone algorithm for HDR liver brachytherapy against Monte Carlo simulations.

Brachytherapy 2021 Jul-Aug;20(4):936-947. Epub 2021 May 15.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Garching, Germany. Electronic address:

Purpose: To validate the collapsed cone (CC) algorithm against Monte Carlo (MC) simulations for model-based dose calculations in high-dose-rate (HDR) liver brachytherapy.

Methods And Materials: Doses for liver brachytherapy treatment plans of 10 cases were retrospectively recalculated with a model-based approach using Monte Carlo n-Particle Code (MCNP) 6 (Dm,m-MC) and Oncentra Brachy ACE (Dm,m-ACE). Tissue segmentation consisted of assigning uniform compositions and mass densities to predefined Hounsfield Unit (HU) thresholds. Resulting doses were compared according to dose volume histogram parameters typical for clinical routine. These included the percentage liver volume receiving 5 Gy (V5Gy) or 10 Gy (V10Gy), the maximum dose to one cubic centimeter (D1cc) of organs at risk, the clinical target volume (CTV) fractions receiving 150% (V150), 100% (V100), 95% (V95) and 90% (V90) of the prescribed dose and the absolute doses to 95% (D95) and 90% (D90) of the CTV volumes.

Results: Doses from Oncentra Brachy ACE agreed well with MC simulations. Differences were seen far from the source, in low-density regions and bone structures. Median percentage deviations were 1.1% for the liver V5Gy and 0.4% for the liver V10Gy, with deviations of largest magnitude amounting to 2.2% and 1.0%, respectively. Organs at risk had median deviations ranging from 0.3% to 1.5% for D1cc, with outliers ranging up to 4.6%. CTV volume parameter deviations ranged between -1.5% and 0.5%, dose parameter deviations ranged mostly between -2% and 1%, with two outliers at -4.0% and -3.4% for a small CTV.
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http://dx.doi.org/10.1016/j.brachy.2021.03.018DOI Listing
May 2021

Performance evaluation of a staggered three-layer DOI PET detector using a 1 mm LYSO pitch with PETsys TOFPET2 ASIC: comparison of HAMAMATSU and KETEK SiPMs.

Phys Med Biol 2021 Jun 16;66(12). Epub 2021 Jun 16.

Ludwig-Maximilians-Universität, Munich, Germany.

In this study, we propose a staggered three-layer depth-of-interaction (DOI) detector with a 1 mm crystal pitch and 19.8 mm total crystal thickness for a high-resolution and high-sensitivity small animal in-beam PET scanner. A three-layered stacked LYSO scintillation array (0.9 × 0.9 × 6.6 mmcrystals, 23 × 22 mmsurface area) read out by a SiPM array (8 × 8 channels, 3 × 3 mmactive area/channel and 50m microcell size) with data acquisition, signal processing and digitization performed using the PETsys Electronics Evaluations kit (based on the TOFPET v2c ASIC) builds a DOI LYSO detector block. The performance of the DOI detector was evaluated in terms of crystal resolvability, energy resolution, and coincidence resolving time (CRT). A comparative performance evaluation of the staggered three-layer LYSO block was conducted with two different SiPM arrays from KETEK and HAMAMATSU. 100% (KETEK) and 99.8% (HAMAMATSU) of the crystals were identified, by using a flood irradiation the front- and back-side. The average energy resolutions for the 1st, 2nd, and 3rd layers were 16.5 (±2.3)%, 20.9(±4.0)%, and 32.7 (±21.0)% (KETEK) and 19.3 (±3.5)%, 21.2 (±4.1)%, and 26.6 (±10.3)% (HAMAMATSU) for the used SiPM arrays. The measured CRTs (FWHM) for the 1st, 2nd, and 3rd layers were 532 (±111) ps, 463 (±108) ps, and 447 (±111) ps (KETEK) and 402 (±46) ps, 392 (±54) ps, and 408 (±196) ps (HAMAMATSU). In conclusion, the performance of the staggered three-layer DOI detector with 1 mm LYSO pitch and 19.8 mm total crystal thickness was fully characterized. The feasibility of a highly performing readout of a high resolution DOI PET detector via SiPM arrays from KETEK and HAMAMATSU employing the PETsys TOFPET v2c ASIC could be demonstrated.
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http://dx.doi.org/10.1088/1361-6560/abfbf3DOI Listing
June 2021

On the potential of ROI imaging in x-ray CT - A comparison of novel dynamic beam attenuators with current technology.

Med Phys 2021 Jul 2;48(7):3479-3499. Epub 2021 Jun 2.

Siemens Healthcare GmbH, Forchheim, Germany.

Purpose: In this work, we explore the potential of region-of-interest (ROI) imaging in x-ray computed tomography (CT). Using two dynamic beam attenuator (DBA) concepts for fluence field modulation (FFM) previously developed, we investigate and evaluate the potential dose savings in comparison with current FFM technology.

Methods: ROI imaging is a special application of FFM where the bulk of x-ray radiation is propagated toward a certain anatomical target (ROI), specified by the imaging task, while the surrounding tissue is spared from radiation. We introduce a criterion suitable to quantitatively describe the balance between image quality inside an ROI and total radiation dose with respect to a given ROI imaging task. It accounts for the mean image variance at the ROI and the effective patient dose calculated from Monte Carlo simulations. The criterion is further used to compile task-specific DBA trajectories determining the primary x-ray fluence, and eventually used for comparing different FFM techniques, namely the sheet-based dynamic beam attenuator (sbDBA), the z-aligned sbDBA (z-sbDBA), and an adjustable static operation mode of the z-sbDBA. Furthermore, two static bowtie filters and the influence of tube current modulation (TCM) are included in the comparison.

Results: Our findings demonstrate by simulations that the presented trajectory optimization method determines reasonable DBA trajectories. The influence of TCM is strongly depending on the imaging task. The narrow bowtie filter allows for dose reductions of about 10% compared to the regular bowtie filter in the considered ROI imaging tasks. The DBAs are shown to realize substantially larger dose reductions. In our cardiac imaging scenario, the DBAs can reduce the effective dose by about 30% (z-sbDBA) or 60% (sbDBA). We can further verify that the noise characteristics are not adversely affected by the DBAs.

Conclusion: Our research demonstrates that ROI imaging using the presented DBA concepts is a promising technique toward a more patient- and task-specific CT imaging requiring lower radiation dose. Both the sbDBA and the z-sbDBA are potential technical solutions for realizing ROI imaging in x-ray CT.
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http://dx.doi.org/10.1002/mp.14879DOI Listing
July 2021

The impact of path estimates in iterative ion CT reconstructions for clinical-like cases.

Phys Med Biol 2021 04 23;66(9). Epub 2021 Apr 23.

Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Garching b. München, Germany.

Ion computed tomography (CT) promises to mitigate range uncertainties inherent in the conversion of x-ray Hounsfield units into ion relative stopping power (RSP) for ion beam therapy treatment planning. To improve accuracy and spatial resolution of ion CT by accounting for statistical multiple Coulomb scattering deflection of the ion trajectories from a straight line path (SLP), the most likely path (MLP) and the cubic spline path (CSP) have been proposed. In this work, we use FLUKA Monte Carlo simulations to investigate the impact of these path estimates in iterative tomographic reconstruction algorithms for proton, helium and carbon ions. To this end the ordered subset simultaneous algebraic reconstruction technique was used and coupled with a total variation superiorization (TVS). We evaluate the image quality and dose calculation accuracy in proton therapy treatment planning of cranial patient anatomies. CSP and MLP generally yielded nearly equal image quality with an average RSP relative error improvement over the SLP of 0.6%, 0.3% and 0.3% for proton, helium and carbon ion CT, respectively. Bone and low density materials have been identified as regions of largest enhancement in RSP accuracy. Nevertheless, only minor differences in dose calculation results were observed between the different models and relative range errors of better than 0.5% were obtained in all cases. Largest improvements were found for proton CT in complex scenarios with strong heterogeneities along the beam path. The additional TVS provided substantially reduced image noise, resulting in improved image quality in particular for soft tissue regions. Employing the CSP and MLP for iterative ion CT reconstructions enabled improved image quality over the SLP even in realistic and heterogeneous patient anatomy. However, only limited benefit in dose calculation accuracy was obtained even though an ideal detector system was simulated.
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http://dx.doi.org/10.1088/1361-6560/abf1ffDOI Listing
April 2021

Distant metastasis time to event analysis with CNNs in independent head and neck cancer cohorts.

Sci Rep 2021 03 19;11(1):6418. Epub 2021 Mar 19.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, 81377, Germany.

Deep learning models based on medical images play an increasingly important role for cancer outcome prediction. The standard approach involves usage of convolutional neural networks (CNNs) to automatically extract relevant features from the patient's image and perform a binary classification of the occurrence of a given clinical endpoint. In this work, a 2D-CNN and a 3D-CNN for the binary classification of distant metastasis (DM) occurrence in head and neck cancer patients were extended to perform time-to-event analysis. The newly built CNNs incorporate censoring information and output DM-free probability curves as a function of time for every patient. In total, 1037 patients were used to build and assess the performance of the time-to-event model. Training and validation was based on 294 patients also used in a previous benchmark classification study while for testing 743 patients from three independent cohorts were used. The best network could reproduce the good results from 3-fold cross validation [Harrell's concordance indices (HCIs) of 0.78, 0.74 and 0.80] in two out of three testing cohorts (HCIs of 0.88, 0.67 and 0.77). Additionally, the capability of the models for patient stratification into high and low-risk groups was investigated, the CNNs being able to significantly stratify all three testing cohorts. Results suggest that image-based deep learning models show good reliability for DM time-to-event analysis and could be used for treatment personalisation.
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http://dx.doi.org/10.1038/s41598-021-85671-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979766PMC
March 2021

A comprehensive Monte Carlo study of out-of-field secondary neutron spectra in a scanned-beam proton therapy gantry room.

Z Med Phys 2021 May 20;31(2):215-228. Epub 2021 Feb 20.

LMU Munich, Faculty of Physics, Department of Medical Physics, Am Coulombwall 1, 85748 Garching bei München, Germany.

Purpose: To simulate secondary neutron radiation fields that had been measured at different relative positions during phantom irradiation inside a scanning proton therapy gantry treatment room. Further, to identify origin, energy distribution, and angular emission of the secondary neutrons as a function of proton beam energy.

Methods: The FLUKA Monte Carlo code was used to model the relevant parts of the treatment room in a scanned pencil beam proton therapy gantry including shielding walls, floor, major metallic gantry-components, patient table, and a homogeneous PMMA target. The proton beams were modeled based on experimental beam ranges in water and spot shapes in air. Neutron energy spectra were simulated at 0°, 45°, 90° and 135° relative to the beam axis at 2m distance from isocenter for monoenergetic 11×11cm fields from 200MeV, 140MeV, 75MeV initial proton beams, as well as for 118MeV protons with a 5cm thick PMMA range shifter. The total neutron spectra were scored for these four positions and proton energies. FLUKA neutron spectra simulations were crosschecked with Geant4 simulations using initial proton beam properties from FLUKA-generated phase spaces. Additionally, the room-components generating secondary neutrons in the room and their contributions to the total spectrum were identified and quantified.

Results: FLUKA and Geant4 simulated neutron spectra showed good general agreement with published measurements in the whole simulated neutron energy range of 10 to 10MeV. As in previous studies, high-energy (E≥19.6MeV) neutrons from the phantom are most prevalent along 0°, while thermalized (1meV≤E<0.4eV) and fast (100keV≤E<19.4MeV) neutrons dominate the spectra in the lateral and backscatter direction. The iron of the large bending magnet and its counterweight mounted on the gantry were identified as the most determinant sources of secondary fast-neutrons, which have been lacking in simplified room simulations.

Conclusions: The results helped disentangle the origin of secondary neutrons and their dominant contributions and were strengthened by the fact that a cross comparison was made using two independent Monte Carlo codes. The complexity of such room model can in future be limited using the result. They may further be generalized in that they can be used for an assessment of neutron fields, possibly even at facilities where detailed neutron measurements and simulations cannot be performed. They may also help to design future proton therapy facilities and to reduce unwanted radiation doses from secondary neutrons to patients.
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http://dx.doi.org/10.1016/j.zemedi.2021.01.001DOI Listing
May 2021

Enhancement of the ionoacoustic effect through ultrasound and photoacoustic contrast agents.

Sci Rep 2021 Feb 1;11(1):2725. Epub 2021 Feb 1.

Department for Medical Physics, Ludwig-Maximilians-Universität München (LMU Munich), 85748, Garching b. München, Germany.

The characteristic depth dose deposition of ion beams, with a maximum at the end of their range (Bragg peak) allows for local treatment delivery, resulting in better sparing of the adjacent healthy tissues compared to other forms of external beam radiotherapy treatments. However, the optimal clinical exploitation of the favorable ion beam ballistic is hampered by uncertainties in the in vivo Bragg peak position. Ionoacoustics is based on the detection of thermoacoustic pressure waves induced by a properly pulsed ion beam (e.g., produced by modern compact accelerators) to image the irradiated volume. Co-registration between ionoacoustics and ultrasound imaging offers a promising opportunity to monitor the ion beam and patient anatomy during the treatment. Nevertheless, the detection of the ionoacoustic waves is challenging due to very low pressure amplitudes and frequencies (mPa/kHz) observed in clinical applications. We investigate contrast agents to enhance the acoustic emission. Ultrasound microbubbles are used to increase the ionoacoustic frequency around the microbubble resonance frequency. Moreover, India ink is investigated as a possible mean to enhance the signal amplitude by taking advantage of additional optical photon absorption along the ion beam and subsequent photoacoustic effect. We report amplitude increase of up to 200% of the ionoacoustic signal emission in the MHz frequency range by combining microbubbles and India ink contrast agents.
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http://dx.doi.org/10.1038/s41598-021-81964-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851171PMC
February 2021

Proof of concept image artifact reduction by energy-modulated proton computed tomography (EMpCT).

Phys Med 2021 Jan 20;81:237-244. Epub 2021 Jan 20.

Department of Medical Physics, Fakultät für Physik, Ludwig-Maximilians-Universität München (LMU Munich), Am Coulombwall 1, Garching bei München, Germany. Electronic address:

Purpose: To reduce imaging artifacts and improve image quality of a specific proton computed tomography (pCT) prototype scanner by combining pCT data acquired at two different incident proton energies to avoid protons stopping in sub-optimal detector sections.

Methods: Image artifacts of a prototype pCT scanner are linked to protons stopping close to internal structures of the scanner's multi-stage energy detector. We aimed at avoiding such protons by acquiring pCT data at two different incident energies and combining the data in post-processing from which artifact-reduced images of the relative stopping power (RSP) were calculated. Energy-modulated pCT (EMpCT) images were assessed visually and quantitatively and compared to the original mono-energetic images in terms of RSP accuracy and noise. Data were acquired for a homogeneous water phantom.

Results: RSP images reconstructed from the mono-energetic datasets displayed local image artifacts which were ring-shaped due to the homogeneity of the phantom. The merged EMpCT dataset achieved a superior visual image quality with reduced artifacts and only minor remaining rings. The inter-quartile range (25/75) of RSP values was reduced from 0.7% with the current standard acquisition to 0.2% with EMpCT due to the reduction of ring artifacts. In this study, dose was doubled compared to a standard scan, but we discuss strategies to reduce excess dose.

Conclusions: EMpCT allows to effectively avoid regions of the energy detector that cause image artifacts. Thereby, image quality is improved.
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http://dx.doi.org/10.1016/j.ejmp.2020.12.012DOI Listing
January 2021

Developments in deep learning based corrections of cone beam computed tomography to enable dose calculations for adaptive radiotherapy.

Phys Imaging Radiat Oncol 2020 Jul 12;15:77-79. Epub 2020 Aug 12.

Department of Medical Physics/Oncology, Danish Centre for Particle Therapy, Aarhus University Hospital/Aarhus University, Denmark.

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http://dx.doi.org/10.1016/j.phro.2020.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807621PMC
July 2020

Incoming Editor-in-Chief.

Authors:
Katia Parodi

Phys Med Biol 2021 01 8;66(1):010301. Epub 2021 Jan 8.

Ludwig-Maximilians-Universität München, Munich, Germany.

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http://dx.doi.org/10.1088/1361-6560/abd3eeDOI Listing
January 2021

Dose quantification in carbon ion therapy using in-beam positron emission tomography.

Phys Med Biol 2020 12 5;65(23):235052. Epub 2020 Dec 5.

Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522, Australia. Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, NSW 2234, Australia.

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - C, C and O. A library of basis functions is constructed by simulating a range of monoenergetic C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the C, C, O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.
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http://dx.doi.org/10.1088/1361-6560/abaa23DOI Listing
December 2020

Anthropomorphic lung phantom based validation of in-room proton therapy 4D-CBCT image correction for dose calculation.

Z Med Phys 2020 Nov 25. Epub 2020 Nov 25.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München (LMU Munich), Garching, Germany. Electronic address:

Purpose: Ventilation-induced tumour motion remains a challenge for the accuracy of proton therapy treatments in lung patients. We investigated the feasibility of using a 4D virtual CT (4D-vCT) approach based on deformable image registration (DIR) and motion-aware 4D CBCT reconstruction (MA-ROOSTER) to enable accurate daily proton dose calculation using a gantry-mounted CBCT scanner tailored to proton therapy.

Methods: Ventilation correlated data of 10 breathing phases were acquired from a porcine ex-vivo functional lung phantom using CT and CBCT. 4D-vCTs were generated by (1) DIR of the mid-position 4D-CT to the mid-position 4D-CBCT (reconstructed with the MA-ROOSTER) using a diffeomorphic Morphons algorithm and (2) subsequent propagation of the obtained mid-position vCT to the individual 4D-CBCT phases. Proton therapy treatment planning was performed to evaluate dose calculation accuracy of the 4D-vCTs. A robust treatment plan delivering a nominal dose of 60Gy was generated on the average intensity image of the 4D-CT for an approximated internal target volume (ITV). Dose distributions were then recalculated on individual phases of the 4D-CT and the 4D-vCT based on the optimized plan. Dose accumulation was performed for 4D-vCT and 4D-CT using DIR of each phase to the mid position, which was chosen as reference. Dose based on the 4D-vCT was then evaluated against the dose calculated on 4D-CT both, phase-by-phase as well as accumulated, by comparing dose volume histogram (DVH) values (D, D, D, D) for the ITV, and by a 3D-gamma index analysis (global, 3%/3mm, 5Gy, 20Gy and 30Gy dose thresholds).

Results: Good agreement was found between the 4D-CT and 4D-vCT-based ITV-DVH curves. The relative differences ((CT-vCT)/CT) between accumulated values of ITV D, D, D and D for the 4D-CT and 4D-vCT-based dose distributions were -0.2%, 0.0%, -0.1% and -0.1%, respectively. Phase specific values varied between -0.5% and 0.2%, -0.2% and 0.5%, -3.5% and 1.5%, and -5.7% and 2.3%. The relative difference of accumulated D over the lungs was 2.3% and D for the phases varied between -5.4% and 5.8%. The gamma pass-rates with 5Gy, 20Gy and 30Gy thresholds for the accumulated doses were 96.7%, 99.6% and 99.9%, respectively. Phase-by-phase comparison yielded pass-rates between 86% and 97%, 88% and 98%, and 94% and 100%.

Conclusions: Feasibility of the suggested 4D-vCT workflow using proton therapy specific imaging equipment was shown. Results indicate the potential of the method to be applied for daily 4D proton dose estimation.
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http://dx.doi.org/10.1016/j.zemedi.2020.09.004DOI Listing
November 2020

Roadmap: proton therapy physics and biology.

Phys Med Biol 2020 Nov 23. Epub 2020 Nov 23.

Department of Radiation Medicine, Paul Scherrer Institute, CH-5232 Villigen PSI, Villigen, SWITZERLAND.

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200,000 patients have been treated with proton beams worldwide and the number of operating proton therapy facilities will soon reach one hundred. Proton therapy has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While proton therapy has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of proton therapy cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effects differ from photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because proton therapy treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in proton therapy categorized into four different themes, "improving efficiency", "improving planning and delivery", "improving imaging", and "improving patient selection".
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http://dx.doi.org/10.1088/1361-6560/abcd16DOI Listing
November 2020

Radioactive Beams in Particle Therapy: Past, Present, and Future.

Front Phys 2020 Aug;8:00326

Department of Experimental Physics-Medical Physics, Ludwig-Maximilians-Universität München, Munich, Germany.

Heavy ion therapy can deliver high doses with high precision. However, image guidance is needed to reduce range uncertainty. Radioactive ions are potentially ideal projectiles for radiotherapy because their decay can be used to visualize the beam. Positron-emitting ions that can be visualized with PET imaging were already studied for therapy application during the pilot therapy project at the Lawrence Berkeley Laboratory, and later within the EULIMA EU project, the GSI therapy trial in Germany, MEDICIS at CERN, and at HIMAC in Japan. The results show that radioactive ion beams provide a large improvement in image quality and signal-to-noise ratio compared to stable ions. The main hindrance toward a clinical use of radioactive ions is their challenging production and the low intensities of the beams. New research projects are ongoing in Europe and Japan to assess the advantages of radioactive ion beams for therapy, to develop new detectors, and to build sources of radioactive ions for medical synchrotrons.
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http://dx.doi.org/10.3389/fphy.2020.00326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116396PMC
August 2020

Variance-based sensitivity analysis for uncertainties in proton therapy: A framework to assess the effect of simultaneous uncertainties in range, positioning, and RBE model predictions on RBE-weighted dose distributions.

Med Phys 2021 Feb 18;48(2):805-818. Epub 2020 Dec 18.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, 81377, Germany.

Purpose: Treatment plans in proton therapy are more sensitive to uncertainties than in conventional photon therapy. In addition to setup uncertainties, proton therapy is affected by uncertainties in proton range and relative biological effectiveness (RBE). While to date a constant RBE of 1.1 is commonly assumed, the actual RBE is known to increase toward the distal end of the spread-out Bragg peak. Several models for variable RBE predictions exist. We present a framework to evaluate the combined impact and interactions of setup, range, and RBE uncertainties in a comprehensive, variance-based sensitivity analysis (SA).

Material And Methods: The variance-based SA requires a large number (10 -10 ) of RBE-weighted dose (RWD) calculations. Based on a particle therapy extension of the research treatment planning system CERR we implemented a fast, graphics processing unit (GPU) accelerated pencil beam modeling of patient and range shifts. For RBE predictions, two biological models were included: The mechanistic repair-misrepair-fixation (RMF) model and the phenomenological Wedenberg model. All input parameters (patient position, proton range, RBE model parameters) are sampled simultaneously within their assumed probability distributions. Statistical formalisms rank the input parameters according to their influence on the overall uncertainty of RBE-weighted dose-volume histogram (RW-DVH) quantiles and the RWD in every voxel, resulting in relative, normalized sensitivity indices (S = 0: noninfluential input, S = 1: only influential input). Results are visualized as RW-DVHs with error bars and sensitivity maps.

Results And Conclusions: The approach is demonstrated for two representative brain tumor cases and a prostate case. The full SA including RWD calculations took 39, 11, and 55 min, respectively. Range uncertainty was an important contribution to overall uncertainty at the distal end of the target, while the relatively smaller uncertainty inside the target was governed by biological uncertainties. Consequently, the uncertainty of the RW-DVH quantile D for the target was governed by range uncertainty while the uncertainty of the mean target dose was dominated by the biological parameters. The SA framework is a powerful and flexible tool to evaluate uncertainty in RWD distributions and DVH quantiles, taking into account physical and RBE uncertainties and their interactions. The additional information might help to prioritize research efforts to reduce physical and RBE uncertainties and could also have implications for future approaches to biologically robust planning and optimization.
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http://dx.doi.org/10.1002/mp.14596DOI Listing
February 2021

Porcine lung phantom-based validation of estimated 4D-MRI using orthogonal cine imaging for low-field MR-Linacs.

Phys Med Biol 2021 02 16;66(5):055006. Epub 2021 Feb 16.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Real-time motion monitoring of lung tumors with low-field magnetic resonance imaging-guided linear accelerators (MR-Linacs) is currently limited to sagittal 2D cine magnetic resonance imaging (MRI). To provide input data for improved intrafractional and interfractional adaptive radiotherapy, the 4D anatomy has to be inferred from data with lower dimensionality. The purpose of this study was to experimentally validate a previously proposed propagation method that provides continuous time-resolved estimated 4D-MRI based on orthogonal cine MRI for a low-field MR-Linac. Ex vivo porcine lungs were injected with artificial nodules and mounted in a dedicated phantom that allows for the simulation of periodic and reproducible breathing motion. The phantom was scanned with a research version of a commercial 0.35 T MR-Linac. Respiratory-correlated 4D-MRI were reconstructed and served as ground truth images. Series of interleaved orthogonal slices in sagittal and coronal orientation, intersecting the injected targets, were acquired at 7.3 Hz. Estimated 4D-MRI at 3.65 Hz were created in post-processing using the propagation method and compared to the ground truth 4D-MRI. Eight datasets at different breathing frequencies and motion amplitudes were acquired for three porcine lungs. The overall median (95[Formula: see text] percentile) deviation between ground truth and estimated deformation vector fields was 2.3 mm (5.7 mm), corresponding to 0.7 (1.6) times the in-plane imaging resolution (3.5 × 3.5 mm). Median (95[Formula: see text] percentile) estimated nodule position errors were 1.5 mm (3.8 mm) for nodules intersected by orthogonal slices and 2.1 mm (7.1 mm) for nodules located more than 2 cm away from either of the orthogonal slices. The estimation error depended on the breathing phase, the motion amplitude and the location of the estimated position with respect to the orthogonal slices. By using the propagation method, the 4D motion within the porcine lung phantom could be accurately and robustly estimated. The method could provide valuable information for treatment planning, real-time motion monitoring, treatment adaptation, and post-treatment evaluation of MR-guided radiotherapy treatments.
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http://dx.doi.org/10.1088/1361-6560/abc937DOI Listing
February 2021

Accounting for prompt gamma emission and detection for range verification in proton therapy treatment planning.

Phys Med Biol 2021 02 16;66(5):055005. Epub 2021 Feb 16.

Ludwig-Maximilians-Universität München, Department of Medical Physics, Munich, Germany. These authors have contributed to this work equally.

Prompt gamma (PG) imaging is widely investigated as one of the most promising methods for proton range verification in proton therapy. The performance of this technique is affected by several factors like tissue heterogeneity, number of protons in the considered pencil beam and the detection device. Our previous work proposed a new treatment planning concept which boosts the number of protons of a few PG monitoring-friendly pencil beams (PBs), selected on the basis of two proposed indicators quantifying the conformity between the dose and PG at the emission level, above the desired detectability threshold. To further explore this method at the detection level, in this work we investigated the response of a knife-edge slit PG camera which was deployed in the first clinical application of PG to proton therapy monitoring. The REGistration Graphical User Interface (REGGUI) is employed to simulate the PG emission, PG detection as well as the corresponding dose distribution. As the PG signal detected by this kind of PG camera is sensitive to the relative position of the camera and PG signal falloff, we optimized our PB selection method for this camera by introducing a new camera position indicator identifying whether the expected falloff of the PG signal is centered in the field of view of the camera or not. Our camera-adapted PB selection method is investigated using computed tomography (CT) scans at two different treatment time points of a head and neck, and a prostate cancer patient under scenarios considering different statistics level. The results show that a precision of 0.8 mm for PG falloff identification can be achieved when a PB has more than 2 × 10 primary protons. Except for one case due to unpredictable and comparably large anatomical changes, the PG signals of most of the PBs recommended by all our indicators are observed to be reliable for proton range verification with deviations between the inter-fractional shift of proton range (as deduced from the PB dose distribution) and the detected PG signal within 2.0 mm. In contrast, a shift difference up to 9.6 mm has been observed for the rejected PBs. The magnitude of the proton range shift due to the inter-fractional anatomical changes is observed to be up to 23 mm. The proposed indicators are shown to be valuable for identifying and recommending reliable PBs to create new PG monitoring-friendly TPs. Comparison between our PB boosting method and the alternative PB aggregation, which combines the signal of nearby PBs to reach the desired counting statistics, is also discussed.
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http://dx.doi.org/10.1088/1361-6560/abc939DOI Listing
February 2021

Animal tissue-based quantitative comparison of dual-energy CT to SPR conversion methods using high-resolution gel dosimetry.

Phys Med Biol 2020 Sep 30. Epub 2020 Sep 30.

Department of Medical Physics, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, GERMANY.

Dual-energy computed tomography (DECT) has been shown to allow for more accurate ion therapy treatment planning by improving the estimation of tissue stopping power ratio (SPR) relative to water, among other tissue properties. In this study, we measured and compared the accuracy of SPR values derived using both dual- and single-energy CT (SECT) based on different published conversion algorithms. For this purpose, a phantom setup containing either fresh animal soft tissue samples (beef, pork) and a water reference or tissue equivalent plastic materials was designed and irradiated in a clinical proton therapy facility. Dosimetric polymer gel was positioned downstream of the samples to obtain a three-dimensional proton range distribution with high spatial resolution. The mean proton range in gel for each tissue relative to the water sample was converted to a SPR value. Additionally, the homogeneous samples were probed with a variable water column encompassed by two ionization chambers to benchmark the SPR accuracy of the gel dosimetry. The SPR values measured with both methods were consistent with a mean deviation of 0.2%, but the gel dosimetry captured range variations up to 5 mm within individual samples. Across all fresh tissue samples the SECT approach yielded significantly greater mean absolute deviations from the SPR deduced using gel range measurements, with an average difference of 1.2%, compared to just 0.3% for the most accurate DECT-based algorithm. These results show a significant advantage of DECT over SECT for stopping power prediction in a realistic setting, and for the first time allow to compare a large set of methods under the same conditions.
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http://dx.doi.org/10.1088/1361-6560/abbd14DOI Listing
September 2020

3D Compton image reconstruction method for whole gamma imaging.

Phys Med Biol 2020 11 24;65(22):225038. Epub 2020 Nov 24.

National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.

Compton imaging or Compton camera imaging has been studied well, but its advantages in nuclear medicine and molecular imaging have not been demonstrated yet. Therefore, the aim of this work was to compare Compton imaging with positron emission tomography (PET) by using the same imaging platform of whole gamma imaging (WGI). WGI is a concept that combines PET with Compton imaging by inserting a scatterer ring into a PET ring. This concept utilizes diverse types of gamma rays for 3D tomographic imaging. In this paper, we remodeled our previous WGI prototype for small animal imaging, and we developed an image reconstruction method based on a list-mode ordered subset expectation maximization algorithm incorporating detector response function modeling, random correction and normalization (sensitivity correction) for either PET and Compton imaging. To the best of our knowledge, this is the world's first realization of a full-ring Compton imaging system. We selected Zr as an imaging target because a Zr nuclide emits a 909 keV single-gamma ray as well as a positron, and we can directly compare Compton imaging of 909 keV photons with PET, a well-established modality. We measured a cylindrical phantom and a small rod phantom filled with Zr solutions of 10.3 MBq and 10.2 MBq activity, respectively, for 1 h each. The uniform radioactivity distribution of the cylindrical phantom was reconstructed with normalization in both PET and Compton imaging. Coefficients of variation for region-of-interest values were 4.2% for Compton imaging and 3.3% for PET; the difference might be explained by the difference in the detected count number. The small rod phantom experiment showed that the WGI Compton imaging had spatial resolution better than 3.0 mm at the peripheral region although the center region had lower resolution. PET resolved 2.2 mm rods clearly at any location. We measured a mouse for 1 h, 1 d after injection of 9.8 MBq Zr oxalate. The Zr assimilated in the mouse bony structures was clearly depicted, and Compton imaging results agreed well with PET images, especially for the region inside the scatterer ring. In conclusion, we demonstrated the performance of WGI using the developed Compton image reconstruction method. We realized Compton imaging with a quality approaching that of PET, which is supporting a future expectation that Compton imaging outperforms PET.
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http://dx.doi.org/10.1088/1361-6560/abb92eDOI Listing
November 2020

The role of Monte Carlo simulation in understanding the performance of proton computed tomography.

Z Med Phys 2020 Aug 11. Epub 2020 Aug 11.

Department of Radiation Oncology, Department of Medical Physics, University Hospital, LMU Munich, Munich, Germany; German Cancer Consortium, (DKTK), Munich, Germany; Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München (LMU Munich), Garching b. München, Germany.

Proton computed tomography (pCT) is a promising tomographic imaging modality allowing direct reconstruction of proton relative stopping power (RSP) required for proton therapy dose calculation. In this review article, we aim at highlighting the role of Monte Carlo (MC) simulation in pCT studies. After describing the requirements for performing proton computed tomography and the various pCT scanners actively used in recent research projects, we present an overview of available MC simulation platforms. The use of MC simulations in the scope of investigations of image reconstruction, and for the evaluation of optimal RSP accuracy, precision and spatial resolution omitting detector effects is then described. In the final sections of the review article, we present specific applications of realistic MC simulations of an existing pCT scanner prototype, which we describe in detail.
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http://dx.doi.org/10.1016/j.zemedi.2020.06.006DOI Listing
August 2020

The z-sbDBA, a new concept for a dynamic sheet-based fluence field modulator in x-ray CT.

Med Phys 2020 Oct 28;47(10):4827-4837. Epub 2020 Aug 28.

Siemens Healthcare GmbH, Siemensstr. 3, Forchheim, 91301, Germany.

Purpose: We present a new concept for dynamic fluence field modulation (FFM) in x-ray computed tomography (CT). The so-called z-aligned sheet-based dynamic beam attenuator (z-sbDBA) is developed to dynamically compensate variations in patient attenuation across the fan beam and the projection angle. The goal is to enhance image quality and to reduce patient radiation dose.

Methods: The z-sbDBA consists of an array of attenuation sheets aligned along the direction. In neutral position, the array is focused toward the focal spot. Tilting the z-sbDBA defocuses the sheets, thus reducing the transmission for larger fan beam angles. The structure of the z-sbDBA significantly differs from the previous sheet-based dynamic beam attenuator (sbDBA) in two features: (a) The sheets of the z-sbDBA are aligned parallel to the detector rows, and (b) the height of the sheets increases from the center toward larger fan beam angles. We built a motor actuated prototype of the z-sbDBA integrated into a clinical CT scanner. In experiments, we investigated its feasibility for FFM. We compared the z-sbDBA to common CT bowtie filters in terms of the spectral dependency of the transmission and possible image variance distribution in reconstructed phantom images. Additionally, the potential radiation dose saving using z-sbDBA for region-of-interest (ROI) imaging was studied.

Results: Our experimental results confirm that the z-sbDBA can realize variable transmission profiles of the radiation fluence by only small tilts. Compared to the sbDBA, the z-sbDBA can mitigate some practical and mechanical issues. In comparison to bowtie filters, the spectral dependency is considerably reduced when using the z-sbDBA. Likewise, more homogeneous image variance distributions can be attained in reconstructed phantom images. The z-sbDBA allows controlling the spatial image variance distribution which makes it suitable for ROI imaging. Our comparison on ROI imaging reveals skin dose reductions of up to 35% at equal ROI image quality by using the z-sbDBA.

Conclusion: Our new concept for FFM in x-ray CT, the z-sbDBA, was experimentally validated on a clinical CT scanner. It facilitates dynamic FFM by realizing variable transmission profiles across the fan beam angle on a projection-wise basis. This key feature allows for substantial improvements in image quality, a reduction in patient radiation dose, and additionally provides a technical solution for ROI imaging.
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http://dx.doi.org/10.1002/mp.14430DOI Listing
October 2020

Radiation protection modelling for 2.5 Petawatt-laser production of ultrashort x-ray, proton and ion bunches: Monte Carlo model of the Munich CALA facility.

J Radiol Prot 2020 Jul 23. Epub 2020 Jul 23.

Department of Medical Physics, Ludwig-Maximilians-Universitaet Muenchen, Am Coulombwall 1, 85748 Garching, Munich, Bavaria, GERMANY.

The 'Centre for Advanced Laser Applications' (CALA) is a new research institute for laser-based accelerationelectron beams for brilliant x-ray generation, laser-driven sub-nanosecond bunches of protons and heavy ionsbiomedical applications like imaging and tumour therapy as well as for nuclear and high-field physics. The radiation sources emerging from experiments using the up to 2.5 petawatt laser pulses with 25 femtosecond duration will be mixed particle-species of high intensity, high energy and pulsed, thus posing new challenges compared to conventional radiation protection. Such worldwide pioneering laser experiments result in source characteristics that require careful a-priori radiation safety simulations. The FLUKA Monte-Carlo code was used to model the five CALA experimental caves, including the corridors, halls and air spaces surrounding the caves. Beams of electrons (< 5 GeV), protons (< 200 MeV), C (< 400 MeV/u) and 97Au (< 10 MeV/u) ions were simulated using spectra, divergences and bunch-charges based on expectations from recent scientific progress. Simulated dose rates locally can exceed 1.5 kSv/h inside beam dumps. Vacuum pipes in the cave walls for laser transport and extraction channels for the generated X-rays result in small dose leakage to neighboring areas. Secondary neutrons contribute to most of the prompt dose rate outside caves into which the beam is delivered. This secondary radiation component causes non-negligible dose rates to occur behind walls to which large fluences of secondary particles are directed. By employing adequate beam dumps matched to beam-divergence, magnets, passive shielding and laser pulse repetition limits, average dose rates in- and outside the experimental building stay below design specifications (< 0.5 μSv/hunclassified areas, < 2.5 μSv/h for supervised areas, < 7.5 μSv/h maximum local dose rate) and regulatory limits (< 1 mSv/a for unclassified areas).
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http://dx.doi.org/10.1088/1361-6498/aba8e4DOI Listing
July 2020

Patient-specific CT calibration based on ion radiography for different detector configurations in H, He and C ion pencil beam scanning.

Phys Med Biol 2020 12 22;65(24):245014. Epub 2020 Dec 22.

Department of Medical Physics - Experimental Physics, Ludwig-Maximilians-Universität München, Munich, Germany. Author to whom any correspondence should be addressed.

The empirical conversion of the treatment planning x-ray computed tomography (CT) image to ion stopping power relative to water causes dose calculation inaccuracies in ion beam therapy. A patient-specific calibration of the CT image is enabled by the combination of an ion radiography (iRad) with the forward-projection of the empirically converted CT image along the estimated ion trajectories. This work investigated the patient-specific CT calibration for list-mode and integration-mode detector configurations, with reference to a ground truth ion CT (iCT) image. Analytical simulations of idealized carbon ion and proton trajectories in a numerical anthropomorphic phantom and realistic Monte Carlo simulations of proton, helium and carbon ion pencil beam scanning in a clinical CT image of a head-and-neck patient were considered. Controlled inaccuracy and noise levels were applied to the calibration curve and to the iRad, respectively. The impact of the selection of slices and angles of the iRads, as well as the choice of the optimization algorithm, were investigated. Accurate and robust CT calibration was obtained in analytical simulations of straight carbon ion trajectories. Analytical simulations of non-straight proton trajectories due to scattering suggested limitations for integration-mode but not for list-mode. To make the most of integration-mode, a dedicated objective function was proposed, demonstrating the desired accuracy for sufficiently high proton statistics in analytical simulations. In clinical data the inconsistencies between the iRad and the forward-projection of the ground truth iCT image were in the same order of magnitude as the applied inaccuracies (up to 5%). The accuracy of the CT calibration were within 2%-5% for integration-mode and 1%-3% for list-mode. The feasibility of successful patient-specific CT calibration depends on detector technologies and is primarily limited by these above mentioned inconsistencies that slightly penalize protons over helium and carbon ions due to larger scattering and beam spot size.
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http://dx.doi.org/10.1088/1361-6560/aba319DOI Listing
December 2020
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