Miriam Krieger

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Krieger

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Miriam

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0000-0002-1914-1220

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Publications 1 - 9 of 9

Anthropomorphic phantom for deformable lung and liver CT and MR imaging for radiotherapy
Colvill, Emma; Krieger, Miriam; Bosshard, Patrick; et al. (2020)
Physics in Medicine and Biology
ITV or tumour tracking for dose painting of NSCLC? A comparison of target coverage and out-of-target dose in proton treatments
Giovannelli, Anna C.; Köthe, Andreas; Zhang, Ye; et al. (2021)
Introduction: Dose-escalation radiotherapy is used to calculate biologically adapted plan. When treating moving tumours the boost on the dose can be lost. We investigated the possibility to use tumour tracking for high precision dose painting in lung cancers. We chose a case where the target motion was below 5mm, normally recruited under free-breathing/rescanning-only protocol. We performed a comparative 4D dose calculation (4DDC) analysis for two extreme planning approaches: tracking and free-breathing. Material and Methods: The plan has been calculated on a Mid-Position reference image with a 17% dose boost on the dose escalated volume (DE). The planning CT has been warped into a different 4DCT and animated thanks to deformable image registration. The margins applied to the PTV were 5 mm for the tracking plan and 10 mm for the free-breathing one. For both the cases, the 4DDC included a different numbers of rescans RS (1-6). Results: Considering ICRU definitions, we calculated the conformity index (CI) for DE, the tumour coverage for the CTV and the hot-spot index (HS). CI and HS improved for the tracking plan with the number or rescans. These proportionality were not found in free-breathing. CI is respectively 1.41 and 1.48 for the tracking and the free-breathing plan considering RS=6. V95 is respectively 98.7 and 99.7 for the tracking and the free-breathing plan, on average and for RS=1,4,6. For the tracking plan, HS is 1.41,0.9,0.86 for RS=1,4,6 and 58.19,56.98,58,4 for free-breathing. Summary: Tracking the tumour allowed to keep a better conformity on the boosted volume while giving less dose to healthy tissues in the lungs. The tracking plan shown a loss of coverage in the CTV. This effect is due to the fact that fully continuous energy modulation is not provided from the used treatment-planning-system and can be improved working on its dept-dose-curves resolution.
ITV or tumour tracking for dose painting of NSCLC? A comparison of target coverage and out-of-target dose in proton treatments
Giovannelli, Anna C.; Köthe, Andreas; Zhang, Ye; et al. (2021)
Joint Conference of the ÖGMP, DGMP & SGSMP/Dreiländertagung der Medizinischen Physik – Abstracts
Towards ultrasound-guided proton beam tracking for lung tumours
Krieger, Miriam (2020)
In the radiation therapy of cancer, proton therapy offers the opportunity to conform the delivered dose precisely to the tumour, sparing healthy tissues more than conventional photon therapy. This is due to protons delivering most of their dose at a well-defined depth, in the so-called Bragg peak. In order to spread this narrow peak over the whole tumour, in the Pencil Beam Scanning (PBS) technique, the narrow pencil beam is deflected laterally using dipole magnets and the depth of its peak in the patient is varied by changing the proton energy. However, interference between this highly dynamic delivery and respiratory motion of the tumour, for instance if the tumour is in the thorax or abdomen, can lead to substantial distortions of the delivered dose, which need to be mitigated in order to guarantee an effective treatment. One way to do so is to adapt the pencil beam position and energy during the delivery in order to follow the tumour motion, a technique known as ‘tumour tracking’. For this, knowledge of the three-dimensional tumour position in real-time is required, which is the main challenge holding back the clinical implementation of tracking for proton therapy. As such, this thesis investigates the feasibility and benefits of a respiratory motion model, based on real-time abdominal ultrasound, for tracking lung tumours using PBS proton therapy. This thesis is divided into four parts. Part I introduces the motion problem for PBS proton therapy, and describes the main tools and methodologies used in the work, which are then validated in Part II. Part III then presents three individual studies in which different motion mitigation techniques are described and validated, leading towards the ultimate goal of ultrasound-guided lung tumour tracking. Part IV finally summarises the main findings of the work, as well as it provides an outlook to future work. After the introductory chapters of Part I, Part II starts with a chapter (Chapter 3) which validates the so-called 4DCT(MRI) approach, which combines CT and 4DMRI data sets to create temporally varying, simulated CT volumes. In this work it is found that under ideal conditions, 4DCT(MRI) can reproduce the original 4DCT with high accuracy. However, careful consideration needs to be given to the quality of the 4DMRI data and the deformable registration approach used to extract motions. Such data sets are important to provide the geometrical representations of the anatomical motion of patients for 4D dose calculations (4DDC), which simulate the delivered dose to the patient. As such, the 4DDC used in this work is experimentally validated in Chapter 4. Under various motion and delivery conditions, the dose is measured using a scintillating CCD dosimeter and a water phantom, and compared to the corresponding 4D dose distributions calculated using the 4DDC. The results show very high agreement between measurements and calculations when both the motion and delivery dynamics are well known. When this not the case, residual differences can however be reduced using motion mitigation techniques. Finally in Part II, Chapter 5 presents a detailed commissioning of the code used to simulate tumour tracking. In this, computational phantoms of increasing complexity have been used to test every component of the beam adaptation simulation code and confirmed that the developed tracking code properly adapts the beam positions and energies under the well known motion and geometrical conditions provided by the developed numerical phantoms. Part III opens with Chapter 6, which investigates how information about variable breathing patterns affect proton dose distributions and how they can be included in the treatment planning process. As such, a novel, probabilistic target definition approach is introduced and validated, which is shown to provide reliable target coverage whilst reducing dose to the healthy lung. A respiratory motion model for the lung, based on abdominal ultrasound imaging, is then introduced in Chapter 7. This study investigates the geometrical accuracy of such a model and analyses the impact of geometrical errors on proton dose distributions. The results show a good geometrical agreement between model estimation and ground truth motion, which also results in clinically acceptable dose accuracy. Finally, Chapter 8 makes use of this respiratory motion model as an input into proton beam tracking simulations, which are in turn compared to tracking simulations using ‘ground truth’ motions. From this work, ultrasound guided motion modelling has been found to lead to results which are very similar to ‘ground truth’ tracking. However, regardless of the motion information used, tracking alone is not always capable of restoring clinically acceptable dose distributions, especially when the tumour compresses or stretches during respiration.
Liver-ultrasound based motion modelling to estimate 4D dose distributions for lung tumours in scanned proton therapy
Giger, Alina; Krieger, Miriam; Jud, Christoph; et al. (2020)
Physics in Medicine and Biology
Motion mitigation strategies are crucial for scanned particle therapy of mobile tumours in order to prevent geometrical target miss and interplay effects. We developed a patient-specific respiratory motion model based on simultaneously acquired time-resolved volumetric MRI and 2D abdominal ultrasound images. We present its effects on 4D pencil beam scanned treatment planning and simulated dose distributions. Given an ultrasound image of the liver and the diaphragm, principal component analysis and Gaussian process regression were applied to infer dense motion information of the lungs. 4D dose calculations for scanned proton therapy were performed using the estimated and the corresponding ground truth respiratory motion; the differences were compared by dose difference volume metrics. We performed this simulation study on 10 combined CT and 4DMRI data sets where the motion characteristics were extracted from 5 healthy volunteers and fused with the anatomical CT data of two lung cancer patients. Median geometrical estimation errors below 2 mm for all data sets and maximum dose differences of Vdiff > 5% = 43.2% and Vdiff > 10% = 16.3% were found. Moreover, it was shown that abdominal ultrasound imaging allows to monitor organ drift. This study demonstrated the feasibility of the proposed ultrasound-based motion modelling approach for its application in scanned proton therapy of lung tumours. (© 2020 Institute of Physics and Engineering in Medicine.)
Liver-ultrasound-guided lung tumour tracking for scanned proton therapy: a feasibility study
Krieger, Miriam; Giger, Alina; Jud, Christoph; et al. (2021)
Physics in Medicine and Biology
Pencil beam scanned (PBS) proton therapy of lung tumours is hampered by respiratory motion and the motion-induced density changes along the beam path. In this simulation study, we aim to investigate the effectiveness of proton beam tracking for lung tumours both under ideal conditions and in conjunction with a respiratory motion model guided by real-time ultrasound imaging of the liver. Multiple-breathing-cycle 4DMRIs of the thorax and abdominal 2D ultrasound images were acquired simultaneously for five volunteers. Deformation vector fields extracted from the 4DMRI, referred to as ground truth motion, were used to generate 4DCT(MRI) data sets of two lung cancer patients, resulting in 10 data sets with variable motion patterns. Given the 4DCT(MRI) and the corresponding ultrasound images as surrogate data, a patient-specific motion model was built. The model consists of an autoregressive model and Gaussian process regression for the temporal and spatial prediction, respectively. Two-field PBS plans were optimised on the reference CTs, and 4D dose calculations (4DDC) were used to simulate dose delivery for (a) unmitigated motion, (b) ideal 2D and 3D tracking (both beam adaption and 4DDC based on ground truth motion), and (c) realistic 2D and 3D tracking (beam adaption based on motion predictions, 4DDC on ground truth motion). Model-guided tracking retrieved clinically acceptable target dose homogeneity, as seen in a substantial reduction of the D5%–D95% compared to the non-mitigated simulation. Tracking in 2D and 3D resulted in a similar improvement of the dose homogeneity, as did ideal and realistic tracking simulations. In some cases, however, the tracked deliveries resulted in a shift towards higher or lower dose levels, leading to unacceptable target over- or under-coverage. The presented motion modelling framework was shown to be an accurate motion prediction tool for the use in proton beam tracking. Tracking alone, however, may not always effectively mitigate motion effects, making it necessary to combine it with other techniques such as rescanning.
A quantitative FLASH effectiveness model to reveal potentials and pitfalls of high dose rate proton therapy
Krieger, Miriam; van de Water, Steven; Folkerts, Michael M.; et al. (2022)
Medical Physics
Purpose In ultrahigh dose rate radiotherapy, the FLASH effect can lead to substantially reduced healthy tissue damage without affecting tumor control. Although many studies show promising results, the underlying biological mechanisms and the relevant delivery parameters are still largely unknown. It is unclear, particularly for scanned proton therapy, how treatment plans could be optimized to maximally exploit this protective FLASH effect. Materials and Methods To investigate the potential of pencil beam scanned proton therapy for FLASH treatments, we present a phenomenological model, which is purely based on experimentally observed phenomena such as potential dose rate and dose thresholds, and which estimates the biologically effective dose during FLASH radiotherapy based on several parameters. We applied this model to a wide variety of patient geometries and proton treatment planning scenarios, including transmission and Bragg peak plans as well as single- and multifield plans. Moreover, we performed a sensitivity analysis to estimate the importance of each model parameter. Results Our results showed an increased plan-specific FLASH effect for transmission compared with Bragg peak plans (19.7% vs. 4.0%) and for single-field compared with multifield plans (14.7% vs. 3.7%), typically at the cost of increased integral dose compared to the clinical reference plan. Similar FLASH magnitudes were found across the different treatment sites, whereas the clinical benefits with respect to the clinical reference plan varied strongly. The sensitivity analysis revealed that the threshold dose as well as the dose per fraction strongly impacted the FLASH effect, whereas the persistence time only marginally affected FLASH. An intermediate dependence of the FLASH effect on the dose rate threshold was found. Conclusions Our model provided a quantitative measure of the FLASH effect for various delivery and patient scenarios, supporting previous assumptions about potentially promising planning approaches for FLASH proton therapy. Positive clinical benefits compared to clinical plans were achieved using hypofractionated, single-field transmission plans. The dose threshold was found to be an important factor, which may require more investigation.
Impact of spot reduction on the effectiveness of rescanning in pencil beam scanned proton therapy for mobile tumours
Bertschi, Stefanie; Krieger, Miriam; Weber, Damien C.; et al. (2022)
Physics in Medicine and Biology
Objective. In pencil beam scanning proton therapy, individually calculated and positioned proton pencil beams, also referred to as 'spots', are used to achieve a highly conformal dose distributions to the target. Recent work has shown that this number of spots can be substantially reduced, resulting in shorter delivery times without compromising dosimetric plan quality. However, the sensitivity of spot-reduced plans to tumour motion is unclear. Although previous work has shown that spot-reduced plans are slightly more sensitive to small positioning inaccuracies of the individual pencil beams, the resulting shorter delivery times may allow for more rescanning. The aim of this study was to assess the impact of tumour motion and the effectiveness of 3D volumetric rescanning for spot-reduced treatment plans. Approach. Three liver and two lung cancer patients with non-negligible motion amplitudes were analysed. Conventional and probabilistic internal target volume definitions were used for planning considering single or multiple breathing cycles respectively. For each patient, one clinical and two spot-reduced treatment plans were created using identical field geometries. 4D dynamic dose calculations were then performed and resulting target coverage (V95%), dose homogeneity (D5%-D95%) and hot spots (D2%) evaluated for 1-25 rescans. Main results. Over all patients investigated, spot reduction reduced the number of spots by 91% in comparison to the clinical plan, reducing field delivery times by approximately 50%. This reduction, together with the substantially increased dose per spot resulting from the spot reduction process, allowed for more rescans in the same amount of time as for clinical plans and typically improved dosimetric parameters, in some cases to values better than the reference static (3D calculated) plans. However, spot-reduced plans had an increased possibility of interference with the breathing cycle, especially for simulations of perfectly repeatable breathing. Significance. For the patients analysed in this study, spot-reduced plans were found to be a valuable option to increase the efficiency of 3D volumetric rescanning for motion mitigation, if attention is paid to possible interference patterns.
Impact of internal target volume definition for pencil beam scanned proton treatment planning in the presence of respiratory motion variability for lung cancer: A proof of concept
Krieger, Miriam; Giger, Alina; Salomir, Rares; et al. (2020)
Radiotherapy & Oncology

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