Antje Knopf

Mapping motion from 4D-MRI to 3D-CT for use in 4D dose calculations: a technical feasibility study

PURPOSEnTarget sites affected by organ motion require a time resolved (4D) dose calculation. Typical 4D dose calculations use 4D-CT as a basis. Unfortunately, 4D-CT images have the disadvantage of being a snap-shot of the motion during acquisition and of assuming regularity of breathing. In addition, 4D-CT acquisitions involve a substantial additional dose burden to the patient making many, repeated 4D-CT acquisitions undesirable. Here the authors test the feasibility of an alternative approach to generate patient specific 4D-CT data sets.nnnMETHODSnIn this approach motion information is extracted from 4D-MRI. Simulated 4D-CT data sets [which the authors call 4D-CT(MRI)] are created by warping extracted deformation fields to a static 3D-CT data set. The employment of 4D-MRI sequences for this has the advantage that no assumptions on breathing regularity are made, irregularities in breathing can be studied and, if necessary, many repeat imaging studies (and consequently simulated 4D-CT data sets) can be performed on patients and/or volunteers. The accuracy of 4D-CT(MRI)s has been validated by 4D proton dose calculations. Our 4D dose algorithm takes into account displacements as well as deformations on the originating 4D-CT/4D-CT(MRI) by calculating the dose of each pencil beam based on an individual time stamp of when that pencil beam is applied. According to corresponding displacement and density-variation-maps the position and the water equivalent range of the dose grid points is adjusted at each time instance.nnnRESULTSn4D dose distributions, using 4D-CT(MRI) data sets as input were compared to results based on a reference conventional 4D-CT data set capturing similar motion characteristics. Almost identical 4D dose distributions could be achieved, even though scanned proton beams are very sensitive to small differences in the patient geometry. In addition, 4D dose calculations have been performed on the same patient, but using 4D-CT(MRI) data sets based on variable breathing patterns to show the effect of possible irregular breathing on active scanned proton therapy. Using a 4D-CT(MRI), including motion irregularities, resulted in significantly different proton dose distributions.nnnCONCLUSIONSnThe authors have demonstrated that motion information from 4D-MRI can be used to generate realistic 4D-CT data sets on the basis of a single static 3D-CT data set. 4D-CT(MRI) presents a novel approach to test the robustness of treatment plans in the circumstance of patient motion.PURPOSEnTarget sites affected by organ motion require a time resolved (4D) dose calculation. Typical 4D dose calculations use 4D-CT as a basis. Unfortunately, 4D-CT images have the disadvantage of being a snap-shot of the motion during acquisition and of assuming regularity of breathing. In addition, 4D-CT acquisitions involve a substantial additional dose burden to the patient making many, repeated 4D-CT acquisitions undesirable. Here the authors test the feasibility of an alternative approach to generate patient specific 4D-CT data sets.nnnMETHODSnIn this approach motion information is extracted from 4D-MRI. Simulated 4D-CT data sets [which the authors call 4D-CT(MRI)] are created by warping extracted deformation fields to a static 3D-CT data set. The employment of 4D-MRI sequences for this has the advantage that no assumptions on breathing regularity are made, irregularities in breathing can be studied and, if necessary, many repeat imaging studies (and consequently simulated 4D-CT data sets) can be performed on patients and/or volunteers. The accuracy of 4D-CT(MRI)s has been validated by 4D proton dose calculations. Our 4D dose algorithm takes into account displacements as well as deformations on the originating 4D-CT/4D-CT(MRI) by calculating the dose of each pencil beam based on an individual time stamp of when that pencil beam is applied. According to corresponding displacement and density-variation-maps the position and the water equivalent range of the dose grid points is adjusted at each time instance.nnnRESULTSn4D dose distributions, using 4D-CT(MRI) data sets as input were compared to results based on a reference conventional 4D-CT data set capturing similar motion characteristics. Almost identical 4D dose distributions could be achieved, even though scanned proton beams are very sensitive to small differences in the patient geometry. In addition, 4D dose calculations have been performed on the same patient, but using 4D-CT(MRI) data sets based on variable breathing patterns to show the effect of possible irregular breathing on active scanned proton therapy. Using a 4D-CT(MRI), including motion irregularities, resulted in significantly different proton dose distributions.nnnCONCLUSIONSnThe authors have demonstrated that motion information from 4D-MRI can be used to generate realistic 4D-CT data sets on the basis of a single static 3D-CT data set. 4D-CT(MRI) presents a novel approach to test the robustness of treatment plans in the circumstance of patient motion.

Comparative study of layered and volumetric rescanning for different scanning speeds of proton beam in liver patients

In recent years, particle therapy has become a widely accepted form of cancer treatment and technological advances in beam delivery technology (i.e. pencil beam scanning (PBS)) have enabled the application of highly conformal dose distributions to static targets. Current research focuses on the possibilities for the treatment of mobile targets with these techniques. Of different motion mitigation methods being investigated, rescanning is perhaps the easiest to apply clinically. In general however, different PBS delivery systems exhibit a different temporal parameter space between delivery and target motions, due to the system specific beam position adjustment times (BPATs). Depending on these BPATs, dosimetric effects appearing during irradiation of moving targets vary significantly. In this work, volumetric and layered rescanning were compared for four different scenarios--a combination of fast and slow BPATs laterally (4 ms and 10 ms) and in depth (80 ms and 1 s); and nine different treatment plan arrangements for two clinical liver cases. 4D dose calculations were performed assuming regular, sinusoidal rigid motion as a worst-case motion scenario to model interplay effects. Calculations were sampled over three different starting phases resulting in a total of 432 dose distributions. It was found that layered rescanning is the method of choice for slow scanning systems, both in terms of dose homogeneity (D5-95 values are lower by up to 16% with layered rescanning) and in the estimated treatment delivery times (reduction of up to 300 s with layered rescanning). Analysis of dose homogeneity showed that layered rescanning leads to a smoother decrease in dose inhomogeneity as a function of the number of rescans than volumetric rescanning, which shows larger fluctuations. However, layered rescanning appears to be more sensitive to the starting phase. When analyzing the performance of both approaches and different scanning speeds as a function of delivery time, layered rescanning appears to be the only viable approach for slow energy changing systems, even approaching the performance of fast energy changing systems, as long as lateral scanning speeds are kept high. Similar results were found for multiple field plans and when analyzing different field directions.

Special report: Workshop on 4D-treatment planning in actively scanned particle therapy—Recommendations, technical challenges, and future research directions

This article reports on a 4D-treatment planning workshop (4DTPW), held on 7-8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D-treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state-of-the-art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically.

Challenges of radiotherapy: Report on the 4D treatment planning workshop 2013

This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop.

Online image guided tumour tracking with scanned proton beams: a comprehensive simulation study

Tumour tracking with scanned particle beams potentially requires accurate 3D information on both tumour motion and related density variations. We have previously developed a model-based motion reconstruction method, which allows for the prediction of deformable motions from sparsely sampled surrogate motions tracked via an on-board imaging system (Zhang et al (2013 Phys. Med. Biol. 58 8621)). Here, we investigate the potential effectiveness of tumour tracking for scanned proton beam therapy using such an approach to guide scanned beam tracking, together with the effectiveness of re-tracking for reducing residual motion effects due to tracking uncertainties. Three different beam tracking strategies (2D, 2D deformable and 3D) have been applied to three different liver motion cases, with mean magnitudes ranging from 10-20u2009mm. All simulations have been performed using simulated 4DCTs derived from 4DMRI datasets, whereby inter-breath-cycle motion variability is taken into account. The results show that, without beam tracking, large interplay effects are observed for all motion cases, resulting in CTV D5-95 values of 34.9/58.5/79.4% for the three cases, respectively. These can be reduced to 16.9/18.8/29.1% with 2D tracking, to 15.5/17.9/23.3% with 2D deformable tracking and to 15.1/17.8/21.0% with 3D tracking. Clear inverse interplay effects have also been observed in the proximal portion of the field. However, with three-times re-tracking, D5-95 for the largest motions (20u2009mm) can be reduced to 13.0/12.8% for 2D and 3D tracking, respectively, and hot spots resulting from the inverse interplay effect can be substantially reduced. In summary, we have found that, for motions over 10u2009mm, tracking alone cannot fully mitigate motion effects, and can lead to substantially increased doses to normal tissues in the entrance path of the field. However, three-times re-tracking substantially improves the effectiveness of all types of beam tracking, with substantial advantages of 3D over 2D re-tracking only being observed for the largest motion scenario investigated.

Deformable motion reconstruction for scanned proton beam therapy using on-line x-ray imaging

Organ motion is a major problem for any dynamic radiotherapy delivery technique, and is particularly so for spot scanned proton therapy. On the other hand, the use of narrow, magnetically deflected proton pencil beams is potentially an ideal delivery technique for tracking tumour motion on-line. At PSI, our new Gantry is equipped with a Beams Eye View (BEV) imaging system which will be able to acquire 2D x-ray images in fluoroscopy mode during treatment delivery. However, besides precisely tracking motion from BEVs, it is also essential to obtain information on the 3D motion vector throughout the whole region of interest, and any sparsely acquired surrogate motion is generally not sufficient to describe the deformable behaviour of the whole volume in three dimensions. In this study, we propose a method by which 3D deformable motions can be estimated from surrogate motions obtained using this monoscopic imaging system. The method assumes that example motions over a number of breathing cycles can be acquired before treatment for each patient using 4DMRI. In this study, for each of 11 different subjects, 100 continuous breathing cycles have been extracted from extended 4DMRI studies in the liver and then subject specific motion models have been built using principle component analysis (PCA). To simulate treatment conditions, a different set of 30 continuous breathing cycles from the same subjects have then been used to generate a set of simulated 4DCT data sets (so-called 4DCT(MRI) data sets), from which time-resolved digitally reconstructed radiographs (DRRs) were calculated using the BEV geometry for three treatment fields respectively. From these DRRs, surrogate motions from fiducial markers or the diaphragm have been used as a predictor to estimate 3D motions in the liver region for each subject. The prediction results have been directly compared to the ground truth motions extracted from the same 30 breath cycles of the originating 4DMRI data set. Averaged over all 11 subjects, and for three field directions, for 99% of predicted positions, median (max) error magnitudes of better than 2.63(5.67) mm can be achieved when fiducial markers was chosen as predictor. Furthermore, three single fields, 4D dose calculations have been performed as a verification tool to evaluate the prediction performance of such a model in the context of scanned proton beam therapy. These show a high similarity between plans considering either PCA predicted motion or ground truth motion, where absolute dose differences of more than 5% (V(dosediff = 5%)) occur for the worst field scenarios in only 3.61% (median) or 15.13% (max) of dose calculation points in the irradiated volume. The magnitude of these dose differences were insignificantly dependent on whether surrogate motions were tracked by monoscopic or stereoscopic imaging systems, or whether fiducial markers or diaphragm were chosen as surrogate. This study has demonstrated that on-line deformable motion reconstruction from sparse surrogate motions is feasible, even when using only a monoscopic imaging system. In addition, it has also been found that diaphragm motion can be considered as a good predictor for respiratory deformable liver motion prediction, implying that fiducial markers might not be compulsory if used in conjunction with a patient specific PCA based model.

Consensus Guidelines for Implementing Pencil-Beam Scanning Proton Therapy for Thoracic Malignancies on Behalf of the PTCOG Thoracic and Lymphoma Subcommittee

Pencil-beam scanning (PBS) proton therapy (PT), particularly intensity modulated PT, represents the latest advanced PT technology for treating cancers, including thoracic malignancies. On the basis of virtual clinical studies, PBS-PT appears to have great potential in its ability to tightly tailor the dose to the target while sparing critical structures, thereby reducing treatment-related toxicities, particularly for tumors in areas with complicated anatomy. However, implementing PBS-PT for moving targets has several additional technical challenges compared with intensity modulated photon radiation therapy or passive scattering PT. Four-dimensional computed tomography-based motion management and robust optimization and evaluation are crucial for minimizing uncertainties associated with beam range and organ motion. Rigorous quality assurance is required to validate dose delivery both before and during the course of treatment. Active motion management (eg, breath hold), beam gating, rescanning, tracking, or adaptive planning may be needed for cases involving significant motion or changes in motion or anatomy over the course of treatment.

Quantifying the impact of respiratory-gated 4D CT acquisition on thoracic image quality: a digital phantom study

PURPOSEnProspective respiratory-gated 4D CT has been shown to reduce tumor image artifacts by up to 50% compared to conventional 4D CT. However, to date no studies have quantified the impact of gated 4D CT on normal lung tissue imaging, which is important in performing dose calculations based on accurate estimates of lung volume and structure. To determine the impact of gated 4D CT on thoracic image quality, the authors developed a novel simulation framework incorporating a realistic deformable digital phantom driven by patient tumor motion patterns. Based on this framework, the authors test the hypothesis that respiratory-gated 4D CT can significantly reduce lung imaging artifacts.nnnMETHODSnOur simulation framework synchronizes the 4D extended cardiac torso (XCAT) phantom with tumor motion data in a quasi real-time fashion, allowing simulation of three 4D CT acquisition modes featuring different levels of respiratory feedback: (i) conventional 4D CT that uses a constant imaging and couch-shift frequency, (ii) beam paused 4D CT that interrupts imaging to avoid oversampling at a given couch position and respiratory phase, and (iii) respiratory-gated 4D CT that triggers acquisition only when the respiratory motion fulfills phase-specific displacement gating windows based on prescan breathing data. Our framework generates a set of ground truth comparators, representing the average XCAT anatomy during beam-on for each of ten respiratory phase bins. Based on this framework, the authors simulated conventional, beam-paused, and respiratory-gated 4D CT images using tumor motion patterns from seven lung cancer patients across 13 treatment fractions, with a simulated 5.5 cm(3) spherical lesion. Normal lung tissue image quality was quantified by comparing simulated and ground truth images in terms of overall mean square error (MSE) intensity difference, threshold-based lung volume error, and fractional false positive/false negative rates.nnnRESULTSnAveraged across all simulations and phase bins, respiratory-gating reduced overall thoracic MSE by 46% compared to conventional 4D CT (p ∼ 10(-19)). Gating leads to small but significant (p < 0.02) reductions in lung volume errors (1.8%-1.4%), false positives (4.0%-2.6%), and false negatives (2.7%-1.3%). These percentage reductions correspond to gating reducing image artifacts by 24-90 cm(3) of lung tissue. Similar to earlier studies, gating reduced patient image dose by up to 22%, but with scan time increased by up to 135%. Beam paused 4D CT did not significantly impact normal lung tissue image quality, but did yield similar dose reductions as for respiratory-gating, without the added cost in scanning time.nnnCONCLUSIONSnFor a typical 6 L lung, respiratory-gated 4D CT can reduce image artifacts affecting up to 90 cm(3) of normal lung tissue compared to conventional acquisition. This image improvement could have important implications for dose calculations based on 4D CT. Where image quality is less critical, beam paused 4D CT is a simple strategy to reduce imaging dose without sacrificing acquisition time.

SU-D-BRE-01: A Realistic Breathing Phantom of the Thorax for Testing New Motion Mitigation Techniques with Scanning Proton Therapy

PURPOSEnA prototype breathing phantom (named LuCa) has been developed which simulates the anatomy and motion of a patient thorax.In this work, we describe the results of the first commissioning tests with LuCa.nnnMETHODSnThe phantom provides a close representation of the human thorax. The lungs,contained within a tissue-equivalent ribcage and skin,are made from a polymer foam,which is inflated and deflated using a custommade ventilator. A tumor is simulated using a wooden ball with cutplanes for placing GafChromic films. The ventilator,controlled with Labview software,simulates a full range of breathing motion types.Commissioning tests were performed to assess its performance using imaging (CT and radiographic) and film dosimetry as follows:i)maximum Tumor excursion at acceptable pressure ranges, ii)tumor Motion repeatability between breathing periods,iii)reproducibility between measurement days,iv)tumor-to-surface motion correlation and v)reproducibility of film positioning in phantom.nnnRESULTSnThe phantom can generate repeatable motion patterns with sin4 ,sin,breath-hold (tumor amplitude repeatability <0.5mm over 10min),aswell as patient-specific motion types. Maximum excursions of the tumor are 20mm and 14mm for the large and small tumor inserts respectively. Amplitude reproducibility (Coefficient of Variation) averaged at 16% for the workable pressure range over 2 months. Good correlation between tumor and surface motion was found with R2 =0.92. Reproducibility of film positioning within the thorax was within 0.9mm, and maximum 3° error from the coronal plane. Film measurements revealed that the film repositioning error yields relative errors in the mean dose over the planned target volume (PTV) of up to 2.5% and 4.5% for films at the center and on the edge of the PTV respectively.nnnCONCLUSIONnCommissioning tests have shown that the LuCa phantom can produce tumor motion with excellent repeatability. However,a poorer performance in reproducibility of tumor amplitude for a given peak pressure week-to-week. Film set-up reproducibility is adequate for detection of dosimetric errors resulting from motion of >3%. This work is funded by Swiss National Fund Grants 320030_127569 and 320030_1493942-1.

An anthropomorphic breathing phantom of the thorax for testing new motion mitigation techniques for pencil beam scanning proton therapy

Motion-induced range changes and incorrectly placed dose spots strongly affect the quality of pencil-beam-scanned (PBS) proton therapy, especially in thoracic tumour sites, where density changes are large. Thus motion-mitigation techniques are necessary, which must be validated in a realistic patient-like geometry. We report on the development and characterisation of a dynamic, anthropomorphic, thorax phantom that can realistically mimic thoracic motions and anatomical features for verifications of proton and photon 4D treatments. The presented phantom is of an average thorax size, and consists of inflatable, deformable lungs surrounded by a skeleton and skin. A mobile tumour is embedded in the lungs in which dosimetry devices (such as radiochromic films) can be inserted. Motion of the tumour and deformation of the thorax is controlled via a custom made pump system driving air into and out of the lungs. Comprehensive commissioning tests have been performed to evaluate the mechanical performance of the phantom, its visibility on CT and MR imaging and its feasibility for dosimetric validation of 4D proton treatments. The phantom performed well on both regular and irregular pre-programmed breathing curves, reaching peak-to-peak amplitudes in the tumour ofu2009u2009<20u2009mm. Some hysteresis in the inflation versus deflation phases was seen. All materials were clearly visualised in CT scans, and all, except the bone and lung components, were MRI visible. Radiochromic film measurements in the phantom showed that imaging for repositioning was required (as for a patient treatment). Dosimetry was feasible with Gamma Index agreements (4%/4u2009mm) between film dose and planned doseu2009u2009>90% in the central planes of the target. The results of this study demonstrate that this anthropomorphic thorax phantom is suitable for imaging and dosimetric studies in a thoracic geometry closely-matched to lung cancer patients under realistic motion conditions.