Continuous time-resolved estimated synthetic 4D-CTs for dose reconstruction of lung tumor treatments at a 0.35 T MR-linac.

Objective.To experimentally validate a method to create continuous time-resolved estimated synthetic 4D-computed tomography datasets (tresCTs) based on orthogonal cine MRI data for lung cancer treatments at a magnetic resonance imaging (MRI) guided linear accelerator (MR-linac).Approach.A breathing porcine lung phantom was scanned at a CT scanner and 0.35 T MR-linac. Orthogonal cine MRI series (sagittal/coronal orientation) at 7.3 Hz, intersecting tumor-mimicking gelatin nodules, were deformably registered to mid-exhale 3D-CT and 3D-MRI datasets. The time-resolved deformation vector fields were extrapolated to 3D and applied to a reference synthetic 3D-CT image (sCTref), while accounting for breathing phase-dependent lung density variations, to create 82 s long tresCTs at 3.65 Hz. Ten tresCTs were created for ten tracked nodules with different motion patterns in two lungs. For each dataset, a treatment plan was created on the mid-exhale phase of a measured ground truth (GT) respiratory-correlated 4D-CT dataset with the tracked nodule as gross tumor volume (GTV). Each plan was recalculated on the GT 4D-CT, randomly sampled tresCT, and static sCTrefimages. Dose distributions for corresponding breathing phases were compared in gamma (2%/2 mm) and dose-volume histogram (DVH) parameter analyses.Main results.The mean gamma pass rate between all tresCT and GT 4D-CT dose distributions was 98.6%. The mean absolute relative deviations of the tresCT with respect to GT DVH parameters were 1.9%, 1.0%, and 1.4% for the GTVD98%,D50%, andD2%, respectively, 1.0% for the remaining nodulesD50%, and 1.5% for the lungV20Gy. The gamma pass rate for the tresCTs was significantly larger (p< 0.01), and the GTVD50%deviations with respect to the GT were significantly smaller (p< 0.01) than for the sCTref.Significance.The results suggest that tresCTs could be valuable for time-resolved reconstruction and intrafractional accumulation of the dose to the GTV for lung cancer patients treated at MR-linacs in the future.

Synthetic CT in Carbon Ion Radiotherapy of the Abdominal Site.

The generation of synthetic CT for carbon ion radiotherapy (CIRT) applications is challenging, since high accuracy is required in treatment planning and delivery, especially in an anatomical site as complex as the abdomen. Thirty-nine abdominal MRI-CT volume pairs were collected and a three-channel cGAN (accounting for air, bones, soft tissues) was used to generate sCTs. The network was tested on five held-out MRI volumes for two scenarios: (i) a CT-based segmentation of the MRI channels, to assess the quality of sCTs and (ii) an MRI manual segmentation, to simulate an MRI-only treatment scenario. The sCTs were evaluated by means of similarity metrics (e.g., mean absolute error, MAE) and geometrical criteria (e.g., dice coefficient). Recalculated CIRT plans were evaluated through dose volume histogram, gamma analysis and range shift analysis. The CT-based test set presented optimal MAE on bones (86.03 ± 10.76 HU), soft tissues (55.39 ± 3.41 HU) and air (54.42 ± 11.48 HU). Higher values were obtained from the MRI-only test set (MAEBONE = 154.87 ± 22.90 HU). The global gamma pass rate reached 94.88 ± 4.9% with 3%/3 mm, while the range shift reached a median (IQR) of 0.98 (3.64) mm. The three-channel cGAN can generate acceptable abdominal sCTs and allow for CIRT dose recalculations comparable to the clinical plans.

The role of multiple anatomical scenarios in plan optimization for carbon ion radiotherapy of pancreatic cancer.

PURPOSE /OBJECTIVE: To quantify benefits of robust optimization on multiple 4DCT acquisitions combined with off-line treatment adaptation for neoadjuvant carbon ion therapy (CIRT) of pancreatic cancer. MATERIAL/METHODS: For 10 previously treated patients, 4DCTs were acquired around -15 (CTPlan), -5 (RE1), -1 (RE2) and +6 (RE3) days from RT start. Treatment plans were newly optimized to a dose prescription of 38.4 Gy(RBE) (8 fractions) with a constraint of 38 Gy(RBE) to 1% of the gastrointestinal organs at risk volume (D1%). Three strategies were tested: (A) robust optimization on CTPlan maximum exhale (0Ex) with 3 mm set-up, 3% range uncertainty, including 30%-inhale; (B) addition of the RE1-0Ex scenario; (C) plan recalculation at each REi and adaptation (RPi) according to deviation thresholds from clinical goals. The cumulative variation of target coverage and GI-OARs doses was evaluated. Duodenum contours of all 4DCTs of each patient were registered on CTPlan-0Ex. The capacity of pre-RT acquisitions to predict duodenum position was investigated by computing the intersection of contours at CTplan, RE1, or their union, with respect to subsequent 4DCTs and the CTV, coupled with increasing margin. RESULTS: (A) No recalculation exceeded the D1% constraint. (B) The inclusion of RE1-0Ex in the optimization problem improved inter-fraction robustness on a patient-specific basis, but was non-significant on average. (C) Half of the plans would be re-optimized to recover target coverage and/or minimize duodenum dose, at least once. A significant difference was observed between pre-RT duodenum contours when intersecting subsequent contours, either with a margin expansion. CONCLUSION: Anatomical variations highlighted at multiple REi proved that a fast and efficient online adaptation is essential to optimize treatment quality of CIRT for pancreatic cancer.

Time-resolved MRI for off-line treatment robustness evaluation in carbon-ion radiotherapy of pancreatic cancer.

PURPOSE: In this study, we investigate the use of magnetic resonance imaging (MRI) for the clinical evaluation of gating treatment robustness in carbon-ion radiotherapy (CIRT) of pancreatic cancer. Indeed, MRI allows radiation-free repeated scans and fast dynamic sequences for time-resolved (TR) imaging (cine-MRI), providing information on inter- and intra-fraction cycle-to-cycle variations of respiratory motion. MRI can therefore support treatment planning and verification, overcoming the limitations of the current clinical standard, that is, four-dimensional computed tomography (4DCT), which describes an "average" breathing cycle neglecting breathing motion variability. METHODS: We integrated a technique to generate a virtual CT (vCT) from 3D MRI with a method for 3D reconstruction from 2D cine-MRI, to produce TR vCTs for dose recalculations. For eight patients, the method allowed evaluating inter-fraction variations at end-exhale and intra-fraction cycle-to-cycle variability within the gating window in terms of tumor displacement and dose to the target and organs at risk. RESULTS: The median inter-fraction tumor motion was in the range 3.33-12.16 mm, but the target coverage was robust (-0.4% median D95% variation). Concerning cycle-to-cycle variations, the gating technique was effective in limiting tumor displacement (1.35 mm median gating motion) and corresponding dose variations (-3.9% median D95% variation). The larger exposure of organs at risk (duodenum and stomach) was caused by inter-fraction motion, whereas intra-fraction cycle-to-cycle dose variations were limited. CONCLUSIONS: This study proposed a method for the generation of TR vCTs from MRI, which enabled an off-line evaluation of gating treatment robustness and suggested its feasibility to support treatment planning of pancreatic tumors in CIRT.

Dosimetric impact of geometric distortions in an MRI-only proton therapy workflow for lung, liver and pancreas.

In a radiation therapy workflow based on Magnetic Resonance Imaging (MRI), dosimetric errors may arise due to geometric distortions introduced by MRI. The aim of this study was to quantify the dosimetric effect of system-dependent geometric distortions in an MRI-only workflow for proton therapy applied at extra-cranial sites. An approach was developed, in which computed tomography (CT) images were distorted using an MRI displacement map, which represented the MR distortions in a spoiled gradient-echo sequence due to gradient nonlinearities and static magnetic field inhomogeneities. A retrospective study was conducted on 4DCT/MRI digital phantoms and 18 4DCT clinical datasets of the thoraco-abdominal site. The treatment plans were designed and separately optimized for each beam in a beam specific Planning Target Volume on the distorted CT, and the final dose distribution was obtained as the average. The dose was then recalculated in undistorted CT using the same beam geometry and beam weights. The analysis was performed in terms of Dose Volume Histogram (DVH) parameters. No clinically relevant dosimetric impact was observed on organs at risk, whereas in the target structure, geometric distortions caused statistically significant variations in the planned dose DVH parameters and dose homogeneity index (DHI). The dosimetric variations in the target structure were smaller in abdominal cases (ΔD2%, ΔD98%, and ΔDmean all below 0.1% and ΔDHI below 0.003) compared to the lung cases. Indeed, lung patients with tumors isolated inside lung parenchyma exhibited higher dosimetric variations (ΔD2%≥0.3%, ΔD98%≥15.9%, ΔDmean≥3.3% and ΔDHI≥0.102) than lung patients with tumor close to soft tissue (ΔD2%≤0.4%, ΔD98%≤5.6%, ΔDmean≤0.9% and ΔDHI≤0.027) potentially due to higher density variations along the beam path. Results suggest the potential applicability of MRI-only proton therapy, provided that specific analysis is applied for isolated lung tumors.

Investigating the use of virtual 4DCT from 4DMRI in gated carbon ion radiation therapy of abdominal tumors.

PURPOSE: To generate virtual 4DCT from 4DMRI with field of view (FOV) extended to the entire involved patient anatomy, in order to evaluate its use in carbon ion radiation therapy (CIRT) of the abdominal site in a clinical scenario. MATERIALS AND METHODS: The virtual 4DCT was generated by deforming a reference CT in order to (1) match the anatomy depicted in the 4DMRI within its FOV, by calculating deformation fields with deformable image registration to describe inter-fractional and breathing motion, and (2) obtain physically plausible deformation outside of the 4DMRI FOV, by propagating and modulating the previously obtained deformation fields. The implemented method was validated on a digital anthropomorphic phantom, for which a ground truth (GT) 4DCT was available. A CIRT treatment plan was optimized at the end-exhale reference CT and the RBE-weighted dose distribution was recalculated on both the virtual and GT 4DCTs. The method estimation error was quantified by comparing the virtual and GT 4DCTs and the corresponding recomputed doses. The method was then evaluated on 8 patients with pancreas or liver tumors treated with CIRT using respiratory gating at end-exhale. The clinical treatment plans adopted at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) were considered and the dose distribution was recomputed on all respiratory phases of the planning and virtual 4DCTs. By comparing the two datasets and the corresponding dose distributions, the geometrical and dosimetric impact of organ motion was assessed. RESULTS: For the phantom, the error outside of the 4DMRI FOV was up to 4.5mm, but it remained sub-millimetric in correspondence to the target within the 4DMRI FOV. Although the impact of motion on the target D95% resulted in variations ranging from 22% to 90% between the planned dose and the doses recomputed on the GT 4DCT phases, the corresponding estimation error was ≤2.2%. In the patient cases, the variation of the baseline tumor position between the planning and the virtual end-exhale CTs presented a median (interquartile range) value of 6.0 (4.9) mm. For baseline variations larger than 5mm, the tumor D95% variation between the plan and the dose recomputed on the end-exhale virtual CT resulted larger than 10%. Median variations higher than 10% in the target D95% and gastro-intestinal OARs D2% were quantified at the end-inhale, whereas close to the end-exhale phase, limited variations of relevant dose metrics were found for both tumor and OARs. CONCLUSIONS: The negligible impact of the geometrical inaccuracy in the estimated anatomy outside of the 4DMRI FOV on the overall dosimetric accuracy suggests the feasibility of virtual 4DCT with extended FOV in CIRT of the abdominal site. In the analyzed patient group, inter-fractional variations such as baseline variation and breathing variability were quantified, demonstrating the method capability to support treatment planning in gated CIRT of the abdominal site.

An MRI framework for respiratory motion modelling validation.

INTRODUCTION: Respiratory motion models establish a correspondence between respiratory-correlated (RC) 4-dimensional (4D) imaging and respiratory surrogates, to estimate time-resolved (TR) 3D breathing motion. To evaluate the performance of motion models on real patient data, a validation framework based on magnetic resonance imaging (MRI) is proposed, entailing the use of RC 4DMRI to build the model, and on both (i) TR 2D cine-MRI and (ii) additional 4DMRI data for testing intra-/inter-fraction breathing motion variability. METHODS: Repeated MRI data were acquired in 7 patients with abdominal lesions. The considered model relied on deformable image registration (DIR) for building the model and compensating for inter-fraction baseline variations. Both 2D and 3D validation were performed, by comparing model estimations with the ground truth 2D cine-MRI and 4DMRI respiratory phases, respectively. RESULTS: The median DIR error was comparable to the voxel size (1.33 × 1.33 × 5 mm3 ), with higher values in the presence of large inter-fraction motion (median value: 2.97 mm). In the 2D validation, the median estimation error on anatomical landmarks' position resulted below 4 mm in every scenario, whereas in the 3D validation it was 1.33 mm and 4.21 mm when testing intra- and inter-fraction motion, respectively. The range of motion described in the cine-MRI was comparable to the motion of the building 4DMRI, being always above the estimation error. Overall, the model performance was dependent on DIR error, presenting reduced accuracy when inter-fraction baseline variations occurred. CONCLUSIONS: Results suggest the potential of the proposed framework in evaluating global motion models for organ motion management in MRI-guided radiotherapy.

Organ motion quantification and margins evaluation in carbon ion therapy of abdominal lesions.

PURPOSE: In image-guided particle radiotherapy of abdominal lesions, respiratory motion hinders treatment accuracy. In this study, 2D cineMRI data were used to quantify the tumor (GTV) motion and to evaluate the clinical approach based on deriving an internal target volume (ITV) from a planning 4DCT for gating treatments. METHODS: Seven patients with abdominal lesions were treated with carbon-ion therapy at the National Centre of Oncological Hadron-therapy (Italy). The MR scan was performed on the same day of the 4DCT acquisition. For four patients, an additional MR was acquired approximately after 1 week. The cineMRI combined with deformable image registration algorithm was used to quantify tumor motion. Afterwards, two ITVs were defined considering (1) all phases (ITVFB) and (2) only phases within the gating window (ITVG), and then compared with the clinical (4DCT-derived) ITVs (ITVCG and ITVCFB). RESULTS: Tumor residual motion estimated by cineMRI data in the two MRI sessions resulted not significantly different from 4DCT, although cineMRI accounted for cycle-to-cycle variations. The ITV normalized for the GTV median values were higher for ITVFB with respect to ITVG, ITVCFB and ITVCG. The Hausdorff distances with respect to the GTV were up to 10.55 mm, 3.13 mm, 5.56 mm and 2.51 mm, for ITVFB, ITVG, ITVCFB and ITVCG, respectively. According to both metrics, ITVCG and ITVG were not found significantly different. CONCLUSIONS: CineMRI acquisitions allowed to quantify organ motion without delivering additional dose to the patient and to verify treatment margins in gated carbon-ion therapy of abdominal lesions.

Modeling RBE-weighted dose variations in irregularly moving abdominal targets treated with carbon ion beams.

PURPOSE: To model four-dimensional (4D) relative biological effectiveness (RBE)-weighted dose variations in abdominal lesions treated with scanned carbon ion beam in case of irregular breathing motion. METHODS: The proposed method, referred to as bioWED method, combines the simulation of tumor motion in a patient- and beam-specific water equivalent depth (WED)-space with RBE modeling, aiming at the estimation of RBE-weighted dose changes due to respiratory motion. The method was validated on a phantom, simulating gated and free breathing dose delivery, and on a patient case, for which free breathing irradiation was assumed and both amplitude and baseline breathing irregularities were simulated through a respiratory motion model. We quantified (a) the effect of motion on the equivalent uniform dose (EUD) and the RBE-weighted dose-volume histograms (DVH), by comparing the planned dose distribution with "ground truth" 4D RBE-weighted doses computed using 4D computed tomography data, and (ii) the estimation error, by comparing the doses estimated with the bioWED method to "ground truth" 4D RBE-weighted doses. RESULTS: In the phantom validation, the estimation error on the EUD was limited with respect to the motion effect and the median estimation error on relevant RBE-weighted DVH metrics remained within 5%. In the patient study, the estimation error as computed on the EUD was smaller than the corresponding motion effect, exhibiting the largest values in the baseline irregularity simulation. However, the median estimation error over all simulations was below 3.2% considering relevant DVH metrics. CONCLUSIONS: In the evaluated cases, the bioWED method showed proper accuracy when compared to deformable image registration-based 4D dose calculation. Therefore, it can be seen as a tool to test treatment plan robustness against irregular breathing motion, although its accuracy decreases as a function of increasing soft tissue deformation and should be evaluated on a larger patient dataset.

Virtual 4DCT from 4DMRI for the management of respiratory motion in carbon ion therapy of abdominal tumors.

PURPOSE: To evaluate a method for generating virtual four-dimensional computed tomography (4DCT) from four-dimensional magnetic resonance imaging (4DMRI) data in carbon ion radiotherapy with pencil beam scanning for abdominal tumors. METHODS: Deformable image registration is used to: (a) register each respiratory phase of the 4DMRI to the end-exhale MRI; (b) register the reference end-exhale CT to the end-exhale MRI volume; (c) generate the virtual 4DCT by warping the registered CT according to the obtained deformation fields. A respiratory-gated carbon ion treatment plan is optimized on the planning 4DCT and the corresponding dose distribution is recalculated on the virtual 4DCT. The method was validated on a digital anthropomorphic phantom and tested on eight patients (18 acquisitions). For the phantom, a ground truth dataset was available to assess the method performances from the geometrical and dosimetric standpoints. For the patients, the virtual 4DCT was compared with the planning 4DCT. RESULTS: In the phantom, the method exhibits a geometrical accuracy within the voxel size and Dose Volume Histograms deviations up to 3.3% for target V95% (mean dose difference ≤ 0.2% of the prescription dose, gamma pass rate > 98%). For patients, the virtual and the planning 4DCTs show good agreement at end-exhale (3% median D95% difference), whereas other respiratory phases exhibit moderate motion variability with consequent dose discrepancies, confirming the need for motion mitigation strategies during treatment. CONCLUSIONS: The virtual 4DCT approach is feasible to evaluate treatment plan robustness against intra- and interfraction motion in carbon ion therapy delivered at the abdominal site.

Validation of a model for physical dose variations in irregularly moving targets treated with carbon ion beams.

PURPOSE: In particle therapy, conventional treatment planning systems rely on an imaging representation of the irradiated region to compute the dose. For irregular breathing, when an imaging dataset describing the actual motion is not available, a different approach for dose estimation is needed. To this aim, we validate a method for the estimation of physical dose variations in gated carbon ion treatments, providing also a demonstration of the feasibility of physical dose metrics to assess the method performance. Finally, we describe a sample use case, in which this method is used to assess plan robustness with respect to undetected irregular tumor motion. METHODS: The method entails the definition of a patient- and beam-specific water equivalent depth (WED) space, the simulation of motion as a translation equal to tumor displacement, and the reconstruction of the altered dose. We validated the approach using four-dimensional computed tomographies (4DCTs) and clinical plans in 12 patients, treated with respiratory gated carbon ion beams at the National Centre for Oncological Hadrontherapy (Pavia, Italy). Using the end-exhale CT and dose distribution as a reference, the physical dose delivered at the end-inhale tumor position was estimated and compared to the ground-truth dose recalculation on the end-inhale CT. Biologically effective and physical dose variations between the plan and the recalculation were compared as well. As a use case, we evaluated dose changes caused by simulated irregular tumor motion, that is, linear and nonlinear baseline shifts and/or amplitude variations with hysteresis. RESULTS: The ratio between biologically effective and physical equivalent uniform dose (EUD) variations due to end-exhale to end-inhale motion was less than one for 96% of investigated structures. In the validation study, we found a median error corresponding to a 14% EUD overestimation for the tumor and 4% EUD underestimation for a subgroup of organs at risk, together with a high EUD variation due to motion [median 352% EUD variation between end-exhale and end-inhale doses in the planning tumor volume (PTV)]. Considering relevant dose-volume histogram (DVH) metrics, the median difference between estimated and ground truth doses was ≤ 4%. Gamma analysis between estimated and recalculated dose distributions resulted in a pass rate > 80% for 83% of the target volumes. For the two patients selected for the sample use case, a patient-specific assessment of the method performance was performed on the 4DCT and it was possible to relate EUD variations of both tumor and organs at risk to the simulated target motion. CONCLUSIONS: The physical dose distribution was found to be more sensitive to motion with respect to the biologically effective one, suggesting the suitability of the physical dose metrics for the WED-space method validation. We showed that the method can compensate for intra-fractional tumor motion with proper accuracy in the selected patient group, although its use is recommended when limited deformations are expected. In conclusion, the WED-space method can provide simulations of dose alteration due to irregular breathing when imaging data are lacking, and, once integrated with relative biological effectiveness (RBE) modeling, it would be useful in evaluating the robustness of carbon ion treatment plans.

A clustering approach to 4D MRI retrospective sorting for the investigation of different surrogates.

PURPOSE: In retrospective 4-Dimensional Magnetic Resonance Imaging (4D MRI) sorting, respiratory surrogate selection affects the image quality of reconstructed volumes. We propose a method for retrospective 4D MRI sorting based on clustering, which allowed us to compare the performance of single or multiple internal surrogates vs. a conventional external signal. METHODS: A k-medoids clustering algorithm was exploited for sorting 2D MRI into 4D MRI, relying on (A) multiple or (B) single automatically tracked internal landmarks or (C) respiratory belt signal. 4D MRI reconstructions for seven liver cancer patients were compared to those of the state-of-the-art mutual information (MI) approach. Sorting artifacts were measured by the root mean square error (RMSE) between the diaphragm profile and a fitted second order curve. Diaphragm and tumor motions were evaluated. RESULTS: The median RMSEs ranged 0.97-1.66 mm, 1.24-1.89 mm, 1.43-2.27 mm, 1.74-3.72 mm for the MI, (A), (B) and (C) methods, respectively. Significant differences (Friedman, α = 5%) were found between (C) and all other methods, and between (B) and MI approaches. The discrepancies between (A) and MI approaches ranged 1.1-6.2 mm and 0.7-5.3 mm respectively in diaphragm and tumor motions. Methods (A) and (B) showed similar ranges of motion. CONCLUSION: With multiple internal points, our method yielded the description of a higher range of motion and similar image quality with respect to the MI approach. The single point method led to more artifacts, suggesting the superior suitability of multiple internal surrogates for retrospective 4D MRI sorting. Considering internal rather than external information favored superior performance.

A ROI-based global motion model established on 4DCT and 2D cine-MRI data for MRI-guidance in radiation therapy.

In-room magnetic resonance imaging (MRI) allows the acquisition of fast 2D cine-MRI centered in the tumor for advanced motion management in radiotherapy. To achieve 3D information during treatment, patient-specific motion models can be considered the most viable solution. However, conventional global motion models are built using a single motion surrogate, independently from the anatomical location. In this work, we present a novel motion model based on regions of interest (ROIs) established on 4D computed tomography (4DCT) and 2D cine-MRI, aiming at accurately compensating for changes during treatment. In the planning phase, a motion model is built on a 4DCT dataset, through 3D deformable image registration (DIR). ROIs are then defined and correlated with motion fields derived by 2D DIR between CT slices centered in the tumor. In the treatment phase, the model is applied to in-room cine-MRI data to compensate for organ motion in a multi-modal framework, aiming at estimating a time-resolved 3DCT. The method is validated on a digital phantom and tested on two lung patients. Analysis is performed by considering different anatomical planes (coronal, sagittal and a combination of the two) and evaluating the performance of the method on tumor and diaphragm. For the phantom study, the ROI-based model results in a uniform median error on both diaphragm and tumor below 1.5 mm. For what concerns patients, median errors on both diaphragm and tumor are around 2 mm (maximum patient resolution), confirming the capability of the method to regionally compensate for motion. A novel ROI-based motion model is proposed as an integral part of an envisioned clinical MRI-guided workflow aiming at enhanced image guidance compared to conventional strategies.

"Patient-specific validation of deformable image registration in radiation therapy: Overview and caveats".

Over the last few decades, deformable image registration (DIR) has gained popularity in image-guided radiation therapy for a number of applications, such as contour propagation, dose warping, and accumulation. Although this raises promising perspectives for the improvement of treatment outcomes and quality of radiotherapy clinical practice, the variety of proposed DIR algorithms, combined with the lack of an effective quantitative quality control metric of the registration, is slowing the transfer of DIR into the clinical routine. Recently, a task group (AAPM TG132) report was published outlining the essential aspects of DIR for image guidance in radiotherapy. However, an accurate and efficient patient-specific validation is not yet defined, and appropriate metrics should be identified to achieve the definition of both geometric and dosimetric accuracy. In this respect, the use of a dense set of anatomical landmarks, along with additional evaluations on contours or deformation field analysis, are likely to drive patient-specific DIR validation in clinical image-guided radiotherapy applications to account for geometric inaccuracies. Automatic and efficient strategies able to provide spatial information of DIR uncertainties and to evaluate monomodal and multimodal image registration, as well as to describe homogenous and un-contrasted regions are believed to represent the future direction in DIR validation. But especially in the case of DIR applications for dose mapping and accumulation, the need of accurate patient-specific validation is not only limited to the evaluation of geometric accuracy. In fact, the need to account for dosimetric inaccuracies due to DIR represents another important area in the field of adaptive treatments. Different approaches are currently being investigated to quantify the effect of DIR error on dose analysis, mainly relying on clinically relevant dose metrics, or on the study of deformation field properties for a voxel-by-voxel evaluation. However, novel research is required for the definition of dedicated and personalized measures capable to relate the geometric and dosimetric inaccuracies, thus bearing useful information for a safe use of DIR by clinical end users. In this paper we provide insights on DIR results evaluation on a patient-specific basis, facing the issues of both geometric and dosimetric paradigms. Challenges on DIR validation are overviewed and discussed, in order to push preliminary clinical guidelines forward on this fundamental topic and boost the implementation of more robust and reliable patient-specific evaluation metrics.

Evaluation of residual abdominal tumour motion in carbon ion gated treatments through respiratory motion modelling.

At the Italian National Centre for Oncologic Hadrontherapy (CNAO) patients with upper-abdominal tumours are being treated with carbon ion therapy, adopting the respiratory gating technique in combination with layered rescanning and abdominal compression to mitigate organ motion. Since online imaging of the irradiated volume is not feasible, this study proposes a modelling approach for the estimation of residual motion of the target within the gating window. The model extracts a priori respiratory motion information from the planning 4DCT using deformable image registration (DIR), then combines such information with the external surrogate signal recorded during dose delivery. This provides estimation of a CT volume corresponding to any given respiratory phase measured during treatment. The method was applied for the retrospective estimation of tumour residual motion during irradiation, considering 16 patients treated at CNAO with the respiratory gating protocol. The estimated tumour displacement, calculated with respect to the reference end-exhale position, was always limited (average displacement is 0.32±0.65mm over all patients) and below the maximum motion defined in the treatment plan. This supports the hypothesis of target position reproducibility, which is the crucial assumption in the gating approach. We also demonstrated the use of the model as a simulation tool to establish a patient-specific relationship between residual motion and the width of the gating window. In conclusion, the implemented method yields an estimation of the repeatability of the internal anatomy configuration during gated treatments, which can be used for further studies concerning the dosimetric impact of the estimated residual organ motion.