Left-right Directions Research Articles

Characterizing cardiac contractile motion for noninvasive radioablation of ventricular tachycardia

BackgroundRespiratory motion management strategies are used to minimize the effects of breathing on the precision of stereotactic ablative radiotherapy for ventricular tachycardia, but the extent of cardiac contractile motion of the human heart has not been systematically explored. ObjectiveWe aim to assess the magnitude of cardiac contractile motion between different directions and locations in the heart. MethodsPatients with intracardiac leads or valves who underwent 4D cardiac computed tomography (4DCT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. The displacement of transvenous right atrial appendage (RA), right ventricle (RV) ICD, coronary sinus (CS) lead tips and prosthetic cardiac devices across the cardiac cycle were measured in orthogonal 3D views on a maximal-intensity projection CT reconstruction. ResultsA total of 31 pre-ablation cardiac 4DCTs were analyzed. The LV lead tip had significantly greater motion compared to the RV lead in the anterior-posterior direction (6.0±2.2mm vs 3.8±1.7mm; p=0.01) and superior-inferior direction (4.4±2.9mm vs 3.5±2.0mm; p=0.049). The prosthetic aortic valves had the least movement of all fiducials, specifically compared to the RV lead tip in the left-right direction (3.2±1.2mm vs 6.1±3.8mm, p=0.04) and the LV lead tip in the antero-posterior direction (3.8±1.7mm vs 6.0±2.2mm, p=0.03). ConclusionThe degree of cardiac contractile motion varies significantly (1mm to 15.2 mm) across different locations in the heart. The effect of contractile motion on the precision of radiotherapy should be assessed on a patient-specific basis.

Optimal planning target margin for prostate radiotherapy based on interfractional and intrafractional variability assessment during 1.5T MRI-guided radiotherapy.

We analyzed daily pre-treatment- (PRE) and real-time motion monitoring- (MM) MRI scans of patients receiving definitive prostate radiotherapy (RT) with 1.5 T MRI guidance to assess interfractional and intrafractional variability of the prostate and suggest optimal planning target volume (PTV) margin. Rigid registration between PRE-MRI and planning CT images based on the pelvic bone and prostate anatomy were performed. Interfractional setup margin (SM) and interobserver variability (IO) were assessed by comparing the centroid values of prostate contours delineated on PRE-MRIs. MM-MRIs were used for internal margin (IM) assessment, and PTV margin was calculated using the van Herk formula. We delineated 400 prostate contours on PRE-MRI images. SM was 0.57 ± 0.42, 2.45 ± 1.98, and 2.28 ± 2.08 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively, after bone localization and 0.76 ± 0.57, 1.89 ± 1.60, and 2.02 ± 1.79 mm in the LR, AP, and SI directions, respectively, after prostate localization. IO was 1.06 ± 0.58, 2.32 ± 1.08, and 3.30 ± 1.85 mm in the LR, AP, and SI directions, respectively, after bone localization and 1.11 ± 0.55, 2.13 ± 1.07, and 3.53 ± 1.65 mm in the LR, AP, and SI directions, respectively, after prostate localization. Average IM was 2.12 ± 0.86, 2.24 ± 1.07, and 2.84 ± 0.88 mm in the LR, AP, and SI directions, respectively. Calculated PTV margin was 2.21, 5.16, and 5.40 mm in the LR, AP, and SI directions, respectively. Movements in the SI direction were the largest source of variability in definitive prostate RT, and interobserver variability was a non-negligible source of margin. The optimal PTV margin should also consider the internal margin.

A Patient-Specific correspondence model to track tumor location in thorax during radiation therapy

PurposeWe present a patient-specific model to estimate tumor location in the thorax during radiation therapy using chest surface displacement as the surrogate signal. MethodsTwo types of data are used for model construction: Four-dimensional computed tomography (4D-CT) images of the patient and the displacement of two points on the patient’s skin on the thoracic area. Principal component analysis is used to fit the correspondence model. This model incorporates the recorded surrogate signals during radiation delivery as input and delivers the 3D trajectory of the tumor as output. We evaluated the accuracy of the proposed model on a respiratory phantom and five lung cancer patients. ResultsFor the respiratory phantom, the location of the center of the sphere during treatment was calculated in three directions: Left-Right (LR), Anterior-Posterior (AP) and, Superior-Inferior (SI). The error of localization was less than 1 mm in the LR and AP directions and less than 2 mm in the SI direction. The location of the tumor center for two of the patients, and the location of the apex of the diaphragm for the other three, was calculated in three directions. For all patients, the localization error in the LR and AP directions was less than 1.1 mm for two fractions and the maximum localization error in the SI direction was 6.4 mm. ConclusionsThis work presents a feasibility study of utilizing surface displacement data to locate the tumor in the thorax during radiation treatment. Future work will validate the model on a larger patient population.

MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma

BackgroundIn pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT).Materials and methodsTen randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position.ResultsThe median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from − 3.5 to 5.8 Gy for the pancreatic tail and − 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation.ConclusionInter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.

Generating 3-D auditory stimuli for the evaluation of spatial impression in musical instruments

Spatial hearing plays an important, but not well understood, role in the perception of musical instruments and audio equipment. Psychophysical experiments are necessary to elucidate the processes which convey the spatial impression of sound sources. To this end, we propose a way to generate virtual stimuli for research on the spatial impression of musical instruments, specifically pianos. Our proposal, based on acoustical holography, takes a series of measurements over a dense grid and designs a virtual vibrating plate with the same directivity as the piano, as observed from the measuring grid. The number of active modes in the left-right and front-back directions of this virtual source can be controlled to reduce the radiation pattern complexity and generate a wide range of virtual stimuli. The resulting sound fields are rendered using binaural Ambisonics, using the position of the piano player as the spherical harmonic expansion center. The proposal was used in actual psychophysical experiments looking to shed light into the spatial impression of digital and acoustic pianos. The results show that the proposal does generate spatial sound signals which are consistently associated with different degrees of richness in the spatial impression.

Optimal Planning Target Margin for Prostate Radiotherapy Based on Interfractional and Intrafractional Variability Assessment during 1.5T MR-Guided Radiotherapy.

MR-guided radiotherapy (MRgRT) provides superior soft-tissue contrast over CT-based image guidance. We collected and analyzed daily pre-treatment (PRE) and real-time motion-monitoring (MM) MR images of patients receiving prostate radiotherapy to assess interfractional and intrafractional variability of prostate using two localization methods: pelvic bony anatomy (bone) and prostate during online adaptive radiotherapy (ART). PRE and MM MRIs for the first five fractions of twenty prostate cancer patients who received definitive MRgRT with 1.5T MRI were collected. Using MIM software, rigid registration between PRE MRI and planning CT images based on pelvic bony anatomy and prostate reproduced bone localization and online ART, respectively. To determine interfractional setup margin (SM), prostate was delineated on all PRE MRIs registered after bone and prostate localizations by a radiation oncologist, and centroid values of prostate contours between planning CT and PRE MRIs were compared. To determine interobserver variability, another radiation oncologist, a medical physicist, and a radiotherapist contoured prostate for both localization methods. For internal margin (IM) assessment, we used MM MRIs of the five patients who had all three sets of coronal, sagittal, and axial cine images and determined the maximum contour displacement using in-house MATLAB-based software converting binary image files to 2D cine images with a superimposed grid of 1 mm spacing. A total of 100 PRE and 25 MM MRIs were analyzed. Four hundred prostate contours were delineated on MR images registered with planning CT based on both bony anatomy and prostate. After bone localization, SM was 0.57±0.42 mm in left-right (LR), 2.45±1.98 mm in anterior-posterior (AP), and 2.28±2.08 mm in superior-inferior (SI) directions, and IO was 1.06±0.58 mm in LR, 2.32±1.08 mm in AP, and 3.30±1.85 mm in SI directions. After prostate localization, SM was 0.76±0.57 mm in LR, 1.89±1.60 mm in AP, and 2.2±1.79 mm in SI directions, and IO was 1.11±0.55 mm in LR, 2.13±1.07 mm in AP, and 3.53±1.65 mm in SI directions. Average IM was 2.12±0.86 mm, 2.24±1.07 mm, and 2.84±0.88 mm in LR, AP, and SI directions, respectively. Using daily MRIs from MRgRT, we showed that movements in the SI direction were the largest source of variability in prostate definitive RT. In addition, interobserver variability was a non-negligible source of margin. Optimal PTV margin should also consider internal margin, especially in the SI direction.

Dose Coverage Variation Caused by Setup Uncertainties in VMAT-TBI Treatment

Volumetric Modulated Arc Therapy Total Body Irradiation (VMAT TBI) offers several advantages over conventional TBI techniques, including reduced cost of the treatment room (a normal-sized vault versus a large shielded vault), increased patient comfort during treatment, lung sparing without the need for physical blocks, and a more homogeneous dose distribution. In VMAT-TBI treatment, plans at multiple isocenters are utilized to cover the entire body, and patients are positioned with the aid of image guidance. However, aligning the patient's entire body during setup can be challenging due to its pliability, and the setup time is heavily dependent on the tolerance allowed by the image guidance. Therefore, studying the variation in dose coverage caused by setup uncertainties in VMAT-TBI treatments can help optimize the clinical workflow and determine the optimal tolerance for patient positioning. New plans were generated to simulate the uncertainties that occur during treatment setup for each patient. These plans were created by shifting the original VMAT TBI plans at the head, chest, abdomen (or pelvis) isocenters by 5mm and 1cm in the left-right (LR), inferior-superior (IS), and anterior-posterior (AP) directions, respectively. Dose DicomRT files were exported, and the dose change due to the shifts was analyzed. The statistical quantification of the percentage of the body that experienced a dose change of over 2%, 5%, and 10% of the prescription due to the shifts from the original plans was calculated for all patients. Histograms were generated, showing the percentage of body getting dose change of 1-2%, 2-3%, 3-5%, 5-7%, 7-10%, 10-15%. The table below displays the percent volume receiving a dose change of 2%, 5%, and 10% of the prescription for a 5mm shift. Among the shift directions, the dose change is most sensitive in the IS direction, with similar impact observed the in LR and AP directions. Among different sites, the chest experiences the largest dose change, followed by the pelvis. For a 5mm shift in the IS direction, the average percent volume receiving a dose change of 2%, 5%, and 10% in the chest is 9.25%, 2.64%, and 0.27%, respectively. For a 1cm shift, the numbers are 12.23%, 6.75%, and 1.29%. In the pelvis (abdomen), these values are 9.03%, 1.67%, and 0.17% for a 5mm shift and 13.28%, 6.1%, and 0.85% for a 1cm shift. For head plans, the values are 2.72%, 0.9%, and 0.14% for a 5mm shift and 3.77%, 1.66%, and 0.53% for a 1cm shift. Accurate alignment in the chest region is crucial in VMAT TBI treatment. Efforts should be made to minimize shifts over 1cm in the IS direction.

Voxel Based Analysis of Local Dose Patterns on Radiation Induced Xerostomia in Head and Neck Cancer with Machine Learning Methods

Despite the technological advancements, xerostomia caused by the irradiation of parotid and/or submandibular glands significantly impacts a patient's quality of life and remains a clinical challenge. The mean dose within the salivary glands that neglects the local dose effect is an oversimplified predictor thus its efficacy is severely limited. This study aims to uncover the local dose patterns associated with the xerostomia by performing a voxel-based analysis of the spatial parotid dose. A cohort of 143 patients who underwent intensity modulated radiation therapy treatment were retrospectively selected for this study. A binary classification was adopted for predictive modeling: group 1 (102 patients) if grade 0 or 1 and group 2 (41 patients) if grade 2 or 3. The anatomy of the parotid gland from the computed tomography (CT) of these patients were standardized to that of a reference patient with rigid and multistage B-spline deformable registration. The resultant deformation field vectors were subsequently utilized to warp the parotid doses and dose gradients to the reference ones. To facilitate pattern recognition, the bilateral parotid doses and dose gradients were further regrouped into contra- and ipsi-lateral depending on their proximity to the tumor targets. Four supervised machine learning (ML) models including ReliefF, L1 regularized logistic regression (L1LR), ridge regression (RR), and random forest (RF) were employed to determine the feature importance of each voxel and discover the dose patterns within the glands that are correlated with xerostomia. The predictive performance of each model was evaluated with the area under the curves (AUC) of the receiver operating characteristic. The image registration accuracy of an average of 95.6% for the parotid gland standardization on CT images was achieved. The four ML models were assessed with 10-fold cross validation showing comparable performance and the AUC scores were 0.74 ± 0.09, 0.75 ± 0.08, 0.73 ± 0.10, and 0.77 ± 0.09 for ReliefF, L1LR, RR, and RF, respectively. The importance patterns showed that the doses to the superior and medial region of the contralateral parotid gland were more correlated with xerostomia from the ReliefF model but not others. Similar importance patterns were observed from the dose gradient distributions along the left-right and anterior-posterior directions. The voxel-based model, which takes into account the spatial information of dose and dose gradient within the parotid gland, demonstrated an improvement in xerostomia predictive modeling as compared to the mean dose predictor, particularly in the local dose effect on xerostomia. If these findings are validated with more patient data and independent studies, they could be incorporated into treatment planning of head and neck patients to reduce the toxicity occurrence.

Biomechanical role can vary depending on the conditions of the motor task

Expert players in throwing sports may reduce the variability of projectile arrival position by systematically relating release parameters (e.g., release position, velocity, and angular velocity of the projectile). Reducing the variability of the projectile arrival position is often believed to increase the success rate of throwing task, but it may not be always true. Here, we experimentally illustrate that the systematic relationship between release parameters that reduce the variability of the ball arrival position may not increase the number of hitting trials during a throwing task. Furthermore, we demonstrate that the role of the release parameters in increasing successful trials can vary depending on the target size. Each participant threw balls at two different-sized targets (small and large target conditions). Additionally, they alternately threw balls with overhead and sidearm throwing for both the small and large targets. Our results showed that the release position and velocity in the left-right direction reduced the variability of the ball arrival position and increased the successful trials in the small target condition. In the large target condition, the two release parameters reduced the variability of the ball arrival position, but they did not increase the successful trials. Consequently, reducing the variability of the ball arrival position did not always equate to an increase in successful trials, as it depended on the target size. These findings indicate that the role of the release parameters in increasing hitting trials is not constant but varies depending on the condition of the motor task.

Investigation of uncertainty in internal target volume definition for lung stereotactic body radiotherapy

This study evaluated the validity of internal target volumes (ITVs) defined by three- (3DCT) and four-dimensional computed tomography (4DCT), and subsequently compared them with actual movements during treatment. Five patients with upper lobe lung tumors were treated with stereotactic body radiotherapy (SBRT) at 48 Gy in four fractions. Planning 3DCT images were acquired with peak-exhale and peak-inhale breath-holds, and 4DCT images were acquired in the cine mode under free breathing. Cine images were acquired using an electronic portal imaging device during irradiation. Tumor coverage was evaluated based on the manner in which the peak-to-peak breathing amplitude on the planning CT covered the range of tumor motion (± 3 SD) during irradiation in the left–right, anteroposterior, and cranio-caudal (CC) directions. The mean tumor coverage of the 4DCT-based ITV was better than that of the 3DCT-based ITV in the CC direction. The internal margin should be considered when setting the irradiation field for 4DCT. The proposed 4DCT-based ITV can be used as an efficient approach in free-breathing SBRT for upper-lobe tumors of the lung because its coverage is superior to that of 3DCT.

A Framework for Assessing the Effect of Cardiac and Respiratory Motion for Stereotactic Arrhythmia Radioablation Using a Digital Phantom With a 17-Segment Model: A STOPSTORM.eu Consortium Study

The optimal motion management strategy for patients receiving stereotactic arrhythmia radioablation (STAR) for the treatment of ventricular tachycardia (VT) is not fully known. We developed a framework using a digital phantom to simulate cardiorespiratory motion in combination with different motion management strategies to gain insight into the effect of cardiorespiratory motion on STAR. The 4-dimensional (4D) extended cardiac-torso (XCAT) phantom was expanded with the 17-segment left ventricular (LV) model, which allowed placement of STAR targets in standardized ventricular regions. Cardiac- and respiratory-binned 4D computed tomography (CT) scans were simulated for free-breathing, reduced free-breathing, respiratory-gating, and breath-hold scenarios. Respiratory motion of the heart was set to population-averaged values of patients with VT: 6, 2, and 1 mm in the superior-inferior, posterior-anterior, and left-right direction, respectively. Cardiac contraction was adjusted by reducing LV ejection fraction to 35%. Target displacement was evaluated for all segments using envelopes encompassing the cardiorespiratory motion. Envelopes incorporating only the diastole plus respiratory motion were created to simulate the scenario where cardiac motion is not fully captured on 4D respiratory CT scans used for radiation therapy planning. The average volume of the 17 segments was 6 cm3 (1-9 cm3). Cardiac contraction-relaxation resulted in maximum segment (centroid) motion of 4, 6, and 3.5 mm in the superior-inferior, posterior-anterior, and left-right direction, respectively. Cardiac contraction-relaxation resulted in a motion envelope increase of 49% (24%-79%) compared with individual segment volumes, whereas envelopes increased by 126% (79%-167%) if respiratory motion also was considered. Envelopes incorporating only the diastole and respiration motion covered on average 68% to 75% of the motion envelope. The developed LV-segmental XCAT framework showed that free-wall regions display the most cardiorespiratory displacement. Our framework supports the optimization of STAR by evaluating the effect of (cardio)respiratory motion and motion management strategies for patients with VT.

Real-Time Tracking of Laryngeal Motion via the Surface Depth-Sensing Technique for Radiotherapy in Laryngeal Cancer Patients.

Radiotherapy (RT) is an important modality for laryngeal cancer treatment to preserve laryngeal function. During beam delivery, laryngeal motion remains uncontrollable and may compromise tumor-targeting efficacy. We aimed to examine real-time laryngeal motion by developing a surface depth-sensing technique with preliminary testing during RT-based treatment of patients with laryngeal cancer. A surface depth-sensing (SDS) camera was set up and integrated into RT simulation procedures. By recording the natural swallowing of patients, SDS calculation was performed using the Pose Estimation Model and deep neural network technique. Seven male patients with laryngeal cancer were enrolled in this prospective study. The calculated motion distances of the laryngeal prominence (mean ± standard deviation) were 1.6 ± 0.8 mm, 21.4 ± 5.1 mm, 6.4 ± 3.3 mm, and 22.7 ± 4.9 mm in the left-right, cranio-caudal, and anterior-posterior directions and for the spatial displacement, respectively. The calculated differences in the 3D margins for generating the planning tumor volume by senior physicians with and without SDS data were -0.7 ± 1.0 mm (-18%), 11.3 ± 6.8 mm (235%), and 1.8 ± 2.6 mm (45%) in the left-right, cranio-caudal, and anterior-posterior directions, respectively. The SDS technique developed for detecting laryngeal motion during swallowing may be a practical guide for individualized RT design in the treatment of laryngeal cancer.

Assessment of intrafraction motion and its dosimetric impact on prostate radiotherapy using an in-house developed position monitoring system.

To implement an in-house developed position monitoring software, SeedTracker, for conventional fractionation prostate radiotherapy, and study the effect on dosimetric impact and intrafraction motion. Thirty definitive prostate radiotherapy patients with implanted fiducial markers were included in the study. All patients were treated with VMAT technique and plans were generated using the Pinnacle planning system using the 6MV beam model for Elekta linear accelerator. The target dose of 60 Gy in 20 fractions was prescribed for 29 of 30 patients, and one patient was treated with the target dose of 78 Gy in 39 fractions. The SeedTracker position monitoring system, which uses the x-ray images acquired during treatment delivery in the Elekta linear accelerator and associated XVI system, was used for online prostate position monitoring. The position tolerance for online verification was progressively reduced from 5mm, 4mm, and to 3mm in 10 patient cohorts to effectively manage the treatment interruptions resulting from intrafraction motion in routine clinical practice. The delivered dose to target volumes and organs at risk in each of the treatment fractions was assessed by incorporating the observed target positions into the original treatment plan. In 27 of 30 patients, at least one gating event was observed, with a total of 177 occurrences of position deviation detected in 146 of 619 treatment fractions. In 5mm, 4mm, and 3mm position tolerance cohorts, the position deviations were observed in 13%, 24%, and 33% of treatment fractions, respectively. Overall, the mean (range) deviation of -0.4 (-7.2 to 5.3) mm, -0.9 (-6.1 to 15.6) mm, and -1.7 (-7.0 to 6.1) mm was observed in Left-Right, Anterior-Posterior, and Superior-Inferior directions, respectively. The prostate CTV D99 would have been reduced by a maximum value of 1.3 Gy compared to the planned dose if position deviations were uncorrected, but with corrections, it was 0.3 Gy. Similarly, PTV D98 would have been reduced by a maximum value of 7.6 Gy uncorrected, with this difference reduced to 2.2 Gy with correction. The V60 to the rectum increased by a maximum of 1.0% uncorrected, which was reduced to 0.5%. Online target position monitoring for conventional fractionation prostate radiotherapy was successfully implemented on a standard Linear accelerator using an in-house developed position monitoring software, with an improvement in resultant dose to prostate target volume.

Diaphragm and abdominal organ motion during radiotherapy: a comprehensive multicenter study in 189 children

BackgroundFor accurate thoracic and abdominal radiotherapy, inter- and intrafractional geometrical uncertainties need to be considered to enable accurate margin sizes. We aim to quantify interfractional diaphragm and abdominal organ position variations, and intrafractional diaphragm motion in a large multicenter cohort of pediatric cancer patients (< 18 years). We investigated the correlation of interfractional position variations and intrafractional motion with age, and with general anesthesia (GA).MethodsIn 189 children (mean age 8.1; range 0.4–17.9 years) from six institutes, interfractional position variation of both hemidiaphragms, spleen, liver, left and right kidneys was quantified using a two-step registration. CBCTs were registered to the reference CT relative to the bony anatomy, followed by organ registration. We calculated the group mean, systematic and random errors (standard deviations Σ and σ, respectively) in cranial-caudal (CC), left-right and anterior-posterior directions. Intrafractional right hemidiaphragm motion was quantified using CBCTs on which the breathing amplitude, defined as the difference between end-inspiration and end-expiration peaks, was assessed (N = 79). We investigated correlations with age (Spearman’s ρ), and differences in motion between patients treated with and without GA (N = 75; all < 5.5 years).ResultsInterfractional group means were largest in CC direction and varied widely between patients, with largest variations in the right hemidiaphragm (range -13.0–17.5 mm). Interfractional group mean of the left kidney showed a borderline significant correlation with age (p = 0.047; ρ = 0.17). Intrafractional right hemidiaphragm motion in patients ≥ 5.5 years (mean 10.3 mm) was significantly larger compared to patients < 5.5 years treated without GA (mean 8.3 mm) (p = 0.02), with smaller Σ and σ values. We found a significant correlation between breathing amplitude and age (p < 0.001; ρ = 0.43). Interfractional right hemidiaphragm position variations were significantly smaller in patients < 5.5 years treated with GA than without GA (p = 0.004), but intrafractional motion showed no significant difference.ConclusionIn this large multicenter cohort of children undergoing thoracic and abdominal radiotherapy, we found that interfractional position variation does not depend on age, but the use of GA in patients < 5.5 years showed smaller systematic and random errors. Furthermore, our results showed that breathing amplitude increases with age. Moreover, variations between patients advocate the need for a patient-specific margin approach.

Evaluation of tumour motion and internal/External Correlation in lung SABR.

This study aims to analyse lung tumour motion and to investigate the correlation between the internal tumour motion acquired from four-dimensional computed tomography (4DCT) and the motion of an external surrogate. A dataset of 363 4DCT images was analysed. Tumours were classified based on their anatomical lobes. The recorded gross tumour volume (GTV) information included the centroid GTV motion in the superior-inferior (SI), anteroposterior (AP) and left-right (LR) directions, and in three-dimensions (3D). For the internal/external correlation, the RPM surrogate breathing signals of 260 patients were analysed via an in-house script. The external motion was correlated with the 3D centroid motion, and the maximum tumour motion via Spearman's correlation. The effect of tumour volume on the amount of motion was evaluated. The greatest 3D tumour amplitude was found for tumours located in the lower part of the lung, with a maximum of 26.7 mm. The Spearman's correlation of the internal 3D motion was weak in the upper (r = 0.21) and moderate in the middle (r = 0.51) and the lower (r = 0.52) lobes. There was no obvious difference in the correlation coefficients between the maximum tumour displacement and the centroid motion. No correlation was found between the tumour volume and the magnitude of motion. Our results suggest that tumour location can be a good predictor of its motion. However, tumour size is a poor predictor of the motion. This knowledge of the distribution of tumour motion throughout the thorax will be valuable for research areas where motion management is still in its infancy.

Technical note: Multi-MATE, a high-throughput platform for automated image-guidedsmall-animal irradiation.

Small animal irradiation is essential to study the radiation response of new interventions before or parallel to human therapy. Image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) are recently adopted in small animal irradiation to more closely mimic human treatments. However, sophisticated techniques require exceedingly high time, resources, and expertize that are often impractical. We propose a high throughput and high precision platform named Multiple Mouse Automated Treatment Environment (Multi-MATE) to streamline image-guided small animal irradiation. Multi-MATE consists of six parallel and hexagonally arranged channels, each equipped with a transfer railing, a 3D-printed immobilization pod, and an electromagnetic control unit, computer-controlled via an Arduino interface. The mouse immobilization pods are transferred along the railings between the home position outside the radiation field and the imaging/irradiation position at the irradiator isocenter. All six immobilization pods are transferred to the isocenter in the proposed workflow for parallel CBCT scans and treatment planning. The immobilization pods are then sequentially transported to the imaging/therapy position for dose delivery. The positioning reproducibility of Multi-MATE are evaluated using CBCT and radiochromic films. While parallelizing and automating the image-guided small animal radiation delivery, Multi-MATE achieved the average pod position reproducibility of 0.17 ± 0.04 mm in the superior-inferior direction, 0.20 ± 0.04 mm in the left-right direction, and 0.12 ± 0.02mm in the anterior-posterior direction in repeated CBCT tests. Additionally, in image-guided dose delivery tasks, Multi-MATE demonstrated the positioning reproducibility of 0.17 ± 0.06 mm in the superior-inferior direction, 0.19 ± 0.06 mm in the left-right direction. We designed, fabricated, and tested a novel automated irradiation platform, Multi-MATE to accelerate and automate image-guided small animal irradiation. The automated platform minimizes human operation and achieves high setup reproducibility and image-guided dose delivery accuracy. Multi-MATE thus removes a major barrier to implementing high-precision preclinical radiation research.

Assessing target localization accuracy across different soft-tissue matching protocols using end-exhalation breath-hold cone-beam computed tomography in patients with pancreatic cancer.

The purpose of this study was to retrospectively assess target localization accuracy across different soft-tissue matching protocols using cone-beam computed tomography (CBCT) in a large sample of patients with pancreatic cancer and to estimate the optimal margin size for each protocol. Fifty-four consecutive patients with pancreatic cancer who underwent 15-fraction volumetric modulated arc therapy under the end-exhalation breath-hold condition were enrolled. Two soft-tissue matching protocols were used according to the resectability classification, including gross tumor volume (GTV) matching for potentially resectable tumors and planning target volume (PTV) matching for borderline resectable or unresectable tumors. The tolerance of the target localization error in both matching protocols was set to 5mm in any direction. The optimal margin size for each soft-tissue matching protocol was calculated from the systematic and random errors of the inter- and intrafraction positional variations using the van Herk formula. The inter- and intrafraction positional variations of PTV matching were smaller than those of GTV matching. The percentage of target localization errors exceeding 5mm in the first CBCT scan of each fraction in the superior-inferior direction was 12.6 and 4.8% for GTV and PTV matching, respectively. The optimal margin sizes for GTV and PTV matching were 3.7 and 2.7, 5.4 and 4.1 and 3.9 and 3.0mm in the anterior-posterior, superior-inferior and left-right directions, respectively. Target localization accuracy in PTV matching was higher than that in GTV matching. By setting the tolerance of the target localization error, treatment can be successful within the planned margin size.

Factors Affecting Prostate Displacement During Volumetric Modulated Arc Therapy in Prone Position After High-Dose-Rate Brachytherapy for Prostate Cancer

In irradiating the prostate and pelvic lymph node regions, registration based on bony structures matches the pelvic lymph node regions but not necessarily the prostate position, and it is important to identify factors that influence prostate displacement. Therefore, we investigated factors influencing prostate displacement during volumetric modulated arc therapy after single-fraction high-dose-rate brachytherapy (HDR-BT) for prostate cancer and the trends in displacement for each fraction. Seventy patients who underwent pelvic volumetric modulated arc therapy of 46 Gy in the prone position 15 days after 13 Gy HDR-BT were included. Prostate displacement relative to bony structures was calculated using cone beam computed tomography. Systematic error (SE) and random error (RE) were evaluated in the right-left (RL), craniocaudal (CC), and anteroposterior (AP) directions. The association with clinical and anatomic factors on the planning computed tomography or magneticresonanceimaging was analyzed. Prostate volume change (PVC) was defined as the volume change at 2 days after HDR-BT. Displacement trends were individually examined from the first to 23rd fractions. The mean SE in the RL, CC, and AP directions was -0.01 mm, -2.34 mm, and -0.47 mm, respectively. The root mean square of the RE in the RL, CC, and AP directions was 0.44 mm, 1.14 mm, and 1.10 mm, respectively. SE in the CC direction was independently associated with bladder volume (P=.021, t statistic=2.352) and PVC (P < .001, t statistic=-8.526). SE in the AP direction was independently associated with bladder volume (P=.013, t statistic=-2.553), PVC (P < .001, t statistic=5.477), and rectal mean area (P=.008, t statistic=2.743). RE in the CC direction was independently associated with smoking (P=.035). RE in the AP direction was associated with PVC (P=.043). Gradual displacement caudally and posteriorly occurred during the irradiation period. Anatomic characteristics of the bladder, rectum, and prostate predict SE. Smoking and PVC predict RE. In particular, whether PVC is ≥140% affects setting internal margins.

Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy.

This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.

Accuracy of abdominal organ motion estimation in radiotherapy using the right hemidiaphragm top as a surrogate during prolonged breath-holds quantified with MRI.

Respiratory motion presents a challenge in radiotherapy of thoracic and upper abdominal tumors. Techniques to account for respiratory motion include tracking. Using magnetic resonance imaging (MRI) guided radiotherapy systems, tumors can be tracked continuously. Using conventional linear accelerators, tracking of lung tumors is possible by determining tumor motion on kilo voltage (kV) imaging. But tracking of abdominal tumors with kV imaging is hampered by limited contrast. Therefore, surrogates for the tumor are used. One of the possible surrogates is the diaphragm. However, there is no universal method for establishing the error when using a surrogate and there are particular challenges in establishing such errors during free breathing (FB). Prolonged breath-holding might address these challenges. The aim of this study was to quantify the error when using the right hemidiaphragm top (RHT) as surrogate for abdominal organ motion during prolonged breath-holds (PBH) for possible application in radiation treatments. Fifteen healthy volunteers were trained to perform PBHs in two subsequent magnetic resonance imaging (MRI) sessions (PBH-MRI1 and PBH-MRI2). From each MRI acquisition, we selected seven images (dynamics) to determine organ displacement during PBH by using deformable image registration (DIR). On the first dynamic, the RHT, right and left hemidiaphragm, liver, spleen and right and left kidney were segmented. We used the deformation vector fields (DVF), generated by DIR, to determine the displacement of each organ between two dynamics in inferior-superior (IS), anterior-posterior (AP), left-right (LR) direction and we calculated the 3D vector magnitude (|d|). The displacements of the RHT, both hemidiaphragms and the abdominal organs were compared using a linear fit to determine the correlation (R2 of the fit) and the displacement ratio (DR, slope of the fit) between displacements of the RHT and each organ. We quantified the median difference between the DRs of PBH-MRI1 and PBH-MRI2 for each organ. Additionally, we estimated organ displacement in the second PBH by applying the DR from the first PBH to the displacement of the RHT measured during the second PBH. We compared the estimated organ displacement to the measured organ displacement during the second PBH. The difference between the two values was defined as the estimation error of using the RHT as a surrogate and assuming a constant DR over MRI sessions. The linear relationships were confirmed by the high R2 values of the linear fit between the displacements of the RHT and the abdominal organs (R2 > 0.96) in the IS and AP direction and |d|, and high to moderate correlations in the LR direction (0.93 > R2 > 0.64). The median DR difference between PBH-MRI1 and PBH-MRI2 varied between 0.13 to 0.31 for all organs. The median estimation error of the RHT as a surrogate varied between 0.4 and 0.8 mm/min for all organs. The RHT could serve as an accurate surrogate for abdominal organ motion during radiation treatments, e.g. in tracking, provided the error of the RHT as motion surrogate is taken into account in the margins. The study was registered in the Netherlands Trial Register (NL7603). This article is protected by copyright. All rights reserved.