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To differentiate arytenoid subluxation and vocal fold paralysis by CT cine mode scanning combined with three-dimensional (3D) reconstruction image.Seventy-six patients with suspected vocal fold dyskinesia were collected. All patients were examined being asked to inhale deeply and then make "Yi" sound continuously during CT scanning with cine mode. The optimal maximum opening and minimum closing phases of glottis were selected and 3D reconstruction images were performed. The length of vocal fold, the width of glottis, and the subglottal convergence angle, anteversion angle, elevation angle, valgus angle, and varus angle of cricoarytenoid joints were measured. Vocal fold deformation was divided into three types: type I, type II, and type III. Kappa test was used to compare the consistency between CT diagnosis and clinical diagnosis. Single-factor analysis of variance was used to analyze the statistical differences among arytenoid subluxation, vocal fold paralysis, and normal vocal fold.There was high consistency between CT diagnosis and clinical diagnosis (k = 0.731, P0.05), as well as significant differences in the opening width of glottis between type I and type III, the valgus and varus angles of cricoarytenoid joints between type I and type II or type III, and the subglottal convergence angles among the three types of vocal fold deformation.CT scanning with cine mode combined with 3D reconstruction can display the changes of larynx structures in vocal fold dyskinesia, and can be used for the differential diagnosis of arytenoid cartilage subluxation and vocal fold paralysis.

International audience; Purpose. Motion-mask segmentation from thoracic computed tomography (CT) images is the process of extracting the region that encompasses lungs and viscera, where large displacements occur during breathing. It has been shown to help image registration between different respiratory phases. This registration step is, for example, useful for radiotherapy planning or calculating local lung ventilation. Knowing the location of motion discontinuity, that is, sliding motion near the pleura, allows a better control of the registration preventing unrealistic estimates. Nevertheless, existing methods for motion-mask segmentation are not robust enough to be used in clinical routine. This article shows that it is feasible to overcome this lack of robustness by using a lightweight deep-learning approach usable on a standard computer, and this even without data augmentation or advanced model design.Methods. A convolutional neural-network architecture with three 2D U-nets for the three main orientations (sagittal, coronal, axial) was proposed. Predictions generated by the three U-nets were combined by majority voting to provide a single 3D segmentation of the motion mask. The networks were trained on a database of nonsmall cell lung cancer 4D CT images of 43 patients. Training and evaluation were done with a K-fold cross-validation strategy. Evaluation was based on a visual grading by two experts according to the appropriateness of the segmented motion mask for the registration task, and on a comparison with motion masks obtained by a baseline method using level sets. A second database (76 CT images of patients with early-stage COVID-19), unseen during training, was used to assess the generalizability of the trained neural network.Results. The proposed approach outperformed the baseline method in terms of quality and robustness: the success rate increased from urn:x-wiley:00942405:media:mp15347:mp15347-math-0001 to urn:x-wiley:00942405:media:mp15347:mp15347-math-0002 without producing any failure. It also achieved a speed-up factor of 60 with GPU, or 17 with CPU. The memory footprint was low: less than 5 GB GPU RAM for training and less than 1 GB GPU RAM for inference. When evaluated on a dataset with images differing by several characteristics (CT device, pathology, and field of view), the proposed method improved the success rate from urn:x-wiley:00942405:media:mp15347:mp15347-math-0003 to urn:x-wiley:00942405:media:mp15347:mp15347-math-0004.Conclusion. With 5-s processing time on a mid-range GPU and success rates around urn:x-wiley:00942405:media:mp15347:mp15347-math-0005, the proposed approach seems fast and robust enough to be routinely used in clinical practice. The success rate can be further improved by incorporating more diversity in training data via data augmentation and additional annotated images from different scanners and diseases. The code and trained model are publicly available.

Purpose This paper presents a novel strategy for feature-based breathing-phase estimation on ultra low-dose X-ray projections for tumor motion control in radiation therapy . Methods Coarse-scaled Curvelet coefficients are identified as motion sensitive but noise-robust features for this purpose. For feature-based breathing-phase estimation, an ensemble strategy with two classifiers is used. This consensus-based estimation substantially increases tracking reliability by rejection of false positives. The algorithm is evaluated on both synthetic and measured phantom data: Monte Carlo simulated ultra low dose projections for a C-arm X-ray and on the basis of 4D-chest-CTs of eight patients on one hand side and real measurements based on a motion phantom. Results To achieve an accuracy of breathing-phase estimation of more than 95% a fluence between 20 and 400 photons per pixel (open field) is required depending on the patient. Furthermore, the algorithm is evaluated on real ultra low dose projections from an XVI R5.0 system (Elekta AB, Stockholm, Sweden) using an additional lead filter to reduce fluence. The classifiers-consensus-based-gating method estimated the correct position of the test projections in all test cases at a fluence of ∼180 photons per pixel and 92% at a fluence of ∼40 photons per pixel. The deposited dose to patient per image is in the range of nGy. Conclusions A novel method is presented for estimation of breathing-phases for real-time tumor localization at ultra low dose both on a simulation and a phantom basis. Its accuracy is comparable to state of the art X-ray based algorithms while the released dose to patients is reduced by two to three orders of magnitude compared to conventional template-based approaches. This allows for continuous motion control during irradiation without the need of external markers.

The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers’ positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior–inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.

OBJECTIVES: To evaluate the performance of 4-dimensional computed tomography (4D-CT) in assessing upper airway obstruction (UAO) in patients with Robin Sequence (RS) and compare the accuracy and reliability of 4D-CT and flexible fiberoptic laryngoscopy (FFL). STUDY DESIGN: Prospective survey of retrospective clinical data. SETTING: Single, tertiary care pediatric hospital. METHODS: At initial and 30-day timepoints, a multidisciplinary group of 11 clinicians who treat RS rated UAO severity in 36 sets of 4D-CT visualizations and FFL videos (dynamic modalities), and static CT images. Raters assessed UAO at the velopharynx and oropharynx (1-none to 5-complete) and noted confidence levels (LOC) of each rating. Intraclass correlation and Krippendorff’s Alpha were used to assess intra- and inter-rater reliability, respectively. Accuracy was assessed by comparing clinician ratings with Quantitative Percent Constriction (QPC) Ratings, calculated based on 4D-CT airway cross-sectional area. Results were compared using Wilcoxon rank-sum and signed-rank tests. RESULTS: 4D-CT and FFL demonstrated similar intra-rater agreement (moderate to substantial) and both demonstrated fair inter-rater agreement. Both modalities underestimated UAO severity, though 4D-CT ratings were significantly more accurate, as determined by QPC similarity, than FFL (−1.06 and −1.46 vs QPC Ratings, p=0.004). Overall LOC was similar for 4D-CT and FFL, but other specialists were significantly less confident in FFL ratings than were otolaryngologists (2.25 and 3.92, p

This study investigates agreement between ventilation and perfusion for lung cancer patients undergoing radiotherapy. Ventilation-perfusion scans of nineteen patients with stage III lung cancer from a prospective protocol were compared using voxel-wise Spearman correlation- coefficients. The presented results show in about 25% of patients, ventilation and perfusion exhibit lower agreement.

PURPOSE A novel variable cycle-based respiratory guidance method was proposed to synchronize the patterns between patients' breathing and the magnetic excitation of synchrotron under the mode of full-energy depth scanning beam delivery, in order to improve the treatment precision and efficiency for carbon ion therapy. METHODS Audio-visual biofeedback system with variable cycle-based respiratory guidance method was developed. We enrolled 6 healthy volunteers and a simulation study of the fixed cycle-based and variable cycle-based respiratory guidance with three treatment fractions was performed. A total of 72 breathing curves were collected for 4D dose calculations with three 4DCT datasets of lung tumor cases. Target dose coverage (D95: the percent dose covering 95% of the target), dose homogeneity (D5-D95), and treatment time were analyzed. The Wilcoxon signed-rank test was used for statistical difference analysis, and p

Purpose For mobile lung tumors, four‐dimensional computer tomography (4D CT) is often used for simulation and treatment planning. Localization accuracy remains a challenge in lung stereotactic body radiation therapy (SBRT) treatments. An attractive image guidance method to increase localization accuracy is 4D cone‐beam CT (CBCT) as it allows for visualization of tumor motion with reduced motion artifacts. However, acquisition and reconstruction of 4D CBCT differ from that of 4D CT. This study evaluates the discrepancies between the reconstructed motion of 4D CBCT and 4D CT imaging over a wide range of sine target motion parameters and patient waveforms. Methods A thorax motion phantom was used to examine 24 sine motions with varying amplitudes and cycle times and seven patient waveforms. Each programmed motion was imaged using 4D CT and 4D CBCT. The images were processed to auto segment the target. For sine motion, the target centroid at each phase was fitted to a sinusoidal curve to evaluate equivalence in amplitude between the two imaging modalities. The patient waveform motion was evaluated based on the average 4D data sets. Results The mean difference and root‐mean‐square‐error between the two modalities for sine motion were −0.35 ± 0.22 and 0.60 mm, respectively, with 4D CBCT slightly overestimating amplitude compared with 4D CT. The two imaging methods were determined to be significantly equivalent within ±1 mm based on two one‐sided t tests (p

Purpose: To analyze radiation induced changes in Hounsfield units and determine their correlation with changes in perfusion and ventilation. Additionally, to compare the post-RT changes in human subjects to those measured in a swine model used to quantify perfusion changes, and validate their use as a preclinical model. Methods: A cohort of 5 Wisconsin Miniature Swine (WMS™) were studied. Additionally, 19 human subjects were recruited as part of an IRB approved clinical trial studying functional avoidance radiation therapy for lung cancer and were treated with SBRT. Imaging (a contrast enhanced dynamic perfusion CT in the swine and 4DCT in the humans) was performed prior to and post-RT. Jacobian elasticity maps were calculated on all 4DCT images. Contours were created from the isodose lines to discretize analysis into 10 Gy dose bins. B-spline deformable image registration allowed for voxel-by-voxel comparative analysis in these contours between timepoints. The WMS™ underwent a research course of 60 Gy in 5 fractions delivered locally to a target in the lung using an MRI-LINAC system. In the WMS™ subjects, the dose-bin contours were copied onto the contralateral lung, which received < 5 Gy for comparison. Changes in HU and changes in Jacobian were analyzed in these contours.Results: Statistically significant (p < 0.05) changes in the mean HU value post-RT compared to pre-RT were observed in both the human and WMS™ groups at all timepoints analyzed. The HU increased linearly with dose for both groups. Strong linear correlation was observed between the changes seen in the swine and humans (Pearson coefficient > 0.97, p< 0.05) at all timepoints. Changes seen in the swine closely modeled the changes seen in the humans at 12 months post RT (slope=0.95). Jacobian analysis showed between 30-60% of voxels were damaged post-RT. Perfusion analysis in the swine showed a statistically significant (p < 0.05) reduction in contrast inside the vasculature 3 months post-RT compared to pre-RT. The increases in contrast outside the vasculature was strongly correlated (Pearson Correlation 0.88) with the reduction in HU inside the vasculature but were not correlated with the changes in Jacobians. Conclusions: Radiation induces changes in pulmonary anatomy at 3 months post-RT, with a strong linear correlation with dose. The change in HU seen in the non-vessel lung parenchyma suggests this metric is a potential biomarker for change in perfusion. Finally, this work suggests that the WMS™ swine model is a promising pre-clinical model for analyzing radiation-induced changes in humans and poses several benefits over conventional swine models.

Respiratory motion estimation is an important part in image-guided radiation therapy and clinical diagnosis. However, most of the respiratory motion estimation methods rely on indirect measurements of external breathing indicators, which will not only introduce great estimation errors, but also bring invasive injury for patients. In this paper, we propose a method of lung respiratory motion estimation based on fast Kalman filtering and 4D CT image registration (LRME-4DCT). In order to perform dynamic motion estimation for continuous phases, a motion estimation model is constructed by combining two kinds of GPU-accelerated 4D CT image registration methods with fast Kalman filtering method. To address the high computational requirements of 4D CT image sequences, a multi-level processing strategy is adopted in the 4D CT image registration methods, and respiratory motion states are predicted from three independent directions. In the DIR-lab dataset and POPI dataset with 4D CT images, the average target registration error (TRE) of the LRME-4DCT method can reach 0.91 mm and 0.85 mm respectively. Compared with traditional estimation methods based on pair-wise image registration, the proposed LRME-4DCT method can estimate the physiological respiratory motion more accurately and quickly. Our proposed LRME-4DCT method fully meets the practical clinical requirements for rapid dynamic estimation of lung respiratory motion.

Purpose In this study we present a novel method for re‐calculating a treatment plan on different respiratory phases by accurately modeling the panning and tilting beam motion during DTT (the “rotation method”). This method is used to re‐calculate the dose distribution of a plan on multiple breathing phases to accurately assess the dosimetry. Methods sIMRT plans were optimized on a breath hold computed tomography (CT) image taken at exhale (BHexhale) for 10 previous liver stereotactic ablative radiotherapy patients. Our method was used to re‐calculate the plan on the inhale (0%) and exhale (50%) phases of the four‐dimensional CT (4DCT) image set. The dose distributions were deformed to the BHexhale CT and summed together with proper weighting calculated from the patient’s breathing trace. Subsequently, the plan was re‐calculated on all ten phases using our method and the dose distributions were deformed to the BHexhale CT and accumulated together. The maximum dose for certain organs at risk (OARs) was compared between calculating on two phases and all ten phases. Results In total, 26 OARs were examined from 10 patients. When the dose was calculated on the inhale and exhale phases six OARs exceeded their dose limit, and when all 10 phases were used five OARs exceeded their limit. Conclusion Dynamic tumor tracking plans optimized for a single respiratory phase leave an OAR vulnerable to exceeding its dose constraint during other respiratory phases. The rotation method accurately models the beam’s geometry. Using deformable image registration to accumulate dose from all 10 breathing phases provides the most accurate results, however it is a time consuming procedure. Accumulating the dose from two extreme breathing phases (exhale and inhale) and weighting them properly provides accurate results while requiring less time. This approach should be used to confirm the safety of a DTT treatment plan prior to delivery.

Purpose The purpose of this study was to provide guidance in developing and implementing a process for the accurate delivery of free breathing respiratory amplitude‐gated treatments. Methods A phase‐based 4DCT scan is acquired at time of simulation and motion is evaluated to determine the exhale phases that minimize respiratory motion to an acceptable level. A phase subset average CT is then generated for treatment planning and a tracking structure is contoured to indicate the location of the target or a suitable surrogate over the planning phases. Prior to treatment delivery, a 4DCBCT is acquired and a phase subset average is created to coincide with the planning phases for an initial match to the planning CT. Fluoroscopic imaging is then used to set amplitude gate thresholds corresponding to when the target or surrogate is in the tracking structure. The final imaging prior to treatment is an amplitude‐gated CBCT to verify both the amplitude gate thresholds and patient positioning. An amplitude‐gated treatment is then delivered. This technique was commissioned using an in‐house lung motion phantom and film measurements of a simple two‐field 3D plan. Results The accuracy of 4DCBCT motion and target position measurements were validated relative to 4DCT imaging. End to end testing showed strong agreement between planned and film measured dose distributions. Robustness to interuser variability and changes in respiratory motion were demonstrated through film measurements. Conclusions The developed workflow utilizes 4DCBCT, respiratory‐correlated fluoroscopy, and gated CBCT imaging in an efficient and sequential process to ensure the accurate delivery of free breathing respiratory‐gated treatments.

Purpose Our study aimed to improve the dosimetry of post modified radical mastectomy intensity‐modulated radiotherapy (PMRM‐IMRT) for left‐sided breast cancer patients by tailoring and minimizing PTV expansion three‐dimensionally utilizing 4D CT combined with on‐board cone beam CT (CBCT). Methods We enrolled a total of 10 consecutive left‐sided breast cancer patients to undergo PMRM‐IMRT. We measured the intra‐fractional CTV displacement attributed to respiratory movement by defining 9 points on the left chest wall and quantifying their displacement by using the 4D CT, and measured the inter‐fractional CTV displacement resulting from the integrated effect of respiratory movement, thoracic deformation and set up errors by using CBCT. We created 3 different PMRM‐IMRT plans for each of the patients using PTVt (tailored PTV expansion three‐dimensionally), PTV0.5 and PTV0.7 (isotropic 0.5‐ cm and isotropic 0.7‐ cm expanding margin of CTV), respectively. We performed paired samples t test to establish a hierarchy in terms of plan quality and dosimetric benefits. P

Accurate calculation of set-up margin is a prerequisite to arrive at the most optimal clinical to planning target volume margin. The aim of this study was to evaluate the compatibility of different on-board and in-room stereoscopic imaging modalities by calculating the set-up margins (SM) in stereotactic body radiotherapy technique accounting and unaccounting for rotational positional errors (PE). Further, we calculated separate SMs one based on residual positional errors and another based on residual + intrafraction positional errors from the imaging data obtained in a dual imaging environment. A total of 22 lung cancer patients were included in this study. For primary image guidance, four-dimensional cone beam computed tomography (4-D CBCT) was used and stereoscopic ExacTrac was used as the auxiliary imaging. Following table position correction (TPC) based on the initial 4-D CBCT, another 4-D CBCT (post-TPC) and a pair of stereoscopic ExacTrac images were obtained. Further, during the treatment delivery, a series of ExacTrac images were acquired to identify the intrafraction PE. If a, b and c were the observed translational shifts in lateral (x-axis), longitudinal (y-axis) and vertical direction (z-axis) and α, β and γ were the rotational shifts in radians about the same axes, respectively, then the resultant translational vectors (A, B and C) were calculated on the basis of translational and rotational values. Set-up margins were calculated using residual errors post-TPC only and also using intrafraction positional errors in addition to the residual errors. Residual and residual + intrafraction SM were calculated from a dataset of 82 CBCTs and 189 ExacTrac imaging sessions. CBCT-based mean ± SD shifts in translational and rotational directions were 0.3 ± 1.8 mm, 0.1 ± 1.8 mm, − 0.4 ± 1.6 mm, 0.1 ± 0.4°, 0.0 ± 1.0° and 0.3 ± 0.7°, respectively, and for ExacTrac − 0.1 ± 1.8 mm, 0.2 ± 2.4 mm, − 0.6 ± 1.8 mm, 0.1 ± 1.2°, − 0.2 ± 1.3° and − 0.1 ± 0.6°, respectively. Residual SM without considering the rotational correction in x, y and z directions were 5.0 mm, 4.5 mm and 4.4 mm; rotation-corrected SM were 4.4 mm, 4.0 mm and 5.5 mm, respectively. Residual plus intrafraction SM were 5.5 mm, 6.6 mm and 6.2 mm without considering the rotational corrections, whereas they were 5.0 mm, 6.3 mm and 6.2 mm with rotational errors accounted for. Accurate calculation of set-up margin is required to find the clinical to planning target volume margin. Primary and auxiliary imaging margins fall in the range of 4.0 to 5.5 mm and 5.0 to 7.0 mm, respectively, indicating a higher SM for X-ray-based planar imaging techniques over three-dimensional cone beam images. This study established the degree of mutual compatibility between two different kinds of widely used set-up imaging modalities, on-board CBCT and in-room stereoscopic imaging ExacTrac. It also describes the technique to calculate the residual and residual plus intrafraction SM and its variation in a dual imaging environment accounting for rotational PE in stereotactic body radiotherapy of lung.

Intracranial arterial stiffening is a potential early marker of emerging cerebrovascular dysfunction and could be mechanistically involved in disease processes detrimental to brain function via several pathways. A prominent consequence of arterial wall stiffening is the increased velocity at which the systolic pressure pulse wave propagates through the vasculature. Previous non-invasive measurements of the pulse wave propagation have been performed on the aorta or extracranial arteries with results linking increased pulse wave velocity to brain pathology. However, there is a lack of intracranial “target-organ” measurements. Here we present a 4D flow MRI method to estimate pulse wave velocity in the intracranial vascular tree. The method utilizes the full detectable branching structure of the cerebral vascular tree in an optimization framework that exploits small temporal shifts that exists between waveforms sampled at varying depths in the vasculature. The method is shown to be stable in an internal consistency test, and of sufficient sensitivity to robustly detect age-related increases in intracranial pulse wave velocity.

PurposeRespiratory-induced motion of oesophageal tumours and lymph nodes can influence positron emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases. MethodsThis prospective observational study (NCT02424864) included thirty-seven newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing 18F-fluorodeoxyglucose uptake for their degree of suspicion. ResultsThe mean (95% CI) SUVmax of the primary tumour was 13.1(10.6-15.5) versus 13.0(10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08(-3.60 - 3.75), -0.26(-2.34 – 1.82), 4.66(-29.61 – 38.92)cm3 and -0.95(-19.9 – 18.0)cm3 for tumour SUVmax, lymph node SUVmax, for MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6(4.3-8.8) and 6.8(4.5-9.1) for 3D and motion-compensated, respectively.ConclusionsSUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection. Trial registration(www.clinicaltrials.gov: NCT02424864)

Purpose To use Discrete Cosine Transform to include tumor motion variations on ITV definition of SBRT patients. Methods Data from 66 patients was collected. 2D planar fluoroscopy images (FI) were available for 54 patients. Daily CBCT projections (CBCTp) from 29 patients were employed to measure interfraction amplitude variability. Systematic amplitude variations were obtained from 17 patients with data from both FI and CBCTp. Tumor motion curves obtained from FI were characterized with a Cosine model (CM), based on cosine functions to the power of 2, 4 or 6, and DCT. Performance of both models was evaluated by means of R2 coefficient and by comparing their results on Internal Target Volume (ITV) margins against those calculated from original tumor motion curves. Amplitude variations from CBCTp, as well as estimations of baseline shift variations were added to the DCT model to account for their effect on ITV margins. Results DCT replicated tumor motion curves with a mean R2 values for all patients of 0.86, 0.91 and 0.96 for the lateral (LAT), anterior-posterior (AP) and cranio-caudal (CC) directions respectively. CM yielded worst results, with R2 values of 0.64, 0.61 and 0.74 in the three directions. Interfraction amplitude variation increased ITV margins by a 9%, while baseline shift variability implied a 40% and 80–100% increase for normalized values of baseline shift of 0.2 and 0.4 respectively. Conclusions Probability distribution functions of tumor positions can be successfully characterized with DCT. This permits to include tumor motion variablilities obtained from patient population into patient specific ITVs.

Background The use of imaging is indispensable in modern radiation therapy, both for simulation and treatment delivery. For safe and sure utilization, dose delivery from imaging must be evaluated. Objective This study aims to investigate the dose to organ at risk (OAR) delivered by imaging during lung stereotactic body radiation therapy (SBRT) and to evaluate its contribution to the treatment total dose. Material and methods In this retrospectively study, imaging total dose to organs at risk (OARs) (spinal cord, esophagus, lungs, and heart) and effective dose were retrospectively evaluated from 100 consecutive patients of a single institution who had lung SBRT. For each patient, dose was estimated using Monte-Carlo convolution for helical computed tomography (helical CT), Four-Dimensional CT (4D-CT), and kilovoltage Cone-Beam CT (kV-CBCT). Helical CT and kV-CBCT dose were evaluated for the entire thorax acquisition, while 4D-CT dose was analyzed on upper lobe (UL) or lower lobe (LL) acquisition. Treatment dose was extracted from treatment planning system and compared to imaging total dose. Results Imaging total dose maximum values were 117 mGy to the spinal cord, 127 mGy to the esophagus, 176 mGy to the lungs and 193 mGy to the heart. The maximum effective dose was 19.65 mSv for helical CT, 10.62 mSv for kV-CBCT, 25.95 mSv and 38.45 mSv for 4D-CT in UL and LL regions, respectively. Depending on OAR, treatment total dose was higher from 1.7 to 8.2 times than imaging total dose. Imaging total dose contributed only to 0.3% of treatment total dose. Conclusion Imaging dose delivered with 4D-CT to the OARs is higher than those of others modalities. The heart received the highest imaging dose for both UL and LL. Total imaging dose is negligible since it contributed only to 0.3% of treatment total dose.

Purpose Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer. Methods From 2010–2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used. Results A total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2–29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6–86.9) and 16.0 months (range 0.2–86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5–36.4) and 12.1 months (95% CI 8.2–16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients. Conclusions Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.

PURPOSE Computed tomography (CT)-derived ventilation methods compute respiratory induced volume changes as a surrogate for pulmonary ventilation. Currently, there are no known methods to derive perfusion information from noncontrast CT. We introduce a novel CT-Perfusion (CT-P) method for computing the magnitude mass changes apparent on dynamic noncontrast CT as a surrogate for pulmonary perfusion. METHODS CT-Perfusion is based on a mass conservation model which describes the unknown mass change as a linear combination of spatially corresponding inhale and exhale HU estimated voxel densities. CT-P requires a deformable image registration (DIR) between the inhale/exhale lung CT pair, a preprocessing lung volume segmentation, and an estimate for the Jacobian of the DIR transformation. Given this information, the CT-P image, which provides the magnitude mass change for each voxel within the lung volume, is formulated as the solution to a constrained linear least squares problem defined by a series of subregional mean magnitude mass change measurements. Similar to previous robust CT-ventilation methods, the amount of uncertainty in a subregional sample mean measurement is related to measurement resolution and can be characterized with respect to a tolerance parameter τ . Spatial Spearman correlation between single photon emission CT perfusion (SPECT-P) and the proposed CT-P method was assessed in two patient cohorts via a parameter sweep of τ . The first cohort was comprised of 15 patients diagnosed with pulmonary embolism (PE) who had SPECT-P and 4DCT imaging acquired within 24 h of PE diagnosis. The second cohort was comprised of 15 nonsmall cell lung cancer patients who had SPECT-P and 4DCT images acquired prior to radiotherapy. For each test case, CT-P images were computed for 30 different uncertainty parameter values, uniformly sampled from the range [0.01, 0.125], and the Spearman correlation between the SPECT-P and the resulting CT-P images were computed. RESULTS The median correlations between CT-P and SPECT-P taken over all 30 test cases ranged between 0.49 and 0.57 across the parameter sweep. For the optimal tolerance τ = 0.0385, the CT-P and SPECT-P correlations across all 30 test cases ranged between 0.02 and 0.82. A one-sample sign test was applied separately to the PE and lung cancer cohorts. A low Spearmen correlation of 15% was set as the null median value and two-sided alternative was tested. The PE patients showed a median correlation of 0.57 (IQR = 0.305). One-sample sign test was statistically significant with 96.5 % confidence interval: 0.20-0.63, P

Purpose The interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order (“down” and “up” directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan. Method The current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst‐case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases. Results The number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95% ≥ 98% and D99% ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1%

PURPOSE Current radiotherapy planning procedures are generally designed based on anatomical information only and use computed tomography (CT) images that do not incorporate organ-functional information. In this study, we developed a method for estimating liver elasticity using the finite element method (FEM) and four-dimensional CT (4DCT) images acquired during radiotherapy planning, and we subsequently evaluated its feasibility as a biomarker for liver fibrosis. MATERIALS AND METHODS Twenty patients who underwent 4DCT and ultrasound-based transient elastography (UTE) were enrolled. All patients had chronic liver disease or cirrhosis. Liver elasticity measurements of the UTE were performed on the right lobe of the patient's liver in 20 patients. The serum biomarkers of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) were available in 18 of the 20 total patients, which were measured within 1 week after undergoing 4DCT. The displacement between the 4DCT images obtained at the endpoints of exhalation and inspiration was determined using the actual (via deformable image registration) and simulated (via FEM) respiration-induced displacement. The elasticity of each element of the liver model was optimized by minimizing the error between the actual and simulated respiration-induced displacement. Then, each patient's estimated liver elasticity was defined as the mean Young's modulus of the liver's right lobe and that of the whole liver using the estimated elasticity map. The estimated liver elasticity was evaluated for correlations with the elasticity obtained via UTE and with two serum biomarkers (APRI and FIB-4). RESULTS The mean ± standard deviation (SD) of the errors between the actual and simulated respiration-induced displacement in the liver model was 0.54 ± 0.33 mm. The estimated liver's right lobe elasticity was statistically significantly correlated with the UTE (r = 0.87, P

Objective We aimed to establish a quantitative description of motion patterns and establish test-retest reliability of the four-dimensional CT when quantifying in vivo kinematics of the scaphoid, lunate, and capitate. Materials and methods We assessed in vivo kinematics of both wrists of 20 healthy volunteers (11 men and 9 women) between the ages of 20 and 40 years. All volunteers performed active flexion-extension and radial-ulnar deviation with both wrists. To test for reliability, one motion cycle was rescanned for both wrists approximately 15 min after the first scan. The coefficient of multiple correlation was used to analyze reliability. When two motion patterns are similar, the coefficient of multiple correlation tends towards 1, whereas in dissimilar motion patterns, it tends towards 0. The root mean square deviation was used to analyze the total motion patterns variability between the two scans. Results Overall, mean or median coefficient of multiple correlations were higher than 0.86. The root mean square deviations were low and ranged from 1.17° to 4.29°. Conclusion This innovative non-invasive imaging technique can reliably describe in vivo carpal kinematics of uninjured wrists in healthy individuals. It provides us with a better understanding and reference values of carpal kinematics of the scaphoid, lunate, and capitate.

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field.

The sliding motion along the boundaries of discontinuous regions has been actively studied in B-spline free-form deformation framework. This study focusses on the sliding motion for a velocity field-based 3D+t registration. The discontinuity of the tangent direction guides the deformation of the object region, and a separate control of two regions provides a better registration accuracy. The sliding motion under the velocity field-based transformation is conducted under the [Formula: see text] -Rényi entropy estimator using a minimum spanning tree (MST) topology. Moreover, a new topology changing method of the MST is proposed. The topology change is performed as follows: inserting random noise, constructing the MST, and removing random noise while preserving a local connection consistency of the MST. This random noise process (RNP) prevents the [Formula: see text] -Rényi entropy-based registration from degrading in sliding motion, because the RNP creates a small disturbance around special locations. Experiments were performed using two publicly available datasets: the DIR-Lab dataset, which consists of 4D pulmonary computed tomography (CT) images, and a benchmarking framework dataset for cardiac 3D ultrasound. For the 4D pulmonary CT images, RNP produced a significantly improved result for the original MST with sliding motion (p

Objective This study aims to determine if low iodine dynamic computed tomography angiography performed after a fixed delay or test bolus acquisition demonstrates high concordance with clinical computed tomography angiography (using a routine amount of iodinated contrast) to display lower extremity peripheral arterial disease. Methods After informed consent, low iodine dynamic computed tomography angiography examination (using either a fixed delay or test bolus) using 50 ml of iodine contrast media was performed. A subsequent clinical computed tomography angiography using standard iodine dose (115 or 145 ml) served as the reference standard. A vascular radiologist reviewed dynamic and clinical computed tomography angiography images to categorize the lumen into “not opacified”, “70% stenosis”, and “occluded” for seven arterial segments in each lower extremity. Concordance between low iodine dynamic computed tomography angiography and the routine iodine reference standard was calculated. The clinical utility of 4D volume-rendered images was also evaluated. Results Sixty-eight patients (average age 66.1 ± 12.3 years, male; female = 49: 19) were enrolled, with 34 patients each undergoing low iodine dynamic computed tomography angiography using fixed delay and test bolus techniques, respectively. One patient assigned to the test bolus group did not undergo low iodine computed tomography angiography due to unavailable delayed time. The fixed delay was 13 s, with test bolus acquisition resulting in a mean variable delay prior to image acquisition of 19.5 s (range; 8–32 s). Run-off to the ankle was observed using low iodine dynamic computed tomography angiography following fixed delay and test bolus acquisition in 76.4% (26/34) and 100% (33/33) of patients, respectively ( p = 0.005). Considering extremities with run-off to the ankle and without severe artifact, the concordance rate between low iodine dynamic computed tomography angiography and the routine iodine reference standard was 86.8% (310/357) using fixed delay and 97.9% (425/434) using test bolus ( p Conclusion Low iodine dynamic computed tomography angiography with test bolus acquisition has a high concordance with routine peripheral computed tomography angiography performed with standard iodine dose, resulting in improved run-off to the ankle compared to dynamic computed tomography angiography performed after a fixed delay. This method is useful for minimizing iodine dose in patients at risk for contrast-induced nephropathy. 4D volume-rendered computed tomography angiography images provide useful dynamic information.

BACKGROUND AND PURPOSE: There are several alternatives to the widespread ITV strategy in order to account for breathing-induced motion in PTV margins. The most sophisticated one includes the generation of a motion-compensated CT scan with the CTV placed in its average position - the mid-position approach (MidP). In such configuration, PTV margins integrate breathing as another random error. Despite overall irradiated volume reduction, such approach is barely used in clinical practice because of its dependence to deformable registration and its unavailability in commercial treatment planning systems. As an alternative, the mid-ventilation approach (MidV) selects the phase in the 4D-CT scan that is the closest to the MidP, with a residual error accounted for in the PTV margin. We propose a treatment planning system-integrated strategy, aiming at better approximating the MidP approach without its drawbacks: Hybrid MidV-MidP approach, i.e., the delineation on the MidV-CT and translation at the mid-position coordinates using treatment planning system built-in capabilities. MATERIAL AND METHODS: Forty-five lung lesions treated with stereotactic radiotherapy were selected. PTV was defined using MidP, MidV, Hybrid MidV-MidP and ITV strategies. Margin definitions were adapted and resulting PTVs were compared. RESULTS: Hybrid MidV-MidP showed similar target volume and location than the MidP and confirmed that margin-incorporated tumor motion strategies lead to significantly smaller PTVs than the ITV with mean reduction of 26 ± 7%. CONCLUSION: We report on the successful implementation of a pseudo-MidP solution without its inherent drawbacks. It answers the need for TPS-embedded tumor motion range identification and related margin's component calculation. ispartof: MEDICAL DOSIMETRY vol:46 issue:3 pages:253-258 ispartof: location:United States status: published

The present study was undertaken to investigate the suitability of alternative internal target volume (ITV) delineation strategies based on maximum intensity projection (MIP), average intensity projection (AIP), 2 extreme phases and 4 phases images relative to the ITV10phase in stereotactic body radiation therapy (SBRT) for lung cancer. The 4-dimensional computed tomography (4DCT) data of 15 lung cancer patients treated with SBRT in our clinic were used. Five different ITVs were generated as follows: merging GTVs from 10 phases (ITV10Phase); merging GTVs from 2 extreme phases (0%, 50%) (ITV2Phase); merging GTVs from 4 phases (0%, 20%, 50%, and 70%) (ITV4Phase); delineating GTV on MIP (ITVMIP), and delineating GTV on AIP (ITVAIP). PTV10Phase, PTV2Phase, PTV4Phase, PTVMIP, and PTVAIP were generated by adding a 5-mm margin around the related ITV. Volumetric analyses were performed for 4 ITVs and PTVs relative to ITV10phase and PTV10phase. SBRT plans made for all PTVs were evaluated for dosimetric effect of alternative ITV delineation strategies. The mean percentage overlap volume (POV) for PTV2phase, PTV4phase, PTVMIP, and PTVAIP relative to PTV10phase were 84.2 ± 5.4%, 92.0 ± 2.9%, 82.2 ± 5.7%, and 73.8 ± 9.3%, for lower-lobe tumors, respectively. The mean POV for PTV2phase, PTV4phase, PTVMIP, and PTVAIP relative to PTV10phase were 93.2 ± 2.5%, 95.9 ± 1.0%, 87.5 ± 6.7%, and 83.3 ± 6.8% for upper-lobe, respectively. For lower-lobe tumors the mean differences in V20 and MLD for plans based on PTV2phase and PTV4phase were

Aims NeoSCOPE is a trial of two different neoadjuvant chemoradiotherapy regimens for resectable oesophageal cancer and was the first multicentre trial in the UK to incorporate four-dimensional computed tomography (4D-CT) into radiotherapy planning. Despite 4D-CT being increasingly accepted as a standard of care for lower third and junctional oesophageal tumours, there is limited evidence of its benefit over standard three-dimensional computed tomography (3D-CT). Materials Using NeoSCOPE 4D-CT cases, we undertook a dosimetric comparison study of 3D-CT versus 4D-CT plans comparing target volume coverage and dose to organs at risk. We used established normal tissue complication probability models to evaluate the potential toxicity reduction of using 4D-CT plans in oesophageal cancer. Results 4D-CT resulted in a smaller median absolute PTV volume and lower dose levels for all reported constraints with comparable target volume coverage. NTCP modelling suggests a significant relative risk reduction of cardiac and pulmonary toxicity endpoints with 4D-CT. Conclusion Our work shows that incorporating 4D-CT into treatment planning may significantly reduce the toxicity burden from this treatment.

Our markerless tumor tracking algorithm requires 4DCT data to train models. 4DCT cannot be used for markerless tracking for respiratory-gated treatment due to inaccuracies and a high radiation dose. We developed a deep neural network (DNN) to generate 4DCT from 3DCT data.We used 2420 thoracic 4DCT datasets from 436 patients to train a DNN, designed to export 9 deformation vector fields (each field representing one-ninth of the respiratory cycle) from each CT dataset based on a 3D convolutional autoencoder with shortcut connections using deformable image registration. Then 3DCT data at exhale were transformed using the predicted deformation vector fields to obtain simulated 4DCT data. We compared markerless tracking accuracy between original and simulated 4DCT datasets for 20 patients. Our tracking algorithm used a machine learning approach with patient-specific model parameters. For the training stage, a pair of digitally reconstructed radiography images was generated using 4DCT for each patient. For the prediction stage, the tracking algorithm calculated tumor position using incoming fluoroscopic image data.Diaphragmatic displacement averaged over 40 cases for the original 4DCT were slightly higher (1.3 mm) than those for the simulated 4DCT. Tracking positional errors (95th percentile of the absolute value of displacement, "simulated 4DCT" minus "original 4DCT") averaged over the 20 cases were 0.56 mm, 0.65 mm, and 0.96 mm in the X, Y and Z directions, respectively.We developed a DNN to generate simulated 4DCT data that are useful for markerless tumor tracking when original 4DCT is not available. Using this DNN would accelerate markerless tumor tracking and increase treatment accuracy in thoracoabdominal treatment.

Introduction This study aimed to assess the carpal arch dynamics during active finger and wrist motion following carpal tunnel release using four-dimensional computed tomography (4D-CT). Materials and Methods Four patients who diagnosed with bilateral carpal tunnel syndrome and underwent unilateral carpal tunnel release were prospectively included. 4D-CT of the bilateral wrists during active finger and wrist motion was performed for 10 seconds at five frames per second. The distances between the tip of tuberosity of the scaphoid and the volar ridge of the pisiform (S–P distance) and volar ridge of trapezium and the tip of hook of hamate (T–H distance) were measured at each position and the values of S–P and T–H distances were compared between the postoperative and contralateral wrists. Results During finger motion, the S–P and T–H distances were not different at any position between the postoperative side and contralateral side. Conversely, S–P and T–H distances gradually increased in the postoperative wrists. The differences between the sides of S–P distance were significant, with >0 degrees of wrist extension, and differences of T–H distance were significant with >15 degrees of wrist extension. Conclusion This study demonstrated the carpal arch dynamics using 4D-CT and revealed that the carpal arch was widened with the wrist in extension after carpal tunnel release. This study suggests that the transverse carpal ligament plays an important role in maintaining carpal arch stability.

Background and purposeWhen treating patients for esophageal cancer (EC) with photon or proton radiotherapy (RT), breathing motion of the target and neighboring organs may result in deviations from the planned dose distribution. The aim of this study was to evaluate the magnitude and dosimetric impact of breathing motion. Results were based on comparing weekly 4D computed tomography (4D CT) scans with the planning CT, using the diaphragm as an anatomical landmark for EC.Material and methodsA total of 20 EC patients were included in this study. Diaphragm breathing amplitudes and off-sets (changes in position with respect to the planning CT) were determined from delineated left diaphragm structures in weekly 4D CT-scans. The potential dosimetric impact of respiratory motion was shown in several example patients for photon and proton radiotherapy.ResultsVariation in diaphragm amplitudes were relatively small and ranged from 0 to 0.8 cm. However, the measured off-sets were larger, ranging from -2.1 to 1.9 cm. Of the 70 repeat CT-scans, the off-set exceeded the ITV-PTV margin of 0.8 cm during expiration in 4 CT-scans (5.7%) and during inspiration in 13 CT-scans (18.6%). The dosimetric validation revealed under- and overdosages in the VMAT and IMPT plans.ConclusionsDespite relatively constant breathing amplitudes, the variation in the diaphragm position (off-set), and consequently tumor position, was clinically relevant. These motion effects may result in either treatments that miss the target volume, or dose deviations in the form of highly localized over- or underdosed regions.

Eisuke Mochizuki,1 Yoshiihiro Kawai,2 Keisuke Morikawa,1 Yutaro Ito,1 Namio Kagoo,1 Tsutomu Kubota,1 Koshiro Ichijyo,1 Masahiro Uehara,1 Masanori Harada,1 Shun Matsuura,1 Masaru Tsukui,1 Naoki Koshimizu1 1Department of Respiratory Medicine, Fujieda Municipal Hospital, Fujieda 426-8677, Japan; 2Department of Radiology, Fujieda Municipal Hospital, Fujieda 426-8677, JapanCorrespondence: Eisuke Mochizuki Tel +81-54-646-1111Fax +81-54-646-1122Email eisukefukui@gmail.comBackground: The validity of four-dimensional dynamic-ventilation CT scan for distinguishing COPD from asthma has not been established.Purpose: To assess whether four-dimensional dynamic-ventilation CT scan can aid in the diagnosis of COPD by comparing local lung movement during tidal breathing between COPD and asthma.Patients and Methods: Thirty-three COPD patients (30 males and three females; median age 74; range 44– 89 years) and 11 asthma patients (five males and six females; median age 55; range: 32– 75 years) underwent whole-lung dynamic-ventilation CT scan. CT data were reconstructed, one respiratory cycle to 10 phases, and in addtion we reconstructed threefold new phase data sets. We then analyzed local lung movement during tidal breathing using unpaired t-tests and chi-squared tests.Results: The local lung movement in COPD patients was significantly smaller than in asthma patients, especially in the ventral part of the lung. This was so even in patients who had mild emphysema (Goddard score < 8).Conclusion: Quantitative evaluation using four-dimensional dynamic-ventilation CT scan demonstrated that local lung movement during tidal breathing, particularly in the ventral lung, was smaller in COPD than in asthma patients, which may help distinguish COPD from asthma.Keywords: COPD, asthma four-dimensional dynamic-ventilation CT

Purpose Emerging evidence suggests that the heart is more radiosensitive than previously assumed; therefore, accounting for heart motion in radiation therapy planning is becoming more critical. In this study, we determined how much heart delineations based on 3-dimensional (3D) computed tomography (CT), 4-dimensional (4D) average projection (AVG), and maximum intensity projection (MIP) images should be extended to represent the full extent of heart motion during 4D imaging acquisition. Methods and Materials The 3D and 4D CT scans of 10 lung cancer patients treated with stereotactic ablative radiation therapy were used. Median surfaces were derived from heart delineations of 3 observers on the 3D CT, AVG, MIP, and 25% exhale scans. Per patient, the 25% exhale contour was propagated on every phase of the 4D scan. The union of all 4D phase delineations (U4D) represented the full extent of heart motion during imaging acquisition. Surface distances from U4D to 3D, AVG, and MIP volumes were calculated. Distances in the most extreme surface points (1.5 cm most superoinferior, 10% most right/left/anteroposterior) were used to derive margins accounting only for systematic (delineation) errors. Results Heart delineations on the MIP were the closest to the full extent of motion, requiring only ≤2.5-mm margins. Delineations on the AVG and 3D scans required margins up to 3.4 and 7.1 mm, respectively. The largest margins were for the inferior, right, and anterior aspects for the delineations on the 3D, AVG, and MIP scans, respectively. Conclusion Delineations on 3D, AVG, or MIP scans required extensions for representing the heart’s full extent of motion, with the MIP requiring the smallest margins. Research including daily imaging to determine the random components for the margins and dosimetric measurements to determine the relevance of creating a planning organ at risk volume of the heart is required.

Interplay effects in highly modulated stereotactic body radiation therapy lung cases treated with volumetric modulated arc therapy. Purpose To evaluate the influence of tumor motion on dose delivery in highly modulated stereotactic body radiotherapy (SBRT) of lung cancer using volumetric modulated arc therapy (VMAT). Methods 4D‐CT imaging data of the quasar respiratory phantom were acquired, using a GE Lightspeed 16‐slice CT scanner, while the phantom reproduced patient specific respiratory traces. Flattening filter‐free (FFF) dual‐arc VMAT treatment plans were created on the acquired images in Pinnacle3 treatment planning system. Each plan was generated with varying levels of complexity characterized by the modulation complexity score. Static and dynamic measurements were delivered to GafChromic EBT3 film inside the respiratory phantom using an Elekta Versa HD linear accelerator. The treatment prescription was 10 Gy per fraction for 5 fractions. Comparisons of the planned and delivered dose distribution were performed using Radiological Imaging Technology (RIT) software. Results For the motion amplitudes and periods studied, the interplay effect is insignificant to the GTV coverage. The mean dose deviations between the planned and delivered dose distribution never went below −2.00% and a minimum dose difference of −5.05% was observed for a single fraction. However for amplitude of 2 cm, the dose error could be as large as 20.00% near the edges of the PTV at increased levels of complexity. Additionally, the modulation complexity score showed an ability to provide information related to dose delivery. A correlation value (R) of 0.65 was observed between the complexity score and the gamma passing rate for GTV coverage. Conclusions As expected, respiratory motion effects are most evident for large amplitude respirations, complex fields, and small field margins. However, under all tested conditions target coverage was maintained.

PURPOSE. The computed tomography (CT) derived ventilation imaging methodology employs deformable image registration (DIR) to recover respiratory motion-induced volume changes from an inhale/exhale CT image pair, as a surrogate for ventilation. The Integrated Jacobian Formulation (IJF) and Mass Conserving Volume Change (MCVC) numerical methods for volume change estimation represent two classes of ventilation methods, namely transformation-based and intensity (Hounsfield Unit) based, respectively. Both the IJF and MCVC methods utilize subregional volume change measurements that satisfy a specified uncertainty tolerance. In previous publications, the ventilation images resulting from this numerical strategy demonstrated robustness to DIR variations. However, the reduced measurement uncertainty comes at the expense of measurement resolution. The purpose of this study is to examine the spatial correlation between robust CT ventilation images and single photon emission CT ventilation (SPECT-V). METHODS: Previously described implementations of IJF and MCVC require the solution of a large scale, constrained linear least squares problem defined by a series of robust subregional volume change measurements. We introduce a simpler parameterized implementation that reduces the number of unknowns while increasing the number of data points in the resulting least squares problem. A parameter sweep of the measurement uncertainty tolerance, τ, was conducted using the 4DCT and SPECT-V images acquired for fifteen non-small cell lung cancer patients prior to radiotherapy. For each test case, MCVC and IJF CT-ventilation images were created for 30 different uncertainty parameter values, uniformly sampled from the range [0.01, 0.25]. Voxel-wise Spearman correlation between the SPECT-V and the resulting CT-ventilation images were computed. RESULTS: The median correlations between MCVC and SPECT-V ranged from 0.20 to 0.48 across the parameter sweep, while the median correlations for IJF and SPECT-V ranged between 0.79 and 0.82. For the optimal IJF tolerance τ = 0.07, the IJF and SPECT-V correlations across all fifteen test cases ranged between 0.12 and 0.90. For the optimal MCVC tolerance τ = 0.03, the MCVC and SPECT-V correlations across all fifteen test cases ranged between −0.06 and 0.84. CONCLUSION: The reported correlations indicate that robust methods generate ventilation images that are spatially consistent with SPECT-V, with the transformation-based IJF method yielding higher correlations than those previously reported in the literature. For both methods, overall correlations were found to marginally vary for τ ∈ [0.03, 0.15], indicating that the clinical utility of both methods is robust to both uncertainty tolerance and DIR solution.

Purpose Four-dimensional cone-beam computed tomography (4D CBCT) imaging has been suggested as a solution to account for interfraction motion variability of moving targets like lung and liver during radiotherapy (RT) of moving targets. However, due to severe sparse view sampling artifacts, current 4D CBCT data lack sufficient image quality for accurate motion quantification. In the present paper, we introduce a deep learning-based framework for boosting the image quality of 4D CBCT image data that can be combined with any CBCT reconstruction approach and clinical 4D CBCT workflow. Methods Boosting is achieved by learning the relationship between so-called sparse view pseudo-time-average CBCT images obtained by a projection selection scheme introduced to mimic phase image sparse view artifact characteristics and corresponding time-average CBCT images obtained by full view reconstruction. The employed convolutional neural network architecture is the residual dense network (RDN). The underlying hypothesis is that the RDN learns the appearance of the streaking artifacts that is typical for 4D CBCT phase images - and removes them without influencing the anatomical image information. After training the RDN, it can be applied to the 4D CBCT phase images to enhance the image quality without affecting the contained temporal and motion information. Different to existing approaches, no patient-specific prior knowledge about anatomy or motion characteristics is needed, that is, the proposed approach is self-contained. Results Application of the trained network to reconstructed phase images of an external (SPARE challenge) as well as in-house 4D CBCT patient and motion phantom data set reduces the phase image streak artifacts consistently for all patients and state-of-the-art reconstruction approaches. Using the SPARE data set, we show that the root mean squared error compared to ground truth data provided by the challenge is reduced by approximately 50% while normalized cross correlation of reconstruction and ground truth is improved up to 10%. Compared to direct deep learning-based 4D CBCT to 4D CT mapping, our proposed method performs better because inappropriate prior knowledge about the patient anatomy and physiology is taken into account. Moreover, the image quality enhancement leads to more plausible motion fields estimated by deformable image registration (DIR) in the 4D CBCT image sequences. Conclusions The presented framework enables significantly boosting of 4D CBCT image quality as well as improved DIR and motion field consistency. Thus, the proposed method facilitates extraction of motion information from severely artifact-affected images, which is one of the key challenges of integrating 4D CBCT imaging into RT workflows.

Purpose To investigate the differences between internal target volumes (ITVs) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT) and determine the dose delivered on 4D planning technique. Methods For nine patients, 4DCBCTs were acquired before each fraction to assess tumor motion. An ITV was contoured on each phase of the 4DCBCT and a union of the 10 ITVs was used to create a composite ITV. Another ITV was drawn on the average 3DCBCT (avgCBCT) to compare with current clinical practice. The Dice coefficient, Hausdorff distance, and center of mass (COM) were averaged over four fractions to compare the ITVs contoured on the 4DCT, avgCBCT, and 4DCBCT for each patient. Planning was done on the average CT, and using the online registration, plans were calculated on each phase of the 4DCBCT and on the avgCBCT. Plan dose calculations were tested by measuring ion chamber dose in the CIRS lung phantom. Results The Dice coefficients were similar for all three comparisons: avgCBCT‐to‐4DCBCT (0.7 ± 0.1), 4DCT‐to‐avgCBCT (0.7 ± 0.1), and 4DCT‐to‐4DCBCT (0.7 ± 0.1); while the mean COM differences were also comparable (2.6 ± 2.2mm, 2.3 ± 1.4mm, and 3.1 ± 1.1mm, respectively). The Hausdorff distances for the comparisons with 4DCBCT (8.2 ± 2.9mm and 8.1 ± 3.2mm) were larger than the comparison without (6.5 ± 2.5mm). The differences in ITV D95% between the treatment plan and avgCBCT calculations were 4.3 ± 3.0% and −0.5 ± 4.6%, between treatment plan and 4DCBCT plans, respectively, while the ITV V100% coverages were 99.0 ± 1.9% and 93.1 ± 8.0% for avgCBCT and 4DCBCT, respectively. Conclusion There is great potential for 4DCBCT to evaluate the extent of tumor motion before treatment, but image quality challenges the clinician to consistently delineate lung target volumes.

Purpose: The aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health. Methods: Vascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated. Results: The volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status. Conclusion: It was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.

We evaluated four-dimensional cone beam computed tomography (4D-CBCT) ventilation images (VICBCT) acquired with two different linear accelerator systems at various gantry speeds using a deformable lung phantom. The 4D-CT and 4D-CBCT scans were performed using a computed tomography (CT) scanner, an X-ray volume imaging system (Elekta XVI) mounted in Versa HD, and an On-Board Imager (OBI) system mounted in TrueBeam. Intensity-based deformable image registration (DIR) was performed between peak-exhale and peak-inhale images. VICBCT- and 4D-CT-based ventilation images (VICT) were derived by DIR using two metrics: one based on the Jacobian determinant and one on changes in the Hounsfield unit (HU). Three different DIR regularization values (λ) were used for VICBCT. Correlations between the VICBCT and VICT values were evaluated using voxel-wise Spearman’s rank correlation coefficient (r). In case of both metrics, the Jacobian-based VICBCT with a gantry speed of 0.6 deg/sec in Versa HD showed the highest correlation for all the gantry speeds (e.g., λ = 0.05 and r = 0.68). Thus, the r value of the Jacobian-based VICBCT was greater or equal to that of the HU-based VICBCT. In addition, the ventilation accuracy of VICBCT increased at low gantry speeds. Thus, the image quality of VICBCT was affected by the change in gantry speed in both the imaging systems. Additionally, DIR regularization considerably influenced VICBCT in both the imaging systems. Our results have the potential to assist in designing CBCT protocols, incorporating VICBCT imaging into the functional avoidance planning process.

Functional imaging modalities enable practitioners to identify functional lung regions. This analysis evaluated the feasibility of nuclear medicine imaging to avoid doses to the functional lung in radiotherapy (RT) planning for patients with lung cancer. This systematic review and meta-analysis was carried out according to PRISMA-P guidelines. A search of EMBASE and PubMed for studies published throughout the last 20 years was performed using the following search criteria: (a) ‘lung cancer’ or ‘lung malignancy’ and (b) ‘radiotherapy’ or ‘radiation therapy’ or ‘RT planning’ and (c) ‘SPECT’ or ‘single positron emission computed tomography’ or ‘functional image.’ The analyzed planning parameters were the volumes of the normal lung that have received ≥ 10 Gy and ≥ 20 Gy of radiation (V10 and V20, respectively) and the mean lung dose (MLD). We compared the planning parameters obtained from anatomical RT planning and functional RT planning using perfusion or ventilation imaging (‘V10, V20 or MLD’ in anatomical plan vs. ‘fV10, fV20 or fMLD’ in functional plan). A total of 309 patients with 344 RT plan sets from 15 publications (11 perfusion SPECT, 2 ventilation SPECT, and 1 SPECT and 1 PET with both perfusion and ventilation) were included in the meta-analysis. The standard mean differences in planning parameters in functional plans using nuclear imaging were significantly reduced compared to those of anatomical plans (P . fV10′, − 0.41 (95% CI − 0.64 to − 0.17) for ‘V20 vs. fV20′, and − 0.24 (95% CI − 0.45 to − 0.03) for ‘MLD vs. fMLD’. In subgroup analysis, the functional plan using perfusion was significantly lower than the anatomical plan in all planning parameters, but there was no significant difference for ventilation. RT planning with nuclear functional lung imaging has potential to reduce radiation-induced lung injury. Perfusion imaging seems to be more promising than ventilation imaging for all planning parameters. There were not enough studies using ventilation imaging to determine what the effect is on the lung plan parameters.

Purpose Directly extracting the respiratory phase pattern of the tumor using cone-beam computed tomography (CBCT) projections is challenging due to the poor tumor visibility caused by the obstruction of multiple anatomic structures on the beam's eye view. Predicting tumor phase information using external surrogate also has intrinsic difficulties as the phase patterns between surrogates and tumors are not necessary to be congruent. In this work, we developed an algorithm to accurately recover the primary oscillation components of tumor motion using the combined information from both CBCT projections and external surrogates. Methods The algorithm involved two steps. First, a preliminary tumor phase pattern was acquired by applying local principal component analysis (LPCA) on the cropped Amsterdam Shroud (AS) images. In this step, only the cropped image of the tumor region was used to extract the tumor phase pattern in order to minimize the impact of pattern recognition from other anatomic structures. Second, by performing multivariate singular spectrum analysis (MSSA) on the combined information containing both external surrogate signal and the original waveform acquired in the first step, the primary component of the tumor phase oscillation was recovered. For the phantom study, a QUASAR respiratory motion phantom with a removable tumor-simulator insert was employed to acquire CBCT projection images. A comparison between LPCA only and our method was assessed by power spectrum analysis. Also, the motion pattern was simulated under the phase shift or various amplitude conditions to examine the robustness of our method. Finally, anatomic obstruction scenarios were simulated by attaching a heart model, PVC tubes, and RANDO® phantom slabs to the phantom, respectively. Each scenario was tested with five real-patient breathing patterns to mimic real clinical situations. For the patient study, eight patients with various tumor locations were selected. The performance of our method was then evaluated by comparing the reference waveform with the extracted signal for overall phase discrepancy, expiration phase discrepancy, peak, and valley accuracy. Results In tests of phase shifts and amplitude variations, the overall peak and valley accuracy was -0.009 ± 0.18 sec, and no time delay was found compared to the reference. In anatomical obstruction tests, the extracted signal had 1.6 ± 1.2 % expiration phase discrepancy, -0.12 ± 0.28 sec peak accuracy, and 0.01 ± 0.15 sec valley accuracy. For patient studies, the extracted signal using our method had -1.05 ± 3.0 % overall phase discrepancy, -1.55 ± 1.45% expiration phase discrepancy, 0.04 ± 0.13 sec peak accuracy, and -0.01 ± 0.15 sec valley accuracy, compared to the reference waveforms. Conclusions An innovative method capable of accurately recognizing tumor phase information was developed. With the aid of extra information from the external surrogate, an improvement in prediction accuracy, as compared with traditional statistical methods, was obtained. It enables us to employ it as the ground truth for 4D-CBCT reconstruction, gating treatment, and other clinic implementations that require accurate tumor phase information.

Purpose The application value of 18 F-FDG PET-CT combined with MRI in the radiotherapy of esophageal carcinoma was discussed by comparing the differences in position, volume, and the length of GTVs delineated on the end-expiration (EE) phase of 4DCT, 18 F-FDG PET-CT, and T2 W-MRI. Methods A total of 26 patients with thoracic esophageal cancer sequentially performed 3DCT, 4DCT, 18 F-FDG PET-CT, and MRI simulation for thoracic localization. All images were fused with the 3DCT images by deformable registration. GTVCT and GTV50% were delineated on 3DCT and the EE phase of 4DCT images, respectively. The GTV based on PET-CT images was determined by thresholds of SUV ≥ 2.5 and designated as GTVPET2.5 . The images of T2 -weighted sequence and diffusion-weighted sequence were referred as GTVMRI and GTVDWI , respectively. The length of the abnormality seen on the 4DCT, PET-CT, and DWI was compared. Results GTVPET2.5 was significantly larger than GTV50% and GTVMRI (P = .000 and 0.008, respectively), and the volume of GTVMRI was similar to that of GTV50% (P = .439). Significant differences were observed between the CI of GTVMRI to GTV50% and GTVPET2.5 to GTV50% (P = .004). The CI of GTVMRI to GTVCT and GTVPET2.5 to GTVCT were statistically significant (P = .039). The CI of GTVMRI to GTVPET2.5 was significantly lower than that of GTVMRI to GTV50% , GTVMRI to GTVCT , GTVPET2.5 to GTV50% , and GTVPET2.5 to GTVCT (P = .000-0.021). Tumor length measurements by endoscopy were similar to the tumor length as measured by PET and DWI scan (P > .05), and there was no significant difference between the longitudinal length of GTVPET2.5 and GTVDWI (P = .072). Conclusion The volumes of GTVMRI and GTV50% were similar. However, GTVMRI has different volumes and poor spatial matching compared with GTVPET2.5 .The MRI imaging could not include entire respiration. It may be a good choice to guide target delineation and construction of esophageal carcinoma by combining 4DCT with MRI imaging. Utilization of DWI in treatment planning for esophageal cancer may provide further information to assist with target delineation. Further studies are needed to determine if this technology will translate into meaningful differences in clinical outcome.

Aim To mimic chest compression during cardiopulmonary resuscitation (CPR), this study aimed to produce time-resolved 3D (volumetric) reformats of thoracic and upper abdominal tissue movement during incremental closed chest compression/decompression from 0 to 8 to 0 cm. Methods Sequential angiography enhanced computed tomography (CT) scans were acquired from a recently deceased, consented adult cadaver with 1 cm incremental closed chest compression/decompression. Three compression/decompression sequences from 0 to 3 cm, 0 to 5 cm, and 0 to 8 cm, respectively, were scanned using a radio-opaque, manually operated, chest compression device. The multiphase volumetric data sets were compiled into 4D models that allowed for multiplanar reformatted and volume rendered image manipulation. Results Time-resolved volumetric (4D) models were produced using freeware to post-process the static CT scans. The 4D models allowed the study of simulated thoracic and upper abdominal content movement during closed chest compression. Conclusions The method described could assist CPR researchers and educators in the development and demonstration of effective CPR protocols.

This is a proof-of-concept study to create a four-dimensional (4-D) cine model of the heart and visualize it in virtual reality by using freely available open-source software and inexpensive hardware. Four-dimensional cine models allow for real-time visualization of cardiac structures during processes such as complex congenital heart disease. Such models can be used for patient and trainee education, and potentially for surgical planning. Currently, 3-D printed models are more commonly used, but they are static, showing only one selected phase of the cardiac cycle. Second, they are limited by the selection of clipping planes before printing. Four-dimensional segmentation and virtual reality visualization overcome these limitations. Currently, most of the work in virtual/augmented reality models involves the segmentation of one cardiac phase or the use of expensive software for multiphase segmentation. In this study, we show an approach for multiphase cardiac segmentation as well as its display using free open-source software and relatively inexpensive hardware.

Purpose: For locally advanced-stage non-small cell lung cancer (NSCLC), inter-fraction target motion variations during the whole time span of a fractionated treatment course are assessed in a large and representative patient cohort. The primary objective is to develop a suitable motion monitoring strategy for pencil beam scanning proton therapy (PBS-PT) treatments of NSCLC patients during free breathing. Methods: Weekly 4D computed tomography (4DCT; 41 patients) and daily 4D cone beam computed tomography (4DCBCT; 10 of 41 patients) scans were analyzed for a fully fractionated treatment course. Gross tumor volumes (GTVs) were contoured and the 3D displacement vectors of the centroid positions were compared for all scans. Furthermore, motion amplitude variations in different lung segments were statistically analyzed. The dosimetric impact of target motion variations and target motion assessment was investigated in exemplary patient cases. Results: The median observed centroid motion was 3.4 mm (range: 0.2–12.4 mm) with an average variation of 2.2 mm (range: 0.1–8.8 mm). Ten of 32 patients (31.3%) with an initial motion 2 mm, 4DCBCT should be considered for motion monitoring due to substantial motion variations observed.

More efforts are required to minimise late radiation side-effects for paediatric patients. Pencil beam scanning proton beam therapy (PBS-PT) allows increased sparing of normal tissues while maintaining conformality, but is prone to dose degradation from interplay effects due to respiratory motion. We report our clinical experience of motion mitigation with volumetric rescanning (vRSC) and outcomes of children with neuroblastoma.Nineteen patients with high-risk (n = 16) and intermediate-risk (n = 3) neuroblastoma received PBS-PT. The median age at PBS-PT was 3.5 years (range 1.2-8.6) and the median PBS-PT dose was 21 Gy (relative biological effectiveness). Most children (89%) were treated under general anaesthesia. Seven patients (37%) underwent four-dimensional computed tomography for motion assessment and were treated with vRSC for motion mitigation.The mean result of maximum organ motion was 2.7 mm (cranial-caudal), 1.2 mm (left-right), 1.0 mm (anterior-posterior). Four anaesthetised children (21%) showing5 mm motion had four-dimensional dose calculations (4DDC) to guide the number of vRSC. The mean deterioration or improvement to the planning target volume covered by 95% of the prescribed dose compared with static three-dimensional plans were: 4DDC no vRSC, -0.6%; 2 vRSC, +0.3%; 4 vRSC, +0.3%; and 8 vRSC, +0.1%. With a median follow-up of 14.9 months (range 2.7-49.0) there were no local recurrences. The 2-year overall survival was 94% and distant progression-free survival was 76%. Acute grade 2-4 toxicity was 11%. During the limited follow-up time, no late toxicities were observed.The early outcomes of mainly high-risk patients with neuroblastoma treated with PBS-PT were excellent. With a subset of our cohort undergoing PBS-PT with vRSC we have shown that it is logistically feasible and safe. The clinical relevance of vRSC is debatable in anaesthetised children with small pre-PBS-PT motion of5 mm.

Background Localized pleural adhesion (LPA) evaluation in the apical region is difficult even with four-dimensional ultra-low-dose computed tomography (4D-ULDCT) in the supine position due to smaller pleural movements. Purpose To assess usability of 4D-ULDCT in the lateral decubitus (LD) position for LPA detection in the apical region. Material and Methods Forty-seven patients underwent 4D-ULDCT of a single respiration cycle with 16-cm coverage of body axis in supine and LD positions with the affected lung uppermost. Intraoperative thoracoscopic findings confirmed LPA presence. A pleural point and a corresponding point on costal outer edge were placed in identical axial planes at end-inspiration. Pleuro-chest wall distance between two points (PCD) was calculated at each respiratory phase. In the affected lung, average change in amount of PCD (PCDACA) was compared between patients with and without LPA in total and two sub-groups (non-COPD and COPD, non-emphysematous and emphysematous patients) in supine and non-dependent (ND) LD positions. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal thresholds in PCDACA for differentiating patients with LPA from those without. Results In COPD/emphysematous patients and total population, PCDACA with LPA was smaller than in those without in the supine and NDLD positions for overall, lateral, and dorsal regions. For the lateral region in COPD patients, area under ROC curve (AUC) increased from supine (0.64) to NDLD position (0.81). For the dorsal region in emphysematous patients, AUC increased from supine (0.76) to NDLD position (0.96). Conclusion 4D-ULDCT in LD position may be useful for LPA detection in apical regions for COPD and/or emphysematous patients.

The predominant pulmonary imaging findings on chest CT in the novel 2019 coronavirus infection (COVID-19) are bilateral ground glass opacities. The reverse halo sign is uncommon. This is a report of the new “bullseye sign,” which is considered a variant of the reverse halo sign and favored to represent a focus of organizing pneumonia. The specificity of this finding is unclear, however its presence should alert radiologists to the possibility of COVID-19 infection., Highlights • The “bullseye sign” is a new chest CT sign that has not been described before the novel coronavirus pandemic. • The “bullseye sign” is considered a variant of the reverse halo sign and likely represents organizing pneumonia. • The “bullseye sign” could potentially be used to distinguish COVID-19 pneumonia from other viral pneumonias.

Background and purpose: 4D CT images often contain artifacts that are suspected to affect treatment planning quality and clinical outcome of lung and liver SBRT. The present study investigates the correlation between the presence of artifacts in SBRT planning 4D CT data and local metastasis control. Materials and methods: The study includes 62 patients with 102 metastases (49 in the lung and 53 in the liver), treated between 2012 and 2016 with SBRT for mainly curative intent. For each patient, 10-phase 4D CT images were acquired and used for ITV definition and treatment planning. Follow-up intervals were 3 weeks after treatment and every 3–6 months thereafter. Based on the number and type of image artifacts, a strict rule-based two-class artifact score was introduced and assigned to the individual 4D CT data sets. Correlation between local control and artifact score (consensus rating based on two independent observers) were analyzed using uni- and multivariable Cox proportional hazards models with random effects. Metastatic site, target volume, metastasis motion, breathing irregularity-related measures, and clinical data (chemotherapy prior to SBRT, target dose, treatment fractionation) were considered as covariates. Results: Local recurrence was observed in 17/102 (17%) metastases. Significant univariable factors for local control were artifact score (severe CT artifacts vs. few CT artifacts; hazard ratio 8.22; 95%-CI 2.04–33.18) and mean patient breathing period ( > 4.8 s vs. ≤ 4.8 s; hazard ratio 3.58; 95%-CI 1.18–10.84). Following multivariable analysis, artifact score remained as dominating prognostic factor, although statistically not significant (hazard ratio 10.28; 95%-CI 0.57–184.24). Conclusion: The results support the hypothesis that image artifacts in 4D CT treatment planning data negatively influence clinical outcome in SBRT of lung and liver metastases, underlining the need to account for 4D CT artifacts and improve image quality.