Machine Learning Applications in Head and Neck Radiation Oncology: Lessons From Open-Source Radiomics Challenges.

Radiomics leverages existing image datasets to provide non-visible data extraction via image post-processing, with the aim of identifying prognostic, and predictive imaging features at a sub-region of interest level. However, the application of radiomics is hampered by several challenges such as lack of image acquisition/analysis method standardization, impeding generalizability. As of yet, radiomics remains intriguing, but not clinically validated. We aimed to test the feasibility of a non-custom-constructed platform for disseminating existing large, standardized databases across institutions for promoting radiomics studies. Hence, University of Texas MD Anderson Cancer Center organized two public radiomics challenges in head and neck radiation oncology domain. This was done in conjunction with MICCAI 2016 satellite symposium using Kaggle-in-Class, a machine-learning and predictive analytics platform. We drew on clinical data matched to radiomics data derived from diagnostic contrast-enhanced computed tomography (CECT) images in a dataset of 315 patients with oropharyngeal cancer. Contestants were tasked to develop models for (i) classifying patients according to their human papillomavirus status, or (ii) predicting local tumor recurrence, following radiotherapy. Data were split into training, and test sets. Seventeen teams from various professional domains participated in one or both of the challenges. This review paper was based on the contestants' feedback; provided by 8 contestants only (47%). Six contestants (75%) incorporated extracted radiomics features into their predictive model building, either alone (n = 5; 62.5%), as was the case with the winner of the "HPV" challenge, or in conjunction with matched clinical attributes (n = 2; 25%). Only 23% of contestants, notably, including the winner of the "local recurrence" challenge, built their model relying solely on clinical data. In addition to the value of the integration of machine learning into clinical decision-making, our experience sheds light on challenges in sharing and directing existing datasets toward clinical applications of radiomics, including hyper-dimensionality of the clinical/imaging data attributes. Our experience may help guide researchers to create a framework for sharing and reuse of already published data that we believe will ultimately accelerate the pace of clinical applications of radiomics; both in challenge or clinical settings.

TG-51 reference dosimetry for the Halcyon™: A clinical experience.

Halcyon™ is a single-energy (6 MV-FFF), bore-enclosed linear accelerator. Patient setup is performed by first aligning to external lasers mounted to the front of the bore, and then loading to isocenter through pre-defined couch shifts. There is no light field, optical distance indicator or front pointer mechanism, so positioning is verified through MV imaging with kV imaging scheduled to become available in the future. TG-51 reference dosimetry was successfully performed for Halcyon™ in this imaging-based setup paradigm. The beam quality conversion factor, kQ , was determined by measuring %dd(10)x three ways: (a) using a Farmer chamber with lead filtering, (b) using a Farmer chamber without lead filtering, and (c) using a PinPoint chamber without lead filtering. Values of kQ were determined to be 0.995, 0.996, and 0.996 by each measurement technique, respectively. Halcyon™'s 6 MV-FFF beam was found to be broader than other FFF beams produced by Varian accelerators, and profile measurements at dmax showed the beam to vary less than 0.5% over the dimensions of our Farmer chamber's active volume. Reference dosimetry can be performed for the Halcyon™ accelerator simply, without specialized equipment or lead filtering with minimal dosimetric impact. This simplicity will prove advantageous in clinics with limited resources or physics support.

Correction to: A predictive model for distinguishing radiation necrosis from tumour progression after gamma knife radiosurgery based on radiomic features from MR images.

The original version of this article, published on 24 November 2017, unfortunately contained a mistake.

Effect of tube current on computed tomography radiomic features.

Variability in the x-ray tube current used in computed tomography may affect quantitative features extracted from the images. To investigate these effects, we scanned the Credence Cartridge Radiomics phantom 12 times, varying the tube current from 25 to 300 mA∙s while keeping the other acquisition parameters constant. For each of the scans, we extracted 48 radiomic features from the categories of intensity histogram (n = 10), gray-level run length matrix (n = 11), gray-level co-occurrence matrix (n = 22), and neighborhood gray tone difference matrix (n = 5). To gauge the size of the tube current effects, we scaled the features by the coefficient of variation of the corresponding features extracted from images of non-small cell lung cancer tumors. Variations in the tube current had more effect on features extracted from homogeneous materials (acrylic, sycamore wood) than from materials with more tissue-like textures (cork, rubber particles). Thirty-eight of the 48 features extracted from acrylic were affected by current reductions compared with only 2 of the 48 features extracted from rubber particles. These results indicate that variable x-ray tube current is unlikely to have a large effect on radiomic features extracted from computed tomography images of textured objects such as tumors.

Correction: Harmonizing the pixel size in retrospective computed tomography radiomics studies.

[This corrects the article DOI: 10.1371/journal.pone.0178524.].

A predictive model for distinguishing radiation necrosis from tumour progression after gamma knife radiosurgery based on radiomic features from MR images.

OBJECTIVES: To develop a model using radiomic features extracted from MR images to distinguish radiation necrosis from tumour progression in brain metastases after Gamma Knife radiosurgery. METHODS: We retrospectively identified 87 patients with pathologically confirmed necrosis (24 lesions) or progression (73 lesions) and calculated 285 radiomic features from four MR sequences (T1, T1 post-contrast, T2, and fluid-attenuated inversion recovery) obtained at two follow-up time points per lesion per patient. Reproducibility of each feature between the two time points was calculated within each group to identify a subset of features with distinct reproducible values between two groups. Changes in radiomic features from one time point to the next (delta radiomics) were used to build a model to classify necrosis and progression lesions. RESULTS: A combination of five radiomic features from both T1 post-contrast and T2 MR images were found to be useful in distinguishing necrosis from progression lesions. Delta radiomic features with a RUSBoost ensemble classifier had an overall predictive accuracy of 73.2% and an area under the curve value of 0.73 in leave-one-out cross-validation. CONCLUSIONS: Delta radiomic features extracted from MR images have potential for distinguishing radiation necrosis from tumour progression after radiosurgery for brain metastases. KEY POINTS: • Some radiomic features showed better reproducibility for progressive lesions than necrotic ones • Delta radiomic features can help to distinguish radiation necrosis from tumour progression • Delta radiomic features had better predictive value than did traditional radiomic features.

Harmonizing the pixel size in retrospective computed tomography radiomics studies.

Consistent pixel sizes are of fundamental importance for assessing texture features that relate intensity and spatial information in radiomics studies. To correct for the effects of variable pixel sizes, we combined image resampling with Butterworth filtering in the frequency domain and tested the correction on computed tomography (CT) scans of lung cancer patients reconstructed 5 times with pixel sizes varying from 0.59 to 0.98 mm. One hundred fifty radiomics features were calculated for each preprocessing and field-of-view combination. Intra-patient agreement and inter-patient agreement were compared using the overall concordance correlation coefficient (OCCC). To further evaluate the corrections, hierarchical clustering was used to identify patient scans before and after correction. To assess the general applicability of the corrections, they were applied to 17 CT scans of a radiomics phantom. The reduction in the inter-scanner variability relative to non-small cell lung cancer patient scans was quantified. The variation in pixel sizes caused the intra-patient variability to be large (OCCC <95%) relative to the inter-patient variability in 79% of the features. However, with the resampling and filtering corrections, the intra-patient variability was relatively large in only 10% of the features. With the filtering correction, 8 of 8 patients were correctly clustered, in contrast to only 2 of 8 without the correction. In the phantom study, resampling and filtering the images of a rubber particle cartridge substantially reduced variability in 61% of the radiomics features and substantially increased variability in only 6% of the features. Surprisingly, resampling without filtering tended to increase the variability. In conclusion, applying a correction based on resampling and Butterworth low-pass filtering in the frequency domain effectively reduced variability in CT radiomics features caused by variations in pixel size. This correction may also reduce the variability introduced by other CT scan acquisition parameters.

Cost-effective immobilization for whole brain radiation therapy.

To investigate the inter- and intra-fraction motion associated with the use of a low-cost tape immobilization technique as an alternative to thermoplastic immobilization masks for whole-brain treatments. The results of this study may be of interest to clinical staff with severely limited resources (e.g., in low-income countries) and also when treating patients who cannot tolerate standard immobilization masks. Setup reproducibility of eight healthy volunteers was assessed for two different immobilization techniques. (a) One strip of tape was placed across the volunteer's forehead and attached to the sides of the treatment table. (b) A second strip was added to the first, under the chin, and secured to the table above the volunteer's head. After initial positioning, anterior and lateral photographs were acquired. Volunteers were positioned five times with each technique to allow calculation of inter-fraction reproducibility measurements. To estimate intra-fraction reproducibility, 5-minute anterior and lateral videos were taken for each technique per volunteer. An in-house software was used to analyze the photos and videos to assess setup reproducibility. The maximum intra-fraction displacement for all volunteers was 2.8 mm. Intra-fraction motion increased with time on table. The maximum inter-fraction range of positions for all volunteers was 5.4 mm. The magnitude of inter-fraction and intra-fraction motion found using the "1-strip" and "2-strip" tape immobilization techniques was comparable to motion restrictions provided by a thermoplastic mask for whole-brain radiotherapy. The results suggest that tape-based immobilization techniques represent an economical and useful alternative to the thermoplastic mask.

Delta-radiomics features for the prediction of patient outcomes in non-small cell lung cancer.

Radiomics is the use of quantitative imaging features extracted from medical images to characterize tumor pathology or heterogeneity. Features measured at pretreatment have successfully predicted patient outcomes in numerous cancer sites. This project was designed to determine whether radiomics features measured from non-small cell lung cancer (NSCLC) change during therapy and whether those features (delta-radiomics features) can improve prognostic models. Features were calculated from pretreatment and weekly intra-treatment computed tomography images for 107 patients with stage III NSCLC. Pretreatment images were used to determine feature-specific image preprocessing. Linear mixed-effects models were used to identify features that changed significantly with dose-fraction. Multivariate models were built for overall survival, distant metastases, and local recurrence using only clinical factors, clinical factors and pretreatment radiomics features, and clinical factors, pretreatment radiomics features, and delta-radiomics features. All of the radiomics features changed significantly during radiation therapy. For overall survival and distant metastases, pretreatment compactness improved the c-index. For local recurrence, pretreatment imaging features were not prognostic, while texture-strength measured at the end of treatment significantly stratified high- and low-risk patients. These results suggest radiomics features change due to radiation therapy and their values at the end of treatment may be indicators of tumor response.

Potential Use of (18)F-fluorodeoxyglucose Positron Emission Tomography-Based Quantitative Imaging Features for Guiding Dose Escalation in Stage III Non-Small Cell Lung Cancer.

PURPOSE: To determine whether previously identified quantitative image features (QIFs) based on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) (co-occurrence matrix energy and solidity) are able to isolate subgroups of patients who would receive a benefit or detriment from dose escalation in terms of overall survival (OS) or progression-free survival (PFS). METHODS AND MATERIALS: Subgroups of a previously analyzed 225 patient cohort were generated with the use of 5-percentile increment cutoff values of disease solidity and primary tumor co-occurrence matrix energy. The subgroups were analyzed with a log-rank test to determine whether there was a difference in OS and PFS between patients treated with 60 to 70 Gy and those receiving 74 Gy. RESULTS: In the entire patient cohort, there was no statistical difference in terms of OS or PFS between patients receiving 74 Gy and those receiving 60 to 70 Gy. It was qualitatively observed that as disease solidity and primary co-occurrence matrix energy increased, patients receiving 74 Gy had an improved OS and PFS compared with those receiving 60 to 70 Gy. The opposite trend (detriment of receiving 74 Gy) was also observed regarding low values of disease solidity and primary co-occurrence matrix energy. CONCLUSIONS: FDG-PET-based QIFs were found to be capable of isolating subgroups of patients who received a benefit or detriment from dose escalation.

Uncertainty analysis of quantitative imaging features extracted from contrast-enhanced CT in lung tumors.

PURPOSE: To assess the uncertainty of quantitative imaging features extracted from contrast-enhanced computed tomography (CT) scans of lung cancer patients in terms of the dependency on the time after contrast injection and the feature reproducibility between scans. METHODS: Eight patients underwent contrast-enhanced CT scans of lung tumors on two sessions 2-7 days apart. Each session included 6 CT scans of the same anatomy taken every 15s, starting 50s after contrast injection. Image features based on intensity histogram, co-occurrence matrix, neighborhood gray-tone difference matrix, run-length matrix, and geometric shape were extracted from the tumor for each scan. Spearman's correlation was used to examine the dependency of features on the time after contrast injection, with values over 0.50 considered time-dependent. Concordance correlation coefficients were calculated to examine the reproducibility of each feature between times of scans after contrast injection and between scanning sessions, with values greater than 0.90 considered reproducible. RESULTS: The features were found to have little dependency on the time between the contrast injection and the CT scan. Most features were reproducible between times of scans after contrast injection and between scanning sessions. Some features were more reproducible when they were extracted from a CT scan performed at a longer time after contrast injection. CONCLUSION: The quantitative imaging features tested here are mostly reproducible and show little dependency on the time after contrast injection.

Stage III Non-Small Cell Lung Cancer: Prognostic Value of FDG PET Quantitative Imaging Features Combined with Clinical Prognostic Factors.

PURPOSE: To determine whether quantitative imaging features from pretreatment positron emission tomography (PET) can enhance patient overall survival risk stratification beyond what can be achieved with conventional prognostic factors in patients with stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The institutional review board approved this retrospective chart review study and waived the requirement to obtain informed consent. The authors retrospectively identified 195 patients with stage III NSCLC treated definitively with radiation therapy between January 2008 and January 2013. All patients underwent pretreatment PET/computed tomography before treatment. Conventional PET metrics, along with histogram, shape and volume, and co-occurrence matrix features, were extracted. Linear predictors of overall survival were developed from leave-one-out cross-validation. Predictive Kaplan-Meier curves were used to compare the linear predictors with both quantitative imaging features and conventional prognostic factors to those generated with conventional prognostic factors alone. The Harrell concordance index was used to quantify the discriminatory power of the linear predictors for survival differences of at least 0, 6, 12, 18, and 24 months. Models were generated with features present in more than 50% of the cross-validation folds. RESULTS: Linear predictors of overall survival generated with both quantitative imaging features and conventional prognostic factors demonstrated improved risk stratification compared with those generated with conventional prognostic factors alone in terms of log-rank statistic (P = .18 vs P = .0001, respectively) and concordance index (0.62 vs 0.58, respectively). The use of quantitative imaging features selected during cross-validation improved the model using conventional prognostic factors alone (P = .007). Disease solidity and primary tumor energy from the co-occurrence matrix were found to be selected in all folds of cross-validation. CONCLUSION: Pretreatment PET features were associated with overall survival when adjusting for conventional prognostic factors in patients with stage III NSCLC.

Can radiomics features be reproducibly measured from CBCT images for patients with non-small cell lung cancer?

PURPOSE: Increasing evidence suggests radiomics features extracted from computed tomography (CT) images may be useful in prognostic models for patients with nonsmall cell lung cancer (NSCLC). This study was designed to determine whether such features can be reproducibly obtained from cone-beam CT (CBCT) images taken using medical Linac onboard-imaging systems in order to track them through treatment. METHODS: Test-retest CBCT images of ten patients previously enrolled in a clinical trial were retrospectively obtained and used to determine the concordance correlation coefficient (CCC) for 68 different texture features. The volume dependence of each feature was also measured using the Spearman rank correlation coefficient. Features with a high reproducibility (CCC > 0.9) that were not due to volume dependence in the patient test-retest set were further examined for their sensitivity to differences in imaging protocol, level of scatter, and amount of motion by using two phantoms. The first phantom was a texture phantom composed of rectangular cartridges to represent different textures. Features were measured from two cartridges, shredded rubber and dense cork, in this study. The texture phantom was scanned with 19 different CBCT imagers to establish the features' interscanner variability. The effect of scatter on these features was studied by surrounding the same texture phantom with scattering material (rice and solid water). The effect of respiratory motion on these features was studied using a dynamic-motion thoracic phantom and a specially designed tumor texture insert of the shredded rubber material. The differences between scans acquired with different Linacs and protocols, varying amounts of scatter, and with different levels of motion were compared to the mean intrapatient difference from the test-retest image set. RESULTS: Of the original 68 features, 37 had a CCC >0.9 that was not due to volume dependence. When the Linac manufacturer and imaging protocol were kept consistent, 4-13 of these 37 features passed our criteria for reproducibility more than 50% of the time, depending on the manufacturer-protocol combination. Almost all of the features changed substantially when scatter material was added around the phantom. For the dense cork, 23 features passed in the thoracic scans and 11 features passed in the head scans when the differences between one and two layers of scatter were compared. Using the same test for the shredded rubber, five features passed the thoracic scans and eight features passed the head scans. Motion substantially impacted the reproducibility of the features. With 4 mm of motion, 12 features from the entire volume and 14 features from the center slice measurements were reproducible. With 6-8 mm of motion, three features (Laplacian of Gaussian filtered kurtosis, gray-level nonuniformity, and entropy), from the entire volume and seven features (coarseness, high gray-level run emphasis, gray-level nonuniformity, sum-average, information measure correlation, scaled mean, and entropy) from the center-slice measurements were considered reproducible. CONCLUSIONS: Some radiomics features are robust to the noise and poor image quality of CBCT images when the imaging protocol is consistent, relative changes in the features are used, and patients are limited to those with less than 1 cm of motion.

Measuring Computed Tomography Scanner Variability of Radiomics Features.

OBJECTIVES: The purpose of this study was to determine the significance of interscanner variability in CT image radiomics studies. MATERIALS AND METHODS: We compared the radiomics features calculated for non-small cell lung cancer (NSCLC) tumors from 20 patients with those calculated for 17 scans of a specially designed radiomics phantom. The phantom comprised 10 cartridges, each filled with different materials to produce a wide range of radiomics feature values. The scans were acquired using General Electric, Philips, Siemens, and Toshiba scanners from 4 medical centers using their routine thoracic imaging protocol. The radiomics feature studied included the mean and standard deviations of the CT numbers as well as textures derived from the neighborhood gray-tone difference matrix. To quantify the significance of the interscanner variability, we introduced the metric feature noise. To look for patterns in the scans, we performed hierarchical clustering for each cartridge. RESULTS: The mean CT numbers for the 17 CT scans of the phantom cartridges spanned from -864 to 652 Hounsfield units compared with a span of -186 to 35 Hounsfield units for the CT scans of the NSCLC tumors, showing that the phantom's dynamic range includes that of the tumors. The interscanner variability of the feature values depended on both the cartridge material and the feature, and the variability was large relative to the interpatient variability in the NSCLC tumors for some features. The feature interscanner noise was greatest for busyness and least for texture strength. Hierarchical clustering produced different clusters of the phantom scans for each cartridge, although there was some consistent clustering by scanner manufacturer. CONCLUSIONS: The variability in the values of radiomics features calculated on CT images from different CT scanners can be comparable to the variability in these features found in CT images of NSCLC tumors. These interscanner differences should be considered, and their effects should be minimized in future radiomics studies.

Preliminary investigation into sources of uncertainty in quantitative imaging features.

Several recent studies have demonstrated the potential for quantitative imaging features to classify non-small cell lung cancer (NSCLC) patients as high or low risk. However applying the results from one institution to another has been difficult because of the variations in imaging techniques and feature measurement. Our study was designed to determine the effect of some of these sources of uncertainty on image features extracted from computed tomography (CT) images of non-small cell lung cancer (NSCLC) tumors. CT images from 20 NSCLC patients were obtained for investigating the impact of four sources of uncertainty: Two region of interest (ROI) selection conditions (breathing phase and single-slice vs. whole volume) and two imaging protocol parameters (peak tube voltage and current). Texture values did not vary substantially with the choice of breathing phase; however, almost half (12 out of 28) of the measured textures did change significantly when measured from the average images compared to the end-of-exhale phase. Of the 28 features, 8 showed a significant variation when measured from the largest cross sectional slice compared to the entire tumor, but 14 were correlated to the entire tumor value. While simulating a decrease in tube voltage had a negligible impact on texture features, simulating a decrease in mA resulted in significant changes for 13 of the 23 texture values. Our results suggest that substantial variation exists when textures are measured under different conditions, and thus the development of a texture analysis standard would be beneficial for comparing features between patients and institutions.

IBEX: an open infrastructure software platform to facilitate collaborative work in radiomics.

PURPOSE: Radiomics, which is the high-throughput extraction and analysis of quantitative image features, has been shown to have considerable potential to quantify the tumor phenotype. However, at present, a lack of software infrastructure has impeded the development of radiomics and its applications. Therefore, the authors developed the imaging biomarker explorer (IBEX), an open infrastructure software platform that flexibly supports common radiomics workflow tasks such as multimodality image data import and review, development of feature extraction algorithms, model validation, and consistent data sharing among multiple institutions. METHODS: The IBEX software package was developed using the MATLAB and c/c++ programming languages. The software architecture deploys the modern model-view-controller, unit testing, and function handle programming concepts to isolate each quantitative imaging analysis task, to validate if their relevant data and algorithms are fit for use, and to plug in new modules. On one hand, IBEX is self-contained and ready to use: it has implemented common data importers, common image filters, and common feature extraction algorithms. On the other hand, IBEX provides an integrated development environment on top of MATLAB and c/c++, so users are not limited to its built-in functions. In the IBEX developer studio, users can plug in, debug, and test new algorithms, extending IBEX's functionality. IBEX also supports quality assurance for data and feature algorithms: image data, regions of interest, and feature algorithm-related data can be reviewed, validated, and/or modified. More importantly, two key elements in collaborative workflows, the consistency of data sharing and the reproducibility of calculation result, are embedded in the IBEX workflow: image data, feature algorithms, and model validation including newly developed ones from different users can be easily and consistently shared so that results can be more easily reproduced between institutions. RESULTS: Researchers with a variety of technical skill levels, including radiation oncologists, physicists, and computer scientists, have found the IBEX software to be intuitive, powerful, and easy to use. IBEX can be run at any computer with the windows operating system and 1GB RAM. The authors fully validated the implementation of all importers, preprocessing algorithms, and feature extraction algorithms. Windows version 1.0 beta of stand-alone IBEX and IBEX's source code can be downloaded. CONCLUSIONS: The authors successfully implemented IBEX, an open infrastructure software platform that streamlines common radiomics workflow tasks. Its transparency, flexibility, and portability can greatly accelerate the pace of radiomics research and pave the way toward successful clinical translation.

Differential interaction kinetics of a bipolar structure-specific endonuclease with DNA flaps revealed by single-molecule imaging.

As DNA repair enzymes are essential for preserving genome integrity, understanding their substrate interaction dynamics and the regulation of their catalytic mechanisms is crucial. Using single-molecule imaging, we investigated the association and dissociation kinetics of the bipolar endonuclease NucS from Pyrococcus abyssi (Pab) on 5' and 3'-flap structures under various experimental conditions. We show that association of the PabNucS with ssDNA flaps is largely controlled by diffusion in the NucS-DNA energy landscape and does not require a free 5' or 3' extremity. On the other hand, NucS dissociation is independent of the flap length and thus independent of sliding on the single-stranded portion of the flapped DNA substrates. Our kinetic measurements have revealed previously unnoticed asymmetry in dissociation kinetics from these substrates that is markedly modulated by the replication clamp PCNA. We propose that the replication clamp PCNA enhances the cleavage specificity of NucS proteins by accelerating NucS loading at the ssDNA/dsDNA junctions and by minimizing the nuclease interaction time with its DNA substrate. Our data are also consistent with marked reorganization of ssDNA and nuclease domains occurring during NucS catalysis, and indicate that NucS binds its substrate directly at the ssDNA-dsDNA junction and then threads the ssDNA extremity into the catalytic site. The powerful techniques used here for probing the dynamics of DNA-enzyme binding at the single-molecule have provided new insight regarding substrate specificity of NucS nucleases.

Upright cone beam CT imaging using the onboard imager.

PURPOSE: Many patients could benefit from being treated in an upright position. The objectives of this study were to determine whether cone beam computed tomography (CBCT) could be used to acquire upright images for treatment planning and to demonstrate whether reconstruction of upright images maintained accurate geometry and Hounsfield units (HUs). METHODS: A TrueBeam linac was programmed in developer mode to take upright CBCT images. The gantry head was positioned at 0°, and the couch was rotated to 270°. The x-ray source and detector arms were extended to their lateral positions. The x-ray source and gantry remained stationary as fluoroscopic projections were taken and the couch was rotated from 270° to 90°. The x-ray tube current was normalized to deposit the same dose (measured using a calibrated Farmer ion chamber) as that received during a clinical helical CT scan to the center of a cylindrical, polyethylene phantom. To extend the field of view, two couch rotation scans were taken with the detector offset 15 cm superiorly and then 15 cm inferiorly. The images from these two scans were stitched together before reconstruction. Upright reconstructions were compared to reconstructions from simulation CT scans of the same phantoms. Two methods were investigated for correcting the HUs, including direct calibration and mapping the values from a simulation CT. RESULTS: Overall geometry, spatial linearity, and high contrast resolution were maintained in upright reconstructions. Some artifacts were created and HU accuracy was compromised; however, these limitations could be removed by mapping the HUs from a simulation CT to the upright reconstruction for treatment planning. CONCLUSIONS: The feasibility of using the TrueBeam linac to take upright CBCT images was demonstrated. This technique is straightforward to implement and could be of enormous benefit to patients with thoracic tumors or those who find a supine position difficult to endure.