Phylogenetic inference of inter-population transmission rates for infectious diseases.

Estimating transmission rates is a challenging yet essential aspect of comprehending and controlling the spread of infectious diseases. Various methods exist for estimating transmission rates, each with distinct assumptions, data needs, and constraints. This study introduces a novel phylogenetic approach called transRate, which integrates genetic information with traditional epidemiological approaches to estimate inter-population transmission rates. The phylogenetic method is statistically consistent as the sample size (i.e. the number of pathogen genomes) approaches infinity under the multi-population susceptible-infected-recovered model. Simulation analyses indicate that transRate can accurately estimate the transmission rate with a sample size of 200 ~ 400 pathogen genomes. Using transRate, we analyzed 40,028 high-quality sequences of SARS-CoV-2 in human hosts during the early pandemic. Our analysis uncovered significant transmission between populations even before widespread travel restrictions were implemented. The development of transRate provides valuable insights for scientists and public health officials to enhance their understanding of the pandemic's progression and aiding in preparedness for future viral outbreaks. As public databases for genomic sequences continue to expand, transRate is increasingly vital for tracking and mitigating the spread of infectious diseases.

Landmark-based auto-contouring of clinical target volumes for radiotherapy of nasopharyngeal cancer.

BACKGROUND: The delineation of clinical target volumes (CTVs) for radiotherapy for nasopharyngeal cancer is complex and varies based on the location and extent of disease. PURPOSE: The current study aimed to develop an auto-contouring solution following one protocol guidelines (NRG-HN001) that can be adjusted to meet other guidelines, such as RTOG-0225 and the 2018 International guidelines. METHODS: The study used 2-channel 3-dimensional U-Net and nnU-Net framework to auto-contour 27 normal structures in the head and neck (H&N) region that are used to define CTVs in the protocol. To define the CTV-Expansion (CTV1 and CTV2) and CTV-Overall (the outer envelope of all the CTV contours), we used adjustable morphological geometric landmarks and mimicked physician interpretation of the protocol rules by partially or fully including select anatomic structures. The results were evaluated quantitatively using the dice similarity coefficient (DSC) and mean surface distance (MSD) and qualitatively by independent reviews by two H&N radiation oncologists. RESULTS: The auto-contouring tool showed high accuracy for nasopharyngeal CTVs. Comparison between auto-contours and clinical contours for 19 patients with cancers of various stages showed a DSC of 0.94 ± 0.02 and MSD of 0.4 ± 0.4 mm for CTV-Expansion and a DSC of 0.83 ± 0.02 and MSD of 2.4 ± 0.5 mm for CTV-Overall. Upon independent review, two H&N physicians found the auto-contours to be usable without edits in 85% and 75% of cases. In 15% of cases, minor edits were required by both physicians. Thus, one physician rated 100% of the auto-contours as usable (use as is, or after minor edits), while the other physician rated 90% as usable. The second physician required major edits in 10% of cases. CONCLUSIONS: The study demonstrates the ability of an auto-contouring tool to reliably delineate nasopharyngeal CTVs based on protocol guidelines. The tool was found to be clinically acceptable by two H&N radiation oncology physicians in at least 90% of the cases.

Resection cavity auto-contouring for patients with pediatric medulloblastoma using only CT information.

PURPOSE: Target delineation for radiation therapy is a time-consuming and complex task. Autocontouring gross tumor volumes (GTVs) has been shown to increase efficiency. However, there is limited literature on post-operative target delineation, particularly for CT-based studies. To this end, we trained a CT-based autocontouring model to contour the post-operative GTV of pediatric patients with medulloblastoma. METHODS: One hundred four retrospective pediatric CT scans were used to train a GTV auto-contouring model. Eighty patients were then preselected for contour visibility, continuity, and location to train an additional model. Each GTV was manually annotated with a visibility score based on the number of slices with a visible GTV (1 = < 25%, 2 = 25-50%, 3 = > 50-75%, and 4 = > 75-100%). Contrast and the contrast-to-noise ratio (CNR) were calculated for the GTV contour with respect to a cropped background image. Both models were tested on the original and pre-selected testing sets. The resulting surface and overlap metrics were calculated comparing the clinical and autocontoured GTVs and the corresponding clinical target volumes (CTVs). RESULTS: Eighty patients were pre-selected to have a continuous GTV within the posterior fossa. Of these, 7, 41, 21, and 11 were visibly scored as 4, 3, 2, and 1, respectively. The contrast and CNR removed an additional 11 and 20 patients from the dataset, respectively. The Dice similarity coefficients (DSC) were 0.61 ± 0.29 and 0.67 ± 0.22 on the models without pre-selected training data and 0.55 ± 13.01 and 0.83 ± 0.17 on the models with pre-selected data, respectively. The DSC on the CTV expansions were 0.90 ± 0.13. CONCLUSION: We successfully automatically contoured continuous GTVs within the posterior fossa on scans that had contrast > ± 10 HU. CT-Based auto-contouring algorithms have potential to positively impact centers with limited MRI access.

Identifying the optimal deep learning architecture and parameters for automatic beam aperture definition in 3D radiotherapy.

PURPOSE: Two-dimensional radiotherapy is often used to treat cervical cancer in low- and middle-income countries, but treatment planning can be challenging and time-consuming. Neural networks offer the potential to greatly decrease planning time through automation, but the impact of the wide range of hyperparameters to be set during training on model accuracy has not been exhaustively investigated. In the current study, we evaluated the effect of several convolutional neural network architectures and hyperparameters on 2D radiotherapy treatment field delineation. METHODS: Six commonly used deep learning architectures were trained to delineate four-field box apertures on digitally reconstructed radiographs for cervical cancer radiotherapy. A comprehensive search of optimal hyperparameters for all models was conducted by varying the initial learning rate, image normalization methods, and (when appropriate) convolutional kernel size, the number of learnable parameters via network depth and the number of feature maps per convolution, and nonlinear activation functions. This yielded over 1700 unique models, which were all trained until performance converged and then tested on a separate dataset. RESULTS: Of all hyperparameters, the choice of initial learning rate was most consistently significant for improved performance on the test set, with all top-performing models using learning rates of 0.0001. The optimal image normalization was not consistent across architectures. High overlap (mean Dice similarity coefficient = 0.98) and surface distance agreement (mean surface distance < 2 mm) were achieved between the treatment field apertures for all architectures using the identified best hyperparameters. Overlap Dice similarity coefficient (DSC) and distance metrics (mean surface distance and Hausdorff distance) indicated that DeepLabv3+ and D-LinkNet architectures were least sensitive to initial hyperparameter selection. CONCLUSION: DeepLabv3+ and D-LinkNet are most robust to initial hyperparameter selection. Learning rate, nonlinear activation function, and kernel size are also important hyperparameters for improving performance.

Dosimetric impact and detectability of multi-leaf collimator positioning errors on Varian Halcyon.

The purpose of this study is to investigate the dosimetric impact of multi-leaf collimator (MLC) positioning errors on a Varian Halcyon for both random and systematic errors, and to evaluate the effectiveness of portal dosimetry quality assurance in catching clinically significant changes caused by these errors. Both random and systematic errors were purposely added to 11 physician-approved head and neck volumetric modulated arc therapy (VMAT) treatment plans, yielding a total of 99 unique plans. Plans were then delivered on a preclinical Varian Halcyon linear accelerator and the fluence was captured by an opposed portal dosimeter. When comparing dose-volume histogram (DVH) values of plans with introduced MLC errors to known good plans, clinically significant changes to target structures quickly emerged for plans with systematic errors, while random errors caused less change. For both error types, the magnitude of clinically significant changes increased as error size increased. Portal dosimetry was able to detect all systematic errors, while random errors of ±5 mm or less were unlikely to be detected. Best detection of clinically significant errors, while minimizing false positives, was achieved by following the recommendations of AAPM TG-218. Furthermore, high- to moderate correlation was found between dose DVH metrics for normal tissues surrounding the target and portal dosimetry pass rates. Therefore, it may be concluded that portal dosimetry on the Halcyon is robust enough to detect errors in MLC positioning before they introduce clinically significant changes to VMAT treatment plans.

A snapshot of medical physics practice patterns.

A large number of surveys have been sent to the medical physics community addressing many clinical topics for which the medical physicist is, or may be, responsible. Each survey provides an insight into clinical practice relevant to the medical physics community. The goal of this study was to create a summary of these surveys giving a snapshot of clinical practice patterns. Surveys used in this study were created using SurveyMonkey and distributed between February 6, 2013 and January 2, 2018 via the MEDPHYS and MEDDOS listserv groups. The format of the surveys included questions that were multiple choice and free response. Surveys were included in this analysis if they met the following criteria: more than 20 responses, relevant to radiation therapy physics practice, not single-vendor specific, and formatted as multiple-choice questions (i.e., not exclusively free-text responses). Although the results of free response questions were not explicitly reported, they were carefully reviewed, and the responses were considered in the discussion of each topic. Two-hundred and fifty-two surveys were available, of which 139 passed the inclusion criteria. The mean number of questions per survey was 4. The mean number of respondents per survey was 63. Summaries were made for the following topics: simulation, treatment planning, electron treatments, linac commissioning and quality assurance, setup and treatment verification, IMRT and VMAT treatments, SRS/SBRT, breast treatments, prostate treatments, brachytherapy, TBI, facial lesion treatments, clinical workflow, and after-hours/emergent treatments. We have provided a coherent overview of medical physics practice according to surveys conducted over the last 5 yr, which will be instructive for medical physicists.

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.

The species coalescent indicates possible bat and pangolin origins of the COVID-19 pandemic.

A consensus species tree is reconstructed from 11 gene trees for human, bat, and pangolin beta coronaviruses from samples taken early in the pandemic (prior to April 1, 2020). Using coalescent theory, the shallow (short branches relative to the hosts) consensus species tree provides evidence of recent gene flow events between bat and pangolin beta coronaviruses predating the zoonotic transfer to humans. The consensus species tree was also used to reconstruct the ancestral sequence of human SARS-CoV-2, which was 2 nucleotides different from the Wuhan sequence. The time to most recent common ancestor was estimated to be Dec 8, 2019 with a bat origin. Some human, bat, and pangolin coronavirus lineages found in China are phylogenetically distinct, a rare example of a class II phylogeography pattern (Avise et al. in Ann Rev Eco Syst 18:489-422, 1987). The consensus species tree is a product of evolutionary factors, providing evidence of repeated zoonotic transfers between bat and pangolin as a reservoir for future zoonotic transfers to humans.

Fully-automated, CT-only GTV contouring for palliative head and neck radiotherapy.

Planning for palliative radiotherapy is performed without the advantage of MR or PET imaging in many clinics. Here, we investigated CT-only GTV delineation for palliative treatment of head and neck cancer. Two multi-institutional datasets of palliative-intent treatment plans were retrospectively acquired: a set of 102 non-contrast-enhanced CTs and a set of 96 contrast-enhanced CTs. The nnU-Net auto-segmentation network was chosen for its strength in medical image segmentation, and five approaches separately trained: (1) heuristic-cropped, non-contrast images with a single GTV channel, (2) cropping around a manually-placed point in the tumor center for non-contrast images with a single GTV channel, (3) contrast-enhanced images with a single GTV channel, (4) contrast-enhanced images with separate primary and nodal GTV channels, and (5) contrast-enhanced images along with synthetic MR images with separate primary and nodal GTV channels. Median Dice similarity coefficient ranged from 0.6 to 0.7, surface Dice from 0.30 to 0.56, and 95th Hausdorff distance from 14.7 to 19.7 mm across the five approaches. Only surface Dice exhibited statistically-significant difference across these five approaches using a two-tailed Wilcoxon Rank-Sum test (p ≤ 0.05). Our CT-only results met or exceeded published values for head and neck GTV autocontouring using multi-modality images. However, significant edits would be necessary before clinical use in palliative radiotherapy.

A real-time contouring feedback tool for consensus-based contour training.

Purpose: Variability in contouring structures of interest for radiotherapy continues to be challenging. Although training can reduce such variability, having radiation oncologists provide feedback can be impractical. We developed a contour training tool to provide real-time feedback to trainees, thereby reducing variability in contouring. Methods: We developed a novel metric termed localized signed square distance (LSSD) to provide feedback to the trainee on how their contour compares with a reference contour, which is generated real-time by combining trainee contour and multiple expert radiation oncologist contours. Nine trainees performed contour training by using six randomly assigned training cases that included one test case of the heart and left ventricle (LV). The test case was repeated 30 days later to assess retention. The distribution of LSSD maps of the initial contour for the training cases was combined and compared with the distribution of LSSD maps of the final contours for all training cases. The difference in standard deviations from the initial to final LSSD maps, ΔLSSD, was computed both on a per-case basis and for the entire group. Results: For every training case, statistically significant ΔLSSD were observed for both the heart and LV. When all initial and final LSSD maps were aggregated for the training cases, before training, the mean LSSD ([range], standard deviation) was -0.8 mm ([-37.9, 34.9], 4.2) and 0.3 mm ([-25.1, 32.7], 4.8) for heart and LV, respectively. These were reduced to -0.1 mm ([-16.2, 7.3], 0.8) and 0.1 mm ([-6.6, 8.3], 0.7) for the final LSSD maps during the contour training sessions. For the retention case, the initial and final LSSD maps of the retention case were aggregated and were -1.5 mm ([-22.9, 19.9], 3.4) and -0.2 mm ([-4.5, 1.5], 0.7) for the heart and 1.8 mm ([-16.7, 34.5], 5.1) and 0.2 mm ([-3.9, 1.6],0.7) for the LV. Conclusions: A tool that uses real-time contouring feedback was developed and successfully used for contour training of nine trainees. In all cases, the utility was able to guide the trainee and ultimately reduce the variability of the trainee's contouring.

Synthetic Megavoltage Cone Beam Computed Tomography Image Generation for Improved Contouring Accuracy of Cardiac Pacemakers.

In this study, we aimed to enhance the contouring accuracy of cardiac pacemakers by improving their visualization using deep learning models to predict MV CBCT images based on kV CT or CBCT images. Ten pacemakers and four thorax phantoms were included, creating a total of 35 combinations. Each combination was imaged on a Varian Halcyon (kV/MV CBCT images) and Siemens SOMATOM CT scanner (kV CT images). Two generative adversarial network (GAN)-based models, cycleGAN and conditional GAN (cGAN), were trained to generate synthetic MV (sMV) CBCT images from kV CT/CBCT images using twenty-eight datasets (80%). The pacemakers in the sMV CBCT images and original MV CBCT images were manually delineated and reviewed by three users. The Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD) were used to compare contour accuracy. Visual inspection showed the improved visualization of pacemakers on sMV CBCT images compared to original kV CT/CBCT images. Moreover, cGAN demonstrated superior performance in enhancing pacemaker visualization compared to cycleGAN. The mean DSC, HD95, and MSD for contours on sMV CBCT images generated from kV CT/CBCT images were 0.91 ± 0.02/0.92 ± 0.01, 1.38 ± 0.31 mm/1.18 ± 0.20 mm, and 0.42 ± 0.07 mm/0.36 ± 0.06 mm using the cGAN model. Deep learning-based methods, specifically cycleGAN and cGAN, can effectively enhance the visualization of pacemakers in thorax kV CT/CBCT images, therefore improving the contouring precision of these devices.

Deep learning-based dose prediction to improve the plan quality of volumetric modulated arc therapy for gynecologic cancers.

BACKGROUND: In recent years, deep-learning models have been used to predict entire three-dimensional dose distributions. However, the usability of dose predictions to improve plan quality should be further investigated. PURPOSE: To develop a deep-learning model to predict high-quality dose distributions for volumetric modulated arc therapy (VMAT) plans for patients with gynecologic cancer and to evaluate their usability in driving plan quality improvements. METHODS: A total of 79 VMAT plans for the female pelvis were used to train (47 plans), validate (16 plans), and test (16 plans) 3D dense dilated U-Net models to predict 3D dose distributions. The models received the normalized CT scan, dose prescription, and target and normal tissue contours as inputs. Three models were used to predict the dose distributions for plans in the test set. A radiation oncologist specializing in the treatment of gynecologic cancers scored the test set predictions using a 5-point scale (5, acceptable as-is; 4, prefer minor edits; 3, minor edits needed; 2, major edits needed; and 1, unacceptable). The clinical plans for which the dose predictions indicated that improvements could be made were reoptimized with constraints extracted from the predictions. RESULTS: The predicted dose distributions in the test set were of comparable quality to the clinical plans. The mean voxel-wise dose difference was -0.14 ± 0.46 Gy. The percentage dose differences in the predicted target metrics of D 1 % ${D}_{1{\mathrm{\% }}}$ and D 98 % ${D}_{98{\mathrm{\% }}}$ were -1.05% ± 0.59% and 0.21% ± 0.28%, respectively. The dose differences in the predicted organ at risk mean and maximum doses were -0.30 ± 1.66 Gy and -0.42 ± 2.07 Gy, respectively. A radiation oncologist deemed all of the predicted dose distributions clinically acceptable; 12 received a score of 5, and four received a score of 4. Replanning of flagged plans (five plans) showed that the original plans could be further optimized to give dose distributions close to the predicted dose distributions. CONCLUSIONS: Deep-learning dose prediction can be used to predict high-quality and clinically acceptable dose distributions for VMAT female pelvis plans, which can then be used to identify plans that can be improved with additional optimization.

Deep Learning-Based Dose Prediction for Automated, Individualized Quality Assurance of Head and Neck Radiation Therapy Plans.

PURPOSE: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. METHODS AND MATERIALS: A total of 245 volumetric modulated arc therapy HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included computed tomography images, target prescriptions, and contours for targets and organs at risk (OARs). The model's performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared with manual flags by 3 HN radiation oncologists. RESULTS: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D1%,D95%, and D99% across the targets were within -2.53% ± 1.34%, -0.42% ± 1.27%, and -0.12% ± 1.97%, respectively, and the OAR mean and maximum doses were within -0.33 ± 1.40 Gy and -0.96 ± 2.08 Gy, respectively. For the plan quality assessment study, radiation oncologists flagged 47 OARs for possible plan improvement. There was high interphysician variability; 83% of physician-flagged OARs were flagged by only one of 3 physicians. The comparative dose prediction model flagged 63 OARs, including 30 of 47 physician-flagged OARs. CONCLUSIONS: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality.

Automated Contouring and Planning in Radiation Therapy: What Is 'Clinically Acceptable'?

Developers and users of artificial-intelligence-based tools for automatic contouring and treatment planning in radiotherapy are expected to assess clinical acceptability of these tools. However, what is 'clinical acceptability'? Quantitative and qualitative approaches have been used to assess this ill-defined concept, all of which have advantages and disadvantages or limitations. The approach chosen may depend on the goal of the study as well as on available resources. In this paper, we discuss various aspects of 'clinical acceptability' and how they can move us toward a standard for defining clinical acceptability of new autocontouring and planning tools.

Multi-organ segmentation of abdominal structures from non-contrast and contrast enhanced CT images.

Manually delineating upper abdominal organs at risk (OARs) is a time-consuming task. To develop a deep-learning-based tool for accurate and robust auto-segmentation of these OARs, forty pancreatic cancer patients with contrast-enhanced breath-hold computed tomographic (CT) images were selected. We trained a three-dimensional (3D) U-Net ensemble that automatically segments all organ contours concurrently with the self-configuring nnU-Net framework. Our tool's performance was assessed on a held-out test set of 30 patients quantitatively. Five radiation oncologists from three different institutions assessed the performance of the tool using a 5-point Likert scale on an additional 75 randomly selected test patients. The mean (± std. dev.) Dice similarity coefficient values between the automatic segmentation and the ground truth on contrast-enhanced CT images were 0.80 ± 0.08, 0.89 ± 0.05, 0.90 ± 0.06, 0.92 ± 0.03, 0.96 ± 0.01, 0.97 ± 0.01, 0.96 ± 0.01, and 0.96 ± 0.01 for the duodenum, small bowel, large bowel, stomach, liver, spleen, right kidney, and left kidney, respectively. 89.3% (contrast-enhanced) and 85.3% (non-contrast-enhanced) of duodenum contours were scored as a 3 or above, which required only minor edits. More than 90% of the other organs' contours were scored as a 3 or above. Our tool achieved a high level of clinical acceptability with a small training dataset and provides accurate contours for treatment planning.

OpenKBP-Opt: an international and reproducible evaluation of 76 knowledge-based planning pipelines.

Objective.To establish an open framework for developing plan optimization models for knowledge-based planning (KBP).Approach.Our framework includes radiotherapy treatment data (i.e. reference plans) for 100 patients with head-and-neck cancer who were treated with intensity-modulated radiotherapy. That data also includes high-quality dose predictions from 19 KBP models that were developed by different research groups using out-of-sample data during the OpenKBP Grand Challenge. The dose predictions were input to four fluence-based dose mimicking models to form 76 unique KBP pipelines that generated 7600 plans (76 pipelines × 100 patients). The predictions and KBP-generated plans were compared to the reference plans via: the dose score, which is the average mean absolute voxel-by-voxel difference in dose; the deviation in dose-volume histogram (DVH) points; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models.Main results.The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50-0.62, which indicates that the quality of the predictions was generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P< 0.05; one-sided Wilcoxon test) on 18 of 23 DVH points. Similarly, each optimization model generated plans that satisfied a higher percentage of criteria than the reference plans, which satisfied 3.5% more criteria than the set of all dose predictions. Lastly, our theoretical investigation demonstrated that the dose mimicking models generated plans that are also optimal for an inverse planning model.Significance.This was the largest international effort to date for evaluating the combination of KBP prediction and optimization models. We found that the best performing models significantly outperformed the reference dose and dose predictions. In the interest of reproducibility, our data and code is freely available.

Technical Note: Dose prediction for head and neck radiotherapy using a three-dimensional dense dilated U-net architecture.

PURPOSE: Radiation therapy treatment planning is a time-consuming and iterative manual process. Consequently, plan quality varies greatly between and within institutions. Artificial intelligence shows great promise in improving plan quality and reducing planning times. This technical note describes our participation in the American Association of Physicists in Medicine Open Knowledge-Based Planning Challenge (OpenKBP), a competition to accurately predict radiation therapy dose distributions. METHODS: A three-dimensional (3D) densely connected U-Net with dilated convolutions was developed to predict 3D dose distributions given contoured CT images of head and neck patients as input. While traditional augmentation techniques such as rotations and translations were explored, it was found that training on random patches alone resulted in the greatest model performance. A custom-weighted mean squared error loss function was employed. Finally, an ensemble of best-performing networks was used to generate the final challenge predictions. RESULTS: Our team (SuperPod) placed second in the dose stream of the OpenKBP challenge. The average mean absolute difference between the predicted and clinical dose distributions of the testing dataset was 2.56 Gy. On average, the predicted normalized target DVH metrics were within 3% of the clinical plans, and the predicted organ at risk DVH metrics were within 2 Gy of the clinical plans. CONCLUSIONS: The developed 3D dense dilated U-Net architecture can accurately predict 3D radiotherapy dose distributions and can be used as part of a fully automated radiation therapy planning pipeline.

Development and dosimetric assessment of an automatic dental artifact classification tool to guide artifact management techniques in a fully automated treatment planning workflow.

PURPOSE: We conducted our study to develop a tool capable of automatically detecting dental artifacts in a CT scan on a slice-by-slice basis and to assess the dosimetric impact of implementing the tool into the Radiation Planning Assistant (RPA), a web-based platform designed to fully automate the radiation therapy treatment planning process. METHODS: We developed an automatic dental artifact identification tool and assessed the dosimetric impact of its use in the RPA. Three users manually annotated 83,676 head-and-neck (HN) CT slices (549 patients). Majority-voting was applied to the individual annotations to determine the presence or absence of dental artifacts. The patients were divided into train, cross-validation, and test data sets (ratio: 3:1:1, respectively). A random subset of images without dental artifacts was used to balance classes (1:1) in the training data set. The Inception-V3 deep learning model was trained with the binary cross-entropy loss function. With use of this model, we automatically identified artifacts on 15 RPA HN plans on a slice-by-slice basis and investigated three dental artifact management methods applied before and after volumetric modulated arc therapy (VMAT) plan optimization. The resulting dose distributions and target coverage were quantified. RESULTS: Per-slice accuracy, sensitivity, and specificity were 99 %, 91 %, and 99 %, respectively. The model identified all patients with artifacts. Small dosimetric differences in total plan dose were observed between the various density-override methods (±1 Gy). For the pre- and post-optimized plans, 90 % and 99 %, respectively, of dose comparisons resulted in normal structure dose differences of ±1 Gy. Differences in the volume of structures receiving 95 % of the prescribed dose (V95[%]) were ≤0.25 % for 100 % of plans. CONCLUSION: The dosimetric impact of applying dental artifact management before and after artifact plan optimization was minor. Our results suggest that not accounting for dental artifacts in the current RPA workflow (where only post-optimization dental artifact management is possible) may result in minor dosimetric differences. If RPA users choose to override CT densities as a solution to managing dental artifacts, our results suggest segmenting the volume of the artifact and overriding its density to water is a safe option.

Generating High-Quality Lymph Node Clinical Target Volumes for Head and Neck Cancer Radiation Therapy Using a Fully Automated Deep Learning-Based Approach.

PURPOSE: To develop a deep learning model that generates consistent, high-quality lymph node clinical target volumes (CTV) contours for head and neck cancer (HNC) patients, as an integral part of a fully automated radiation treatment planning workflow. METHODS AND MATERIALS: Computed tomography (CT) scans from 71 HNC patients were retrospectively collected and split into training (n = 51), cross-validation (n = 10), and test (n = 10) data sets. All had target volume delineations covering lymph node levels Ia through V (Ia-V), Ib through V (Ib-V), II through IV (II-IV), and retropharyngeal (RP) nodes, which were previously approved by a radiation oncologist specializing in HNC. Volumes of interest (VOIs) about nodal levels were automatically identified using computer vision techniques. The VOI (cropped CT image) and approved contours were used to train a U-Net autosegmentation model. Each lymph node level was trained independently, with model parameters optimized by assessing performance on the cross-validation data set. Once optimal model parameters were identified, overlap and distance metrics were calculated between ground truth and autosegmentations on the test set. Lastly, this final model was used on 32 additional patient scans (not included in original 71 cases) and autosegmentations visually rated by 3 radiation oncologists as being "clinically acceptable without requiring edits," "requiring minor edits," or "requiring major edits." RESULTS: When comparing ground truths to autosegmentations on the test data set, median Dice Similarity Coefficients were 0.90, 0.90, 0.89, and 0.81, and median mean surface distance values were 1.0 mm, 1.0 mm, 1.1 mm, and 1.3 mm for node levels Ia-V, Ib-V, II-IV, and RP nodes, respectively. Qualitative scoring varied among physicians. Overall, 99% of autosegmented target volumes were either scored as being clinically acceptable or requiring minor edits (ie, stylistic recommendations, <2 minutes). CONCLUSIONS: We developed a fully automated artificial intelligence approach to autodelineate nodal CTVs for patients with intact HNC. Most autosegmentations were found to be clinically acceptable after qualitative review when considering recommended stylistic edits. This promising work automatically delineates nodal CTVs in a robust and consistent manner; this approach can be implemented in ongoing efforts for fully automated radiation treatment planning.

Matching and Homogenizing Convolution Kernels for Quantitative Studies in Computed Tomography.

The sharpness of the kernels used for image reconstruction in computed tomography affects the values of the quantitative image features. We sought to identify the kernels that produce similar feature values to enable a more effective comparison of images produced using scanners from different manufactures. We also investigated a new image filter designed to change the kernel-related component of the frequency spectrum of a postreconstruction image from that of the initial kernel to that of a preferred kernel. A radiomics texture phantom was imaged using scanners from GE, Philips, Siemens, and Toshiba. Images were reconstructed multiple times, varying the kernel from smooth to sharp. The phantom comprised 10 cartridges of various textures. A semiautomated method was used to produce 8 × 2 × 2 cm regions of interest for each cartridge and for all scans. For each region of interest, 38 radiomics features from the categories intensity direct (n = 12), gray-level co-occurrence matrix (n = 21), and neighborhood gray-tone difference matrix (n = 5) were extracted. We then calculated the fractional differences of the features from those of the baseline kernel (GE Standard). To gauge the importance of the differences, we scaled them by the coefficient of variation of the same feature from a cohort of patients with non-small cell lung cancer. The noise power spectra for each kernel were estimated from the phantom's solid acrylic cartridge, and kernel-homogenization filters were developed from these estimates. The Philips C, Siemens B30f, and Toshiba FC24 kernels produced feature values most similar to GE Standard. The kernel homogenization filters reduced the median differences from baseline to less than 1 coefficient of variation in the patient population for all of the GE, Philips, and Siemens kernels except for GE Edge and Toshiba kernels. For prospective computed tomographic radiomics studies, the scanning protocol should specify kernels that have been shown to produce similar feature values. For retrospective studies, kernel homogenization filters can be designed and applied to reduce the kernel-related differences in the feature values.