Creating patient-specific digital phantoms with a longitudinal atlas for evaluating deformable CT-CBCT registration in adaptive lung radiotherapy.

BACKGROUND: Quality assurance of deformable image registration (DIR) is challenging because the ground truth is often unavailable. In addition, current approaches that rely on artificial transformations do not adequately resemble clinical scenarios encountered in adaptive radiotherapy. PURPOSE: We developed an atlas-based method to create a variety of patient-specific serial digital phantoms with CBCT-like image quality to assess the DIR performance for longitudinal CBCT imaging data in adaptive lung radiotherapy. METHODS: A library of deformations was created by extracting the longitudinal changes observed between a planning CT and weekly CBCT from an atlas of lung radiotherapy patients. The planning CT of an inquiry patient was first deformed by mapping the deformation pattern from a matched atlas patient, and subsequently appended with CBCT artifacts to imitate a weekly CBCT. Finally, a group of digital phantoms around an inquiry patient was produced to simulate a series of possible evolutions of tumor and adjacent normal structures. We validated the generated deformation vector fields (DVFs) to ensure numerically and physiologically realistic transformations. The proposed framework was applied to evaluate the performance of the DIR algorithm implemented in the commercial Eclipse treatment planning system in a retrospective study of eight inquiry patients. RESULTS: The generated DVFs were inverse consistent within less than 3 mm and did not exhibit unrealistic folding. The deformation patterns adequately mimicked the observed longitudinal anatomical changes of the matched atlas patients. Worse Eclipse DVF accuracy was observed in regions of low image contrast or artifacts. The structure volumes exhibiting a DVF error magnitude of equal or more than 2 mm ranged from 24.5% (spinal cord) to 69.2% (heart) and the maximum DVF error exceeded 5 mm for all structures except the spinal cord. Contour-based evaluations showed a high degree of alignment with dice similarity coefficients above 0.8 in all cases, which underestimated the overall DVF accuracy within the structures. CONCLUSIONS: It is feasible to create and augment digital phantoms based on a particular patient of interest using multiple series of deformation patterns from matched patients in an atlas. This can provide a semi-automated procedure to complement the quality assurance of CT-CBCT DIR and facilitate the clinical implementation of image-guided and adaptive radiotherapy that involve longitudinal CBCT imaging studies.

Preoperative 18F-FDG PET/CT and CT radiomics for identifying aggressive histopathological subtypes in early stage lung adenocarcinoma.

Lung adenocarcinoma (ADC) is the most common non-small cell lung cancer. Surgical resection is the primary treatment for early-stage lung ADC while lung-sparing surgery is an alternative for non-aggressive cases. Identifying histopathologic subtypes before surgery helps determine the optimal surgical approach. Predominantly solid or micropapillary (MIP) subtypes are aggressive and associated with a higher likelihood of recurrence and metastasis and lower survival rates. This study aims to non-invasively identify these aggressive subtypes using preoperative 18F-FDG PET/CT and diagnostic CT radiomics analysis. We retrospectively studied 119 patients with stage I lung ADC and tumors ≤ 2 cm, where 23 had aggressive subtypes (18 solid and 5 MIPs). Out of 214 radiomic features from the PET/CT and CT scans and 14 clinical parameters, 78 significant features (3 CT and 75 PET features) were identified through univariate analysis and hierarchical clustering with minimized feature collinearity. A combination of Support Vector Machine classifier and Least Absolute Shrinkage and Selection Operator built predictive models. Ten iterations of 10-fold cross-validation (10 ×10-fold CV) evaluated the model. A pair of texture feature (PET GLCM Correlation) and shape feature (CT Sphericity) emerged as the best predictor. The radiomics model significantly outperformed the conventional predictor SUVmax (accuracy: 83.5% vs. 74.7%, p = 9e-9) and identified aggressive subtypes by evaluating FDG uptake in the tumor and tumor shape. It also demonstrated a high negative predictive value of 95.6% compared to SUVmax (88.2%, p = 2e-10). The proposed radiomics approach could reduce unnecessary extensive surgeries for non-aggressive subtype patients, improving surgical decision-making for early-stage lung ADC patients.

Seq2Morph: A deep learning deformable image registration algorithm for longitudinal imaging studies and adaptive radiotherapy.

PURPOSE: To simultaneously register all the longitudinal images acquired in a radiotherapy course for analyzing patients' anatomy changes for adaptive radiotherapy (ART). METHODS: To address the unique needs of ART, we designed Seq2Morph, a novel deep learning-based deformable image registration (DIR) network. Seq2Morph was built upon VoxelMorph which is a general-purpose framework for learning-based image registration. The major upgrades are (1) expansion of inputs to all weekly cone-beam computed tomography (CBCTs) acquired for monitoring treatment responses throughout a radiotherapy course, for registration to their planning CT; (2) incorporation of 3D convolutional long short-term memory between the encoder and decoder of VoxelMorph, to parse the temporal patterns of anatomical changes; and (3) addition of bidirectional pathways to calculate and minimize inverse consistency errors (ICEs). Longitudinal image sets from 50 patients, including a planning CT and 6 weekly CBCTs per patient, were utilized for network training and cross-validation. The outputs were deformation vector fields for all the registration pairs. The loss function was composed of a normalized cross-correlation for image intensity similarity, a DICE for contour similarity, an ICE, and a deformation regularization term. For performance evaluation, DICE and Hausdorff distance (HD) for the manual versus predicted contours of tumor and esophagus on weekly basis were quantified and further compared with other state-of-the-art algorithms, including conventional VoxelMorph and large deformation diffeomorphic metric mapping (LDDMM). RESULTS: Visualization of the hidden states of Seq2Morph revealed distinct spatiotemporal anatomy change patterns. Quantitatively, Seq2Morph performed similarly to LDDMM, but significantly outperformed VoxelMorph as measured by GTV DICE: (0.799±0.078, 0.798±0.081, and 0.773±0.078), and 50% HD (mm): (0.80±0.57, 0.88±0.66, and 0.95±0.60). The per-patient inference of Seq2Morph took 22 s, much less than LDDMM (∼30 min). CONCLUSIONS: Seq2Morph can provide accurate and fast DIR for longitudinal image studies by exploiting spatial-temporal patterns. It closely matches the clinical workflow and has the potential to serve both online and offline ART.

Inter- and intrafraction motion assessment and accumulated dose quantification of upper gastrointestinal organs during magnetic resonance-guided ablative radiation therapy of pancreas patients.

BACKGROUND AND PURPOSE: Stereotactic body radiation therapy (SBRT) of locally advanced pancreatic cancer (LAPC) is challenging due to significant motion of gastrointestinal (GI) organs. The goal of our study was to quantify inter and intrafraction deformations and dose accumulation of upper GI organs in LAPC patients. MATERIALS AND METHODS: Five LAPC patients undergoing five-fraction magnetic resonance-guided radiation therapy (MRgRT) using abdominal compression and daily online plan adaptation to 50 Gy were analyzed. A pre-treatment, verification, and post-treatment MR imaging (MRI) for each of the five fractions (75 total) were used to calculate intra and interfraction motion. The MRIs were registered using Large Deformation Diffeomorphic Metric Mapping (LDDMM) deformable image registration (DIR) method and total dose delivered to stomach_duodenum, small bowel (SB) and large bowel (LB) were accumulated. Deformations were quantified using gradient magnitude and Jacobian integral of the Deformation Vector Fields (DVF). Registration DVFs were geometrically assessed using Dice and 95th percentile Hausdorff distance (HD95) between the deformed and physician's contours. Accumulated doses were then calculated from the DVFs. RESULTS: Median Dice and HD95 were: Stomach_duodenum (0.9, 1.0 mm), SB (0.9, 3.6 mm), and LB (0.9, 2.0 mm). Median (max) interfraction deformation for stomach_duodenum, SB and LB was 6.4 (25.8) mm, 7.9 (40.5) mm and 7.6 (35.9) mm. Median intrafraction deformation was 5.5 (22.6) mm, 8.2 (37.8) mm and 7.2 (26.5) mm. Accumulated doses for two patients exceeded institutional constraints for stomach_duodenum, one of whom experienced Grade1 acute and late abdominal toxicity. CONCLUSION: LDDMM method indicates feasibility to measure large GI motion and accumulate dose. Further validation on larger cohort will allow quantitative dose accumulation to more reliably optimize online MRgRT.

Deep learning driven predictive treatment planning for adaptive radiotherapy of lung cancer.

BACKGROUND AND PURPOSE: To develop a novel deep learning algorithm of sequential analysis, Seq2Seq, for predicting weekly anatomical changes of lung tumor and esophagus during definitive radiotherapy, incorporate the potential tumor shrinkage into a predictive treatment planning paradigm, and improve the therapeutic ratio. METHODS AND MATERIALS: Seq2Seq starts with the primary tumor and esophagus observed on the planning CT to predict their geometric evolution during radiotherapy on a weekly basis, and subsequently updates the predictions with new snapshots acquired via weekly CBCTs. Seq2Seq is equipped with convolutional long short term memory to analyze the spatial-temporal changes of longitudinal images, trained and validated using a dataset including sixty patients. Predictive plans were optimized according to each weekly prediction and made ready for weekly deployment to mitigate the clinical burden of online weekly replanning. RESULTS: Seq2Seq tracks structural changes well: DICE between predicted and actual weekly tumor and esophagus were (0.83 ± 0.10, 0.79 ± 0.14, 0.78 ± 0.12, 0.77 ± 0.12, 0.75 ± 0.12, 0.71 ± 0.17), and (0.72 ± 0.16, 0.73 ± 0.11, 0.75 ± 0.08, 0.74 ± 0.09, 0.72 ± 0.14, 0.71 ± 0.14), respectively, while the average Hausdorff distances were within 2 mm. Evaluating dose to the actual weekly tumor and esophagus, a 4.2 Gy reduction in esophagus mean dose while maintaining 60 Gy tumor coverage was achieved with the predictive weekly plans, compared to the plan optimized using the initial tumor and esophagus alone, primarily due to noticeable tumor shrinkage during radiotherapy. CONCLUSION: It is feasible to predict the longitudinal changes of tumor and esophagus with the Seq2Seq, which could lead to improving the efficiency and effectiveness of lung adaptive radiotherapy.

Deformation driven Seq2Seq longitudinal tumor and organs-at-risk prediction for radiotherapy.

PURPOSE: Radiotherapy presents unique challenges and clinical requirements for longitudinal tumor and organ-at-risk (OAR) prediction during treatment. The challenges include tumor inflammation/edema and radiation-induced changes in organ geometry, whereas the clinical requirements demand flexibility in input/output sequence timepoints to update the predictions on rolling basis and the grounding of all predictions in relationship to the pre-treatment imaging information for response and toxicity assessment in adaptive radiotherapy. METHODS: To deal with the aforementioned challenges and to comply with the clinical requirements, we present a novel 3D sequence-to-sequence model based on Convolution Long Short-Term Memory (ConvLSTM) that makes use of series of deformation vector fields (DVFs) between individual timepoints and reference pre-treatment/planning CTs to predict future anatomical deformations and changes in gross tumor volume as well as critical OARs. High-quality DVF training data are created by employing hyper-parameter optimization on the subset of the training data with DICE coefficient and mutual information metric. We validated our model on two radiotherapy datasets: a publicly available head-and-neck dataset (28 patients with manually contoured pre-, mid-, and post-treatment CTs), and an internal non-small cell lung cancer dataset (63 patients with manually contoured planning CT and 6 weekly CBCTs). RESULTS: The use of DVF representation and skip connections overcomes the blurring issue of ConvLSTM prediction with the traditional image representation. The mean and standard deviation of DICE for predictions of lung GTV at weeks 4, 5, and 6 were 0.83 ± 0.09, 0.82 ± 0.08, and 0.81 ± 0.10, respectively, and for post-treatment ipsilateral and contralateral parotids, were 0.81 ± 0.06 and 0.85 ± 0.02. CONCLUSION: We presented a novel DVF-based Seq2Seq model for medical images, leveraging the complete 3D imaging information of a relatively large longitudinal clinical dataset, to carry out longitudinal GTV/OAR predictions for anatomical changes in HN and lung radiotherapy patients, which has potential to improve RT outcomes.

Multitask 3D CBCT-to-CT translation and organs-at-risk segmentation using physics-based data augmentation.

PURPOSE: In current clinical practice, noisy and artifact-ridden weekly cone beam computed tomography (CBCT) images are only used for patient setup during radiotherapy. Treatment planning is performed once at the beginning of the treatment using high-quality planning CT (pCT) images and manual contours for organs-at-risk (OARs) structures. If the quality of the weekly CBCT images can be improved while simultaneously segmenting OAR structures, this can provide critical information for adapting radiotherapy mid-treatment as well as for deriving biomarkers for treatment response. METHODS: Using a novel physics-based data augmentation strategy, we synthesize a large dataset of perfectly/inherently registered pCT and synthetic-CBCT pairs for locally advanced lung cancer patient cohort, which are then used in a multitask three-dimensional (3D) deep learning framework to simultaneously segment and translate real weekly CBCT images to high-quality pCT-like images. RESULTS: We compared the synthetic CT and OAR segmentations generated by the model to real pCT and manual OAR segmentations and showed promising results. The real week 1 (baseline) CBCT images which had an average mean absolute error (MAE) of 162.77 HU compared to pCT images are translated to synthetic CT images that exhibit a drastically improved average MAE of 29.31 HU and average structural similarity of 92% with the pCT images. The average DICE scores of the 3D OARs segmentations are: lungs 0.96, heart 0.88, spinal cord 0.83, and esophagus 0.66. CONCLUSIONS: We demonstrate an approach to translate artifact-ridden CBCT images to high-quality synthetic CT images, while simultaneously generating good quality segmentation masks for different OARs. This approach could allow clinicians to adjust treatment plans using only the routine low-quality CBCT images, potentially improving patient outcomes. Our code, data, and pre-trained models will be made available via our physics-based data augmentation library, Physics-ArX, at https://github.com/nadeemlab/Physics-ArX.

Deep cross-modality (MR-CT) educed distillation learning for cone beam CT lung tumor segmentation.

PURPOSE: Despite the widespread availability of in-treatment room cone beam computed tomography (CBCT) imaging, due to the lack of reliable segmentation methods, CBCT is only used for gross set up corrections in lung radiotherapies. Accurate and reliable auto-segmentation tools could potentiate volumetric response assessment and geometry-guided adaptive radiation therapies. Therefore, we developed a new deep learning CBCT lung tumor segmentation method. METHODS: The key idea of our approach called cross-modality educed distillation (CMEDL) is to use magnetic resonance imaging (MRI) to guide a CBCT segmentation network training to extract more informative features during training. We accomplish this by training an end-to-end network comprised of unpaired domain adaptation (UDA) and cross-domain segmentation distillation networks (SDNs) using unpaired CBCT and MRI datasets. UDA approach uses CBCT and MRI that are not aligned and may arise from different sets of patients. The UDA network synthesizes pseudo MRI from CBCT images. The SDN consists of teacher MRI and student CBCT segmentation networks. Feature distillation regularizes the student network to extract CBCT features that match the statistical distribution of MRI features extracted by the teacher network and obtain better differentiation of tumor from background. The UDA network was implemented with a cycleGAN improved with contextual losses separately on Unet and dense fully convolutional segmentation networks (DenseFCN). Performance comparisons were done against CBCT only using 2D and 3D networks. We also compared against an alternative framework that used UDA with MR segmentation network, whereby segmentation was done on the synthesized pseudo MRI representation. All networks were trained with 216 weekly CBCTs and 82 T2-weighted turbo spin echo MRI acquired from different patient cohorts. Validation was done on 20 weekly CBCTs from patients not used in training. Independent testing was done on 38 weekly CBCTs from patients not used in training or validation. Segmentation accuracy was measured using surface Dice similarity coefficient (SDSC) and Hausdroff distance at 95th percentile (HD95) metrics. RESULTS: The CMEDL approach significantly improved (p < 0.001) the accuracy of both Unet (SDSC of 0.83 ± 0.08; HD95 of 7.69 ± 7.86 mm) and DenseFCN (SDSC of 0.75 ± 0.13; HD95 of 11.42 ± 9.87 mm) over CBCT only 2DUnet (SDSC of 0.69 ± 0.11; HD95 of 21.70 ± 16.34 mm), 3D Unet (SDSC of 0.72 ± 0.20; HD95 15.01 ± 12.98 mm), and DenseFCN (SDSC of 0.66 ± 0.15; HD95 of 22.15 ± 17.19 mm) networks. The alternate framework using UDA with the MRI network was also more accurate than the CBCT only methods but less accurate the CMEDL approach. CONCLUSIONS: Our results demonstrate feasibility of the introduced CMEDL approach to produce reasonably accurate lung cancer segmentation from CBCT images. Further validation on larger datasets is necessary for clinical translation.

Generalizable cone beam CT esophagus segmentation using physics-based data augmentation.

Automated segmentation of the esophagus is critical in image-guided/adaptive radiotherapy of lung cancer to minimize radiation-induced toxicities such as acute esophagitis. We have developed a semantic physics-based data augmentation method for segmenting the esophagus in both planning CT (pCT) and cone beam CT (CBCT) using 3D convolutional neural networks. One hundred and ninety-one cases with their pCTs and CBCTs from four independent datasets were used to train a modified 3D U-Net architecture and a multi-objective loss function specifically designed for soft-tissue organs such as the esophagus. Scatter artifacts and noises were extracted from week-1 CBCTs using a power-law adaptive histogram equalization method and induced to the corresponding pCT were reconstructed using CBCT reconstruction parameters. Moreover, we leveraged physics-based artifact induction in pCTs to drive the esophagus segmentation in real weekly CBCTs. Segmentations were evaluated using the geometric Dice coefficient and Hausdorff distance as well as dosimetrically using mean esophagus dose and D 5cc. Due to the physics-based data augmentation, our model trained just on the synthetic CBCTs was robust and generalizable enough to also produce state-of-the-art results on the pCTs and CBCTs, achieving Dice overlaps of 0.81 and 0.74, respectively. It is concluded that our physics-based data augmentation spans the realistic noise/artifact spectrum across patient CBCT/pCT data and can generalize well across modalities, eventually improving the accuracy of treatment setup and response analysis.

Early Prediction of Acute Esophagitis for Adaptive Radiation Therapy.

PURPOSE: Acute esophagitis (AE) is a common dose-limiting toxicity in radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). We developed an early AE prediction model from weekly accumulated esophagus dose and its associated local volumetric change. METHODS AND MATERIALS: Fifty-one patients with LA-NSCLC underwent treatment with intensity modulated radiation therapy to 60 Gy in 2-Gy fractions with concurrent chemotherapy and weekly cone beam computed tomography (CBCT). Twenty-eight patients (55%) developed grade ≥2 AE (≥AE2) at a median of 4 weeks after the start of radiation therapy. For early ≥AE2 prediction, the esophagus on CBCT of the first 2 weeks was deformably registered to the planning computed tomography images, and weekly esophagus dose was accumulated. Week 1-to-week 2 (w1→w2) esophagus volume changes including maximum esophagus expansion (MEex%) and volumes with ≥x% local expansions (VEx%; x = 5, 10, 15) were calculated from the Jacobian map of deformation vector field gradients. Logistic regression model with 5-fold cross-validation was built using combinations of the accumulated mean esophagus doses (MED) and the esophagus change parameters with the lowest P value in univariate analysis. The model was validated on an additional 18 and 11 patients with weekly CBCT and magnetic resonance imaging (MRI), respectively, and compared with models using only planned mean dose (MEDPlan). Performance was assessed using area under the curve (AUC) and Hosmer-Lemeshow test (PHL). RESULTS: Univariately, w1→w2 VE10% (P = .004), VE5% (P = .01) and MEex% (P = .02) significantly predicted ≥AE2. A model combining MEDW2 and w1→w2 VE10% had the best performance (AUC = 0.80; PHL = 0.43), whereas the MEDPlan model had a lower accuracy (AUC = 0.67; PHL = 0.26). The combined model also showed high accuracy in the CBCT (AUC = 0.78) and MRI validations (AUC = 0.75). CONCLUSIONS: A CBCT-based, cross-validated, and internally validated model on MRI with a combination of accumulated esophagus dose and local volume change from the first 2 weeks of chemotherapy significantly improved AE prediction compared with conventional models using only the planned dose. This model could inform plan adaptation early to lower the risk of esophagitis.

Reproducible and Interpretable Spiculation Quantification for Lung Cancer Screening.

Spiculations are important predictors of lung cancer malignancy, which are spikes on the surface of the pulmonary nodules. In this study, we proposed an interpretable and parameter-free technique to quantify the spiculation using area distortion metric obtained by the conformal (angle-preserving) spherical parameterization. We exploit the insight that for an angle-preserved spherical mapping of a given nodule, the corresponding negative area distortion precisely characterizes the spiculations on that nodule. We introduced novel spiculation scores based on the area distortion metric and spiculation measures. We also semi-automatically segment lung nodule (for reproducibility) as well as vessel and wall attachment to differentiate the real spiculations from lobulation and attachment. A simple pathological malignancy prediction model is also introduced. We used the publicly-available LIDC-IDRI dataset pathologists (strong-label) and radiologists (weak-label) ratings to train and test radiomics models containing this feature, and then externally validate the models. We achieved AUC = 0.80 and 0.76, respectively, with the models trained on the 811 weakly-labeled LIDC datasets and tested on the 72 strongly-labeled LIDC and 73 LUNGx datasets; the previous best model for LUNGx had AUC = 0.68. The number-of-spiculations feature was found to be highly correlated (Spearman's rank correlation coefficient ρ=0.44) with the radiologists' spiculation score. We developed a reproducible and interpretable, parameter-free technique for quantifying spiculations on nodules. The spiculation quantification measures was then applied to the radiomics framework for pathological malignancy prediction with reproducible semi-automatic segmentation of nodule. Using our interpretable features (size, attachment, spiculation, lobulation), we were able to achieve higher performance than previous models. In the future, we will exhaustively test our model for lung cancer screening in the clinic.

Predicting spatial esophageal changes in a multimodal longitudinal imaging study via a convolutional recurrent neural network.

Acute esophagitis (AE) occurs among a significant number of patients with locally advanced lung cancer treated with radiotherapy. Early prediction of AE, indicated by esophageal wall expansion, is critical, as it can facilitate the redesign of treatment plans to reduce radiation-induced esophageal toxicity in an adaptive radiotherapy (ART) workflow. We have developed a novel machine learning framework to predict the patient-specific spatial presentation of the esophagus in the weeks following treatment, using magnetic resonance imaging (MRI)/ cone-beam CT (CBCT) scans acquired earlier in the 6 week radiotherapy course. Our algorithm captures the response patterns of the esophagus to radiation on a patch level, using a convolutional neural network. A recurrence neural network then parses the evolutionary patterns of the selected features in the time series, and produces a predicted esophagus-or-not label for each individual patch over future weeks. Finally, the esophagus is reconstructed, using all the predicted labels. The algorithm is trained and validated by means of ∼ 250 000 patches taken from MRI scans acquired weekly from a variety of patients, and tested using both weekly MRI and CBCT scans under a leave-one-patient-out scheme. In addition, our approach is externally validated using a publicly available dataset (Hugo 2017). Using the first three weekly scans, the algorithm can predict the condition of the esophagus over the succeeding 3 weeks with a Dice coefficient of 0.83 ± 0.04, estimate esophagus volume highly (0.98), correlated with the actual volume, using our institutional MRI/CBCT data. When evaluated using the external weekly CBCT data, the averaged Dice coefficient is 0.89 ± 0.03. Our novel algorithm may prove useful in enabling radiation oncologists to monitor and detect AE in its early stages, and could potentially play an important role in the ART decision-making process.

Predictive dose accumulation for HN adaptive radiotherapy.

During radiation therapy (RT) of head and neck (HN) cancer, the shape and volume of the parotid glands (PG) may change significantly, resulting in clinically relevant deviations of delivered dose from the planning dose. Early and accurate longitudinal prediction of PG anatomical changes during the RT can be valuable to inform decisions on plan adaptation. We developed a deep neural network for longitudinal predictions using the displacement fields (DFs) between the planning computed tomography (pCT) and weekly cone beam computed tomography (CBCT). Sixty-three HN patients treated with volumetric modulated arc were retrospectively studied. We calculated DFs between pCT and week 1-3 CBCT by B-spline and Demon deformable image registration (DIR). The resultant DFs were subsequently used as input to our novel network to predict the week 4 to 6 DFs for generating predicted weekly PG contours and weekly dose distributions. For evaluation, we measured dice similarity (DICE), and the uncertainty of accumulated dose. Moreover, we compared the detection accuracies of candidates for adaptive radiotherapy (ART) when the trigger criteria were mean dose difference more than 10%, 7.5%, and 5%, respectively. The DICE of ipsilateral/contralateral PG at week 4 to 6 using the prediction model trained with B-spline were 0.81 [Formula: see text] 0.07/0.81 [Formula: see text] 0.04 (week 4), 0.79 [Formula: see text] 0.06/0.81 [Formula: see text] 0.05 (week 5) and 0.78 [Formula: see text] 0.06/0.82 [Formula: see text] (week 6). The DICE with the Demons model were 0.78 [Formula: see text] 0.08/0.82 [Formula: see text] 0.03 (week 4), 0.77 [Formula: see text] 0.07/0.82 [Formula: see text] 0.04 (week 5) and 0.75 [Formula: see text] 0.07/0.82 [Formula: see text] 0.02 (week 6). The dose volume histogram (DVH) analysis with the predicted accumulated dose showed the feasibility of predicting dose uncertainty due to the PG anatomical changes. The AUC of ART candidate detection with our predictive model was over 0.90. In conclusion, the proposed network was able to predict future anatomical changes and dose uncertainty of PGs with clinically acceptable accuracy, and hence can be readily integrated into the ART workflow.

External validation of radiomics-based predictive models in low-dose CT screening for early lung cancer diagnosis.

PURPOSE: Low-dose CT screening allows early lung cancer detection, but is affected by frequent false positive results, inter/intra observer variation and uncertain diagnoses of lung nodules. Radiomics-based models have recently been introduced to overcome these issues, but limitations in demonstrating their generalizability on independent datasets are slowing their introduction to clinic. The aim of this study is to evaluate two radiomics-based models to classify malignant pulmonary nodules in low-dose CT screening, and to externally validate them on an independent cohort. The effect of a radiomics features harmonization technique is also investigated to evaluate its impact on the classification of lung nodules from a multicenter data. METHODS: Pulmonary nodules from two independent cohorts were considered in this study; the first cohort (110 subjects, 113 nodules) was used to train prediction models, and the second cohort (72 nodules) to externally validate them. Literature-based radiomics features were extracted and, after feature selection, used as predictive variables in models for malignancy identification. An in-house prediction model based on artificial neural network (ANN) was implemented and evaluated, along with an alternative model from the literature, based on a support vector machine (SVM) classifier coupled with a least absolute shrinkage and selection operator (LASSO). External validation was performed on the second cohort to evaluate models' generalization ability. Additionally, the impact of the Combat harmonization method was investigated to compensate for multicenter datasets variabilities. A new training of the models based on harmonized features was performed on the first cohort, then tested separately on the harmonized and non-harmonized features of the second cohort. RESULTS: Preliminary results showed a good accuracy of the investigated models in distinguishing benign from malignant pulmonary nodules with both sets of radiomics features (i.e., non-harmonized and harmonized). The performance of the models, quantified in terms of Area Under the Curve (AUC), was > 0.89 in the training set and > 0.82 in the external validation set for all the investigated scenarios, outperforming the clinical standard (AUC of 0.76). Slightly higher performance was observed for the SVM-LASSO model than the ANN in the external dataset, although they did not result significantly different. For both harmonized and non-harmonized features, no statistical difference was found between Receiver operating characteristic (ROC) curves related to training and test set for both models. CONCLUSIONS: Although no significant improvements were observed when applying the Combat harmonization method, both in-house and literature-based models were able to classify lung nodules with good generalization to an independent dataset, thus showing their potential as tools for clinical decision-making in lung cancer screening.

Quantification of accumulated dose and associated anatomical changes of esophagus using weekly Magnetic Resonance Imaging acquired during radiotherapy of locally advanced lung cancer.

BACKGROUND AND PURPOSE: Minimizing acute esophagitis (AE) in locally advanced non-small cell lung cancer (LA-NSCLC) is critical given the proximity between the esophagus and the tumor. In this pilot study, we developed a clinical platform for quantification of accumulated doses and volumetric changes of esophagus via weekly Magnetic Resonance Imaging (MRI) for adaptive radiotherapy (RT). MATERIAL AND METHODS: Eleven patients treated via intensity-modulated RT to 60-70 Gy in 2-3 Gy-fractions with concurrent chemotherapy underwent weekly MRIs. Eight patients developed AE grade 2 (AE2), 3-6 weeks after RT started. First, weekly MRI esophagus contours were rigidly propagated to planning CT and the distances between the medial esophageal axes were calculated as positional uncertainties. Then, the weekly MRI were deformably registered to the planning CT and the total dose delivered to esophagus was accumulated. Weekly Maximum Esophagus Expansion (MEex) was calculated using the Jacobian map. Eventually, esophageal dose parameters (Mean Esophagus Dose (MED), V90% and D5cc) between the planned and accumulated dose were compared. RESULTS: Positional esophagus uncertainties were 6.8 ± 1.8 mm across patients. For the entire cohort at the end of RT: the median accumulated MED was significantly higher than the planned dose (24 Gy vs. 21 Gy p = 0.006). The median V90% and D5cc were 12.5 cm3 vs. 11.5 cm3 (p = 0.05) and 61 Gy vs. 60 Gy (p = 0.01), for accumulated and planned dose, respectively. The median MEex was 24% and was significantly associated with AE2 (p = 0.008). CONCLUSIONS: MRI is well suited for tracking esophagus volumetric changes and accumulating doses. Longitudinal esophagus expansion could reflect radiation-induced inflammation that may link to AE.

Intra- and Interobserver Variability of Cochlear Length Measurements in Clinical CT.

HYPOTHESIS: The cochlear A-value measurement exhibits significant inter- and intraobserver variability, and its accuracy is dependent on the visualization method in clinical computed tomography (CT) images of the cochlea. BACKGROUND: An accurate estimate of the cochlear duct length (CDL) can be used to determine electrode choice, and frequency map the cochlea based on the Greenwood equation. Studies have described estimating the CDL using a single A-value measurement, however the observer variability has not been assessed. METHODS: Clinical and micro-CT images of 20 cadaveric cochleae were acquired. Four specialists measured A-values on clinical CT images using both standard views and multiplanar reconstructed (MPR) views. Measurements were repeated to assess for intraobserver variability. Observer variabilities were evaluated using intra-class correlation and absolute differences. Accuracy was evaluated by comparison to the gold standard micro-CT images of the same specimens. RESULTS: Interobserver variability was good (average absolute difference: 0.77 ±â€Š0.42 mm) using standard views and fair (average absolute difference: 0.90 ±â€Š0.31 mm) using MPR views. Intraobserver variability had an average absolute difference of 0.31 ±â€Š0.09 mm for the standard views and 0.38 ±â€Š0.17 mm for the MPR views. MPR view measurements were more accurate than standard views, with average relative errors of 9.5 and 14.5%, respectively. CONCLUSION: There was significant observer variability in A-value measurements using both the standard and MPR views. Creating the MPR views increased variability between experts, however MPR views yielded more accurate results. Automated A-value measurement algorithms may help to reduce variability and increase accuracy in the future.