Synthetic CT in Carbon Ion Radiotherapy of the Abdominal Site.

The generation of synthetic CT for carbon ion radiotherapy (CIRT) applications is challenging, since high accuracy is required in treatment planning and delivery, especially in an anatomical site as complex as the abdomen. Thirty-nine abdominal MRI-CT volume pairs were collected and a three-channel cGAN (accounting for air, bones, soft tissues) was used to generate sCTs. The network was tested on five held-out MRI volumes for two scenarios: (i) a CT-based segmentation of the MRI channels, to assess the quality of sCTs and (ii) an MRI manual segmentation, to simulate an MRI-only treatment scenario. The sCTs were evaluated by means of similarity metrics (e.g., mean absolute error, MAE) and geometrical criteria (e.g., dice coefficient). Recalculated CIRT plans were evaluated through dose volume histogram, gamma analysis and range shift analysis. The CT-based test set presented optimal MAE on bones (86.03 ± 10.76 HU), soft tissues (55.39 ± 3.41 HU) and air (54.42 ± 11.48 HU). Higher values were obtained from the MRI-only test set (MAEBONE = 154.87 ± 22.90 HU). The global gamma pass rate reached 94.88 ± 4.9% with 3%/3 mm, while the range shift reached a median (IQR) of 0.98 (3.64) mm. The three-channel cGAN can generate acceptable abdominal sCTs and allow for CIRT dose recalculations comparable to the clinical plans.

Integrating Biological and Radiological Data in a Structured Repository: a Data Model Applied to the COSMOS Case Study.

Integrating the information coming from biological samples with digital data, such as medical images, has gained prominence with the advent of precision medicine. Research in this field faces an ever-increasing amount of data to manage and, as a consequence, the need to structure these data in a functional and standardized fashion to promote and facilitate cooperation among institutions. Inspired by the Minimum Information About BIobank data Sharing (MIABIS), we propose an extended data model which aims to standardize data collections where both biological and digital samples are involved. In the proposed model, strong emphasis is given to the cause-effect relationships among factors as these are frequently encountered in clinical workflows. To test the data model in a realistic context, we consider the Continuous Observation of SMOking Subjects (COSMOS) dataset as case study, consisting of 10 consecutive years of lung cancer screening and follow-up on more than 5000 subjects. The structure of the COSMOS database, implemented to facilitate the process of data retrieval, is therefore presented along with a description of data that we hope to share in a public repository for lung cancer screening research.

A segmentation tool for pulmonary nodules in lung cancer screening: Testing and clinical usage.

PURPOSE: With the future goal of defining a large dataset based on low-dose CT with labelled pulmonary lesions for lung cancer screening (LCS) research, the aim of this work is to propose and evaluate into a clinical context a tool for semi-automatic segmentation able to facilitate the process of labels collection from a LCS study (COSMOS, Continuous Observation of SMOking Subjects). METHODS: Considering a preliminary set of manual annotations, a segmentation model based on a 2D-Unet was trained from scratch. Contour quality of the final 2D-Unet was assessed on an internal test set of manual annotations and on a subset of the public available LIDC dataset used as external test set. The tool for semi-automatic segmentation was then designed integrating the tested model into a Graphical User Interface. According to the opinion of two clinical users, the percentage of lesions properly contoured through the tool was quantified (Acceptance Rate, AR). The variability between segmentations derived by the two readers was estimated as mean percentage of difference (MPD) between the two sets of volumes and comparing the likelihood of malignancy derived from Volume Doubling Time (VDT). RESULTS: Performance in test sets were found similar (DICE ~ 0.75(0.15)). Accordingly, a good mean AR (80.1%) resulted from the two readers. Variability in terms of MPD was equal to 23.6% while 2.7% was the VDTs percentage of disagreement. CONCLUSIONS: A semi-automatic segmentation tool was developed and its applicability evaluated into a clinical context demonstrating the efficacy of the tool in facilitating the collection of labelled data.

The Challenge of Choosing the Best Classification Method in Radiomic Analyses: Recommendations and Applications to Lung Cancer CT Images.

Radiomics uses high-dimensional sets of imaging features to predict biological characteristics of tumors and clinical outcomes. The choice of the algorithm used to analyze radiomic features and perform predictions has a high impact on the results, thus the identification of adequate machine learning methods for radiomic applications is crucial. In this study we aim to identify suitable approaches of analysis for radiomic-based binary predictions, according to sample size, outcome balancing and the features-outcome association strength. Simulated data were obtained reproducing the correlation structure among 168 radiomic features extracted from Computed Tomography images of 270 Non-Small-Cell Lung Cancer (NSCLC) patients and the associated to lymph node status. Performances of six classifiers combined with six feature selection (FS) methods were assessed on the simulated data using AUC (Area Under the Receiver Operating Characteristics Curves), sensitivity, and specificity. For all the FS methods and regardless of the association strength, the tree-based classifiers Random Forest and Extreme Gradient Boosting obtained good performances (AUC ≥ 0.73), showing the best trade-off between sensitivity and specificity. On small samples, performances were generally lower than in large-medium samples and with larger variations. FS methods generally did not improve performances. Thus, in radiomic studies, we suggest evaluating the choice of FS and classifiers, considering specific sample size, balancing, and association strength.

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.

A ROI-based global motion model established on 4DCT and 2D cine-MRI data for MRI-guidance in radiation therapy.

In-room magnetic resonance imaging (MRI) allows the acquisition of fast 2D cine-MRI centered in the tumor for advanced motion management in radiotherapy. To achieve 3D information during treatment, patient-specific motion models can be considered the most viable solution. However, conventional global motion models are built using a single motion surrogate, independently from the anatomical location. In this work, we present a novel motion model based on regions of interest (ROIs) established on 4D computed tomography (4DCT) and 2D cine-MRI, aiming at accurately compensating for changes during treatment. In the planning phase, a motion model is built on a 4DCT dataset, through 3D deformable image registration (DIR). ROIs are then defined and correlated with motion fields derived by 2D DIR between CT slices centered in the tumor. In the treatment phase, the model is applied to in-room cine-MRI data to compensate for organ motion in a multi-modal framework, aiming at estimating a time-resolved 3DCT. The method is validated on a digital phantom and tested on two lung patients. Analysis is performed by considering different anatomical planes (coronal, sagittal and a combination of the two) and evaluating the performance of the method on tumor and diaphragm. For the phantom study, the ROI-based model results in a uniform median error on both diaphragm and tumor below 1.5 mm. For what concerns patients, median errors on both diaphragm and tumor are around 2 mm (maximum patient resolution), confirming the capability of the method to regionally compensate for motion. A novel ROI-based motion model is proposed as an integral part of an envisioned clinical MRI-guided workflow aiming at enhanced image guidance compared to conventional strategies.