Optimisation of Positron Emission Tomography based target volume delineation in head and neck radiotherapy

Automatic segmentation of tumours using Positron Emission Tomography (PET) was recommended for radiotherapy treatment (RT) planning of head and neck (H&N) cancer patients, and investigated in the scientific literature without reaching a consensus on the optimal process. This project aimed at evaluating the performance of PETCbased automatic segmentation (PETCAS) methods and developing an optimal PETC AS process to be used at Velindre Cancer Centre (VCC). For this purpose, ten algorithms were implemented to represent the most promising PETCAS approaches from a systematic review of the literature. The algorithms’ performance was evaluated on filled phantom inserts with variable size, geometry, tumour intensity and image noise. The impact of thick insert plastic walls on both image quantification and segmentation was thoroughly assessed. The PETCAS methods were further applied to realistic H&N tumours, modelled using a printed subresolution sandwich phantom developed and calibrated in house. Results showed that different PETCAS performed best for different types of target objects. An Advanced decision TreeCbased Learning Algorithm for Automatic Segmentation (ATLAAS) was therefore developed and validated for the selection of the optimal PETCAS approach according to the target object characteristics. Finally, a protocol was designed for the use of PETCAS within RT planning at VCC. The protocol was used retrospectively on a group of 10 oropharyngeal cancer patients, and the results highlighted the additional information brought by PET beyond anatomical imaging. In a prospective study on 10 additional patients, PETCAS replaced manual PET/CT delineation, and accounted for up to 33% of the modifications of manually drawn CT/MRI contours to derive the final planning contour. This study demonstrated the usefulness and reliability of the PETCAS method in RT planning, and led to modifying the clinical workflow for H&N patients at VCC. This work has the potential to be extended to other tumour sites and institutions

ATLAAS: an automatic decision tree-based learning algorithm for advanced image segmentation in positron emission tomography

Accurate and reliable tumour delineation on positron emission tomography (PET) is crucial for radiotherapy treatment planning. PET automatic segmentation (PET-AS) eliminates intra- and interobserver variability, but there is currently no consensus on the optimal method to use, as different algorithms appear to perform better for different types of tumours. This work aimed to develop a predictive segmentation model, trained to automatically select and apply the best PET-AS method, according to the tumour characteristics. ATLAAS, the automatic decision tree-based learning algorithm for advanced segmentation is based on supervised machine learning using decision trees. The model includes nine PET-AS methods and was trained on a 100 PET scans with known true contour. A decision tree was built for each PET-AS algorithm to predict its accuracy, quantified using the Dice similarity coefficient (DSC), according to the tumour volume, tumour peak to background SUV ratio and a regional texture metric. The performance of ATLAAS was evaluated for 85 PET scans obtained from fillable and printed subresolution sandwich phantoms. ATLAAS showed excellent accuracy across a wide range of phantom data and predicted the best or near-best segmentation algorithm in 93% of cases. ATLAAS outperformed all single PET-AS methods on fillable phantom data with a DSC of 0.881, while the DSC for H&N phantom data was 0.819. DSCs higher than 0.650 were achieved in all cases. ATLAAS is an advanced automatic image segmentation algorithm based on decision tree predictive modelling, which can be trained on images with known true contour, to predict the best PET-AS method when the true contour is unknown. ATLAAS provides robust and accurate image segmentation with potential applications to radiation oncology

A novel phantom technique for evaluating the performance of PET auto-segmentation methods in delineating heterogeneous and irregular lesions

Background Positron Emission Tomography (PET)-based automatic segmentation (PET-AS) methods can improve tumour delineation for radiotherapy treatment planning, particularly for Head and Neck (H&N) cancer. Thorough validation of PET-AS on relevant data is currently needed. Printed subresolution sandwich (SS) phantoms allow modelling heterogeneous and irregular tracer uptake, while providing reference uptake data. This work aimed to demonstrate the usefulness of the printed SS phantom technique in recreating complex realistic H&N radiotracer uptake for evaluating several PET-AS methods. Methods Ten SS phantoms were built from printouts representing 2mm-spaced slices of modelled H&N uptake, printed using black ink mixed with 18F-fluorodeoxyglucose, and stacked between 2mm thick plastic sheets. Spherical lesions were modelled for two contrasted uptake levels, and irregular and spheroidal tumours were modelled for homogeneous, and heterogeneous uptake including necrotic patterns. The PET scans acquired were segmented with ten custom PET-AS methods: adaptive iterative thresholding (AT), region growing, clustering applied to 2 to 8 clusters, and watershed transform-based segmentation. The difference between the resulting contours and the ground truth from the image template was evaluated using the Dice Similarity Coefficient (DSC), Sensitivity and Positive Predictive value. Results Realistic H&N images were obtained within 90 min of preparation. The sensitivity of binary PET-AS and clustering using small numbers of clusters dropped for highly heterogeneous spheres. The accuracy of PET-AS methods dropped between 4% and 68% for irregular lesions compared to spheres of the same volume. For each geometry and uptake modelled with the SS phantoms, we report the number of clusters resulting in optimal segmentation. Radioisotope distributions representing necrotic uptakes proved most challenging for most methods. Two PET-AS methods did not include the necrotic region in the segmented volume. Conclusions Printed SS phantoms allowed identifying advantages and drawbacks of the different methods, determining the most robust PET-AS for the segmentation of heterogeneities and complex geometries, and quantifying differences across methods in the delineation of necrotic lesions. The printed SS phantom technique provides key advantages in the development and evaluation of PET segmentation methods and has a future in the field of radioisotope imaging

Development and validation of a prognostic model incorporating texture analysis derived from standardised segmentation of PET in patients with oesophageal cancer

Objectives This retrospective cohort study developed a prognostic model incorporating PET texture analysis in patients with oesophageal cancer (OC). Internal validation of the model was performed. Methods Consecutive OC patients (n = 403) were chronologically separated into development (n = 302, September 2010-September 2014, median age = 67.0, males = 227, adenocarcinomas = 237) and validation cohorts (n = 101, September 2014-July 2015, median age = 69.0, males = 78, adenocarcinomas = 79). Texture metrics were obtained using a machine-learning algorithm for automatic PET segmentation. A Cox regression model including age, radiological stage, treatment and 16 texture metrics was developed. Patients were stratified into quartiles according to a prognostic score derived from the model. A p-value < 0.05 was considered statistically significant. Primary outcome was overall survival (OS). Results Six variables were significantly and independently associated with OS: age [HR =1.02 (95% CI 1.01-1.04), p < 0.001], radiological stage [1.49 (1.20-1.84), p < 0.001], treatment [0.34 (0.24–0.47), p < 0.001], log(TLG) [5.74 (1.44–22.83), p = 0.013], log(Histogram Energy) [0.27 (0.10–0.74), p = 0.011] and Histogram Kurtosis [1.22 (1.04–1.44), p = 0.017]. The prognostic score demonstrated significant differences in OS between quartiles in both the development (X2 143.14, df 3, p < 0.001) and validation cohorts (X2 20.621, df 3, p < 0.001). Conclusions This prognostic model can risk stratify patients and demonstrates the additional benefit of PET texture analysis in OC staging

Toward a standard for the evaluation of PET-Auto-Segmentation methods following the recommendations of AAPM task group No. 211: Requirements and implementation

Purpose: The aim of this paper is to define the requirements and describe the design and implementation of a standard benchmark tool for evaluation and validation of PET-auto-segmentation (PET-AS) algorithms. This work follows the recommendations of Task Group 211 (TG211) appointed by the American Association of Physicists in Medicine (AAPM).Methods: The recommendations published in the AAPM TG211 report were used to derive a set of required features and to guide the design and structure of a benchmarking software tool. These items included the selection of appropriate representative data and reference contours obtained from established approaches and the description of available metrics. The benchmark was designed in a way that it could be extendable by inclusion of bespoke segmentation methods, while maintaining its main purpose of being a standard testing platform for newly developed PET-AS methods. An example of implementation of the proposed framework, named PETASset, was built. In this work, a selection of PET-AS methods representing common approaches to PET image segmentation was evaluated within PETASset for the purpose of testing and demonstrating the capabilities of the software as a benchmark platform.Results: A selection of clinical, physical, and simulated phantom data, including "best estimates" reference contours from macroscopic specimens, simulation template, and CT scans was built into the PETASset application database. Specific metrics such as Dice Similarity Coefficient (DSC), Positive Predictive Value (PPV), and Sensitivity (S), were included to allow the user to compare the results of any given PET-AS algorithm to the reference contours. In addition, a tool to generate structured reports on the evaluation of the performance of PET-AS algorithms against the reference contours was built. The variation of the metric agreement values with the reference contours across the PET-AS methods evaluated for demonstration were between 0.51 and 0.83, 0.44 and 0.86, and 0.61 and 1.00 for DSC, PPV, and the S metric, respectively. Examples of agreement limits were provided to show how the software could be used to evaluate a new algorithm against the existing state-of-the art.Conclusions: PETASset provides a platform that allows standardizing the evaluation and comparison of different PET-AS methods on a wide range of PET datasets. The developed platform will be available to users willing to evaluate their PET-AS methods and contribute with more evaluation datasets. </p