Thyroidiomics: An Automated Pipeline for Segmentation and Classification of Thyroid Pathologies from Scintigraphy Images

The objective of this study was to develop an automated pipeline that enhances thyroid disease classification using thyroid scintigraphy images, aiming to decrease assessment time and increase diagnostic accuracy. Anterior thyroid scintigraphy images from 2,643 patients were collected and categorized into diffuse goiter (DG), multinodal goiter (MNG), and thyroiditis (TH) based on clinical reports, and then segmented by an expert. A ResUNet model was trained to perform auto-segmentation. Radiomic features were extracted from both physician (scenario 1) and ResUNet segmentations (scenario 2), followed by omitting highly correlated features using Spearman's correlation, and feature selection using Recursive Feature Elimination (RFE) with XGBoost as the core. All models were trained under leave-one-center-out cross-validation (LOCOCV) scheme, where nine instances of algorithms were iteratively trained and validated on data from eight centers and tested on the ninth for both scenarios separately. Segmentation performance was assessed using the Dice similarity coefficient (DSC), while classification performance was assessed using metrics, such as precision, recall, F1-score, accuracy, area under the Receiver Operating Characteristic (ROC AUC), and area under the precision-recall curve (PRC AUC). ResUNet achieved DSC values of 0.84$\pm$0.03, 0.71$\pm$0.06, and 0.86$\pm$0.02 for MNG, TH, and DG, respectively. Classification in scenario 1 achieved an accuracy of 0.76$\pm$0.04 and a ROC AUC of 0.92$\pm$0.02 while in scenario 2, classification yielded an accuracy of 0.74$\pm$0.05 and a ROC AUC of 0.90$\pm$0.02. The automated pipeline demonstrated comparable performance to physician segmentations on several classification metrics across different classes, effectively reducing assessment time while maintaining high diagnostic accuracy. Code available at: https://github.com/ahxmeds/thyroidiomics.git.

A cascaded deep network for automated tumor detection and segmentation in clinical PET imaging of diffuse large B-cell lymphoma

Accurate detection and segmentation of diffuse large B-cell lymphoma (DLBCL) from PET images has important implications for estimation of total metabolic tumor volume, radiomics analysis, surgical intervention and radiotherapy. Manual segmentation of tumors in whole-body PET images is time-consuming, labor-intensive and operator-dependent. In this work, we develop and validate a fast and efficient three-step cascaded deep learning model for automated detection and segmentation of DLBCL tumors from PET images. As compared to a single end-to-end network for segmentation of tumors in whole-body PET images, our three-step model is more effective (improves 3D Dice score from 58.9% to 78.1%) since each of its specialized modules, namely the slice classifier, the tumor detector and the tumor segmentor, can be trained independently to a high degree of skill to carry out a specific task, rather than a single network with suboptimal performance on overall segmentation.

Observer study-based evaluation of TGAN architecture used to generate oncological PET images

The application of computer-vision algorithms in medical imaging has increased rapidly in recent years. However, algorithm training is challenging due to limited sample sizes, lack of labeled samples, as well as privacy concerns regarding data sharing. To address these issues, we previously developed (Bergen et al. 2022) a synthetic PET dataset for Head and Neck (H and N) cancer using the temporal generative adversarial network (TGAN) architecture and evaluated its performance segmenting lesions and identifying radiomics features in synthesized images. In this work, a two-alternative forced-choice (2AFC) observer study was performed to quantitatively evaluate the ability of human observers to distinguish between real and synthesized oncological PET images. In the study eight trained readers, including two board-certified nuclear medicine physicians, read 170 real/synthetic image pairs presented as 2D-transaxial using a dedicated web app. For each image pair, the observer was asked to identify the real image and input their confidence level with a 5-point Likert scale. P-values were computed using the binomial test and Wilcoxon signed-rank test. A heat map was used to compare the response accuracy distribution for the signed-rank test. Response accuracy for all observers ranged from 36.2% [27.9-44.4] to 63.1% [54.8-71.3]. Six out of eight observers did not identify the real image with statistical significance, indicating that the synthetic dataset was reasonably representative of oncological PET images. Overall, this study adds validity to the realism of our simulated H&N cancer dataset, which may be implemented in the future to train AI algorithms while favoring patient confidentiality and privacy protection.

Comprehensive Evaluation and Insights into the Use of Deep Neural Networks to Detect and Quantify Lymphoma Lesions in PET/CT Images

This study performs comprehensive evaluation of four neural network architectures (UNet, SegResNet, DynUNet, and SwinUNETR) for lymphoma lesion segmentation from PET/CT images. These networks were trained, validated, and tested on a diverse, multi-institutional dataset of 611 cases. Internal testing (88 cases; total metabolic tumor volume (TMTV) range [0.52, 2300] ml) showed SegResNet as the top performer with a median Dice similarity coefficient (DSC) of 0.76 and median false positive volume (FPV) of 4.55 ml; all networks had a median false negative volume (FNV) of 0 ml. On the unseen external test set (145 cases with TMTV range: [0.10, 2480] ml), SegResNet achieved the best median DSC of 0.68 and FPV of 21.46 ml, while UNet had the best FNV of 0.41 ml. We assessed reproducibility of six lesion measures, calculated their prediction errors, and examined DSC performance in relation to these lesion measures, offering insights into segmentation accuracy and clinical relevance. Additionally, we introduced three lesion detection criteria, addressing the clinical need for identifying lesions, counting them, and segmenting based on metabolic characteristics. We also performed expert intra-observer variability analysis revealing the challenges in segmenting ``easy'' vs. ``hard'' cases, to assist in the development of more resilient segmentation algorithms. Finally, we performed inter-observer agreement assessment underscoring the importance of a standardized ground truth segmentation protocol involving multiple expert annotators. Code is available at: https://github.com/microsoft/lymphoma-segmentation-dnn

Semi-supervised learning towards automated segmentation of PET images with limited annotations: Application to lymphoma patients

The time-consuming task of manual segmentation challenges routine systematic quantification of disease burden. Convolutional neural networks (CNNs) hold significant promise to reliably identify locations and boundaries of tumors from PET scans. We aimed to leverage the need for annotated data via semi-supervised approaches, with application to PET images of diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL). We analyzed 18F-FDG PET images of 292 patients with PMBCL (n=104) and DLBCL (n=188) (n=232 for training and validation, and n=60 for external testing). We employed FCM and MS losses for training a 3D U-Net with different levels of supervision: i) fully supervised methods with labeled FCM (LFCM) as well as Unified focal and Dice loss functions, ii) unsupervised methods with Robust FCM (RFCM) and Mumford-Shah (MS) loss functions, and iii) Semi-supervised methods based on FCM (RFCM+LFCM), as well as MS loss in combination with supervised Dice loss (MS+Dice). Unified loss function yielded higher Dice score (mean +/- standard deviation (SD)) (0.73 +/- 0.03; 95% CI, 0.67-0.8) compared to Dice loss (p-value<0.01). Semi-supervised (RFCM+alpha*LFCM) with alpha=0.3 showed the best performance, with a Dice score of 0.69 +/- 0.03 (95% CI, 0.45-0.77) outperforming (MS+alpha*Dice) for any supervision level (any alpha) (p<0.01). The best performer among (MS+alpha*Dice) semi-supervised approaches with alpha=0.2 showed a Dice score of 0.60 +/- 0.08 (95% CI, 0.44-0.76) compared to another supervision level in this semi-supervised approach (p<0.01). Semi-supervised learning via FCM loss (RFCM+alpha*LFCM) showed improved performance compared to supervised approaches. Considering the time-consuming nature of expert manual delineations and intra-observer variabilities, semi-supervised approaches have significant potential for automated segmentation workflows.

Biomedical image analysis competitions: The state of current participation practice

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Assessing Privacy Leakage in Synthetic 3-D PET Imaging using Transversal GAN

Training computer-vision related algorithms on medical images for disease diagnosis or image segmentation is difficult in large part due to privacy concerns. For this reason, generative image models are highly sought after to facilitate data sharing. However, 3-D generative models are understudied, and investigation of their privacy leakage is needed. We introduce our 3-D generative model, Transversal GAN (TrGAN), using head & neck PET images which are conditioned on tumour masks as a case study. We define quantitative measures of image fidelity, utility and privacy for our model. These metrics are evaluated in the course of training to identify ideal fidelity, utility and privacy trade-offs and establish the relationships between these parameters. We show that the discriminator of the TrGAN is vulnerable to attack, and that an attacker can identify which samples were used in training with almost perfect accuracy (AUC = 0.99). We also show that an attacker with access to only the generator cannot reliably classify whether a sample had been used for training (AUC = 0.51). This suggests that TrGAN generators, but not discriminators, may be used for sharing synthetic 3-D PET data with minimal privacy risk while maintaining good utility and fidelity.

Tensor Radiomics: Paradigm for Systematic Incorporation of Multi-Flavoured Radiomics Features

Radiomics features extract quantitative information from medical images, towards the derivation of biomarkers for clinical tasks, such as diagnosis, prognosis, or treatment response assessment. Different image discretization parameters (e.g. bin number or size), convolutional filters, segmentation perturbation, or multi-modality fusion levels can be used to generate radiomics features and ultimately signatures. Commonly, only one set of parameters is used; resulting in only one value or flavour for a given RF. We propose tensor radiomics (TR) where tensors of features calculated with multiple combinations of parameters (i.e. flavours) are utilized to optimize the construction of radiomics signatures. We present examples of TR as applied to PET/CT, MRI, and CT imaging invoking machine learning or deep learning solutions, and reproducibility analyses: (1) TR via varying bin sizes on CT images of lung cancer and PET-CT images of head & neck cancer (HNC) for overall survival prediction. A hybrid deep neural network, referred to as TR-Net, along with two ML-based flavour fusion methods showed improved accuracy compared to regular rediomics features. (2) TR built from different segmentation perturbations and different bin sizes for classification of late-stage lung cancer response to first-line immunotherapy using CT images. TR improved predicted patient responses. (3) TR via multi-flavour generated radiomics features in MR imaging showed improved reproducibility when compared to many single-flavour features. (4) TR via multiple PET/CT fusions in HNC. Flavours were built from different fusions using methods, such as Laplacian pyramids and wavelet transforms. TR improved overall survival prediction. Our results suggest that the proposed TR paradigm has the potential to improve performance capabilities in different medical imaging tasks.

Segmentation and Risk Score Prediction of Head and Neck Cancers in PET/CT Volumes with 3D U-Net and Cox Proportional Hazard Neural Networks

We utilized a 3D nnU-Net model with residual layers supplemented by squeeze and excitation (SE) normalization for tumor segmentation from PET/CT images provided by the Head and Neck Tumor segmentation chal-lenge (HECKTOR). Our proposed loss function incorporates the Unified Fo-cal and Mumford-Shah losses to take the advantage of distribution, region, and boundary-based loss functions. The results of leave-one-out-center-cross-validation performed on different centers showed a segmentation performance of 0.82 average Dice score (DSC) and 3.16 median Hausdorff Distance (HD), and our results on the test set achieved 0.77 DSC and 3.01 HD. Following lesion segmentation, we proposed training a case-control proportional hazard Cox model with an MLP neural net backbone to predict the hazard risk score for each discrete lesion. This hazard risk prediction model (CoxCC) was to be trained on a number of PET/CT radiomic features extracted from the segmented lesions, patient and lesion demographics, and encoder features provided from the penultimate layer of a multi-input 2D PET/CT convolutional neural network tasked with predicting time-to-event for each lesion. A 10-fold cross-validated CoxCC model resulted in a c-index validation score of 0.89, and a c-index score of 0.61 on the HECKTOR challenge test dataset.

3-D PET Image Generation with tumour masks using TGAN

Training computer-vision related algorithms on medical images for disease diagnosis or image segmentation is difficult due to the lack of training data, labeled samples, and privacy concerns. For this reason, a robust generative method to create synthetic data is highly sought after. However, most three-dimensional image generators require additional image input or are extremely memory intensive. To address these issues we propose adapting video generation techniques for 3-D image generation. Using the temporal GAN (TGAN) architecture, we show we are able to generate realistic head and neck PET images. We also show that by conditioning the generator on tumour masks, we are able to control the geometry and location of the tumour in the generated images. To test the utility of the synthetic images, we train a segmentation model using the synthetic images. Synthetic images conditioned on real tumour masks are automatically segmented, and the corresponding real images are also segmented. We evaluate the segmentations using the Dice score and find the segmentation algorithm performs similarly on both datasets (0.65 synthetic data, 0.70 real data). Various radionomic features are then calculated over the segmented tumour volumes for each data set. A comparison of the real and synthetic feature distributions show that seven of eight feature distributions had statistically insignificant differences (p>0.05). Correlation coefficients were also calculated between all radionomic features and it is shown that all of the strong statistical correlations in the real data set are preserved in the synthetic data set.