Beyond Conventional Parametric Modeling: Data-Driven Framework for Estimation and Prediction of Time Activity Curves in Dynamic PET Imaging

Dynamic Positron Emission Tomography (dPET) imaging and Time-Activity Curve (TAC) analyses are essential for understanding and quantifying the biodistribution of radiopharmaceuticals over time and space. Traditional compartmental modeling, while foundational, commonly struggles to fully capture the complexities of biological systems, including non-linear dynamics and variability. This study introduces an innovative data-driven neural network-based framework, inspired by Reaction Diffusion systems, designed to address these limitations. Our approach, which adaptively fits TACs from dPET, enables the direct calibration of diffusion coefficients and reaction terms from observed data, offering significant improvements in predictive accuracy and robustness over traditional methods, especially in complex biological scenarios. By more accurately modeling the spatio-temporal dynamics of radiopharmaceuticals, our method advances modeling of pharmacokinetic and pharmacodynamic processes, enabling new possibilities in quantitative nuclear medicine.

Segmentation-Free Outcome Prediction in Head and Neck Cancer: Deep Learning-based Feature Extraction from Multi-Angle Maximum Intensity Projections (MA-MIPs) of PET Images

We introduce an innovative, simple, effective segmentation-free approach for outcome prediction in head \& neck cancer (HNC) patients. By harnessing deep learning-based feature extraction techniques and multi-angle maximum intensity projections (MA-MIPs) applied to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) volumes, our proposed method eliminates the need for manual segmentations of regions-of-interest (ROIs) such as primary tumors and involved lymph nodes. Instead, a state-of-the-art object detection model is trained to perform automatic cropping of the head and neck region on the PET volumes. A pre-trained deep convolutional neural network backbone is then utilized to extract deep features from MA-MIPs obtained from 72 multi-angel axial rotations of the cropped PET volumes. These deep features extracted from multiple projection views of the PET volumes are then aggregated and fused, and employed to perform recurrence-free survival analysis on a cohort of 489 HNC patients. The proposed approach outperforms the best performing method on the target dataset for the task of recurrence-free survival analysis. By circumventing the manual delineation of the malignancies on the FDG PET-CT images, our approach eliminates the dependency on subjective interpretations and highly enhances the reproducibility of the proposed survival analysis method.

IgCONDA-PET: Implicitly-Guided Counterfactual Diffusion for Detecting Anomalies in PET Images

Minimizing the need for pixel-level annotated data for training PET anomaly segmentation networks is crucial, particularly due to time and cost constraints related to expert annotations. Current un-/weakly-supervised anomaly detection methods rely on autoencoder or generative adversarial networks trained only on healthy data, although these are more challenging to train. In this work, we present a weakly supervised and Implicitly guided COuNterfactual diffusion model for Detecting Anomalies in PET images, branded as IgCONDA-PET. The training is conditioned on image class labels (healthy vs. unhealthy) along with implicit guidance to generate counterfactuals for an unhealthy image with anomalies. The counterfactual generation process synthesizes the healthy counterpart for a given unhealthy image, and the difference between the two facilitates the identification of anomaly locations. The code is available at: https://github.com/igcondapet/IgCONDA-PET.git

MEDDAP: Medical Dataset Enhancement via Diversified Augmentation Pipeline

The effectiveness of Deep Neural Networks (DNNs) heavily relies on the abundance and accuracy of available training data. However, collecting and annotating data on a large scale is often both costly and time-intensive, particularly in medical cases where practitioners are already occupied with their duties. Moreover, ensuring that the model remains robust across various scenarios of image capture is crucial in medical domains, especially when dealing with ultrasound images that vary based on the settings of different devices and the manual operation of the transducer. To address this challenge, we introduce a novel pipeline called MEDDAP, which leverages Stable Diffusion (SD) models to augment existing small datasets by automatically generating new informative labeled samples. Pretrained checkpoints for SD are typically based on natural images, and training them for medical images requires significant GPU resources due to their heavy parameters. To overcome this challenge, we introduce USLoRA (Ultrasound Low-Rank Adaptation), a novel fine-tuning method tailored specifically for ultrasound applications. USLoRA allows for selective fine-tuning of weights within SD, requiring fewer than 0.1\% of parameters compared to fully fine-tuning only the UNet portion of SD. To enhance dataset diversity, we incorporate different adjectives into the generation process prompts, thereby desensitizing the classifiers to intensity changes across different images. This approach is inspired by clinicians' decision-making processes regarding breast tumors, where tumor shape often plays a more crucial role than intensity. In conclusion, our pipeline not only outperforms classifiers trained on the original dataset but also demonstrates superior performance when encountering unseen datasets. The source code is available at https://github.com/yasamin-med/MEDDAP.

A slice classification neural network for automated classification of axial PET/CT slices from a multi-centric lymphoma dataset

Automated slice classification is clinically relevant since it can be incorporated into medical image segmentation workflows as a preprocessing step that would flag slices with a higher probability of containing tumors, thereby directing physicians attention to the important slices. In this work, we train a ResNet-18 network to classify axial slices of lymphoma PET/CT images (collected from two institutions) depending on whether the slice intercepted a tumor (positive slice) in the 3D image or if the slice did not (negative slice). Various instances of the network were trained on 2D axial datasets created in different ways: (i) slice-level split and (ii) patient-level split; inputs of different types were used: (i) only PET slices and (ii) concatenated PET and CT slices; and different training strategies were employed: (i) center-aware (CAW) and (ii) center-agnostic (CAG). Model performances were compared using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC), and various binary classification metrics. We observe and describe a performance overestimation in the case of slice-level split as compared to the patient-level split training. The model trained using patient-level split data with the network input containing only PET slices in the CAG training regime was the best performing/generalizing model on a majority of metrics. Our models were additionally more closely compared using the sensitivity metric on the positive slices from their respective test sets.

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

Generalized Dice Focal Loss trained 3D Residual UNet for Automated Lesion Segmentation in Whole-Body FDG PET/CT Images

Automated segmentation of cancerous lesions in PET/CT images is a vital initial task for quantitative analysis. However, it is often challenging to train deep learning-based segmentation methods to high degree of accuracy due to the diversity of lesions in terms of their shapes, sizes, and radiotracer uptake levels. These lesions can be found in various parts of the body, often close to healthy organs that also show significant uptake. Consequently, developing a comprehensive PET/CT lesion segmentation model is a demanding endeavor for routine quantitative image analysis. In this work, we train a 3D Residual UNet using Generalized Dice Focal Loss function on the AutoPET challenge 2023 training dataset. We develop our models in a 5-fold cross-validation setting and ensemble the five models via average and weighted-average ensembling. On the preliminary test phase, the average ensemble achieved a Dice similarity coefficient (DSC), false-positive volume (FPV) and false negative volume (FNV) of 0.5417, 0.8261 ml, and 0.2538 ml, respectively, while the weighted-average ensemble achieved 0.5417, 0.8186 ml, and 0.2538 ml, respectively. Our algorithm can be accessed via this link: https://github.com/ahxmeds/autosegnet.

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.