In the last decade, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment and improved prognosis. However, severe checkpoint inhibitor-induced liver injury (CHILI), which can lead to treatment discontinuation or death, occurs in up to 18% of the patients. The aim of this study is to evaluate the value of PET/CT radiomics analysis for the detection of CHILI. Patients with CHILI grade 2 or higher who underwent liver function tests and liver biopsy were retrospectively included. Minors, patients with cognitive impairments, and patients with viral infections were excluded from the study. The patients' liver and spleen were contoured on the anonymized PET/CT imaging data, followed by radiomics feature extraction. Principal component analysis (PCA) and Bonferroni corrections were used for statistical analysis and exploration of radiomics features related to CHILI. Sixteen patients were included and 110 radiomics features were extracted from PET images. Liver PCA-5 showed significance as well as one associated feature but did not remain significant after Bonferroni correction. Spleen PCA-5 differed significantly between CHILI and non-CHILI patients even after Bonferroni correction, possibly linked to the higher metabolic function of the spleen in autoimmune diseases due to the recruitment of immune cells. This pilot study identified statistically significant differences in PET-derived radiomics features of the spleen and observable changes in the liver on PET/CT scans before and after the onset of CHILI. Identifying these features could aid in diagnosing or predicting CHILI, potentially enabling personalized treatment. Larger multicenter prospective studies are needed to confirm these findings and develop automated detection methods.

Positron emission tomography-computed tomography (PET-CT) is recommended for response evaluation in aggressive large B-cell lymphoma (LBCL) but cannot detect minimal residual disease (MRD). Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for real-time disease monitoring. This study evaluated longitudinal ctDNA monitoring as an MRD marker in LBCL. In this prospective, single-center study, 14 newly diagnosed LBCL patients receiving first-line immunochemotherapy underwent frequent longitudinal blood sampling. A 53-gene targeted sequencing panel quantified ctDNA and evaluated its kinetics, correlating it with clinical parameters and PET-CT, including total metabolic tumor volume (TMTV) calculated using AI-based analysis via RECOMIA. Baseline ctDNA was detected in 11 out of 14 patients (79%), with a median variant allele frequency of 6.88% (interquartile range: 1.19-10.20%). ctDNA levels correlated significantly with TMTV (ρ = 0.91, p < 0.0001) and lactate dehydrogenase. Circulating tumor DNA kinetics, including after one treatment cycle, mirrored PET-CT metabolic changes and identified relapsing or refractory cases. This study demonstrates ctDNA-based MRD monitoring in LBCL using a fixed targeted assay with an analytical sensitivity of at least 10-3. The kinetics of ctDNA reflects the clinical course and PET-CT findings, underscoring its complementary potential to PET-CT.

This study proposes a deep learning-based framework for automated segmentation of brain regions and classification of amyloid positivity using positron emission tomography (PET) images alone, without the need for structural MRI or CT. A 3D U-Net architecture with four layers of depth was trained and validated on a dataset of 200 F18-florbetapir amyloid-PET scans, with an 130/20/50 train/validation/test split. Segmentation performance was evaluated using Dice similarity coefficients across 30 brain regions, with scores ranging from 0.45 to 0.88, demonstrating high anatomical accuracy, particularly in subcortical structures. Quantitative fidelity of PET uptake within clinically relevant regions. Precuneus, prefrontal cortex, gyrus rectus, and lateral temporal cortex was assessed using normalized root mean square error, achieving values as low as 0.0011. Furthermore, the model achieved a classification accuracy of 0.98 for amyloid positivity based on regional uptake quantification, with an area under the ROC curve (AUC) of 0.99. These results highlight the model's potential for integration into PET only diagnostic pipelines, particularly in settings where structural imaging is not available. This approach reduces dependence on coregistration and manual delineation, enabling scalable, reliable, and reproducible analysis in clinical and research applications. Future work will focus on clinical validation and extension to diverse PET tracers including C11 PiB and other F18 labeled compounds.

Unsupervised anomaly detection (UAD) plays a crucial role in neuroimaging for identifying deviations from healthy subject data and thus facilitating the diagnosis of neurological disorders. In this work, we focus on Bayesian flow networks (BFNs), a novel class of generative models, which have not yet been applied to medical imaging or anomaly detection. BFNs combine the strength of diffusion frameworks and Bayesian inference. We introduce AnoBFN, an extension of BFNs for UAD, designed to: i) perform conditional image generation under high levels of spatially correlated noise, and ii) preserve subject specificity by incorporating a recursive feedback from the input image throughout the generative process. We evaluate AnoBFN on the challenging task of Alzheimer's disease-related anomaly detection in FDG PET images. Our approach outperforms other state-of-the-art methods based on VAEs (beta-VAE), GANs (f-AnoGAN), and diffusion models (AnoDDPM), demonstrating its effectiveness at detecting anomalies while reducing false positive rates.

Though ultra-low dose (ULD) imaging offers notable benefits, its widespread clinical adoption faces challenges. Long-axial field-of-view (LAFOV) PET/CT systems are expensive and scarce, while artificial intelligence (AI) shows great potential but remains largely limited to specific systems and is not yet widely used in clinical practice. However, integrating AI techniques and technological advancements into ULD imaging is helping bridge the gap between standard axial field-of-view (SAFOV) and LAFOV PET/CT systems. This paper offers an initial evaluation of ULD capabilities using one of the latest SAFOV PET/CT device. A patient injected with 16.4 MBq ¹⁸F-FDG underwent a local protocol consisting of a dynamic acquisition (first 30 min) of the abdominal section and a static whole body 74 min post-injection on a GE Omni PET/CT. From the acquired images we computed the dosimetry and compared clinical output from kidney function and brain uptake to kidney model and normal databases, respectively. The effective PET dose for this patient was 0.27 ± 0.01 mSv and the absorbed doses were 0.56 mGy, 0.89 mGy and 0.20 mGy, respectively to the brain, heart, and kidneys. The recorded kidney concentration closely followed the kidney model, matching the increase and decrease in activity concentration over time. Normal values for the z-score were observed for the brain uptake, indicating typical brain function and activity patterns consistent with healthy individuals. The signal to noise ration obtained in this study (13.1) was comparable to the LAFOV reported values. This study shows promising capabilities of ultra-low-dose imaging in SAFOV PET devices, previously deemed unattainable with SAFOV PET imaging.

Diffusion models have shown great promise in medical image denoising and reconstruction, but their application to Positron Emission Tomography (PET) imaging remains limited by tracer-specific contrast variability and high computational demands. In this work, we proposed an anatomical prior-guided PET image reconstruction method based on diffusion models, inspired by the deep diffusion image prior (DDIP) framework. The proposed method alternated between diffusion sampling and model fine-tuning guided by the PET sinogram, enabling the reconstruction of high-quality images from various PET tracers using a score function pretrained on a dataset of another tracer. To improve computational efficiency, the half-quadratic splitting (HQS) algorithm was adopted to decouple network optimization from iterative PET reconstruction. The proposed method was evaluated using one simulation and two clinical datasets. For the simulation study, a model pretrained on [$^{18}$F]FDG data was tested on amyloid-negative PET data to assess out-of-distribution (OOD) performance. For the clinical-data validation, ten low-dose [$^{18}$F]FDG datasets and one [$^{18}$F]Florbetapir dataset were tested on a model pretrained on data from another tracer. Experiment results show that the proposed PET reconstruction method can generalize robustly across tracer distributions and scanner types, providing an efficient and versatile reconstruction framework for low-dose PET imaging.

The integration of artificial intelligence (AI) into [¹⁸F]FDG PET/CT imaging continues to expand, offering new opportunities for more precise, consistent, and personalized oncologic evaluations. Building on the foundation established in Part I, this second part explores AI-driven innovations across a broader range of malignancies, including hematological, genitourinary, melanoma, and central nervous system tumors as well applications of AI in pediatric oncology. Radiomics and machine learning algorithms are being explored for their ability to enhance diagnostic accuracy, reduce interobserver variability, and inform complex clinical decision-making, such as identifying patients with refractory lymphoma, assessing pseudoprogression in melanoma, or predicting brain metastases in extracranial malignancies. Additionally, AI-assisted lesion segmentation, quantitative feature extraction, and heterogeneity analysis are contributing to improved prediction of treatment response and long-term survival outcomes. Despite encouraging results, variability in imaging protocols, segmentation methods, and validation strategies across studies continues to challenge reproducibility and remains a barrier to clinical translation. This review evaluates recent advancements of AI, its current clinical applications, and emphasizes the need for robust standardization and prospective validation to ensure the reproducibility and generalizability of AI tools in PET imaging and clinical practice.

Glioma, the most common primary intracranial tumor, poses significant challenges to precision diagnosis and treatment due to its heterogeneity and invasiveness. With the introduction of the 2021 WHO classification standard based on molecular biomarkers, the role of imaging in non-invasive subtyping and therapeutic monitoring of gliomas has become increasingly crucial. While conventional MRI shows limitations in assessing metabolic status and differentiating tumor recurrence, positron emission tomography (PET) combined with radiomics and artificial intelligence technologies offers a novel paradigm for precise diagnosis and treatment monitoring through quantitative extraction of multimodal imaging features (e.g., intensity, texture, dynamic parameters). This review systematically summarizes the technical workflow of PET radiomics (including tracer selection, image segmentation, feature extraction, and model construction) and its applications in predicting molecular subtypes (such as IDH mutation and MGMT methylation), distinguishing recurrence from treatment-related changes, and prognostic stratification. Studies demonstrate that amino acid tracers (e.g., ¹⁸F-FET, ¹¹C-MET) combined with multimodal radiomics models significantly outperform traditional parametric analysis in diagnostic efficacy. Nevertheless, current research still faces challenges including data heterogeneity, insufficient model interpretability, and lack of clinical validation. Future advancements require multicenter standardized protocols, open-source algorithm frameworks, and multi-omics integration to facilitate the transformative clinical translation of PET radiomics from research to practice.

Organ segmentation using ¹⁸F-FDG PET images alone has not been extensively explored. Segmentation based methods based on deep learning (DL) have traditionally relied on CT or MRI images, which are vulnerable to alignment issues and artifacts. This study aimed to develop a DL approach for segmenting the entire liver based solely on ¹⁸F-FDG PET images. We analyzed data from 120 patients who were assessed using ¹⁸F-FDG PET. A three-dimensional (3D) U-Net model from nnUNet and preprocessed PET images served as DL and input images, respectively, for the model. The model was trained with 5-fold cross-validation on data from 100 patients, and segmentation accuracy was evaluated on an independent test set of 20 patients. Accuracy was assessed using Intersection over Union (IoU), Dice coefficient, and liver volume. Image quality was evaluated using mean (SUVmean) and maximum (SUVmax) standardized uptake value and signal-to-noise ratio (SNR). The model achieved an average IoU of 0.89 and an average Dice coefficient of 0.94 based on test data from 20 patients, indicating high segmentation accuracy. No significant discrepancies in image quality metrics were identified compared with ground truth. Liver regions were accurately extracted from ¹⁸F-FDG PET images which allowed rapid and stable evaluation of liver uptake in individual patients without the need for CT or MRI assessments.

Accurate identification of bone marrow invasion (BMI) is critical for determining the prognosis of and treatment strategies for lymphoma. Although bone marrow biopsy (BMB) is the current gold standard, its invasive nature and sampling errors highlight the necessity for noninvasive alternatives. We aimed to develop and validate an interpretable machine learning model that integrates clinical data, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) parameters, radiomic features, and deep learning features to predict BMI in lymphoma patients. We included 159 newly diagnosed lymphoma patients (118 from Center I and 41 from Center II), excluding those with prior treatments, incomplete data, or under 18 years of age. Data from Center I were randomly allocated to training (n = 94) and internal test (n = 24) sets; Center II served as an external validation set (n = 41). Clinical parameters, PET/CT features, radiomic characteristics, and deep learning features were comprehensively analyzed and integrated into machine learning models. Model interpretability was elucidated via Shapley Additive exPlanations (SHAPs). Additionally, a comparative diagnostic study evaluated reader performance with and without model assistance. BMI was confirmed in 70 (44%) patients. The key clinical predictors included B symptoms and platelet count. Among the tested models, the ExtraTrees classifier achieved the best performance. For external validation, the combined model (clinical + PET/CT + radiomics + deep learning) achieved an area under the receiver operating characteristic curve (AUC) of 0.886, outperforming models that use only clinical (AUC 0.798), radiomic (AUC 0.708), or deep learning features (AUC 0.662). SHAP analysis revealed that PET radiomic features (especially PET_lbp_3D_m1_glcm_DependenceEntropy), platelet count, and B symptoms were significant predictors of BMI. Model assistance significantly enhanced junior reader performance (AUC improved from 0.663 to 0.818, p = 0.03) and improved senior reader accuracy, although not significantly (AUC 0.768 to 0.867, p = 0.10). Our interpretable machine learning model, which integrates clinical, imaging, radiomic, and deep learning features, demonstrated robust BMI prediction performance and notably enhanced physician diagnostic accuracy. These findings underscore the clinical potential of interpretable AI to complement medical expertise and potentially reduce the reliance on invasive BMB for lymphoma staging.