Developing Foundation Models for Universal Segmentation from 3D Whole-Body Positron Emission Tomography
Authors: Yichi Zhang, Le Xue, Wenbo Zhang, Lanlan Li, Feiyang Xiao, Yuchen Liu, Xiaohui Zhang, Hongwei Zhang, Shuqi Wang, Gang Feng, Liling Peng, Xin Gao, Yuanfan Xu, Yuan Qi, Kuangyu Shi, Hong Zhang, Yuan Cheng, Mei Tian, Zixin Hu
Organizations: Artificial Intelligence Innovation and Incubation Institute, Fudan University, Shanghai, China. · Shanghai Academy of Artificial Intelligence for Science, Shanghai, China. · Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China. · Human Phenome Institute, Fudan University, Shanghai, China. · Department of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China. · Shanghai Universal Medical Imaging Diagnostic Center, Shanghai, China. · Hangzhou Universal Medical Imaging Diagnostic Center, Hangzhou, China. · Department of Information and Intelligence Development, Zhongshan Hospital, Fudan University, Shanghai, China. · Department of Nuclear Medicine, Inselspital, University of Bern, Switzerland.
Positron emission tomography (PET) is a key nuclear medicine imaging modality that visualizes radiotracer distributions to quantify in vivo physiological and metabolic processes, playing an irreplaceable role in disease management. Despite its clinical importance, the development of deep learning models for quantitative PET image analysis remains severely limited, driven by both the inherent segmentation challenge from PET's paucity of anatomical contrast and the high costs of data acquisition and annotation. To bridge this gap, we develop generalist foundational models for universal segmentation from 3D whole-body PET imaging. We first build the largest and most comprehensive PET dataset to date, comprising 11041 3D whole-body PET scans with 59831 segmentation masks for model development. Based on this dataset, we present SegAnyPET, an innovative foundational model with general-purpose applicability to diverse segmentation tasks. Built on a 3D architecture with a prompt engineering strategy for mask generation, SegAnyPET enables universal and scalable organ and lesion segmentation, supports efficient human correction with minimal effort, and enables a clinical human-in-the-loop workflow. Extensive evaluations on multi-center, multi-tracer, multi-disease datasets demonstrate that SegAnyPET achieves strong zero-shot performance across a wide range of segmentation tasks, highlighting its potential to advance the clinical applications of molecular imaging.
Figures & tables
Figure 1: Figure 1 : Overview of dataset construction, model development and validation in our study. (a) We construct PETWB-Seg11K, a large-scale whole-body PET scans from multi-tracer, multi-vendor, and multi-disease cohorts, with diverse heterogeneity in data distribution. (b) We develop SegAnyPET, a foundation model for universal volumetric PET segmentation. It takes volumetric PET input, encodes features via Image Encoder, and combines with sparse or dense prompts encoded by Prompt Encoder, then outputs segmentation through Mask Decoder. SegAnyPET supports a human-in-the-loop workflow with interactive prompting for rectification of segmentation results. (c) Comprehensive evaluation on in-distribution segmentation tasks validates the consistent and reliable performance of SegAnyPET on data with similar distribution to the training set. (d) Extensive assessment on out-of-distribution segmentation tasks demonstrates the generalization capability of SegAnyPET on unseen data scenarios in cross-center and cross-tracer settings.
Figure 2: Figure 2: Comparison of SegAnyPET with task-specific segmentation models on internal evaluation for multi-organ segmentation. (a) Quantitative performance comparison with four representative task-specific segmentation models. The center line within each box indicates the median value; the bottom and top bounds indicate the 25th percentiles and 75th percentiles, respectively. Outlier classes are plotted as individual dots. (b) Performance comparison between SegAnyPET and the most competitive task-specific model nnU-Net on five training visible target organs. (c) Compared with task-specific models that are trained for the segmentation of training visible targets, SegAnyPET retains the generalization capability to new targets. In contrast, additional annotation and training are required for task-specific models when adapted to training invisible targets.
Figure 3: Figure 3: Quantitative and qualitative evaluation of SegAnyPET with other foundation models for promptable PET segmentation. (a) Illustration of slice-wise and volumetric prompting strategies using 2D and 3D segmentation foundation models. For 2D models (e.g., SAM, MedSAM), the PET volume is decomposed into individual slices, where point prompts are provided on selected slices and the resulting 2D predictions are aggregated to form a 3D segmentation. In contrast, 3D foundation models (e.g., SegAnyPET) directly operate on the entire volumetric input and perform end-to-end volumetric segmentation. (b) Quantitative performance comparison of different promptable segmentation foundation models across multiple internal PET segmentation tasks. The DSC score is calculated in a volume-wise manner.
Figure 4: Figure 4: Comprehensive evaluation of generalization capability in external cohorts and clinical utility in downstreeam applications. (a) Quantitative comparison of model generalization performance on out-of-distribution datasets with unseen targer organs, modality variations, and novel radiotracer uptake patterns. (b) Evaluation of clinical utility in terms of annotation efficiency. In both lymphoma and lung cancer scenarios, the SegAnyPET-assisted interactive workflow significantly reduces the manual burden compared to conventional manual delineation. (c) Whole-body metabolic covariance network built from SegAnyPET segmentation results. The network verifies that SegAnyPET outputs have high biological fidelity, enabling robust downstream metabolic network analysis for systemic disease clinical research.
Figure 5: Figure 5: Comparison of point-prompt interaction efficacy between continuous organs and distributed pathological lesions. (a) Segmentation of continuous holistic organs. For such single-entity structures, precise and comprehensive segmentation can be efficiently achieved using only one point prompt. (b) Segmentation of disseminated lesion like lymphoma. In contrast to organs, systemic oncological findings frequently present as multiple, spatially discrete lesions across the whole body. This example illustrates the practical constraints of the point-based paradigm, demonstrating that a limited number of point prompts are insufficient to simultaneously capture the entire distributed tumor burden. (c) Practical interactive workflow for disseminated lesions. Since a single prompt cannot capture all spatially separated tumor sites, each lesion is individually prompted and segmented in a sequential lesion-wise manner.
Cohort ID
Dataset
Modality
Segmentation Task
Num. Scans
Num. Masks
C1
AutoPET-FDG
FDG-PET
Tumor Lesion
1,014
9,696
C2
UDPET
FDG-PET
Multi-Organ
1,371
6,855
C3
PETS-A
FDG-PET
Multi-Organ
5,731
28,655
C4
PETS-B
FDG-PET
Multi-Organ
2,925
14,625
Dev
PETWB-Seg11K (Model Development)
11,041
59,831
C3
PETS-Organ
FDG-PET
Multi-Organ
100
1,100
Table 1: Table 1 : Information summary of subsets PETWB-Seg11K dataset involved in the development and evaluation of SegAnyPET. * denotes PET/MRI-derived PET imaging other than PET/CT-derived PET imaging
Figure 6: Figure 6: Network architectural and promptable segmentation pipeline of SegAnyPET for volumetric PET segmentation. (a) SegAnyPET employs 3D transformer-based components to directly capture spatial correlations within volumetric data. The pipeline integrates 3D image feature extraction with absolute positional encoding, a prompt encoder supporting both sparse (points) and dense (masks) inputs, and a mask decoder process utilizing 3D transformer blocks and transposed convolutions for end-to-end volumetric segmentation. (b) The iterative evaluation loop simulates an interactive segmentation process by automatically generating clicks based on the discrepancy between the current mask prediction and the ground truth. These accumulating points, combined with the previous mask and image embeddings, are fed back into SegAnyPET to progressively refine the prediction.
Figure 7: Figure 7: Training data composition of representative 3D medical segmentation foundation models. (a) Number of 3D training samples across imaging modalities (CT, MRI, and PET), with whole-body and regional datasets shown separately. This modality disparity underscores the fundamental limitation of current models, which are heavily biased toward structural priors and struggle to represent complex metabolic uptake patterns. (b) Anatomical coverage of the training data across major body regions. Most existing models are trained on structural CT or MRI data with region-specific coverage, whereas SegAnyPET is trained on large-scale whole-body PET data spanning all major anatomical regions. By bridging this critical data scarcity with comprehensive whole-body PET volumes, SegAnyPET establishes a robust and domain-specific feature space tailored for functional PET image analysis.
Model
Liver
Kidney-L
Kidney-R
Heart
Spleen
nnUNet
0.9379 (0.9298–0.9419)
0.9026 (0.8920–0.9155)
0.8704 (0.8513–0.8893)
0.9118 (0.9016–0.9180)
0.8869 (0.8635–0.9010)
SegResNet
0.9362 (0.9291–0.9410)
0.9071 (0.8822–0.9188)
0.8585 (0.8415–0.8829)
0.9031 (0.8956–0.9137)
0.8938 (0.8774–0.9052)
STUNet
0.9351 (0.9265–0.9407)
0.9031 (0.8941–0.9143)
0.8769 (0.8315–0.8958)
0.9176 (0.8960–0.9315)
0.8795 (0.8592–0.9013)
SwinUNETR
0.9351 (0.9291–0.9413)
0.8991 (0.8788–0.9102)
0.8461 (0.8355–0.8968)
0.8904 (0.8852–0.9119)
0.8857 (0.8570–0.8994)
SegAnyPET (1p)
0.9262 (0.9156–0.9331)
0.8746 (0.8520–0.8877)
0.8700 (0.8546–0.8880)
0.8922 (0.8818–0.9002)
0.8763 (0.8560–0.8944)
SegAnyPET (3p)
0.9386 (0.9298–0.9460)
0.8867 (0.8662–0.9020)
0.8875 (0.8682–0.9031)
0.9052 (0.8967–0.9136)
0.8908 (0.8732–0.9200)
Table 2: Supplementary Table 1 : Quantitative comparison of DSC performance across task-specific models and SegAnyPET under different prompting conditions. The results are presented as the median Dice score along with the interquartile range (Q1–Q3).
Model
Liver
Kidney-L
Kidney-R
Heart
Spleen
nnUNet
0.5076 (0.4615–0.5402)
0.5204 (0.4804–0.5995)
0.5257 (0.4549–0.5985)
0.4737 (0.4280–0.5175)
0.5231 (0.4439–0.5715)
SegResNet
0.4818 (0.4418–0.5399)
0.5288 (0.4768–0.5871)
0.4954 (0.4213–0.5849)
0.4625 (0.4308–0.5137)
0.5116 (0.4499–0.5688)
STUNet
0.4919 (0.4623–0.5325)
0.5259 (0.4845–0.6064)
0.5118 (0.4411–0.5872)
0.4702 (0.4139–0.5033)
0.5145 (0.4540–0.5573)
SwinUNETR
0.4801 (0.4157–0.5168)
0.4960 (0.4249–0.5649)
0.4641 (0.3943–0.5530)
0.4597 (0.4137–0.4865)
0.4781 (0.4264–0.5214)
SegAnyPET (1p)
0.4982 (0.4550–0.5364)
0.5123 (0.4681–0.5754)
0.5170 (0.4512–0.5827)
0.4689 (0.4257–0.5094)
0.5096 (0.4475–0.5608)
SegAnyPET (3p)
0.5225 (0.4758–0.5614)
0.5394 (0.4956–0.6028)
0.5441 (0.4785–0.6079)
0.4873 (0.4421–0.5286)
0.5378 (0.4689–0.5884)
Table 3: Supplementary Table 2 : Quantitative comparison of NSD performance across task-specific models and SegAnyPET under different prompting conditions. The results are presented as the median NSD score along with the interquartile range (Q1–Q3).
Methods
Prompt
DSC Performance of Each Target Organ
Inference
Liver
Kidney-L
Kidney-R
Brain
Heart
Spleen
Time (s)
SAM
3N points
0.2607 (0.2277–0.2976)
0.2751 (0.2391–0.3136)
0.2619 (0.2218–0.2948)
0.1764 (0.1545–0.2017)
0.2238 (0.1835–0.2611)
0.3132 (0.2685–0.3579)
19.6
SAM
5N points
0.3673 (0.3257–0.4014)
0.3450 (0.3067–0.3834)
0.3518 (0.3082–0.3937)
0.2249 (0.2014–0.2542)
0.3119 (0.2754–0.3522)
0.3944 (0.3490–0.4441)
32.1
MedSAM
5N points
0.3488 (0.3211–0.3799)
0.3244 (0.2792–0.3667)
0.3349 (0.2791–0.3836)
0.2364 (0.2225–0.2489)
0.2286 (0.2103–0.2502)
0.3212 (0.2760–0.3757)
22.8
nnIteractive
1 point
0.2955 (0.0040–0.7949)
0.5970 (0.0065–0.7687)
0.4816 (0.0104–0.7612)
0.9027 (0.8871–0.9151)
0.0649 (0.0088–0.5149)
0.5020 (0.0279–0.7914)
7.4
SAM-Med3D
1 point
0.7020 (0.6346–0.7504)
0.5894 (0.4877–0.6751)
0.6083 (0.4376–0.7040)
0.8101 (0.6313–0.8582)
0.4661 (0.3779–0.5584)
0.6136 (0.5192–0.6702)
1.8
Table 4: Supplementary Table 3 : Performance comparison with best-performing 2D and 3D foundation models for organ segmentation in UMD-PETCT with corresponding prompting efforts and inference time per case. N denotes the number of slices containing the target organ ranging from around 15 to 30 in our task. The results are presented as the median NSD score along with the interquartile range (Q1–Q3).
Model
SAM-Med3D
SAT
VISTA3D
SegVol
nnIteractive
SegAnyPET(1p)
SegAnyPET-Lesion
Prompt
1 point
text
target id
1 point
1 point
1 point
1 point
PETS-Organ for Multi-Organ Segmentation
Liver
0.6455 (0.3114–0.7590)
0.0000 (0.0000–0.0000)
0.0512 (0.0309–0.0848)
0.4398 (0.0629–0.6184)
0.7021 (0.0162–0.8533)
0.9262 (0.9156–0.9331)
—
Kidney-L
0.6635 (0.5631–0.7200)
0.0000 (0.0000–0.0000)
0.0000 (0.0000–0.0000)
0.1521 (0.0992–0.2639)
0.7897 (0.5655–0.8305)
0.8746 (0.8520–0.8877)
—
Kidney-R
0.5812 (0.4768–0.6290)
0.0000 (0.0000–0.0000)
0.0000 (0.0000–0.0000)
0.1274 (0.0793–0.2432)
0.7493 (0.3269–0.8165)
0.8700 (0.8546–0.8880)
—
Heart
0.6112 (0.4622–0.6846)
0.0000 (0.0000–0.0000)
0.0000 (0.0000–0.0000)
0.3459 (0.1143–0.6201)
0.1518 (0.0239–0.6027)
0.8922 (0.8818–0.9002)
—
Table 5: Supplementary Table 4 : Quantitative comparison of DSC performance with other promptable segmentation foundation models and SegAnyPET on multi-organ, lymphoma, lung cancer, prostate carcinoma, UMD-CT organ and UMD-MRI organ tasks. The results are presented as the median Dice score along with the interquartile range (Q1–Q3). The best performing score for each target structure is highlighted in bold.
The synergistic interpretation of anatomical information from computed tomography (CT) and metabolic information from positron emission tomography (PET) is important to oncologic imaging. However, existing deep learning methods for PET/CT remain largely task-specific, are often trained on single-center cohorts, or adopt dual-branch fusion schemes that delay cross-modal interaction and underutilize early spatial correspondence between PET and CT. To address these limitations, we present an open-source, multi-center, whole-body FDG PET/CT foundation model utilizing 4,997 harmonized scans from four public datasets. Our framework employs hierarchical UNet-shaped backbones with early channel-wise concatenation, enabling anatomical and metabolic features to interact from the first embedding layer onward. We further introduce a masked autoencoding objective based on zero-mean imputation, combined with a weighted global reconstruction loss. This design avoids non-physical intensity discontinuities at masked-region boundaries that arise from learnable mask tokens. On downstream AutoPET lesion segmentation, the proposed models demonstrate strong label efficiency: with only 10% of the labeled training data, they achieve performance comparable to models trained from scratch on the full dataset. Under extreme 5-shot linear probing, joint PET/CT pretraining also achieves higher Dice scores than separated-modality pretraining. This multi-center foundation model demonstrates label efficiency and cross-modality representation learning for PET/CT tumor segmentation. It provides a robust, open-source basis for advancing automated oncologic imaging, significantly reducing the need for large-scale manual annotations in clinical practice.
Xiaofeng Liu, Qianru Zhang, Thibault Marin +4
Department of Radiology and Biomedical Imaging, Yale Biomedical Imaging Institute, Yale University, New Haven, CT, USA
Organ segmentation from PET/CT is critical for quantitative analysis and radiotherapy planning in oncology. To ease the high annotation cost of PET/CT segmentation, semi-supervised learning (SSL) provides a practical and effective solution for developing deep models with limited labeled data. Recent developments in visual foundation models have demonstrated remarkable adaptability with improved efficiency. In this work, we propose a mutual distillation framework that seamlessly exploits both structural and functional foundation models, which act as modality-specific generalists for distilling knowledge from structural CT and metabolic PET imaging. By bridging the gap between the task-specific precision of student models and the segmentation priors of generalist foundation models, we propose MuDuo, a mutual distillation framework that synergistically leverages SAM-Med3D for CT and SegAnyPET for PET to distill their knowledge into a lightweight student network. Our approach eliminates the need for manual prompts while maximizing the utility of unlabeled data for automatic segmentation, achieving state-of-the-art performance on the AutoPET dataset with only 5 labeled cases. Our source code is available at https://github.com/Wu-beining/MuDuo.
Fuyou Mao, Beining Wu, Yanfeng Jiang +5
Central South University, Changsha 410083, China · Hangzhou Dianzi University, Hangzhou 310018, China · Communication University of Zhejiang, Hangzhou 310018, China +1
Deep learning-based whole-body PET-CT lesion segmentation can support cancer staging, treatment planning, and response assessment, but generalization is limited by scarce annotations and domain shifts. Self-supervised learning (SSL) can address these challenges but remains underexplored in pan-cancer, multi-tracer PET-CT. In this work, we propose MUST-PET (MUltimodal Self-Supervised learning across Tracers), a multimodal, multi-tracer SSL framework for generalizable whole-body PET-CT lesion segmentation. MUST-PET is trained and validated on a diverse, multi-institutional collection of pan-cancer PET-CT scans acquired with FDG and prostate-specific membrane antigen (PSMA)-targeted radiotracers. MUST-PET uses context-aware masked reconstruction, where one modality is partially masked and reconstructed using complementary information from both PET and CT. The pretrained model is subsequently fine-tuned with labeled samples and evaluated for reconstruction quality, lesion segmentation, label efficiency, and generalizability across independent held-out datasets. MUST-PET reduces reconstruction error, improves lesion segmentation over training from scratch, and performs well with limited labeled data and on unseen external datasets, demonstrating the potential of multi-tracer SSL for label-efficient, generalizable whole-body PET-CT. segmentation.
Department of Biomedical Data Science Geisel School of Medicine at Dartmouth Hanover, NH 03755, USA · Radiology Dartmouth Hitchcock Medical Center Lebanon, NH 03766, USA · Radiation Oncology Dartmouth Hitchcock Medical Center Lebanon, NH 03766, USA