Organizations: Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211, USA · Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA · Department of Applied Computing, Lander University, Greenwood, SC 29649, USA · Department of Electronics and Computer Engineering, Sagarmatha Engineering College, Tribhuvan University, Nepal · Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
Accurate nuclei segmentation underpins quantitative computational pathology, yet remains challenging due to morphological variability, weak boundaries, nuclear crowding, and pronounced domain shifts arising from differences in tissue preparation, staining, and acquisition. While deep learning and recent foundation models have improved segmentation performance under matched distributions with the original training data, their generalization across heterogeneous histopathology domains remains limited. We introduce GDBA-Net, a parameter-efficient nuclei segmentation framework built around the proposed Gated Dual-Branch Adapter (GDBA). GDBA-Net adapts a frozen SAM2 encoder by integrating pretrained semantic representations with explicit frequency-derived structural priors. The complementary representations are independently transformed through Grid MLP branches and dynamically integrated using sample-adaptive channel-wise gating, selectively emphasizing structural cues relevant to nuclear delineation. Despite using only 4.3 million trainable parameters, GDBA-Net achieves state-of-the-art in-dataset performance and consistently superior cross-dataset generalization across six diverse nuclei segmentation benchmarks under fully supervised, cross-dataset, and five-shot adaptation protocols, outperforming competing CNN-, transformer-, and foundation model based methods. Comprehensive ablations confirm that these gains arise from the coordinated design of semantic-frequency complementarity and adaptive gating rather than increased model capacity. By uniting transferable semantic representations with explicit structural priors, GDBA-Net provides a robust, annotation-efficient solution to domain variability in nuclei segmentation. https://github.com/biplabpoudel25/GDBA_Net
Figures & tables
Fig. 1: Overall architecture of the proposed Gated Dual-Branch Adapter Network (GDBA-Net) framework for nuclei segmentation. The input H&E image is processed through multiple encoder stages, while the extracted frequency-derived structural and semantic features are integrated by the GDBA modules at the corresponding stages. The resulting representations are subsequently used to generate the predicted nuclei mask. The frequency and semantic feature extraction modules are detailed in Figure 2 .
Fig. 2: Frequency and semantic feature extraction process used in GDBA framework. The upper panel illustrates the frequency branch, whereas the lower panel shows the semantic feature extraction process. These complementary features are subsequently integrated by the GDBA modules.
Fig. 3: Overview of the proposed Gated Dual-Branch Adapter (GDBA). The upper light-gray shaded region illustrates the GDBA module, which integrates independently adapted handcrafted and semantic features to generate prompt features. The lower-left inset presents the branch adapter architecture, which is applied independently to the handcrafted and semantic feature streams. The generated prompts are combined with the current SAM2 tokens and passed to the corresponding transformer block.
Dataset
Tissue / Condition
Images
Resolution
Nuclei
Split (Train/Val/Test)
Kumar [ 25 ]
Multi-organ (7 organs)
30
1000 × 1000
21,623
12/4/14
MoNuSeg [ 26 ]
Multi-organ (9 organs)
51
1000 × 1000
∼ 28,500
33/7/11
CryoNuSeg [ 27 ]
Multi-organ (10 organs)
30
512 × 512
∼ 7,596
15/5/10
Combined CPM [ 28 ]
Brain, Head & Neck, Lung
79
Variable
∼ 10,000
30/10/39
TNBC [ 29 ]
Breast (TNBC subtype)
50
512 × 512
4,022
32/8/10
CoNSeP [ 5 ]
Colorectal adenocarcinoma
41
1000 × 1000
24,319
22/5/14
TABLE I: Summary of benchmark datasets used for nuclei segmentation evaluation.
Models
MoNuSeg
Kumar
CryoNuSeg
Dice
Jaccard
Precision
Specificity
Dice
Jaccard
Precision
Specificity
Dice
Jaccard
Precision
Specificity
U-Net [ 8 ]
0.8021
0.6712
0.7929
0.9411
0.7278
0.5775
0.6332
0.8149
0.7737
0.6349
0.7400
0.8531
Attn. U-Net [ 30 ]
0.7903
0.6551
0.7615
0.9264
0.7609
0.6212
0.7451
0.8833
0.7596
0.6176
0.7164
0.8410
nnU-Net [ 31 ]
0.8218
0.7091
0.8015
0.9396
0.8199
0.6966
0.8177
0.9424
0.8108
0.6845
0.8144
0.9186
PSPNet [ 32 ]
0.5922
0.4311
0.4347
0.6061
0.6014
0.4348
0.4402
0.6274
0.6805
0.5204
0.5361
0.6042
HoVer-Net [ 5 ]
0.8208
0.7086
0.7996
0.9399
0.7981
0.6749
0.7741
0.9223
0.8284
0.7125
0.8452
0.9231
TABLE II: In-dataset nuclei segmentation performance comparison of GDBA-Net and competing methods on the MoNuSeg, CryoNuSeg, and Kumar datasets. Best and second-best results are highlighted in bold and underline, respectively.
Methods
Test dataset
Combined CPM
TNBC
Combined CoNSeP
Dice
Jaccard
Precision
Specificity
Dice
Jaccard
Precision
Specificity
Dice
Jaccard
Precision
Specificity
Trained on MoNuSeg
U-Net
0.7329
0.5878
0.8281
0.9640
0.6732
0.5187
0.7145
0.9642
0.6236
0.4678
0.5698
0.9000
Attn U-Net
0.7262
0.5799
0.8170
0.9589
0.7027
0.5529
0.7438
0.9629
0.6003
0.4477
0.5147
0.8568
nnU-Net
0.7801
0.6604
0.8004
0.9440
0.7025
0.5712
0.6132
0.9065
0.6322
0.4854
0.5444
0.8407
PSPNet
0.6062
0.4565
0.4674
0.6863
0.2606
0.1634
0.1639
0.1928
0.4142
0.2844
0.2900
0.4596
TABLE III: Cross-dataset generalization performance of GDBA-Net and competing methods trained on MoNuSeg, CryoNuSeg, or CoNSeP and directly evaluated on the unseen Combined CPM, TNBC, and Combined CoNSeP test datasets. For each source–target dataset pair and metric, the best and second-best results are highlighted in bold and underline, respectively.
Fig. 4: Boxplot-based comparison of nuclei segmentation performance under in-dataset and cross-dataset evaluation. The top panel presents results when models are trained and tested on CryoNuSeg, whereas the bottom panel shows cross-dataset performance when models are trained on CryoNuSeg and evaluated on CPM dataset. Boxes represent the interquartile range, horizontal lines indicate the median, whiskers show the non-outlier range, and circular markers denote outlier samples.
Fig. 5: Comparison of dice scores for GDBA across cross-dataset transfer, five-shot adaptation, and full target-domain fine-tuning on the CPM, TNBC, and CoNSeP datasets. Cross-dataset models are trained on MoNuSeg or CryoNuSeg and evaluated directly on each unseen target dataset.
Fig. 6: Qualitative comparison of nuclei segmentation results on representative samples. Ground-truth masks and overlap maps produced by the competing methods are shown for visual comparison. In the overlay, white denotes correctly segmented nuclei pixels, red denotes false positives predictions, and blue indicates false negatives predictions.
Fig. 7: Comparison of trainable parameter counts for GDBA and competing segmentation methods.
Models
ISIC 2018 [ 44 , 45 ]
DRIVE [ 43 ]
Dice
Jaccard
Dice
Jaccard
U-Net
0.858
0.776
0.816
0.701
nnU-Net
0.855
0.766
0.780
0.640
Attn U-Net
0.867
0.785
0.808
0.681
NucleiSegNet
0.881
0.808
0.650
0.482
MedSAM
0.863
0.759
0.806
0.676
TABLE IV: Performance comparison of GDBA-Net and competing methods on ISIC 2018 and DRIVE for skin lesion and retinal vessel segmentation.
Frequency branch
Semantic branch
Adaptive gate
Shared projections
Params (M)
MoNuSeg
CryoNuSeg
Dice
Jacc.
Prec.
Spec.
Dice
Jacc.
Prec.
Spec.
×
✓
✓
✓
4.11
0.8145
0.6893
0.8028
0.9332
0.8331
0.7156
0.8618
0.9369
✓
×
✓
✓
4.07
0.8087
0.6813
0.7954
0.9292
0.8360
0.7196
0.8248
0.9123
✓
✓
×
✓
4.28
0.8108
0.6841
0.7982
0.9306
0.8340
0.7173
0.8686
0.9396
✓
✓
✓
×∗
4.88
0.8048
0.6758
0.7907
0.9268
0.8402
0.7260
0.8568
0.9311
✓
✓
✓
✓
4.30
0.8408
0.7259
0.8388
0.9516
0.8481
0.7381
0.8519
0.9286
TABLE V: Component-wise ablation analysis of the proposed GDBA framework on the MoNuSeg and CryoNuSeg datasets.
α
Params (M)
MoNuSeg
CryoNuSeg
Dice
Jacc.
Prec.
Spec.
Dice
Jacc.
Prec.
Spec.
8
10.23
0.8176
0.6941
0.8068
0.9347
0.8368
0.7213
0.8591
0.9332
16
5.54
0.8189
0.6958
0.8087
0.9359
0.8352
0.7189
0.8618
0.9250
32
4.30
0.8408
0.7259
0.8388
0.9516
0.8481
0.7381
0.8519
0.9286
64
3.97
0.8194
0.6963
0.8096
0.9361
0.8372
0.7213
0.8475
0.9276
TABLE VI: Effect on bottleneck scaling factor α on model performance and parameter efficiency. Larger α corresponds to stronger dimensionality reduction.
Histopathology nuclei segmentation is crucial for quantitative tissue analysis and cancer diagnosis. Although existing segmentation methods have achieved strong performance, they are often computationally heavy and show limited generalization across datasets, which constrains their practical deployment. Recent SAM-based approaches have shown great potential in general and medical imaging, but typically rely on prompt guidance or complex decoders, making them less suitable for histopathology images with dense nuclei and heterogeneous appearances. We propose a prompt-free and lightweight SAM adaptation that leverages multi-level encoder features and residual decoding for accurate and efficient nuclei segmentation. The framework fine-tunes only LoRA modules within the frozen SAM encoder, requiring just 4.1M trainable parameters. Experiments on three benchmark datasets TNBC, MoNuSeg, and PanNuke demonstrate state-of-the-art performance and strong cross-dataset generalization, highlighting the effectiveness and practicality of the proposed framework for histopathology applications.
Muhammad Hassan Maqsood, Yanming Zhu, Alfred Lam +3
School of Information and Communication Technology, Griffith University, QLD, Australia · School of MDP – Clinical Medicine, Griffith University, QLD, Australia
Accurate classification of nuclei subtypes in histopathology images is critical for downstream tasks including tumor grading, immune infiltrate quantification, and prognosis prediction. Existing approaches rely on either convolutional or transformer-based encoders in isolation, limiting their ability to simultaneously capture fine-grained local texture and long-range spatial context. We present AMN (Adaptive Multi-Scale Nuclei Network), a dual-encoder segmentation framework that jointly leverages a Swin Transformer and a ResNet-50 feature pyramid, fused via a learned per-channel gating mechanism that dynamically weighs each encoder's contribution at every scale. AMN is trained with a multi-objective loss combining class-weighted focal loss, boundary-aware loss with positive-pixel emphasis, and a novel uncertainty-modulated classification term that suppresses overconfident erroneous predictions. Evaluated on the CoNIC benchmark across seven nuclei classes, AMN achieves a mean Dice of 0.82 and mean F1 of 0.68, with an F1 of 0.67 on the diagnostically challenging lymphocyte class. AMN outperforms eight baseline models spanning pure-CNN, pure-transformer, and recent hybrid architectures: U-Net, ResU-Net, DeepLabV3+, SegNet, ViT-Small, HmsU-Net, ConvFormer-UNet, and BEFUnet. Cross-dataset evaluation on MoNuSeg demonstrates strong generalization without retraining and validating the domain robustness of the learned representations.
Spoorthi M, Suja Palaniswamy
Department of Computer Science & Engineering, Amrita School of Computing, Bengaluru, Amrita Vishwa Vidyapeetham, India
Nuclei instance segmentation is critical in computational pathology for cancer diagnosis and prognosis. Recently, the Segment Anything Model has demonstrated exceptional performance in various segmentation tasks, leveraging its rich priors and powerful global context modeling capabilities derived from large-scale pre-training on natural images. However, directly applying SAM to the medical imaging domain faces significant limitations: it lacks sufficient perception of the local structural features that are crucial for nuclei segmentation, and full fine-tuning for downstream tasks requires substantial computational costs. To efficiently transfer SAM's robust prior knowledge to nuclei instance segmentation while supplementing its task-aware local perception, we propose a parameter-efficient fine-tuning framework, named Cooperative Fine-Grained Refinement of SAM, consisting of three core components: 1) a Multi-scale Adaptive Local-aware Adapter, which enables effective capability transfer by augmenting the frozen SAM backbone with minimal parameters and instilling a powerful perception of local structures through dynamically generated, multi-scale convolutional kernels; 2) a Hierarchical Modulated Fusion Module, which dynamically aggregates multi-level encoder features to preserve fine-grained spatial details; and 3) a Boundary-Guided Mask Refinement, which integrates multi-context boundary cues with semantic features through explicit supervision, producing a boundary-focused signal to refine initial mask predictions for sharper delineation. These three components work cooperatively to enhance local perception, preserve spatial details, and refine boundaries, enabling SAM to perform accurate nuclei instance segmentation directly.
Jingze Su, Tianle Zhu, Jiaxin Cai +6
College of Computer and Data Science, Fuzhou University, Fuzhou, China · College of Physics and Information Engineering, Fuzhou University, Fuzhou, China · School of Mechanical Engineering and Automation, Fuzhou University, Fuzhou, China