Beyond Isotropic Assumptions: Continuity-Constrained Segmentation and GPU Morphometry for Nanoscale GBM Analysis
Authors: Arash Fatehi, Robin Ebbestad, Linus Butt, Hans Blom, Sigrid Lundberg, Hannes Olauson, Hjalmar Brismar, David Unnersjö-Jess, +2 more
Abstract
Confocal microscopy of optically cleared and swelled tissue resolves complex biological structures in 3D, but such acquisitions are highly anisotropic: along the under-sampled axial direction the structure can appear discontinuous, hampering reconstruction and automated quantitative analysis. The usual remedy upsamples the axial dimension to an isotropic volume before training a segmentation model, which requires dense annotations in the upsampled space, a prohibitive labeling burden. We present an end-to-end, GPU-accelerated framework that overcomes this without additional annotations. The model is trained on the native acquisition volume; random rotation of training patches leverages the well-resolved lateral plane to supply the missing axial information, and a z-axis continuity loss keeps neighboring slices consistent. We adapt both a convolutional (3D U-Net) and a transformer (SwinUNETR) backbone, aggregate overlapping patches by Gaussian consensus, and compute point-spread-function-corrected membrane thickness by ray-surface intersection on the GPU. We apply the method to the glomerular basement membrane (GBM), a thin, highly convoluted part of the kidney's filtration barrier that grows more irregular in disease. Segmentation accuracy matches inter-expert agreement. Continuity-aware training improves reconstruction smoothness and suppresses a periodic terracing artifact at minimal accuracy cost. We quantify GBM thickness across the reconstructed 3D surface and capture disease-related thickening, enabling fully automated anisotropic 3D morphometry of biological structures without dense volumetric labels or image restoration.
Tracking residual tumor after surgery is essential for catching recurrence early, but automating post-operative glioma segmentation remains a difficult task. Although transformer-based architectures, such as SwinUNETR, achieved impressive results, few studies test how well they generalize across clinical protocols. In this paper, we conduct an ablation study on the MU-GLIOMA-POST and UCSF-ALPTDG datasets and show that the standard Generalized Dice Loss (GDL) is unstable under domain shift: the Whole Lesion (WL) Dice drops from 0.88 on the internal validation set to 0.73 on the external UCSF test set. To address this, we pair brain-masked percentile normalization with voxel-level contrastive learning. We also propose a Subspace-Aware Class Attention (SACA) module that re-calibrates the bottleneck features and raises Enhancing Tumor (ET) sensitivity by 8% (9.1% relative improvement) on internal validation. Ensembling these refinements with nnU-Net brings every stable configuration to a WL Dice of 0.94, and the SACA variant ensemble achieves the best boundary error (HD95) of 2.92 mm on MU-GLIOMA-POST.
Accurate 3D medical image segmentation requires both long-range volumetric context and fine boundary preservation. CNN-based methods have limited global dependency modeling, while Transformer-based models are often computationally expensive for dense 3D inputs. Recent Mamba-based methods provide an efficient alternative, but existing volumetric designs still depend on repeated high-resolution scanning, forward-only sequential modeling, and fixed directional summation, causing high cost, scan-order bias, and suboptimal directional aggregation. We propose BiSegMamba, an efficient bidirectional tri-oriented Mamba network for 3D medical image segmentation. BiSegMamba follows a compact-to-detail design, where a progressive compacting stem (PCS) enables efficient latent-space reasoning while retaining shallow high-resolution features for reconstruction. A multi-scale spatial mixer (MSSM) captures local anatomical patterns in early stages, and the proposed bidirectional tri-oriented Ortho Mamba (Bi-ToOM) block models long-range dependencies from multiple orthogonal views using jointly processed forward and backward scan sequences. Adaptive directional fusion (ADF) learns input-dependent channel-wise weights across scan orientations, replacing fixed summation with orientation-aware fusion. Experiments on a collected carotid CTA dataset and three public benchmarks, BraTS2023, ACDC, and AMOS-CT, show that BiSegMamba generalizes well across vascular, cardiac, brain tumor, and abdominal multi-organ segmentation tasks. Compared with SegMamba-V2, BiSegMamba achieves slightly better performance on BraTS2023 and clear improvements on ACDC and the carotid dataset, while reducing computational cost by up to 77.9% FLOPs, demonstrating a strong accuracy-efficiency balance for general 3D medical image segmentation.
Foundation models such as Segment Anything Model 2 (SAM2) have transformed natural-image and video segmentation, and recent work has begun adapting them to medical imaging. These adaptations, however, are largely general-purpose models that treat MRI as one modality among many; large-scale, MRI-specific modelling and benchmarking remain limited, even though MRI's low soft-tissue contrast leaves many boundaries effectively invisible on individual slices. We present SAMRI-3D, a benchmark and method for 3D MRI segmentation with SAM2. The SAMRI-3D benchmark is the largest MRI-only evaluation to date - 10,392 volumes from 34 datasets (27 public, 7 in-house) spanning 12 anatomical domains and 10+ sequences, with explicit seen/unseen splits. Freezing the image encoder and fine-tuning only the lightweight decoder and memory modules raises mean Dice from 0.58 (zero-shot SAM2) to 0.76, surpassing recent SAM-based medical models (SAMed-2 0.69, Medical-SAM2 0.49, SAM-Med3D 0.37) with strong statistical significance. To target invisible boundaries, we introduce Global Volume Tokens (GVT): persistent memory tokens trained with a Truncated Signed Distance Field (TSDF) reconstruction objective that is discarded at inference (zero added cost). This full model, SAMRI-3D, attains the best accuracy (0.78) and lowest variance across all 34 datasets and, uniquely, shows no drop on 8 held-out datasets (0.79 unseen vs. 0.78 seen); per-sequence analysis confirms the TSDF objective helps most where per-slice contrast is weakest. We will release the benchmark, code, and models in this paper.