MBFormer: Microbubble Transformer for 3D Time-Series Da-ta Processing to Improve Bound Bubble Detection in...

Development of nondestructive ultrasound molecular imaging (UMI) is essential for early cancer detection through real-time screening using clinical ultrasound systems. Current techniques face challenges in accurately detecting targeted microbubbles (MBs) bound to specific biomarkers, primarily due to false-positive detections of unbound free-floating MBs. We propose a transformer model for time-series video processing to improve the differentiation of bound MBs. We propose a hierarchical transformer, termed MBFormer (microbubble transformer), featuring a positional-embedding-free encoder and a lightweight decoder. Leveraging attention within 3D spatio-temporal data to effectively capture stationary signals from bound MBs while suppressing nonstationary signals from unbound MBs. Since MBs appears as relatively small textures compared with conventional segmentation targets in medical imaging, such as organs and tumors, we optimized the model with two hierarchical layers, each with an attention block, to process ultrasound video data. The network outputs the molecular signal amplitude to visualize fine MB textures. Performance was evaluated using an in vivo breast cancer model, compared against a prior CNN-based UMI method and SegFormer3D baseline, a representative 3D transformer. MBFormer (AUC = 0.943) outperformed both CNN (AUC = 0.897) and SegFormer3D (AUC = 0.766) in detecting bound MBs. The CNN showed residual molecular signal from free MBs in the cardiac chambers, whereas SegFormer3D failed to detect fine MB textures. Overall, MBFormer demonstrated enhanced detection of bound MBs while suppressing free MBs and achieved a frame rate of 16.7 to 18.1 FPS, demonstrating its potential for real-time application. We anticipate that this transformer-based UMI model can facilitate real-time, free-hand nondestructive UMI in clinical systems.