CycleULM: A unified label-free deep learning framework for ultrasound localisation microscopy

Super-resolution ultrasound via microbubble (MB) localisation and tracking, also known as ultrasound localisation microscopy (ULM), can resolve microvasculature beyond the acoustic diffraction limit. However, significant challenges remain in localisation performance and data acquisition and processing time. Deep learning methods for ULM have shown promise to address these challenges, however, they remain limited by in vivo label scarcity and the simulation-to-reality domain gap. We present CycleULM, the first unified label-free deep learning framework for ULM. CycleULM learns a physics-emulating translation between the real contrast-enhanced ultrasound (CEUS) data domain and a simplified MB-only domain, leveraging the power of CycleGAN without requiring paired ground truth data. With this translation, CycleULM removes dependence on high-fidelity simulators or labelled data, and makes MB localisation and tracking substantially easier. Deployed as modular plug-and-play components within existing pipelines or as an end-to-end processing framework, CycleULM delivers substantial performance gains across both in silico and in vivo datasets. Specifically, CycleULM improves image contrast (contrast-to-noise ratio) by up to 15.3 dB and sharpens CEUS resolution with a 2.5{\times} reduction in the full width at half maximum of the point spread function. CycleULM also improves MB localisation performance, with up to +40% recall, +46% precision, and a -14.0 μm mean localisation error, yielding more faithful vascular reconstructions. Importantly, CycleULM achieves real-time processing throughput at 18.3 frames per second with order-of-magnitude speed-ups (up to ~14.5{\times}). By combining label-free learning, performance enhancement, and computational efficiency, CycleULM provides a practical pathway toward robust, real-time ULM and accelerates its translation to clinical applications.

Learning-based Reconstruction of FRI Signals

Finite Rate of Innovation (FRI) sampling theory enables reconstruction of classes of continuous non-bandlimited signals that have a small number of free parameters from their low-rate discrete samples. This task is often translated into a spectral estimation problem that is solved using methods involving estimating signal subspaces, which tend to break down at a certain peak signal-to-noise ratio (PSNR). To avoid this breakdown, we consider alternative approaches that make use of information from labelled data. We propose two model-based learning methods, including deep unfolding the denoising process in spectral estimation, and constructing an encoder-decoder deep neural network that models the acquisition process. Simulation results of both learning algorithms indicate significant improvements of the breakdown PSNR over classical subspace-based methods. While the deep unfolded network achieves similar performance as the classical FRI techniques and outperforms the encoder-decoder network in the low noise regimes, the latter allows to reconstruct the FRI signal even when the sampling kernel is unknown. We also achieve competitive results in detecting pulses from in vivo calcium imaging data in terms of true positive and false positive rate while providing more precise estimations.