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    We developed backscattering functional ultrasound localization microscopy (B-fULM) to improve 3D brain activity mapping. B-fULM enhances sensitivity and robustness in functional neuroimaging, overcoming limitations of conventional methods.

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    Area of Science:

    • Neuroimaging
    • Biomedical Engineering
    • Signal Processing

    Background:

    • Functional ultrasound localization microscopy (fULM) offers micron-scale resolution for brain-wide neural activity mapping.
    • Challenges in 3D fULM include limited sensitivity due to sparse microbubble (MB) detections, data sparsity, and reduced localization efficiency.

    Purpose of the Study:

    • To develop a novel statistical framework to enhance sensitivity and overcome limitations in 3D fULM.
    • To integrate microbubble backscattered amplitude with count-based detection for improved functional neuroimaging.

    Main Methods:

    • Developed a 3D statistical framework modeling MB arrivals as a Poisson process.
    • Incorporated localization efficiency, detection probability, and backscattered amplitude into the model.
    • Validated the approach using 3D MB advection simulations and in vivo rat brain experiments.

    Main Results:

    • Backscattering fULM (B-fULM) improves functional sensitivity, especially at high MB concentrations where conventional fULM saturates.
    • B-fULM maintained sensitivity in simulations where conventional fULM failed.
    • In vivo experiments showed significant SNR gains (18% in somatosensory cortex, 61% in thalamus) with B-fULM.

    Conclusions:

    • B-fULM provides a practical and sensitive method for super-resolved 3D functional neuroimaging.
    • The integration of amplitude and count-based methods enhances the robustness of neural activity mapping.
    • B-fULM preserves high spatial resolution while improving functional sensitivity.