O18 - Non-invasive deep-brain volumetric imaging with integrated photoacoustic tomography and ultrasound localization microscopy

Introduction: : Photoacoustic computed tomography (PACT) is a proven technology for imaging hemodynamics in deep brain of small animal models. PACT is inherently compatible with ultrasound (US) imaging, providing complementary contrast mechanisms. While PACT can quantify the brain’s oxygen saturation of hemoglobin (sO2), US imaging can probe the blood flow based on the Doppler effect. Further, by tracking gas-filled microbubbles, ultrasound localization microscopy (ULM) can map the blood flow velocity with sub-diffraction spatial resolution. We present 3D Photoacoustic Ultrasound Localization Microscopy (3D-PAULM), a non-invasive imaging platform that integrates photoacoustic computed tomography (PACT) and ultrasound localization microscopy (ULM) for volumetric deep-brain imaging. The system addresses major limitations in deep-tissue and transcranial imaging by combining the functional sensitivity of PACT with the super-resolution capability of ULM.

Materials and

Methods: : 3D-PAULM employs a 256-channel 2D hemispherical transducer array. The low central frequency operating at 4 MHz is designed to achieve deep penetration. The hemispherical geometry mitigates limited-view artifacts and reduce acoustic aberrations, yielding a more isotropic point spread function (PSF) compared to traditional matrix arrays. At each imaging location, 3D-PAULM provides volumetric imaging at up to 430 Hz for ultrasound and 30 Hz for photoacoustics, over an 8×8×8 mm³ field of view (FOV). Whole-brain imaging is achieved by stitching multiple volumes while maintaining high spatial and temporal resolution.The achieved resolution for PA imaging achieves 390 µm (axial) and 260 µm (lateral), while US imaging is 440 µm (axial) and 270 µm (lateral). The 3D ULM resolution is further improved to 48 µm estimated by Fourier Shell Curve (FSC).

Results, Conclusions, and Discussions:: 3D-PAULM enables co-registered anatomical and functional imaging, including vessel density, blood flow velocity, and oxygen saturation (sO₂) mapping across large volumes. Its capabilities are demonstrated in serval neurovascular applications: 1) Post-surgical stroke imaging, revealing ischemia, hypoxia, and altered vascular architecture in the affected hemisphere. 2) Epinephrine-induced cerebrovascular response, showing rapid vasodilation and perfusion changes. 3) Glymphatic clearance, tracking tracer transport in the CSF pathway. We expect that 3D-PAULM can find broad applications in studying deep brain functions on small animal models.

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