  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
(sO$_2$), 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. In this work, we present a 3D deep-brain imaging system that
seamlessly integrates PACT and ULM into a single device, 3D-PAULM. Using a low
ultrasound frequency of 4 MHz, 3D-PAULM is capable of imaging the whole-brain
hemodynamic functions with intact scalp and skull in a totally non-invasive
manner. Using 3D-PAULM, we studied the mouse brain functions with ischemic
stroke. Multi-spectral PACT, US B-mode imaging, microbubble-enhanced power
Doppler (PD), and ULM were performed on the same mouse brain with intrinsic
image co-registration. From the multi-modality measurements, we future
quantified blood perfusion, sO$_2$, vessel density, and flow velocity of the
mouse brain, showing stroke-induced ischemia, hypoxia, and reduced blood flow.
We expect that 3D-PAULM can find broad applications in studying deep brain
functions on small animal models.
