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In photoacoustic computed tomography (PACT) with short-pulsed laser excitation, wideband acoustic signals are generated in biological tissues with frequencies related to the effective shapes and sizes of the optically absorbing targets. Low-frequency photoacoustic signal components correspond to slowly varying spatial features and are often omitted during imaging due to the limited detection bandwidth of the ultrasound transducer, or during image reconstruction as undesired background that degrades image contrast. Here we demonstrate that low-frequency photoacoustic signals, in fact, contain functional and molecular information, and can be used to enhance structural visibility, improve quantitative accuracy, and reduce spare-sampling artifacts. We provide an in-depth theoretical analysis of low-frequency signals in PACT, and experimentally evaluate their impact on several representative PACT applications, such as mapping temperature in photothermal treatment, measuring blood oxygenation in a hypoxia challenge, and detecting photoswitchable molecular probes in deep organs. Our results strongly suggest that low-frequency signals are important for functional and molecular PACT.

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., Comment: 10 pages

Photoacoustic computed tomography (PACT) detects light-induced ultrasound waves to reconstruct the optical absorption contrast of the biological tissues. Due to its relatively deep penetration (several centimeters in soft tissue), high spatial resolution, and inherent functional sensitivity, PACT has great potential for imaging mouse brains with endogenous and exogenous contrasts, which is of immense interest to the neuroscience community. However, conventional PACT either assumes homogenous optical fluence within the brain or uses a simplified attenuation model for optical fluence estimation. Both approaches underestimate the complexity of the fluence heterogeneity and can result in poor quantitative imaging accuracy. To optimize the quantitative performance of PACT, we explore for the first time 3D Monte Carlo simulation to study the optical fluence distribution in a complete mouse brain model. We apply the MCX Monte Carlo simulation package on a digital mouse (Digimouse) brain atlas that has complete anatomy information. To evaluate the impact of the brain vasculature on light delivery, we also incorporate the whole-brain vasculature in the Digimouse atlas. The simulation results clearly show that the optical fluence in the mouse brain is heterogeneous at the global level and can decrease by a factor of five with increasing depth. Moreover, the strong absorption and scattering of the brain vasculature also induce the fluence disturbance at the local level. Our results suggest that both global and local fluence heterogeneity contributes to the reduced quantitative accuracy of the reconstructed PACT images of mouse brain., Comment: 16 pages, 6 figures, 1 table

Algorithms often appear as 'black boxes' to non-expert users. While prior work focuses on explainable representations and expert-oriented exploration, we propose and study an interactive approach using question answering to explain deterministic algorithms to non-expert users who need to understand the algorithms' internal states (e.g., students learning algorithms, operators monitoring robots, admins troubleshooting network routing). We construct XAlgo -- a formal model that first classifies the type of question based on a taxonomy and generates an answer based on a set of rules that extract information from representations of an algorithm's internal states, e.g., the pseudocode. A design probe in an algorithm learning scenario with 18 participants (9 for a Wizard-of-Oz XAlgo and 9 as a control group) reports findings and design implications based on what kinds of questions people ask, how well XAlgo responds, and what remain as challenges to bridge users' gulf of understanding algorithms.