Imaging the human body's morphological and angiographic information is essential for diagnosing, monitoring, and treating medical conditions. Ultrasonography performs the morphological assessment of the soft tissue based on acoustic impedance variations, whereas photoacoustic tomography (PAT) can visualize blood vessels based on intrinsic hemoglobin absorption. Three-dimensional (3D) panoramic imaging of the vasculature is generally not practical in conventional ultrasonography with limited field-of-view (FOV) probes, and PAT does not provide sufficient scattering-based soft tissue morphological contrast. Complementing each other, fast panoramic rotational ultrasound tomography (RUST) and PAT are integrated for hybrid rotational ultrasound and photoacoustic tomography (RUS-PAT), which obtains 3D ultrasound structural and PAT angiographic images of the human body quasi-simultaneously. The RUST functionality is achieved in a cost-effective manner using a single-element ultrasonic transducer for ultrasound transmission and rotating arc-shaped arrays for 3D panoramic detection. RUST is superior to conventional ultrasonography, which either has a limited FOV with a linear array or is high-cost with a hemispherical array that requires both transmission and receiving. By switching the acoustic source to a light source, the system is conveniently converted to PAT mode to acquire angiographic images in the same region. Using RUS-PAT, we have successfully imaged the human head, breast, hand, and foot with a 10 cm diameter FOV, submillimeter isotropic resolution, and 10 s imaging time for each modality. The 3D RUS-PAT is a powerful tool for high-speed, 3D, dual-contrast imaging of the human body with potential for rapid clinical translation.

Simultaneous acquisition of functional near-infrared spectroscopy (fNIRS) and magnetoencephalography (MEG) provides complementary hemodynamic and electrophysiological information for studies of neurovascular coupling and has previously been demonstrated using fiber-based fNIRS implementations. Compared with fiber-based systems, fiberless fNIRS is lightweight and eliminates fiber-induced mechanical constraints; however, its integration with MEG remains challenging due to stringent magnetic compatibility requirements. Here, we present a magnetically compatible and fiberless fNIRS system enabling flexible and non-invasive multimodal imaging with optically pumped magnetometer (OPM) MEG. We developed magnetically compatible source/detector optodes and implemented a multipole moment flexible printed circuit design that suppresses driving-current-induced magnetic fields by more than 1000-fold. The optodes and cables generated less than 1 nT of magnetic field at ∼1 cm from the OPM sensor, with no measurable impact on OPM sensitivity. Simultaneous fiberless fNIRS and OPM-MEG acquisition was demonstrated in a somatosensory paradigm, capturing concurrent hemodynamic and evoked magnetic responses, thereby demonstrating the feasibility and robustness of our integrated multimodal system. By addressing a key magnetic-compatibility barrier between fiberless fNIRS and OPM-MEG, this work paves the way for neurovascular coupling studies using flexible multimodal platforms, and supports future developments in wearable multimodal neuroimaging and multimodal brain-computer interface systems.

Background Microcirculatory disturbances emerging during ischemia–reperfusion critically influence tissue perfusion in acute ischemic stroke. However, existing imaging approaches are limited in their ability to continuously capture brain-wide cerebrovascular dynamics across spatial scales, restricting observation of rapid vascular and microcirculatory changes during the ischemia–reperfusion process. Methods We developed a 2.10-g dual-plane wearable ultrasound imaging platform that enables stable, long-duration monitoring of cerebrovascular dynamics throughout the entire ischemia–reperfusion process in mice. Functional ultrasound imaging was used to assess vascular function and cerebral blood volume dynamics, while ultrasound localization microscopy provided micrometer-resolution mapping of the microvascular architecture. Spatiotemporal analyses were performed to characterize hemodynamic wave propagation, vascular structural deformation, and regional differences in reperfusion dynamics. Results Simultaneous assessment of cerebral blood volume and microvascular architecture revealed multiple dimensions of cerebrovascular dynamics during ischemia–reperfusion, including recurrent spreading depolarization–associated hemodynamic waves, progressive vascular deformation and heterogeneous patterns of microvascular reperfusion. Continuous ULM imaging further enabled longitudinal tracking of perfused vascular pathways, highlighting dynamic changes in the spatial organization of microvascular networks over time. Conclusions This wearable dual-plane ultrasound platform enables long-duration monitoring of brain-wide cerebrovascular dynamics while providing super-resolution characterization of the microvascular network. The approach offers a methodological framework for investigating the temporal evolution of cerebrovascular organization during acute ischemia–reperfusion.

Photoacoustic computed tomography is promising for noninvasive imaging of cerebral function but is limited by skull-induced acoustic aberrations. Moreover, strong superficial signals from the scalp often produce reverberations within the skull, which interfere with cortical signals and introduce artifacts in the cortical imaging region. Conventional universal back-projection (UBP) and full-wave-based reconstruction algorithms fail to adequately mitigate these effects, resulting in degraded image fidelity. To address these challenges, we propose a hybrid framework, termed Radon Transform–Full Waveform Inversion (RT–FWI), to simultaneously suppress scalp artifacts and correct for skull-induced acoustic aberrations. The method begins with a high-resolution linear Radon transform to isolate scalp-related multiple reflections without relying on prior velocity models. The separated signal components are used to reconstruct a cleaned wavefield and to formulate a spatially adaptive regularization term that constrains the subsequent elastic FWI process, thereby preventing artifact reinforcement. Numerical simulations and ex vivo experiments demonstrate that RT–FWI outperforms both UBP and conventional FWI, improving the axial spatial resolution from 1.14mm to 0.28mm and the structural similarity index from 0.415 to 0.875. The proposed approach constitutes an advancement toward transcranial photoacoustic brain imaging.

Photoacoustic computed tomography (PACT) combines optical absorption contrast with acoustic detection for high-resolution deep-tissue imaging. A persistent challenge is that unknown speed-of-sound (SoS) heterogeneity changes acoustic time-of-flight, causing defocusing artifacts when reconstruction assumes a uniform SoS. Existing SoS-adaptive methods either rely on calibrated acoustic priors or optimize dense physical medium models, which becomes expensive and difficult to scale in 3D. We propose PAGS, a differentiable framework for blind autofocusing PACT via speed-of-sound-adaptive Gaussian splatting. PAGS represents the initial pressure field with sparse Gaussian photoacoustic (PA) sources and replaces explicit medium recovery with a compact anisotropic path-averaged SoS (ASoS) field parameterized by spherical harmonic probes. This latent propagation field directly controls source-to-transducer arrival-time alignment, while an analytic Gaussian acoustic projection maps the source representation to transducer signals efficiently. The resulting closed-loop signal-domain optimization jointly updates the Gaussian PA source parameters and the ASoS field from measured data, without calibrated SoS priors. Experiments on simulated and physical phantom data demonstrate improved reconstruction sharpness under heterogeneous acoustic media, robustness to sparse-view sampling, and computational benefits from the analytic Gaussian projection.

Electrical conductivity is a critical biomarker for cellular activity and a fundamental parameter in material science. However, achieving label-free, contact-free conductivity measurements with optical-scale resolution remains a challenge. Here, we introduce a magneto-photoacoustic coupling effect that enables conductivity mapping through photoacoustic excitation in the presence of a static magnetic field. The governing equation for this phenomenon is derived, demonstrating a linear relationship between the induced photoacoustic pressure and the product of the local magnetic flux density squared and electrical conductivity. This theoretical framework is further validated using numerical simulation, which showcases the method’s capability for optical-resolution conductivity imaging. The proposed approach unlocks new opportunities for applications ranging from real-time tracking of neuronal ion channel dynamics to nanoscale defect characterization in metallic and semiconductor materials.

Transcranial photoacoustic computed tomography presents challenges in human brain imaging due to skull-induced acoustic aberration. Existing full-wave image reconstruction methods rely on a unified elastic wave equation for skull shear and longitudinal wave propagation, therefore demanding substantial computational resources. We propose an efficient discrete imaging model based on finite element discretization. The elastic wave equation for solids is solely applied to the hard-tissue skull region, while the soft-tissue or coupling-medium region that dominates the simulation domain is modeled with the simpler acoustic wave equation for liquids. The solid-liquid interfaces are explicitly modeled with elastic-acoustic coupling. Furthermore, finite element discretization allows coarser, irregular meshes to conform to object geometry. These factors significantly reduce the linear system size by 20 times to facilitate accurate whole-brain simulations with improved speed. We derive a matched forward-adjoint operator pair based on the model to enable integration with various optimization algorithms. We validate the reconstruction framework through numerical simulations and phantom experiments.

Miniaturized spin-exchange relaxation-free (SERF) magnetometers are recognized for their exceptional sensitivity and ability to function without the need for cryogenic cooling. These devices are particularly valuable for detecting ultra-weak magnetic fields, such as those generated by the human brain. However, the use of miniaturized SERF magnetometers has been limited due to their narrow bandwidth. In this study, we developed a compact triaxial SERF magnetometer that incorporates closed-loop feedback, significantly broadening its bandwidth to 1.1 kHz. This magnetometer achieves high sensitivity, approximately 35 fT/(Hz)(1/2) across each axis and remains compact, with dimensions of 13.8 x 21.0 x 44.0 mm. It accurately measured the time course of pulsed sinusoidal magnetic fields, with each pulse containing a single cycle of a 1030 Hz sinusoidal signal at a 1 pT amplitude. Our magnetometer also successfully detected various magnetic fields generated by the human brain, including alpha rhythms, auditory evoked fields (AEFs), and steady-state visual evoked fields. Looking forward, this high-bandwidth, high-sensitivity, and compact triaxial SERF magnetometer showcases its great potential for advancing magnetoencephalography (MEG) and opening new research avenues in neuroscience and clinical research.

The current magnetoencephalography (MEG) systems, which rely on cables for control and signal transmission, do not fully realize the potential of wearable optically pumped magnetometers (OPM). This study presents a significant advancement in wireless OPM-MEG by reducing magnetization in the electronics and developing a tailored wireless communication protocol. Our protocol effectively eliminates electromagnetic interference, particularly in the critical frequency bands of MEG signals, and accurately synchronizes the acquisition and stimulation channels with the host computer's clock. We have successfully achieved single-channel wireless OPM-MEG measurement and demonstrated its reliability by replicating three well-established experiments: The alpha rhythm, auditory evoked field, and steady-state visual evoked field in the human brain. Our prototype wireless OPM-MEG system not only streamlines the measurement process but also represents a major step forward in the development of wearable OPM-MEG applications in both neuroscience and clinical research.

A miniaturized photoacoustic fiberscope has been developed, featuring a lateral resolution of 9 microns and a lightweight design at 4.5 grams. Engineered to capture hemodynamic processes at single-blood-vessel resolution at a rate of 0.2 Hz, this device represents an advancement in head-mounted tools for exploring intricate brain activities in mobile animals. A head-mounted photoacoustic fiberscope enables hemodynamic imaging in mobile mice.

Geometric calibration of ultrasound transducer arrays is critical to optimizing the performance of photoacoustic computed tomography (PACT) systems. We present a geometric calibration method that is applicable to a wide range of PACT systems. We obtain the speed of sound and point source locations using surrogate methods, which results in a linear problem in the transducer coordinates. We characterize the estimation error, which informs our choice of the point source arrangement. We demonstrate our method in a three-dimensional PACT system and show that our method improves the contrast-to-noise ratio, the size, and the spread of point source reconstructions by 80±19%, 19±3%, and 7±1%, respectively. We reconstruct the images of a healthy human breast before and after calibration and find that the calibrated image reveals vasculatures that were previously invisible. Our work introduces a method for geometric calibration in PACT and paves the way for improving PACT image quality.

Photoacoustic computed tomography (PACT) is emerging as a new technique for functional brain imaging, primarily due to its capabilities in label-free hemodynamic imaging. Despite its potential, the transcranial application of PACT has encountered hurdles, such as acoustic attenuations and distortions by the skull and limited light penetration through the skull. To overcome these challenges, we have engineered a PACT system that features a densely packed hemispherical ultrasonic transducer array with 3072 channels, operating at a central frequency of 1 MHz. This system allows for single-shot 3D imaging at a rate equal to the laser repetition rate, such as 20 Hz. We have achieved a single-shot light penetration depth of approximately 9 cm in chicken breast tissue utilizing a 750 nm laser (withstanding 3295-fold light attenuation and still retaining an SNR of 74) and successfully performed transcranial imaging through an ex vivo human skull using a 1064 nm laser. Moreover, we have proven the capacity of our system to perform single-shot 3D PACT imaging in both tissue phantoms and human subjects. These results suggest that our PACT system is poised to unlock potential for real-time, in vivo transcranial functional imaging in humans.

Complementary to mainstream cardiac imaging modalities for preclinical research, photoacoustic computed tomography (PACT) can provide functional optical contrast with high imaging speed and resolution. However, PACT has not been demonstrated to reveal the dynamics of whole cardiac anatomy or vascular system without surgical procedure (thoracotomy) for tissue penetration. Here, we achieved non-invasive imaging of rat hearts using the recently developed three-dimensional PACT (3D-PACT) platform, demonstrating the regulated illumination and detection schemes to reduce the effects of optical attenuation and acoustic distortion through the chest wall; thereby, enabling unimpeded visualization of the cardiac anatomy and intracardiac hemodynamics following rapidly scanning the heart within 10 s. We further applied 3D-PACT to reveal distinct cardiac structural and functional changes among the healthy, hypertensive, and obese rats, with optical contrast to uncover differences in cardiac chamber size, wall thickness, and hemodynamics. Accordingly, 3D-PACT provides high imaging speed and nonionizing penetration to capture the whole heart for diagnosing the animal models, holding promises for clinical translation to cardiac imaging of human neonates.

Herein we report the first in-human transcranial imaging of brain function using photoacoustic computed tomography. Functional responses to benchmark motor tasks were imaged on both the skull-less and the skull-intact hemispheres of a hemicraniectomy patient. The observed brain responses in these preliminary results demonstrate the potential of photoacoustic computed tomography for achieving transcranial functional imaging.

Recent advances in functional ultrasound imaging (fUS) and photoacoustic tomography (PAT) offer powerful tools for studying brain function. Complementing each other, fUS and PAT, respectively, measure the cerebral blood flow (CBF) and hemoglobin concentrations, allowing synergistic characterization of cerebral hemodynamics. Here, cross‐ray ultrasound tomography (CRUST) and its combination with PAT are presented. CRUST employs a virtual point source from a spherically focused ultrasonic transducer (SFUST) to provide widefield excitation at a 4‐kHz pulse repetition frequency. A full‐ring‐shaped ultrasonic transducer array whose imaging plane is orthogonal to the SFUST's acoustic axis receives scattered ultrasonic waves. Superior to conventional fUS, whose sensitivity to blood flow is angle‐dependent and low for perpendicular flow, the crossed transmission and panoramic detection fields of CRUST provide omnidirectional sensitivity to CBF. Using CRUST‐PAT, the CBF, oxygen saturation, and hemoglobin concentration changes of the mouse brain during sensory stimulation are measured, with a field of view of ≈7 mm in diameter, spatial resolution of ≈170 µm, and temporal resolution of 200 Hz. The results demonstrate CRUST‐PAT as a unique tool for studying cerebral hemodynamics.

Multimodal neuroimaging plays an important role in neuroscience research. Integrated noninvasive neuroimaging modalities, such as magnetoencephalography (MEG), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), allow neural activity and related physiological processes in the brain to be precisely and comprehensively depicted, providing an effective and advanced platform to study brain function. Noncryogenic optically pumped magnetometer (OPM) MEG has high signal power due to its on-scalp sensor layout and enables more flexible configurations than traditional commercial superconducting MEG. Here, we integrate OPM-MEG with EEG and fNIRS to develop a multimodal neuroimaging system that can simultaneously measure brain electrophysiology and hemodynamics. We conducted a series of experiments to demonstrate the feasibility and robustness of our MEG-EEG-fNIRS acquisition system. The complementary neural and physiological signals simultaneously collected by our multimodal imaging system provide opportunities for a wide range of potential applications in neurovascular coupling, wearable neuroimaging, hyperscanning and brain-computer interfaces.

Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.

The successes of magnetic resonance imaging and modern optical imaging of human brain function have stimulated the development of complementary modalities that offer molecular specificity, fine spatiotemporal resolution, and sufficient penetration simultaneously. By virtue of its rich optical contrast, acoustic resolution, and imaging depth far beyond the optical transport mean free path (∼1 mm in biological tissues), photoacoustic computed tomography (PACT) offers a promising complementary modality. In this article, PACT for functional human brain imaging is reviewed in its hardware, reconstruction algorithms, in vivo demonstration, and potential roadmap.