A head-mounted photoacoustic fiberscope for hemodynamic imaging in mobile mice.

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 method for the geometric calibration of ultrasound transducer arrays with arbitrary geometries.

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.

Single-shot 3D photoacoustic computed tomography with a densely packed array for transcranial functional imaging.

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.

Non-invasive photoacoustic computed tomography of rat heart anatomy and function.

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.

Clinical and fundus imaging features of acute macular neuroretinopathy associated with COVID-19 / 中华眼底病杂志

Objective:To observe the clinical and fundus imaging features of acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective case study. A total of 32 eyes of 18 patients diagnosed of AMN associated with COVID-19 at Chengdu Aidi Eye Hospital from December 2022 to February 2023 were included. All patients had a history of fever 1 to 5 days prior to ocular onset and tested positive for SARS CoV-2 antigen. All patients were examined by best-corrected visual acuity (BCVA), color fundus photography, scanning laser ophthalmoscope (SLO), infrared fundus photography (IR), and optical coherence tomography (OCT); OCT angiography, visual field and multifocal electroretinogram (mf-ERG) were performed in 6 patients (11 eyes), 3 patients (6 eyes) and 1 patient (2 eyes), respectively. Follow-up time was 8-10 weeks. The clinical and fundus imaging features were observed and analyzed.Results:There were 6 males (12 eyes) and 12 females (20 eyes), aged from 15 to 36 years, with the mean age of (28.00±5.86) years. Fourteen patients were bilateral and 4 patients were unilateral. The time from the onset of eye symptoms to seeing a doctor was ranged from 1 day to 8 weeks. Among them, 6 patients (10 eyes) visited the doctor within 3 days of onset, while 12 patients (22 eyes) visited the doctor after 3 days of onset. The BCVA was 0.80±0.29. Fundus color photography and SLO examination showed that only 2 patients (4 eyes) showed sheet or petal-like dark red lesions in the macular area, and no obvious abnormal changes were observed in other patients. No obvious abnormalities were found in AF examination of all patients. IR examination showed no significant abnormality in 6 cases which came to hospital within 3 days after the onset, but irregular hyporeflective dark shadow lesions in the macular region of patients with more than 3-day course of disease was observed. OCT examinations of all eyes showed hyperreflective band or patchy lesion on the outer plexiform layer (OPL) and outer nuclear layer (ONL) and affect the ellipsoid zone (EZ) and interdigitation zone (IZ). In 11 eyes of 6 patients undergoing OCTA examination, the blood flow density of the choroidal capillary layer in the focal area decreased. In 6 eyes of 3 patients who underwent visual field examination, the physiologic scotoma was slightly enlarged. One patient (2 eyes) receiving mf-ERG showed a concave reduction in macular center amplitude. The hyperreflective band lesion on OPL and ONL disappear rapidly within 2 weeks, while the continuity of EZ recovered slowly, and the disruption of IZ kept existing for more than 10 weeks.Conclusions:Most AMN associated with COVID-19 are young women; IR showed irregular weak reflex in the lesion area. OCT showed strong OPL and ONL reflection. OCTA was characterized by decreased blood flow density in the choroidal capillary layer of the focal area.

Cross-Ray Ultrasound Tomography and Photoacoustic Tomography of Cerebral Hemodynamics in Rodents.

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 with optically pumped magnetometers: A simultaneous MEG-EEG-fNIRS acquisition system.

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.

Massively parallel functional photoacoustic computed tomography of the human brain.

Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging of the human brain requires bulky equipment for the generation of magnetic fields. Photoacoustic computed tomography obviates the need for magnetic fields by using light and sound to measure deoxyhaemoglobin and oxyhaemoglobin concentrations to then quantify oxygen saturation and blood volumes. Yet, the available imaging speeds, fields of view (FOV), sensitivities and penetration depths have been insufficient for functional imaging of the human brain. Here, we show that massively parallel ultrasonic transducers arranged hemispherically around the human head can produce tomographic images of the brain with a 10-cm-diameter FOV and spatial and temporal resolutions of 350 µm and 2 s, respectively. In patients who had a hemicraniectomy, a comparison of functional photoacoustic computed tomography and 7 T BOLD functional magnetic resonance imaging showed a strong spatial correspondence in the same FOV and a high temporal correlation between BOLD signals and photoacoustic signals, with the latter enabling faster detection of functional activation. Our findings establish the use of photoacoustic computed tomography for human brain imaging.

Photoacoustic computed tomography for functional human brain imaging [Invited].

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.

High-speed three-dimensional photoacoustic computed tomography for preclinical research and clinical translation.

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.

Transcranial photoacoustic computed tomography based on a layered back-projection method.

A major challenge of transcranial human brain photoacoustic computed tomography (PACT) is correcting for the acoustic aberration induced by the skull. Here, we present a modified universal back-projection (UBP) method, termed layered UBP (L-UBP), that can de-aberrate the transcranial PA signals by accommodating the skull heterogeneity into conventional UBP. In L-UBP, the acoustic medium is divided into multiple layers: the acoustic coupling fluid layer between the skull and detectors, the skull layer, and the brain tissue layer, which are assigned different acoustic properties. The transmission coefficients and wave conversion are considered at the fluid-skull and skull-tissue interfaces. Simulations of transcranial PACT using L-UBP were conducted to validate the method. Ex vivo experiments with a newly developed three-dimensional PACT system with 1-MHz center frequency demonstrated that L-UBP can substantially improve the image quality compared to conventional UBP.

Iterative image reconstruction in transcranial photoacoustic tomography based on the elastic wave equation.

Photoacoustic computed tomography (PACT) is an emerging computed imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the photoacoustically induced initial pressure distribution within tissue. The PACT reconstruction problem corresponds to a time-domain inverse source problem, where the initial pressure distribution is recovered from the measurements recorded on an aperture outside the support of the source. A major challenge in transcranial PACT of the brain is to compensate for aberrations and attenuation in the measured data due to the propagation of the photoacoustic wavefields through the skull. To properly account for these effects, a wave equation-based inversion method can be employed that can model the heterogeneous elastic properties of the medium. In this study, an optimization-based image reconstruction method for 3D transcranial PACT is developed based on the elastic wave equation. To accomplish this, a forward-adjoint operator pair based on a finite-difference time-domain discretization of the 3D elastic wave equation is utilized to compute penalized least squares estimates of the initial pressure distribution. Computer-simulation and experimental studies are conducted to investigate the robustness of the reconstruction method to model mismatch and its ability to effectively resolve cortical and superficial brain structures.

Microwave-induced thermoacoustic tomography through an adult human skull.

PURPOSE: To demonstrate the feasibility of microwave-induced thermoacoustic tomography (TAT) of adult human brain. METHODS: We analyzed the electric field distribution radiated from an antenna to acquire homogeneous illumination. We first imaged the anatomical structures in a rat's trunk to validate the thermoacoustic contrast in vivo. We then imaged an agar cylinder through an adult human skull ex vivo to demonstrate transcranial penetration of both microwave and ultrasound. We also analyzed the specific absorption rate to show the conformance to the safety standard for human electromagnetic exposure. RESULTS: We successfully acquired cross-sectional images of the rat's trunk in vivo. Major blood vessels and organs are clearly visible. The transcranial image shows that TAT can image through the adult human skull and reveal an agar enclosed by the skull. CONCLUSIONS: Microwave-induced TAT of a rat's trunk in vivo and an agar phantom through an adult human skull ex vivo has been demonstrated experimentally. This study demonstrates both the TAT contrasts in vivo and the capability of transcranial imaging, showing potential of TAT for adult human brain imaging with high contrast and penetration.

An Optimization and Comparative Study of Air-Coupled CMUT Cells With Circular and Annular Geometries.

Air-coupled capacitive micromachined ultrasonic transducers (CMUTs) with annular cell geometry have recently been reported to have a promising transmit sensitivity. This paper reports three optimization schemes, which further improve the transmit sensitivity and also help achieve a reasonable comparison between the novel annular and conventional circular cells. Lumped element models of both cell types with laminate plate structures are presented. Based on these models, a design optimization flowchart was constructed to facilitate analytical optimization on the three schemes. Circular and annular CMUTs with a common 97-kHz natural resonance frequency were fabricated and characterized to verify the efficacy of the optimization principle. Using the optimization flowchart, annular and circular cells with frequencies ranging from 100 to 300 kHz were analytically optimized and then compared. The comparison results demonstrate that, given the same dc bias and ac excitation voltage, the output power density at the plate surface of the optimized annular cell is double that of the optimized circular cell. Additionally, when generating the same surface power density, an optimized annular cell requires either half the dc bias or half the ac excitation voltage of an optimized circular cell. This paper provides a practical optimization framework for CMUT cell design and demonstrates the superiority of annular cells for air-coupled applications.

Lumped element modeling of air-coupled capacitive micromachined ultrasonic transducers with annular cell geometry.

Air-coupled capacitive micromachined ultrasonic transducers (CMUTs) based on annular cell geometry have recently been reported. Finite element analysis and experimental studies have demonstrated their significant improvement in transmit efficiency compared with the conventional circular-cell CMUTs. Extending the previous work, this paper proposed a lumped element model of annular-cell CMUTs. Explicit expressions of the resonance frequency, modal vector, and static displacement of a clamped annular plate under uniform pressure were first derived based on the plate theory and curve fitting method. The lumped model of an annular CMUT cell was then developed by adopting the average displacement as the spatial variable. Using the proposed model, the ratio of average-to-maximum displacement was derived to be 8/15. Experimental and simulation studies on a fabricated annular CMUT cell verified the effectiveness of the lumped model. The proposed model provides an effective and efficient way to analyze and design air-coupled annular-cell CMUTs.

Capacitive micromachined ultrasonic transducers based on annular cell geometry for air-coupled applications.

A novel design of an air-coupled capacitive micromachined ultrasonic transducer (CMUT) with annular cell geometry (annular CMUT) is proposed. Finite element analysis shows that an annular cell has a ratio of average-to-maximum displacement (RAMD) of 0.52-0.58 which is 58-76% higher than that of a conventional circular cell. The increased RAMD leads to a larger volume displacement which results in a 48.4% improved transmit sensitivity and 127.3% improved power intensity. Single-cell annular CMUTs were fabricated with 20-µm silicon plates on 13.7-µm deep and 1.35-mm wide annular cavities using the wafer bonding technique. The measured RAMD of the fabricated CMUTs is 0.54. The resonance frequency was measured to be 94.5kHz at 170-V DC bias. The transmit sensitivity was measured to be 33.83Pa/V and 25.85Pa/V when the CMUT was excited by a continuous wave and a 20-cycle burst, respectively. The receive sensitivity at 170-V DC bias was measured to be 7.7mV/Pa for a 20-cycle burst, and 15.0mV/Pa for a continuous incident wave. The proposed annular CMUT design demonstrates a significant improvement in transmit efficiency, which is an important parameter for air-coupled ultrasonic transducers.