Photoacoustic computed tomography for functional human brain imaging [Invited

Capitalizing on endogenous hemoglobin contrast, photoacoustic-computed tomography (PACT), a deep-tissue high-resolution imaging modality, has drawn increasing interest in neuroimaging. However, most existing studies are limited to functional imaging on the cortical surface and the deep brain structural imaging capability of PACT has never been demonstrated. Here, we explicitly studied the limiting factors of deep brain PACT imaging. We found that the skull distorted the acoustic signal and blood suppressed the structural contrast from other chromophores. When the two effects are mitigated, PACT can potentially provide high-resolution label-free imaging of structures in the entire mouse brain. With [Formula: see text] in-plane resolution, we can clearly identify major structures of the brain, which complements magnetic resonance microscopy for imaging small-animal brain structures. Spectral PACT studies indicate that structural contrasts mainly originate from cytochrome distribution and that the presence of lipid sharpens the image contrast; brain histology results provide further validation. The feasibility of imaging the structure of the brain in vivo is also discussed. Our results demonstrate that PACT is a promising modality for both structural and functional brain imaging.

Photoacoustic imaging (PAI) provides optical contrast at depth beyond the optical transport mean free path. From the generation of ultrasound by light absorption, images can be reconstructed at the acoustic resolution ( 100 μm) with a penetration of a few cm. The design of imaging systems often leads to limited view artifacts, where a part of the information needed for a complete reconstruction of the objects is missing. We theoretically show that a dynamic approach based on the analysis of fluctuations induced by blood flow can suppress visibility artefacts. We demonstrate the performance of 3D Photoacoustic Fluctuation imaging (PAFI) using a spherical array with limited number of channels (256 elements, 8 MHz) in the chicken embryo model. Due to the low number of channels, standard PAI reconstructions additionally suffer from a poor contrast, which is enhanced by 2 to 3-fold using PAFI. We present an implementation of simultaneous PAFI and Ultrasound Power Doppler and present some results with coupled flow direction evaluations and optical contrast. Photoacoustic fluctuation imaging overcomes many limitations of conventional imaging and will be further evaluated for in-vivo imaging.

Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a PACT system equipped with a high frequency linear transducer array for mapping the microvascular network of a whole mouse brain with the skull intact and studying its hemodynamic activities. The linear array was scanned in the coronal plane to collect data from different angles, and full-view images were synthesized from the limited-view images in which vessels were only partially revealed. We investigated spontaneous neural activities in the deep brain by monitoring the concentration of hemoglobin in the blood vessels and observed strong interhemispherical correlations between several chosen functional regions, both in the cortical layer and in the deep regions. We also studied neural activities during an epileptic seizure and observed the epileptic wave spreading around the injection site and the wave propagating in the opposite hemisphere.

Photoacoustic computed tomography (PACT) reveals biological structures, pharmacokinetics, and physiological functions. Although a premium PACT system with many ultrasound (US) transducers delivers high‐quality volumetric imaging, it suffers from high system costs and slow temporal resolution. Here, using a limited number of US elements, a hybrid diffusion model (HD‐PACT) is demonstrated that enhances dynamic multiparametric (structural, functional, and contrast‐enhanced) 3D PACT. Using just 256 out of the 1024 elements in a premier hemispherical US array for PACT, HD‐PACT improves structural images acquired in different planes, organisms, and wavelengths. In functional imaging, HD‐PACT enables 256‐element PACT to observe hypoxia, pharmacokinetics, and angiogenesis during tumor progression. Lastly, HD‐PACT is transferable to low‐end PACT (only 128 US elements), where it dynamically captures contrast‐free/enhanced organs, oxygen‐perturbed brains, and cardiac dynamics with high spatiotemporal resolution in live animals. It is believed that HD‐PACT will be valuable in oncology, cardiology, pharmacology, and endocrinology.

Photoacoustic computed tomography (PACT) is an emerging computed imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the absorbed optical energy density within tissue. If the object possesses spatially variant acoustic properties that are unaccounted for by the reconstruction algorithm, the estimated image can contain distortions. While reconstruction algorithms have recently been developed for compensating for this effect, they generally require the objects acoustic properties to be known a priori. To circumvent the need for detailed information regarding an objects acoustic properties, we have previously proposed a half-time reconstruction method for PACT. A half-time reconstruction method estimates the PACT image from a data set that has been temporally truncated to exclude the data components that have been strongly aberrated. In this approach, the degree of temporal truncation is the same for all measurements. However, this strategy can be improved upon it when the approximate sizes and locations of strongly heterogeneous structures such as gas voids or bones are known. In this work, we investigate PACT reconstruction algorithms that are based on a variable temporal data truncation (VTDT) approach that represents a generalization of the half-time reconstruction approach. In the VTDT approach, the degree of temporal truncation for each measurement is determined by the distance between the corresponding transducer location and the nearest known bone or gas void location. Reconstructed images from a numerical phantom is employed to demonstrate the feasibility and effectiveness of the approach.

We report on a new experimental method for enhanced backscattering spectroscopy (EBS) of strongly scattering media over a bandwidth from 530-1000 nm. The instrument consists of a supercontinuum light source and an angle-dependent detection system using a fiber-coupled grating spectrometer. Using a combination of two setups, the backscattered intensity is obtained over a large angular range and using circularly polarized light. We present broadband EBS of a TiO(2) powder and of a strongly scattering porous GaP layer. In combination with theoretical model fits, the EBS system yields the optical transport mean free path over the available spectral window.

Coherent backscattering measurement was applied for the study of microstructures in emulsified liquids. An enhanced component towards the backscattering direction emerges superimposed on the diffuse light scattering from a sample with randomly dispersed scatterers, giving evidence of the weak localization of light in random systems. Accurate measurement of the coherent backscattering peak gives us information on the optical transport mean free path in the sample, which leads to an estimation of the droplet size in emulsion. A new measurement system was developed and the clear backscattering peaks were successfully observed for various kinds of emulsions. The key technique of the present experiment was to decrease the laser speckle by stirring the liquid. The result obtained for heptane/AOT/water emulsion was qualitatively related to the droplet size which could be controlled by changing the amount of added salt. The effect of excluded volume on the scattering mean free path was discussed.

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.

Conventional photoacoustic computed tomography (PACT) images the spatial distribution of optical absorption, which is approximated as an isotropic optical property. The optical absorption of many biological tissues, however, is anisotropic. This anisotropy, known as dichroism or diattenuation, encodes rich information about molecular conformation and structural alignment. Here we report a novel imaging method called dichroism-sensitive PACT (DS-PACT). Using a lock-detection strategy, our method can measure the amplitude of tissue’s dichroism and the orientation of the optic axis of uniaxial dichroic tissue, even at a depth of 3.25 transport mean free paths. We experimentally demonstrated DS-PACT by imaging plastic polarizers and ex vivo bovine tendons deep inside scattering media. Our method extends the functionality of PACT to include a new capability, imaging tissue absorption anisotropy.

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.

To study patients with crossed aphasia (aphasia secondary to lesions in the right hemisphere in right-handed patients) with functional brain imaging using positron emission tomography (PET) or single photon emission computed tomography (SPECT); to see whether left hemisphere structures were metabolically depressed during the acute phase and, in 1 patient, during recovery; and to review the modern literature on crossed aphasia, with special reference to left hemisphere involvement. Case studies of 3 patients with crossed aphasia, including language testing, computed tomographic scanning, and functional imaging with PET or SPECT. Hospital case studies. Three right-handed patients with crossed aphasia secondary to acute infarctions in the right hemisphere and left hemiparesis. All 3 patients were studied by means of bedside language testing, computed tomographic scanning, and functional brain imaging with PET or SPECT. Patient 1 also underwent serial testing with the Boston Diagnostic Aphasia Examination and follow-up PET scanning after 2 months of recovery. Clinical examination in all 3 patients and follow-up Boston Diagnostic Aphasia Examination and PET scanning in patient 1. Two patients had severe global aphasia and 1 had Broca aphasia. In all cases, computed tomographic scans failed to reveal any left hemispheric lesions. Functional imaging with PET or SPECT showed extensive hypometabolism or hypoperfusion in the right hemisphere, with initial reductions in the left hemisphere as well. In patient I, a follow-up PET image showed only persistent hypometabolism in the right hemisphere. These findings suggest that abnormal dominance for at least some language functions in the right hemisphere underlies the syndrome of crossed aphasia. Diaschisis, or functional depression of the anatomically normal left hemisphere, was seen in all 3 patients during the acute phase, but not in patient 1 after recovery had begun.

Photoacoustic computed tomography (PACT) has emerged as a unique and promising technology for multiscale biomedical imaging. To fully realize its potential for various preclinical and clinical applications, development of systems with high imaging speed, reasonable cost, and manageable data flow are needed. Sparse-sampling PACT with advanced reconstruction algorithms, such as compressed-sensing reconstruction, has shown potential as a solution to this challenge. However, most such algorithms require iterative reconstruction and thus intense computation, which may lead to excessively long image reconstruction times. Here, we developed a principal component analysis (PCA)-based PACT (PCA-PACT) that can rapidly reconstruct high-quality, three-dimensional (3-D) PACT images with sparsely sampled data without requiring an iterative process. In vivo images of the vasculature of a human hand were obtained, thus validating the PCA-PACT method. The results showed that, compared with the back-projection (BP) method, PCA-PACT required ∼50% fewer measurements and ∼40% less time for image reconstruction, and the imaging quality was almost the same as that for BP with full sampling. In addition, compared with compressed sensing-based PACT, PCA-PACT had approximately sevenfold faster imaging speed with higher imaging accuracy. This work suggests a promising approach for low-cost, 3-D, rapid PACT for various biomedical applications.

Deep Learning for scaling large-aperture photoacoustic computed tomography : From single fingers to the human hand.

Functional brain imaging has tremendous applications. The existing methods for functional brain imaging include functional Magnetic Resonant Imaging (fMRI), scalp electroencephalography (EEG), implanted EEG, magnetoencephalography (MEG) and Positron Emission Tomography (PET), which have been widely and successfully applied to various brain imaging studies. To develop a new method for functional brain imaging, here we show that the dielectric at a brain functional site has a dynamic nature, varying with local neuronal activation as the permittivity of the dielectric varies with the ion concentration of the extracellular fluid surrounding neurons in activation. Therefore, the neuronal activation can be sensed by a radiofrequency (RF) electromagnetic (EM) wave propagating through the site as the phase change of the EM wave varies with the permittivity. Such a dynamic nature of the dielectric at a brain functional site provides the basis for an RF EM wave approach to detecting and imaging neuronal activation at brain functional sites, leading to an RF EM wave approach to functional brain imaging.

.SignificanceSkin color affects light penetration leading to differences in its absorption and scattering properties. COVID-19 highlighted the importance of understanding of the interaction of light with different skin types, e.g., pulse oximetry (PO) unreliably determined oxygen saturation levels in people from Black and ethnic minority backgrounds. Furthermore, with increased use of other medical wearables using light to provide disease information and photodynamic therapies to treat skin cancers, a thorough understanding of the effect skin color has on light is important for reducing healthcare disparities.AimThe aim of this work is to perform a thorough review on the effect of skin color on optical properties and the implication of variation on optical medical technologies.ApproachPublished in vivo optical coefficients associated with different skin colors were collated and their effects on optical penetration depth and transport mean free path (TMFP) assessed.ResultsVariation among reported values is significant. We show that absorption coefficients for dark skin are to 74% greater than for light skin in the 400 to 1000 nm spectrum. Beyond 600 nm, the TMFP for light skin is greater than for dark skin. Maximum transmission for all skin types was beyond 940 nm in this spectrum. There are significant losses of light with increasing skin depth; in this spectrum, depending upon Fitzpatrick skin type (FST), on average 14% to 18% of light is lost by a depth of 0.1 mm compared with 90% to 97% of the remaining light being lost by a depth of 1.93 mm.ConclusionsCurrent published data suggest that at wavelengths beyond 940 nm light transmission is greatest for all FSTs. Data beyond 1000 nm are minimal and further study is required. It is possible that the amount of light transmitted through skin for all skin colors will converge with increasing wavelength enabling optical medical technologies to become independent of skin color.