Three-dimensional Photoacoustic Imaging Research Articles

Beyond synthetic aperture focusing: deconvolution-based elevation resolution enhancement using simulated point spread function for linear array-based three-dimensional photoacoustic imaging.

This paper introduces a deconvolution-based method to enhance the elevation resolution of a linear array-based three-dimensional (3D) photoacoustic (PA) imaging system. PA imaging combines the high contrast of optical imaging with the deep, multi-centimeter spatial resolution of ultrasound (US) imaging, providing structural and functional information about biological tissues. Linear array-based 3D PA imaging is easily accessible and applicable for ex vivo studies, small animal research, and clinical applications in humans. However, its elevation resolution is limited by the acoustic lens geometry, which establishes a single elevation focus. Previous work used synthetic aperture focusing (SAF) to enhance elevation resolution, but the resolution achievable by SAF is constrained by the size of the elevation focus. Here, we introduce the application of Richardson-Lucy deconvolution, grounded in simulated point-spread-functions, to surpass the elevation resolution attainable with SAF alone. We validated this approach using both simulation and experimental data, demonstrating that the full-width-at-half-maximum of point targets on the elevation plane was reduced compared to using SAF only, suggesting resolution improvement. This method shows promise for improving 3D image quality of existing linear array-based PA imaging systems, offering potential benefits for disease diagnosis and monitoring.

Subcutaneous injection of hyaluronic acid leading to emboliom and recanalization process monitored in real time by three-dimensional photoacoustic imaging

This study describes a method for real-time examination of the microvascular system based on the three-dimensional photoacoustic imaging system to prevent arterial complications, especially vascular embolism, during hyaluronic acid (HA) injections. Chicken embryos were used to simulate the superficial blood vessels of human skin, and then the target area was imaged by the photoacoustic imaging system for three-dimensional vascular imaging, and then the syringe and blood vessels were monitored, and the syringe angle and penetration depth were adjusted in time using an injection device to avoid puncturing the arterial vasculature and clogging the blood vessels. HA was then injected into smaller vessels on the dorsum of the tongue in mice and into thicker vessels on the dorsal portion of the tongue in rats to mimic embolization, and the post-operative recovery was reflected by the changes in the pixel dots of the extracted part of the blocked blood vessels, and it was observed that the blood flow in the area of the fine vessels was restored in about 3 days, whereas blood flow in the area of the large vessels was restored in only about 1 h. The method presented in this paper allows precise guidance of injectable filler HA, which has good application prospects in improving the safety of injection micro-plastic surgery and reducing the experience requirements for medical personnel.

PreFlap: From Photoacoustic Tomography Images to Vascular Mapping Sheets for Improved Preoperative Flap Evaluation.

Advancements in technology have improved image acquisition and processing in the field of medical imaging, giving medical doctors the tools to implement effective medical care. In plastic surgery, despite advances in anatomical knowledge and technology, problems in preoperative planning for flap surgery remain. In this study, we propose a new protocol to analyze three-dimensional (3D) Photoacoustic tomography images and generate two-dimensional (2D) mapping sheets that can help surgeons identify perforators and the perfusion territory during preoperative planning. The core of this protocol is PreFlap, a new algorithm that converts 3D photoacoustic tomography images into 2D vascular mapping images. Experimental results demonstrate that PreFlap can improve preoperative flap evaluation, thus can greatly saving surgeons' time and improving surgical outcomes.

Compressed single-shot 3D photoacoustic imaging with a single-element transducer

Three-dimensional (3D) photoacoustic imaging (PAI) can provide rich information content and has gained increasingly more attention in various biomedical applications. However, current 3D PAI methods either involves pointwise scanning of the 3D volume using a single-element transducer, which can be time-consuming, or requires an array of transducers, which is known to be complex and expensive. By utilizing a 3D encoder and compressed sensing techniques, we develop a new imaging modality that is capable of single-shot 3D PAI using a single-element transducer. The proposed method is validated with phantom study, which demonstrates single-shot 3D imaging of different objects and 3D tracking of a moving object. After one-time calibration, while the system could perform single-shot 3D imaging for different objects, the calibration could remain effective over 7 days, which is highly beneficial for practical translation. Overall, the experimental results showcase the potential of this technique for both scientific research and clinical applications.

Photoacoustic tomography as a method to estimate the optical fluence distribution in turbid media.

Currently, there are no non-invasive experimental methods available for measuring optical fluence distributions in tissue. We present photoacoustic tomography (PAT) as a method to approximate the relative optical fluence distribution in a homogeneous optically scattering medium. Three-dimensional photoacoustic images were captured with a near-full view PAT scanner in phantoms with known optical absorption and scatter properties. Resultant 3D PAT images were compared to the expected optical fluence distributions from Monte Carlo simulations and diffusion theory using volumetric and shape analysis. Volumetric analysis of PAT images compared well with the optical fluence distributions from simulation. Dice similarity coefficients ranged from 51 to 82%. The reduced scattering coefficient estimated from PAT images compared well to estimates from simulations for values below 0.5 mm-1. Near full-view PAT has been found to be useful for estimating the optical fluence distribution in an optically scattering medium. Further development is needed to extend the measurement range.

Blood–Brain Barrier Permeable Photoacoustic Probe for High-Resolution Imaging of Nitric Oxide in the Living Mouse Brain

Alternations in the brain nitric oxide (NO) homeostasis are associated with a variety of neurodegeneration diseases; therefore, high-resolution imaging of NO in the brain is essential for understanding pathophysiological processes. However, currently available NO probes are unsuitable for this purpose due to their poor ability to cross the blood-brain barrier (BBB) or to image in deep tissues with spatial resolution. Herein, we developed a photoacoustic (PA) probe with BBB crossing ability to overcome this obstacle. The probe shows a highly selective ratiometric response toward NO, which enables the probe to image NO with micron resolution in the whole brain of living mice. Using three-dimensional PA imaging, we demonstrated that the probe could be used to visualize the detailed NO distribution in varying depth cross-sections (0-8 mm) of the living Parkinson's disease (PD) mouse brain. We also investigated the therapeutic properties of natural polyphenols in the PD mouse brain using the probe as an imaging agent and suggested the potential of the probe for screening therapeutic agents. This study provides a promising imaging agent for imaging of NO in the mouse brain with high resolution. We anticipate that these findings may open up new possibilities for understanding the biological functions of NO in the brain and the development of new imaging agents for the diagnosis and treatment of brain diseases.

Elevational Synthetic Aperture Focusing for Three-Dimensional Photoacoustic Imaging Using a Clinical One-Dimensional Array Transducer.

Two-dimensional (2D) photoacoustic (PA) imaging based on array transducers provide high spatial resolution in the lateral direction by adopting receive dynamic focusing. However, the quality of PA image is often deteriorated by poor elevational resolution which is achieved by an acoustic lens. To overcome this limitation, we present a three-dimensional (3D) image reconstruction method using a commercial one-dimensional (1D) array transducer. In the method, the elevational resolution is improved by applying synthetic aperture focusing (SAF) technique along the elevational direction. For this, a commercially available 1D array transducer with an acoustic lens is modeled and appropriate synthetic focusing delay that can minimize the effect of the acoustic lens is derived by mathematical analysis. From the simulation and experiment results, it was demonstrated that the proposed method can enhance the image quality of PA imaging, i.e., elevational resolution and signal-to-noise ratio (SNR). 3D PA images with improved elevational resolution were achieved using a clinical 1D array transducer. The presented method may be useful for clinical application such as detecting microcalcification, imaging of tumor vasculature and guidance of biopsy in real time.

3D ultrasound imaging by synthetic transmit aperture beamforming using a spherically curved array transducer

Visualization of dermal circulation is important in the field of skin healthcare. We have developed a three-dimensional (3D) photoacoustic (PA) imaging system using a spherically curved array transducer that can visualize the microscale circulation in the skin layers, but limited anatomical information was available around the microvasculature. To provide such anatomical information, this study was aimed at devising a high-quality and high-speed ultrasound (US) imaging framework, particularly, for the spherical array transducer. We tested three synthetic transmit aperture (STA) methods, all-elements, outer-track, and inner-track, for transmission by evaluating the spatial resolution and uniformity of 3D images of point and copper-wire targets. The results demonstrated that the all-elements and outer-track STA methods could provide uniform and clear 3D images. In addition, the outer-track STA could be performed with fewer transmissions than the all-elements STA, and it will be useful for realizing real-time, high-resolution 3D PA/US imaging.

Three-dimensional Multistructural Quantitative Photoacoustic and US Imaging of Human Feet in Vivo.

Background Monitoring the microcirculation in human feet is crucial in assessing peripheral vascular diseases, such as diabetic foot. However, conventional imaging modalities are more focused on diagnosis in major arteries, and there are limited methods to provide microvascular information in early stages of the disease. Purpose To investigate a three-dimensional (3D) noncontrast bimodal photoacoustic (PA)/US imaging system that visualizes the human foot morphologically and also reliably quantifies podiatric vascular parameters noninvasively. Materials and Methods A clinically relevant PA/US imaging system was combined with a foot scanner to obtain 3D PA and US images of the human foot in vivo. Healthy participants were recruited from September 2020 to June 2021. The collected 3D PA and US images were postprocessed to present structural information about the foot. The quantitative reliability was evaluated in five repeated scans of 10 healthy feet by calculating the intraclass correlation coefficient and minimal detectable change, and the detectability of microvascular changes was tested by imaging 10 healthy feet intentionally occluded with use of a pressure cuff (160 mm Hg). Statistically significant difference is indicated with P values. Results Ten feet from six healthy male volunteers (mean age ± standard deviation, 27 years ± 3) were included. The foot images clearly visualized the structure of the vasculature, bones, and skin and provided such functional information as the total hemoglobin concentration (HbT), hemoglobin oxygen saturation (SO2), vessel density, and vessel depth. Functional information from five independent measurements of 10 healthy feet was moderately reliable (intraclass correlation coefficient, 0.51-0.74). Significant improvements in HbT (P = .006) and vessel density (P = .046) as well as the retention of SO2 were observed, which accurately described the microvascular change due to venous occlusion. Conclusion Three-dimensional photoacoustic and US imaging was able to visualize morphologic and physiologic features of the human foot, including the peripheral microvasculature, in healthy volunteers. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mezrich in this issue.

Second-Generation Dual Scan Mammoscope With Photoacoustic, Ultrasound, and Elastographic Imaging Capabilities.

We recently developed the photoacoustic dual-scan mammoscope (DSM), a system that images the patient in standing pose analog to X-ray mammography. The system simultaneously acquires three-dimensional photoacoustic and ultrasound (US) images of the mildly compressed breast. Here, we describe a second-generation DSM (DSM-2) system that offers a larger field of view, better system stability, higher ultrasound imaging quality, and the ability to quantify tissue mechanical properties. In the new system, we doubled the field of view through laterally shifted round-trip scanning. This new design allows coverage of the entire breast tissue. We also adapted precisely machined holders for the transducer-fiber bundle sets. The new holder increased the mechanical stability and facilitated image registration from the top and bottom scanners. The quality of the US image is improved by increasing the firing voltage and the number of firing angles. Finally, we incorporated quasi-static ultrasound elastography to allow comprehensive characterization of breast tissue. The performance of the new system was demonstrated through in vivo human imaging experiments. The experimental results confirmed the capability of the DSM-2 system as a powerful tool for breast imaging.

Method for the biomechanical analysis of aqueous veins and perilimbal sclera by three-dimensional photoacoustic imaging and strain field calculation

A method motivated by the eye’s aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein—perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors’ knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature.

Sparsity-Based Recovery of Three-Dimensional Photoacoustic Images from Compressed Single-Shot Optical Detection.

Photoacoustic (PA) imaging combines optical excitation with ultrasonic detection to achieve high-resolution imaging of biological samples. A high-energy pulsed laser is often used for imaging at multi-centimeter depths in tissue. These lasers typically have a low pulse repetition rate, so to acquire images in real-time, only one pulse of the laser can be used per image. This single pulse necessitates the use of many individual detectors and receive electronics to adequately record the resulting acoustic waves and form an image. Such requirements make many PA imaging systems both costly and complex. This investigation proposes and models a method of volumetric PA imaging using a state-of-the-art compressed sensing approach to achieve real-time acquisition of the initial pressure distribution (IPD) at a reduced level of cost and complexity. In particular, a single exposure of an optical image sensor is used to capture an entire Fabry–Pérot interferometric acoustic sensor. Time resolved encoding as achieved through spatial sweeping with a galvanometer. This optical system further makes use of a random binary mask to set a predetermined subset of pixels to zero, thus enabling recovery of the time-resolved signals. The Two-Step Iterative Shrinking and Thresholding algorithm is used to reconstruct the IPD, harnessing the sparsity naturally occurring in the IPD as well as the additional structure provided by the binary mask. We conduct experiments on simulated data and analyze the performance of our new approach.

Photoacoustic imaging of fresh human surgically and endoscopically resected gastrointestinal specimens.

ObjectivePhotoacoustic (PA) imaging is a novel noninvasive technique that offers high‐contrast tomographic imaging with ultrasound‐like resolution at depths of centimeters, enabling visualization of deep small vessels. The aim of this pilot study was to survey the characteristics of deep vessel networks in the mucosa of neoplastic gastrointestinal (GI) lesions using PA imaging.MethodsSpecimens of patients who had undergone surgical and endoscopic resection for GI lesions were included in this study. The PA/ultrasound imaging system for clinical research is characterized by a technology that can superimpose a PA image over an ultrasound image. Three‐dimensional PA images were acquired for the resected specimen before fixation. The stomach and colon of live pigs were incised, and the walls were scanned from the mucosa.ResultsA total of 32 specimens (nine esophageal, 12 gastric, 11 colorectal) were scanned. The pathological diagnoses were adenomas (n = 2), intramucosal cancers (n = 14), and invasive cancers (n = 16). The deep vessel networks of all lesions could be visualized. In the intramucosal lesions, the deep vessel network was similar to that of a normal tissue. In invasive cancers, the thick and prominent vessel network was visible in the surface layer of esophageal cancers, infiltrated area of gastric cancers, and surface layer and infiltrated area of colorectal cancers. In the images of living pigs, visualizing the vascular network deeper than the submucosa in both the stomach and large intestine was possible.ConclusionOur study confirmed that the deep vessel networks of neoplastic GI lesions were visible by PA imaging.

Intravital NIR-II three-dimensional photoacoustic imaging of biomineralized copper sulfide nanoprobes

Photoacoustic (PA) imaging with functional nanoprobes in the second near-infrared region (NIR-II, 1000-1700 nm) has aroused much interest due to its deep tissue penetration and high maximum laser permissible exposure. However, most NIR-II PA imaging is performed using the two-dimensional (2D) imaging modality, which impedes the comprehension of the in vivo biodistribution, angiography and molecular-targeted performance of NIR-II nanoprobes (NPs). Herein, we report the systematic monitoring of biomineralized copper sulfide (CuS) NPs, typical NIR-II NPs, in mouse models by employing NIR-II three-dimensional (3D) PA imaging. The advanced imaging modality provides dynamic information about the 3D biodistribution and metabolic pathway of CuS NPs. We also achieved contrast-enhanced 3D PA imaging of abdominal and cerebral vessels at a high signal-to-background ratio. Moreover, the tumor-targeted CuS NPs conjugated with the bombesin peptide endowed NIR-II 3D PA with superior performance in imaging orthotopic tumors both deep in the prostate and in the brain beneath the intact scalp and skull. Our results highlight the potential of NIR-II 3D PA imaging for the evaluation of the in vivo behavior of NPs, thus providing a promising strategy for screening NPs in clinical translational studies.

Abstract P226: The Analysis Of Regional Placental Hemodynamics Using Combined Photoacoustic Imaging And Contrast-enhanced Ultrasound

Placental insufficiency is often associated with pregnancies at risk for fetal growth restriction or preeclampsia. We have previously demonstrated that three-dimensional ultrasound-guided photoacoustic imaging (PAI) is a sensitive tool for assessing regional variations in placental oxygenation in mice. However, whether changes in placental oxygenation determined by the PAI correlate with changes in placental perfusion is unknown and was tested in this study. PAI combines optical contrast of photoacoustic laser technology with a high spatial resolution of ultrasound. Placental vascular oxygen saturation (sO2) was quantified in C57Bl/6 mice by the PAI using Vevo 2100 LAZR instrument (Fujifilm, VisualSonics). 50 microliters of Vevo MicroMarker contrast agent was delivered via a bolus tail-vein injection. Placental perfusion parameters were determined at day 15 of gestation in C57Bl/6 mice. Our data demonstrated significantly greater oxygenation in the placental labyrinth versus maternal triangle area (53.01±1.7 vs. 42.7±4.2 % sO2; n=6, p<0.05). No regional differences were detected in relative blood flow in these mice (dB or a.u.). However “time-to-peak” (perfusion kinetics parameter) was greater in the labyrinth compared with maternal triangle area (2.3 times, p<0.05, n=5). Our data show that the overall blood flow is similar throughout the placenta at mid-late gestation, while the perfusion is greater in the labyrinth (fetal) side of the placenta consistent with greater vascularization of this area. Our data suggest that placental sO2 measured by the PAI is associated with coordinated changes in placental perfusion during late stages of mouse pregnancy. This approach provides a novel tool for non-invasively investigating placental environment and pregnancy outcomes particularly in pregnancies complicated by IUGR or preeclampsia.

Unique spectral signature of human cutaneous squamous cell carcinoma by photoacoustic imaging.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with metastatic potential. To reduce reoperations due to nonradical excision, there is a need to develop a technique for identification of tumor margins preoperatively. Photoacoustic (PA) imaging is a novel imaging technology that combines the strengths of laser optics and ultrasound. Our aim was to determine the spectral signature of cSCC using PA imaging and to use this signature to visualize tumor architecture and borders. Two-dimensional PA images of 33 cSCCs and surrounding healthy skin were acquired ex vivo, using 59 excitation wavelengths from 680 to 970 nm. The spectral response of the cSCCs was compared to healthy tissue, and the difference was found to be greatest at wavelengths in the range 765 to 960 nm (P < .05). Three-dimensional PA images were constructed from spectra obtained in the y-z plane using a linear stepper motor moving along the x-plane. Spectral unmixing was then performed which provided a clear three-dimensional view of the distribution of tumor masses and their borders.

Rapid Three-Dimensional Photoacoustic Imaging Reconstruction for Irregularly Layered Heterogeneous Media.

Photoacoustic imaging (PAI) is susceptible to speed of sound (SOS) differences in heterogeneous media which greatly reduce the resolutions and qualities of the imaging results. Several reconstruction methods have been reported to adapt for heterogenous media, but they are limited by specific deficiencies such as efficiency, accuracy, and model limitation problems. Among them, the plane wave model based on wavefield reconstruction is the most efficient and promising one for high-efficiency three-dimensional PAI. However, the classic plane wave model only suits for planar layered media, severely limiting its applications in practice. To this end, we modify the plane wave model to apply for irregularly layered heterogeneous media and propose a corresponding wavefield extrapolation to reconstruct photoacoustic image. This method employs split-step Fourier to compensate the SOS differences, extrapolates wavefields and reconstructs the image depth by depth. Furthermore, a floating discretization strategy is introduced to control and balance the efficiency and accuracy with a hyperparameter. The simulation and experiment results demonstrate that the proposed method can reconstruct the image with an equivalent resolution to time reversal's and even have higher efficiency and robustness. To reconstruct a three-dimensional image with 50×50×600 pixels, the proposed method takes only 5.5 seconds using a laptop loaded with Intel(R) Core (TM) i7-8550U CPU @1.8GHz.

In vivo photoacoustic imaging of major blood vessels in the pancreas and liver during surgery.

.Abdominal surgeries carry considerable risk of gastrointestinal and intra-abdominal hemorrhage, which could possibly cause patient death. Photoacoustic imaging is one solution to overcome this challenge by providing visualization of major blood vessels during surgery. We investigate the feasibility of in vivo blood vessel visualization for photoacoustic-guided liver and pancreas surgeries. In vivo photoacoustic imaging of major blood vessels in these two abdominal organs was successfully achieved after a laparotomy was performed on two swine. Three-dimensional photoacoustic imaging with a robot-controlled ultrasound (US) probe and color Doppler imaging were used to confirm vessel locations. Blood vessels in the in vivo liver were visualized with energies of 20 to 40 mJ, resulting in 10 to 15 dB vessel contrast. Similarly, an energy of 36 mJ was sufficient to visualize vessels in the pancreas with up to 17.3 dB contrast. We observed that photoacoustic signals were more focused when the light source encountered a major vessel in the liver. This observation can be used to distinguish major blood vessels in the image plane from the more diffuse signals associated with smaller blood vessels in the surrounding tissue. A postsurgery histopathological analysis was performed on resected pancreatic and liver tissues to explore possible laser-related damage. Results are generally promising for photoacoustic-guided abdominal surgery when the US probe is fixed and the light source is used to interrogate the surgical workspace. These findings are additionally applicable to other procedures that may benefit from photoacoustic-guided interventional imaging of the liver and pancreas (e.g., biopsy and guidance of radiofrequency ablation lesions in the liver).

Vascular branching point counts using photoacoustic imaging in the superficial layer of the breast: A potential biomarker for breast cancer

This study aimed to identify the characteristics of the vascular network in the superficial subcutaneous layer of the breast and to analyze differences between breasts with cancer and contralateral unaffected breasts using vessel branching points (VBPs) detected by three-dimensional photoacoustic imaging with a hemispherical detector array. In 22 patients with unilateral breast cancer, the average VBP counts to a depth of 7 mm below the skin surface were significantly greater in breasts with cancer than in the contralateral unaffected breasts (p < 0.01). The ratio of the VBP count in the breasts with cancer to that in the contralateral breasts was significantly increased in patients with a high histologic grade (p = 0.03), those with estrogen receptor-negative disease (p < 0.01), and those with highly proliferative disease (p < 0.01). These preliminary findings indicate that a higher number of VBPs in the superficial subcutaneous layer of the breast might be a biomarker for primary breast cancer.

Preclinical Ultrasound-Guided Photoacoustic Imaging of the Placenta in Normal and Pathologic Pregnancy.

Placental oxygenation varies throughout pregnancy. The detection of early changes in placental oxygenation as pregnancy progresses is important for early identification of preeclampsia or other complications. This invited commentary discusses a recent preclinical study on the application of 3-dimensional photoacoustic imaging (PAI) for assessment of regional variations in placental oxygenation and longitudinal analysis of differences in placental oxygenation throughout normal pregnancy and pregnancy associated with hypertension or placental insufficiency in mice. Three-dimensional PAI more accurately reflects oxygen saturation, hemoglobin concentrations, and changes in oxygen saturation in whole placenta compared to 2-dimensional imaging. These studies suggest that PAI is a sensitive tool to detect different levels of oxygen saturation in the placental and fetal vasculature in pathologic and normal pregnancy in mice.