Photoacoustic remote sensing elastography.

The mechanical properties of organisms are important indicators for clinical disputes and disease monitoring, yet most existing elastography techniques are based on contact measurements, which are limited in many application scenarios. Photoacoustic remote sensing elastography (PARSE) is the first, to the best of our knowledge, elastography modality based on acoustic pressure monitoring, where elastic contrast information is obtained by using an all-optical non-contact and non-coherent intensity monitoring method through the time-response properties of laser-induced photoacoustic pressure. To validate PARSE, sections of different elastic organs were measured and this modality was applied to differentiate between bronchial cartilage and soft tissue to confirm the validity of the elasticity evaluation. PARSE, through a mathematical derivation process, has a 9.5-times greater distinction detection capability than photoacoustic remote sensing (PARS) imaging in stained bronchial sections, expands the scope of conventional PARS imaging, and has potential to become an important complementary imaging modality.

High-robustness intravascular photoacoustic endoscope with a hermetically sealed opto-sono capsule.

The prevailing open-structure intravascular photoacoustic (IVPA) endoscope emits a gradually deformed laser beam with exposed optical or acoustical components bearing pollution and damage in arterial lumen. Deformed laser beam scanning, which causes a low excitation efficiency and serious deterioration of the transverse resolution, is a current big obstacle to the application of photoacoustic endoscopy in intravascular imaging. Hence, the stable and reliable IVPA endoscope is indispensable. In this letter, we designed a high-robustness intravascular photoacoustic (HR-IVPA) endoscope with a hermetically sealed opto-sono capsule. The distal end of the opto-sono capsule was integrated with miniaturized optics, including a customized C-Lens and a customized total-reflection prism (TRP). The TRP was first applied to a side-viewing IVPA endoscope, featuring a high-throughput energy coupling efficiency of 90% and a cut-off free damage threshold. The optical path structure of the endoscope, optimized using optical simulation tools, overcame the ambiguous focus shift caused by chromatic dispersion and achieved a waist size of 20 µm as well as a focus depth of 4 mm in water at the wavelength of 1200 nm. The mass phantom experiments demonstrated that the HR-IVPA endoscope afforded repeatable IVPA images with a relatively constant signal-to-noise ratio (SNR) of about ∼41.8 dB and a transverse resolution of about ∼23 µm. The imaging experiments of the stent and lipid further demonstrated the robustness and validated the imaging ability of the HR-IVPA endoscope, which opens a new avenue for improving the endoscopic imaging capability, strengthening the credible detection of atherosclerotic cardiovascular disease.

Electrothermal-MEMS-induced nonlinear distortion correction in photoacoustic laparoscopy.

Micro-electro-mechanical systems (MEMS) scanner has significant advantages of miniature size, fast response and high stability, which is particularly applicable to photoacoustic laparoscopy (PAL). However, tilt angle-voltage curve of electrothermal MEMS shows a nonlinear character, which leads to inevitable nonlinear distortion in photoacoustic imaging. To overcome this problem, a nonlinear distortion correction was developed for the high-resolution forward-scanning electrothermal-MEMS-based PAL. The adaptive resampling method (ARM) was introduced to adaptively calibrate the projection of non-uniform scanning region to match the uniform scanning region. The correction performed low time complexity and high portability owing to the adaptive capacity of distortion decomposition in the reconstruction of physical models. Compared with the sample structure, phantom experiments demonstrated that the distortion was calibrated in all directions and the corrected image provided up to 96.82% high structural similarity in local subset. Furthermore, ARM was applied to imaging the abdominal cavity of rat and the vascular morphology was corrected in real-time display within a delay less than 2 seconds. All these results demonstrated that the nonlinear distortion correction possessed timely and effective correction in PAL, which suggested that it had the potential to employ to any other electrothermal-MEMS-based photoacoustic imaging systems for accurate and quantitative functional imaging.

High-speed dual-view photoacoustic imaging pen.

Today, photoacoustic imaging (PAI) is widely used to study diseases in the skin, brain, cardiovascular, and other parts. However, these studies are often carried out using physiological slices or model animals, which indicate that many PAI techniques can only be used in the laboratory. In order to promote the transformation of PAI into clinical applications or, more specifically, to extend the application of photoacoustic (PA) microscopy to areas such as the oral cavity, throat, cervix, and abdominal viscera which are difficult to detect with conventional PA microscopy systems, a PAI pen was developed. The PAI pen can be handheld and can perform forward detection and lateral detection. The imaging area is a 2.4 mm diameter circular area. In addition, it can provide a high-speed imaging mode of four frames per second and a high-resolution imaging mode of 0.25 frames per second to meet the different needs of clinical users. In this Letter, the performance of the PAI pen was tested by imaging the phantom and the human oral cavity. The experimental results prove that the PAI pen can clearly image the microvessels of the oral cavity, which indicates that it has the same imaging capability for other similar areas and has a good prospect for assisting the diagnosis of related diseases.

High-resolution and extended-depth-of-field photoacoustic endomicroscopy by scanning-domain synthesis of optical beams.

Photoacoustic endomicroscopy (PAEM) is capable of imaging fine structures in digestive tract. However, conventional PAEM employs a tightly focused laser beam to irradiate the object, which results in a limited depth-of-field (DOF). Here, we propose a scanning-domain synthesis of optical beams (SDSOB) to optimize both transverse resolution and the DOF by synthetic effective focused beams in scanning domain for the PAEM. By utilizing the SDSOB technique, multiple defocused and scattered beams are refocused to synthesize virtual focuses covering a large range of depth. A transverse point spread function that is 5.7-time sharper, and a transverse spatial bandwidth that is 8.5-time broader than those of the conventional PAEM were simulatively obtained through SDSOB-PAEM at the defocus distance of 2.4 mm. We validated the transverse resolution improvement at both in- and out-focus positions via phantom experiments of carbon fibers. In addition, in vivo rabbit experiments were conducted to acquire vascular images over radial depth range of 900 µm. And further morphological analysis revealed that the SDSOB images were acquired with abundant vascular branches and nodes, large total-length and small average-length of blood vessels, which indicated that the SDSOB-PAEM achieved high-resolution imaging in distinct rectal layers. All these results suggest that the SDSOB-PAEM possesses high transverse resolution and extended DOF, which demonstrates the SDSOB-PAEM can provide more accurate information for clinical assessment.

Fast controllable confocal focus photoacoustic microscopy using a synchronous zoom opto-sono objective.

Although variable optical focus lenses have been exploited in photoacoustic microscopy (PAM) to improve imaging performance, an optical and acoustic synchronous zoom lens-based confocal PAM system has not yet been achieved previously, to the best of our knowledge. Here we develop a fast controllable confocal focus PAM (FC-PAM) equipped with a synchronous zoom opto-sono objective to facilitate horizontal slice imaging of specimens with irregular surfaces or multilayered structures at different depths. The integration of an opto-sono objective of an electrowetting-based zoom lens allows for the adjustment of the confocal focal length. Using this objective, the FC-PAM achieved a confocal focus-shifting range of approximately 6 to 43 millimeters with a high transverse resolution, and the confocal focus-shifting time was substantially reduced. Phantom experiments and human skin imaging were performed to demonstrate that the opto-sono objective has great potential for studying living biological tissue and promoting the development of in vivo rapid-noninvasive PAM depth imaging.

Autofocusing optical-resolution photoacoustic endoscopy.

Photoacoustic (PA) endoscopy has the potential to diagnose early diseases in the gastrointestinal tract. For the first time, to our knowledge, we developed an autofocusing PA endoscope (AF-PAE) for the usually irregular gastrointestinal tract imaging to solve the deterioration of transverse resolution caused by the defocus scanning of the probe. The 9-mm-diameter AF-PAE probe integrated a 6-mm aspheric lens and 6-mm liquid lens to automatically adjust the optical focal length, and an unfocused ultrasonic transducer with a center frequency of 15 MHz is coaxially set for detecting PA signals. With this probe, the AF-PAE achieved a focus-shifting range from approximately 2 to 10 mm with high transverse resolution and image contrast in a 360° field of view. Phantom experiment and vasculature distribution of a resected rabbit rectum have been performed to demonstrate the imaging ability of the AF-PAE for potential clinical applications in colorectal vessel imaging and subsequent diagnosis.

Intravascular confocal photoacoustic endoscope with dual-element ultrasonic transducer.

We have developed an intravascular confocal photoacoustic (PA) endoscope with symmetrically aligned dual-element ultrasonic transducers. By combining focused laser excitation and focused acoustic collection, the intravascular confocal PA endoscope is capable of realizing resolution enhanced intravascular PA imaging with improved signal-to-noise ratio (SNR) to ameliorate the resolution reduction caused by laser scattering with increasing tissue depth. The detection sensitivity of the endoscope is improved by 5 dB compared with that of single transducer endoscope, and the transverse resolution of the system can up to 13 µm. Intravascular PA tomography of a normal vessel and an atherosclerotic vessel have been performed to demonstrate the imaging ability of the system. This intravascular confocal PA endoscope with an outer diameter of 1.2 mm supports potential for clinical applications in intravascular plaque imaging and subsequent diagnosis.

Homogeneous-resolution photoacoustic microscopy for ultrawide field-of-view neurovascular imaging in Alzheimer's disease.

Neurovascular imaging is essential for investigating neurodegenerative diseases. However, the existing neurovascular imaging technology suffers from a trade-off between a field of view (FOV) and resolution in the whole brain, resulting in an inhomogeneous resolution and lack of information. Here, homogeneous-resolution arched-scanning photoacoustic microscopy (AS-PAM), which has an ultrawide FOV to cover the entire mouse cerebral cortex, was developed. Imaging of the neurovasculature was performed with a homogenous resolution of 6.9 µm from the superior sagittal sinus to the middle cerebral artery and caudal rhinal vein in an FOV of 12 × 12 mm2. Moreover, using AS-PAM, vascular features of the meninges and cortex were quantified in early Alzheimer's disease (AD) and wild-type (WT) mice. The results demonstrated high sensitivity to the pathological progression of AD on tortuosity and branch index. The high-fidelity imaging capability in large FOV enables AS-PAM to be a promising tool for precise brain neurovascular visualization and quantification.

Quantitative multilayered assessment of skin lightening by photoacoustic microscopy.

BACKGROUND: With the emergence of various new skin-lightening products, there is an urgent need to scientifically evaluate the efficacy and toxicology of these products, and provide scientific guidance for their use based on physiological differences between individuals. Visualized imaging methods and quantitative evaluation criteria play key roles in evaluating the efficacy of skin-lightening products. In order to quantify the changes in the multilayered morphology and endogenous components of human skin before and after the use of lightening products, high-resolution three-dimensional (3D) imaging of human skin is required. METHODS: In this study, photoacoustic microscopy (PAM; SSPM-532, Guangdong Photoacoustic Medical Technology Co., Ltd.) was used to capture the morphological structures of human skin and reveal skin components quantitatively. The efficacy and safety of skin-lightening products were evaluated by measuring skin melanin concentration and observing skin morphology. The melanin concentration in the epidermis was obtained by examining the linear relationship between photoacoustic (PA) signals. Further, the epidermal thickness and the melanin distribution were obtained in the cross-sectional (x-z) and lateral (x-y) images. Finally, the efficacy of skin-lightening products was evaluated according to the concentration and distribution of melanin in the epidermis, and the safety of cosmetics was assessed by observing the vascular morphology in the dermis. RESULTS: PAM noninvasively could assess the multilayered morphological structures of human skin, which allowed for quantification of epidermal thickness and melanin concentration of different skin sites. Based on this, the efficacy and safety of skin-lightening products in multilayer structures were quantitatively evaluated. CONCLUSIONS: As a quantitative imaging method, PAM, has the potential to accurately evaluate the use of skin-lightening products. The method can also be extended to assessments within the larger field of aesthetic medicine.

Spherical-matching hyperbolic-array photoacoustic computed tomography.

Linear-array photoacoustic computed tomography (LA-PACT), for its flexibility and simplicity, has great potential in providing anatomical and functional information of tissues. However, the limited coverage view impedes the LA-PACT obtaining high-quality images. In this study, a photoacoustic tomographic system with a hyperbolic-array transducer was developed for stereoscopic PA imaging of carotid artery. The hyperbolic-array PACT increases the receiving sensitivity for PA signal detection due to its transducer's geometric structure matching with the spherical wave. The control phantom experiment shows that the proposed system can expand the angular coverage of ∼1/3 more than that of the LA-PACT system, and the volumetric PA images of rat's carotid artery demonstrates the potential of the system for carotid artery imaging. Furthermore, volumetric imaging of the human forearm verifies that the system has significant capability in human imaging, which indicates that it has bright prospect for assisting diagnosis in the vascular disease.

Spatial weight matrix in dimensionality reduction reconstruction for micro-electromechanical system-based photoacoustic microscopy.

A micro-electromechanical system (MEMS) scanning mirror accelerates the raster scanning of optical-resolution photoacoustic microscopy (OR-PAM). However, the nonlinear tilt angular-voltage characteristic of a MEMS mirror introduces distortion into the maximum back-projection image. Moreover, the size of the airy disk, ultrasonic sensor properties, and thermal effects decrease the resolution. Thus, in this study, we proposed a spatial weight matrix (SWM) with a dimensionality reduction for image reconstruction. The three-layer SWM contains the invariable information of the system, which includes a spatial dependent distortion correction and 3D deconvolution. We employed an ordinal-valued Markov random field and the Harris Stephen algorithm, as well as a modified delay-and-sum method during a time reversal. The results from the experiments and a quantitative analysis demonstrate that images can be effectively reconstructed using an SWM; this is also true for severely distorted images. The index of the mutual information between the reference images and registered images was 70.33 times higher than the initial index, on average. Moreover, the peak signal-to-noise ratio was increased by 17.08% after 3D deconvolution. This accomplishment offers a practical approach to image reconstruction and a promising method to achieve a real-time distortion correction for MEMS-based OR-PAM.

Reliability assessment on intravascular photoacoustic imaging of lipid: ex vivo animal and human sample validation.

Although the lipid-detecting IVPA imaging system has been developed in resolution, speed, and catheter size, there is no parameterization study of the reliability on the IVPA imaging for lipid diagnosis. Here, the sensitivity, specificity, and accuracy were calculated to assess the reliability of the IVPA imaging of lipid. Abdominal aortas from six rabbits with atherosclerosis, were subjected to the IVPA imaging and Oil Red O staining, and 75 groups of IVPA as well as corresponding histological images were obtained. Similarly, 125 groups of IVPA and histological results were obtained from five human carotid plaque samples. The sensitivity, specificity, and accuracy, calculated from the statistical data, were 96.8%, 83.3%, 94.6% and 97.3%, 72.7%, 95.2%, respectively. The numerical values of sensitivity, specificity, and accuracy demonstrated the reliability of IVPA imaging on distinguishing the lesions vessel with lipid-rich plaque, which provided the foundation for IVPA translation to clinical application.