Correction of a transcranial acoustic field using a transient ultrasound field visualization technique.

Ultrasound, due to its noninvasive nature, has the potential to enhance or suppress neural activity, making it highly promising for regulating intractable brain disorders. Precise ultrasound stimulation is crucial for improving the efficiency of neural modulation and studying its mechanisms. However, the presence of the skull can cause distortion in the ultrasound field, thereby affecting the accuracy of stimulation. Existing correction methods primarily rely on magnetic resonance guidance and numerical simulation. Due to the large size and high cost, the MR-guided transcranial ultrasound is difficult to be widely applied in small animals. The numerical simulation usually requires further validation and optimization before application, and the most effective method is to visualize the excited ultrasound field. However, the ultrasound field correction methods based on acoustic field visualization are still lacking. Therefore, a shadowgraph-based transient ultrasonic field visualization system is developed, and an ex vivo transcranial ultrasound field correction is performed. By visualizing the ultrasound field with or without a rat skull and then calculating the time difference of each element's ultrasound wavefront, the parameters for ultrasound field correction can be achieved. The experimental results show that this method can improve both the shape and the size of the focal spot, as well as enhance the acoustic pressure at the focus. Overall, the results demonstrate that the ultrasonic field visualization technology can effectively improve the transcranial ultrasound focusing effect and provide a new tool for achieving precise ultrasonic neural modulation.

Transcranial ultrasound neuromodulation facilitates isoflurane-induced general anesthesia recovery and improves cognition in mice.

Delayed arousal and cognitive dysfunction are common, especially in older patients after general anesthesia (GA). Elevating central nervous system serotonin (5-HT) levels can promote recovery from GA and increase synaptic plasticity to improve cognition. Ultrasound neuromodulation has become a noninvasive physical intervention therapy with high spatial resolution and penetration depth, which can modulate neuronal excitability to treat psychiatric and neurodegenerative diseases. This study aims to use ultrasound to noninvasively modulate the brain 5-HT levels of mice to promote recovery from GA and improve cognition in mice. The dorsal raphe nucleus (DRN) of mice during GA was stimulated by the 1.1 MHz ultrasound with a negative pressure of 356 kPa, and the liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) method was used to measure the DRN 5-HT concentrations. The mice's recovery time from GA was assessed, and the cognition was evaluated through spontaneous alternation Y-maze and novel object recognition (NOR) tests. After ultrasound stimulation, the mice's DRN 5-HT levels were significantly increased (control: 554.0 ± 103.2 ng/g, anesthesia + US: 664.2 ± 84.1 ng/g, *p = 0.0389); the GA recovery time (return of the righting reflex (RORR) emergence latency time) of mice was significantly reduced (anesthesia: 331.6 ± 70 s, anesthesia + US: 223.2 ± 67.7 s, *p = 0.0215); the spontaneous rotation behavior score of mice was significantly increased (anesthesia: 59.46 ± 5.26 %, anesthesia + US: 68.55 ± 5.24 %; *p = 0.0126); the recognition index was significantly increased (anesthesia: 55.02 ± 6.23 %, anesthesia + US: 78.52 ± 12.21 %; ***p = 0.0009). This study indicates that ultrasound stimulation of DRN increases serotonin levels, accelerates recovery from anesthesia, and improves cognition, which could be an important strategy for treating delayed arousal, postoperative delirium, or even lasting cognitive dysfunction after GA.

Ultrasound neuromodulation ameliorates chronic corticosterone-induced depression- and anxiety-like behaviors in mice.

Objective.Monoamine dysfunction has been implicated as a pathophysiological basis of several mental disorders, including anxiety and depression. Transcranial ultrasound stimulation (TUS) is a noninvasive nerve stimulation technic showing great potential in treating depression/anxiety disorders. This study aims to investigate whether TUS can ameliorate depression with anxiety in mice by regulating brain monoamine levels.Approach.Mice received repeated subcutaneous injections of corticosterone (CORT, 20 mg kg-1) for 3 weeks to produce depression- and anxiety-like behaviors. Ultrasound stimulated the dorsal lateral nucleus (DRN) for 30 min daily for 3 weeks without interruption of CORT injection. Behavioral phenotypes of depression and anxiety were estimated by sucrose preference test (SPT), tail suspension test (TST), and elevated plus-maze test (EPM). Liquid chromatography-mass spectrometry (LC-MS) was used to quantify brain levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Western blotting was performed to detect brain-derived neurotrophic factor (BDNF) levels in hippocampal.Main results.TUS of DRN significantly ameliorated the depression-like behaviors in SPT (p= 0.0004) and TST (p= 0.0003) as well as anxiety-like behaviors in EPM (open arm entry frequencies,p< 0.05). Moreover, TUS increased c-Fos-positive cell expression (p= 0.0127) and induced no tissue damage. LC-MS results showed TUS of DRN resulted in a non-significant increase in the 5-HT levels and a significant decrease in the NE levels, but did not affect the levels of DA and BDNF.Significance.These results suggest TUS of DRN has safely and effectively ameliorated CORT-induced depression- and anxiety-like behaviors, possibly by restoring brain levels of 5-HT and NE. TUS may be a safe and effective technique for remedying depression and anxiety comorbidity.

Photoacoustic maximum amplitude projection microscopy by ultra-low data sampling.

Photoacoustic microscopy (PAM) has attracted increasing research interest in the biomedical field due to its unique merit of combining light and sound. In general, the bandwidth of a photoacoustic signal reaches up to tens or even hundreds of MHz, which requires a high-performance acquisition card to meet the high requirement of precision of sampling and control. For most depth-insensitive scenes, it is complex and costly to capture the photoacoustic maximum amplitude projection (MAP) images. Herein, we propose a simple and low-cost MAP-PAM system based on a custom-made peak holding circuit to obtain the extremum values by Hz data sampling. The dynamic range of the input signal is 0.01-2.5 V, and the -6-dB bandwidth of the input signal can be up to 45 MHz. Through in vitro and in vivo experiments, we have verified that the system has the same imaging ability as conventional PAM. Owing to its compact size and ultra-low price (approximately $18), it provides a new performance paradigm for PAM and opens up a new way for an optimal photoacoustic sensing and imaging device.

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer.

Objective.Ultrasound neuromodulation has become an emerging method for the therapy of neurodegenerative and psychiatric diseases. The phased array ultrasonic transducer enables multi-target ultrasound neuromodulation in small animals, but the relatively large size and mass and the thick cables of the array limit the free movement of small animals. Furthermore, spatial interference may occur during multi-target ultrasound brain stimulation with multiple micro transducers.Approach.In this study, we developed a miniature power ultrasound transducer and used the virtual source time inversion method and 3D printing technology to design, optimize, and manufacture the acoustic holographic lens to construct a multi-target ultrasound neuromodulation system for free-moving mice. The feasibility of the system was verified byin vitrotranscranial ultrasound field measurements,in vivodual-target blood-brain barrier (BBB) opening experiments, andin vivodual-target ultrasound neuromodulation experiments.Main results.The developed miniature transducer had a diameter of 4.0 mm, a center frequency of 1.1 MHz, and a weight of 1.25 g. The developed miniature acoustic holographic lens had a weight of 0.019 g to generate dual-focus transcranial ultrasound. The ultrasonic field measurements' results showed that the bifocal's horizontal distance was 3.0 mm, the -6 dB focal spot width in thex-direction was 2.5 and 2.25 mm, and 2.12 and 2.24 mm in they-direction. Finally, thein vivoexperimental results showed that the system could achieve dual-target BBB opening and ultrasound neuromodulation in freely-moving mice.Significance.The ultrasonic neuromodulation system based on a miniature single-element transducer and the miniature acoustic holographic lens could achieve dual-target neuromodulation in awake small animals, which is expected to be applied to the research of non-invasive dual-target ultrasonic treatment of brain diseases in awake small animals.

Portable Microwave-Acoustic Coaxial Thermoacoustic Probe With Miniaturized Vivaldi Antennas for Breast Tumor Screening.

Microwave-induced thermoacoustic (TA) imaging (MTAI), which exploits dielectric contrasts to provide images with high contrast and spatial resolution, holds the potential to serve as an additional means of clinical diagnosis and treatment. However, conventional MTAI usually uses large and heavy metal antennas to radiate pulsed microwaves, making it challenging to image different target areas flexibly. In this work, we presented the design and evaluation of a portable microwave-acoustic coaxial TA probe (51 mm × 63 mm × 138 mm) that can flexibly image the region of interest. The TA probe contains two miniaturized symmetrically distributed Vivaldi antennas (7.5 g) and a 128-element linear ultrasonic transducer. By adjusting the geometry of the antennas and the ultrasonic transducer, the TA probe's acoustic field and microwave field can be designed to be coaxial, which helps achieve homogeneous microwave illumination and high-sensitivity ultrasonic detection. The practical feasibility of the proposed probe was tested on an in vitro ewe breast and a healthy volunteer. The results demonstrate that the MTAI system with the proposed TA probe can visualize the anatomical structure of the breast tumor in ewe breast and a healthy volunteer breast with resolutions in hundreds of microns (transverse: 910 µm, axial: 780 µm) and an excellent signal-to-noise ratio can be obtained in deep adipose tissue (10 dB in 6 cm fat). The miniaturized portable TA probe takes a solid step forward in translating MTAI technology to clinical breast tumor diagnosis.

Transcranial ultrasound stimulation relieves depression in mice with chronic restraint stress.

Objective.Exhaustion of Serotonin (5-hydroxytryptamine, 5-HT) is a typical cause of the depression disorder's development and progression, including depression-like behaviors. Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique treating various neurodegenerative diseases. This study aims to investigate whether TUS ameliorates depression-like behaviors by restoring 5-HT levels.Methods.The depression model mice are established by chronic restraint stress (CRS). Ultrasound waves (FF = 1.1 MHz, PRF = 1000 Hz, TBD = 0.5 ms, SD = 1 s, ISI = 1 s, and DC = 50%) were delivered into the dorsal raphe nucleus (DRN) for 30 min per day for 2 weeks. Depression-like behavior changes are evaluated with the sucrose preference and tail suspension tests. Liquid chromatography-mass spectrometry is performed to quantitatively detect the concentration of 5-HT in the DRN to explore its potential mechanism. The effectiveness and safety of TUS were assessed by c-Fos immunofluorescence and hematoxylin and eosin (HE) staining, respectively.Results.Three weeks after CRS, 22 depressive mice models were screened by sucrose preference index (SPI). After 2 weeks of ultrasound stimulation of the DRN (DRN-TUS) in depressive mice, the SPI was increased (p= 0.1527) and the tail suspension immobility duration was significantly decreased (p= 0.0038) compared with the non-stimulated group. In addition, TUS significantly enhances the c-Fos (p= 0.05) positive cells' expression and the 5-HT level (p= 0.0079) in the DRN. Importantly, HE staining shows no brain tissue damage.Conclusion.These results indicate that DRN-TUS has safely and effectively improved depression-like behaviors including anhedonia and hopelessness, potentially by reversing the depletion of 5-TH.SignificanceTUS may provide a new perspective on depression therapy, possibly through restoring monoamine levels.

Multiscale confocal photoacoustic dermoscopy to evaluate skin health.

Background: Photoacoustic dermoscopy (PAD) is a promising branch of photoacoustic microscopy (PAM) that can provide a range of functional and morphologic information for clinical assessment and diagnosis of dermatological conditions. However, most PAM setups are unsuitable for clinical dermatology because their single-scale mode and narrow frequency band result in insufficient imaging depth or poor spatiotemporal resolution when visualizing the internal texture of the skin. Methods: We developed a multiscale confocal photoacoustic dermoscopy (MC-PAD) with a multifunction opto-sono objective that could achieve high quality dermatological imaging. Using the objective to coordinate the spatial resolution and penetration depth, the MC-PAD was used to visualize pathophysiological biomarkers and vascular morphology from the epidermis (EP) to the dermis, which enabled us to quantify skin abnormalities without using exogenous contrast agents for human skin. Results: The MC-PAD was shown to have the ability to differentiate between different types of cells (such as red blood cells and melanoma cells), image and quantify pigment of the skin, and visualize skin morphology and blood capillary landmarks. The MC-PAD detected a significant difference in the structures of some pigmented and vascular lesions of skin diseases compared with that of healthy skin (P<0.01). The café au lait macule (CALM) skin type was found to have a relatively higher melanin concentration and thicker stratum basale (SB) in the EP than healthy skin. The dermal vascular network of skin that had a port wine stain (PWS) had greater diameters and a denser distribution than healthy skin, as reported in clinical trials. Conclusions: The MC-PAD has a broad range of applications for the diagnosis of human skin diseases and evaluation of the curative effect of treatments, and it can offer new perspectives in biomedical sciences.

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.

A Handheld Microwave Thermoacoustic Imaging System With an Impedance Matching Microwave-Sono Probe for Breast Tumor Screening.

Microwave-induced thermoacoustic imaging (MTAI) is a promising alternative for breast tumor detection due to its deep imaging depth, high resolution, and minimal biological hazards. However, due to the bulky size and complicated system configuration of conventional benchtop MTAI, it is limited to imaging various anatomical sites and its application in different clinical scenarios. In this study, a handheld MTAI system equipped with a compact impedance matching microwave-sono and an ergonomically designed probe was presented and evaluated. The probe integrates a flexible coaxial cable for microwave delivery, a miniaturized microwave antenna, a linear transducer array, and wedge-shaped polystyrene blocks for efficient acoustic coupling, achieving microwave illumination and ultrasonic detection coaxially, and enabling high signal-to-noise ratio (SNR). Phantom experiments demonstrated that the maximum imaging depth is 5 cm (SNR = 8 dB), and the lateral and axial resolutions are 1.5 mm and 0.9 mm, respectively. Finally, three healthy female volunteers of different ages were subjected to breast thermoacoustic tomography and ultrasound imaging. The results showed that the h-MTAI data are correlated with the data of ultrasound imaging, indicating the safety and effectiveness of the system. Thus, the proposed h-MTAI system might contribute to breast tumor screening.

Quantitative and anatomical imaging of dermal angiopathy by noninvasive photoacoustic microscopic biopsy.

The ability to noninvasively acquire the fine structure of deep tissues is highly valuable but remains a challenge. Here, a photoacoustic microscopic biopsy (PAMB) combined switchable spatial-scale optical excitation with single-element depth-resolved acoustic detection mode was developed, which effectively coordinated the spatial resolution and the penetration depth for visualizations of skin delamination and chromophore structures up to reticular dermis depth, with the lateral resolution from 1.5 to 104 µm and the axial resolution from 34 to 57 µm. The PAMB obtained anatomical imaging of the pigment distribution within the epidermis and the vascular patterns of the deep dermal tissue, enabling quantification of morphological abnormalities of angiopathy without the need for exogenous contrast agents. The features of healthy skin and scar skin, and the abnormal alteration of dermal vasculature in port wine stains (PWS) skin were first precisely displayed by PAMB-shown multi-layered imaging. Moreover, the quantitative vascular parameters evaluation of PWS were carried out by the detailed clinical PAMB data on 174 patients, which reveals distinct differences among different skin types. PAMB captured the PWS changes in capillary-loop depth, diameter, and vascular volume, making it possible to perform an objective clinical evaluation on the severity of PWS. All the results demonstrated the PAMB can provide vascular biopsy and new indexes deep into the dermal skin noninvasively, which should be meaningful to timely evaluate the pathological types and treatment response of skin diseases. This opens up a new perspective for label-free and non-invasive biopsies of dermal angiopathy.

An Excitation-Reception Collinear Probe for Ultrasonic, Photoacoustic, and Thermoacoustic Tri-Modal Volumetric Imaging.

Imaging systems that integrate multiple modalities can reveal complementary anatomic and functional information as they exploit different contrast mechanisms, which have shown great application potential and advantages in preclinical studies. A portable and easy-to-use imaging probe will be more conducive to transfer to clinical practice. Here, we present a tri-modal ultrasonic (US), photoacoustic (PA), and thermoacoustic (TA) imaging system with an excitation-reception collinear probe. The acoustic field, light field, and electric field of the probe were designed to be coaxial, realizing homogeneous illumination and high-sensitivity detection at the same detection position. US images can provide detailed information about structures, PA images can delineate the morphology of blood vessels in tissues, and TA images can reveal dielectric properties of the tissues. Moreover, phantoms and in vivo human finger experiments were performed by the tri-modal imaging system to demonstrate its performance. The results show that the tri-modal imaging system with the proposed probe has the ability to detect small breast tumors with a radius of only 2.5 mm and visualize the anatomical structure of the finger in three dimensions. Our work confirms that the tri-modal imaging system equipped with a collinear probe can be applied to a variety of different scenarios, which lays a solid foundation for the application of the tri-modality system in clinical trials.

An Ellipsoidal Focused Ultrasound Transducer for Extend-Focus Photoacoustic Microscopy.

OBJECTIVE: Limited by spherical focused ultrasound transducer (SUT) with a high acoustic numerical aperture, photoacoustic microscopy (PAM) suffers a rapidly degrading sensitivity and lateral resolution as increased depth. In this study, an ellipsoidal focused ultrasound transducer (EUT) was developed to address the above restriction via providing high sensitivity and lateral resolution over a large depth of field (DOF). METHODS: To fabricate the EUT, the piezoelectric element was laminated onto a curved steel surface for self-focusing (the ellipsoidal continuous-focus geometry was employed instead of the spherical single-focus one). Additionally, phantoms and in vivo animal experiments were performed by an extend-focus PAM equipped with EUT to characterize its performance. RESULTS: The EUT involved over 30 MHz center frequency and -6 dB bandwidth of 124% with a resolution-invariant focal depth of 1.39 mm, more than 3 times the DOF of the SUT. CONCLUSION: The in vivo imaging results demonstrated that the EUT was capable of extending the focal depth to get rid of the restriction of the visual field, while the DOF of the SUT was limited by the nature of spherical geometry. SIGNIFICANCE: The EUT markedly enhances the image quality at different imaging depths, which has great potential for promoting the biomedical development of in vivo rapid-noninvasive PAM.

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.

Photoacoustic and ultrasound (PAUS) dermoscope with high sensitivity and penetration depth by using a bimorph transducer.

A bimorph transducer was proposed to improve the detection sensitivity and imaging depth of photoacoustic and ultrasound (PAUS) dermoscope. By applying the bimorph transducer, the imaging depth and sensitivity of PAUS dermoscope were enhanced by simultaneously improving excitation efficiency and reception bandwidth. The integrated design of the imaging head of the dermoscope makes it highly convenient for detecting human skin. The PAUS imaging performance was demonstrated via visualizing subcutaneous tumor and depicting full structures of different skin layers from epidermis to subcutaneous tissue. The results confirm that the dermoscope with the bimorph transducer is well suited for PA and US dual-modality imaging, which can provide multi-information for skin 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.

Wide-field monitoring and real-time local recording of microvascular networks on small animals with a dual-raster-scanned photoacoustic microscope.

Photoacoustic microscopy (PAM) provides a new method for the imaging of small-animals with high-contrast and deep-penetration. However, the established PAM systems have suffered from a limited field-of-view or imaging speed, which are difficult to both monitor wide-field activity of organ and record real-time change of local tissue. Here, we reported a dual-raster-scanned photoacoustic microscope (DRS-PAM) that integrates a two-dimensional motorized translation stage for large field-of-view imaging and a two-axis fast galvanometer scanner for real-time imaging. The DRS-PAM provides a flexible transition from wide-field monitoring the vasculature of organs to real-time imaging of local dynamics. To test the performance of DRS-PAM, clear characterization of angiogenesis and functional detail was illustrated, hemodynamic activities of vasculature in cerebral cortex of a mouse were investigated. Furthermore, response of tumor to treatment were successfully monitored during treatment. The experimental results demonstrate the DRS-PAM holds the great potential for biomedical research of basic biology.

In vivo volumetric monitoring of revascularization of traumatized skin using extended depth-of-field photoacoustic microscopy.

Faster and better wound healing is a critical medical issue. Because the repair process of wounds is closely related to revascularization, accurate early assessment and postoperative monitoring are very important for establishing an optimal treatment plan. Herein, we present an extended depth-of-field photoacoustic microscopy system (E-DOF-PAM) that can achieve a constant spatial resolution and relatively uniform excitation efficiency over a long axial range. The superior performance of the system was verified by phantom and in vivo experiments. Furthermore, the system was applied to the imaging of normal and trauma sites of volunteers, and the experimental results accurately revealed the morphological differences between the normal and traumatized skin of the epidermis and dermis. These results demonstrated that the E-DOF-PAM is a powerful tool for observing and understanding the pathophysiology of cutaneous wound healing.

Miniaturized photoacoustic probe for in vivo imaging of subcutaneous microvessels within human skin.

BACKGROUND: Subcutaneous microvascular visualization is important for accurate diagnosis and precise treatment of those diseases that are associated with subcutaneous microangiopathy. Pure optical imaging technology and ultrasound imaging technology are commonly used to observe subcutaneous blood vessels non-invasively. However, pure optical imaging is limited to visualizing superficial skin features due to the strong scattering of light by biological tissues, while ultrasound imaging which can detect deep tissues has poor resolution and low contrast to reveal microvascular networks. This results in a lack of intuitive understanding of the disease lesion. METHODS: A miniaturized photoacoustic (PA) probe, which is capable of imaging subcutaneous microvessels with high resolution and deep penetration, was built in this work. The probe is small enough to be hand-held and takes 16 seconds to obtain a maximum amplitude projection image of 400×400 pixels with the imaging area of 2×2 mm2. RESULTS: The miniaturized PA probe was measured to have a lateral resolution of about 8.9 µm and an imaging depth of about 2.4 mm. Besides, in vivo animal experiments and human skin imaging have been implemented. The results show that the miniaturized PA probe not only visualizes the subcutaneous microvessels, but also obtains quantitative information such as the diameters and the depths of blood vessels. CONCLUSIONS: The miniaturized PA probe has potential been used into clinic, and providing quantitative blood vessel information for the diagnosis and monitoring of vascular diseases.