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A novel 0.9 mm-diameter intravascular photoacoustic catheter with coaxial excitation and detection was developed to overcome the limitation of imaging range. A miniature ring-shaped ultrasound transducer with a 0.18 mm-diameter orifice in the center was successfully fabricated. The results demonstrated that the coaxial catheter exhibited much better photoacoustic/ultrasound imaging performance from the intima to the adventitia. Further details can be found in the article by Riqiang Lin, Qi Zhang, Shengmiao Lv, Jiaming Zhang, Xiatian Wang, Dongliang Shi, Xiaojing Gong, and Kwok-ho La ( e202200269 ).

     

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.     

Intravascular molecular-structural imaging with a miniaturized integrated near-infrared fluorescence and ultrasound catheter

Coronary artery disease (CAD) remains a leading cause of mortality and warrants new imaging approaches to better guide clinical care. We report on a miniaturized, hybrid intravascular catheter and imaging system for comprehensive coronary artery imaging in vivo. Our catheter exhibits a total diameter of 1.0 mm (3.0 French), equivalent to standalone clinical intravascular ultrasound (IVUS) catheters but enables simultaneous near-infrared fluorescence (NIRF) and IVUS molecular-structural imaging. We demonstrate NIRF-IVUS imaging in vitro in coronary stents using NIR fluorophores, and compare NIRF signal strengths for prism and ball lens sensor designs in both low and high scattering media. Next, in vivo intravascular imaging in pig coronary arteries demonstrates simultaneous, co-registered molecular-structural imaging of experimental CAD inflammation on IVUS and distance-corrected NIRF images. The obtained results suggest substantial potential for the NIRF-IVUS catheter to advance standalone IVUS, and enable comprehensive phenotyping of vascular disease to better assess and treat patients with CAD.     

High-resolution volumetric information fusion for depth of field enhancement in photoacoustic microscopy

Optical-resolution photoacoustic microscopy suffers from limited depth of field due to the strongly focused laser beam. Here, a novel volumetric information fusion is proposed to achieve large volumetric and high-resolution imaging. First, three-dimensional stationary wavelet transform was performed on the multi-focus data to obtain eight wavelet coefficients. Differential evolution based on joint weighted evaluation was then employed to optimize the block size of division for each wavelet coefficient. The proposed fusion rule using standard deviation for focus detection was used to fuse the corresponding sub-coefficients. Finally, photoacoustic imaging with large depth of field can be achieved by the inverse stationary wavelet transform. Performance test shows that the depth of field of photoacoustic imaging can be doubled without sacrificing lateral resolution. The proposed volumetric information fusion can further promote the capability of volumetric imaging of optical-resolution photoacoustic microscopy and will be helpful in the acquisition of physiological and pathological process.     

Miniature probe for dual‐modality photoacoustic microscopy and white‐light microscopy for image guidance: A prototype toward an endoscope

In this study, a novel photoacoustic microscopy (PAM) probe integrating white‐light microscopy (WLM) modality that provides guidance for PAM imaging and complementary information is implemented. One single core of an imaging fiber bundle is employed to deliver a pulsed laser for photoacoustic excitation for PAM mode, which provides high resolution with deep penetration. Meanwhile, for WLM mode, the imaging fiber bundle is used to transmit two‐dimensional superficial images. Lateral resolution of 7.2 μm for PAM is achieved. Since miniature components are used, the probe diameter is only 1.7 mm. Imaging of phantom and animals in vivo is conducted to show the imaging capability of the probe. The probe has several advantages by introducing the WLM mode, such as being able to conveniently identify regions of interest and align the focus for PAM mode. The prototype of an endoscope shows potential to facilitate clinical photoacoustic endoscopic applications.     

Label-free high frame rate imaging of circulating blood clots using a dual modal ultrasound and photoacoustic system

Deep vein thrombosis (DVT) is a disorder when a blood clot (thrombus) is formed in one of the deep veins. These clots detach from the original sites and circulate in the blood stream at high velocities. Diagnosing these blood clots at an early stage is necessary to decide the treatment strategy. For label-free, in vivo, and real-time detection, high framerate photoacoustic imaging can be used. In this work, a dual modal clinical ultrasound and photoacoustic (PA) system is used for the high framerate PA imaging of circulating blood clots in blood at linear velocities up to 107 cm/sec. Blood clot had 1.4 times higher signal-to-noise ratio (SNR) in the static mode and 1.3 times higher SNR compared to blood PA signal in the flow experiments. This work demonstrates that fast-moving circulating blood clots are easy to recognize against the background PA signal and may aid in early diagnosis.     

Deep learning protocol for improved photoacoustic brain imaging

One of the key limitations for the clinical translation of photoacoustic imaging is penetration depth that is linked to the tissue maximum permissible exposures (MPE) recommended by the American National Standards Institute (ANSI). Here, we propose a method based on deep learning to virtually increase the MPE in order to enhance the signal‐to‐noise ratio of deep structures in the brain tissue. The proposed method is evaluated in an in vivo sheep brain imaging experiment. We believe this method can facilitate clinical translation of photoacoustic technique in brain imaging, especially in transfontanelle brain imaging in neonates.     

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.     

Hand‐held,clinical dual mode ultrasound ‐ photoacoustic imaging of rat urinary bladder and its applications

Urinary bladder imaging is critical to diagnose urinary tract disorders, and bladder cancer. There is a great need for safe, non‐invasive, and sensitive imaging technique which enables bladder imaging. Photoacoustic imaging is a rapidly growing imaging technique for various biological applications. It can be combined with clinical ultrasound imaging system for hand‐held, dual modal ultrasound‐photoacoustic real‐time imaging. Structural (bladder wall) and functional (accretion of nanoparticles) bladder imaging is shown here with combined ultrasound and photoacoustic imaging in rats. Photoacoustic images of bladder wall is shown using black ink as the contrast agent. Chicken tissues were stacked on the abdomen of the animal to demonstrate the feasibility of photoacoustic imaging till a depth of 2 cm. Also, the feasibility of photoacoustic imaging for a common bladder disorder, vesicoureteral reflux is studied using urinary tract mimicking phantom. It is also shown that a clinical ultrasound system can be used for photoacoustic imaging of non‐invasive clearance study of gold nanorods from circulation by monitoring the gradual accumulation of the gold nanorods in the bladder. The time taken for accumulation of nanorods in the bladder can be used as an indicator of the clearance rate of the nanoparticle circulation from the body.      

Sentinel lymph node detection by combining nonradioactive techniques with contrast agents: State of the art and prospects

The status of sentinel lymph nodes (SLNs) has a substantial prognostic value because these nodes are the first place where cancer cells accumulate along their spreading route. Routine SLN biopsy (“gold standard”) involves peritumoral injections of radiopharmaceuticals, such as technetium-99m, which has obvious disadvantages. This review examines the methods used as “gold standard” analogs to diagnose SLNs. Nonradioactive preoperative and intraoperative methods of SLN detection are analyzed. Promising photonic tools for SLNs detection are reviewed, including NIR-I/NIR-II fluorescence imaging, photoswitching dyes for SLN detection, in vivo photoacoustic detection, imaging and biopsy of SLNs. Also are discussed methods of SLN detection by magnetic resonance imaging, ultrasonic imaging systems including as combined with photoacoustic imaging, and methods based on the magnetometer-aided detection of superparamagnetic nanoparticles. The advantages and disadvantages of nonradioactive SLN-detection methods are shown. The review concludes with prospects for the use of conservative diagnostic methods in combination with photonic tools.     

Photoacoustic imaging of the human placental vasculature

Minimally invasive fetal interventions require accurate imaging from inside the uterine cavity. Twin‐to‐twin transfusion syndrome (TTTS), a condition considered in this study, occurs from abnormal vascular anastomoses in the placenta that allow blood to flow unevenly between the fetuses. Currently, TTTS is treated fetoscopically by identifying the anastomosing vessels, and then performing laser photocoagulation. However, white light fetoscopy provides limited visibility of placental vasculature, which can lead to missed anastomoses or incomplete photocoagulation. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, two PA systems were used to visualize chorionic (fetal) superficial and subsurface vasculature in human placentas. The first system comprised an optical parametric oscillator for PA excitation and a 2D Fabry‐Pérot cavity ultrasound sensor; the second, light emitting diode arrays and a 1D clinical linear‐array ultrasound imaging probe. Volumetric photoacoustic images were acquired from ex vivo normal term and TTTS‐treated placentas. It was shown that superficial and subsurface branching blood vessels could be visualized to depths of approximately 7 mm, and that ablated tissue yielded negative image contrast. This study demonstrated the strong potential of PA imaging to guide minimally invasive fetal therapies.      

Biophotonic technologies for assessment of breast tumor surgical margins—A review

Breast conserving surgery (BCS) offering similar surgical outcomes as mastectomy while retaining breast cosmesis is becoming increasingly popular for the management of early stage breast cancers. However, its association with reoperation rates of 20% to 40% following incomplete tumor removal warrants the need for a fast and accurate intraoperative surgical margin assessment tool that offers cellular, structural and molecular information of the whole specimen surface to a clinically relevant depth. Biophotonic technologies are evolving to qualify as such an intraoperative tool for clinical assessment of breast cancer surgical margins at the microscopic and macroscopic scale. Herein, we review the current research in the application of biophotonic technologies such as photoacoustic imaging, Raman spectroscopy, multimodal multiphoton imaging, diffuse optical imaging and fluorescence imaging using medically approved dyes for breast cancer detection and/or tumor subtype differentiation toward intraoperative assessment of surgical margins in BCS specimens, and possible challenges in their route to clinical translation.     

Optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation

Fast functional and molecular photoacoustic microscopy requires pulsed laser excitations at multiple wavelengths with enough pulse energy and short wavelength‐switching time. Recent development of stimulated Raman scattering in optical fiber offers a low‐cost laser source for multiwavelength photoacoustic imaging. In this approach, long fibers temporally separate different wavelengths via optical delay. The time delay between adjacent wavelengths may eventually limits the highest A‐line rate. In addition, a long‐time delay in fiber may limit the highest pulse energy, leading to poor image quality. In order to achieve high pulse energy and ultrafast dual‐wavelength excitation, we present optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation and a signal separation method. The signal separation method is validated in numerical simulation and phantom experiments. We show that when two photoacoustic signals are partially overlapped with a 50‐ns delay, they can be recovered with 98% accuracy. We apply this ultrafast dual‐wavelength excitation technique to in vivo OR‐PAM. Results demonstrate that A‐lines at two wavelengths can be successfully separated, and sO₂ values can be reliably computed from the separated data. The ultrafast dual‐wavelength excitation enables fast functional photoacoustic microscopy with negligible misalignment among different wavelengths and high pulse energy, which is important for in vivo imaging of microvascular dynamics.     

Non‐invasive sentinel lymph node mapping and needle guidance using clinical handheld photoacoustic imaging system in small animal

Translating photoacoustic imaging (PAI) into clinical setup is a challenge. Handheld clinical real‐time PAI systems are not common. In this work, we report an integrated photoacoustic (PA) and clinical ultrasound imaging system by combining light delivery with the ultrasound probe for sentinel lymph node imaging and needle guidance in small animal. The open access clinical ultrasound platform allows seamless integration of PAI resulting in the development of handheld real‐time PAI probe. Both methylene blue and indocyanine green were used for mapping the sentinel lymph node using 675 and 690 nm wavelength illuminations, respectively. Additionally, needle guidance with combined ultrasound and PAI was demonstrated using this imaging system. Up to 1.5 cm imaging depth was observed with a 10 Hz laser at an imaging frame rate of 5 frames per second, which is sufficient for future translation into human sentinel lymph node imaging and needle guidance for fine needle aspiration biopsy.      

Detecting hemodynamic changes in the foot vessels of diabetic patients by photoacoustic tomography

Limb perfusion monitoring is critical for diabetes mellitus (DM) patients as they are vulnerable to vascular complications due to prolonged hyperglycemia. However, current clinical approaches are ineffective in vascular imaging and in assessing vascular function in lower limbs. In this work, a concave ultrasound transducer array‐based photoacoustic tomography (PAT) system was used to image the foot dorsal section of a subject, and a total of seven DM patients and seven healthy volunteers were enrolled in this study. Hemodynamic changes in foot vessels during vascular occlusion as well as oxygen saturation (SO₂) in rest were analyzed for both groups. The results obtained showed that DM patients have a unique peripheral hemodynamic response to occlusion and a lower level SO₂, compared to that for healthy subjects. This suggests that PAT has the potential to detect vascular dysfunction in DM patients and to measure the effect of treatment.     

High-security photoacoustic identity recognition by capturing hierarchical vascular structure of finger

Currently, most biometric methods mainly use single features, making them easily forged and cracked. In this study, a novel triple-layers biometric recognition method, based on photoacoustic microscopy, is proposed to improve the security of biometric identity recognition. Using the photoacoustic (PA) dermoscope, three-dimensional absorption-structure information of the fingers was obtained. Then, by combining U-Net, Gabor filtering, wavelet analysis and morphological transform, a lightweight algorithm called photoacoustic depth feature recognition algorithm (PADFR) was developed to automatically realize stratification (the fingerprint, blood vessel fingerprint and venous vascular), extracting feature points and identity recognition. The experimental results show that PADFR can automatically recognize the PA hierarchical features with an average accuracy equal to 92.99%. The proposed method is expected to be widely used in biometric identification system due to its high security.     

Near-infrared double-illumination optical-resolution photoacoustic microscopy

Label-free chemical bond imaging is of great importance in biology and medicine. Photoacoustic imaging at the third near-infrared windows (1600-1870 nm, near-infrared-III) provides a stable molecular vibrational imaging tool for lipid-rich tissue owing to the first overtone transition of the C H bond at 1.7 μm. However, lacking high-energy pulsed laser sources at 1.7 μm and the strong water absorption significantly limit the signal-to-noise ratio of the lipid imaging, especially for thin lipid tissues. To circumvent this barrier, we develop near-infrared-III double-illumination optical-resolution photoacoustic microscopy (DIOR-PAM) for improving the sensitivity of label-free lipid imaging. Using the same laser, DIOR-PAM can enhance the sensitivity by nearly 100%, which we prove in the Monte Carlo simulation. We experimentally demonstrated 50% ~ 100% sensitivity enhancements on nonbiological and biological lipid-rich samples.     

Inside Cover

A novel volumetric information fusion based on joint weighted evaluation and stationary wavelet transform is proposed. Threedimensional stationary wavelet transform was performed on multi-focus data to obtain wavelet coefficients. Differential evolution based on joint weighted evaluation was then employed to optimize the block size of division. Corresponding sub-coefficients of multi-focus data were fused with the proposed fusion rule. Finally, large volumetric and high-resolution photoacoustic imaging can be achieved by applying the inverse stationary wavelet transform. Further details can be found in the article by Xianlin Song, Sihang Li, Zhuangzhuang Wang, and| Xiongjun Cao ( e202200234 )

     

Optical coherence hyperspectral microscopy with a single supercontinuum light source

In the paper, we have developed an optical coherence hyperspectral microscopy with a single supercontinuum light source. The microscopy consists of optical coherence tomography (OCT) and hyperspectral imaging (HSI), which can visualize the structural and functional characteristics of biological tissues. The 500 to 700 nm band is selected for HSI and OCT imaging, where HSI enables imaging of oxygen saturation and hemoglobin (Hb) content, while OCT acquires structural characteristics to assess the morphology of biological tissues. The system performance of the optical coherence hyperspectral microscopy is verified by normal mice ears, and the practical applications of the microscopy is further performed in 4T1 and inflammation Balb/c mice ears in vivo. The experimental results demonstrate that the microscopy has potential to provide complementary information for clinical applications.     

A feasibility study of OCT for anatomical and vascular phenotyping of mouse embryo

The embryo phenotyping of genetic murine model is invaluable when investigating functions of genes underlying embryonic development and birth defect. Although traditional imaging technologies such as ultrasound are very useful for evaluating phenotype of murine embryos, the use of advanced techniques for phenotyping is desirable to obtain more information from genetic research. This letter tests the feasibility of optical coherence tomography (OCT) as a high‐throughput phenotyping tool for murine embryos. Three‐dimensional OCT imaging is performed for live and cleared mouse embryos in the late developmental stage (embryonic day 17.5). By using a dynamic focusing method and OCT angiography (OCTA) approach, our OCT imaging of the embryo exhibits rapid and clean visualization of organ structures deeper than 5 mm and complex microvasculature of perfused blood vessels in the murine embryonic body. This demonstration suggests that OCT imaging can be useful for comprehensively assessing embryo anatomy and angiography of genetically engineered mice.