Robot-assisted minimally invasive photoacoustic imaging for monitoring liver ablation using diffusing fiber illumination.

In this paper, we introduce a miniaturized intracardiac photoacoustic (PA) imaging system based on a phased-array intracardiac echocardiography catheter. This PA imaging system enhances imaging feedback during radiofrequency (RF) ablation for atrial fibrillation (A-fib) by providing ablation-induced lesion mapping. The PA imaging catheter with a 4-mm diameter was designed, featuring flexible tip for bending and navigation through the vessels. The catheter’s imaging resolution was evaluated using a phantom study with 0.2-mm-diameter wires. In an ex vivo study, the catheter was used to detect ablation-induced necrosis in porcine cardiac tissue, evaluating its capability to image through blood layer and differentiate necrotic tissue based on spectral characteristics. The catheter achieved an imaging resolution of 647.35 ± 61.60 µm in the phantom study. In the ex vivo study, it successfully identified necrotic lesions on porcine cardiac tissue, distinguishing these from surrounding tissue based on spectral analysis. The catheter system successfully imaged through an 8-mm blood layer, effectively highlighting necrotic regions. The proposed miniaturized PA imaging catheter demonstrated high-resolution imaging capability and effective detection of ablation-induced tissue boundary. Its flexibility and small diameter allow for maneuverability through cardiac vessels, enhancing its utility for intraoperative feedback during RF ablation procedures. This advancement offers a practical tool for improving the precision and effectiveness of RF ablation in A-fib treatment by integrating high-resolution imaging and maneuverability into a PA imaging catheter, potentially facilitating its adoption in clinical practice.

Compared to piezoelectric based photoacoustic (PA) scanners, the planar Fabry-Perot (FP) scanner has several advantages. It can provide small element size with high sensitivity, a smooth broadband frequency response, and is transparent to excitation light. This enables the FP scanner to provide excellent high-resolution in vivo PA images of soft tissue to depths up to approximately 10 mm. However, unlike piezoelectric scanners, the FP scanner in its current form cannot provide a pulse-echo ultrasound (US) as well as a PA image, which is useful because of the additional tissue contrast it provides. To address this, a dual mode FP scanner-based system that, for the first time, can acquire co-registered 3D PA and US images has been developed. In order to provide an optical US generation capability, the FP ultrasound sensor was coated with a novel Gold-Nanoparticle-PDMS composite which was excited with nanosecond laser pulses to generate plane wave US pulses. By modifying the FP sensor in this way, it now acts as an US transmitter as well as a receiver. The coating is highly absorbing at the US generation wavelength (>95%) but transparent at the PA excitation wavelength, the latter to allow the system to also operate in PA imaging mode as before. The generated US pulses exhibited peak pressures in the MPa range, which is comparable to the output of conventional piezoelectric based medical US scanners. The pulses had a broad bandwidth (>40 MHz) and the emitted wavefront was planar to within λ/10 at 10 MHz. PA and pulse-echo US signals were mapped in turn by the FP scanner over centimetre scale areas with a step size of 100 μm and an element size of 64 μm. The -3dB bandwidth of the FP sensor was 30 MHz. Reconstruction methods using a k-space formulation recovered co-registered 3D PA and US images. The system’s lateral spatial resolution was evaluated by imaging a line target at depths up to 10 mm and ranged between 50 and 120 μm for both modes. Arbitrarily shaped 3D objects were imaged to demonstrate the volumetric US imaging capability of the scanner. Tissue mimicking phantoms, with impedance mismatches representative of soft tissues, and ex vivo tissue samples were imaged with the system as well as a conventional clinical US scanner for comparison. Finally, the system obtained promising high-resolution 3D dual mode PA-US images for a variety of phantoms with contrast based on both optical absorption and acoustic impedance. This novel all-optical system has the potential to add complementary morphological contrast to photoacoustic vascular images which could aid the clinical assessment of superficial tumours, lymph node disease and other conditions.

Background: Tumor angiogenesis and hypoxia are associated with breast cancer growth and metastasis. Photoacoustic (PA) tomography is an optical imaging technology that visualizes distribution and oxygenation status of hemoglobin with high spatial resolution. Initially we developed a photoacoustic mammography (PAM) having a flat-shaped scanning detector that could detect breast tumors. Nevertheless, the flat-shaped detector array has the drawback of a limited view. Here we developed a novel PAM system with a hemispherical-shaped detector array (HDA), which enables us to identify microvasculatures non-invasively and allow the collection of nearly spatially isotropic three-dimensional reconstructed image of blood vessels. This non-invasive vascular imaging system may be able to characterize tumor angiogenesis and analyze the status of microcirculation. The aim of this study was to analyze the imaging findings of tumor-related vasculature in breast cancer patients. Patients and method: A PAM system with HDA has been generated in a cooperation project between Canon Inc., Japan, and Kyoto University. Twenty-two primary breast cancer patients, including 5 patients with non-invasive cancer and 17 patients with invasive cancer, diagnosed between December 2014 and December 2015 underwent the PAM imaging analysis. We also applied the breast deformation algorithm from the breast shape in a MRI image to that in a PA image in order to create a fusion image of the two modalities for the analysis. Features of peri- and intra-tumoral vasculature, and their oxygenation status were evaluated. The study protocol was approved by the institutional review board at Kyoto University Hospital (UMIN000012251). All patients provided informed consent to participate in this study. Results: The abnormal peri-tumoral vasculature was detected in 86% of all non-invasive and invasive disease cases. In invasive cancer cases, most tumor-related blood vessels were centripetally directed toward the tumor, and 93% of centripetal blood vessels appeared to be disrupted or rapidly narrowed at the tumor boundary. The centripetal blood vessel structure was frequently observed in invasive cancer compared with non-invasive cancer (61% vs 35%). PA images before and after preoperative chemotherapy were obtained in one case, where intra-tumoral blood vessels became finer after chemotherapy, reflecting normalization of intra-tumoral microcirculation induced by chemotherapy. Conclusions: A PAM system with HDA has provided a high-resolution vascular images of primary breast cancers. The morphological differences of peri-tumoral vasculature were observed between invasive disease and non-invasive disease. These results suggest the potential of PA imaging as a non-invasive tool to analyze tumor vasculature of human breast cancers and maybe be helpful for breast cancer diagnosis. (Acknowledgements) This work was partially supported by the Innovative Techno-Hub for Integrated Medical Bio-imaging Project of the Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Citation Format: Toi M, Asao Y, Takada M, Kataoka M, Endo T, Kawashima M, Yamaga I, Nakayama Y, Tokiwa M, Fakhrejahani E, Torii M, Kawaguchi-Sakita N, Kanao S, Matsumoto Y, Yagi T, Sakurai T, Togashi K, Shiina T. Development of photoacoustic vascular imaging system for breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-10.

Adaptation of a Clinical High-Frequency Transrectal Ultrasound System for Prostate Photoacoustic Imaging: Implementation and Pre-clinical Demonstration

Our previous research has demonstrated that photoacoustic (PA) imaging is capable of evaluating the pathological condition in human peripheral joints affected by inflammatory arthritis. In this work, we tested the performance of a PA imaging system based on the LED light source and its performance for arthritis imaging. The LED-based PA imaging system not only has less cost but also has smaller footprint and, hence, is more portable and convenient for use in rheumatology clinic. 2D B-scan PA and US images of each metacarpophalangeal (MCP) joint were acquired along the sagittal sections. Along the same sections, US Doppler images were also acquired. Images from 12 joints with clinically active arthritis (i.e., positive on Doppler US), 5 joints with subclinically active arthritis (i.e., negative on Doppler US), and 12 joints of normal volunteers were compared. The blood volume in each joint reflecting hyperemia was quantified by counting the density of the color pixels in each pseudo-color PA image. T-tests were conducted to evaluate whether PA imaging can differentiate the three groups. The results from this study suggest that LED-based PA imaging is capable of detecting hyperemia as an important biomarker of joint inflammation. In addition, PA imaging could differentiate the subclinically active arthritis group and the normal group while Doppler US could not, suggesting that PA imaging has higher sensitivity to mildly hyperemia when compared to Doppler US. The imaging technique presented may contribute to rheumatology clinic by providing a new tool for early diagnosis and treatment evaluation of joint inflammation.

Globally, cancer is a major health issue as advances in modern medicine continue to extend the human life span. Breast cancer ranks second as a cause of cancer death in women in the United States. Photoacoustic (PA) imaging (PAI) provides high molecular contrast at greater depths in tissue without the use of ionizing radiation. In this work, we describe the development of a PA tomography (PAT) system and a rapid wavelength-cycling Alexandrite laser designed for clinical PAI applications. The laser produces 450 mJ/pulse at 25 Hz to illuminate the entire breast, which eliminates the need to scan the laser source. Wavelength cycling provides a pulse sequence in which the output wavelength repeatedly alternates between 755 nm and 797 nm rapidly within milliseconds. We present imaging results of breast phantoms with inclusions of different sizes at varying depths, obtained with this laser source, a 5-MHz 128-element transducer and a 128-channel Verasonics system. Results include PA images and 3D reconstruction of the breast phantom at 755 and 797 nm, delineating the inclusions that mimic tumors in the breast.

One of the features of photoacoustic (PA) imaging is small-vessel visualization realized without injection of a contrast agent or exposure to X-rays. For carrying out clinical studies in this field, a prototype PA imaging system has been developed. The PA imaging system utilizes a technological platform of FUJIFILM's clinical ultrasound (US) imaging system mounting many-core MPU for enhancing the image quality of US B-mode and US Doppler mode, which can be superposed onto PA images. By evaluating the PA and US Doppler images of the prototyped system, the applicability of the prototype system to small-vessel visualization has been discussed. The light source for PA imaging was on a compact cart of a US unit and emitted 750 nm wavelength laser pulses. The laser light was transferred to illumination optics in a handheld US transducer, which was connected to the US unit. Obtained PA rf data is reconstructed into PA images in the US unit. 3D images were obtained by scanning a mechanical stage, which the transducer is attached to. Several peripheral parts such as fingers, palms and wrists were observed by PA and US Doppler imaging. As for small arteries, US Doppler images were able to visualize the bow-shaped artery in the tip of the finger. Though PA images cannot distinguish arteries and veins, it could visualize smaller vessels and showed good resolution and vascular connectivity, resulting in a complementary image for the US Doppler images. Therefore, superposed images of the PA, US B-mode and US Doppler can visualize from large to small vessels without a contrast agent, which should be a differentiating feature of US/PA combined technology from other clinical vascular imaging modalities.

PurposeVaricose veins in the lower extremities are dilated subcutaneous varicose veins with a diameter of ≥ 3 mm, caused by increased venous pressure resulting from backflow of blood due to venous valve insufficiency (Gloviczki in Handbook of venous disorders: guidelines of the American venous forum, Hodder Arnold, London, 2009). When diagnosing varicose veins, the shape and thickness of the blood vessels should be accurately visualized in three dimensions. In this study, we investigated a new method for numerical evaluation of vascular morphology related to varicose veins in the lower extremities, using a photoacoustic imaging (PAI) system, which can acquire high-resolution and three-dimensional images noninvasively.MethodsNine patients with varicose veins participated in the study, and their images were captured using an optical camera and PAI system. We visualized the vascular structure, created a blood presence density (BPD) heat map, and examined the correlation between BPD and location of varicose veins.ResultsThe obtained photoacoustic (PA) images demonstrated the ability of this method to visualize vessels ranging from as small as 0.2 mm in diameter to large, dilated vessels in three dimensions. Furthermore, the study revealed a correlation between the high-density part of the BPD heat map generated from the PAI images and the presence of varicose veins.ConclusionPAI is a promising technique for noninvasive and accurate diagnosis of varicose veins in the lower extremities. By providing valuable information on the morphology and hemodynamics of the varicose veins, PAI may facilitate their early detection and treatment.

Simultaneous evaluation of articular cartilage and subchondral bone from immobilized knee in rats by photoacoustic imaging system

Photoacoustic (PA) Imaging can estimate the spatial distribution of oxygen saturation (sO 2 ) and total hemoglobin concentration (HbT) in blood, and be co-registered with B-Mode ultrasound images of the surrounding anatomy. This study will focus on the development of a PA imaging mode on a commercially available array based micro-ultrasound ( US) system that is capable of creating such images. The syst em will then be validated in vivo against a complementary technique for measuring partial pressure of oxygen in blood (pO 2 ). The pO 2 estimates are converted to sO 2 values based on a standard dissociation curve found in the literature. Finally, the system will be used for assessing oxygenation in a murine model of ischemia, both during injury and recovery. Keywords: Photoacoustics; Micro-ultrasound; Small animal imaging; Oxygen saturation; Hemoglobin; Ischemia. 1. INTRODUCTION Photoacoustic (PA) Imaging is sensitive to differences in optical absorption from biological tissues but detects these signals with ultrasound. PA Imaging exploits the photoacoustic effect, whereby an acoustic wave is generated from an object that is illuminated by pulsed electromagnetic radiation. By illuminating tissue, a thermoelastic expansion can occur, and is dependent on the optical absorption at the excitation wavelength of the light. This expansion creates an ultrasound wave that can be detected with an ultrasound transducer. The most commonly accepted PA scanners use either a tomographic (PAT) [1] or a plan ar geometry with a linear array trans ducer [2],[3]. The tomographic approach offers a large effective aperture for data collection, but suffers from a low frame rate, due to the need for hundreds to thousands of laser pulses per frame. The use of a linear array allows a 2-D frame to be acquired with just a few laser pulses, providing much higher frame rates. Because PA Imaging is dependent on op tical absorption, it may be used for discriminating blood from tissue signals. Specifically, the oxygenation of hemoglobin (Hb), the blood pr otein that carries oxygen to tissues, can be assessed with PA Imaging. Hemoglobin with bound oxygen (HbO

Photoacoustic (PA) imaging has shown tremendous promise for imaging tumor vasculature and its function at deeper penetration depths without the use of exogenous contrast agents. Traditional PA imaging systems employ expensive and bulky class IV lasers with low pulse repetition rate, due to which its availability for preclinical cancer research is hampered. In this study, we evaluated the capability of a Light-Emitting Diode (LED)-based PA and ultrasound (US) imaging system for monitoring heterogeneous microvasculature in tumors (up to 10 mm in depth) and quantitatively compared the PA images with gold standard histology images. We used a combination of a 7 MHz linear array US transducer and 850 nm excitation wavelength LED arrays to image blood vessels in a subcutaneous tumor model. After imaging, the tumors were sectioned and stained for endothelial cells to correlate with PA images across similar cross-sections. Analysis of 30 regions of interest in tumors from different mice showed a statistically significant R-value of 0.84 where the areas with high blood vessel density had high PA response while low blood vessel density regions had low PA response. Our results confirm that LED-based PA and US imaging can provide 2D and 3D images of tumor vasculature and the potential it has as a valuable tool for preclinical cancer research.

This paper reports on an aluminum nitride (AlN) piezoelectric micromachined ultrasound transducer (PMUT) array for photoacoustic (PA) imaging, where the high-order resonance modes of the PMUT are utilized to improve imaging resolution. A flexural vibration mode (FVM) PMUT is fabricated and applied in a photoacoustic imaging (PAI) system. Specifically, the microelectromechanical system (MEMS)-based PMUT is suitable for PA endoscopic imaging of blood vessels and bronchi due to its miniature size and high sensitivity. More importantly, AlN is a nontoxic material, which makes it harmless for biomedical applications. In the PAI system, the AlN PMUT array is used to detect PA signals, and the acousto–mechanical response is designed and optimized at the PMUT’s fundamental resonance. In this work, we focus on the high-order resonance performance of the PMUT PAI beyond the fundamental resonance. The acoustic and electrical responses of the PMUT’s high-order resonance modes are characterized and analyzed. The fundamental and three high-order resonance bandwidths are 2.2, 8.8, 18.5, and 48.2 kHz. Compared with the resolution at the fundamental resonance mode, the resolutions at third- and fourth-order resonance modes increase by 38.7% and 76.9% in a phantom experiment. The high-order resonance modes of the AlN PMUT sensor array provide higher central frequency and wider bandwidth for PA signal detection, which increase the resolution of PAI compared to the PMUT working at the fundamental resonance mode.

Introduction: Imaging technologies have been developed to assist physicians and dentists in detecting various diseases. Photoacoustic imaging (PAI) is a new technique that shows great applicability to soft tissues. This study aimed to investigate the effect of diode laser intensity modulation on photoacoustic (PA) image quality. Methods: The prototype of the PAI system in this study utilized a non-ionizing 532 nm continuouswave (CW) diode laser illumination. Samples in this study were oral soft tissues of Sprague-Dawley rats fixed in 10% formalin solution. PA images were taken ex vivo by using the PAI system. The laser exposure for oral soft tissue imaging was set in various duty cycles (16%, 24%, 31%, 39%, and 47%). The samples were embedded in paraffin, and PA images were taken from the paraffinembedded tissue blocks in a similar method by using duty cycles of 40%, 45%, 50%, 55%, 60% respectively to reveal the influence of the laser duty cycle on PA image quality. Results: The oral soft tissue is clearly shown as a yellow to red area in PA images, whereas the nonbiological material appears as a blue background. The color of the PA image is determined by the PA intensity. Hence, the PA intensity of oral soft tissue was generally higher than that of the nonbiological material around it. The Kruskal-Wallis test followed by Mann-Whitney post-hoc analysis revealed significant differences (P<0.05) in the quality of PA images produced by using a 16%-47% duty cycle of laser intensity modulation for direct imaging of oral soft tissue fixed in 10% formalin solution. The PA image quality of paraffin-embedded tissue was higher than that of direct oral soft tissue images, but no significant differences in PA image quality were found between the groups. Conclusion: The PAI system built in this study can image oral soft tissue. The sample preparation and the diode laser intensity modulation may influence the PA image quality for oral soft tissue imaging. Nonetheless, the influence of diode laser intensity modulation is not significant for the PA image quality of paraffin-embedded tissue.

&lt;p&gt;An inexpensive noncontact photoacoustic (PA) imaging system using a low-power continuous wave laser and a kilohertz-range microphone has been developed. The system operates in both optical and PA imaging modes and is designed to be compatible with conventional optical microscopes. Aqueous coupling fluids are not required for the detection of the PA signals; air is used as the coupling medium. The main component of the PA system is a custom designed PA imaging sensor that consists of an air-filled sample chamber and a resonator chamber that isolates a standard kilohertz frequency microphone from the input laser. A sample to be examined is placed on the glass substrate inside the chamber. A laser focused to a small spot by a 40× objective onto the substrate enables generation of PA signals from the sample. Raster scanning the laser over the sample with micrometer-sized steps enables high-resolution PA images to be generated. A lateral resolution of 1.37 μm was achieved in this proof of concept study, which can be further improved using a higher numerical aperture objective. The application of the system was investigated on a red blood cell, with a noise-equivalent detection sensitivity of 43,887 hemoglobin molecules (72.88 × 10−21 mol or 72.88 zeptomol). The minimum pressure detectable limit of the system was 19.1 μPa. This inexpensive, compact noncontact PA sensor is easily integrated with existing commercial optical microscopes, enabling optical and PA imaging of the same sample. Applications include forensic measurements, blood coagulation tests, and monitoring the penetration of drugs into human membrane.&lt;/p&gt;

&lt;p&gt;An inexpensive noncontact photoacoustic (PA) imaging system using a low-power continuous wave laser and a kilohertz-range microphone has been developed. The system operates in both optical and PA imaging modes and is designed to be compatible with conventional optical microscopes. Aqueous coupling fluids are not required for the detection of the PA signals; air is used as the coupling medium. The main component of the PA system is a custom designed PA imaging sensor that consists of an air-filled sample chamber and a resonator chamber that isolates a standard kilohertz frequency microphone from the input laser. A sample to be examined is placed on the glass substrate inside the chamber. A laser focused to a small spot by a 40× objective onto the substrate enables generation of PA signals from the sample. Raster scanning the laser over the sample with micrometer-sized steps enables high-resolution PA images to be generated. A lateral resolution of 1.37 μm was achieved in this proof of concept study, which can be further improved using a higher numerical aperture objective. The application of the system was investigated on a red blood cell, with a noise-equivalent detection sensitivity of 43,887 hemoglobin molecules (72.88 × 10−21 mol or 72.88 zeptomol). The minimum pressure detectable limit of the system was 19.1 μPa. This inexpensive, compact noncontact PA sensor is easily integrated with existing commercial optical microscopes, enabling optical and PA imaging of the same sample. Applications include forensic measurements, blood coagulation tests, and monitoring the penetration of drugs into human membrane.&lt;/p&gt;