Project description:Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats' eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.
Project description:Objective and Impact Statement. Simultaneous imaging of ultrasound and optical contrasts can help map structural, functional, and molecular biomarkers inside living subjects with high spatial resolution. There is a need to develop a platform to facilitate this multimodal imaging capability to improve diagnostic sensitivity and specificity. Introduction. Currently, combining ultrasound, photoacoustic, and optical imaging modalities is challenging because conventional ultrasound transducer arrays are optically opaque. As a result, complex geometries are used to coalign both optical and ultrasound waves in the same field of view. Methods. One elegant solution is to make the ultrasound transducer transparent to light. Here, we demonstrate a novel transparent ultrasound transducer (TUT) linear array fabricated using a transparent lithium niobate piezoelectric material for real-time multimodal imaging. Results. The TUT-array consists of 64 elements and centered at ~6 MHz frequency. We demonstrate a quad-mode ultrasound, Doppler ultrasound, photoacoustic, and fluorescence imaging in real-time using the TUT-array directly coupled to the tissue mimicking phantoms. Conclusion. The TUT-array successfully showed a multimodal imaging capability and has potential applications in diagnosing cancer, neurological, and vascular diseases, including image-guided endoscopy and wearable imaging.
Project description:The standard-of-care for evaluating lymph node status in breast cancers and melanoma metastasis is sentinel lymph node (SLN) assessment performed with a handheld gamma probe and radioisotopes. However, this method inevitably exposes patients and physicians to radiation, and the special facilities required limit its accessibility. Here, we demonstrate a non-ionizing, cost-effective, handheld photoacoustic finder (PAF) fully integrated with a solid-state dye laser and transparent ultrasound transducer (TUT). The solid-state dye laser handpiece is coaxially aligned with the spherically focused TUT. The integrated finder readily detected photoacoustic signals from a tube filled with methylene blue (MB) beneath a 22 mm thick layer of chicken tissue. In live animals, we also photoacoustically detected both SLNs injected with MB and subcutaneously injected melanomas. We believe that our radiation-free and inexpensive PAF can play a vital role in SLN assessment.
Project description:Combining focused optical excitation and high-frequency ultrasound detection, optical-resolution photoacoustic microscopy (OR-PAM) can provide micrometer-level spatial resolution with millimeter-level penetration depth and has been employed in a variety of biomedical applications. However, it remains a challenge for OR-PAM to achieve a high imaging speed and a large field of view at the same time. In this work, we report a new approach to implement high-speed wide-field OR-PAM, using a cylindrically-focused transparent ultrasound transducer (CFT-UT). The CFT-UT is made of transparent lithium niobate coated with indium-tin-oxide as electrodes. A transparent cylindrical lens is attached to the transducer surface to provide an acoustic focal line with a length of 9 mm. The excitation light can pass directly through the CFT-UT from the above and thus enables a reflection imaging mode. High-speed imaging is achieved by fast optical scanning of the focused excitation light along the CFT-UT focal line. With the confocal alignment of the optical excitation and acoustic detection, a relatively high detection sensitivity is maintained over the entire scanning range. The CFT-UT-based OR-PAM system has achieved a cross-sectional frame rate of 500 Hz over the scanning range of 9 mm. We have characterized the system’s performance on phantoms and demonstrated its application on small animal models in vivo. We expect the new CFT-UT-based OR-PAM will find matched biomedical applications that need high imaging speed over a large field of view.
Project description:This work extends the effective aperture size by coherently compounding the received radio frequency data from multiple transducers. As a result, it is possible to obtain an improved image, with enhanced resolution, an extended field of view (FoV), and high-acquisition frame rates. A framework is developed in which an ultrasound imaging system consisting of N synchronized matrix arrays, each with partly shared FoV, take turns to transmit plane waves (PWs). Only one individual transducer transmits at each time while all N transducers simultaneously receive. The subwavelength localization accuracy required to combine information from multiple transducers is achieved without the use of any external tracking device. The method developed in this study is based on the study of the backscattered echoes received by the same transducer and resulting from a targeted scatterer point in the medium insonated by the multiple ultrasound probes of the system. The current transducer locations along with the speed of sound in the medium are deduced by optimizing the cross correlation between these echoes. The method is demonstrated experimentally in 2-D for two linear arrays using point targets and anechoic lesion phantoms. The first demonstration of a free-hand experiment is also shown. Results demonstrate that the coherent multi-transducer ultrasound imaging method has the potential to improve ultrasound image quality, improving resolution, and target detectability. Compared with coherent PW compounding using a single probe, lateral resolution improved from 1.56 to 0.71 mm in the coherent multi-transducer imaging method without acquisition frame rate sacrifice (acquisition frame rate 5350 Hz).
Project description:Photoacoustic microscopy (PAM) does not rely on contrast agent to image the optical absorption contrast in biological tissue. It is uniquely suited for measuring several tissue physiological parameters, such as hemoglobin oxygen saturation, that would otherwise remain challenging. Researchers are designing new clinical diagnostic tools and multimodal microscopic systems around PAM to fully unleash its potential. However, the sizeable and opaque piezoelectric ultrasonic detectors commonly used in PAM impose a serious constraint. Our solution is a coverslip-style optically transparent ultrasound detector based on a polymeric optical micro-ring resonator (MRR) with a total thickness of 250 μm. It enables highly-sensitive ultrasound detection over a wide receiving angle with a bandwidth of 140 MHz, which corresponds to a photoacoustic saturation limit of 287 cm(-1), at an estimated noise-equivalent pressure (NEP) of 6.8 Pa. We also established a theoretical framework for designing and optimizing the MRR for PAM.
Project description:Photoacoustic imaging (PAI) combines optical contrast with ultrasound spatial resolution and can be obtained up to a depth of a few centimeters. Hand-held PAI systems using linear array usually operate in reflection mode using a dark-field illumination scheme, where the optical fiber output is attached to both sides of the elevation plane (short-axis) of the transducer. More recently, bright-field strategies where the optical illumination is coaxial with acoustic detection have been proposed to overcome some limitations of the standard dark-field approach. In this paper, a novel multiangle long-axis lateral illumination is proposed. Monte Carlo simulations were conducted to evaluate light delivery for three different illumination schemes: bright-field, standard dark-field, and long-axis lateral illumination. Long-axis lateral illumination showed remarkable improvement in light delivery for targets with a width smaller than the transducer lateral dimension. A prototype was developed to experimentally demonstrate the feasibility of the proposed approach. In this device, the fiber bundle terminal ends are attached to both sides of the transducer's long-axis and the illumination angle of each fiber bundle can be independently controlled. The final PA image is obtained by the coherent sum of subframes acquired using different angles. The prototype was experimentally evaluated by taking images from a phantom, a mouse abdomen, forearm, and index finger of a volunteer. The system provided light delivery enhancement taking advantage of the geometry of the target, achieving sufficient signal-to-noise ratio at clinically relevant depths.
Project description:Three-dimensional (3D) photoacoustic imaging (PAI) can provide rich information content and has gained increasingly more attention in various biomedical applications. However, current 3D PAI methods either involves pointwise scanning of the 3D volume using a single-element transducer, which can be time-consuming, or requires an array of transducers, which is known to be complex and expensive. By utilizing a 3D encoder and compressed sensing techniques, we develop a new imaging modality that is capable of single-shot 3D PAI using a single-element transducer. The proposed method is validated with phantom study, which demonstrates single-shot 3D imaging of different objects and 3D tracking of a moving object. After one-time calibration, while the system could perform single-shot 3D imaging for different objects, the calibration could remain effective over 7 days, which is highly beneficial for practical translation. Overall, the experimental results showcase the potential of this technique for both scientific research and clinical applications.
Project description:Ultrasound detection is one of the major components of photoacoustic imaging systems. Advancement in ultrasound transducer technology has a significant impact on the translation of photoacoustic imaging to the clinic. Here, we present an overview on various ultrasound transducer technologies including conventional piezoelectric and micromachined transducers, as well as optical ultrasound detection technology. We explain the core components of each technology, their working principle, and describe their manufacturing process. We then quantitatively compare their performance when they are used in the receive mode of a photoacoustic imaging system.
Project description:Photoacoustic (PA) imaging has gained much attention, providing structural and functional information in combination with clinical ultrasound (US) imaging systems. 2D PA and US imaging is easily implemented, but its heavy dependence on operator skills makes 3D imaging preferable. In this study, we propose a panoramic volumetric clinical PA and US imaging system equipping a handheld imaging scanner weighing 600 g and measuring 70 × 62 × 110 mm3. Multiple PA/US scans were performed to cover a large field-of-view (FOV), and the acquired PA/US volumes were mosaic-stitched after manually correcting the positions and rotations in a total of 6 degrees of freedom. PA and US maximum amplitude projection images were visualized online, while spectral unmixed data was quantified offline. The performance of the system was tested via tissue-mimicking phantom experiments. The system's potential was confirmed in vivo by panoramically imaging vascular networks in human arms and necks, with FOVs of 331 × 38 and 129 × 120 mm2, respectively. Further, we quantified hemoglobin oxygen saturation levels in the radial artery, brachial artery, carotid artery, and jugular vein. We hope that this system can be applied for various clinical fields such as cardiovascular imaging, dermatology, vascular surgery, internal medicine, and oncology.