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:Dual-mode photoacoustic/ultrasound endoscopy (ePAUS) is a promising tool for preclinical and clinical interventions. To be clinically useful, ePAUS must deliver high-performance ultrasound imaging comparable to commercial systems and maintain high photoacoustic imaging performance at long working distances. This requires a transducer with an intact physical aperture and coaxial alignment of acoustic and optical beams within the probe, a challenging integration task. We present a high-performance ePAUS probe with a miniaturized, optically transparent ultrasonic transducer (TUT) called ePAUS-TUT. The 1.8-mm-diameter probe, fitting into standard endoscopic channels, aligns acoustic and optical beams efficiently, achieving commercial-level ultrasound and high-resolution photoacoustic imaging over long distances. These imaging capabilities were validated through in vivo imaging of a rat's rectum and a pig's esophagus. The ePAUS-TUT system substantially enhances feasibility and potential for clinical applications.
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:Sodium has many vital and diverse roles in the human body, including maintaining the cellular pH, generating action potential, and regulating osmotic pressure. In cancer, sodium dysregulation has been correlated with tumor growth, metastasis, and immune cell inhibition. However, most in vivo sodium measurements are performed via Na23 NMR, which is handicapped by slow acquisition times, a low spatial resolution (in mm), and low signal-to-noise ratios. We present here a plasticizer-free, ionophore-based sodium-sensing nanoparticle that utilizes a solvatochromic dye transducer to circumvent the pH cross-sensitivity of most previously reported sodium nano-sensors. We demonstrate that this nano-sensor is non-toxic, boasts a 200 μM detection limit, and is over 1000 times more selective for sodium than potassium. Further, the in vitro photoacoustic calibration curve presented demonstrates the potential of this nano-sensor for performing the in vivo chemical imaging of sodium over the entire physiologically relevant concentration range.
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:Ultrafast and sensitive response of surface plasmon polaritons to the ultrasonically-modulated changes in refractive index of the water allows photoacoustic impulses to be measured using surface plasmon resonance (SPR) sensors. However, the sensing modalities always suffer from either low sensitivity or instable signal output, possibly precluding imaging recovery. By exploiting that pressure transients can substantially produce phase shift in p-polarized optical reflection but have no impact on s-polarized component in SPR sensing, we develop a common-path interferometric SPR sensor for photoacoustic measurement, in which time-varying light interference between photoacoustically-perturbed p-polarized beam and its orthogonal s-polarized component of a single interrogation laser is monitored. Such configuration retains optimum photoacoustic measurement with concurrent very stable signal output, high sensitivity (noise-equivalent-pressure sensitivity of ∼95.6 Pa), and broad bandwidth (∼173 MHz). Volumetric microvascular imaging from mouse ear in vivo is obtained, suggesting that the novel sensing approach potentially advances biomedical photoacoustic applications.
Project description:A comprehensive understanding of a tumor is required for accurate diagnosis and effective treatment. However, currently, there is no single imaging modality that can provide sufficient information. Photoacoustic (PA) imaging is a hybrid imaging technique with high spatial resolution and detection sensitivity, which can be combined with ultrasound (US) imaging to provide both optical and acoustic contrast. Elastography can noninvasively map the elasticity distribution of biological tissue, which reflects pathological conditions. In this study, we incorporated PA elastography into a commercial US/PA imaging system to develop a tri-modality imaging system, which has been tested for tumor detection using four mice with different physiological conditions. The results show that this tri-modality imaging system can provide complementary information on acoustic, optical, and mechanical properties. The enabled visualization and dimension estimation of tumors can lead to a more comprehensive tissue characterization for diagnosis and treatment.
Project description:Conventional intravascular ultrasound (IVUS) uses piezoelectric transducers to electrically generate and receive ultrasound. However, it remains a challenge to achieve large bandwidth for high resolution without compromising imaging depth. We report an all-optical IVUS (AO-IVUS) imaging system using picosecond laser pulse-pumped carbon composite for ultrasound excitation and π-phase-shifted fiber Bragg gratings for ultrasound detection. Using this all-optical technique, we achieved ultrawide-bandwidth (147%) and high-resolution (18.6 micrometers) IVUS imaging, which is unattainable by conventional technique. Imaging performance has been characterized in phantoms, presenting 18.6-micrometer axial resolution, 124-micrometer lateral resolution, and 7-millimeter imaging depth. Rotational pullback imaging scans are performed in rabbit iliac artery, porcine coronary artery, and rabbit arteries with drug-eluting metal stents, in parallel with commercial intravenous ultrasound scans as reference. Results demonstrated the advantages of high-resolution AO-IVUS in delineating details in vascular structures, showing great potential in clinical applications.