Explore the vast range of titles available.

The opacity of conventional ultrasound transducers can impede the miniaturization and workflow of current photoacoustic systems. In particular, optical-resolution photoacoustic microscopy (OR-PAM) requires the coaxial alignment of optical illumination and acoustic-detection paths through complex beam combiners and a thick coupling medium. To overcome these hurdles, we developed a novel OR-PAM method on the basis of our recently reported transparent lithium niobate (LiNbO3) ultrasound transducer (Dangi et al., Optics Letters, 2019), which was centered at 13 MHz ultrasound frequency with 60% photoacoustic bandwidth. To test the feasibility of wearable OR-PAM, optical-only raster scanning of focused light through a transducer was performed while the transducer was fixed above the imaging subject. Imaging experiments on resolution targets and carbon fibers demonstrated a lateral resolution of 8.5 µm. Further, we demonstrated vasculature mapping using chicken embryos and melanoma depth profiling using tissue phantoms. In conclusion, the proposed OR-PAM system using a low-cost transparent LiNbO3 window transducer has a promising future in wearable and high-throughput imaging applications, e.g., integration with conventional optical microscopy to enable a multimodal microscopy platform capable of ultrasound stimulation.

BackgroundOperative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor.MethodsA dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo.ResultsSeven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue.ConclusionsThe safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.

Vascular diseases are becoming an epidemic with an increasing aging population and increases in obesity and type II diabetes. Point-of-care (POC) diagnosis and monitoring of vascular diseases is an unmet medical need. Photoacoustic imaging (PAI) provides label-free multiparametric information of deep vasculature based on strong absorption of light photons by hemoglobin molecules. However, conventional PAI systems use bulky nanosecond lasers which hinders POC applications. Recently, light-emitting diodes (LEDs) have emerged as cost-effective and portable optical sources for the PAI of living subjects. However, state-of-art LED arrays carry significantly lower optical energy (<0.5 mJ/pulse) and high pulse repetition frequencies (PRFs) (4 KHz) compared to the high-power laser sources (100 mJ/pulse) with low PRFs of 10 Hz. Given these tradeoffs between portability, cost, optical energy and frame rate, this work systematically studies the deep tissue PAI performance of LED and laser illuminations to help select a suitable source for a given biomedical application. To draw a fair comparison, we developed a fiberoptic array that delivers laser illumination similar to the LED array and uses the same ultrasound transducer and data acquisition platform for PAI with these two illuminations. Several controlled studies on tissue phantoms demonstrated that portable LED arrays with high frame averaging show higher signal-to-noise ratios (SNRs) of up to 30 mm depth, and the high-energy laser source was found to be more effective for imaging depths greater than 30 mm at similar frame rates. Label-free in vivo imaging of human hand vasculature studies further confirmed that the vascular contrast from LED-PAI is similar to laser-PAI for up to 2 cm depths. Therefore, LED-PAI systems have strong potential to be a mobile health care technology for diagnosing vascular diseases such as peripheral arterial disease and stroke in POC and resource poor settings.

We report flexible thin-film lead zirconate titanate (PZT)-based ultrasonic transducers on polyimide substrates. The transducers are bar resonators designed to operate in the width extension mode. The active elements are 1 µm thick PZT films that were crystallized on Si substrates at 700 °C and transferred to 5 µm thick solution-cast polyimide via dissolution of an underlying release layer. Underwater pitch–catch testing between two neighboring 100 µm × 1000 µm elements showed a 0.2 mV signal at a 1.5 cm distance for a driving voltage of 5 V peak at 9.5 MHz. With the same excitation, a 33 kPa sound pressure output at a 6 mm distance and a 32% bandwidth at −6 dB were measured by hydrophone.

The receive sensitivity of lead zirconate titanate (PZT) piezoelectric micromachined ultrasound transducers (PMUTs) was improved by applying a DC bias during operation. The PMUT receive sensitivity is governed by the voltage piezoelectric coefficient, h31,f. With applied DC biases (up to 15 V) on a 2 μm PbZr0.52Ti0.48O3 film, e31,f increased 1.6 times, permittivity decreased by a factor of 0.6, and the voltage coefficient increased by ~2.5 times. For released PMUT devices, the ultrasound receive sensitivity improved by 2.5 times and the photoacoustic signal improved 1.9 times with 15 V applied DC bias. B-mode photoacoustic imaging experiments showed that with DC bias, the PMUT received clearer photoacoustic signals from pencil leads at 4.3 cm, compared to 3.7 cm without DC bias.

Photoacoustic computed tomography (PACT) has been widely explored for non-ionizing functional and molecular imaging of humans and small animals. In order for light to penetrate deep inside tissue, a bulky and high-cost tunable laser is typically used. Light-emitting diodes (LEDs) have recently emerged as cost-effective and portable alternative illumination sources for photoacoustic imaging. In this study, we have developed a portable, low-cost, five-dimensional (x, y, z, t, λ ) PACT system using multi-wavelength LED excitation to enable similar functional and molecular imaging capabilities as standard tunable lasers. Four LED arrays and a linear ultrasound transducer detector array are housed in a hollow cylindrical geometry that rotates 360 degrees to allow multiple projections through the subject of interest placed inside the cylinder. The structural, functional, and molecular imaging capabilities of the LED–PACT system are validated using various tissue-mimicking phantom studies. The axial, lateral, and elevational resolutions of the system at 2.3 cm depth are estimated as 0.12 mm, 0.3 mm, and 2.1 mm, respectively. Spectrally unmixed photoacoustic contrasts from tubes filled with oxy- and deoxy-hemoglobin, indocyanine green, methylene blue, and melanin molecules demonstrate the multispectral molecular imaging capabilities of the system. Human-finger-mimicking phantoms made of a bone and blood tubes show structural and functional oxygen saturation imaging capabilities. Together, these results demonstrate the potential of the proposed LED-based, low-cost, portable PACT system for pre-clinical and clinical applications.

Photoacoustic imaging combines the high contrast of optical imaging with the spatial resolution and penetration depth of ultrasound. This technique holds tremendous potential for imaging in small animals and importantly, is clinically translatable. At present, there is no accepted standard physical phantom that can be used to provide routine quality control and performance evaluation of photoacoustic imaging instruments. With the growing popularity of the technique and the advent of several commercial small animal imaging systems, it is important to develop a strategy for assessment of such instruments. Here, we developed a protocol for fabrication of physical phantoms for photoacoustic imaging from polyvinyl chloride plastisol (PVCP). Using this material, we designed and constructed a range of phantoms by tuning the optical properties of the background matrix and embedding spherical absorbing targets of the same material at different depths. We created specific designs to enable: routine quality control; the testing of robustness of photoacoustic signals as a function of background; and the evaluation of the maximum imaging depth available. Furthermore, we demonstrated that we could, for the first time, evaluate two small animal photoacoustic imaging systems with distinctly different light delivery, ultrasound imaging geometries and center frequencies, using stable physical phantoms and directly compare the results from both systems.

Studying brain‐wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help gain new insights into the mechanisms of neuro‐ diseases and ‐disorders. Nonetheless, this task is challenging, primarily due to the complexity of neurovascular coupling, which encompasses interdependent hemodynamic parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral oxygen saturation (SO2). The current brain imaging technologies exhibit inherent limitations in resolution, sensitivity, and imaging depth, restricting their capacity to comprehensively capture the intricacies of cerebral functions. To address this, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform is reported, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head‐mountable device, to quantitatively map individual dynamics of CBV, CBF, and SO2 as well as contrast agent enhanced brain imaging at high spatiotemporal resolutions. Following systematic characterization, the fUSPA system is applied to study brain‐wide cerebrovascular reactivity (CVR) at single‐vessel resolution via relative changes in CBV, CBF, and SO2 in response to hypercapnia stimulation. These results show that cortical veins and arteries exhibit differences in CVR in the stimulated state and consistent anti‐correlation in CBV oscillations during the resting state, demonstrating the multiparametric fUSPA system's unique capabilities in investigating complex mechanisms of brain functions. In this work, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging system capable of comprehensively mapping brain‐wide hemodynamics (microvascular blood volume, blood flow, oxygen saturation, and vasoreactivity) in response to various stimuli with high spatiotemporal resolutions is presented. The head‐mountable fUSPA device has the potential to gain new insights into the mechanisms of several neurological disorders, including studies on behaving and freely moving animals.

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.

In recent years, multimodal thermoacoustic imaging has demonstrated superior imaging quality compared to other emerging modalities. It provides functional and molecular information, arising due to electromagnetic absorption contrast, at ultrasonic resolution using inexpensive and non-ionizing imaging methods. The development of optical- as well as radio frequency (RF)-induced thermoacoustic imaging systems would benefit from reliable numerical simulations. To date, most numerical models use a combination of different software in order to model the hybrid thermoacoustic phenomenon. Here, we demonstrate the use of a single open source finite element software platform (ONELAB) for photo- and RF-acoustic computed tomography. The solutions of the optical diffusion equation, frequency domain Maxwell’s equations, and time-domain wave equation are used to solve the optical, electromagnetic, and acoustic propagation problems, respectively, in ONELAB. The results on a test homogeneous phantom and an approximate breast phantom confirm that ONELAB is a very effective software for both photo- and RF-acoustic simulations, and invaluable for developing new reconstruction algorithms and hardware systems.