The feasibility to individually localize and manipulate individual particles flowing in blood can lead to important advances in super-resolution imaging, targeted drug delivery, and other fields. State-of-the-art optoacoustic (OA) tomographic imaging systems provide a unique high frame rate imaging capability in three dimensions, which can be exploited for this purpose if particles are sufficiently absorbing. In this work, we introduce silica-core microparticles with a polypyrrole-gold composite shell deposited with a layer-by-layer approach. Microparticles as small as 2 microns could be individually detected. Laser-induced motion of the particles was also observed, which provides a new means for motion control.
KEYWORDS: Sensors, Signal detection, Optoacoustics, Ultrasonography, Capacitance, Signal to noise ratio, In vivo imaging, Image processing, Objectives, Design and modelling
A wideband sensitive needle ultrasound sensor based on a polarized PVDF-TrFE copolymer piezoelectric film has been developed, which is capable of providing a noise equivalent pressure of 14 Pa and a uniform frequency response ranging from 1 to 25 MHz. Its high sensitivity (1.6 μV / Pa) and compact size were achieved by capitalizing on the large electromechanical coupling coefficient of PVDF-TrFE and minimizing parasitic capacitance in a two-stage amplifier structure. The detection sensitivity of the newly designed sensor outperformed commercially available hydrophones with an equivalent sensing element area by a factor of 9. The sensor has been successfully integrated into a light scanning optoacoustic microscopy (OAM) system with a limited working space. Submicrometer resolution images were subsequently attained from living mice without employing signal averaging. The miniature sensor design can readily be integrated into various OAM systems and further facilitate multimodal imaging system implementations.
The feasibility of real-time tracking of microparticles intravenously injected into living organisms can significantly facilitate the development of new biomedical applications, including blood flow characterization, drug delivery, and many others. However, existing imaging modalities generally lack the sensitivity to detect the weak signals generated by individual particles flowing through vascular networks deep within biological tissues. Also, the temporal resolution is usually insufficient to track the particles in an entire three-dimensional region. Herein, we capitalize on the unique advantages of a state-of-the-art high-frame-rate optoacoustic tomographic imaging system to visualize and track monodisperse core-shell microparticles with a diameter of ~4 μm in the mouse brain vasculature. The feasibility of localizing individual solid particles smaller than red blood cells opens new opportunities for mapping the blood flow velocity, enhancing the resolution and visibility of optoacoustic images, and developing new biosensing assays.
We present a fast, multispectral acoustic resolution optoacoustic microscope using a new burst-mode triggering scheme. Three pulsed laser sources are combined to retrieve spectral images across large field-of-views extending over 25mm by 25mm at 28μm lateral and 14μm axial resolution with an overfly scan of a few minutes. Highly sensitive PVDF transducer allows detection of structures 3.8mm below the human skin surface with per pulse energies of only 25μJ. The newly developed system overcomes limitations of previously reported scanning optoacoustic microscopy and mesoscopy implementations, offering a major leap forward in terms of clinical usability, laser safety, effective penetration depth and spectral unmixing capabilities.
Acoustic-resolution optoacoustic microscopy (AR-OAM) visualizes internal tissue structures at millimeter to centimeter scale depths with high spatial resolution. The imaging performance mainly depends on the geometry and detection characteristics of the ultrasound transducer. Reconstruction methods incorporating transducer effects are essential to optimize achievable resolution, contrast and overall image quality. Model-based (MB) reconstruction has been shown to provide excellent imaging performance in several optoacoustic embodiments, due to its capacity to accurately model the transducer. However, the applicability of MB reconstruction methods in AR-OAM has been hampered by the high computational cost. Here, we propose an efficient MB reconstruction framework for largescale AR-OAM by considering scanning symmetries, which enabled capitalizing the computational power of a graphics processing unit. The suggested MB reconstruction method is shown to significantly improve the imaging performance of AR-OAM compared to synthetic aperture focusing technique, as validated in in vivo mouse skin experiment.
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