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.
Bio-compatible contrast agents based on clinically-approved indocyanine green (ICG) can greatly enhance the deep-tissue imaging performance of optoacoustic (OA) imaging systems and facilitate the clinical translation of this modality. In this work, we propose an inverse emulsion approach to synthetize bio-based, bio-degradable nano- and micro-capsules consisting of an aqueous core of ICG and a cross-linked casein shell. The feasibility to visualize and track individual capsules with a diameter of 4-5 micrometers is demonstrated in vitro and in vivo. This can pave the way towards clinical approval of contrast agents capable of being detected at a single-particle level.
Optoacoustic tomography is typically implemented with bulky solid-state lasers delivering per-pulse energies in the millijoule range. Light emitting diodes (LEDs) represent a cost-effective and portable alternative for signal excitation further offering excellent pulse-to-pulse stability. Herein, we describe a full-view LED-based optoacoustic tomography (FLOAT) system for deep-tissue in vivo imaging. A custom-made electronic unit driving a stacked array of LEDs attains stable light pulses with total per-pulse energy of 0.48 mJ and 100 ns pulse width. The LED array was arranged on a circular configuration and integrated in a full-ring ultrasound array enabling full-view tomographic imaging performance in cross-sectional (2D) geometry. As a proof of concept, we scanned the medial phalanx of the index finger without extrinsic administration of a contrast agent. We anticipate that this compact, affordable, and versatile illumination technology will facilitate dissemination of the optoacoustic technology in resource-limited settings.
Comprehensive evaluation of microvascular function under normal and pathological conditions requires high-resolution three-dimensional microangiography capable of providing both morphological and functional information. Herein, we propose the stereovision Diffuse Optical Localization imaging (sDOLI) approach to attain transcranial volumetric brain microangiography through triangulation and stereo-matching of images collected with two short-wave infrared cameras. The spatio-temporal sparsity of flowing microparticles allows their precise localization while minimizing structural overlaps occurring in the dual-view projections. sDOLI is shown to preserve high spatial resolution which enables transcranial mapping of murine cortical microcirculation at capillary resolution while retrieving quantitative functional information across the entire mouse cortex.
Localization optoacoustic tomography (LOT) can significantly enhance the optoacoustic imaging capabilities by providing a spatial resolution beyond the acoustic diffraction barrier and further enabling mapping the blood flow velocity. Higher resolution results in an enhanced sensitivity to cardiac and breathing motion, which can degrade the LOT imaging performance even if the animal is constrained. We suggest a new approach based on aligning the motion-affected frames of the acquired sequence with a reference frame. Localization and tracking of particles is then performed in the corrected sequence. This results in an enhanced imaging performance and more accurate velocity readings.
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.
Photosynthetic single-celled diatom algae, due to their unique structure and properties, represent promising candidates for various applications in technology and biomedicine. These nanostructured objects, enveloped within a silica cell wall called a frustule, play a significant role in Earth’s ecology. In this study, we proposed new techniques for monitoring the growth of diatoms—in situ fluorescence measurements using the IVIS imaging system and photoacoustic measurements with a raster scanning optoacoustic mesoscopy (RSOM) setup. Two different diatom cultures, Achnanthidium sibiricum and Encyonema silesiacum, were cultivated under the optimal conditions in the incubator and monitored over the period of 70 days. Our results showed that the total radiant efficiency increases with increasing incubation time for E. silesiacum. Simultaneously, for A. sibiricum it slightly decreases after 56 days, indicating that diatoms were at the end of their exponential growth phase. The photoacoustic signal from E. silesiacum was lower than from A. sibiricum, which is in good agreement with spectroscopic characterization results. The IVIS imaging system made it possible to assess the growth and viability of diatom cells without compromising cell integrity. In contrast, photoacoustic imaging has proved to be suitable for the rapid detection and thorough in situ assessment of the density of diatom colonies due to the presence of light-absorbing chromophores. These methods can be used to monitor the growth of diatoms and facilitate the harvesting of bioactive substances derived from diatoms for pharmaceutical and biomedical purposes.
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