Photoacoustic tomography (PAT) is a noninvasive imaging modality combining the benefits of optical contrast at ultrasonic resolution. Analytical reconstruction algorithms for photoacoustic (PA) ...signals require a large number of data points for accurate image reconstruction. However, in practical scenarios, data are collected using the limited number of transducers along with data being often corrupted with noise resulting in only qualitative images. Furthermore, the collected boundary data are band-limited due to limited bandwidth (BW) of the transducer, making the PA imaging with limited data being qualitative. In this work, a deep neural network-based model with loss function being scaled root-mean-squared error was proposed for super-resolution, denoising, as well as BW enhancement of the PA signals collected at the boundary of the domain. The proposed network has been compared with traditional as well as other popular deep-learning methods in numerical as well as experimental cases and is shown to improve the collected boundary data, in turn, providing superior quality reconstructed PA image. The improvement obtained in the Pearson correlation, structural similarity index metric, and root-mean-square error was as high as 35.62%, 33.81%, and 41.07%, respectively, for phantom cases and signal-to-noise ratio improvement in the reconstructed PA images was as high as 11.65 dB for in vivo cases compared with reconstructed image obtained using original limited BW data. Code is available at https://sites.google.com/site/sercmig/home/dnnpat .
Four new N‐ethylcarbazole‐linked aza‐boron‐dipyrromethene (aza‐BODIPY) dyes (8 a,b and 9 a,b) were synthesized and characterized. The presence of the N‐ethylcarbazole moiety shifts their absorption ...and fluorescence spectra to the near‐infrared region, λ≈650–730 nm, of the electromagnetic spectrum. These dyes possess strong molar absorptivity in the range of 3–4×104 m−1 cm−1 with low fluorescence quantum yields. The triplet excited state and singlet oxygen generation of these dyes were enhanced upon iodination at the core position. The core‐iodinated dyes 9 a,b showed excellent triplet quantum yields of about 90 and 75 %, with singlet oxygen generation efficiency of about 70 and 60 % relative to that of the parent dyes. Derivatives 8 a,b showed dual absorption profiles, in contrast to dyes 9 a,b, which had the characteristic absorption band of aza‐BODIPY dyes. DFT calculations revealed that the electron density was spread over the iodine and dipyrromethene plane of 9 a,b, whereas in 8 a,b the electron density was distributed on the carbazole group and dipyrromethene plane of aza‐BODIPY. The uniqueness of these aza‐BODIPY systems is that they exhibit efficient triplet‐state quantum yields, high singlet oxygen generation yields, and good photostability. Furthermore, the photoacoustic (PA) characteristics of these aza‐BODIPY dyes was explored, and efficient PA signals for 8 a were observed relative to blood serum with in vitro deep‐tissue imaging, thereby confirming its use as a promising PA contrast agent.
Observation at depth: Carbazole‐linked aza‐boron‐dipyrromethene (aza‐BODIPY) dyes show favorable photophysical properties, as well as efficient triplet and singlet oxygen generation quantum yields. Furthermore, the efficient photoacoustic (PA) signals produced by these dyes makes them excellent candidates for photodynamic therapy and as contrast agents for photoacoustic imaging (see figure).
For a circular scanning geometry in photoacoustic tomography, the axial/radial resolution is spatially invariant and is not affected by the ultrasound transducer (UST, detector) aperture. However, ...the tangential resolution is dependent on the detector aperture size and it varies spatially. Many techniques were proposed to improve the tangential resolution, such as attaching a concave lens in front of the nonfocused transducer or using a virtual point detector. Both of these methods have difficulties. Therefore, a modified delay-and-sum reconstruction algorithm has been proposed which can be used together with a standard ultrasound detector (nonfocused) to improve the tangential resolution. In this work, we validate the modified delay-and-sum algorithm experimentally for both flat and cylindrically focused USTs. More than threefold improvement in tangential resolution is observed. It is also shown that the object shape is recovered with this modified algorithm, which is very helpful for diagnosis and treatment purposes.
The reconstruction methods for solving the ill-posed inverse problem of photoacoustic tomography with limited noisy data are iterative in nature to provide accurate solutions. These methods ...performance is highly affected by the noise level in the photoacoustic data. A singular value decomposition (SVD) based plug and play priors method for solving photoacoustic inverse problem was proposed in this work to provide robustness to noise in the data. The method was shown to be superior as compared to total variation regularization, basis pursuit deconvolution and Lanczos Tikhonov based regularization and provided improved performance in case of noisy data. The numerical and experimental cases show that the improvement can be as high as 8.1 dB in signal to noise ratio of the reconstructed image and 67.98% in root mean square error in comparison to the state of the art methods.
Optoacoustic tomography has been established as a powerful modality for preclinical imaging. However, efficient whole-body imaging coverage has not been achieved owing to the arduous requirement for ...continuous acoustic coupling around the animal. In this work, we introduce panoramic (3600) head-to-tail 3D imaging of mice with spiral volumetric optoacoustic tomography (SVOT). The system combines multi-beam illumination and a dedicated head holder enabling uninterrupted acoustic coupling for whole-body scans. Image fidelity is optimized with self-gated respiratory motion rejection and dual speed-of-sound reconstruction algorithms to attain spatial resolution down to 90 µm. The developed system is thus highly suitable for visualizing rapid biodynamics across scales, such as hemodynamic changes in individual organs, responses to treatments and stimuli, perfusion, total body accumulation, or clearance of molecular agents and drugs with unmatched contrast, spatial and temporal resolution.
Optoacoustic tomography is commonly performed with bulky and expensive short-pulsed solid-state lasers providing high per-pulse energies in the millijoule range. Light emitting diodes (LEDs) ...represent a cost-effective and portable alternative for optoacoustic signal excitation that can additionally provide excellent pulse-to-pulse stability. Herein, we introduce a full-view LED-based optoacoustic tomography (FLOAT) system for deep tissue in vivo imaging. It is based on a custom-made electronic unit driving a stacked array of LEDs, which attains 100 ns pulse width and highly stable (0.62 % standard deviation) total per-pulse energy of 0.48 mJ. The illumination source is integrated into a circular array of cylindrically-focused ultrasound detection elements to result in a full-view tomographic configuration, which plays a critical role in circumventing limited-view effects, enhancing the effective field-of-view and image quality for cross-sectional (2D) imaging. We characterized the FLOAT performance in terms of pulse width, power stability, excitation light distribution, signal-to-noise and penetration depth. FLOAT of the human finger revealed a comparable imaging performance to that achieved with the standard pulsed Nd:YAG laser. It is anticipated that this compact, affordable and versatile illumination technology will facilitate optoacoustic imaging developments in resource-limited settings for biological and clinical applications.
Bulky, expensive Nd:YAG lasers are used in conventional photoacoustic tomography (PAT) systems, making them difficult to translate into clinics. Moreover, real-time imaging is not feasible when a ...single-element ultrasound transducer is used with these low-pulse-repetition-rate lasers (10-100 Hz). Low-cost pulsed laser diodes (PLDs) can be used instead for photoacoustic imaging due to their high-pulse-repetition rates and compact size. Together with acoustic-reflector-based multiple single-element ultrasound transducers, a portable desktop PAT system was developed. This second-generation PLD-based PAT achieved 0.5 s cross-sectional imaging time with high spatial resolution of ∼165 μm and an imaging depth of 3 cm. The performance of this system was characterized using phantom and in vivo studies. Dynamic in vivo imaging was also demonstrated by monitoring the fast uptake and clearance of indocyanine green in small animal (rat) brain vasculature.
Major biological discoveries are made by interrogating living organisms with light. However, the limited penetration of un‐scattered photons within biological tissues limits the depth range covered ...by optical methods. Deep‐tissue imaging is achieved by combining light and ultrasound. Optoacoustic imaging exploits the optical generation of ultrasound to render high‐resolution images at depths unattainable with optical microscopy. Recently, laser ultrasound has been suggested as a means of generating broadband acoustic waves for high‐resolution pulse‐echo ultrasound imaging. Herein, an approach is proposed to simultaneously interrogate biological tissues with light and ultrasound based on layer‐by‐layer coating of silica optical fibers with a controlled degree of transparency. The time separation between optoacoustic and ultrasound signals collected with a custom‐made spherical array transducer is exploited for simultaneous 3D optoacoustic and laser ultrasound (OPLUS) imaging with a single laser pulse. OPLUS is shown to enable large‐scale anatomical characterization of tissues along with functional multi‐spectral imaging of chromophores and assessment of cardiac dynamics at ultrafast rates only limited by the pulse repetition frequency of the laser. The suggested approach provides a flexible and scalable means for developing a new generation of systems synergistically combining the powerful capabilities of optoacoustics and ultrasound imaging in biology and medicine.
Simultaneous deep‐tissue imaging with optoacoustic and laser ultrasound (OPLUS) is achieved through the innovative semi‐transparent emitter, using gold/carbon‐coated optical fibers. OPLUS provides high‐resolution anatomical characterization and functional multi‐spectral imaging, propelling advances in biological and medical applications by combining light and ultrasound for in‐depth tissue analysis.
Photoacoustic tomography (PAT) is a noninvasive hybrid imaging modality providing high contrast and resolution in deep tissue imaging. In a typical PAT system, the photoacoustic (PA) waves are ...recorded using an ultrasound transducer rotating around the sample. Being economical and easily available, a single-element transducer (SET) is commonly employed. For each laser pulse, the SET collects one time-resolved PA signal, known as an A-line. The acquisition of A-lines in a circular scanning PAT system by a SET can be done in two ways: 1) Stop-and-go scan, and 2) Continuous scan. In this work, we compared the two types of scanning methods in terms of image quality, signal-to-noise ratio (SNR), spatial accuracy, resolution, and scan-time for phantoms and in vivo imaging. We found that the image quality, spatial accuracy, and the SNR did not change in continuous scans, as compared to stop-and-go scans. However, there was a significant decrease in scan time in continuous scans. This improvement in scan time was 2-4 folds for lasers with low pulse repetition rate (10 Hz), and up to 7-12 folds for lasers with higher pulse repetition rate (7 kHz).
Intricate assembly of multiple molecular chromophores assisted by protein scaffolds is essential in tuning the optical absorption and energy transfer in the light‐harvesting complexes of the ...photosynthetic systems in nature. However, it remains a challenge to achieve such structural complexity and functionality in synthetic polymer‐chromophore systems. Here, we report a series of polyester‐tethered pyrrolopyrrole cyanine derivatives and their colloidal nanoparticles dispersed in water, which show tunable J‐ or H‐aggregation excitonic coupling and near‐infrared fluorescence by precise control of the polymer chain lengths, composition, and temperature. Moreover, the optimal fluorescence or photothermal effect of the J‐aggregate nanoparticles enables broad applications in fluorescence or photoacoustic bioimaging and phototherapy.
Controllable J‐ or H‐aggregation is realized in a series of polyesters covalently tethered from a near‐infrared fluorophore of pyrrolopyrrole cyanine derivative. Colloidal nanoparticles of these polymers show a temperature‐induced reversible transition from J‐ or H‐aggregate to monomeric state of the fluorophore in nanoparticles and on/off switching of near‐infrared fluorescence. The enhanced near‐infrared fluorescence or photothermal effect of these nanoparticles demonstrates application potentials in tumor imaging and phototherapy.
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