Search Results (54)

Photoacoustic tomography (PAT), also known as optoacoustic tomography, has been emerging as a biomedical imaging modality that can provide cross-sectional or three-dimensional (3D) visualization of biological tissues such as blood vessels and lymphatic vessels in vivo at high resolution. The principle behind the visualization involves the light being absorbed by the tissues which results in the generation of ultrasound. Depending on the strength of ultrasound and its decay rate, it could be used to visualize the absorber location. In general, pulsed lasers such as the Q-switched Nd-YAG and OPO lasers that provide high-energy widths in the range of a few nanoseconds operating at low repetition rates are commonly used as a light source in photoacoustic imaging. However, such lasers are expensive and occupy ample space. Therefore, PAT systems that use LED as the source instead of lasers, which have the advantage of being obtainable at low cost and portable, are gaining attention. However, LED light sources have significantly low energy, and the photoacoustic signals generated have a low signal-to-noise ratio (SNR). Therefore, in LED-based systems, one way to strengthen the signal and improve the SNR is to significantly increase the repetition rate of LED pulses and use signal processing, which can be achieved using a high-power LED along M-sequence signal decoding. M-sequence signal decoding is effective, especially under high repetition rates, thus improving the SNR. However, power supplies for high-power LEDs have a circuit jitter, resulting in random temporal fluctuations in the emitted light. Such jitters, in turn, would affect the M-sequence-based signal decoding. Therefore, we propose a new decoding algorithm which compensates for LED jitter in the M-sequence signal processing. We show that the proposed new signal processing method can significantly improve the SNR of the photoacoustic signals. Full article

The complex composition of cultural heritage (CH) items presents significant challenges in assessing their condition and predicting potential risks of material degradation. Typically employed diagnostic optical methods are inevitably limited by light scattering, thus restricting in-depth investigations of objects with complex structural and optical properties. To address this issue, we introduce a novel reflection-mode optoacoustic (OA) diagnostic system for non-contact and non-invasive measurements of CH, placing emphasis on the detection of ageing-related modifications in artistic media such as paints. In this direction, the sensitivity of OA measurements was proven to be up to two orders of magnitude higher than conventional absorption spectroscopy assessments. Furthermore, we have evaluated the in-depth imaging capabilities of the developed OA system, demonstrating that it can offer superior contrast levels of sketches beneath opaque paint layers compared to standard near-infrared diagnostic techniques. The current OA imaging technology may advance state-of-the-art diagnostic capabilities in CH preservation by delivering unprecedented depth-to-resolution ratios combined with exceptional optical absorption sensitivity in a non-invasive manner. These features are crucial for the early detection of material degradation and the comprehensive analysis of CH objects, facilitating the development of optimal conservation strategies to prolong their lifespan and preserve their aesthetic value. Full article

Three-dimensional passive acoustic mapping (PAM) with matrix arrays typically suffers from high demands on the receiving electronics and high computational load. In our study, we investigated, both numerically and experimentally, the influence of matrix array aperture size, element count, and beamforming approaches on defined image metrics. With a numerical Vokurka model, matrix array acquisitions of cavitation signals were simulated. In the experimental part, two 32 × 32 matrix arrays with different pitches and aperture sizes were used. After being reconstructed into 3D cavitation maps, defined metrics were calculated for a quantitative comparison of experimental and numerical data. The numerical results showed that the enlargement of the aperture from 5 to 40 mm resulted in an improvement of the full width at half maximum (FWHM) by factors of 6 and 13 (in lateral and axial dimension, respectively). A larger array sparsity influenced the point spread function (PSF) only slightly, while the grating lobe level (GLL) remained more than 12 dB below the main lobe. These results were successfully experimentally confirmed. To further reduce the GLL caused by array sparsity, we adapted a non-linear filter from optoacoustics for use in PAM. In combination with the delay, multiply, sum, and integrate (DMSAI) algorithm, the GLL was decreased by 20 dB for 64-element reconstructions, resulting in levels that were identical to the fully populated matrix reconstruction levels. Full article

Metal phthalocyaninates and their higher homologues are recognized as deep-red luminophores emitting from their lowest excited singlet state. Herein, we report on the design, synthesis, and in-depth characterization of a new class of dual-emissive (visible and NIR) metal naphthalocyaninates. A 4-N,N-dimethylaminophen-4-yl-substituted naphthalocyaninato zinc(II) complex (Zn-NMe₂Nc) and the derived water-soluble coordination compound (Zn-NMe₃Nc) exhibit a near-infrared fluorescence from the lowest ligand-centered state, along with a unique push–pull-supported luminescence in the visible region of the electromagnetic spectrum. An unprecedentedly broad structural (2D-NMR spectroscopy and mass spectrometry) as well as photophysical characterization (steady-state state and time-resolved photoluminescence spectroscopy) is presented. The unique dual emission was assigned to two independent sets of singlet states related to the intrinsic Q-band of the macrocycle and to the push–pull substituents in the molecular periphery, respectively, as predicted by TD-DFT calculations. In general, the elusive chemical aspects of these macrocyclic compounds are addressed, involving both reaction conditions, thorough purification, and in-depth characterization. Besides the fundamental aspects that are investigated herein, the photoacoustic properties were exemplarily examined using phantom gels to assess their tomographic imaging capabilities. Finally, the robust luminescence in the visible range arising from the push–pull character of the peripheral moieties demonstrated a notable independence from aggregation and was exemplarily implemented for optical imaging (FLIM) through time-resolved multiphoton micro(spectro)scopy. Full article

Photoacoustic tomography (PAT) is an emerging imaging technique with great potential for a wide range of biomedical imaging applications. The transducers impulse response (TIR) is a key factor affecting the performance of photoacoustic imaging (PAI). It is customary in PAI to assume that TIR is known or obtain it from experiments. In this paper, we investigate the possibility of obtaining TIR in another way. A new method is proposed to extract TIR from observed optoacoustic signal (OPAS) data, without prior knowledge, as a known condition. It is based on the relation between the OPAS data and the photoacoustic pressure signal (PAPS) at transducer positions. The relation can be expressed as a homogeneous linear equation. The TIR is solved by solving the homogeneous equation. The numerical test verifies the effectiveness of the presented method. This article also discusses the effect of calculation parameters on the extracting precision of TIR. Full article

There is a growing interest in exploring the therapeutically mediated modulation of tumor vascularization of pancreatic cancer, which is known for its poorly perfused tumor microenvironment limiting the delivery of therapeutic agents to the tumor site. Here, we assessed how magnetic hyperthermia in combination with chemotherapy selectively affects growth, the vascular compartment of tumors, and the presence of tumor cells expressing key regulators of angiogenesis. To that purpose, a orthotopic PANC-1 (fluorescent human pancreatic adenocarcinoma) mouse tumor model (Rj:Athym-Foxn1nu/nu) was used. Magnetic hyperthermia was applied alone or in combination with systemic chemotherapy (gemcitabine 50 mg per kg body weight, nab-pacitaxel 30 mg/kg body weight) on days 1 and 7 following magnetic nanoparticle application (dose: 1 mg per 100 mm³ of tumor). We used ultrasound imaging, immunohistochemistry, multi-spectral optoacoustic tomography (MSOT), and hematology to assess the biological parameters mentioned above. We found that magnetic hyperthermia in combination with gemcitabine/paclitaxel chemotherapy was able to impact tumor growth (decreased volumes and Ki67 expression) and to trigger neo-angiogenesis (increased small vessel diameter) as a result of the therapeutically mediated cell damages/stress in tumors. The applied stressors activated specific pro-angiogenic mechanisms, which differed from those seen in hypoxic conditions involving HIF-1α, since (a) treated tumors showed a significant decrease of cells expressing VEGF, CD31, HIF-1α, and neuropilin-1; and (b) the relative tumor blood volume and oxygen level remained unchanged. Neo-angiogenesis seems to be the result of the activation of cell stress pathways, like MAPK pathways (high number of pERK-expressing tumor cells). In the long term, the combination of magnetic hyperthermia and chemotherapy could potentially be applied to transiently modulate tumor angiogenesis and to improve drug accessibility during oncologic therapies of pancreatic cancer. Full article

Microvascular changes in diabetes affect the function of several critical organs, such as the kidneys, heart, brain, eye, and skin, among others. The possibility of detecting such changes early enough in order to take appropriate actions renders the development of appropriate tools and techniques an imperative need. To this end, several sensing and imaging techniques have been developed or employed in the assessment of microangiopathy in patients with diabetes. Herein, we present such techniques; we provide insights into their principles of operation while discussing the characteristics that make them appropriate for such use. Finally, apart from already established techniques, we present novel ones with great translational potential, such as optoacoustic technologies, which are expected to enter clinical practice in the foreseeable future. Full article

Agriculture plays a pivotal role in food security and food security is challenged by pests and pathogens. Due to these challenges, the yields and quality of agricultural production are reduced and, in response, restrictions in the trade of plant products are applied. Governments have collaborated to establish robust phytosanitary measures, promote disease surveillance, and invest in research and development to mitigate the impact on food security. Classic as well as modernized tools for disease diagnosis and pathogen surveillance do exist, but most of these are time-consuming, laborious, or are less sensitive. To that end, we propose the innovative application of a hybrid imaging approach through the combination of confocal fluorescence and optoacoustic imaging microscopy. This has allowed us to non-destructively detect the physiological changes that occur in plant tissues as a result of a pathogen-induced interaction well before visual symptoms occur. When broccoli leaves were artificially infected with Xanthomonas campestris pv. campestris (Xcc), eventually causing an economically important bacterial disease, the induced optical absorption alterations could be detected at very early stages of infection. Therefore, this innovative microscopy approach was positively utilized to detect the disease caused by a plant pathogen, showing that it can also be employed to detect quarantine pathogens such as Xylella fastidiosa. Full article

With the emergence of sentinel node technology, many patients can be staged histopathologically using lymphatic mapping and selective lymphadenectomy. Structural imaging by using US, CT and MR permits precise measurement of lymph node volume, which is strongly associated with neoplastic involvement. Sentinel lymph node detection has been an ideal field of application for nuclear medicine because anatomical data fails to represent the close connections between the lymphatic system and regional lymph nodes, or, more specifically, to identify the first draining lymph node. Hybrid imaging has demonstrated higher accuracy than standard imaging in SLN visualization on images, but it did not change in terms of surgical detection. New alternatives without ionizing radiations are emerging now from “non-radiological” fields, such as ophthalmology and dermatology, where fluorescence or opto-acoustic imaging, for example, are widely used. In this paper, we will analyze the advantages and limits of the main innovative methods in sentinel lymph node detection, including innovations in lymphoscintigraphy techniques that persist as the gold standard to date. Full article

An experimental study on an innovative contrast agent is presented. This work demonstrates that copper sulfide in the form of small-sized nanoparticles can be exploited in photoacoustic imaging. An advantage of this material is strong light absorption in the near-infrared range, especially in the transparency windows of biological tissues. In order to yield a proper contrast, light absorption must be followed by heat release with high efficiency. Therefore, it is important to evaluate the photochemical conversion efficiency of the material. We applied a method that is strictly related to photoacoustic applications. The nanoparticles were produced according to a well-established synthesis. Subsequently, they were diluted in pure water to obtain an extinction <0.2/cm at 1064 nm. The photoacoustic signals, generated by 1064 nm laser excitation, were analyzed as a function of concentration and incident laser energy below 70 μJ /pulse. The signals were carefully compared with those of a reference aqueous solution, containing a light-absorbing ionic solute. Data analysis yielded a light-to-heat conversion efficiency 1.0 (±0.1). We discuss this result by comparison with related studies on other types of copper sulfide nanoparticles, where the conversion efficiency reportedly varied from 33% to 93%. The high value determined in the present study possibly indicates that resonant light scattering and luminescence are negligible for our material system. Full article

Variations in vascular wall shear stress are often presumed to result in the formation of atherosclerotic lesions at specific arterial regions, where continuous laminar flow is disturbed. The influences of altered blood flow dynamics and oscillations on the integrity of endothelial cells and the endothelial layer have been extensively studied in vitro and in vivo. Under pathological conditions, the Arg-Gly-Asp (RGD) motif binding integrin α_vβ₃ has been identified as a relevant target, as it induces endothelial cell activation. Animal models for in vivo imaging of endothelial dysfunction (ED) mainly rely on genetically modified knockout models that develop endothelial damage and atherosclerotic plaques upon hypercholesterolemia (ApoE^−/− and LDLR^−/−), thereby depicting late-stage pathophysiology. The visualization of early ED, however, remains a challenge. Therefore, a carotid artery cuff model of low and oscillating shear stress was applied in CD-1 wild-type mice, which should be able to show the effects of altered shear stress on a healthy endothelium, thus revealing alterations in early ED. Multispectral optoacoustic tomography (MSOT) was assessed as a non-invasive and highly sensitive imaging technique for the detection of an intravenously injected RGD-mimetic fluorescent probe in a longitudinal (2–12 weeks) study after surgical cuff intervention of the right common carotid artery (RCCA). Images were analyzed concerning the signal distribution upstream and downstream of the implanted cuff, as well as on the contralateral side as a control. Subsequent histological analysis was applied to delineate the distribution of relevant factors within the carotid vessel walls. Analysis revealed a significantly enhanced fluorescent signal intensity in the RCCA upstream of the cuff compared to the contralateral healthy side and the downstream region at all time points post-surgery. The most obvious differences were recorded at 6 and 8 weeks after implantation. Immunohistochemistry revealed a high degree of α_v-positivity in this region of the RCCA, but not in the left common carotid artery (LCCA) or downstream of the cuff. In addition, macrophages could be detected by CD68 immunohistochemistry in the RCCA, showing ongoing inflammatory processes. In conclusion, MSOT is capable of delineating alterations in endothelial cell integrity in vivo in the applied model of early ED, where an elevated expression of integrin α_vβ₃ was detected within vascular structures. Full article

Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn’s disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes. Full article

The ability to rapidly locate blood vessels in patients is important in many clinical applications, e.g., in catheterization procedures. Optical techniques, including visual inspection, generally suffer from a reduced performance at depths below 1 mm, while ultrasound and optoacoustic tomography are better suited to a typical depth on the scale of 1 cm and require an additional spacer between the tissue and transducer in order to image the superficial structures at the focus plane. For this work, we developed a hand-held optoacoustic probe, designed for localizing blood vessels from the contact point down to a depth of 1 cm, without the use of a spacer. The probe employs a flat lens-free ultrasound array, enabling a largely depth-independent response down to a depth of 1 cm, at the expense of low elevational resolution. Specifically, while in lens-based probes, the acoustic signals from outside the focal region suffer from distortion, in our probe, only the amplitude of the signal varies with depth, thus leading to an imaging quality that is largely depth-independent in the imaged region. To facilitate miniaturization, dark-field illumination is used, whereby light scattering from the tissue is exploited to homogenize the sensitivity field. Full article

Chronic, non-healing wounds constitute a major health problem, and the current therapeutic options are limited. Therefore, pharmaceuticals that can be locally applied to complicated wounds are urgently needed. Such treatments should directly target the underlying causes, which include diabetes mellitus, chronic local pressure and/or vascular insufficiency. A common consequence of these disorders is impaired wound angiogenesis. Here, we investigated the effect of topical application of a nitric oxide-releasing phosphodiesterase 5 inhibitor (TOP-N53)-containing liquid hydrogel on wound repair in mice. The drug-loaded hydrogel promoted re-epithelialization and angiogenesis in wounds of healthy and healing-impaired diabetic mice. Using a non-invasive label-free optoacoustic microscopy approach combined with automated vessel analysis, we show that the topical application of TOP-N53 formulation increases the microvascular network density and promotes the functionality of the newly formed blood vessels, resulting in enhanced blood perfusion of the wounds. These results demonstrate a remarkable healing-stimulating activity of topically applied TOP-N53 formulation, supporting its further development as a wound therapeutic. Full article

Optoacoustic imaging relies on the detection of optically induced acoustic waves to offer new possibilities in morphological and functional imaging. As the modality matures towards clinical application, research efforts aim to address multifactorial limitations that negatively impact the resulting image quality. In an endeavor to obtain a clear view on the limitations and their effects, as well as the status of this progressive refinement process, we conduct an extensive search for optoacoustic image quality improvement approaches that have been evaluated with humans in vivo, thus focusing on clinically relevant outcomes. We query six databases (PubMed, Scopus, Web of Science, IEEE Xplore, ACM Digital Library, and Google Scholar) for articles published from 1 January 2010 to 31 October 2021, and identify 45 relevant research works through a systematic screening process. We review the identified approaches, describing their primary objectives, targeted limitations, and key technical implementation details. Moreover, considering comprehensive and objective quality assessment as an essential prerequisite for the adoption of such approaches in clinical practice, we subject 36 of the 45 papers to a further in-depth analysis of the reported quality evaluation procedures, and elicit a set of criteria with the intent to capture key evaluation aspects. Through a comparative criteria-wise rating process, we seek research efforts that exhibit excellence in quality assessment of their proposed methods, and discuss features that distinguish them from works with similar objectives. Additionally, informed by the rating results, we highlight areas with improvement potential, and extract recommendations for designing quality assessment pipelines capable of providing rich evidence. Full article