Optoacoustic imaging of the skin Deán‐Ben, Xosé Luís; Razansky, Daniel
Experimental dermatology,
November 2021, 2021-11-00, 20211101, Letnik:
30, Številka:
11
Journal Article
Recenzirano
Optoacoustic (OA, photoacoustic) imaging capitalizes on the synergistic combination of light excitation and ultrasound detection to empower biological and clinical investigations with rich optical ...contrast while effectively bridging the gap between micro and macroscopic imaging realms. State‐of‐the‐art OA embodiments consistently provide images at micron‐scale resolution through superficial tissue layers by means of focused illumination that can be smoothly exchanged for acoustic‐resolution images at diffuse light depths of several millimetres to centimetres via ultrasound beamforming or tomographic reconstruction. Taken together, this unique multi‐scale imaging capacity opens unprecedented capabilities for high‐resolution in vivo interrogations of the skin at scalable depths. Moreover, diverse anatomical and functional information is retrieved via dynamic mapping of endogenous chromophores such as haemoglobin, melanin, lipids, collagen, water and others. This, along with the use of non‐ionizing radiation, facilitates a clinical translation of the OA modalities. We review recent progress in OA imaging of the skin in preclinical and clinical studies exploiting the rich contrast provided by endogenous substances in tissues. The imaging capabilities of existing approaches are discussed in the context of initial translational studies on skin cancer, inflammatory skin diseases, wounds and other conditions.
Optoacoustics provides a unique set of capabilities for bioimaging, associated with the intrinsic combination of ultrasound- and light-related advantages, such as high spatial and temporal resolution ...as well as powerful spectrally enriched imaging contrast in biological tissues. We demonstrate here, for the first time, the acquisition, processing and visualization of five-dimensional optoacoustic data, thus offering unparallel imaging capacities among the current bioimaging modalities. The newly discovered performance is enabled by simultaneous volumetric detection and processing of multispectral data and is further showcased here by attaining time-resolved volumetric blood oxygenation maps in deep human vessels and real-time tracking of contrast agent distribution in a murine model in vivo.
Current functional neuroimaging methods are not adequate for high-resolution whole-brain visualization of neural activity in real time. Here, we show imaging of fast hemodynamic changes in deep mouse ...brain using fully noninvasive acquisition of five-dimensional optoacoustic data from animals subjected to oxygenation stress. Multispectral video-rate acquisition of three-dimensional tomographic data enables simultaneous label-free assessment of multiple brain hemodynamic parameters, including blood oxygenation, total hemoglobin, cerebral blood volume, oxygenized and deoxygenized hemoglobin, in real time. The unprecedented results indicate that the proposed methodology may serve as a powerful complementary, and potentially superior, method for functional neuroimaging studies in rodents.
Tracking of biodynamics across entire living organisms is essential for understanding complex biology and disease progression. The presently available small‐animal functional and molecular imaging ...modalities remain constrained by factors including long image acquisition times, low spatial resolution, limited penetration or poor contrast. Here flash scanning volumetric optoacoustic tomography (fSVOT), a new approach for high‐speed imaging of fast kinetics and biodistribution of optical contrast agents in whole mice that simultaneously provides reference images of vascular and organ anatomy with unrivaled fidelity and contrast, is presented. The imaging protocol employs continuous overfly scanning of a spherical matrix array transducer, accomplishing a 200 µm resolution 3D scan of the whole mouse body within 45 s without relying on signal averaging. This corresponds to an imaging speed gain of more than an order of magnitude compared with existing state‐of‐the‐art implementations of comparable resolution performance. Volumetric tracking and quantification of gold nanoagent and near infrared (NIR)‐II dye kinetics and their differential uptake in various organs are demonstrated. fSVOT thus offers unprecedented capabilities for multiscale imaging of pharmacokinetics and biodistribution with high contrast, resolution, and speed.
Herein, flash scanning volumetric optoacoustic tomography (fSVOT), a new approach for high‐speed imaging of fast kinetics and biodistribution of optical contrast agents in the second near infrared (NIR‐II) window in entire mice, is introduced. The method effectively reduces high‐resolution total‐body image acquisition times to sub‐minute levels, taking whole‐body small animal molecular imaging to a new level of spatiotemporal resolution performance.
Intense efforts are underway to develop functional imaging modalities for capturing brain activity at the whole organ scale with high spatial and temporal resolution. Functional optoacoustic (fOA) ...imaging is emerging as a new tool to monitor multiple hemodynamic parameters across the mouse brain, but its sound validation against other neuroimaging modalities is often lacking. Here we investigate mouse brain responses to peripheral sensory stimulation using both fOA and functional ultrasound (fUS) imaging. The two modalities operate under similar spatio-temporal resolution regime, with a potential to provide synergistic and complementary hemodynamic readouts. Specific contralateral activation was observed with sub-millimeter spatial resolution with both methods. Sensitivity to hemodynamic activity was found to be on comparable levels, with the strongest responses obtained in the oxygenated hemoglobin channel of fOA. While the techniques attained highly correlated hemodynamic responses, the differential fOA readings of oxygenated and deoxygenated haemoglobin provided complementary information to the blood flow contrast of fUS. The multi-modal approach may thus emerge as a powerful tool providing new insights into brain function, complementing our current knowledge generated with well-established neuroimaging methods.
Clinical translation of optoacoustic imaging is fostered by the rapid technical advances in imaging performance as well as the growing number of clinicians recognizing the immense diagnostic ...potential of this technology. Clinical optoacoustic systems are available in multiple configurations, including hand-held and endoscopic probes as well as raster-scan approaches. The hardware design must be adapted to the accessible portion of the imaged region and other application-specific requirements pertaining the achievable depth, field of view or spatio-temporal resolution. Equally important is the adequate choice of the signal and image processing approach, which is largely responsible for the resulting imaging performance. Thus, new image reconstruction algorithms are constantly evolving in parallel to the newly-developed set-ups. This review focuses on recent progress on optoacoustic image formation algorithms and processing methods in the clinical setting. Major reconstruction challenges include real-time image rendering in two and three dimensions, efficient hybridization with other imaging modalitites as well as accurate interpretation and quantification of bio-markers, herein discussed in the context of ongoing progress in clinical translation.
Analytical (closed-form) inversion schemes have been the standard approach for image reconstruction in optoacoustic tomography due to their fast reconstruction abilities and low memory requirements. ...Yet, the need for quantitative imaging and artifact reduction has led to the development of more accurate inversion approaches, which rely on accurate forward modeling of the optoacoustic wave generation and propagation. In this way, multiple experimental factors can be incorporated, such as the exact detection geometry, spatio-temporal response of the transducers, and acoustic heterogeneities. The model-based inversion commonly results in very large sparse matrix formulations that require computationally extensive and memory demanding regularization schemes for image reconstruction, hindering their effective implementation in real-time imaging applications. Herein, we introduce a new discretization procedure for efficient model-based reconstructions in two-dimensional optoacoustic tomography that allows for parallel implementation on a graphics processing unit (GPU) with a relatively low numerical complexity. By on-the-fly calculation of the model matrix in each iteration of the inversion procedure, the new approach results in imaging frame rates exceeding 10 Hz, thus enabling real-time image rendering using the model-based approach.
Photothermal therapy and ablation are commonplace medical procedures employed for treatment of tumors, vascular and brain abnormalities as well as other disorders that require selective destruction ...of tissues. Yet, accurate mapping of the dynamic temperature field distribution in the treated region represents an unmet clinical need, strongly affecting the clinical outcome of these interventions. We introduce a fast three-dimensional temperature mapping method based on real-time optoacoustic sensing of the treated region coupled with a thermal-diffusion-based model of heat distribution in tissues. Deviations of the optoacoustic temperature readings provided at 40 ms intervals remained below 10% in tissue-mimicking phantom experiments for temperature elevations above 3 °C, as validated by simultaneous thermocouple measurements. Performance of the new method to dynamically estimate the volumetric temperature distribution was further showcased in post-mortem mouse imaging experiments. The newly discovered capacity to non-invasively measure the temperature map in an entire treated volume with both high spatial and temporal resolutions holds potential for improving safety and efficacy of light-based therapeutic interventions.
Optoacoustic (OA) imaging offers powerful capabilities for interrogating biological tissues with rich optical absorption contrast while maintaining high spatial resolution for deep tissue ...observations. The spectrally distinct absorption of visible and near-infrared photons by endogenous tissue chromophores facilitates extraction of diverse anatomic, functional, molecular, and metabolic information from living tissues across various scales, from organelles and cells to whole organs and organisms. The primarily blood-related contrast and limited penetration depth of OA imaging have fostered the development of multimodal approaches to fully exploit the unique advantages and complementarity of the method. We review the recent hybridization efforts, including multimodal combinations of OA with ultrasound, fluorescence, optical coherence tomography, Raman scattering microscopy and magnetic resonance imaging as well as ionizing methods, such as X-ray computed tomography, single-photon-emission computed tomography and positron emission tomography. Considering that most molecules absorb light across a broad range of the electromagnetic spectrum, the OA interrogations can be extended to a large number of exogenously administered small molecules, particulate agents, and genetically encoded labels. This unique property further makes contrast moieties used in other imaging modalities amenable for OA sensing.
Combining optoacoustics with other imaging techniques helps bring its powerful label-free functional readings and molecular sensitivity into precise anatomical context while providing an essential cross-validation against established imaging methods.
Similar to pulse-echo ultrasound, optoacoustic imaging encodes the location of optical absorbers by the time-of-flight of ultrasound waves. Yet, signal generation mechanisms are fundamentally ...different for the two modalities, leading to significant distinction between the optimum image formation strategies. While interference of back-scattered ultrasound waves with random phases causes speckle noise in ultrasound images, speckle formation is hindered by the strong correlation between the optoacoustic responses corresponding to individual sources. However, visibility of structures is severely hampered when attempting to acquire optoacoustic images under limited-view tomographic geometries. In this tutorial article, we systematically describe the basic principles of optoacoustic signal generation and image formation for objects ranging from individual sub-resolution absorbers to a continuous absorption distribution. The results are of relevance for the proper interpretation of optoacoustic images acquired under limited-view scenarios and may also serve as a basis for optimal design of tomographic acquisition geometries and image formation strategies.
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