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.
High-intensity focused ultrasound (HIFU) capitalizes on both heating and cavitation effects for the treatment of several conditions. Optoacoustic (OA) imaging has previously been shown to provide high sensitivity to temperature changes and coagulation in HIFU-ablated tissues. In this work, we demonstrate the feasibility of real-time monitoring of heating and cavitation with a hybrid optoacoustic-ultrasound (OPUS) imaging system based on a multi-segment transducer array. The OPUS results in experiments with liver tissues ex-vivo and a mouse post-mortem were validated with thermal camera measurements and with cryo-sections of the mouse. The suggested approach thus holds promise to be clinically translated.
KEYWORDS: Imaging systems, Data acquisition, Optoacoustics, Transducers, Signal detection, Field programmable gate arrays, Signal processing, Pulsed laser operation
Optoacoustic tomography (OAT) is rapidly becoming an important tool in biological and clinical research. Current OAT system implementations commonly feature bulky and expensive hardware impeding wide-scale adoption. We introduce LightSpeed: a compact, high-speed, low-cost and configurable 3D optoacoustic imager based on an optical-link software-defined acquisition platform and fiber-coupled laser diode illumination. We demonstrate real-time imaging capability of the LightSpeed system by fast handheld scanning of human vasculature. LightSpeed attains image quality comparable to conventional data acquisition electronics at a fraction of hardware costs and significantly faster frame rates. It is then poised to result in new generation compact and high-performance handheld OAT scanners facilitating clinical translation.
Laser ablation (LA) is gaining acceptance for the treatment of tumors as a viable alternative to surgical resection. In parallel, optoacoustic tomography (OAT) has enabled defining new regimes for diagnosis and characterization of malignant neoplastic lesions with high sensitivity and specificity. Even though pulsed nanosecond lasers are commonly used for both imaging and therapeutic purposes, real-time thermal treatment monitoring with a single laser source has not been previously attempted. Herein, we demonstrate the feasibility of combined OAT and LA by percutaneous irradiation of subcutaneous tumors with a 100 mJ short-pulsed (~5 ns) laser operating at 1064 nm and 100 Hz pulse repetition frequency. The OAT images rendered with a spherical ultrasound transducer array enabled real-time monitoring of the LA lesion progression, which is essential for determining the optimal treatment end-point. Local changes in the optoacoustic signal intensity associated with the induced temperature changes as well as structural alterations in the tumor vasculature could clearly be observed. The optoacoustic volumetric projections further correlated with crosssections extracted from the excised tumors. This newly enabled capability anticipates new theranostic approaches in cancer research and treatment with potential applicability in a clinical setting.
Understanding the mechanisms of cardiac disorders largely depends on availability of multi-dimensional and multiparametric imaging methods capable of quantitative assessment of cardiac morphology and function. The imaging modalities commonly employed in cardiac research, such as ultrasonography and magnetic resonance imaging, are lacking sufficient contrast and/or spatio-temporal resolution in 3D in order to reveal the multi-scale nature of rapid electromechanical activity in a beating heart. Our recently developed volumetric optoacoustic tomography (VOT) platform offers versatile observations of the heart function with rich optical contrast at otherwise unattainable temporal and spatial resolutions. Herein, we further advance the imaging performance by developing compressed acquisition scheme to boost the temporal resolution of VOT into the kilohertz range, thus enabling 3D mapping of electromechanical wave propagation in the heart. Experiments in isolated mouse hearts were performed by exciting the entire imaged tissue volume with nanosecond-duration laser pulses at 1 kHz repetition rate pulse operating at 532 nm and sparse tomographic signal sampling using a custom-made 512-element spherical matrix ultrasound array. By analyzing the strain maps obtained from the rapid VOT image sequence, it was possible to quantify the phase velocity of the electromechanical cardiac waves, in good agreement with previously reported values.
Radio-frequency (RF) catheter ablation is routinely used in the clinics to treat arrhythmias, neoplastic lesions and other dysfunctional tissues. It is based on scarring the target tissue via localized heating induced by medium frequency alternating current in the proximity of a metallic ablation catheter. The outcome of RF interventions strongly relies on the temperature distribution within the treated tissue as well as on the exposure time, which cannot be efficiently monitored with existing clinical tools. Optoacoustic (OA) tomography has recently been shown to provide unique capabilities for RF ablation monitoring such as high spatio-temporal resolution, hand-held operation feasibility and high sensitivity to temperature changes and tissue coagulation. However, shallow light penetration in biological tissues strongly limits the accessible regions, particularly for cardiac procedures, while internal illumination through the catheter induces strong responses in the metallic parts that hamper soft tissue visualization. Herein, we present a new endocardial catheter based on saline irrigation that delivers electric current while being transparent for light. The new design averts OA image artifacts due to the presence of metallic electrodes while retaining the ablation efficiency.
Laser ablation (LA) represents a minimally invasive intervention that is gaining acceptance for the treatment of different types of cancer, leading to important advantages such as less pain and shorter recovery time. Accurate monitoring of ablation progression is crucial to prevent damage of non-cancerous tissues and optimize the outcome of the intervention. To this end, imaging techniques such as ultrasound, computed tomography or magnetic resonance imaging have been used for monitoring LA. However, these techniques feature important drawbacks such as the need of contrast agents, poor spatio-temporal resolution or high cost. Optoacoustics (OA, photoacoustic) has recently been shown to provide unique properties to monitor thermal treatments. Herein, we demonstrate the feasibility of optoacoustic laser-ablation (OLA) monitoring in a murine breast tumor model using a single short-pulsed 1064 nm laser source. The effect of irradiation was volumetrically tracked with the OA images acquired with a 256-element spherical array. Structural damage of the tissue was clearly seen during the LA procedure.
KEYWORDS: Tissues, Optoacoustics, Laser ablation, Signal attenuation, 3D image processing, Temperature metrology, Visualization, Imaging systems, Tissue optics, 3D acquisition
Efficient monitoring of radiofrequency ablation procedures is essential to optimize the lesions induced to treat cancer, cardiac arrhythmias and other conditions. Recently, optoacoustic imaging and sensing methods have been suggested as a promising approach to address this challenge, offering unique advantages such as high sensitivity to temperature changes and chemical transformations in coagulated tissues, real-time operation and use of non- ionizing radiation. However, assessing how the ablation lesion boundary progresses is still challenged by changes in optical properties induced during the interventions. Herein, we suggest a new approach for dimensional characterization of the induced lesion based on detecting sharp positive variations in the time derivative of optoacoustic signals. Experiments in porcine tissue samples indicate that such variations are uniquely associated to the onset of ablation and that the method can robustly visualize the evolution of the lesion in three dimensions.
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