The possibilities of optoacoustic microscopy for comparison of vascular network of different tumor models as well as for investigation of tumor vessels response to radiation therapy were demonstrated.
KEYWORDS: Tumors, Tissues, Skin, Algorithm development, 3D image processing, Angiography, 3D image reconstruction, Optoacoustics, Reconstruction algorithms, In vivo imaging
We demonstrate the opportunities of the developed 3D optoacoustic image processing algorithm to characterize numerically the vasculature parameters in different applications including monitoring of tumor angiogenesis and assessing skin aging.
Using optoacoustic microscopy, a radiation-induced increase in the fragmentation of experimental tumor small vessels, as well as the formation of large hemoglobin-containing structures were revealed within first days after treatment.
Our work was devoted to the experimental comparison of two ultra-wideband detectors based on PVDF piezofilms of different thickness demonstrating different quality of optoacoustic imaging of vessels in tumor and normal tissues.
We report on the comparative analysis of the effect of photodynamic therapy performed with red or/and blue light on a tumor model in animals. Results of optical monitoring are in agreement with visual observations and histology studies.
We present the results of combined fluorescence and optoacoustic monitoring of tumor treatment using novel photoactivatable multi-inhibitor liposomes with BPD and Irinotecan providing a synergetic effect of PDT and chemotherapeutic impact.
A novel approach to monitor photosensitizer accumulation and photobleaching in the course of photodynamic therapy (PDT) with the use of nanoconstructs based on the simultaneous fluorescence (FL) and optoacoustic (OA) imaging is implemented. A liposome nanoconstructs employed in this studies contain benzoporphyrin derivatives (BPD) which serve as a photosensitizer and secondly, as a fluorophore, and the fluorescent IRDye800 dye acting as an additional contrasting agent due to its high quantum yield. FL provides visualization of BPD and IRDye800 distribution, while OA principle allows for BPD-absorption based imaging of tumor and its vascular environment. We demonstrate the results of a preliminary in vivo study with combined FL and OA custom-made setups on a NUDE mouse with human glioblastoma U- 87. The results of this studies show a hemorrhage in the tumor area on the OA images obtained @532 nm after PDT that is not visually detected, but confirmed with the following histological verification. Fast nanoconstructs accumulation (< 10 min) was observed using FL imaging with the concentration in tumor only 10% higher than in surrounding tissues. We believe that the ratio of nanoconstructs accumulation in tumor can be significantly increased using target approach.
We propose a new approach to monitoring of photodynamic therapy (PDT) of glioblastoma with the use of targeted nanoconstructs containing a photosensitizer (PS) benzoporphyrin derivative (BPD) and IRDye800 dye, antibodies for efficient accumulation of the drug in a tumor, and a chemotherapeutic agent for combined effect on tumor cells. Monitoring of PDT is based on the simultaneous fluorescent and optoacoustic (OA) imaging. Fluorescent imaging provides visualization of fluorescence agents with high molecular sensitivity, and monitoring of the effectiveness of PDT by PS photobleaching. OA allows to examine the vascular pattern of the tumor environment, as well as assess the tumor depth. IRDye800 is a better contrast agent in comparison to BPD due to red shifted spectral characteristics and higher fluorescence quantum yield. The results of numerical simulations have been verified in phantom studies using fluorescence and optoacoustic experimental setups and an agar phantom with optical characteristics similar to those of murine brain.
KEYWORDS: In vivo imaging, In vitro testing, Blood, Absorption, Blood oxygen saturation, Signal attenuation, Optoacoustics, Blood vessels, Calibration, Veins
We present the comparison of two approaches of blood oxygen saturation determination from multispectral optoacoustic measurements: a calibration-free approach based on evaluation of the effective optical attenuation coefficient derived from in-depth OA signal decay, and an approach based on determination of optical absorption coefficient from OA signal amplitudes. Both approaches were tested in in vitro and in vivo experiments. The results of in vitro and in vivo experiments demonstrated the large difference between experimentally obtained μeff spectra and the literature data, that indicates much lower potential of the OA signal decay approach as compared to OA amplitudes approach. In vivo measurements of the μa spectrum experimentally obtained from OA signal amplitudes give the saturation values of 0.57±0.08 and 0.50±0.07 for two veins of the thoracic spine that agree well with physiological values for venous blood oxygenation in rat. Instead of multiple wavelengths measurements, a pair of wavelengths can be employed for OA measurements. In this case, the saturation maps were obtained at all wavelength pairs from the 658‒1069 nm range. The results demonstrated that the most accurate oxygenation values can be achieved at wavelength pairs of 700 nm and a wavelength from the range 850-1069 nm.
KEYWORDS: Sensors, Monte Carlo methods, Acoustics, In vivo imaging, Image resolution, Optical properties, Antennas, 3D image processing, 3D image reconstruction, Photoacoustic microscopy
We propose a hybrid approach to image enhancement in acoustic resolution photoacoustic microscopy. The developed technique is based on compensation for nonuniform spatial sensitivity of the optoacoustic (OA) system in both optical and acoustic domains. Spatial distribution of optical fluence is derived from full three-dimensional Monte Carlo simulations accounting for conical geometry of tissue laser illumination at the wavelength of 532 nm. Approximate nonuniform spatial response of acoustic detector with numerical aperture of 0.6 is derived from the two-dimensional k-Wave modeling. Application of the developed technique allows to improve the spatial resolution and to balance in-depth signal-level distribution in OA images of phantom and in-vivo objects.
We provide direct experimental comparison of the optoacoustic imaging performance of two different 64-element linear detector array (LDA) units based on polyvinylidene difluoride (PVDF) films. The first LDA unit was based on traditional flexible circuit (FC) technology and consisted of an FC glued to the nonmetalized signal surface of a 28-μm-thick PVDF film providing 300 / 80-μm axial resolution/lateral resolution (AR/LR) and 0.4-kPa noise equivalent pressure of its single element. The other LDA unit was manufactured using a technology of low-temperature photolithographic etching (PE) of a signal electrode onto a 25-μm-thick PVDF film providing 300 / 40-μm AR/LR and 1 kPa noise equivalent pressure. As compared with a previously reported LDA unit based on a 100-μm PVDF thick film, the main advantage of using the thinner PVDF films was 10-fold improvement in axial resolution, whereas the main drawback was 10-fold increased noise equivalent pressure. In terms of in vivo imaging performance, higher bandwidth of PE LDA probe was more important than the higher sensitivity of FC LDA unit.
Non-invasive measurement of blood oxygen saturation in blood vessels is a promising clinical application of optoacoustic imaging. However, unknown spatial and spectral distribution of optical fluence within biotissue challenges precise multispectral optoacoustic measurements of blood oxygen saturation. The accuracy of the blood oxygen saturation measurement can be improved by the choice of optimal laser wavelengths. We propose the numerical approach to determine the optimal wavelengths for two-wavelengths OA measurements of blood oxygen saturation at various depths. The developed approach accounts for acoustic pressure noise, error in determination of optical scattering and absorption coefficients used for the calculation of the optical fluence, and diameter of the investigated blood vessel. We demonstrate that in case of an unknown (or partially known) fluence spatial distribution at depths between 2 and 8 mm, minimal error in the determination of blood oxygen saturation is achieved at the wavelengths of 658±40 nm and 1069±40 nm. We report on the pilot results of OA in vivo measurements of blood oxygen saturation using optimal wavelengths obtained by the proposed approach.
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