An ultrasound detection scheme based on a transparent polyvinylidene-fluoride indium-tin-oxide (PVDF-ITO) piezoelectric film is developed for ultrawideband sensitive detection of optoacoustic (OA) signals down to a noise equivalent pressure (NEP) of 8.4 Pa over an effective detection bandwidth extending beyond 30 MHz. The high signal-to-noise ratio and low noise performance are facilitated by employing a two-stage amplifier structure. The PVDF-ITO detector is directly mounted on a commercial high numerical aperture objective lens of a scanning optical resolution OA microscopy system to obtain submicron resolution images without signal averaging, as demonstrated both in phantoms and in vivo measurements in mice. The transparent detection scheme further allows for the OA imaging modality to be easily integrated with other imaging techniques for diverse multi-modal biomedical imaging investigations.
Optoacoustic (OA) angiography allows high-contrast three-dimensional (3D) visualization of hemoglobin-containing structures ranging from micrometers to millimeters. However, due to the large amount of 3D data acquired by modern high-throughput OA systems the resulting OA vasculature images might be difficult to analyze visually. This problem is especially relevant for monitoring of angiogenesis of experimental tumors, which blood vessels tend to be smaller and more tortuous compared to vasculature of healthy tissue. In this paper a novel algorithm for OA image processing is proposed to quantify vessel structure parameters automatically. The algorithm is based on creation of vasculature graphs which parameters (lengths of branches, number of branches, etc) can serve as a numerical characterization of vasculature: vessel density, vessel length, etc. The results of testing the developed algorithm on numerical simulation phantoms and in vivo OA images of tumor models in a mouse demonstrate a statistically significant difference of all the extracted parameters for tumor and normal tissue. The results show a high potential of the proposed approach for OA angiography in different applications including clinical and experimental oncology.
The newly developed multimodal imaging system combining raster-scan optoacoustic (OA) microscopy and fluorescence (FL) wide-field imaging was used for characterizing the tumor vascular structure with 38/50 μm axial/transverse resolution and assessment of photosensitizer fluorescence kinetics during treatment with novel theranostic agents. A multifunctional photoactivatable multi-inhibitor liposomal (PMILs) nano platform was engineered here, containing a clinically approved photosensitizer, Benzoporphyrin derivative (BPD) in the bilayer, and topoisomerase I inhibitor, Irinotecan (IRI) in its inner core, for a synergetic therapeutic impact. The optimized PMIL was anionic, with the hydrodynamic diameter of 131.6 ± 2.1 nm and polydispersity index (PDI) of 0.05 ± 0.01, and the zeta potential between −14.9 ± 1.04 to −16.9 ± 0.92 mV. In the in vivo studies on BALB/c mice with CT26 tumors were performed to evaluate PMILs’ therapeutic efficacy. PMILs demonstrated the best inhibitory effect of 97% on tumor growth compared to the treatment with BPD-PC containing liposomes (PALs), 81%, or IRI containing liposomes (L-[IRI]) alone, 50%. This confirms the release of IRI within the tumor cells upon PMILs triggering by NIR light, which is additionally illustrated by FL monitoring demonstrating enhancement of drug accumulation in tumor initiated by PDT in 24 h after the treatment. OA monitoring revealed the largest alterations of the tumor vascular structure in the PMILs treated mice as compared to BPD-PC or IRI treated mice. The results were further corroborated with histological data that also showed a 5-fold higher percentage of hemorrhages in PMIL treated mice compared to the control groups. Overall, these results suggest that multifunctional PMILs simultaneously delivering PDT and chemotherapy agents along with OA and FL multi-modal imaging offers an efficient and personalized image-guided platform to improve cancer treatment outcomes.
We propose a GPU-accelerated implementation of frequency-domain synthetic aperture focusing technique (SAFT) employing truncated regularized inverse k-space interpolation. Our implementation achieves sub-1s reconstruction time for data sizes of up to 100 M voxels, providing more than a tenfold decrease in reconstruction time as compared to CPU-based SAFT. We provide an empirical model that can be used to predict the execution time of quasi-3D reconstruction for any data size given the specifications of the computing system.
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