Combined ultrasound and photoacoustic imaging systems are being developed for biomedical and clinical applications. One common probe configuration is to use a linear transducer array with external light delivery to produce coregistered ultrasound and photoacoustic images. The diagnostic capability of these systems is dependent on the effectiveness of light delivery to the imaging target. We use Monte Carlo modeling to investigate the optimal design geometry of an integrated probe. Simulations are conducted with multiple tissue compositions and wavelengths. The effect of a skin layer with the thickness of a mouse or a human is also considered. The model was validated using a tissue-mimicking gelatin phantom and corresponding Monte Carlo simulations. The optimal illumination angle is shallower with human skin thickness, whereas intermediate angles are ideal with mouse skin thickness. The effect of skin thickness explains differences in the results of prior work. The simulations also indicate that even with identical hardware and imaging parameters, light delivery will be up to 3 × smaller in humans than in mice, due to the increased scattering from thicker skin. Our findings have clear implications for the many researchers using mice to test and develop imaging methods for clinical translation.
This study explores photoacoustic (PA) speckle tracking to characterize flow as an alternative to ultrasound (US) speckle tracking or current PA flow imaging methods. In cases where tracking of submicrometer particles is required, the US signal-to-noise ratio and contrast might be low due to limited reflectivity of subwavelength size targets at low concentrations. However, it may be possible to perform more accurate velocimetry using PAs due to different contrast mechanisms utilized in PA imaging. Here, we introduce a PA-based speckle tracking method that overcomes the directional dependence of Doppler imaging and the limited field of view of current correlation-based methods used in PA flow imaging. The feasibility of this method is demonstrated in a potential application—minimally invasive diagnosis of ventricular shunt malfunction, where the velocity of optically absorbing particles was estimated in a shunt catheter using block matching of PA and US signals. Overall, our study demonstrates the potential of the PA-based motion tracking method under various flow rates where US imaging cannot be effectively used for specking tracking because of its low contrast and low signal-to-noise ratio.
Super-resolution ultrasound imaging techniques have shown promising potential in non-invasive imaging of deep-lying tissue. However, these methods utilize microbubbles, limiting its utility to visualization of vasculature with moving bubbles. To resolve extravascular targets, our group previously introduced a method for super-resolution ultrasound imaging based on laser-activated nanodroplets (LANDs) that repeatedly vaporize and recondense in response to optical irradiation. The method resolves the location of LANDs from the difference between two imaging frames capturing vaporization and recondensation of individual LANDs. However, since only two neighboring frames are used to produce a difference frame, this method is sensitive to noise-related errors limiting the improvement in spatial resolution. In this study, we introduce a new approach to super-resolution imaging. In our approach, ultrafast imaging, which typically captures images at over several thousand frames per second, was used for spatio-temporal compounding. Specifically, multiple successive ultrasound frames were used to obtain the difference frame with improved reliability and repeatability thus enhanced spatial resolution. To evaluate our approach, we imaged a phantom containing uniformly-distributed LANDs using an ultrasound system equipped with a linear array transducer and interfaced with pulsed laser. An ultrafast plane-wave compounding approach was used to capture ultrasound images at 6 kHz frame rate. We achieved a four-fold improvement in spatial resolution over the previous approach. In addition, three-dimensional super-resolution imaging of a phantom with microcapillaries containing LANDs was performed illustrating the robustness of our method. These results suggest that our approach has the potential for high-resolution molecular imaging of intravascular and extravascular targets.
Glaucoma is associated with dysfunction of the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising treatment involves delivery of stem cells to the TM to restore tissue function. Currently histology is the gold standard for tracking stem cell delivery and differentiation. To expedite clinical translation, non-invasive longitudinal monitoring in vivo is desired. Our current research explores a technique combining ultrasound (US) and photoacoustic (PA) imaging to track mesenchymal stem cells (MSCs) after intraocular injection. Adipose-derived MSCs were incubated with gold nanospheres to label cells (AuNS-MSCs) for PA imaging. Successful labeling was first verified with in vitro phantom studies. Next, MSC delivery was imaged ex vivo in porcine eyes, while intraocular pressure was hydrostatically clamped to maintain a physiological flow rate through the TM. US/PA imaging was performed before, during, and after AuNS-MSC delivery. Additionally, spectroscopic PA imaging was implemented to isolate PA signals from AuNS-MSCs. In vitro cell imaging showed AuNS-MSCs produce strong PA signals, suggesting that MSCs can be tracked using PA imaging. While the cornea, sclera, iris, and TM region can be visualized with US imaging, pigmented tissues also produce PA signals. Both modalities provide valuable anatomical landmarks for MSC localization. During delivery, PA imaging can visualize AuNS-MSC motion and location, creating a unique opportunity to guide ocular cell delivery. Lastly, distinct spectral signatures of AuNS-MSCs allow unmixing, with potential for quantitative PA imaging. In conclusion, results show proof-of-concept for monitoring MSC ocular delivery, raising opportunities for in vivo image-guided cell delivery.
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