The fundamental physiological function of the iris is to control the amount of light entering the eye, which requires the coordinated constriction or dilation of the pupil, affected by two antagonistic muscles, namely the sphincter and radial muscles. Disorders of the iris, including these muscles, may lead to ocular pathologies, such as primary angle-closure glaucoma. Here, we assessed the regional biomechanical properties of the iris using phase-sensitive optical coherence elastography (PhS-OCE) to quantify the shear wave speed arising from perturbations generated using an acoustic radiation force (ARF) transducer of resonant frequency 3.5 MHz and focal length 19 mm. We determined regional shear wave speeds by tracking elastic wave propagation in ex vivo porcine irides. Results showed that the mean shear wave speed in the pupillary zone (~2.1 m/s) was consistently greater than in the ciliary zone (~1.87 m/s). These findings indicate that the mechanical properties of the iris exhibit regional heterogeneity, which may be related to the microstructure of the iris (muscle locations/extent) and intrinsic elastic properties.
Clinical imaging techniques for the anterior segment of the eye provide excellent anatomical information, but molecular imaging techniques are lacking. Molecular photoacoustic imaging is one option to address this need, but implementation requires use of contrast agents to distinguish molecular targets from background photoacoustic signals. Contrast agents are typically selected based on a priori knowledge of photoacoustic properties of tissues. However, photoacoustic properties of anterior ocular tissues have not been studied yet. Herein, anterior segment anatomy and corresponding photoacoustic signals were analyzed in brown and blue porcine eyes ex vivo. Measured photoacoustic spectra were compared to known optical absorption spectra of endogenous chromophores. In general, experimentally measured photoacoustic spectra matched expectations based on absorption spectra of endogenous chromophores reported in the literature, and similar photoacoustic spectra were observed in blue and brown porcine eyes. However, unique light–tissue interactions at the iris modified photoacoustic signals from melanin. Finally, we demonstrated how the measured PA spectra established herein can be used for one application of molecular PA imaging, detecting photoacoustically labeled stem cells in the anterior segment for glaucoma treatment.
Glaucoma is the leading cause of irreversible blindness in the world, with approximately 75 million patients suffering from the disease. We know that elevated intraocular pressure (IOP) is a key risk factor for the disease, and that sustained lowering of IOP has therapeutic benefit, which point to the importance of biomechanics and mechanobiology in this disease. After providing background information about glaucoma, I will in this talk describe how imaging is helping our understanding of glaucoma. For example, we have used OCT anterior segment imaging to infer mechanical properties of the tissues responsible for controlling IOP, and to relate these properties to the function of these tissues. We have also used photoacoustic imaging to track the location of stem cells delivered into the eye in an attempt to refunctionalize tissues damaged in glaucoma. These efforts are highly collaborative, involving imaging scientists, surgeons, pharmacologists and biomedical engineers.
Our current research explores the applications of sound, light, and nanoparticles in ophthalmology. Specifically, we consider glaucoma, a common blinding disease 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. To expedite clinical translation, non-invasive longitudinal monitoring of stem cell delivery in vivo is desired. We thus investigated ultrasound (US) and photoacoustic (PA) imaging of nanotracer-labeled mesenchymal stem cells (MSCs) and magnetic guidance of cells to the TM in the eye. Adipose-derived MSCs were incubated with photoacoustic nanoparticles to label cells (PA-MSCs), and 1000-4000 cells/µl were delivered to porcine eyes ex vivo while US/PA imaging was performed. Eyes were dissected for histology and additional spectroscopic PA imaging. Results show proof-of-concept for longitudinal detection of cell delivery using gold nanospheres and magnetically-mediated guidance using photomagnetic nanocubes. As cell number increased, the amplitude of spectroscopically unmixed signal from PA-MSCs increased, showing potential for quantitative imaging. Three-dimensional spectroscopic PA imaging and histology of the TM showed a similar ring-like morphology, with concentrations of signal from fluorescently-tagged cells matching the distribution of PA signal from the PA-MSCs. These results provide proof-of-concept for monitoring MSC ocular delivery, indicating new opportunities for development of nanoparticle-augmented imaging technologies in ophthalmic research. Tracking MSCs loaded with gold nanospheres has also provided new insights for improving delivery efficiency with photomagnetic nanoparticles, novel light delivery systems for safe, sensitive detection, and even a more physiologically relevant glaucoma model.
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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