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, "Tracking delivery of a drug surrogate in the porcine heart using photoacoustic imaging and spectroscopy," J. Biomed. Opt. 22(4), 041016 (2017), doi: 10.1117/1.JBO.22.4.041016. Abstract. Although the drug-eluting stent (DES) has dramatically reduced the rate of coronary restenosis, it still occurs in up to 20% of patients with a DES. Monitoring drug delivery could be one way to decrease restenosis rates. We demonstrate real-time photoacoustic imaging and spectroscopy (PAIS) using a wavelength-tunable visible laser and clinical ultrasound scanner to track cardiac drug delivery. The photoacoustic signal was initially calibrated using porcine myocardial samples soaked with a known concentration of a drug surrogate (DiI). Next, an in situ coronary artery was perfused with DiI for 20 min and imaged to monitor dye transport in the tissue. Finally, a partially DiI-coated stent was inserted into the porcine brachiocephalic trunk for imaging. The photoacoustic signal was proportional to the DiI concentration between 2.4 and 120 μg∕ml, and the dye was detected over 1.5 mm from the targeted coronary vessel. Photoacoustic imaging was also able to differentiate the DiI-coated portion of the stent from the uncoated region. These results suggest that PAIS can track drug delivery to cardiac tissue and detect drugs loaded onto a stent with sub-mm precision. Future work using PAIS may help improve DES design and reduce the probability of restenosis.

Although strongly correlated with elevated intraocular pressure, primary open-angle glaucoma (POAG) occurs in normotensive eyes. Mechanical properties of the sclera around the optic nerve head (ONH) may play a role in this disparity. The purpose of this study is to present an automated inverse mechanics based approach to determine the distribution of heterogeneous mechanical properties of the human sclera as derived from its surface deformations arising from pressure inflation experiments. The scleral shell of a 78 year old European Descent male donor eye was utilized to demonstrate the method; the sclera was coated with a speckle pattern on the outer surface and was subjected to inflation pressures of 5, 15, 30, and 45 mmHg. The speckle pattern was imaged at each pressure, and a displacement field was calculated for each pressure step using a previously described sequential digital image correlation (S-DIC) technique. The fiber splay and fiber orientation of the sclera collagen were determined experimentally, and the thickness across the scleral globe was determined using micro CT images. The displacement field from the inflation test was used to calculate the strain and also used as an input for inverse mechanics to determine the heterogeneity of material properties. The scleral geometry was divided into subdomains using the first principal strain. The Holzapfel anisotropic material parameters of matrix and fiber stiffness were estimated within each individual subdomain using an inverse mechanics approach by minimizing the sum of the square of the residuals between the computational and experimental displacement fields. The mean and maximum error in displacement across all subdomains were 8.9 ± 3.0 μm and 13.2 μm, respectively. The full pressure-inflation forward mechanics experiment was done using subdomain-specific mechanical properties on the entire scleral surface. The proposed approach is effective in determining the distribution of heterogeneous mechanical properties of the human sclera in a user-independent manner. Our research group is currently utilizing this approach to better elucidate how scleral stiffness influences those at high risk for POAG.

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