Tracking delivery of a drug surrogate in the porcine heart using photoacoustic imaging and spectroscopy

Abstract

, "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.

Photoacoustic image-guided interventions

“…PAI has been used to track the route of drug administration, 88 and monitor drug release from its carrier, and the subsequent diffusion process and final distribution. 55,89–96 PAI has also been used to observe the therapeutic effects of drugs in real-time.…”

“…86 PAI-guided drug delivery is shown to be successful in cancer therapy, 89–93,95 anticoagulation therapy, 55,96 bipolar disease treatment, 94 and coronary heart disease treatment. 88 The investigation and validation of PAI for continuous monitoring are done on tissue/tumor phantoms, 93 animal models 92,95 and cell cultures 90,91 by either directly using the drug 88,90,91,95 /therapeutic agents 55,94,96 or using a dye that mimics the drug. 89,92,93…”

“…Though the development of drug eluted stent addressed this problem to a considerable extent, about 20% of those with these stents were still facing this problem. 88 To address this problem, the stent was coated with a drug surrogate, 1,1ʹ-dioctadecyl-3,3,3ʹ,3ʹ-tetramethylindocarbocyanine perchlorate. PAI was successful in constantly monitoring the drug delivery in the porcine heart.…”