Photoacoustic Monitoring of Anticoagulant Therapy and Other Imaging Applications

Photoacoustic imaging uses nanosecond laser pulses to excite materials and generate acoustic waves. This “light in, sound out” technique can extend the applications of traditional ultrasound by harnessing the optical properties of materials. These features can be used for the non-invasive monitoring of drugs, molecular interaction, and diseases. In this dissertation, I will present three case studies that use photoacoustic imaging in tandem with nanoparticle contrast agents. The first case leverages photoacoustic imaging for heparin and clotting time monitoring via phenothiazine dyes embedded in nanomaterials. The heparin concentration and clotting time could be determined by the photoacoustic intensity of methylene blue increased by heparin, and this signal enhancement was due to the aggregation between the two molecules. To translate this technique for clinical use, we developed a cellulose sensor loaded with Nile blue A for finger-prick diagnostics. Human studies using 78 blood samples revealed that the photoacoustic intensity of the sensor was strongly correlated to the activated clotting time (Pearson’s r=0.86), which was the gold standard for clotting time measurement. In addition to direct measurements of therapeutic, the second study used photoacoustic imaging to monitor the micellization of sodium dodecyl sulfate (SDS). The micellization can be determined because the photoacoustic intensity of methylene blue shows 492-fold enhancement upon addition of 3.47 mM SDS due to fluorescent quenching, which is caused by the aggregation between methylene blue and SDS. Higher concentrations above the SDS critical micelle concentration at 8.67 mM decreases the intensity signal by 54-fold because of the disassociation of the aggregates. The final case evaluated copper sulfide (CuS) nanodisk and nanoprism as the photoacoustic contrast agents for ovarian tumor detection. We found that the nanodisks have 1.8-fold higher accumulation than nanoprisms in the ovarian tumors indicating the importance of nanoparticle shape for tumor penetration. Versus baseline, the tumors treated with nanodisk revealed three-fold stronger photoacoustic intensity with a characteristic intensity peak at 920 nm. These three photoacoustic applications could improve healthcare because photoacoustic imaging is faster and more cost-effective than most of the imaging modalities in medicine