PHOTOACOUSTIC MONITORING OF ANTICOAGULATION THERAPY
Jesse Jokerst, Junxin Wang
University of California, San Diego, USA
Heparin anticoagulation therapy is an indispensable feature of clinical care, yet has a narrow therapeutic window and is the second most common ICU medication error. The active partial thromboplastin time (aPTT) monitors heparin, but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin, and poor correlation to outcome. Here, we describe an ultrasound-based imaging technique to monitor heparin concentration in real time using methylene blue as a simple and FDA-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) (R2>0.98), respectively. Clinically relevant heparin concentrations were detected in blood with a detection limit of 0.28 U/ mL. We validated this imaging approach by correlation to the aPTT (Pearson’s r = 0.86; p<0.05) using five samples with aPTT times within the clinically relevant range (<300s). The signal was also confirmed with protamine sulfate treatment—addition of this heparin agonist completely neutralizes the photoacoustic signal. This technique also has good utility with low molecular weight heparin (enoxaparin) including a blood detection limit of 72 µg/mL. Finally, we have developed a nanoparticle-based hybrid material that can immobilize methylene blue for potentially applications as a wearable/implantable heparin sensor to maintain drug levels in the therapeutic window. To the best of our knowledge, this is the first report to image anticoagulation therapy.