Magnetic and Contrast Properties of Labeled Platelets for Magnetomotive Optical Coherence Tomography

This article introduces a new functional imaging paradigm that uses optical coherence tomography (OCT) to detect rehydrated, lyophilized platelets (RL platelets) that are in the preclinical trial stage and contain superparamagnetic iron oxides (SPIOs) approved by the U.S. Food and Drug Administration. Platelets are highly functional blood cells that detect and adhere to sites of vascular endothelial damage by forming primary hemostatic plugs. By applying magnetic gradient forces, induced nanoscale displacements (magnetomotion) of the SPIO-RL platelets are detected as optical phase shifts in OCT. In this article, we characterize the iron content and magnetic properties of SPIO-RL platelets, construct a model to predict their magnetomotion in a tissue medium, and demonstrate OCT imaging in tissue phantoms and ex vivo pig arteries. Tissue phantoms containing SPIO-RL platelets exhibited >3 dB contrast/noise ratio at ≥1.5 × 109 platelets/cm3. OCT imaging was performed on ex vivo porcine arteries after infusion of SPIO-RL platelets, and specific contrast was obtained on an artery that was surface-damaged (P < 10−6). This may enable new technologies for in vivo monitoring of the adherence of SPIO-RL platelets to sites of bleeding and vascular damage, which is broadly applicable for assessing trauma and cardiovascular diseases

High Sensitivity Micro-Elastometry: Applications in Blood Coagulopathy

Highly sensitive methods for the assessment of clot structure can aid in our understanding of coagulation disorders and their risk factors. Rapid and simple clot diagnostic systems are also needed for directing treatment in a broad spectrum of cardiovascular diseases. Here we demonstrate a method for micro-elastometry, named Resonant Acoustic Spectroscopy with Optical Vibrometry (RASOV), which measures the clot elastic modulus (CEM) from the intrinsic resonant frequency of a clot inside a microwell. We observed a high correlation between the CEM of human blood measured by RASOV and a commercial Thromboelastograph (TEG), (R=0.966). Unlike TEG, RASOV requires only 150 μL of sample and offers improved repeatability. Since CEM is known to primarily depend upon fibrin content and network structure, we investigated the CEM of purified clots formed with varying amounts of fibrinogen and thrombin. We found that RASOV was sensitive to changes of fibrinogen content (0.5–6 mg/mL), as well as to the amount of fibrinogen converted to fibrin during clot formation. We then simulated plasma hypercoagulability via hyperfibrinogenemia by spiking whole blood to 150% and 200% of normal fibrinogen levels, and subsequently found that RASOV could detect hyperfibrinogenemia-induced changes in CEM and distinguish these conditions from normal blood