Tracing the shear modulus of blood plasma during clotting and based on acoustic radiation force induced vibration of an embedded sphere

Abstract

During coagulation, blood changes from liquid to gel, and the clot viscoelastic properties continue modifying until fibrinolysis. Ultrasound (US) was used in this work to trace the time-changing shear modulus, μ, during plasma clotting, based on the vibration signature induced by an impulsive acoustic radiation force (iARF) on a sphere embedded in a plasma sample along its clotting process induced based on the aPTT (activated partial thromboplastin time) assay. An US push system transmitted bursts of US pulses (2.03 MHz, 1000 cycles and 1.25 Hz of pulse repetition frequency) to generate an iARF on the glass sphere (4.0 mm in diameter and density of 2500 kg/m3), which displacement was monitored by a 5.0 MHz US pulse-echo probing system. The relative delays between the rf-echo signals from the sphere yielded the signal representing the sphere damped oscillation that was fitted with a theoretical-model displacement function whose unknowns are the iARF amplitude and the medium μ and shear viscosity, η. The method was repeated five times and the time-changing mean μ was determined along 2100 s of the clotting process. During the first 15 s μ remained at 20 Pa and then varied rapidly until 60 s, at a rate of 1.9 Pa/s. Between 60 and 800 s, μ varied at a rate of 0.2 Pa/s. From 800 to 2100 s μ remained stable at about 280 Pa. The interval of fast changing μ corresponds to the fibrin formation period and comprehends the clotting time of 25s typically obtained with the aPTT assay for control plasma.