Abnormal formation of solid thrombus inside a blood vessel
can
cause thrombotic morbidity and mortality. This necessitates early
stage diagnosis, which requires quantitative assessment with a small
volume, for effective therapy with low risk to unwanted development
of various diseases. We propose a micro-ultrasonic diagnosis using
an all-optical ultrasound-based spectral sensing (AOUSS) technique
for sensitive and quantitative characterization of early stage and
whole blood coagulation. The AOUSS technique detects and analyzes
minute viscoelastic variations of blood at a micro-ultrasonic spot
(<100 μm) defined by laser-generated focused ultrasound (LGFU).
This utilizes (1) a uniquely designed optical transducer configuration
for frequency-spectral matching and wideband operation (6 dB widths:
7–32 MHz and d.c. ∼ 46 MHz, respectively) and (2) an
empirical mode decomposition (EMD)-based signal process particularly
adapted to nonstationary LGFU signals backscattered from the spot.
An EMD-derived spectral analysis enables one to assess viscoelastic
variations during the initiation of fibrin formation, which occurs
at a very early stage of blood coagulation (1 min) with high sensitivity
(frequency transition per storage modulus increment = 8.81 MHz/MPa).
Our results exhibit strong agreement with those obtained by conventional
rheometry (Pearson’s R > 0.95), which are
also confirmed by optical microscopy. The micro-ultrasonic and high-sensitivity
detection of AOUSS poses a potential clinical significance, serving
as a screening modality to diagnose early stage clot formation (e.g.,
as an indicator for hypercoagulation of blood) and stages of blood-to-clot
transition to check a potential risk for development into thrombotic
diseases.