Micro-ultrasonic Assessment of Early Stage Clot Formation and Whole Blood Coagulation Using an All-Optical Ultrasound Transducer and Adaptive Signal Processing Algorithm

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 quantitati. 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 mu m) 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. similar to 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 hypercoagul ation of blood) and stages of blood-to-clot transition to check a potential risk for development into thrombotic diseases.

Automated summary

This study proposes a micro-ultrasonic diagnosis technique using an all-optical ultrasound-based spectral sensing (AOUSS) method for sensitive and quantitative characterization of early stage and whole blood coagulation. By detecting and analyzing minute viscoelastic variations of blood, the technique enables the assessment of early stage clot formation with high sensitivity. The results show strong agreement with conventional rheometry tests and suggest potential clinical significance.