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BACKGROUND: An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE: This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS: Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S 10 ). RESULTS: W and D in vivo measurements were positively correlated with the ex vivo S 10 index for both measurement sites and shear rates (correlations between 0.35-0.81, p < 0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS: We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated.

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Non-alcoholic fatty liver disease is a highly prevalent condition, which may progress to non-alcoholic steatohepatitis (NASH), an advanced form found in 3 to 5% of the population. As liver biopsy is invasive, there is a need for a non-invasive technique for the assessment of NASH. Due to promising results of shear-wave elastography (SWE) in staging this disease, there is a high interest in developing a multi-parametric approach for assessment of liver steatosis within the same ultrasound (US) examination. The goal of this study was to assess the added value of quantitative US (QUS) parameters to SWE, based on random forest classifiers and area under the ROC curve (AUC). Sixty male Sprague-Dawley rats were either fed a standard chow or a methionine-and choline-deficient diet. Using a research US system (model V1, Verasonics Inc.), SWE measurements were performed while rats were under anesthesia. To generate shear wavefronts within the liver, a linear array US transducer (ATL L7-4, Philips) was used to induce three 40-V 125-μs long radiation force pushes 4 mm apart. For SW tracking, the same transducer was used to acquire plane wave radiofrequency data at a frame rate of 4 kHz; images were reconstructed using the f-k migration algorithm. QUS acquisitions were performed using the same system and transducer. One hundred frames were acquired, migrated, and the echo envelope was obtained with Hilbert transforms. The image post-processing yielded 4 homodyned-K parametric maps within the region-of-interest (ROI), from which 8 features were extracted. The local attenuation coefficient slope within the ROI was also computed using the spectral shift method. QUS parameters improved the classification accuracy of steatohepatitis, liver steatosis, inflammation, and fibrosis compared to SWE alone. For detection of liver steatosis grades 0 vs ≥ 1, ≤ 1 vs ≥ 2, ≤ 2 vs 3, respectively, AUCs increased from 0.70, 0.65, and 0.69 to 0.78, 0.78, and 0.75 (p < 0.001).