A Phantom-Free Approach for Estimating the Backscatter Coefficient of Aggregated Red Blood Cells applied to COVID-19 Patients.

The ultrasound backscatter coefficient is a frequency-dependent quantity intrinsic to biological tissues that can be recovered from backscattered radiofrequency signals, granted acquisitions on a reference phantom are available under the same system's settings. A phantom-free backscatter coefficient estimation method is proposed based on Gaussian-shaped approximation of the point spread function (electronics and piezoelectric characteristics of the scanner's probe) and the effective medium theory combined with the structure factor model, albeit the proposed approach is amenable to other models. Meanwhile, the total attenuation due to intervening tissues is refined from its theoretical value, which is based on reported average behaviors of tissues, while allowing correction for diffraction due to the probe's geometry. The reference phantom method adapted to a similar approach except for the Gaussian approximation is also presented. The proposed phantom-free and reference phantom methods were compared on ten COVID-19 positive patients and twelve control subjects with measures on femoral veins and arteries. In this context, red blood cells are viewed as scatterers that form aggregates increasing the backscatter under the COVID-19 inflammatory condition. The considered model comprises five parameters, including the mean aggregate size estimated according to polydispersity of aggregates' radii, and anisotropy of their shape. The mean aggregate size over the two proposed methods presented an intraclass correlation coefficient of 0.964 for consistency. The aggregate size presented a significant difference between the two groups with either two methods, despite the confounding effect of the maximum Doppler velocity within the blood vessel and its diameter.