Quantification of Very Low Concentrations of Leukocyte Suspensions In Vitro by High-Frequency Ultrasound

Accurate measurement of very low cerebrospinal fluid (CSF) white blood cell (WBC) concentration is key to the diagnosis of bacterial meningitis, lethal if not promptly treated. Here we show that high frequency ultrasound (HFUS) can detect CSF WBC in vitro in concentrations relevant to meningitis diagnosis with a much finer precision than gold standard manual counting in a Fuchs-Rosenthal chamber. WBC concentrations in a mock CSF model, in the range 0-50 WBC/μL, have been tested and compared to gold standard ground truth. In this range, excellent agreement (Cohen's kappa [κ] = 0.78-90) (Cohen 1960) was observed between HFUS and the gold standard method. The presented experimental set-up allowed us to detect WBC concentrations as low as 2 cells/μL. HFUS shows promise as a low-cost, reliable and automated technology to measure very low CSF WBC concentrations for the diagnosis of early meningitis.