title: Quantification of Very Low Concentrations of Leukocyte Suspensions In Vitro by High-Frequency Ultrasound.
abstract: 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.
authors.affiliation: Madrid-MIT M+Vision Consortium, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: javijimenezg@gmail.com.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jimenez
authors.affiliation: Instituto de Tecnologías Físicas y de la Información, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Shiva K
authors.initials: SK
authors.lastname: Shukla
authors.affiliation: Proteomic and Metabolomic Unit, Clinical Laboratory Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ortega
authors.affiliation: Proteomic and Metabolomic Unit, Clinical Laboratory Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Illana
authors.affiliation: Madrid-MIT M+Vision Consortium, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Castro-González
authors.affiliation: Madrid-MIT M+Vision Consortium, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 02129 Charlestown, MA, USA.
authors.forename: Berta
authors.initials: B
authors.lastname: Marti-Fuster
authors.affiliation: Madrid-MIT M+Vision Consortium, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Butterworth
authors.affiliation: Proteomic and Metabolomic Unit, Clinical Laboratory Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Arroyo
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139 Cambridge, MA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Anthony
authors.affiliation: Instituto de Tecnologías Físicas y de la Información, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Elvira
mesh_terms: D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes; D007964:Leukocytosis / Q000097:blood*; D015203:Reproducibility of Results; D014463:Ultrasonography / Q000379:methods*
keywords: Cell count; Cerebrospinal fluid; Cytometry; High frequency ultrasound; Meningitis; White blood cell