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

Xavier Jimenez; Shiva K Shukla; Isabel Ortega; Francisco J Illana; Carlos Castro-González; Berta Marti-Fuster; Ian Butterworth; Manuel Arroyo; Brian Anthony; Luis Elvira

doi:10.1016/j.ultrasmedbio.2016.01.027

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

Ultrasound Med Biol. 2016 Jul;42(7):1568-73. doi: 10.1016/j.ultrasmedbio.2016.01.027. Epub 2016 Apr 7.

Authors

Affiliations

¹ Madrid-MIT M+Vision Consortium, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: javijimenezg@gmail.com.
² Instituto de Tecnologías Físicas y de la Información, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
³ Proteomic and Metabolomic Unit, Clinical Laboratory Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
⁴ Madrid-MIT M+Vision Consortium, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ 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.
⁶ Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139 Cambridge, MA, USA.

PMID: 27067281
DOI: 10.1016/j.ultrasmedbio.2016.01.027

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.

Keywords: Cell count; Cerebrospinal fluid; Cytometry; High frequency ultrasound; Meningitis; White blood cell.

MeSH terms

Humans
In Vitro Techniques
Leukocytes*
Leukocytosis / blood*
Reproducibility of Results
Ultrasonography / methods*