Objective assessment of stored blood quality by deep learning.

Journal: Proceedings of the National Academy of Sciences of the United States of America
Published Date:

Abstract

Stored red blood cells (RBCs) are needed for life-saving blood transfusions, but they undergo continuous degradation. RBC storage lesions are often assessed by microscopic examination or biochemical and biophysical assays, which are complex, time-consuming, and destructive to fragile cells. Here we demonstrate the use of label-free imaging flow cytometry and deep learning to characterize RBC lesions. Using brightfield images, a trained neural network achieved 76.7% agreement with experts in classifying seven clinically relevant RBC morphologies associated with storage lesions, comparable to 82.5% agreement between different experts. Given that human observation and classification may not optimally discern RBC quality, we went further and eliminated subjective human annotation in the training step by training a weakly supervised neural network using only storage duration times. The feature space extracted by this network revealed a chronological progression of morphological changes that better predicted blood quality, as measured by physiological hemolytic assay readouts, than the conventional expert-assessed morphology classification system. With further training and clinical testing across multiple sites, protocols, and instruments, deep learning and label-free imaging flow cytometry might be used to routinely and objectively assess RBC storage lesions. This would automate a complex protocol, minimize laboratory sample handling and preparation, and reduce the impact of procedural errors and discrepancies between facilities and blood donors. The chronology-based machine-learning approach may also improve upon humans' assessment of morphological changes in other biomedically important progressions, such as differentiation and metastasis.

Authors

  • Minh Doan
    Imaging Platform at the Broad Institute of Harvard and MIT, 415 Main St, Cambridge, Massachusetts, 02142.
  • Joseph A Sebastian
    Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada.
  • Juan C Caicedo
    Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Stefanie Siegert
    Flow Cytometry Facility, Department of Formation and Research, University of Lausanne, 1015 Lausanne, Switzerland.
  • Aline Roch
    Doppl SA, Lausanne, Switzerland.
  • Tracey R Turner
    Centre for Innovation, Canadian Blood Services, Edmonton, AB T6G 2R8, Canada.
  • Olga Mykhailova
    Centre for Innovation, Canadian Blood Services, Edmonton, AB T6G 2R8, Canada.
  • Ruben N Pinto
    Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada.
  • Claire McQuin
    Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
  • Allen Goodman
    Imaging Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
  • Michael J Parsons
    Flow Cytometry Core Facilities, Lunenfeld-Tanenbaum Research Institute, Toronto, ON M5G 1X5, Canada.
  • Olaf Wolkenhauer
    Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, Rostock, Germany.
  • Holger Hennig
    Imaging Platform at the Broad Institute of Harvard and MIT, 415 Main St, Cambridge, MA 02142, USA; Dept. of Systems Biology & Bioinformatics, University of Rostock, 18051 Rostock, Germany; College of Engineering, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
  • Shantanu Singh
    Imaging Platform, Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
  • Anne Wilson
    Flow Cytometry Facility, Department of Formation and Research, University of Lausanne, 1015 Lausanne, Switzerland.
  • Jason P Acker
    Centre for Innovation, Canadian Blood Services, Edmonton, AB T6G 2R8, Canada.
  • Paul Rees
    Imaging Platform at the Broad Institute of Harvard and MIT, 415 Main St, Cambridge, MA 02142, USA; College of Engineering, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
  • Michael C Kolios
    Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada; mkolios@ryerson.ca anne@broadinstitute.org.
  • Anne E Carpenter
    The Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, United States. Electronic address: anne@broadinstitute.org.