Noninvasive Quantification of Cell Density in Three-Dimensional Gels by MRI

Brian J. Archer, Till Uberruck, Julia J. Mack, Khalid Youssef, Nanette N. Jarenwattananon, Deniz Rall, Denis Wypysek, Martin Wiese, Bernhard Blumich, Matthias Wessling, M. Luisa Iruela-Arispe, Louis S. Bouchard*

*Corresponding author for this work

Research output: Contribution to journalArticle


Objective: For tissue engineering, there is a need for quantitative methods to map cell density inside three-dimensional (3-D) bioreactors to assess tissue growth over time. The current cell mapping methods in 2-D cultures are based on optical microscopy. However, optical methods fail in 3-D due to increased opacity of the tissue. We present an approach for measuring the density of cells embedded in a hydrogel to generate quantitative maps of cell density in a living, 3-D tissue culture sample. Methods: Quantification of cell density was obtained by calibrating the 1H T2, magnetization transfer (MT) and diffusion-weighted nuclear magnetic resonance (NMR) signals to samples of known cell density. Maps of cell density were generated by weighting NMR images by these parameters post-calibration. Results: The highest sensitivity weighting arose from MT experiments, which yielded a limit of detection (LOD) of 2.5 × 10 8 cells/mL/ Hz in a 400 MHz (9.4 T) magnet. Conclusion: This mapping technique provides a noninvasive means of visualizing cell growth within optically opaque bioreactors. Significance: We anticipate that such readouts of tissue culture growth will provide valuable feedback for controlled cell growth in bioreactors.

Original languageEnglish (US)
Article number8412441
Pages (from-to)821-830
Number of pages10
JournalIEEE Transactions on Biomedical Engineering
Issue number3
StatePublished - Mar 2019


  • MRI
  • Tissue engineering
  • bioreactor
  • cell density
  • cell growth
  • hydrogel

ASJC Scopus subject areas

  • Biomedical Engineering

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    Archer, B. J., Uberruck, T., Mack, J. J., Youssef, K., Jarenwattananon, N. N., Rall, D., Wypysek, D., Wiese, M., Blumich, B., Wessling, M., Iruela-Arispe, M. L., & Bouchard, L. S. (2019). Noninvasive Quantification of Cell Density in Three-Dimensional Gels by MRI. IEEE Transactions on Biomedical Engineering, 66(3), 821-830. [8412441].