Angela Jacobi, Angela Ariza de Schellenberger1, Yavuz Oguz Uca1, Maik Herbig, Jochen Guck2, Ingolf Sack1. 1. Department of Radiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin. 2. From the Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen.
Abstract
OBJECTIVES: Reports on gadolinium (Gd) retention in soft tissues after administration of Gd-based contrast agents (GBCAs) raise concerns about Gd-induced changes in the biophysical properties of cells and tissues. Here, we investigate if clinical GBCAs of both classes of linear and macrocyclic structure cause changes in the mechanical properties of leukocytes in human blood samples. MATERIAL AND METHODS: Real-time deformability cytometry was applied to human blood samples from 6 donors. The samples were treated with 1 mM gadoteric acid (Dotarem), gadopentetic acid (Magnevist), gadobutrol (Gadovist), or Gd trichloride at 37°C for 1 hour to mimic clinical doses of GBCAs and exposure times. Leukocyte subtypes-lymphocytes, monocytes, and neutrophils-were identified based on their size and brightness and analyzed for deformability, which is inversely correlated with cellular stiffness. RESULTS: We observed significant stiffening (3%-13%, P < 0.01) of all investigated leukocyte subtypes, which was most pronounced for lymphocytes, followed by neutrophils and monocytes, and the effects were independent of the charge and steric structure of the GBCA applied. In contrast, no changes in cell size and brightness were observed, suggesting that deformability and cell stiffness measured by real-time deformability cytometry are sensitive to changes in the physical phenotypes of leukocytes after GBCA exposure. CONCLUSIONS: Real-time deformability cytometry might provide a quantitative blood marker for critical changes in the physical properties of blood cells in patients undergoing GBCA-enhanced magnetic resonance imaging.
OBJECTIVES: Reports on gadolinium (Gd) retention in soft tissues after administration of Gd-based contrast agents (GBCAs) raise concerns about Gd-induced changes in the biophysical properties of cells and tissues. Here, we investigate if clinical GBCAs of both classes of linear and macrocyclic structure cause changes in the mechanical properties of leukocytes in human blood samples. MATERIAL AND METHODS: Real-time deformability cytometry was applied to human blood samples from 6 donors. The samples were treated with 1 mM gadoteric acid (Dotarem), gadopentetic acid (Magnevist), gadobutrol (Gadovist), or Gd trichloride at 37°C for 1 hour to mimic clinical doses of GBCAs and exposure times. Leukocyte subtypes-lymphocytes, monocytes, and neutrophils-were identified based on their size and brightness and analyzed for deformability, which is inversely correlated with cellular stiffness. RESULTS: We observed significant stiffening (3%-13%, P < 0.01) of all investigated leukocyte subtypes, which was most pronounced for lymphocytes, followed by neutrophils and monocytes, and the effects were independent of the charge and steric structure of the GBCA applied. In contrast, no changes in cell size and brightness were observed, suggesting that deformability and cell stiffness measured by real-time deformability cytometry are sensitive to changes in the physical phenotypes of leukocytes after GBCA exposure. CONCLUSIONS: Real-time deformability cytometry might provide a quantitative blood marker for critical changes in the physical properties of blood cells in patients undergoing GBCA-enhanced magnetic resonance imaging.