Real-Time Deformability Cytometry Detects Leukocyte Stiffening After Gadolinium-Based Contrast Agent Exposure

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 neutrophilswere 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.

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

“…Due to the life-long disease course patients experience multiple MRI scans, each time accompanied by the exposure to gadolinium-based contrast agents. However, recent reports of long-term gadolinium depositions in brain, bones and skin of patients questions the safety of gadolinium-based contrast agents and ask for a more secure alternative ( White et al, 2006 ; Kanda et al, 2015 ; Robles Cartagena et al, 2015 ; Flood et al, 2017 ; Wang et al, 2019 ; Jacobi et al, 2021 ). A possible alternative for imaging inflammation is an iron oxide-based contrast agent, called very small superparamagnetic iron oxide particles (VSOPs).…”

Human T cells loaded with superparamagnetic iron oxide nanoparticles retain antigen-specific TCR functionality

“…Iron oxide nanoparticles applied as contrast agents, such as Resovist ® or Endorem ® , can have an effect on the actin cytoskeleton and microtubule network, when the intracellular iron concentrations (> 40 pg Fe/cell) are very high, which has already been shown in C17.2 neural progenitor cells and human blood outgrowth endothelial cells ( 60 ). In leukocytes, gadolinium particles applied as contrast agents also caused cell stiffening, as determined by deformability cytometry ( 61 ). Using deformability cytometry, we showed that SPION loading does not alter the mechanical properties of T cells, as quantified by the Young’s modulus ( Figure 1 ), which might be due to the relatively low cellular nanoparticle concentrations around 1 pg Fe/cell ( 23 ).…”