Three‐compartment T₁ relaxation model for intracellular paramagnetic contrast agents

Abstract

The goal of this work was to elaborate a model describing the effective longitudinal relaxation rate constant R 1 for 1 H 2 O in three cellular compartments experiencing possible equilibrium water exchange, and to apply this model to explain the effective R 1 dependence on the overall concentration of a cell-internalized Gd 3؉ -based contrast agent (CA). The model voxel comprises three compartments representing extracellular, cytoplasmic, and vesicular (e.g., endosomal, lysosomal) subcellular spaces. Relaxation parameters were simulated using a modified Bloch-McConnell equation including magnetization exchange between the three compartments. With the model, several possible scenarios for internalized CA distribution were evaluated. Relaxation parameters were calculated for contrast agent restricted to the cytoplasmic or vesicular compartments. The size or the number of CA-loaded vesicles was varied. The simulated data were then separately fitted with empirical monoand biexponential inversion recovery expressions. The voxel CA-concentration dependencies of R 1 can be used to qualitatively and quantitatively understand a number of different experimental observations reported in the literature. Most important, the simulations reproduced the relaxivity "quenching" for cell-internalized contrast agent that has been observed.

Quantitative 1H MRI, 19F MRI, and 19F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

“…NT-emulsion ended up in small 3-4 mm diameter intracellular vesicles, whereas RGD-emulsion was in larger 4-8 mm diameter vesicles. The lower surface to volume ratio of the larger vesicles is associated with a lower water exchange rate across the vesicle membrane, leading to a lower effective relaxivity -an effect coined relaxivity quenching, observed previously for cyclic RGD-conjugated liposomes as well (4,5). For the fluorine MRI and MRS signals water exchange rates obviously play no role and therefore quantification, i.e.…”

Experimental system to detect a labeled cell monolayer in a microfluidic environment

“…16 The relaxation rate was also simulated considering the theoretical model developed by Strijkers et al, 17 based on the Bloch equations including exchanges of water molecules among three different compartments (vesicles, cytoplasm, and the extracellular medium). Their model allows the quantification of the decreased efficiency due to the CA internalization, depending on the location of the paramagnetic chelates.…”

Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging

“…A third disadvantage of endocytic cell labelling is that the vast majority of the contrast agents are trafficked to the endolysosomes where they are exposed to an acidic and overall degrading environment 26,28 . This can lead to degradation of the contrast agent, lowering the signal intensity, as reported for fluorescent labels [28][29][30] as well as MRI contrast agents [31][32][33] . In addition, it has been reported that nanomaterials trapped in endolysosomal vesicles are not distributed equally over daughter cells upon cell division 30,34,35 .…”