Low-field, high-gradient NMR shows diffusion contrast consistent with localization or motional averaging of water near surfaces

Nuclear magnetic resonance(NMR)measurements of water diffusion have been extensively used to probe microstructure in porous materials,such as biological tissue,however primarily using pulsed gradient spin echo(PGSE)methods.Low-field single-sided NMR systems have built-in static gradients(SG)much stronger than typical PGSE maximum gradient strengths,which allows for the signal attenuation at extremely high b-values to be explored.Here,we perform SG spin echo(SGSE)and SG stimulated echo(SGSTE)diffusion measurements on biological cells,tissues,and gels.Measurements on fixed and live neonatal mouse spinal cord,lobster ventral nerve cord,and starved yeast cells all show multiexponential signal attenuation on a scale of b with significant signal fractions observed at b×Do>1 with b as high as 400 ms/um2.These persistent signal fractions trend with surface-to-volume ratios for these systems,as expected from porous media theory.An exception found for the case of fixed vs.live spinal cords was attributed to faster exchange or permeability in live spinal cords than in fixed spinal cords on the millisecond timescale.Data suggests the existence of multiple exchange processes in neural tissue,which may be relevant to the modeling of time-dependent diffusion in gray matter.The observed multi-exponential attenuation is from protons on water and not macromolecules because it remains proportional to the normalized signal when a specimen is washed with D20.The signal that persists to b×Do>1 is also drastically reduced after delipidation,indicating that it originates from lipid membranes that restrict water diffusion.The multiexponential or stretched exponential character of the signal attenuation at b×Do>1 appears mono-exponential when viewed on a scale of(b×Do)/3,suggesting it may originate from localization or motional averaging of water near membranes on sub-micron length scales.To try to disambiguate these two contributions,signal attenuation curves were compared at varying temperatures.While the curves align when normalizing them using the localization length scale,they separate on a motional averaging length scale.This supports localization as the source of non-Gaussian displacements,but this interpretation is still provisional due to the possible confounds of heterogeneity,exchange,and relaxation.Measurements on two types of gel phantoms designed to mimic extracellular matrix.one with charged functional groups synthesized from polyacrylic acid(PAC)and another with uncharged functional groups synthesized from polyacrylamide(PAM),both exhibit signal at b×Do>1,potentially due to water interacting with macromolecules.These preliminary finding motivate future research into contrast and attenuation mechanisms in tissue with low-field,high-gradient NMR。

Efficiently tracking of stem cells in vivo using different kinds of superparamagnetic iron oxide in swine with myocardial infarction

Background Superparamagnetic iron oxide （SPIO） particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging （MRI）. Micrometer-sized superparamagnetic iron oxide （MPIO）particles and nanometer-sized ultrasmall superparamagnetic iron oxide （USPIO） are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction （AMI）.Methods An AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 107 magnetically labeled mesenchymal stem cells （MR-MSCs）. The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.Results MR-MSCs appeared as a local hypointense signal on T2 -weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T2 -weighted MRI, contrast to noise ratio （CNR） decreased in the MPIO-labeled group （16.07±5.85 vs. 10.96±1.34）and USPIO-labeled group （11.72±1.27 vs. 10.03±0.96） from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.Conclusions We demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability.USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.