Enhanced positive‐contrast visualization of paramagnetic contrast agents using phase images

Iron oxide–based MRI contrast agents are increasingly being used to noninvasively track cells, target molecular epitopes, and monitor gene expression in vivo. Detecting regions of contrast agent accumulation can be challenging if resulting contrast is subtle relative to endogenous tissue hypointensities. A postprocessing method is presented that yields enhanced positive‐contrast images from the phase map associated with T₂*‐weighted MRI data. As examples, the method was applied to an agarose gel phantom doped with superparamagnetic iron‐oxide nanoparticles and in vivo and ex vivo mouse brains inoculated with recombinant viruses delivering transgenes that induce overexpression of paramagnetic ferritin. Overall, this approach generates images that exhibit a 1‐ to 8‐fold improvement in contrast‐to‐noise ratio in regions where paramagnetic agents are present compared to conventional magnitude images. This approach can be used in conjunction with conventional T₂* pulse sequences, requires no prescans or increased scan time, and can be applied retrospectively to previously acquired data. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Spatially encoded phase‐contrast MRI—3D MRI movies of 1D and 2D structures at millisecond resolution

This work demonstrates that the principles underlying phase‐contrast MRI may be used to encode spatial rather than flow information along a perpendicular dimension, if this dimension contains an MRI‐visible object at only one spatial location. In particular, the situation applies to 3D mapping of curved 2D structures which requires only two projection images with different spatial phase‐encoding gradients. These phase‐contrast gradients define the field of view and mean spin‐density positions of the object in the perpendicular dimension by respective phase differences. When combined with highly undersampled radial fast low angle shot (FLASH) and image reconstruction by regularized nonlinear inversion, spatial phase‐contrast MRI allows for dynamic 3D mapping of 2D structures in real time. First examples include 3D MRI movies of the acting human hand at a temporal resolution of 50 ms. With an even simpler technique, 3D maps of curved 1D structures may be obtained from only three acquisitions of a frequency‐encoded MRI signal with two perpendicular phase encodings. Here, 3D MRI movies of a rapidly rotating banana were obtained at 5 ms resolution or 200 frames per second. In conclusion, spatial phase‐contrast 3D MRI of 2D or 1D structures is respective two or four orders of magnitude faster than conventional 3D MRI. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Comparison of 1H blood oxygen level–dependent (BOLD) and 19F MRI to investigate tumor oxygenation

Fluorine‐19 [¹⁹F] MRI oximetry and ¹H blood oxygen level–dependent (BOLD) MRI were used to investigate tumor oxygenation in rat breast 13762NF carcinomas, and correlations between the techniques were examined. A range of tissue oxygen partial pressure (pO₂) values was found in the nine tumors while the anesthetized rats breathed air, with individual tumor pO₂ ranging from a mean of 1 to 36 torr and hypoxic fraction (HF10) (<10 torr) ranging from 0% to 75%, indicating a large intra‐ and intertumor heterogeneity. Breathing oxygen produced significant increase in tumor pO₂ (mean ΔpO₂ = 50 torr) and decrease in HF₁₀ (P < 0.01). ¹H BOLD MRI observed using a spin echo‐planar imaging (EPI) sequence revealed a heterogeneous response and significant increase in mean tumor signal intensity (SI) (ΔSI = 7%, P < 0.01). R measured by multigradient‐echo (MGRE) MRI decreased significantly in response to oxygen (mean ΔR = ?4 s^?1; P < 0.05). A significant correlation was found between changes in mean tumor pO₂ and mean EPI BOLD ΔSI accompanying oxygen breathing (r² > 0.7, P < 0.001). Our results suggest that BOLD MRI provides information about tumor oxygenation and may be useful to predict pO₂ changes accompanying interventions. Significantly, the magnitude of the BOLD response appears to be predictive for residual tumor HFs. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

In vivo cytometry of antigen‐specific t cells using 19F MRI

Noninvasive methods to image the trafficking of phenotypically defined immune cells are paramount as we attempt to understand adaptive immunity. A ¹⁹F MRI‐based methodology for tracking and quantifying cells of a defined phenotype is presented. These methods were applied to a murine inflammation model using antigen‐specific T cells. The T cells that were intracellularly labeled ex vivo with a perfluoropolyether (PFPE) nanoemulsion and cells were transferred to a host receiving a localized inoculation of antigen. Longitudinal ¹⁹F MRI over 21 days revealed a dynamic accumulation and clearance of T cells in the lymph node (LN) draining the antigen. The apparent T‐cell numbers were calculated in the LN from the time‐lapse ¹⁹F MRI data. The effect of in vivo T‐cell division on the ¹⁹F MRI cell quantification accuracy was investigated using fluorescence assays. Overall, in vivo cytometry using PFPE labeling and ¹⁹F MRI is broadly applicable to studies of whole‐body cell biodistribution. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Hexafluorobenzene in comparison with perfluoro‐15‐crown‐5‐ether for repeated monitoring of oxygenation using 19F MRI in a mouse model

Hexafluorobenzene (HFB) and perfluoro‐15‐crown‐5‐ether (15C5) were compared as fluorine reporter probes of tissue oxygenation using ¹⁹F MRI for dynamic assessment of muscle oxygenation, with special focus on muscle tissue toxicity of the probes, and consecutive alteration of animal behavior. The latter were also compared in terms of sensitivity to changes in oxygenation as well as of signal‐to‐noise ratio for accurate pO₂ measurements. For that purpose, mouse muscles were imaged at 11.7 T, at 2‐ and 36‐h after intramuscular injection of HFB or 15C5. Histological analysis of the muscle tissue revealed a lack of toxicity for 15C5 from 2 up to 36‐h postinjection, whereas HFB induced tissue necrosis, blood clots and thrombosis as soon as 24‐h postinjection. This muscle toxicity led to a limitation in mice mobility 24‐h after injection of HFB as evidenced by behavioral testing (open‐field, grip strength, and catwalk tests), which was not the case after 15C5 intramuscular injection. Finally, pO₂ measurements assessed 2‐h postinjection showed consistent values with both probes, evidencing cross‐validation of the ¹⁹F MRI oximetry technique for acute measurements. However, the measurement at 36‐h was hampered for HFB, which showed significant lower values of muscle pO₂, whereas 15C5 was able to reliably assess muscle pO₂ at 36‐h postinjection. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.