Temporal and noninvasive monitoring of inflammatory‐cell infiltration to myocardial infarction sites using micrometer‐sized iron oxide particles

Micrometer‐sized iron oxide particles (MPIO) are a more sensitive MRI contrast agent for tracking cell migration compared to ultrasmall iron oxide particles. This study investigated the temporal relationship between inflammation and tissue remodeling due to myocardial infarction (MI) using MPIO‐enhanced MRI. C57Bl/6 mice received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later (n = 7). For controls, two groups underwent either sham‐operated surgery without inducing an MI post‐MPIO injection (n = 7) or MI surgery without MPIO injection (n = 6). The MRIs performed post‐MI showed significant signal attenuation around the MI site for the mice that received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later, compared to the two control groups (P < 0.01). The findings suggested that the prelabeled inflammatory cells mobilized and infiltrated into the MI site. Furthermore, the linear regression of contrast‐to‐noise ratio at the MI site and left ventricular ejection function suggested a positive correlation between the labeled inflammatory cell infiltration and cardiac function attenuation during post‐MI remodeling (r² = 0.98). In conclusion, this study demonstrated an MRI technique for noninvasively and temporally monitoring inflammatory cell migration into the myocardium while potentially providing additional insight concerning the pathologic progression of a myocardial infarction. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

Monitoring bone marrow‐originated mesenchymal stem cell traffic to myocardial infarction sites using magnetic resonance imaging

How stem cells promote myocardial repair in myocardial infarction (MI) is not well understood. The purpose of this study was to noninvasively monitor and quantify mesenchymal stem cells (MSC) from bone marrow to MI sites using magnetic resonance imaging (MRI). MSC were dual‐labeled with an enhanced green fluorescent protein and micrometer‐sized iron oxide particles prior to intra‐bone marrow transplantation into the tibial medullary space of C57Bl/6 mice. Micrometer‐sized iron oxide particles labeling caused signal attenuation in T₂*‐weighted MRI and thus allowed noninvasive cell tracking. Longitudinal MRI demonstrated MSC infiltration into MI sites over time. Fluorescence from both micrometer‐sized iron oxide particles and enhanced green fluorescent protein in histology validated the presence of dual‐labeled cells at MI sites. This study demonstrated that MSC traffic to MI sites can be noninvasively monitored in MRI by labeling cells with micrometer‐sized iron oxide particles. The dual‐labeled MSC at MI sites maintained their capability of proliferation and differentiation. The dual‐labeling, intra‐bone marrow transplantation, and MRI cell tracking provided a unique approach for investigating stem cells' roles in the post‐MI healing process. This technique can potentially be applied to monitor possible effects on stem cell mobilization caused by given treatment strategies. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Magnetic poly(lactide‐co‐glycolide) and cellulose particles for MRI‐based cell tracking

Biodegradable, superparamagnetic microparticles and nanoparticles of poly(lactide‐co‐glycolide) (PLGA) and cellulose were designed, fabricated, and characterized for magnetic cell labeling. Monodisperse nanocrystals of magnetite were incorporated into microparticles and nanoparticles of PLGA and cellulose with high efficiency using an oil‐in‐water single emulsion technique. Superparamagnetic cores had high magnetization (72.1 emu/g). The resulting polymeric particles had smooth surface morphology and high magnetite content (43.3 wt % for PLGA and 69.6 wt % for cellulose). While PLGA and cellulose nanoparticles displayed highest r values per millimole of iron (399 sec^?1 mM^?1 for cellulose and 505 sec^?1 mM^?1 for PLGA), micron‐sized PLGA particles had a much higher r per particle than either. After incubation for a month in citrate buffer (pH 5.5), magnetic PLGA particles lost close to 50% of their initial r molar relaxivity, while magnetic cellulose particles remained intact, preserving over 85% of their initial r molar relaxivity. Lastly, mesenchymal stem cells and human breast adenocarcinoma cells were magnetically labeled using these particles with no detectable cytotoxicity. These particles are ideally suited for noninvasive cell tracking in vivo via MRI and due to their vastly different degradation properties, offer unique potential for dedicated use for either short (PLGA‐based particles) or long‐term (cellulose‐based particles) experiments. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Compensation of slice profile mismatch in combined spin‐ and gradient‐echo echo‐planar imaging pulse sequences

Combined acquisition of gradient‐echo and spin‐echo signals in MRI time series reveals additional information for perfusion‐weighted imaging and functional MRI because of differences in the sensitivity of gradient‐echo and spin‐echo measurements to the properties of the underlying vascular architecture. The acquisition of multiple echo trains within one time frame facilitates the simultaneous estimation of the transversal relaxation parameters R₂ and R. However, the simultaneous estimation of these parameters tends to be incorrect in the presence of slice profile mismatches between signal excitation and subsequent refocusing pulses. It is shown here that improvements in pulse design reduced R₂ and R estimation errors. Further improvements were achieved by augmented parameter estimation through the introduction of an additional parameter δ to correct for discordances in slice profiles to facilitate more quantitative measurements. Moreover, the analysis of time‐resolved acquisitions revealed that the temporal stability of R₂ estimates could be increased with improved pulse design, counteracting low contrast‐to‐noise ratios in spin‐echo‐based perfusion and functional MRI. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Fast CPMG‐based Bloch‐Siegert B1+ mapping

A novel method for B mapping based on the Bloch‐Siegert (BS) shift was recently presented. This method applies off‐resonant pulses before signal acquisition to encode B₁ information into the signal phase. BS‐based methods possess significant advantages in measurement time and accuracy compared to magnitude‐based B methods. This study extends the idea of BS B mapping to Carr, Purcell, Meiboom, Gill (CPMG)‐based multi‐spin‐echo (BS‐CPMG‐MSE) and turbo‐spin‐echo (BS‐CPMG‐TSE) imaging. Compared to BS‐based spin echo imaging (BS‐SE), faster acquisition of the B information was possible using the BS‐CPMG‐TSE sequence. Furthermore, signal loss by T₂* effects could be minimized using these spin echo‐based techniques. These effects are critical for gradient echo‐based BS methods at high field strengths. However, multi‐spin‐echo‐based BS B₁ methods inherently possess high specific absorption rates. Thus, the relative specific absorption rate of BS‐CPMG‐TSE sequences was estimated and compared with the specific absorption rate produced by BS‐SE sequences. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Early detection of lung inflammation: Exploiting T1‐effects of iron oxide particles using UTE MRI

At high magnetic fields diagnostic proton MRI of the lung is problematic, because of fast T relaxation. The application of superparamagnetic contrast agents and the exploitation of the corresponding T effect is inefficient with conventional MRI methods, which limits the early detection of lung diseases. However, a simple theoretical treatment shows that in the lung, by the use of ultra‐short echo time sequences, T effects can be neglected while T₁ shortening effects can be used for signal detection. In our study, we have applied a theoretically and experimentally optimized 3D ultra‐short echo time sequence to lung phantoms and to a mouse model of lung inflammation, which was induced by systemic bacterial infection. Following the systemic application of very small superparamagnetic iron oxide nanoparticles, a significant signal increase in the lung of infected animals was detected already at 24 h postinfection, compared to control mice (17%, P < 0.001). Iron accumulation in the lung parenchyma as consequence of the host immune response was histologically confirmed. By conventional T‐ and T₂‐weighted imaging, neither structural changes nor formation of substantial edema were observed. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Bolus‐tracking MRI with a simultaneous T1‐ and T‐measurement

The aim of this study was to propose and evaluate a methodology to analyze simultaneously acquired T‐weighted dynamic susceptibility contrast (DSC) MRI and T₁‐weighted dynamic contrast enhanced (DCE) MRI data. Two generalized models of T‐relaxation are proposed to account for tracer leakage, and a two‐compartment exchange model is used to separate tracer in intra‐ and extravascular spaces. The methods are evaluated using data extracted from ROIs in three mice with subcutaneously implanted human colorectal tumors. Comparing plasma flow values obtained from DCE‐MRI and DSC‐MRI data defines a practical experimental paradigm to measure T‐relaxivities, and reveals a factor of 15 between values in tissue and blood. Comparing mean transit time values obtained from DCE‐MRI and DSC‐MRI without leakage correction, indicates a significant reduction of susceptibility weighting in DSC‐MRI during tracer leakage. A one‐parameter gradient correction model provides a good approximation for this susceptibility loss, but redundancy of the parameter limits the practical potential of this model for DSC‐MRI. Susceptibility loss is modeled more accurately with a variable T‐relaxivity, which allows to extract new parameters that cannot be derived from DSC‐MRI or DCE‐MRI alone. They reflect the cellular and vessel geometry, and thus may lead to a more complete characterization of tissue structure. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Spectral‐spatial pulse design for through‐plane phase precompensatory slice selection in T‐weighted functional MRI

T‐weighted functional MR images suffer from signal loss artifacts caused by the magnetic susceptibility differences between air cavities and brain tissues. We propose a novel spectral‐spatial pulse design that is slice‐selective and capable of mitigating the signal loss. The two‐dimensional spectral–spatial pulses create precompensatory phase variations that counteract through‐plane dephasing, relying on the assumption that resonance frequency offset and through‐plane field gradient are spatially correlated. The pulses can be precomputed before functional MRI experiments and used repeatedly for different slices in different subjects. Experiments with human subjects showed that the pulses were effective in slice selection and loss mitigation at different brain regions. Magn Reson Med 61:1137–1147, 2009. © 2009 Wiley‐Liss, Inc.     

RT‐GROG: parallelized self‐calibrating GROG for real‐time MRI

A real‐time implementation of self‐calibrating Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) operator gridding for radial acquisitions is presented. Self‐calibrating GRAPPA operator gridding is a parallel‐imaging‐based, parameter‐free gridding algorithm, where coil sensitivity profiles are used to calculate gridding weights. Self‐calibrating GRAPPA operator gridding's weight‐set calculation and image reconstruction steps are decoupled into two distinct processes, implemented in C++ and parallelized. This decoupling allows the weights to be updated adaptively in the background while image reconstruction threads use the most recent gridding weights to grid and reconstruct images. All possible combinations of two‐dimensional gridding weights GG are evaluated for m,n = {?0.5, ?0.4, …, 0, 0.1, …, 0.5} and stored in a look‐up table. Consequently, the per‐sample two‐dimensional weights calculation during gridding is eliminated from the reconstruction process and replaced by a simple look‐up table access. In practice, up to 34× faster reconstruction than conventional (parallelized) self‐calibrating GRAPPA operator gridding is achieved. On a 32‐coil dataset of size 128 × 64, reconstruction performance is 14.5 frames per second (fps), while the data acquisition is 6.6 fps. Magn Reson Med 64:306–312, 2010. © 2010 Wiley‐Liss, Inc.     

Time‐interleaved acquisition of modes: An analysis of SAR and image contrast implications

As the magnetic field strength and therefore the operational frequency in MRI are increased, the radiofrequency wavelength approaches the size of the human head/body, resulting in wave effects which cause signal decreases and dropouts. Especially, whole‐body imaging at 7 T and higher is therefore challenging. Recently, an acquisition scheme called time‐interleaved acquisition of modes has been proposed to tackle the inhomogeneity problems in high‐field MRI. The basic premise is to excite two (or more) different B modes using static radiofrequency shimming in an interleaved acquisition, where the complementary radiofrequency patterns of the two modes can be exploited to improve overall signal homogeneity. In this work, the impact of time‐interleaved acquisition of mode on image contrast as well as on time‐averaged specific absorption rate is addressed in detail. Time‐interleaved acquisition of mode is superior in B homogeneity compared with conventional radiofrequency shimming while being highly specific absorption rate efficient. Time‐interleaved acquisition of modes can enable almost homogeneous high‐field imaging throughout the entire field of view in PD, T₂, and T₂*‐weighted imaging and, if a specified homogeneity criterion is met, in T₁‐weighted imaging as well. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Comparison of amyloid plaque contrast generated by T2‐weighted,T‐weighted,and susceptibility‐weighted imaging methods in transgenic mouse models of Alzheimer's disease

One of the hallmark pathologies of Alzheimer's disease (AD) is amyloid plaque deposition. Plaques appear hypointense on T₂‐weighted and T‐weighted MR images probably due to the presence of endogenous iron, but no quantitative comparison of various imaging techniques has been reported. We estimated the T₁, T₂, T, and proton density values of cortical plaques and normal cortical tissue and analyzed the plaque contrast generated by a collection of T₂‐weighted, T‐weighted, and susceptibility‐weighted imaging (SWI) methods in ex vivo transgenic mouse specimens. The proton density and T₁ values were similar for both cortical plaques and normal cortical tissue. The T₂ and T values were similar in cortical plaques, which indicates that the iron content of cortical plaques may not be as large as previously thought. Ex vivo plaque contrast was increased compared to a previously reported spin‐echo sequence by summing multiple echoes and by performing SWI; however, gradient echo and SWI were found to be impractical for in vivo imaging due to susceptibility interface–related signal loss in the cortex. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Relaxation effects of ferucarbotran‐labeled mesenchymal stem cells at 1.5T and 3T: Discrimination of viable from lysed cells

Human mesenchymal stem cells (hMSCs) were labeled with Ferucarbotran by simple incubation and cultured for up to 14 d. Iron content was determined by spectrometry and the intracellular localization of the contrast agent uptake was studied by electron and confocal microscopy. At various time points after labeling, ranging from 1 to 14 d, samples with viable or lysed labeled hMSCs, as well as nonlabeled controls, underwent MRI. Spin‐echo (SE) and gradient‐echo (GE) sequences with multiple TRs and TEs were used at 1.5T and 3T on a clinical scanner. Spectrometry showed an initial iron oxide uptake of 7.08 pg per cell. Microscopy studies revealed lysosomal compartmentalization. Contrast agent effects of hMSCs were persistent for up to 14 d after labeling. A marked difference in the T₂ effect of compartmentalized iron oxides compared to free iron oxides was found on T₂‐weighted sequences, but not on T‐weighted sequences. The observed differences may be explained by the loss of compartmentalization of iron oxide particles, the uniformity of distribution, and the subsequent increase in dephasing of protons on SE images. These results show that viable cells with compartmentalized iron oxides may—in principle—be distinguished from lysed cells or released iron oxides. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Performance of sampling density‐weighted and postfiltered density‐adapted projection reconstruction in sodium magnetic resonance imaging

Sampling density‐weighted apodization projection reconstruction sequences are evaluated for three‐dimensional radial imaging. The readout gradients of the sampling density‐weighted apodization sequence are designed such that the locally averaged sampling density matches a Hamming filter function. This technique is compared with density‐adapted projection reconstruction with nonfiltered and postfiltered image reconstruction. Sampling density‐weighted apodization theoretically allows for a 1.28‐fold higher signal‐to‐noise ratio compared with postfiltered density‐adapted projection reconstruction sequences, if T decay is negligible compared with the readout duration T_RO. Simulations of the point‐spread functions are performed for monoexponential and biexponential decay to investigate the effects of T decay on the performance of the different sequences. Postfiltered density‐adapted projection reconstruction performs superior to sampling density‐weighted apodization for large T_RO/T ratios [>1.36 (monoexponential decay); >0.35 (biexponential decay with T/T = 10)], if signal‐to‐noise ratio of point‐like objects is considered. In conclusion, it depends on the readout parameters, the T relaxation times, and the dimensions of the subject which of both sequences is most suitable. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Visualization of seminiferous tubules in rat testes in normal and diseased conditions by high‐resolution MRI

Rat seminiferous tubules were visualized for the first time using high‐spatial‐resolution MRI and their MRI features were investigated under normal and various kinds of pathological conditions. All testes images were obtained at 4.7 T with a dedicated quadrature surface coil. T₂‐ and T‐weighted images with in‐plane resolution of 66 × 66 μm² demonstrated numerous tubular structures with low‐signal‐intensity walls and high‐signal‐intensity lumens tightly packed throughout the entire testicle. The tubular structures were attributed to the seminiferous tubules in the histological specimens. In testicular ischemia, T‐weighted images demonstrated prominent low‐signal‐intensity bands along the radiate veins and normal‐appearing seminiferous tubules. As the ischemic condition persisted, the contour of the seminiferous tubules became less visible on both T₂‐ and T‐weighted images, reflecting the disorganization of the seminiferous epithelia and severe interstitial edema. Changes in the images of testes treated with glycerol or diethylstilbestrol, a synthetic estrogen hormone, were also investigated. In the chronic spermatogenic impairment caused by these substances, extensive shrinkage of the seminiferous tubules was demonstrated. High‐resolution MRI aids in noninvasive evaluation of seminiferous tubules, and therefore has potential as a diagnostic test for human testes. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Myocardial T measurement in iron‐overloaded thalassemia: An ex vivo study to investigate optimal methods of quantification

Myocardial T measurement has been increasingly used for iron quantification to assess the risk of cardiac complications in thalassemia patients. In this study the noise effects were evaluated along with different curve‐fitting models on an iron overloaded ex vivo heart in order to determine the optimal method of T measurement and to help understand issues affecting reproducibility and accuracy. Gradient multiecho short axis images were acquired with differing numbers of excitations to generate varying signal‐to‐noise ratio (SNR) images. A noise correction method was implemented; linear and nonlinear curve‐fitting algorithms were compared and different curve‐fitting models (monoexponential, truncation, baseline subtraction, and offset) were evaluated. This study suggests that the T decay curve in an ex vivo heart can be fitted by a monoexponential model and accurate T measurements can be obtained with proper noise correction. With MRI noise, T is generally overestimated by including late low SNR data points, but underestimated by the offset or baseline subtraction models, which are in fact equivalent. In this situation the truncation model proves to be reproducible and more accurate than the other models. The study also shows that the nonlinear algorithm is preferred in T curve fitting. Magn Reson Med 60:350–356, 2008. © 2008 Wiley‐Liss, Inc.     

MRI and histological analysis of beta‐amyloid plaques in both human Alzheimer's disease and APP/PS1 transgenic mice

Purpose

To investigate the relationship between MR image contrast associated with beta‐amyloid (Aβ) plaques and their histology and compare the histopathological basis of image contrast and the relaxation mechanism associated with Aβ plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse tissues.

Materials and Methods

With the aid of the previously developed histological coil, T‐weighted images and R parametric maps were directly compared with histology stains acquired from the same set of Alzheimer's and APP/PS1 tissue slices.

Results

The electron microscopy and histology images revealed significant differences in plaque morphology and associated iron concentration between AD and transgenic APP/PS1 mice tissue samples. For AD tissues, T contrast of Aβ‐plaques was directly associated with the gradation of iron concentration. Plaques with significantly less iron load in the APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR images.

Conclusion

These data suggest a duality in the relaxation mechanism where both high focal iron concentration and highly compact fibrillar beta‐amyloid masses cause rapid proton transverse magnetization decay. For human tissues, the former mechanism is likely the dominant source of R relaxation; for APP/PS1 animals, the latter is likely the major cause of increased transverse proton relaxation rate in Aβ plaques. The data presented are essential for understanding the histopathological underpinning of MRI measurement associated with Aβ plaques in humans and animals. J. Magn. Reson. Imaging 2009;29:997–1007. © 2009 Wiley‐Liss, Inc.     

23Na MRI combined with contrast-enhanced 1H MRI provides in vivo characterization of infarct healing.

Although (23)Na MRI has been shown to delineate acute myocardial infarction (MI), the time course of in vivo (23)Na MRI during infarct healing remains unknown. In this study (23)Na MRI was combined with contrast-enhanced (CE) (1)H MRI to noninvasively characterize infarct healing in vivo. Serial in vivo 3D (23)Na MRI and (1)H MRI were performed for up to 9 weeks postinfarction in 10 dogs. Radioactive microspheres were used to measure myocardial perfusion, and Hematoxylin-Eosin (H&E) and Masson's trichrome (MT) staining were used to assess interstitial cell infiltrate and collagen content. In vivo (23)Na MRI accurately delineated infarct size up to day 5 postinfarction in comparison with (1)H MRI (8.9% +/- 8.1% vs. 8.6% +/- 7.9% on day 1 postinfarction, P = NS; and 6.3% +/- 6.2% vs. 6.2% +/- 6.2% on days 4/5 postinfarction, P = NS). The in vivo (23)Na MRI signal intensity, expressed as the signal intensity ratio of infarcted tissue vs. noninfarcted tissue (MI/R) peaked on day 1 of infarction (2.04 +/- 0.23) but decreased significantly to 1.27 at 9 weeks postinfarction (P < 0.05) due to granulation tissue infiltrate and collagen deposition. To confirm the MI/R decrease during scar formation ex vivo, we performed (23)Na MRI in 12 rats on day 3 post-MI (N = 5) and after 6 weeks (N = 7). H&E and Picrosirius Red staining confirmed granulation tissue infiltrate on day 3 and scar formation after 6 weeks. MI/R decreased significantly from 1.91 +/- 0.45 on day 3 post-MI to 1.3 +/- 0.09 after 6 weeks. Thus, in vivo (23)Na MRI accurately delineates infarct size up to day 5 postinfarction. In vivo (23)Na MRI signal intensity decreases during infarct healing as a result of the underlying infarct healing process.     

B1 mapping by Bloch‐Siegert shift

A novel method for amplitude of radiofrequency field (B) mapping based on the Bloch‐Siegert shift is presented. Unlike conventionally applied double‐angle or other signal magnitude–based methods, it encodes the B₁ information into signal phase, resulting in important advantages in terms of acquisition speed, accuracy, and robustness. The Bloch‐Siegert frequency shift is caused by irradiating with an off‐resonance radiofrequency pulse following conventional spin excitation. When applying the off‐resonance radiofrequency in the kilohertz range, spin nutation can be neglected and the primarily observed effect is a spin precession frequency shift. This shift is proportional to the square of the magnitude of B. Adding gradient image encoding following the off‐resonance pulse allows one to acquire spatially resolved B₁ maps. The frequency shift from the Bloch‐Siegert effect gives a phase shift in the image that is proportional to B. The phase difference of two acquisitions, with the radiofrequency pulse applied at two frequencies symmetrically around the water resonance, is used to eliminate undesired off‐resonance effects due to amplitude of static field inhomogeneity and chemical shift. In vivo Bloch‐Siegert B₁ mapping with 25 sec/slice is demonstrated to be quantitatively comparable to a 21‐min double‐angle map. As such, this method enables robust, high‐resolution B mapping in a clinically acceptable time frame. Magn Reson Med 63:1315–1322, 2010. © 2010 Wiley‐Liss, Inc.     

Broadband slab selection with B mitigation at 7T via parallel spectral‐spatial excitation

Chemical shift imaging benefits from signal‐to‐noise ratio (SNR) and chemical shift dispersion increases at stronger main field such as 7 Tesla, but the associated shorter radiofrequency (RF) wavelengths encountered require B mitigation over both the spatial field of view (FOV) and a specified spectral bandwidth. The bandwidth constraint presents a challenge for previously proposed spatially tailored B mitigation methods, which are based on a type of echovolumnar trajectory referred to as “spokes” or “fast‐k_z”. Although such pulses, in conjunction with parallel excitation methodology, can efficiently mitigate large B inhomogeneities and achieve relatively short pulse durations with slice‐selective excitations, they exhibit a narrow‐band off‐resonance response and may not be suitable for applications that require B mitigation over a large spectral bandwidth. This work outlines a design method for a general parallel spectral‐spatial excitation that achieves a target‐error minimization simultaneously over a bandwidth of frequencies and a specified spatial‐domain. The technique is demonstrated for slab‐selective excitation with in‐plane B mitigation over a 600‐Hz bandwidth. The pulse design method is validated in a water phantom at 7T using an eight‐channel transmit array system. The results show significant increases in the pulse's spectral bandwidth, with no additional pulse duration penalty and only a minor tradeoff in spatial B mitigation compared to the standard spoke‐based parallel RF design. Magn Reson Med 61:493–500, 2009. © 2009 Wiley‐Liss, Inc.     

19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells

Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron‐oxide labeled immune‐cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T‐weighted images. In this study, we tested the feasibility of using a fluorine‐based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine‐19 (¹⁹F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro‐15‐crown‐5‐ether, we observed ¹⁹F‐signal intensity in the organs experiencing rejection by ¹⁹F MRI, and conventional ¹H MRI was used for anatomical context. Immunofluorescense and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, ¹⁹F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.