Magnetic particle imaging (MPI) is a new tomographic imaging method potentially capable of rapid 3D dynamic imaging of magnetic tracer materials. Until now, only dynamic 2D phantom experiments with high tracer concentrations have been demonstrated. In this letter, first in vivo 3D real-time MPI scans are presented revealing details of a beating mouse heart using a clinically approved concentration of a commercially available MRI contrast agent. A temporal resolution of 21.5 ms is achieved at a 3D field of view of 20.4 x 12 x 16.8 mm(3) with a spatial resolution sufficient to resolve all heart chambers. With these abilities, MPI has taken a huge step toward medical application.

T 2 * relaxometry for quantitative MR imaging is strongly hampered by large-scale field inhomogeneities, which lead to signal losses and an overestimation of the relaxation rate R 2 *. This is of particular importance for the sensitive detection of iron oxide contrast agent distributions. To derive an accurate measurement of T 2 *, a main field inhomogeneity correction is applied: the main field inhomogeneity is derived from multislice T 2 * relaxometry data and used as an initial value for an iterative optimization, by which the relaxation signal is corrected for each voxel. These corrected T 2 * maps show reduced influence of the local field variation and contain information about the local SPIO concentration. The method was tested on phantoms and the limit of detection of SPIO labeled cells using T 2 * relaxometry was estimated in volunteers to be 120 Quantitative imaging by means of T 2 * relaxometry is becoming an increasingly requested tool in many areas of MRI. It is applied for BOLD contrast studies (1,2) as well as for the detection of changes in cancellous bone structure (3). The evaluation of perfusion by means of bolus transit methods (4) and the assessment of iron content in brain and liver can also profit from accurate T 2 * mapping methods (5,6). The sensitive detection of iron oxide particlebased contrast agents has become a growing application, especially within the scope of molecular imaging MR. The distribution of these iron oxides is usually determined by acquiring T 2 and T 2 *-weighted images. In Ref. (7) it was already suggested that EPI sequences could be used to study localized magnetic inhomogeneities, since they are introduced by SPIO particles. Hence, a multigradient readout approach can be utilized to come one step closer toward quantification of iron oxide particle distributions by measuring the T 2 * relaxation time.SPIO particles are phagocytosed by macrophages in the liver or lymph nodes. They are also used to label cells ex vivo and track them throughout the body after injection (8,9). For cellularly compartmentalized SPIO particles T 2 is less influenced than T 2 *, which is explained by the static dephasing theory (10). To gain high sensitivity for the detection of compartmentalized SPIOs, the reversible relaxation rate T 2 * should be measured (11). Therefore, this study focuses on the measurement of T 2 *. This includes the challenge that the T 2 * relaxation rate is not only influenced by SPIO contrast agents, but also by macroscopic susceptibilities that arise from air/tissue interfaces, like the lung/liver or the sinus/brain interface. These disturbances cause enhanced signal decay and scale linearly with the field strength, which intensifies their influence at 3.0 T. Therefore, susceptibility artifacts lead to overestimated relaxation rates or obscure small concentrations of SPIO-labeled cells.Several methods have been proposed to correct for the macroscopic magnetic susceptibility influence. The most obvious method involves increasing the spatial resolution (12). Compen...

Quantitative R2 and R2* mapping enables noninvasive estimations of cellular iron load and number of iron-labeled cells. Cell-bound SPIOs can be differentiated from free SPIOs with R2' imaging.

Local susceptibility gradients result in a dephasing of the precessing magnetic moments and thus in a fast decay of the NMR signals. In particular, cells labeled with superparamagnetic iron oxide particles (SPIOs) induce hypointensities, making the in vivo detection of labeled cells from such a negative image contrast difficult. In this work, a new method is proposed to selectively turn this negative contrast into a positive contrast. The proposed method calculates the susceptibility gradient and visualizes it in a parametric map directly from a regular gradient-echo image dataset. The susceptibility gradient map is determined in a postprocessing step, requiring no dedicated pulse sequences or adaptation of the sequence before and during image acquisition. Phantom experiments demonstrated that local susceptibility differences can be quantified. In vivo experiments showed the feasibility of the method for tracking of SPIO-labeled cells. The method bears the potential also for usage in other applications, including the detection of contrast agents and interventional devices as well as metal implants.

Purpose:To evaluate MRI for a qualitative and quantitative in vivo tracking of intraaortal injected iron oxide-labeled mesenchymal stem cells (MSC) into rats with acute kidney injury (AKI). Materials and Methods:In vitro MRI and R 2 * measurement of nonlabeled and superparamagnetic iron oxide (SPIO)-labeled MSC (MSC SPIO ) was performed in correlation to cellular iron content and cytological examination (Prussian blue, electron microscopy). In vivo MRI and R 2 * evaluation were performed before and after ischemic/reperfusion AKI (N ϭ 14) and intraaortal injection of 1.5 ϫ 10 6 MSC SPIO (N ϭ 7), fetal calf serum (FCS) (medium, N ϭ 6), and SPIO alone (N ϭ 1) up to 14 days using a clinical 3T scanner. Signal to noise ratios (SNR), R 2 * of kidneys, liver, spleen, and bone marrow, renal function (creatinine [CREA], blood urea nitrogen [BUN]), and kidney volume were measured and tested for statistical significance (Student's t-test, P Ͻ 0.05) in comparison histology (hematoxylin and eosin [H&E], Prussian blue, periodic acid-Schiff [PAS], CD68). Results:In vitro, MSC SPIO showed a reduction of SNR and T 2 * with R 2 * Ϸ number of MSC SPIO (R 2 ϭ 0.98). In vivo MSC SPIO administration resulted in a SNR decrease (35 Ϯ 15%) and R 2 * increase (101 Ϯ 18.3%) in renal cortex caused by MSC SPIO accumulation in contrast to control animals (P Ͻ 0.01). Liver, spleen, and bone marrow (MSC SPIO ) showed a delayed SNR decline/R 2 * increase (P Ͻ 0.05) resulting from MSC SPIO migration. The increase of kidney volume and the decrease in renal function (P Ͻ 0.05) was reduced in MSC-treated animals. Conclusion:Qualitative and quantitative in vivo cell-tracking and monitoring of organ distribution of intraaortal injected MSC SPIO in AKI is feasible in MRI at 3T.

Positive-contrast techniques are being developed to increase the detection of magnetically labeled cells in tissues. We evaluated a post-processing positive-contrast technique, susceptibility-gradient mapping (SGM), and compared this approach with two pulse sequences, a gradient-compensation-based "White Marker" technique and an off-resonance-based approach, inversion recovery on-resonance water suppression (IRON), for the detection of superparamagnetic iron oxide (SPIO) nanoparticle-labeled C6 glioma cells implanted in the flanks of nude rats. The SGM, White Marker and IRON positive-contrast images were acquired when the labeled C6 glioma tumors were approximately 5 mm (small), approximately 10 mm (medium) and approximately 20 mm (large) in diameter along the largest dimension to evaluate their sensitivity to the dilution of the SPIO nanoparticles as the tumor cells proliferated. In vivo MRI demonstrated that all three positive-contrast techniques can produce hyperintensities in areas around the labeled flank tumors against a dark background. The number of positive voxels detected around small and medium tumors was significantly greater with the SGM technique than with the White Marker and IRON techniques. For large tumors, the SGM resulted in a similar number of positive voxels to the White Marker technique, and the IRON approach failed to generate positive-contrast images with a 200 Hz suppression band. This study also reveals that hemorrhage appears as hyperintensities on positive-contrast images and may interfere with the detection of SPIO-labeled cells.

A new method was developed to measure ultrashort T2* relaxation in tissues that contain a focal area of superparamagnetic iron oxide (SPIO) nanoparticle labeled cells in which the T2* decay is too short to be accurately measured using regular multiple gradient echo T2* mapping. The proposed method utilizes the relatively long T2 relaxation of SPIO labeled cells and acquires a series of spin echo images with the readout echo shifted to sample the T2* decay curve. MRI experiments in phantoms and rats with SPIO labeled tumors demonstrated that this method can detect ultrashort T2* down to 1 millisecond or less. Compared to the ultrashort TE technique, the SSE method overestimates the T2* values by about 11%. The longer the TE, the more the measurements deviates from the UTE technique. Combined with the regular multiple gradient echo T2* mapping, the new technique is expected to provide in vivo quantitation of highly concentrated iron labeled cells in tissues from direct cell transplantation.

No abstract