Charles H. Cunningham

Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles.

Contrast agents incorporating superparamagnetic iron‐oxide nanoparticles have shown promise as a means to visualize labeled cells using MRI. Labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell. With the resulting signal void as the means for detection, the particles behave as a negative contrast agent, which can suffer from partial‐volume effects. In this paper, a new method is described for imaging labeled cells with positive contrast. Spectrally selective RF pulses are used to excite and refocus the off‐resonance water surrounding the labeled cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image. Phantom, in vitro, and in vivo experiments show the feasibility of the new method. A significant linear correlation (r = 0.87, P < 0.005) between the estimated number of cells and the signal was observed. Magn Reson Med 53:999–1005, 2005.

Saturated double-angle method for rapid B1+ mapping

For in vivo magnetic resonance imaging at high field (≥3 T) it is essential to consider the homogeneity of the active B1 field (B1+), particularly if surface coils are used for RF transmission. A new method is presented for highly rapid B1+ magnitude mapping. It combines the double angle method with a B1‐insensitive magnetization‐reset sequence such that the choice of repetition time (TR) is independent of T1 and with a multislice segmented (spiral) acquisition to achieve volumetric coverage with adequate spatial resolution in a few seconds. Phantom experiments confirmed the accuracy of this technique even when TR ≪ T1, with the side effect being lowered SNR. The speed of this method enabled B1+ mapping in the chest and abdomen within a single breath‐hold. In human cardiac imaging, the method enabled whole‐heart coverage within a single 16‐s breath‐hold. Results from phantoms and healthy volunteers at 1.5 T and 3 T are presented. Magn Reson Med, 2006.

Variable‐rate selective excitation for rapid MRI sequences

Balanced steady‐state free precession (SSFP) imaging sequences require short repetition times (TRs) to avoid off‐resonance artifacts. The use of slab‐selective excitations is common, as this can improve imaging speed by limiting the field of view (FOV). However, the necessarily short‐duration excitations have poor slab profiles. This results in unusable slices at the slab edge due to significant flip‐angle variations or aliasing in the slab direction. Variable‐rate selective excitation (VERSE) is a technique by which a time‐varying gradient waveform is combined with a modified RF waveform to provide the same excitation profile with different RF power and duration characteristics. With the use of VERSE, it is possible to design short‐duration pulses with dramatically improved slab profiles. These pulses achieve high flip angles with only minor off‐resonance sensitivity, while meeting SAR limits at 1.5 T. The improved slab profiles will enable more rapid 3D imaging of limited volumes, with more consistent image contrast across the excited slab. Magn Reson Med 52:590–597, 2004.

Real‐time cardiac MRI at 3 tesla

Real‐time cardiac and coronary MRI at 1.5T is relatively “signal starved” and the 3T platform is attractive for its immediate factor of two increase in magnetization. Cardiac imaging at 3T, however, is both subtly and significantly different from imaging at 1.5T because of increased susceptibility artifacts, differences in tissue relaxation, and RF homogeneity issues. New RF excitation and pulse sequence designs are presented which deal with the fat‐suppression requirements and off‐resonance issues at 3T. Real‐time cardiac imaging at 3T is demonstrated with high blood SNR, blood‐myocardium CNR, resolution, and image quality, using new spectral‐spatial RF pulses and fast spiral gradient echo pulse sequences. The proposed sequence achieves 1.5 mm in‐plane resolution over a 20 cm FOV, with a 5.52 mm measured slice thickness and 32 dB of lipid suppression. Complete images are acquired every 120 ms and are reconstructed and displayed at 24 frames/sec using a sliding window. Results from healthy volunteers show improved image quality, a 53% improvement in blood SNR efficiency, and a 232% improvement in blood‐myocardium CNR efficiency compared to 1.5T. Magn Reson Med 51:655–660, 2004.

Design of flyback echo-planar readout gradients for magnetic resonance spectroscopic imaging

The spatial resolution of conventional magnetic resonance spectroscopic imaging‐(MRSI) is typically coarse, mainly due to SNR limitations. The increased signal available with higher field scanners and new array coils now permits higher spatial resolution, but conventional chemical shift imaging (phase encoding) limits the spatial coverage possible in a patient‐acceptable acquisition time. The “flyback” echo‐planar trajectory is particularly insensitive to errors and provides data that are simple to process. In this study, high‐efficiency gradient waveforms for flyback echo‐planar MRSI were designed and implemented. Normal volunteer studies at 3 T showed the feasibility of acquiring high spatial resolution with large coverage in a short scan time (2048 voxels in 2.3 min and 4096 voxels in 8.5 min). The trajectories were insensitive to errors in timing and require only a modest (10 to 30%) penalty in SNR relative to conventional phase encoding using the same acquisition time. Magn Reson Med, 2005.

Single breath-hold whole-heart MRA using variable-density spirals at 3t

Multislice breath‐held coronary imaging techniques conventionally lack the coverage of free‐breathing 3D acquisitions but use a considerably shorter acquisition window during the cardiac cycle. This produces images with significantly less motion artifact but a lower signal‐to‐noise ratio (SNR). By using the extra SNR available at 3 T and undersampling k‐space without introducing significant aliasing artifacts, we were able to acquire high‐resolution fat‐suppressed images of the whole heart in 17 heartbeats (a single breath‐hold). The basic pulse sequence consists of a spectral‐spatial excitation followed by a variable‐density spiral readout. This is combined with real‐time localization and a real‐time prospective shim correction. Images are reconstructed with the use of gridding, and advanced techniques are used to reduce aliasing artifacts. Magn Reson Med, 2006.

Sequence design for magnetic resonance spectroscopic imaging of prostate cancer at 3 T

Magnetic resonance spectroscopic imaging (MRSI) has proven to be a powerful tool for the metabolic characterization of prostate cancer in patients before and following therapy. The metabolites that are of particular interest are citrate and choline because an increased choline‐to‐citrate ratio can be used as a marker for cancer. High‐field systems offer the advantage of improved spectral resolution as well as increased magnetization. Initial attempts at extending MRSI methods to 3 T have been confounded by the J‐modulation of the citrate resonances. A new pulse sequence is presented that controls the J‐modulation of citrate at 3 T such that citrate is upright, with high amplitude, at a practical echo time. The design of short (14 ms) spectral–spatial refocusing pulses and trains of nonselective refocusing pulses are described. Phantom studies and simulations showed that upright citrate with negligible sidebands is observed at an echo time of 85 ms. Studies in a human subject verified that this behavior is reproduced in vivo and demonstrated that the water and lipid suppression of the new pulse sequence are sufficient for application in prostate cancer patients. Magn Reson Med 53:1033–1039, 2005.

High-Speed 3T MR Spectroscopic Imaging of Prostate With Flyback Echo-Planar Encoding

Prostate MR spectroscopic imaging (MRSI) at 3T may provide two‐fold higher spatial resolution over 1.5T, but this can result in longer acquisition times to cover the entire gland using conventional phase‐encoding. In this study, flyback echo‐planar readout trajectories were incorporated into a Malcolm Levitts composite‐pulse decoupling sequence (MLEV)–point‐resolved spectroscopy sequence (PRESS) to accelerate the acquisition of large array (16 × 16 × 8), high spatial (0.154 cm3) resolution MRSI data by eight‐fold to just 8.5 minutes. Artifact free, high‐quality MRSI data was obtained in nine prostate cancer patients. Easy data reconstruction and the robustness of the flyback echo‐planar encoding make this technique particularly suitable for the clinical setting. The short acquisition time provided by this method reduces the 3T prostate MRI/MRSI exam time, allows longer repetition times, and/or allows the acquisition of additional MR acquisitions within the same exam. J. Magn. Reson. Imaging 2007;25:1288–1292.

Design of symmetric-sweep spectral-spatial RF pulses for spectral editing

Spectral‐spatial RF (SSRF) pulses allow simultaneous selection in both frequency and spatial domains. These pulses are particularly important for clinical and research MR spectroscopy (MRS) applications for suppression of large water and lipid resonances. Also, the high bandwidth of the subpulses (5–10 kHz) greatly reduces the spatial‐shift errors associated with different chemical shifts. However, the use of high‐bandwidth subpulses along with enough spectral bandwidth to measure a typical range of metabolite frequencies (e.g., 300 Hz at 3 T) can require RF amplitudes beyond the limits of the RF amplifier of a typical scanner. In this article, a new method is described for designing nonlinear‐phase 180° SSRF pulses that can be used for spectral editing. The novel feature of the pulses is that the spectral profile develops as a symmetric sweep, from the outside edges of the spectral window towards the middle, so that coupled components are tipped simultaneously and over a short interval. Pulses were designed for lactate editing at 1.5 T and 3 T. The spectral and spatial spin‐echo profiles of the new pulses were measured experimentally. Spectra acquired in phantom experiments showed a well‐resolved, edited lactate doublet, with 91% to 93% editing efficiency. Magn Reson Med 52:147–153, 2004.

Positive-Contrast Imaging in the Rabbit Hind-Limb of Transplanted Cells Bearing Endocytosed Superparamagnetic Beads

Positive-contrast methods can augment negative-contrast methods for CMR evaluation of transplanted cell fate in vivo. This study correlated positive-contrast signal characteristics in the rabbit hind-limb with xenograft cell number (rat fibroblasts bearing endocytosed 1 microm Bangs particles) at different stages of Gd-DTPA administration and 1 mm2 in-plane resolution (2 minute scans, 1.5 Tesla). Linear regressions modeled satisfactorily the cell number dependencies of signal-to-noise (SNR) and area-of-enhancement (R > 0.83), over approximately a 50-fold fluctuation in cell number to a lowest detected limit of 25k cells during Gd-DTPA administration. Gd-DTPA administration elevated the slopes of parameter regressions by four or more standard deviations.