Functional contrast based on intermolecular double-quantum coherences: influence of the correlation distance.

A functional MRI (fMRI) study with visual stimulation of healthy subjects was performed at 3T exploiting intermolecular double-quantum coherences. The correlation distance, d(c), was varied between 60 and 300 microm for different evolution times, tau. Robust activation was obtained in all experiments with average signal changes (DeltaS(2)) = 8.4 +/- 0.7% and 9.4 +/- 0.8% for tau = 15 and 20 ms, respectively) exceeding those normally associated with conventional blood oxygen level-dependent (BOLD) fMRI. Relaxation-rate changes (DeltaR(2) = 0.33 +/- 0.36 s(-1) and DeltaR(2)* = 0.77 +/- 0.54 s(-1)) were similar to those commonly obtained for the extravascular BOLD effect. The number of activated voxels increased with increasing d(c) until a plateau was reached at approximately equal 120 microm. Similar trends were observed for the activation-induced percent signal change and for the maximal Z-scores. These effects were quantitatively explained by a reduced sensitivity at short d(c) due to increasing signal attenuation related to diffusion and an increasing amount of signal fluctuations in the fMRI time series due to imperfect suppression of unwanted coherence pathways. Consistent indications of a preferential selection of susceptibility changes in blood vessels of a particular size were not obtained.     

Magnetization structure contrast based on intermolecular multiple-quantum coherences.

In vivo and ex vivo MRI based on intermolecular multiple-quantum coherences (iMQC) is predicted to provide a fundamentally different source of contrast for MRI. This article investigates the dependence of image contrast upon the choice of correlation distance for a heterogeneous material. A closely packed array of parallel hollow cylinders was used to demonstrate signal intensity variations when the correlation distance becomes comparable to the gap size between the cylinders. The observed effects agree well with three-dimensional calculations of the time evolution of magnetization under the nonlinear Bloch equations.     

Functional magnetic resonance imaging with intermolecular double-quantum coherences at 3 T.

Functional magnetic resonance imaging (fMRI) based on the selection of intermolecular double-quantum coherences (iDQC) was performed with a standard birdcage coil at 3 T in a group of normal human volunteers. Suppression of spurious signal contributions from unwanted coherence-transfer pathways was achieved by combining a two-step phase cycle and a long repetition time of 5 s. A gradient-recalled echo iDQC sequence (echo time, T(E) = 80 ms) yielded robust activation with a visual paradigm. Maximum z-scores were about half of those observed with conventional blood-oxygen level dependent fMRI, whereas the functional signal change increased by more than a factor of 5. No activation was obtained with a spin-echo iDQC sequence (T(E) = 160 ms), in which dephasing accumulated during the evolution period was fully rephased by an appropriate delay time. It is hypothesized that substantial inherent diffusion weighting of the iDQC technique efficiently suppresses intravascular contributions to the functional contrast. A consistent quantitative explanation of the observed amount of signal change currently remains speculative.     

Optimization of blood oxygenation level-dependent sensitivity in magnetic resonance imaging using intermolecular double-quantum coherence

PURPOSE: To optimize timing parameters in an intermolecular double-quantum coherence (iDQC) imaging pulse sequence for overall image signal-to-noise ratio (SNR) and blood oxygenation level-dependent (BOLD) sensitivity for brain functional imaging. MATERIAL AND METHODS: Fresh human blood was measured under different oxygenation conditions, and human brain functional magnetic resonance (fMR) images in three normal volunteers were obtained, using iDQC techniques at 1.5 T. The dependence of SNR and BOLD sensitivity was measured as a function of time delays after the iDQC evolution period. RESULTS: A time delay after the iDQC evolution period tau can be adjusted either to refocus the dephasing accumulated during tau, thus increasing SNR, with full rephasing occurring at delay = +/-2tau (for iDQC order n = +/-2), or to enhance BOLD effects with consequent reduced image SNR at delay = 0. CONCLUSION: Image SNR and BOLD sensitivity often impose different requirements for iDQC image sequence design and timing parameter selections. It is therefore important to select properly relevant parameters for different applications.     

High‐resolution MRS in the presence of field inhomogeneity via intermolecular double‐quantum coherences on a 3‐T whole‐body scanner

Signals from intermolecular double‐quantum coherences (iDQCs) have been shown to be insensitive to macroscopic field inhomogeneities and thus enable acquisition of high‐ resolution MR spectroscopy in the presence of large inhomogeneous fields. In this paper, localized iDQC ¹H spectroscopy on a whole‐body 3‐T MR scanner is reported. Experiments with a brain metabolite phantom were performed to quantify characteristics of the iDQC signal under different conditions. The feasibility of in vivo iDQC high‐resolution MR spectroscopy in the presence of large intrinsic and external field inhomogeneity (in the order of hundreds of hertz) was demonstrated in the whole cerebellum of normal volunteers in a scan time of about 6.5 min. Major metabolite peaks were well resolved in the reconstructed one‐dimensional spectra projected from two‐dimensional iDQC acquisitions. Investigations on metabolite ratios, signal‐to‐noise ratio, and line width were performed and compared with results obtained with conventional point‐resolved spectroscopy/MR spectroscopy in homogeneous fields. Metabolite ratios from iDQC results showed excellent consistency under different in vitro and in vivo conditions, and they were similar to those from point‐resolved spectroscopy with small voxel sizes in homogeneous fields. MR spectroscopy with iDQCs can be applied potentially for quantification of gross metabolite changes due to diseases in large brain volumes with high field inhomogeneity. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Contamination of single‐voxel multiple quantum filters by external water signals arising from intermolecular multiple quantum coherences

Multiple‐quantum filtered pulse sequences simplify overlapping metabolite spectra by the elimination of peaks from uncoupled spin species, most notably from methyl groups and water, and the minimization of unwanted coupled‐spin peaks. However, it is shown in this study that a significant contaminant water signal can pass through this family of filters in the form of intermolecular multiple‐quantum coherences. An imaging evaluation of a single‐voxel multiple quantum filter experiment confirms that the water contamination is excited from outside of the voxel of interest, thus having an increased potential for broad spectral contamination. Phantom and in vivo experiments at 3.0 T are used to illustrate, first, significant water contamination of a single‐voxel double quantum filter experiment optimized for the observation of glutamate, and second, the elimination of the unwanted water signal with conventional phase cycling and optimized filter gradient orientations. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

In vivo brown adipose tissue detection and characterization using water–lipid intermolecular zero‐quantum coherences

Brown adipose tissue and white adipose tissue depots are noninvasively characterized in vitro and in vivo in healthy and obese mice using intermolecular zero‐quantum coherence transitions between lipid and water spins. Intermolecular zero‐quantum coherences enable selective detection of spatial correlation between water and lipid spins and thereby the hydration of fatty deposits with subvoxel resolution. At about a 100 mm distance scale, the major observed peaks are between water, methylene protons at 1.3 ppm, and olefinic protons at 5.3 ppm. Our in vitro results show that the methylene–olefinic intermolecular zero‐quantum coherence signal is strong both in brown and white adipose tissues, but that the water–methylene intermolecular zero‐quantum coherence signal is characteristic only of brown adipose tissue. In vivo, the ratio of these peaks is substantially higher in lean or young mice than in old or obese mice. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

In vivo spatially localized high resolution 1H MRS via intermolecular single‐quantum coherence of rat brain at 7 T

Purpose:

To compare the conventional localized point‐resolved spectroscopy (PRESS) with localized 2D intermolecular single‐quantum coherence (iSQC) magnetic resonance spectroscopy (MRS) and obtain in vivo MRS spectrum of rat brain using the latter technique.

Materials and Methods:

A brain phantom, an intact pig brain tissue, and mature Sprague–Dawley rat were studied by PRESS, Nano magic‐angle spinning spectroscopy, and iSQC MRS.

Results:

Using PRESS, high‐resolution MRS can be obtained from the brain phantom and pig brain tissue with a small voxel in a relatively homogeneous field. When a large voxel is selected, the field homogeneity is distinctly reduced. No useful information is obtained from the PRESS spectra. However, using the iSQC MRS, high‐resolution spectra can be obtained from the two samples with a relatively large voxel. In the same way, an iSQC MRS spectrum can be obtained from a relatively large voxel of in vivo rat brain with a comparable resolution to the PRESS spectrum with a small voxel.

Conclusion:

Compared to PRESS, the iSQC MRS may be more feasible and promising for detection of strongly structured tissues with relatively large voxels. J. Magn. Reson. Imaging 2013;37:359–364. © 2012 Wiley Periodicals, Inc.     

Refocused double‐quantum editing for lactate detection at 7 T

Lactate is an important marker for anaerobic glucose metabolism, and it is therefore of particular interest in, for example, cerebral ischemia, skeletal muscle disorders, and in the monitoring of oncology treatments. However, the in vivo detection of lactate with magnetic resonance spectroscopy is complicated by the overlap of the low‐intensity lactate methyl resonance with lipid signal. Therefore, double‐quantum filters have been employed to dephase the overlapping lipid signal, as they allow for a very high lipid suppression efficiency. For reliable lactate detection in lipid‐rich environment, very large crushing gradients have to be employed to dephase the lipid signal under the noise level. Double‐quantum filters are generally associated with signal loss of the metabolite of interest. For lactate, half of the signal is lost by selecting either the double‐ or the zero‐quantum coherences. Moreover, owing to incomplete refocusing, traditional double‐quantum filters with very large crusher gradients exhibit additional loss of the already low‐lactate signal. In this study, a refocused double‐quantum filter is described, which does not suffer from this source of additional signal loss. Therefore, it becomes possible to detect lactate at lower concentrations, or in lipid‐rich environments. Lactate measurements are shown in the human calf muscle at 7 T. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Intracellular bimodal nanoparticles based on quantum dots for high‐field MRI at 21.1 T

Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high‐field MR applications—including biomedical imaging at 21.1 T, the highest magnetic field available for MRI—these nanoparticles capitalize on the improved performance of chelated Dy³⁺ with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell‐penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self‐transfecting high‐field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Safety of gadolinium‐based contrast material in sickle cell disease

Purpose:

To assess the safety of intravenously administered gadolinium‐based contrast material in sickle cell disease (SCD) patients.

Materials and Methods:

All pediatric and adult SCD patients evaluated by magnetic resonance imaging (MRI) at our institution between January 1995 and July 2009 were identified. The medical records of SCD patients who underwent contrast‐enhanced MRI as well as an equal‐sized cohort of SCD patients who underwent unenhanced MRI were reviewed for adverse (vaso‐occlusive and hemolytic) events within 1 week following imaging.

Results:

Eight (five mild and three moderate) adverse events were documented within 1 week following contrast‐enhanced MRI (38 patients and 61 contrast injections), while six (five mild and one moderate) similar events occurred within 1 week following unenhanced MRI (61 patients and 61 unenhanced MRI examinations). This difference in the number of adverse events was not statistically significant (odds ratio = 1.4; 95% confidence interval [CI] 0.4, 5.2). No severe adverse event occurred in either patient cohort.

Conclusion:

Gadolinium‐based contrast materials do not appear to be associated with increased risk of vaso‐occlusive or hemolytic adverse events when administered to SCD patients. Larger, prospective studies using multiple gadolinium‐based contrast materials would be useful to confirm the results of our investigation. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Signal-to-noise ratio enhancement of intermolecular double-quantum coherence MR spectroscopy in inhomogeneous fields with phased array coils on a 3 Tesla whole-body scanner

Purpose

To improve signal‐to‐noise ratio (SNR) of intermolecular double‐quantum coherence (iDQC) MRS on a 3 Tesla (T) whole‐body scanner.

Materials and Methods

A 32‐channel phased array coil was used to acquire iDQC signal of a MRS phantom in the presence of large field inhomogeneity. The obtained individual spectra from the array elements were combined together in the time domain using a multichannel nonparametric singular value decomposition algorithm. The results were compared quantitatively with those acquired with a circularly polarized (CP) head coil.

Results

The achieved gain in SNR ranges from 1.63 to 2.10 relative to the CP coil, mainly depending on the relative position between the surface of the phased array coil and the voxel of acquisition.

Conclusion

SNR enhancement of iDQC MRS in inhomogeneous fields on a 3T whole‐body scanner is feasible with phased array coils. This can facilitate iDQC applications of high‐resolution in vivo spectroscopy in the presence of field inhomogeneity for potential disease diagnosis in humans. J. Magn. Reson. Imaging 2011;33:698–703. © 2011 Wiley‐Liss, Inc.     

Non‐contrast enhanced MR angiography: Established techniques

Until recently, time‐of‐flight (TOF) and phase contrast (PC) were the only non‐contrast MR angiography (NC‐MRA) techniques practically used in clinical. In the decade, NC‐MRA have been gained a revival of an interest among the MR researchers and scientists, in part because of safety concerns related to the possible link between gadolinium‐based contrast agents and nephrogenic systemic fibrosis (NSF). This article introduces other established NC‐MRA techniques, such as ECG‐gated partial Fourier fast spin echo (FSE) and balanced steady‐state free precession (bSSFP), both with and without arterial spin labeling. Then, the article focuses on two main applications: peripheral run‐off and renal MRA. Recently, both applications have achieved remarkable advancements and have become a viable clinical option as an alternative to contrast‐enhanced (CE)‐MRA. In addition, developments on the horizon including whole body MRA applications and further advancement at 3 Tesla are discussed. J. Magn. Reson. Imaging 2012 © 2011 Wiley Periodicals, Inc.     

T2‐based arterial spin labeling measurements of blood to tissue water transfer in human brain

Purpose:

To investigate blood to tissue water transfer in human brain, in vivo and spatially resolved using a T2‐based arterial spin labeling (ASL) method with 3D readout.

Materials and Methods:

A T2‐ASL method is introduced to measure the water transfer processes between arterial blood and brain tissue based on a 3D‐GRASE (gradient and spin echo) pulsed ASL sequence with multiecho readout. An analytical mathematical model is derived based on the General Kinetic Model, including blood and tissue compartment, T1 and T2 relaxation, and a blood‐to‐tissue transfer term. Data were collected from healthy volunteers on a 3 T system. The mean transfer time parameter T_bl→ex (blood to extravascular compartment transfer time) was derived voxelwise by nonlinear least‐squares fitting.

Results:

Whole‐brain maps of T_bl→ex show stable results in cortical regions, yielding different values depending on the brain region. The mean value across subjects and regions of interest (ROIs) in gray matter was 440 ± 30 msec.

Conclusion:

A novel method to derive whole‐brain maps of blood to tissue water transfer dynamics is demonstrated. It is promising for the investigation of underlying physiological mechanisms and development of diagnostic applications in cerebrovascular diseases. J. Magn. Reson. Imaging 2013;37:332–342. © 2012 Wiley Periodicals, Inc.