Design strategies for improved velocity-selective pulse sequences.

Over the years, a variety of MRI methods have been developed for visualizing or measuring blood flow without the use of contrast agents. One particular class of methods uses flow-encoding gradients associated with an RF pulse sequence to distinguish spins in flowing blood from stationary spins. While a strength of these particular methods is that, in general, they can be tailored to capture a desired range of blood flow, such sequences either do not provide a sharp transition from stationary spins to flowing spins, or else are long, generating relaxation losses and undesirable SAR, and have limited immunity to resonance offsets and to RF inhomogeneity. This article provides design methods for improving these longer RF pulse sequences, especially to provide improved immunity to RF inhomogeneity, and also to improve immunity to resonance offsets, as well as to minimize RF sequence length. These design methods retain the flexibility to capture a desired range of blood flow, with sharp transitions between stationary spins and flowing blood. These improvement strategies are demonstrated through Bloch equations simulations of examples of these new sequences in the presence of blood flow. Examples of improved sequences that should prove suitable for use at 3.0Tesla are presented.

Accurate Measurement of Magnetic Resonance Imaging Gradient Characteristics.

Recently, gradient performance and fidelity has become of increasing interest, as the fidelity of the magnetic resonance (MR) image is somewhat dependent on the fidelity of the gradient system. In particular, for high fidelity non-Cartesian imaging, due to non-fidelity of the gradient system, it becomes necessary to know the actual k-space trajectory as opposed to the requested trajectory. In this work we show that, by considering the gradient system as a linear time-invariant system, the gradient impulse response function (GIRF) can be reliably measured to a relatively high degree of accuracy with a simple setup, using a small phantom and a series of simple experiments. It is shown experimentally that the resulting GIRF is able to predict actual gradient performance with a high degree of accuracy. The method captures not only the frequency response but also gradient timing errors and artifacts due to mechanical vibrations of the gradient system. Some discussion is provided comparing the method presented here with other analogous methods, along with limitations of these methods.

Radiofrequency pulse designs for three-dimensional MRI providing uniform tipping in inhomogeneous B1 fields.

Although high-field MRI offers increased signal-to-noise, the nonuniform tipping produced by conventional radiofrequency (RF) pulses leads to spatially dependent contrast and suboptimal signal-to-noise, thus complicating the interpretation of the MR images. For structural imaging, three-dimensional sequences that do not make use of frequency-selective RF pulses have become popular. Therefore, the aim of this research was to develop non-slice-selective (NSS) RF pulses with immunity to both amplitude of (excitation) RF field (B(1) ) inhomogeneity and resonance offset. To accomplish this, an optimization routine based on optimal control theory was used to design new NSS pulses with desired ranges of immunity to B(1) inhomogeneity and resonance offset. The design allows the phase of transverse magnetization produced by the pulses to vary. Although the emphasis is on shallow tip designs, new designs for 30°, 60°, 90°, and 180° NSS RF pulses are also provided. These larger tip angle pulses are compared with recently published NSS pulses. Evidence is presented that the pulses presented in this article have equivalent performance but are shorter than the recently published pulses. Although the NSS pulses generate higher specific absorption rates and larger magnetization transfer effects than the rectangular pulses they replace, they nevertheless show promise for three-dimensional MRI experiments at high field.

Improved pseudo-continuous arterial spin labeling for mapping brain perfusion.

PURPOSE: To investigate arterial spin labeling (ASL) methods for improved brain perfusion mapping. Previously, pseudo-continuous ASL (pCASL) was developed to overcome limitations inherent with conventional continuous ASL (CASL), but the control scan (null pulse) in the original method for pCASL perturbs the equilibrium magnetization, diminishing the ASL signal. Here, a new modification of pCASL, termed mpCASL is reported, in which the perturbation caused by the null pulse is reduced and perfusion mapping improved. MATERIALS AND METHODS: improvements with mpCASL are demonstrated using numerical simulations and experiments. ASL signal intensity as well as contrast and reproducibility of in vivo brain perfusion images were measured in four volunteers who had MRI scans at 4 Tesla and the data compared across the labeling methods. RESULTS: Perfusion maps with mpCASL showed, on average, higher ASL signal intensity and higher image contrast than those from CASL or pCASL. Furthermore, mpCASL yielded better reproducibility in repeat scans than the other methods. CONCLUSION: The experimental results are consistent with the hypothesis that the new null pulse of mpCASL leads to improved brain perfusion images.

(1)H MRS detection of glycine residue of reduced glutathione in vivo.

Glutathione (GSH) is a powerful antioxidant found inside different kinds of cells, including those of the central nervous system. Detection of GSH in the human brain using (1)H MR spectroscopy is hindered by low concentration and spectral overlap with other metabolites. Previous MRS methods focused mainly on the detection of the cysteine residue (GSH-Cys) via editing schemes. This study focuses on the detection of the glycine residue (GSH-Gly), which is overlapped by glutamate and glutamine (Glx) under physiological pH and temperature. The first goal of the study was to obtain the spectral parameters for characterization of the GSH-Gly signal under physiological conditions. The second goal was to investigate a new method of separating GSH-Gly from Glx in vivo. The characterization of the signal was carried out by utilization of numerical simulations as well as experiments over a wide range of magnetic fields (4.0-14T). The proposed separation scheme utilizes J-difference editing to quantify the Glx contribution to separate it from the GSH-Gly signal. The presented method retains 100% of the GSH-Gly signal. The overall increase in signal to noise ratio of the targeted resonance is calculated to yield a significant SNR improvement compared to previously used methods that target GSH-Cys residue. This allows shorter acquisition times for in vivo human clinical studies.

RF pulses for in vivo spectroscopy at high field designed under conditions of limited power using optimal control.

Localized in vivo spectroscopy at high magnetic field strength (>3T) is susceptible to localization artifacts such as the chemical shift artifact and the spatial interference artifact for J-coupled spins. This latter artifact results in regions of anomalous phase for J-coupled spins. These artifacts are exacerbated at high magnetic field due to the increased frequency dispersion, coupled with the limited RF pulse bandwidths used for localization. Approaches to minimize these artifacts include increasing the bandwidth of the frequency selective excitation pulses, and the use of frequency selective saturation pulses to suppress the signals in the regions with anomalous phase. The goal of this article is to demonstrate the efficacy of optimal control methods to provide broader bandwidth frequency selective pulses for in vivo spectroscopy in the presence of limited RF power. It is demonstrated by examples that the use of optimal control methods enable the generation of (i) improved bandwidth selective excitation pulses, (ii) more efficient selective inversion pulses to be used for generation of spin echoes, and (iii) improved frequency selective saturation pulses. While optimal control also allows for the generation of frequency selective spin echo pulses, it is argued that it is more efficient to use dual inversion pulses for broadband generation of spin echoes. Finally, the optimal control routines and example RF pulses are made available for downloading.

Numerical simulations of localized high field 1H MR spectroscopy.

The limited bandwidths of volume selective RF pulses in localized in vivo MRS experiments introduce spatial artifacts that complicate spectral quantification of J-coupled metabolites. These effects are commonly referred to as a spatial interference or "four compartment" artifacts and are more pronounced at higher field strengths. The main focus of this study is to develop a generalized approach to numerical simulations that combines full density matrix calculations with 3D localization to investigate the spatial artifacts and to provide accurate prior knowledge for spectral fitting. Full density matrix calculations with 3D localization using experimental pulses were carried out for PRESS (TE=20, 70 ms), STEAM (TE=20, 70 ms) and LASER (TE=70 ms) pulse sequences and compared to non-localized simulations and to phantom solution data at 4 T. Additional simulations at 1.5 and 7 T were carried out for STEAM and PRESS (TE=20 ms). Four brain metabolites that represented a range from weak to strong J-coupling networks were included in the simulations (lactate, N-acetylaspartate, glutamate and myo-inositol). For longer TE, full 3D localization was necessary to achieve agreement between the simulations and phantom solution spectra for the majority of cases in all pulse sequence simulations. For short echo time (TE=20 ms), ideal pulses without localizing gradients gave results that were in agreement with phantom results at 4 T for STEAM, but not for PRESS (TE=20). Numerical simulations that incorporate volume localization using experimental RF pulses are shown to be a powerful tool for generation of accurate metabolic basis sets for spectral fitting and for optimization of experimental parameters.

Elimination of spatial interference in PRESS-localized editing spectroscopy.

Unambiguous detection of gamma-amino butyric acid (GABA) in the human brain is hindered by low concentration and spectral overlap with other metabolites. The popular MEGA-PRESS (PRESS: point-resolved spectroscopic sequence) method allows spectral separation of GABA from other metabolites, but suffers from a significant signal-to-noise ratio (SNR) reduction due to the 4-compartment artifact. An alternative PRESS localization technique (PRESS+4) was investigated and compared to MEGA-PRESS using numerical simulations, phantom, and in vivo experiments. It was shown that while the MEGA-PRESS method suffers significant signal loss ( approximately equal 20% for the difference spectrum), GABA signal intensity in PRESS+4 is reduced by only 2% compared to the nonlocalized condition at 4T. The improved method retains important features of the popular MEGA-PRESS such as additional water suppression and macromolecular elimination as demonstrated in human brain experiments. This method is not limited to GABA J-difference editing, but can be applied in any PRESS-based experiments. It should prove particularly useful at higher field, where the 4-compartment artifact is especially detrimental.

Sensitive and fast T1 mapping based on two inversion recovery images and a reference image.

We developed a fast method to obtain T1 relaxation maps in magnetic resonance imaging (MRI) based on two inversion recovery acquisitions and a reference acquisition, while maintaining high sensitivity by utilizing the full dynamic range of the MRI signal. Optimal inversion times for estimating T1 in the human brain were predicted using standard error propagation theory. In vivo measurements on nine healthy volunteers yielded T1 values of 1094+/-18 ms in gray matter and 746+/-40 ms in white matter, in reasonable agreement with literature values using conventional approaches. The proposed method should be useful for clinical studies because the T1 maps can be obtained within a few seconds.

Observation of coupled 1H metabolite resonances at long TE.

A PRESS localization (1)H MRS acquisition sequence with a Carr-Purcell train of refocusing pulses (CP-PRESS) has been implemented using global refocusing "sandwich" pulses. The CP pulse train minimized the effects of J-coupled dephasing in metabolites with strongly coupled, multiplet resonance groups as demonstrated in both phantom data and in vivo single-voxel spectroscopy in normal volunteers. Metabolites with multiplet resonance patterns were maintained with greater signal to noise and a simpler resonance pattern at long echo times. T(2) decay times for metabolites with singlet and multiplet resonances were similar to published values, except for the NAA multiplet at 2.5 ppm, which had a significantly shorter T(2) value (147 ms) than that typically reported for the singlet at 2.01 ppm. Metabolite-nulled spectra were acquired in normal volunteers to evaluate the effects of CP-PRESS on baseline signal contributions from residual water, lipids, and macromolecules. The T(2) decay times in four baseline regions in data acquired with the CP-PRESS sequence showed longer decays than corresponding regions in metabolite-nulled spectra from a standard PRESS sequence, but were significantly diminished long before the metabolites of interest were gone. The spectral analysis for spectra with longer TE times also showed less variability due the higher metabolite SNR, simpler spectral patterns, and the decreased baseline contributions.

Summarizing complexity in high dimensions.

High-dimensional, multispectral data on complex physical systems are increasingly common. As the amount of information in data sets increases, the difficulty of effectively utilizing it also increases. For such data, summary information is required for understanding and modeling the underlying dynamics. It is here proposed to use an extension of computational mechanics [C. R. Shalizi and J. P. Crutchfield, J. Stat. Phys. 104, 817 (2001)] to arbitrary spatiotemporal and spectral dimension, for providing such summary information. An example of the use of these tools to identify state evolution in the brain, an archetypal, complex biophysical system, serves as an illustration.

Human brain: reliability and reproducibility of pulsed arterial spin-labeling perfusion MR imaging.

The Committee of Human Research of the University of California San Francisco approved this study, and all volunteers provided written informed consent. The goal of this study was to prospectively determine the global and regional reliability and reproducibility of noninvasive brain perfusion measurements obtained with different pulsed arterial spin-labeling (ASL) magnetic resonance (MR) imaging methods and to determine the extent to which within-subject variability and random noise limit reliability and reproducibility. Thirteen healthy volunteers were examined twice within 2 hours. The pulsed ASL methods compared in this study differ mainly with regard to magnetization transfer and eddy current effects. There were two main results: (a) Pulsed ASL MR imaging consistently had high measurement reliability (intraclass correlation coefficients greater than 0.75) and reproducibility (coefficients of variation less than 8.5%), and (b) random noise rather than within-subject variability limited reliability and reproducibility. It was concluded that low signal-to-noise ratios substantially limit the reliability and reproducibility of perfusion measurements.

Numerical simulation of PRESS localized MR spectroscopy.

Numerical simulations of NMR spectra can provide a rapid and convenient method for optimizing acquisition sequence parameters and generating prior spectral information required for parametric spectral analysis. For spatially resolved spectroscopy, spatially dependent variables affect the resultant spectral amplitudes and phases, which must therefore be taken into account in any spectral simulation model. In this study, methods for numerical simulation of spectra obtained using the PRESS localization pulse sequence are examined. A comparison is made between three different simulation models that include different levels of detail regarding the spatial distributions of the excitation functions, and spin evolution during application of the pulses. These methods were evaluated for measurement of spectra from J-coupled spin systems that are of interest for in vivo proton spectroscopy and results compared with experimental data. It is demonstrated that for optimized refocusing pulses it is sufficient to account for chemical shift effects only, although there is some advantage to implementing a more general numerical simulation approach that includes information on RF pulse excitation profiles, which provides sufficient accuracy while maintaining moderate computational requirements and flexibility to handle different spin systems.

Identification of the epileptogenic lobe in neocortical epilepsy with proton MR spectroscopic imaging.

PURPOSE: The aim of this study was to evaluate the usefulness of multislice magnetic resonance spectroscopic imaging (MRSI) in combination with tissue segmentation for the identification of the epileptogenic focus in neocortical epilepsy (NE). METHODS: Twenty patients with NE (10 with MRI-visible malformations, 10 with normal MRI) and 19 controls were studied. In controls, N-acetylaspartate NAA/Cr and NAA/Cho of all voxels of a given lobe were expressed as a function of white matter, and thresholds were determined by calculating the 95% prediction intervals (PIs) for NAA/Cr and NAA/Cho. Voxels with NAA/Cr or NAA/Cho values less than the 95% PI were defined as "pathological." Z-scores were calculated. Depending on the magnitude of those z-scores, we used two different methods (score-localization or forced-localization) to identify in a given subject the lobe with the highest percentage of pathological voxels, which was supposed to represent the epileptogenic lobe. RESULTS: MRSI correctly identified the lobe containing the epileptogenic focus as defined by EEG in 65% of the NE patients. MRSI localization of the focus was correct in 70% of the patients with an MRI-visible malformation and in 60% of the patients with normal MRI. Of the patients, 15% had metabolically abnormal brain regions outside the epileptogenic lobe, and 35% of the patients had evidence for secondary hippocampal damage. CONCLUSIONS: MRSI may be helpful for the identification of the epileptogenic focus in NE patients, even in NE with normal MRI.

Identification of abnormal neuronal metabolism outside the seizure focus in temporal lobe epilepsy.

PURPOSE: The aim of this study was to identify metabolically abnormal extrahippocampal brain regions in patients with temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) magnetic resonance imaging (MRI) evidence for mesial-temporal sclerosis (MTS) and to assess their value for focus lateralization by using multislice 1H magnetic resonance spectroscopic imaging (MRSI). METHODS: MRSI in combination with tissue segmentation was performed on 14 TLE-MTS and seven TLE-no and 12 age-matched controls. In controls, N-acetylaspartate/(creatine + choline) [NAA/(Cr+Cho)] of all voxels of a given lobe was expressed as a function of white matter content to determine the 95% prediction interval for any additional voxel of a given tissue composition. Voxels with NAA/(Cr+Cho) below the lower limit of the 95% prediction interval were defined as "pathological" in patients and controls. Z-scores were used to identify regions with a higher percentage of pathological voxels than those in controls. RESULTS: Reduced NAA/(Cr+Cho) was found in ipsilateral temporal and parietal lobes and bilaterally in insula and frontal lobes. Temporal abnormalities identified the epileptogenic focus in 70% in TLE-MTS and 83% of TLE-no. Extratemporal abnormalities identified the epileptogenic focus in 78% of TLE-MTS but in only 17% of TLE-no. CONCLUSIONS: TLE is associated with extrahippocampal reductions of NAA/(Cr+Cho) in several lobes consistent with those brain areas involved in seizure spread. Temporal and extratemporal NAA/(Cr+Cho) reductions might be helpful for focus lateralization.

Indirect imaging of ethanol via magnetization transfer at high and low magnetic fields.

Ethanol (EtOH) is believed to exert its neurochemical effects through interactions with brain cellular components, which causes a fraction of brain EtOH to have a lower molecular mobility. This facilitates magnetization transfer to other molecules similarly associated with macromolecules, such as water. It was hypothesized that this effect can be used in vivo to image EtOH indirectly via the much stronger brain tissue water resonance. EtOH-containing bovine serum albumin samples were used to demonstrate magnetic coupling between EtOH and water at 7 T and 1.5 T. Spectroscopy and imaging experiments demonstrated that EtOH signal saturation yielded greater water signal reduction than inversion and that this reduction scaled with EtOH concentration in the BSA samples. In human brain at physiologically relevant brain EtOH concentrations, water signal reductions were measurable when saturating the EtOH resonance. Strengths and limitations of indirectly imaging brain EtOH are discussed.

Improved perfusion-weighted MRI by a novel double inversion with proximal labeling of both tagged and control acquisitions.

A novel pulsed arterial spin labeling (PASL) technique for multislice perfusion-weighted imaging is proposed that compensates for magnetization transfer (MT) effects without sacrificing tag efficiency, and balances transient magnetic field effects (eddy currents) induced by pulsed field gradients. Improved compensation for MT is demonstrated using a phantom. Improvement in perfusion measurement was compared to other PASL techniques by acquiring perfusion images from 13 healthy volunteers (nine women and four men; age range 29-64 years; mean age 45 +/- 14 years) and second-order image texture analysis. The main improvements with the new method were significantly higher image contrast, higher mean signal intensity, and better signal uniformity across slices. In conclusion, this new PASL method should provide improved accuracy in measuring brain perfusion.

Evidence of neuronal injury outside the medial temporal lobe in temporal lobe epilepsy: N-acetylaspartate concentration reductions detected with multisection proton MR spectroscopic imaging--initial experience.

PURPOSE: To determine whether magnetic resonance (MR) spectroscopic imaging reveals metabolic changes, especially decreased N-acetylaspartate (NAA) concentrations outside the medial temporal lobe in patients with mesial temporal lobe epilepsy (TLE), consistent with neuropathologic findings of extratemporal neuronal impairment. MATERIALS AND METHODS: Eleven patients with mesial TLE and 13 control subjects were examined with multisection MR spectroscopic imaging. Three MR spectroscopic imaging sections were acquired. Thirteen brain regions in each hemisphere and the midbrain were analyzed in each patient, and the NAA to creatine-phosphocreatine (Cr) plus choline-containing compounds (Ch) (NAA/[Cr + Ch]) ratios were determined. In addition, hemispheric and whole-brain values were calculated and statistically analyzed. RESULTS: The NAA/(Cr + Ch) ratio in the ipsilateral hippocampus was significantly reduced, compared with that in the contralateral hippocampus (P <.002) and compared with that in control subjects (P <.03), confirming findings in previous studies. In patients, whole-brain NAA/(Cr + Ch) ratio outside the hippocampus was significantly lower than that in control subjects (P <.002). For the ipsilateral hemisphere in patients, NAA/(Cr + Ch) ratio was significantly lower than that in control subjects (P <.0002). Comparisons between individual brain regions revealed trends toward lower NAA/(Cr + Ch) ratios in many areas of the ipsilateral and, to a lesser extent, the contralateral hemisphere outside the hippocampus and temporal lobe, suggesting diffuse impairment. CONCLUSION: Results suggest that repeated seizure activity damages neurons outside of the seizure focus.

Multisection proton MR spectroscopy for mesial temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Extensive metabolic impairments have been reported in association with mesial temporal lobe epilepsy (mTLE). We investigated whether proton MR spectroscopy ((1)H-MRS) depicts metabolic changes beyond the hippocampus in cases of mTLE and whether these changes help lateralize the seizure focus. METHODS: MR imaging and (1)H-MRS were performed in 15 patients with mTLE with a postoperative diagnosis of mesial temporal sclerosis and in 12 control volunteers. Point-resolved spectroscopy and multisection (1)H-MRS measured N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the hippocampus, temporal opercular and lateral cortices, insula and cerebellum, and frontal, parietal, and occipital lobes. Metabolites were assessed as ratios to Cr and in absolute units. RESULTS: Twelve patients had ipsilateral hippocampal atrophy; three had negative imaging results. In the ipsilateral hippocampus, absolute NAA (/NAA/) was 27.3% lower in patients compared with that in control volunteers (P <.001) and 18.5% lower compared with that in the contralateral side (P <.01). /NAA/ averaged over selected regions in the ipsilateral temporal lobes of patients with mTLE was 19.3% lower compared with the mean in the control group (P <.0001) and by 17.7% lower compared with the contralateral values (P <.00001). Using only hippocampal data, 60% of the cases of mTLE were correctly lateralized. Lateralization, determined using whole temporal lobe data, had 87% sensitivity and 92% specificity. /NAA/ was bilaterally reduced in the frontal, parietal, and occipital lobes of patients with mTLE compared with that in control volunteers (P <.01). CONCLUSION: Multisection (1)H-MRS depicts interictal reductions of NAA in the ipsilateral temporal lobe beyond the hippocampus and accurately lateralizes seizure foci.

Transgenic mice expressing human copper-zinc superoxide dismutase exhibit attenuated apparent diffusion coefficient reduction during reperfusion following focal cerebral ischemia.

Since ADC reduction reflects intracellular edema which is an early indicator of ischemic cellular metabolic stress, we hypothesized that a decrease in ADC as determined by diffusion weighted MR imaging could be attenuated by SOD expression in transgenic mice during reperfusion following focal cerebral ischemia. Diffusion weighted imaging (DWI) was performed to evaluate apparent diffusion coefficient (ADC) reduction by constructing ADC maps with a color scale to localize ADC change in transgenic (Tg) mice expressing human CuZn superoxide dismutase (SOD) and wild type (Wt) mice during 1 h middle cerebral artery occlusion (MCAO) and 1 h reperfusion. Heat shock protein (hsp) 70-kDa mRNA analysis was evaluated as a marker of sublethal cell stress by in situ hybridization after 4 h reperfusion for comparison with Nissl staining of adjacent sections to assess infarction. Sequential ADC maps were prepared in Tg mice with sufficient temporal and spatial resolution to permit comparison with Wt mice. Tg mice showed substantial recovery of the ADC lesion after reperfusion, while Wt mice showed no recovery. There was no difference between Tg and Wt mice in the size or distribution of the ADC lesion during ischemia. The area with strong expression of hsp70 mRNA in the ischemic hemisphere was substantially larger in the Tg mice. Nissl staining showed less damage of brain tissue in Tg mice than Wt mice especially in the cortex after 4 h reperfusion following 1 h MCAO. Results demonstrate that antioxidant effects of human CuZn-SOD reduce cellular edema due to oxidative stress during reperfusion but not during ischemia after 1 h MCAO. Hsp70 could be one of the proteins that mediates protection by SOD against oxidative stress.