Faculty Bibliography

Fast, high-resolution, longitudinal relaxation time (T1) mapping is invaluable in clinical and research applications. It has been shown that two spoiled gradient recalled echo (SPGR) images acquired in steady state with variable flip angles is an attractive alternative to the multi-image sets previously acquired with inversion or saturation recovery. The known sensitivity of the two-point method to transmit radiofrequency field (B1) inhomogeneity exacerbated at 3 T and above, however, mandates its combination with an additional, time-consuming and possibly specific-absorption-rate-intensive B1 measurement, preventing direct migration of the method to these fields. To address this, we introduce a method designed to be free of systematic errors caused by B1 inhomogeneity in which the value of T1 is extracted from three SPGR images acquired with echo planar imaging (EPI) readout. The precision of the T1 maps produced is found to be comparable to the two-point method, while the accuracy is greatly improved in the same time and spatial resolution. A welcome byproduct of the method is a map of B1 that can be used to correct other acquisitions in the same session. Tables of the optimal acquisition protocols are provided for several total imaging times

Since the amino acid derivative N-acetylaspartate (NAA) is almost exclusive to neuronal cells in the adult mammalian brain and its concentration has shown local (or global) abnormalities in most focal (or diffuse) neurological diseases, it is considered a specific neuronal marker. Yet despite its biological and clinical prominence, the relative NAA concentration in the gray and white matter (GM, WM) remains controversial, with each reported to be higher than, equal to, or less than the other. To help resolve the controversy and importantly, access the NAA in both compartments in their entirety, we introduce a new approach to distinguish and quantify the whole-brain average GM and WM NAA concentration by integrating MR-image segmentation, localized and non-localized quantitative (1)H-MRS. We demonstrate and validate the method in ten healthy volunteers (5 women) 27+/-6 years old (mean+/-standard-deviation) at 1.5T. The results show that the healthy adult human brain comprises significantly less WM, 39+/-3%, than GM 60+/-4% by volume (p<0.01). Furthermore, the average NAA concentration in the WM, 9.5+/-1.0 mM, is significantly lower than in GM, 14.3+/-1.1 mM (p<0.01)

Glutamate (Glu) is associated with excitotoxic cell damage. Memantine modulates the glutamate induced excitotoxicity in Alzheimer's disease (AD). No information is available as to the influence of memantine on in vivo brain glutamate levels. Hippocampal Glu levels were measured in cognitively impaired and normal individuals (n=10) before and after 6 months of memantine treatment, using three dimensional high spatial resolution (0.5 cm(3) voxels) proton magnetic resonance spectroscopy at 3 T. These measurements were also repeated in a non-treated cognitively normal group (n=6). Treatment with memantine decreased Glu/Cr (creatine) ratio in the left hippocampal region. Memantine reduced hippocampal glutamate levels, which may be consistent with its anti-excitotoxic property

Although the rhesus macaque brain is an excellent model system for the study of neurological diseases and their responses to treatment, its small size requires much higher spatial resolution, motivating use of ultra-high-field (B(0)) imagers. Their weaker radio-frequency fields, however, dictate longer pulses; hence longer TE localization sequences. Due to the shorter transverse relaxation time (T(2)) at higher B(0)s, these longer TEs subject metabolites to T(2)-weighting, that decrease their quantification accuracy. To address this we measured the T(2)s of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in several gray matter (GM) and white matter (WM) regions of four healthy rhesus macaques at 7T using three-dimensional (3D) proton MR spectroscopic imaging at (0.4 cm)(3) = 64 mul spatial resolution. The results show that macaque T(2)s are in good agreement with those reported in humans at 7T: 169 +/- 2.3 ms for NAA (mean +/- SEM), 114 +/- 1.9 ms for Cr, and 128 +/- 2.4 ms for Cho, with no significant differences between GM and WM. The T(2) histograms from 320 voxels in each animal for NAA, Cr, and Cho were similar in position and shape, indicating that they are potentially characteristic of 'healthy' in this species

Estimating the relaxation constant of an exponentially decaying signal from experimental MR data is fundamental in diffusion tensor imaging, fractional anisotropy mapping, measurements of transverse relaxation rates and contrast agent uptake. The precision of such measurements depends on the choice of acquisition parameters made at the design stage of the experiments. In this report, chi(2) fitting of multipoint data is used to demonstrate that the most efficient acquisition strategy is a two-point scheme. We also conjecture that the smallest coefficient of variation of the decay constant achievable in any N-point experiment is 3.6 times larger than that in the image intensity obtained by averaging N acquisitions with minimal exponential weighting

Due to the overall similarity of their brains' structure and physiology to its human counterpart, nonhuman primates provide excellent model systems for the pathogenesis of neurological diseases and their response to treatments. Its much smaller size, 80 versus 1250 cm(3), however, requires proportionally higher spatial resolution to study, nondestructively, as many analogous regions as efficiently as possible in anesthetized animals. The confluence of these requirements underscores the need for the highest sensitivity, spatial coverage, resolution, and exam speed. Accordingly, we demonstrate the feasibility of 3D multi-voxel, proton ((1)H) MRSI at (0.375 cm)(3)=0.05 cm(3) isotropic spatial resolution over 21 cm(3) (approximately 25%) of the anesthetized rhesus macaques brain at 7T in 25 min. These voxels are x10(2)-10(1) times smaller than the 8-1 cm(3) common to (1)H-MRS in humans, retaining similar proportions between the macaque and human brain. The spectra showed a signal-to-noise-ratio (SNR) approximately 9-10 for the major metabolites and the interanimal SNR spatial distribution reproducibility was in the +/-10% range for the standard error of their means (SEMs). Their metabolites' linewidths, 9+/-2 Hz, yield excellent spectral resolution as well. These results indicate that 3D (1)H-MRSI can be integrated into comprehensive MR studies in primates at such high fields

Cardiac MRI at 3T provides a means to increase the contrast-to-noise ratio (CNR) for first-pass perfusion MRI. However, both the static magnetic field (B(0)) and radio frequency (RF) field (B(1)) variations within the heart are comparatively higher at 3T than at 1.5T. The increased field variations can degrade the performance of a single rectangular saturation pulse that is conventionally used for magnetization preparation. The accuracy of T(1)-weighted signal measurement depends on the uniformity of the magnetization saturation. The purpose of this study was to assess the relative effectiveness of the rectangular, pulse train, and adiabatic composite (BIR-4) saturation pulses in the human heart at 3T. In volunteers, after nominal saturation, the mean residual magnetization within the left ventricle (LV) was different between all three pulses (0.13 +/- 0.06 vs. 0.03 +/- 0.02 vs. 0.03 +/- 0.01, respectively; P < 0.001). Within paired groups, the mean residual magnetization was significantly higher for the rectangular pulse than for either the pulse train and BIR-4 pulses (P < 0.001), but not different between the pulse train and BIR-4 pulses. The performances of all three saturation pulses were comparatively poorer in the right ventricle (RV) than in the LV, respectively. Magn Reson Med, 2007. (c) 2007 Wiley-Liss, Inc

OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H-MRS) has been increasingly used to examine striatal neurochemistry in adult major depressive disorder. This study extends the use of this modality to pediatric major depression to test the hypothesis that adolescents with major depression have elevated concentrations of striatal choline and creatine and lower concentrations of N-acetylaspartate. METHOD: Fourteen adolescents (ages 12-19 years, eight female) who had major depressive disorder for at least 8 weeks and a severity score of 40 or higher on the Children's Depression Rating Scale-Revised and 10 healthy comparison adolescents (six female) group-matched for gender, age, and handedness were enrolled. All underwent three-dimensional 3-T (1)H-MRS at high spatial resolution (0.75-cm(3) voxels). Relative levels of choline, creatine, and N-acetylaspartate in the left and right caudate, putamen, and thalamus were scaled into concentrations using phantom replacement, and levels were compared for the two cohorts. RESULTS: Relative to comparison subjects, adolescents with major depressive disorder had significantly elevated concentrations of choline (2.11 mM versus 1.56 mM) and creatine (6.65 mM versus 5.26 mM) in the left caudate. No other neurochemical differences were observed between the groups. CONCLUSIONS: These findings most likely reflect accelerated membrane turnover and impaired metabolism in the left caudate. The results are consistent with prior imaging reports of focal and lateralized abnormalities in the caudate in adult major depression

Proton MR spectroscopy (1H-MR spectroscopy) is a quantitative MR imaging technique often used to complement the sensitivity of conventional MR imaging with specific metabolic information. A key metabolite is the amino acid derivative N-acetylaspartate (NAA), which is almost exclusive to neurons and their processes and is, therefore, an accepted marker of their health and attenuation. Unfortunately, most 1H-MR spectroscopy studies only account for small 1- to 200-cm volumes of interest (VOI), representing less than 20% of the total brain volume. These VOIs have at least 5 additional restrictions: 1) To avoid contamination from subcutaneous and bone marrow lipids, they must be placed away from the skull, thereby missing most of the cortex. 2) They must be image-guided onto MR imaging-visible pathology, subjecting them to the implicit assumption that metabolic changes occur only there. 3) They encounter misregistration errors in serial studies. 4) The time needed to accumulate sufficient signal-intensity quality is often restrictive, and 5) they incur (unknown) T1- and T2-weighting. All these issues are avoided (at the cost of specific localization) by measuring the nonlocalized average NAA concentration over the entire brain. Indeed, whole-brain NAA quantification has been applied to several diffuse neurodegenerative diseases (where specific localization is less important than the total load of the pathology), and the results are presented in this review