Faculty Bibliography

OBJECTIVE: The aim of this study was to assess quantitatively structural changes in myelin content occurring during demyelination and remyelination by magnetization transfer imaging (MTI). MATERIALS AND METHODS: In a reversible model of demyelination with no axonal loss, mice intoxicated by cuprizone were studied by MTI in vivo at 9.4 T. MRI data were compared to histopathological examinations. RESULTS: Data revealed that the magnetization transfer ratio (MTR) decreased significantly during demyelination and increased during remyelination with strong correlation to the myelin content (r=0.79, P=0.01). CONCLUSIONS: This study demonstrated that MTR is a sensitive and reproducible quantitative marker to assess myelin loss and repair. This may lead to in vivo monitoring of therapeutic strategies promoting remyelination

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

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

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)

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

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

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

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

PURPOSE: To quantify proton magnetic resonance (MR) spectroscopy-detectable metabolite concentrations along anteroposterior axis of hippocampus in healthy young and elderly subjects. MATERIALS AND METHODS: Young (three women, three men; age range, 25-35 years) and elderly (four women, two men; age range, 68-72 years) groups underwent MR imaging and proton MR spectroscopic imaging at 3 T in this HIPAA-compliant prospective study and gave institutional review board-approved written consent. Volume of interest was centered on and tilted parallel to hippocampal anteroposterior plane. Absolute N-acetylaspartate (NAA), choline, and creatine levels were obtained in each voxel, with phantom replacement. RESULTS: Mean NAA, creatine, and choline concentrations in the young group were higher in posterior hippocampus (12.9 mmol/L +/- 2.0 [standard deviation], 7.8 mmol/L +/- 1.2, 2.3 mmol/L +/- 0.4, respectively) than anterior hippocampus (8.0 mmol/L +/- 1.1, 6.0 mmol/L +/- 1.4, 1.5 mmol/L +/- 0.2; P = .005, .02, and .0002, respectively). In the elderly group, mean concentrations were higher in posterior hippocampus (8.6 mmol/L +/- 0.9, 5.6 mmol/L +/- 0.6, 1.5 mmol/L +/- 0.2, respectively) than anterior hippocampus (7.2 mmol/L +/- 1.0, 2.4 mmol/L +/- 0.3, 1.0 mmol/L +/- 0.2; P = .006, .0001, .04, respectively). Mean concentrations were significantly higher in the young group (13.2 mmol/L +/- 1.0, 7.4 mmol/L +/- 0.8, 2.1 mmol/L +/- 0.3, respectively) than in the elderly group (9.0 mmol/L +/- 1.0, 5.8 mmol/L +/- 0.8, 1.8 mmol/L +/- 0.3; P = .0001, .01, .05, respectively). Posteroanterior metabolic gradients differed: NAA decreased faster in the young group (-1.0 mmol/L x cm(-1)) than the elderly group (-0.7 mmol/L x cm(-1)); creatine and choline concentrations decreased faster in the elderly group (-0.8 and -0.058 mmol/L x cm(-1), respectively) than the young group (-0.16 and -0.008 mmol/L x cm(-1), respectively). No left-right metabolic differences were found. CONCLUSION: Significant metabolic heterogeneity was observed between groups and along anteroposterior axis of healthy hippocampus in both groups. Age matching and consistent voxel placement are important for correct comparisons of both absolute metabolic levels and metabolite ratios in longitudinal intra- and intersubject cross-sectional studies

Proton MR spectroscopic imaging (MRSI) at higher magnetic fields (B(0)) suffers metabolite localization errors from different chemical-shift displacements (CSDs) if spatially-selective excitation is used. This phenomenon is exacerbated by the decreasing radiofrequency (RF) field strength, B(1), at higher B(0)s, precluding its suppression with stronger gradients. To address this, two new methods are proposed: 1) segmenting the volume-of-interest (VOI) into several slabs, allowing proportionally stronger slice-select gradients; and 2) sequentially cascading rather than superposing the components of the Hadamard selective pulses used for reasons of better point-spread function (PSF) to localize the few slices within each slab. This can reduce the peak B(1) to that of a single slice. Combining these approaches permits us to increase the selective gradient four- to eightfold per given B(1), to 12 or 18mT/m for 4- or 2-cm VOIs. This 'brute force' approach reduces the CSD to under 0.05 cm/ppm at 7T, or less than half that at 3T