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A 1H magnetic resonance spectroscopic imaging study at 3T and short echo time was conducted to evaluate both the reproducibility, as measured by the interscan coefficient of variation (CV), and test-retest reliability, as measured by the intraclass correlation coefficient (ICC), of measurements of glutamate (Glu), combined glutamate and glutamine (Glx), myo-inositol (mI), N-acetylaspartate, creatine, and choline in 21 healthy subjects. The effect of partial volume correction on these measures and the relationship of reproducibility and reliability to data quality were also examined. A 1H magnetic resonance spectroscopic imaging slice was prescribed above the lateral ventricles and single repeat scans were performed within 30 min to minimize physiologic variability. Interscan CVs based on all the voxels varied from 0.05 to 0.07 for N-acetylaspartate, creatine, and choline to 0.10-0.13 for mI, Glu, and Glx. Findings on the reproducibility of gray and white matter estimates of N-acetylaspartate, creatine, and choline are consistent with previous studies using longer echo times, with CVs in the range of 0.02-0.04 and ICC in the range of 0.65-0.90. CVs for Glu, Glx, and mI are much lower than reported in previous studies at 1.5 T, while white matter mI (CV=0.04, ICC=0.93) and gray matter Glx (CV=0.04, ICC=0.68) demonstrated both high reproducibility and test-retest reliability.

Breakdown of the blood-brain barrier (BBB), occurring in many neurological diseases, has been difficult to measure noninvasively in humans. Dynamic contrast-enhanced magnetic resonance imaging measures BBB permeability. However, important technical challenges remain and normative data from healthy humans is lacking. We report the implementation of a method for measuring BBB permeability, originally developed in animals, to estimate BBB permeability in both healthy subjects and patients with white matter pathology. Fast T(1) mapping was used to measure the leakage of contrast agent Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) from plasma into brain. A quarter of the standard Gd-DTPA dose for dynamic contrast-enhanced magnetic resonance imaging was found to give both sufficient contrast-to-noise and high T(1) sensitivity. The Patlak graphical approach was used to calculate the permeability from changes in 1/T(1). Permeability constants were compared with cerebrospinal fluid albumin index. The upper limit of the 95% confidence interval for white matter BBB permeability for normal subjects was 3 × 10(-4) L/g min. MRI measurements were not [corrected] correlated strongly with levels of cerebrospinal fluid albumin in those subjects undergoing lumbar puncture. Dynamic contrast-enhanced magnetic resonance imaging with low dose Gd-DTPA and fast T(1) imaging is a sensitive method to measure subtle differences in BBB permeability in humans and may have advantages over techniques based purely on the measurement of pixel contrast changes.

The use of tissue water as a concentration standard in proton magnetic resonance spectroscopy (1H-MRS) of the brain requires that the water proton signal be adjusted for relaxation and partial volume effects. While single voxel 1H-MRS studies have often included measurements of water proton T1, T2, and density based on additional 1H-MRS acquisitions (e.g., at multiple echo or repetition times), this approach is not practical for 1H-MRS imaging (1H-MRSI). In this report we demonstrate a method for using in situ measurements of water T1, T2, and density to calculate metabolite concentrations from 1H-MRSI data. The relaxation and density data are coregistered with the 1H-MRSI data and provide detailed information on the water signal appropriate to the individual subject and tissue region. We present data from both healthy subjects and a subject with brain lesions, underscoring the importance of water parameter measurements on a subject-by-subject and voxel-by-voxel basis. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc.

Short-echo gradient-enhanced nuclear magnetic resonance (NMR) spectroscopy was utilized to identify mobile lipids in perfused neonate and juvenile rat brain slices. Lipid signals were present at low levels within 1 hr of tissue preparation and increased with time under standard perfusion conditions and in the presence of high phosphocreatine and low lactate levels. Both one- and two-dimensional NMR spectra demonstrate peaks consistent with the generation of free fatty acids or neutral lipids following tissue trauma. The present work demonstrates that injury-induced mobile lipids may make appreciable contributions to regions of brain tissue spectra that have recently been assigned to lactate or polypeptides alone.

A 1H magnetic resonance spectroscopic imaging study at 3T and short echo time was conducted to evaluate both the reproducibility, as measured by the interscan coefficient of variation (CV), and test-retest reliability, as measured by the intraclass correlation coefficient (ICC), of measurements of glutamate (Glu), combined glutamate and glutamine (Glx), myo-inositol (mI), N-acetylaspartate, creatine, and choline in 21 healthy subjects. The effect of partial volume correction on these measures and the relationship of reproducibility and reliability to data quality were also examined. A 1H magnetic resonance spectroscopic imaging slice was prescribed above the lateral ventricles and single repeat scans were performed within 30 min to minimize physiologic variability. Interscan CVs based on all the voxels varied from 0.05 to 0.07 for N-acetylaspartate, creatine, and choline to 0.10-0.13 for mI, Glu, and Glx. Findings on the reproducibility of gray and white matter estimates of N-acetylaspartate, creatine, and choline are consistent with previous studies using longer echo times, with CVs in the range of 0.02-0.04 and ICC in the range of 0.65-0.90. CVs for Glu, Glx, and mI are much lower than reported in previous studies at 1.5 T, while white matter mI (CV=0.04, ICC=0.93) and gray matter Glx (CV=0.04, ICC=0.68) demonstrated both high reproducibility and test-retest reliability.

Breakdown of the blood-brain barrier (BBB), occurring in many neurological diseases, has been difficult to measure noninvasively in humans. Dynamic contrast-enhanced magnetic resonance imaging measures BBB permeability. However, important technical challenges remain and normative data from healthy humans is lacking. We report the implementation of a method for measuring BBB permeability, originally developed in animals, to estimate BBB permeability in both healthy subjects and patients with white matter pathology. Fast T(1) mapping was used to measure the leakage of contrast agent Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) from plasma into brain. A quarter of the standard Gd-DTPA dose for dynamic contrast-enhanced magnetic resonance imaging was found to give both sufficient contrast-to-noise and high T(1) sensitivity. The Patlak graphical approach was used to calculate the permeability from changes in 1/T(1). Permeability constants were compared with cerebrospinal fluid albumin index. The upper limit of the 95% confidence interval for white matter BBB permeability for normal subjects was 3 × 10(-4) L/g min. MRI measurements were not [corrected] correlated strongly with levels of cerebrospinal fluid albumin in those subjects undergoing lumbar puncture. Dynamic contrast-enhanced magnetic resonance imaging with low dose Gd-DTPA and fast T(1) imaging is a sensitive method to measure subtle differences in BBB permeability in humans and may have advantages over techniques based purely on the measurement of pixel contrast changes.

The magnetic properties and water dynamics of human red blood cells were examined by analysis of the water proton spectra of suspensions of oxygenated, deoxygenated, carbon monoxide-treated, and methemoglobin-containing cells at a magnetic field strength of 7.05 T. Total lineshape analysis of spectra from deoxygenated red blood cell suspensions was performed to determine the transmembrane water exchange rate, the contribution of diffusion in local magnetic field gradients to the transverse relaxation rate, and the difference between the intra- and extracellular chemical shifts of water protons. Mathematical models are proposed to account for the dependence of the chemical shifts and linewidths of these spectra on the magnetic susceptibility or density of the cells.

Asymmetric 7 T proton NMR signals of water in RBC suspensions containing intracellular deoxyhemoglobin are composites of chemically shifted extracellular and intracellular resonances broadened by gradient diffusion and modulated by transmembrane water exchange. This allows assessment of field dependences of acute hematoma intensities in proton MRIs at lower field strengths (

Improved detection of J-coupled neurometabolites through the use of modified proton magnetic resonance spectroscopy (1H-MRS) techniques has recently been reported. TE-averaged point-resolved spectroscopy (PRESS) uses the J modulation effects by averaging FIDs with differing echo times to improve detection of glutamate, while standard PRESS detection of glutamate can be improved by using an appropriate single echo determined from J-modulation simulations. In the present study, the reliabilities of TE-averaged PRESS, standard PRESS with TE = 40 ms, and standard PRESS with TE = 30 ms in detecting metabolite levels in the cingulate gyrus of the human brain at 3T were compared in six subjects. TE-averaged PRESS measures showed a mean variability of 9% for N-acetyl aspartate, choline, and creatine, compared with < 4% for the 30- and 40-ms PRESS techniques. The coefficients of variation for glutamate were 10%, 7%, and 5% for TE-averaged, 30-ms, and 40-ms PRESS, respectively. PRESS with a TE of 40 ms also demonstrated improved reliability for GABA and glutamine concentrations. These results show that with the appropriate selection of echo time standard PRESS can be a reliable (1)H-MRS technique for the measurement of J-coupled neurometabolites in the human brain and, moreover, compares favorably with at least one J-edited technique.

In this multicenter study, 2D spatial mapping of J-coupled resonances at 3T and 4T was performed using short-TE (15 ms) proton echo-planar spectroscopic imaging (PEPSI). Water-suppressed (WS) data were acquired in 8.5 min with 1-cm(3) spatial resolution from a supraventricular axial slice. Optimized outer volume suppression (OVS) enabled mapping in close proximity to peripheral scalp regions. Constrained spectral fitting in reference to a non-WS (NWS) scan was performed with LCModel using correction for relaxation attenuation and partial-volume effects. The concentrations of total choline (tCho), creatine + phosphocreatine (Cr+PCr), glutamate (Glu), glutamate + glutamine (Glu+Gln), myo-inositol (Ins), NAA, NAA+NAAG, and two macromolecular resonances at 0.9 and 2.0 ppm were mapped with mean Cramer-Rao lower bounds (CRLBs) between 6% and 18% and approximately 150-cm(3) sensitive volumes. Aspartate, GABA, glutamine (Gln), glutathione (GSH), phosphoethanolamine (PE), and macromolecules (MMs) at 1.2 ppm were also mapped, although with larger mean CRLBs between 30% and 44%. The CRLBs at 4T were 19% lower on average as compared to 3T, consistent with a higher signal-to-noise ratio (SNR) and increased spectral resolution. Metabolite concentrations were in the ranges reported in previous studies. Glu concentration was significantly higher in gray matter (GM) compared to white matter (WM), as anticipated. The short acquisition time makes this methodology suitable for clinical studies.

A strategy for using tissue water as a concentration standard in (1)H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K-means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N-acetyl groups (NAc, primarily N-acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with FAST multispectral segmentation are reported: GM [NAc] = 17.16 +/- 1.19 mM; WM [NAc] = 14.26 +/- 1.38 mM; GM [Ch] = 3.27 +/- 0.47 mM; WM [Ch] = 2.65 +/- 0.25 mM; GM [Cr] = 13.98 +/- 1.20 mM; and WM [Cr] = 7.10 +/- 0.67 mM.

The 31P NMR of aqueous [Dy(P3O10)2]7- demonstrates that it is in slow exchange with P3O5-10 on the NMR time scale. In the presence of tissue, [Dy(P3O10)2]7- decomposes to PO4 with an accompanying slow change of the tissue 23Na NMR of extracellular Na+ ion in several NMR distinguishable extracellular sites.