The functional relationship between the cerebral cortex and deep brain areas in normal individuals

Recent PET or SPECT studies have demonstrated a reduction of blood flow and metabolism in the cortex ipsilateral to a deep-seated lesion, and in the thalamus and/or basal ganglia ipsilateral to a cortical lesion. A close relationship between the cerebral cortex and deep areas of the brain has been shown in pathological conditions, presumably because of functional interconnections between the cortex and deeper area. The present study was designed to investigate the relationship of cerebral blood flow in the cerebral cortex to that in the deep gray matter including the basal ganglia and the thalamus in normal subjects. Twenty-two healthy subjects were studied using SPECT with N-isopropyl-p[123I]iodoamphetamine while in a resting state. The asymmetry index (AI) of blood flow in both the cerebral cortex and deep gray matter was calculated as follows; AI = (R-L)/(R+L)/200 (%) (R: right side, L: left side). The AI in deep gray matter was significantly correlated with the AI values in the upper frontal cortex (r = 0.54, p less than 0.01), and parietal cortex (r = 0.58, p less than 0.01), as well as the mean cortical hemispheric AI (r = 0.48, p less than 0.05). Our results suggest the existence of a functional relationship between the cerebral cortex and deep areas not only in pathological conditions but also in the resting state in normal subjects. This functional relationship is likely to be mediated by neuronal mechanisms through the projectional fiber connections between the cortex and the deep gray matter.     

Metabolic heterogeneity at the level of the anterior and posterior commissures.

Multislice, 2D proton spectroscopic imaging was performed in six healthy volunteers at long echo time (TE = 280 msec). The center of the most inferior of three slices was placed directly at the level of the line connecting the anterior and posterior commissures. Significant regional variations in metabolite levels were observed. In particular, based on statistical analysis, levels of choline were significantly high in insular cortex, thalamus, and centrum semiovale compared to other brain regions such as parietal or occipital gray and white matter. NAA levels were highest in the centrum semiovale white matter, while creatine levels were relatively constant. Globus pallidus exhibited lower signal intensities and increased linewidths for all metabolites. No spectra could be obtained from the inferior frontal lobe because of field inhomogeneity. These data show that the metabolism, and perhaps the underlying cellular composition, of thalamus and insular cortex appears to be different from other neocortical gray matter. Normal regional variations in the brain spectra should be considered when evaluating pathological conditions.     

Asymmetry and gender effect in functionally lateralized cortical regions: a proton MRS imaging study

PURPOSE: to compare metabolite concentrations and ratios in gray matter regions known for their anatomical/functional asymmetry and evaluate gender effect. MATERIALS AND METHODS: Proton MRS imaging was performed at 1.5 T with TR/TE 2300/280 msec in 20 healthy right-handed subjects (mean age 29.6 +/- 5.3 years, 10 men). Concentrations of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), and the peak area ratios NAA/Cho, NAA/Cr, and Cho/Cr were evaluated in hippocampal and parahippocampal gyri, thalamus, insula, Broca's and Wernicke's areas (and corresponding contralateral areas), primary and secondary visual areas, temporal, inferior parietal, cingulate, supplemental motor, dorsolateral prefrontal, and sensorimotor areas. Linear mixed-effects regression models were used for statistical analyses. RESULTS: NAA concentration and NAA/Cho were higher in the left thalamus by 21.9% and 20%, respectively (both P < 0.001). NAA concentration was 13% higher in the region contralateral to Wernicke's area (P < 0.02). No gender differences were found. CONCLUSION: Metabolite concentrations and ratios were symmetric and gender independent in most brain regions, however small hemispheric side differences in the thalamus and in Wernicke's area were found.     

Comparison of longitudinal metabolite relaxation times in different regions of the human brain at 1.5 and 3 Tesla.

In vivo longitudinal relaxation times of N-acetyl compounds (NA), choline-containing substances (Cho), creatine (Cr), myo-inositol (mI), and tissue water were measured at 1.5 and 3 T using a point-resolved spectroscopy (PRESS) sequence with short echo time (TE). T(1) values were determined in six different brain regions: the occipital gray matter (GM), occipital white matter (WM), motor cortex, frontoparietal WM, thalamus, and cerebellum. The T(1) relaxation times of water protons were 26-38% longer at 3 T than at 1.5 T. Significantly longer metabolite T(1) values at 3 T (11-36%) were found for NA, Cho, and Cr in the motor cortex, frontoparietal WM, and thalamus. The amounts of GM, WM, and cerebrospinal fluid (CSF) within the voxel were determined by segmentation of a 3D image data set. No influence of tissue composition on metabolite T(1) values was found, while the longitudinal relaxation times of water protons were strongly correlated with the relative GM content.     

Quantitative proton short-echo-time LASER spectroscopy of normal human white matter and hippocampus at 4 Tesla incorporating macromolecule subtraction.

Accurate quantification of in vivo short-echo-time (TE) (1)H spectra must account for contributions from both mobile metabolites and less mobile macromolecules, which can fluctuate in disease. The purpose of this study was to develop an approach for the acquisition and processing of macromolecule information to optimize metabolite quantification accuracy and precision. Human parietal white matter (8-cm(3) voxel) and posterior hippocampus (1.7-cm(3) voxel) metabolite levels were quantified, following manomolecule subtraction, from short-echo-time spectra (TE = 46 ms) acquired at 4.0 Tesla with localization by adiabatic selective refocusing (LASER). Nineteen metabolites were fit using a time domain Levenberg-Marquardt minimization that incorporated prior knowledge of metabolite lineshapes. The macromolecule contribution to the spectrum was reduced by 87% (P < 0.05) when the acquisition of single averages of the full spectrum and macromolecule spectrum were interleaved to reduce subtraction errors due to motion. Subtracting the Hankel Lanczos singular value decomposition (HLSVD) fit of the macromolecule spectrum, which contained no random noise, did not alter quantified metabolite levels but did not increase metabolite quantification precision. Several metabolites had higher concentrations in the posterior hippocampus compared to parietal white matter, which emphasizes the need to carefully control for partial volume contamination in hippocampal spectroscopy studies.     

Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry

OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. CONCLUSION: Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.     

Quantitative proton magnetic resonance spectroscopic imaging: regional variations in the corpus callosum and cortical gray matter

PURPOSE: To evaluate regional variations of metabolite concentrations in normal adult brain cortical gray matter regions, and the genu and splenium of the corpus callosum, using proton magnetic resonance spectroscopic imaging (MRSI). MATERIALS AND METHODS: Quantitative, multislice proton MRSI (TR/TE = 2000/280 msec) was performed in 12 normal human volunteers (age = 39 +/- 6 years, 7 male). Metabolite concentrations in selected cortical gray matter regions and the corpus callosum were estimated using the phantom replacement methodology. RESULTS: Frontal and parietal gray matter (PGM) showed strong differences in choline-containing compound (Cho) concentrations; in particular, Cho was higher in mesial frontal gray matter than in both dorsolateral prefrontal cortex (P < 0.0005) and PGM (P < 0.004). In contrast, both N-acetylaspartate (NAA) and creatine (Cr) were relatively uniformly distributed in the cortical gray matter regions evaluated. Significant metabolic differences were found between the genu and splenium of the corpus callosum. Cho concentrations were significantly higher in genu than splenium (P < 0.005), while Cr was lower (P < 0.004). NAA showed a trend to be higher in the splenium than the genu (P = 0.05). CONCLUSION: Metabolite concentrations, particularly Cho, showed strong regional variations both within cortical gray matter regions and between the genu and splenium of the corpus callosum. Mesial frontal regions showed the highest Cho signals. Differences in spectra presumably reflect underlying changes in structure and cellular composition. Normal spectral variations should always be considered when evaluating pathology within those brain regions.     

Test-retest reproducibility of extrastriatal dopamine D2 receptor imaging with [123I]epidepride SPECT in humans.

This study evaluated the test-retest reproducibility of D2 receptor quantification in the thalamus and temporal cortex using [123I]epidepride SPECT. METHODS: Ten healthy volunteers (4 men, 6 women; age range, 19-46 y) underwent 2 SPECT studies (interval, 2-26 d) using a bolus-plus-constant-infusion paradigm (bolus-to-infusion ratio = 6 h; infusion time = 9 h). Plasma clearance (in liters per hour) and free fraction (f1) of the parent tracer were measured. Radioactivity (in becquerels per gram) in the thalamus, temporal cortex, and cerebellum were normalized to the infusion rate (in becquerels per hour). Normalized striatal radioactivity was also measured to assess reproducibility in regions with a high density of receptors and better counting statistics. The outcome measures obtained were V3 (receptor density [Bmax]/equilibrium dissociation constant [KD]), V3' (f1 x Bmax/KD), and RT (specific-to-nondisplaceable tissue ratio). RESULTS: Test-retest variability and reliability (intraclass correlation coefficient) were 10.8% and 0.88, respectively, for plasma clearance and 15.3% and 0.77, respectively, for f1. The test-retest variability of brain-specific (target minus nondisplaceable) radioactivity was higher in the thalamus and temporal cortex than in the striatum, although reliability was comparable. Among the outcome measures, V3' showed better test-retest variability and reliability in the thalamus (13.3% and 0.75, respectively) and temporal cortex (13.4% and 0.86, respectively). CONCLUSION: Brain radioactivity was the main source of variability for quantification of extrastriatal D2 receptors with [123I]epidepride. The reproducibility of outcome measures in extrastriatal regions was good. However, because receptor density was lower in extrastriatal regions than in the striatum, the counting statistics in these regions were low and reproducibility was affected by the higher test-retest variability of brain-specific radioactivity. Compared with V3 and V3', RT showed less test-retest variability in the thalamus and temporal cortex but lower reliability. Moreover, measurement of RT may be affected by the presence of potential lipophilic metabolites entering the brain.     

Functional connectivity in the thalamus and hippocampus studied with functional MR imaging

BACKGROUND AND PURPOSE: With functional connectivity functional MR imaging, co-variance in signal intensity has been shown in functionally related regions of brain in participants instructed to perform no cognitive task. These changes are thought to represent synchronous fluctuations in blood flow, which imply neuronal connections between the regions. The purpose of this study was to map functional connectivity in subcortical nuclei with functional connectivity functional MR imaging. METHODS: Imaging data were acquired with an echo-planar sequence from six volunteers who performed no specific cognitive task. For functional connectivity functional MR imaging, a "seed" voxel or group of voxels was selected from the resting data set in the thalamus or in the hippocampus. Control voxels in gray matter presumed not to be eloquent cortex were also chosen. The correlation coefficient of the seed voxels and the control voxels with every other voxel in the resting data set was calculated. The voxels with correlation coefficients greater than or equal to 0.5 were mapped onto anatomic images for the functional connectivity functional MR images. The anatomic location of these voxels was determined by conventional parcellation methods. RESULTS: For each participant, functional connectivity functional MR imaging maps based on four seed voxels in the thalamus or hippocampus showed clusters of voxels in the ipsilateral and contralateral thalamus or hippocampus. For control voxels, few voxels in the hippocampus or thalamus showed significant correlation. Significantly more pixels in the ipsilateral hippocampus correlated with the seed voxel than in the contralateral hippocampus. The differences between numbers of functionally connected voxels in ipsilateral thalamus and those in contralateral thalamus were not significant. CONCLUSIONS: The thalamus and hippocampus show functional connectivity, presumably representing synchronous changes in blood flow.     

In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: effects of normal aging.

Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All subjects also had structural MR scans, and a model, which took into account the underlying structural composition of the brain contributing to each metabolite voxel, was developed and used to estimate the concentration of the N-acetyl-moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter. NAc concentration (signal intensity per unit volume of brain) was higher in gray than white matter and did not differ between young and old subjects despite significant gray matter volume deficits in the older subjects. To the extent that NAc is an index of neuronal integrity, the available gray matter appears to be intact in these older healthy adults. Cr concentrations were much higher in gray than white matter and significantly higher in the old than young subjects. Cho concentration in gray matter was also significantly higher in old than young subjects. Independent determination of metabolite values rather than use of ratios is essential for characterizing age-related changes in brain MRS metabolites.     

正常人脑不同区域^1H磁共振波谱研究

目的：应用１Ｈ磁共振波谱技术研究正常人脑内化合物的含量和分布。材料和方法：应用１．５Ｔ磁共振仪对１８例正常人脑进行１Ｈ波谱测试，测量的感兴趣区包括大脑皮层、白质、丘脑和小脑，所用序列为激励回波探测序列（ｓｔｉｍｕｌａｔｅｄｅｃｈｏａｑｕｉｓｉｔｉｏｎｍｏｄｅ，ＳＴＥＡＭ）。结果：１Ｈ磁共振波谱可以检测出脑内许多化合物，如Ｎ－乙酰门冬氨酸（ＮＡＡ）、含胆碱类化合物（Ｃｈｏ）、肌酸和磷酸肌酸（Ｃｒ＋Ｐｃｒ）、谷氨酸和谷氨酰胺（Ｇｌｕ＋Ｇｌｎ）、脂质、乳酸等。各化合物的浓度在脑的不同区域存在着差异。ＮＡＡ／Ｃｈｏ比值在灰质最高，小脑最低。Ｃｒ／Ｃｈｏ比值在小脑最高、白质最低。设定肌酸的浓度在灰质和小脑为１０ｍｍｏｌ／Ｌ，在白质和丘脑为１１ｍｍｏｌ／Ｌ，计算ＮＡＡ的绝对浓度为１３～２３ｍｍｏｌ／Ｌ，并且灰质的含量高于小脑和丘脑。结论：１Ｈ磁共振波谱技术可无创性检测出脑组织中与能量代谢、氨基酸、脂肪酸及神经递质有关的化合物，并可定量测定，有助于研究生理和疾病时脑生化改变。     

In vivo quantitative proton MRSI study of brain development from childhood to adolescence

PURPOSE: To quantify regional variations in metabolite levels in the developing brain using quantitative proton MR spectroscopic imaging (MRSI). MATERIALS and METHODS: Fifteen healthy subjects three to 19 years old were examined by in vivo multislice proton MRSI. Concentrations of N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), and peak area ratios were determined in selected frontal and parietal gray and white matter regions, basal ganglia, and thalamus. RESULTS: In cortical gray matter regions, the ratio of NAA/Cho increased to a maximum at 10 years and decreased thereafter (P = 0.010). In contrast, in white matter, average ratios NAA/Cho increased linearly with age (P = 0.045). In individual brain regions, age-related changes in NAA/Cho were found in the putamen (P = 0.044). No significant age-related changes in NAA, Cho, Cr, or other metabolite ratios could be determined. CONCLUSION: Consistent with recent studies using other structural and functional neuroimaging techniques, our data suggest that small but significant changes occur in regional cerebral metabolism during childhood and adolescence. Non-linear age related changes of NAA/Cho in frontal and parietal areas, resembling previously reported age related changes in rates of glucose utilization and cortical volumes, may be associated with dendritic and synaptic development and regression. Linear age-related changes of NAA/Cho in white matter are also in agreement with age-related increases in white matter volumes, and may reflect progressive increases in axonal diameter and myelination.     

Interregional variation of longitudinal relaxation rates in human brain at 3.0 T: relation to estimated iron and water contents.

In a study of interregional variation of the longitudinal relaxation rate (R(1)) in human brain at 3 T, R(1) maps were acquired from 12 healthy adults using a multi-slice implementation of the T one by multiple readout pulses (TOMROP) sequence. Mean R(1) values were obtained from the prefrontal cortex (0.567 +/- 0.020 sec(-1)), caudate head (0.675 +/- 0.019 sec(-1)), putamen (0.749 +/- 0.023 sec(-1)), substantia nigra (0.873 +/- 0.037 sec(-1)), globus pallidus (0.960 +/- 0.034 sec(-1)), thalamus (0.822 +/- 0.027 sec(-1)), and frontal white matter (1.184 +/- 0.057 sec(-1)). For gray matter regions other than the thalamus, R(1) showed a strong correlation (r = 0.984, P < 0.0001) with estimated regional nonheme iron concentrations ([Fe]). These R(1) values also showed a strong correlation (r = 0.976, P < 0.0001) with estimates of 1/f(w) obtained from MRI relative proton density measurements, where f(w) represents tissue water content. When white matter is included in the consideration, 1/f(w) is a better predictor of R(1) than is [Fe]. An analysis based on the fast-exchange two-state model of longitudinal relaxation suggests that interregional differences in f(w) account for the majority of the variation of R(1) across gray matter regions. Magn Reson Med 45:71-79, 2001.     

基于体素的形态学分析技术在评价脑灰质体积改变对皮质下缺血性血管性痴呆患者执行功能影响中的应用

目的:采用基于体素的形态学分析(VBM)技术分析皮质下缺血性血管性痴呆(SIVD)患者执行功能障碍与相关脑区灰质体积改变之间的关系.方法:分别纳入SIVD患者和健康志愿者各14例,应用VBM技术比较2组的脑灰质体积差异,分析脑灰质体积变化与执行功能的相关性.结果:与健康对照组相比,SIVD患者灰质体积显著减少,包括全脑...     

Quantitative analysis of short echo time (1)H-MRSI of cerebral gray and white matter.

Quantitative analysis of (1)H-magnetic resonance spectroscopic imaging (MRSI) data was developed using the user-independent spectral analysis routine LCModel. Tissue segmentation was performed using statistical parametric mapping software (SPM 96), and the results were used to correct for cerebrospinal fluid contamination. A correction was developed for the imperfections in the spectroscopic excitation profile in order to improve the uniformity of metabolite images. After validation in phantoms, these techniques were applied to study differences in metabolite concentrations between gray and white matter in normal volunteers (n = 13). A positive correlation was found between concentration and gray matter content for most metabolites studied. The estimated ratios of metabolite concentration in gray vs. white matter were: N-acetyl aspartate + N-acetyl aspartyl glutamate (NAc) = 1.16+/- 0.11; creatine = 1.7+/-0.3; glutamate + glutamine = 2.4+/-0.5; myo-inositol = 1.6+/-0.3; choline = 0.9+/-0.2. The ratio of NAc/Cr was negatively correlated with gray matter content: gray/white = 0.69 +/-0.08. These methods will be useful in the evaluation of metabolite concentrations in MRSI voxels with mixed tissue composition in patient groups.     

Reproducibility of quantitative cerebral T2 relaxometry, diffusion tensor imaging, and 1H magnetic resonance spectroscopy at 3.0 Tesla

OBJECTIVES: The reproducibility of quantitative cerebral T2 relaxometry, diffusion tensor imaging, and H magnetic resonance (MR) spectroscopic imaging was assessed on a clinical 3.0 T MR system. MATERIALS AND METHODS: Repeated measurements in 10 healthy volunteers were used to establish the reproducibility of quantitative measures derived from different quantitative MR techniques, namely the T2 relaxation time, the apparent diffusion coefficient (ADC), the fractional anisotropy (FA), and metabolite concentrations of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI). Results were compared with previously reported reproducibility measures from 1.5 T. RESULTS: The coefficient of variation (CV) was < or =1.6% for T2, < or =1.6% for ADC, and < or =5.3%, for FA in the cerebrum. For metabolites the CV was < or =8.0% in the frontal lobe and < or =20.4% in the temporal lobe. CONCLUSIONS: The reproducibility of quantitative brain MRI at 3.0 T is better than or at least comparable to the reproducibility at 1.5 T.     

Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem.

Quantitative, multislice proton MR spectroscopic imaging (MRSI) was used to investigate regional metabolite levels and ratios in the normal adult human posterior fossa. Six normal volunteers (36 +/- 3 years, five male, one female) were scanned on a 1.5 T scanner using multislice MRSI at long echo time (TE 280 msec). The entire cerebellum was covered using three oblique-axial slice locations, which also included the pons, mid-brain, insular cortex, and parieto-occipital lobe. Concentrations of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were estimated using the phantom replacement technique. Regional variations of the concentrations were assessed using ANOVA (P < 0.05). High-resolution MRSI data was obtained in all subjects and brain regions examined. Metabolite concentrations (mM) (mean +/- SD) were as follows: cerebellar vermis: 2.3 +/- 0.4, 8.8 +/- 1.7 and 7.6 +/- 1.0 for Cho, Cr, and NAA respectively; cerebellar hemisphere: 2.2 +/- 0.6, 8.9 +/- 2.1, 7.5 +/- 0.8; pons 2.2 +/- 0.5, 4.3 +/- 1.1, 8.3 +/- 0.9; insular cortex, 1.8 +/- 0.5, 7.8 +/- 2, 8.0 +/- 1.1, parieto-occipital gray matter, 1.3 +/- 0.3, 5.7 +/- 1.1, 7.2 +/- 0.9, and occipital white matter, 1.4 +/- 0.3, 5.3 +/- 1.3, 7.5 +/- 0.8. Consistent with previous reports, significantly higher levels of Cr were found in the cerebellum compared to parieto-occipital gray and occipital white matter, and pons (P < 0.0001). NAA was essentially uniformly distributed within the regions chosen for analysis, with the highest level in the pons (P < 0.04). Cho was significantly higher in the cerebellum and pons than parieto-occipital gray and occipital white matter (P < 0.002) and was also higher in the pons than in the insular cortex (P < 0.05). Quantitative multislice MRSI of the posterior fossa is feasible and significant regional differences in metabolite concentrations were found.     

Developmental and regional changes in the neurochemical profile of the rat brain determined by in vivo 1H NMR spectroscopy.

Sixteen metabolites were quantified from 11-24 micro l volumes in three different brain regions (hippocampus, striatum, and cerebral cortex) during postnatal development. Rat pups from the same litter were repeatedly measured on postnatal days 7, 10, 14, 21, and 28 using a completely noninvasive and longitudinal study design. Metabolite quantification was based on ultra-short echo-time (1)H NMR spectroscopy at 9.4 T and LCModel processing. Most of the brain metabolites were quantified with Cramer-Rao lower bounds (CRLB) less than 20%, which corresponded to an estimated concentration error <0.2 micro mol/g. Taurine and total creatine were quantified with CRLB < or = 5% from all 114 processed spectra. The resulting high reliability and reproducibility revealed significant regional and age-related changes in metabolite concentrations. The most sensitive markers for developmental and regional variations between hippocampus, striatum, and cerebral cortex were N-acetylaspartate, myo-inositol, taurine, glutamate, and choline compounds. Absolute values of metabolite concentrations were in very good agreement with previously published in vitro results based on chromatographic measurements of brain extracts. The current data may serve as a reference for studies focused on developmental defects and pathologies using neonatal rat models.     

Quantitative MR imaging R2 relaxometry in elderly participants reporting memory loss

BACKGROUND AND PURPOSE: In Alzheimer disease (AD), elevated brain iron concentrations in gray matter suggest a disruption in iron homeostasis, while demyelination processes in white matter increase the water content. Our aim was to assess whether the transverse proton relaxation rate, or R2, an MR imaging parameter affected by changes in brain iron concentration and water content, was different in elderly participants with mild to severe levels of cognitive impairment compared with healthy controls. METHODS: Twelve elderly participants reporting memory problems and 11 healthy volunteers underwent single-spin-echo MR imaging in a 1.5T scanner, with subsequent neuropsychological testing. R2 data were collected from 14 brain regions in cortical and subcortical gray and white matter. Those with memory complaints were separated into 2 further subgroups: MC1 (no objective cognitive impairment) and MC2 (mild to severe objective cognitive impairment). RESULTS: Mean brain R2 values from the 11 controls correlated strongly (r = 0.94, P < .0001) with reference brain iron concentrations for healthy adults. R2 values in the MC1 and MC2 subgroups were significantly higher in the right temporal cortex and significantly lower in the left internal capsule, compared with healthy controls. R2 values in the MC2 subgroup were significantly lower in the left temporal and frontal white matter, compared with healthy controls. CONCLUSIONS: R2 differences between both subgroups and the healthy controls suggest iron has increased in the temporal cortex, and myelin has been lost from several white matter regions in those with memory complaints, consistent with incipient AD pathogenesis and biochemical data.     

Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Spectroscopic examination of multiple sclerosis (MS) patients has revealed abnormally low N-acetyl-aspartate (NAA) signal intensity, even in brain tissue that appears normal on high-resolution structural MR images but has yielded inconclusive evidence to distinguish the well-documented clinical differences between MS subtypes. This study used proton MR spectroscopic imaging (MRSI) and high-resolution MR imaging to characterize metabolite profiles in normal-appearing brain tissue of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive (SP) MS. METHODS: Volumetric spiral MRSI was used together with high-resolution MR imaging to derive absolute measures of metabolite concentrations separately in normal-appearing supratentorial cerebral gray matter and white matter in five RRMS patients, five SPMS patients, and nine age-matched controls. Structural MR images were segmented into compartments of gray matter, white matter, CSF, and lesions, and metabolite signals per unit of tissue volume were calculated for gray matter and white matter separately. RESULTS: Only the SPMS group had significantly lower NAA concentrations in normal-appearing gray matter compared with concentrations in controls. NAA in normal-appearing white matter was equally reduced in RRMS and SPMS patients. The functional relevance of this brain metabolite measure was suggested by the observed but statistically nonsignificant correlation between higher disability scores on the Expanded Disability Status Scale and lower gray matter NAA concentrations. CONCLUSION: The otherwise occult abnormality in supratentorial gray matter in SPMS but not RRMS may explain the more severe physical and cognitive impairments afflicting patients with SPMS that do not correlate well with visible lesion burden.