Relative Concentrations of Proton MR Visible Neurochemicals in Gray and White Matter in Human Brain

The relative distributions of N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG), creatine + phosphocreatine (Cr/PCr), and choline (Cho) in the gray and white matter of human brain were determined by utilizing proton magnetic resonance spectroscopic imaging (SI). The SI data was processed using an automated spectroscopic image processing algorithm, and image segmentation was performed using a supervised technique. Linear regression analysis indicated that the NAA + NAAG (2.01 ppm) and Cr/PCr (3.02 ppm) peaks are greater in gray matter compared with white matter. The large intersubject variation observed in the Cho (3.20 ppm) resonance prevented the assessment of its regional distribution with confidence.     

Age dependence of regional proton metabolites T2 relaxation times in the human brain at 3 T

Although recent studies indicate that use of a single global transverse relaxation time, T₂, per metabolite is sufficient for better than ±10% quantification precision at intermediate and short echo‐time spectroscopy in young adults, the age‐dependence of this finding is unknown. Consequently, the age effect on regional brain choline (Cho), creatine (Cr), and N‐acetylaspartate (NAA) T₂s was examined in four age groups using 3D (four slices, 80 voxels 1 cm³ each) proton MR spectroscopy in an optimized two‐point protocol. Metabolite T₂s were estimated in each voxel and in 10 gray and white matter (GM, WM) structures in 20 healthy subjects: four adolescents (13 ± 1 years old), eight young adults (26 ± 1); two middle‐aged (51 ± 6), and six elderly (74 ± 3). The results reveal that T₂s in GM (average ± standard error of the mean) of adolescents (NAA: 301 ± 30, Cr: 162 ± 7, Cho: 263 ± 7 ms), young adults (NAA: 269 ± 7, Cr: 156 ± 7, Cho: 226 ± 9 ms), and elderly (NAA: 259 ± 13, Cr: 154 ± 8, Cho: 229 ± 14 ms), were 30%, 16%, and 10% shorter than in WM, yielding mean global T₂s of NAA: 343, Cr: 172, and Cho: 248 ms. The elderly NAA, Cr, and Cho T₂s were 12%, 6%, and 10% shorter than the adolescents, a change of under 1 ms/year assuming a linear decline with age. Formulae for T₂ age‐correction for higher quantification precision are provided. Magn Reson Med 60:790–795, 2008. © 2008 Wiley‐Liss, Inc.     

Computation of brain metabolite ratios in single-voxel proton MR spectroscopy: comparison between semiautomatic and automatic software

Purpose

Metabolite ratios are the measurements most commonly utilised for clinical applications of brain proton magnetic resonance spectroscopy (¹H-MRS) [1]. We evaluated the agreement between the metabolite ratios calculated with semiautomatic and automatic software.

Materials and methods

Two single-voxel spectra (3.375 ml) localised in the frontal grey matter (GM) and peritrigonal white matter (WM) were obtained in 20 healthy subjects by using a point-resolved proton spectroscopy sequence (PRESS, TE=144 ms). The spectra were processed using the semiautomatic software J-Magnetic Resonance User Interface (JMRUI) and the automatic software SpectroView. Agreement of the N-acetyl-aspartate (NAA)/creatine (Cr), NAA/choline (Cho) and Cho/Cr ratios calculated with the two methods was assessed by estimating the 95% limits of agreement (LAs) of the differences of the values obtained with the two software packages.

Results

Mean values and standard deviations of NAA/Cr, Cho/Cr and NAA/Cho (semiautomatic//automatic software) were 1.99±0.53//1.73±0.36, 1.13±0.40//1.04±0.33, 1.85±0.62//1.89±0.69 for the GM and 2.24±0.41//2.37±0.27, 0.96±0.17//1.13±0.15, 2.37±0.43//2.11±0.23 for the WM. The 95% LAs were wider for GM spectra and ranged between ?0.51, 0.17 for Cho/Cr in the WM and ?1.54, 1.47 for NAA/Cho in the GM.

Conclusions

The difference between brain metabolite ratios calculated with the two software packages is not negligible and reflects spectral quality.     

Quantitation of automated single-voxel proton MRS using cerebral water as an internal reference

Data from a previously published, multi-site trial (P. G. Webb, N. Sailasuta, S. J. Kohler, T. Raidy, R. A. Moats, R. E. Hurd, Automated single-voxel proton MRS: technical development and multisite verification. Magn. Reson. Med. 31, 365–373 (1994)) of a fully automatic, single-voxel, proton spectroscopy package (PROBE/SV, GE Medical Systems) was re-analyzed in terms of absolute metabolite concentrations using the cerebral water signal as an internal reference. In 100 spectra from parietal white matter in normal volunteers ranging in age from 22 to 34 years at eight sites, overall concentrations of choline (Cho), creatine (Cr), and N-acetyl-aspartate (NAA) resonances were found to be 2.00 ± 0.50, 8.43 ± 1.26, and 12.55 ± 1.76 μmol/g wet weight, respectively. These values are in good general agreement with previously published values from quantitative, single-voxel studies. Metabolite concentrations for NAA, Cr, and Cho across all sites had standard deviations of 14.1%, 14.9%, and 25.1%, respectively. Quantitation of PROBE data sets is routinely possible by using the cerebral water signal as an internal reference.     

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.     

Proton MR spectroscopy in idiopathic spasmodic torticollis

Single-voxel proton magnetic resonance spectroscopy (¹H-MRS), localised to the basal ganglia, was used to determine changes in metabolite levels in idiopathic spasmodic torticollis (IST). We examined nine patients and 13 healthy subjects. The mean values ( ± SD) of peak area ratios were: IST: N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) 1.79 ± 0.39, NAA/creatine and phosphocreatine compounds (Cr) 1.61 ± 0.38, Cho/Cr 0.91 ± 0.19; controls: NAA/Cho 2.07 ± 0.35, NAA/Cr 1.82 ± 0.31, Cho/Cr 0.89 ± 0.12. Statistical analysis showed that NAA/Cho and NAA/Cr were significantly lower in patients than in controls (P = 0.0304 and 0.0431, respectively). These results indicate a reduction in NAA, and suggest striatal involvement in the pathogenesis IST. Received: 8 October 2000 Accepted: 4 December 2000     

Localized brain proton NMR spectroscopy in young adult phenylketonuria patients

Localized proton magnetic resonance spectroscopy with short echo time (TE = 20 ms) was used to investigate biochemical changes in the cerebral white matter of 20 young adult patients (median 19 years) with phenylketonuria (PKU). Results were compared with those of a group of 12 age-matched healthy volunteers (median 25 years). Concentrations of Nacetyl-aspartate (NAA) and choline (Cho) relative to creatine (Cr) were unchanged. However, concentrations of inositol (Ins) relative to creatine were found to be significantly lower (P < 0.001) in the PKU patients (0.30 ± 0.09 versus 0.57 ± 0.17). Individual inositol concentrations did not correlate with age, diet, serum phenylalanine (Phe) levels or extent of pathological regions in the T,-weighted images. The lack of correlation with individual data suggests that the decreased inositol concentration could be related to a metabolic deficiency during fetal development. No signal from the phenyl ring protons of phenylalanine was detected in the PKU patients (phenylalanine serum concentration ? 1.27 mM), which suggests that concentration of phenylalanine may be lower in brain than in serum.     

Regional metabolite T2 in the healthy rhesus macaque brain at 7T

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 (B₀) imagers. Their weaker radio‐frequency fields, however, dictate longer pulses; hence longer TE localization sequences. Due to the shorter transverse relaxation time (T₂) at higher B₀s, these longer TEs subject metabolites to T₂‐weighting, that decrease their quantification accuracy. To address this we measured the T₂s 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 μl spatial resolution. The results show that macaque T₂s 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 T₂ 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. Magn Reson Med 59:1165–1169, 2008. © 2008 Wiley‐Liss, Inc.     

Magnetic resonance imaging of solitary brain metastases: main findings of nonmorphological sequences

Purpose

This study was done to investigate the usefulness of diffusion-weighted (DWI), perfusion-weighted (PWI) and proton magnetic resonance (MR) spectroscopy imaging in characterising solitary brain metastases.

Materials and methods

Fifty-nine solitary brain metastases were evaluated with conventional and nonmorphological MR imaging: DWI, PWI and MR spectroscopy. We evaluated size, signal intensity and contrast enhancement and calculated apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), percentage of signal intensity recovery (PSR) and maximum values of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipids (Lip), NAA/Cr and Cho/Cr. The nonmorphological parameters were compared with those from the literature for brain lesions that frequently enter the differential diagnosis with metastases.

Results

Signal intensity and contrast enhancement patterns were variable. There was a wide range of ADC values: min:max 0.59×10^?3:1.88×10^?3. Compared with normal white matter, rCBV was higher in lesions (3.30±1.59) and lower in perilesional oedema (0.42±0.15). Mean and minimum PSR were 57% and 48%, respectively; lip and Cho were elevated and NAA reduced.

Conclusions

Conventional MR findings of solitary metastases are heterogeneous, and some values of nonmorphological sequences are similar to those of other brain lesions. PWI seems to be the nonmorphological MR technique that may best contribute to the diagnosis of brain metastases.     

Anomalous Transverse Relaxation in 1H Spectroscopy in Human Brain at 4 Tesla

Longitudinal (T₁) and apparent transverse relaxation times (T₂) of choline-containing compounds (Cho), creatine/phospho-creatine (Cr/PCr), and N-acetyl aspartate (NAA) were measured in vivo in human brain at 4 Tesla. Measurements were performed using a water suppressed stimulated echo pulse sequence with complete outside volume presaturation to improve volume localization at short echo times. T₁-values of Cho (1.2 ± 0.1 s), Cr (1.6 ± 0.3 s), and NAA (1.6 ± 0.2 s) at 4 Tesla in occipital brain were only slightly larger than those reported in the literature at 1.5 Tesla. Thus, TR will not adversely affect the expected enhancement of signal-to-noise at 4 Tesla. Surprisingly, apparent T₂-values of Cho (142 ± 34 ms), Cr (140 ± 13 ms), and NAA (185 ± 24 ms) at 4 Tesla were significantly smaller than those at 1.5 Tesla and further decreased when increasing the mixing interval TM. Potential contributing factors, such as diffusion in local susceptibility related gradients, dipolar relaxation due to intracellular paramagnetic substances and motion effects are discussed. The results suggest that short echo time spectroscopy is advantageous to maintain signal to noise at 4 Tesla.     

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.     

Proton MR spectroscopy of the brain in infants

Proton magnetic resonance spectroscopy (MRS) was used to study the brain of 2 normal and 15 abnormal infants aged from 33 weeks postmenstrual age (PMA) to 14 months postnatal age. Eleven of the infants were examined on at least two occasions. The principal clinical diagnoses in the abnormal infants were perinatal ischemic and hemorrhagic brain injury. All proton spectra demonstrated peaks that were assigned to N-acetylaspartate (NAA), choline containing compounds (Cho), and creatine plus phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios increased with age, while the Cho/Cr ratio decreased with age in the majority of infants. The NAA/Cho ratio was generally lower in abnormal infants, but the difference was not apparent before 40 weeks (PMA). This ratio was lowest in infants with the severest degree of neurological abnormality. Proton and phosphorus MRS was compared in seven infants. In those with severe brain lesions, early phosphorus spectra were abnormal. On follow-up the phosphorus spectra became normal, but the proton spectra showed persistently low NAA/Cho and NAA/Cr ratios. Proton MRS provides new information that may be complementary to phosphorus MRS in the diagnosis and monitoring of brain development in normal and neurologically damaged infants.     

Metabolic alterations: A biomarker for radiation‐induced normal brain injury—an MR spectroscopy study

Purpose

To assess if interval changes in metabolic status in normal cerebral tissue after radiation therapy (RT) can be detected by 2D CSI (chemical shift imaging) proton spectroscopy.

Materials and Methods

Eleven patients with primary brain tumors undergoing cranial radiation therapy (RT) were included. 2D‐CSI MRS was performed before, during, and after the course of RT with the following parameters: TE/TR 144/1500 ms, field of view (FOV) 24, thickness 10 mm, matrix 16 × 16. The metabolic ratios choline/creatine (Cho/Cr), N‐acetylaspartate (NAA)/Cr, and NAA/Cho in normal brain tissue were calculated.

Results

NAA/Cr and Cho/Cr were significantly decreased at week 3 during RT and at 1 month and 6 months after RT compared to values prior to RT (P < 0.01). The NAA/Cr ratio decreased by ?0.19 ± 0.05 (mean ± standard error [SE]) at week 3 of RT, ?0.14 ± 0.06 at the last week of RT, ?0.14 ± 0.05 at 1 month after RT, and ?0.30 ± 0.08 at 6 months after RT compared to the pre‐RT value of 1.43 ± 0.04. The Cho/Cr ratio decreased by ?0.27 ± 0.05 at week 3 of RT, ?0.11 ± 0.05 at the last week of RT, ?0.26 ± 0.05 at 1 month after RT and ?0.25 ± 0.07 at 6 months after RT from the pre‐RT value of 1.29 ± 0.03. Changes in Cho/Cr were correlated with the interaction of the radiation dose and dose‐volume at week 3 of RT, during the last week of RT (P < 0.005), and at 1 month after RT (P = 0.017).

Conclusion

The results of this study suggest that MRS can detect early metabolic changes in normal irradiated brain tissue. J. Magn. Reson. Imaging 2009;29:291–297. © 2009 Wiley‐Liss, Inc.

     

Lactate,N-acetylaspartate,choline and creatine concentrations,and spin-spin relaxation in thalamic and occipito-parietal regions of developing human brain

Previous studies of the brains of normal infants demonstrated lower lactate (Lac)/choline (Cho), Lac/creatine (Cr), and Lac/N-acetylaspartate (Naa) peak-area ratios in the thalamic region (predominantly gray matter) compared with occipitoparietal (mainly unmyelinated white matter) values. In the present study, thalamic Cho, Cr, and Naa concentrations between 32–42 weeks' gestational plus postnatal age were greater than occipito-parietal: 4.6 ± 0.8 (mean ± SE), 10.5 ± 2.0, and 9.0 ± 0.7 versus 1.8 ± 0.6, 5.8 ± 1.5, and 3.4 ± 1.1 mmol/kg wet weight, respectively: Lac concentrations were similar, 2.7 ± 0.6 and 3.3 ± 1.3 mmol/kg wet weight, respectively. In the thalamic region, Cho and Naa T₂s increased, and Cho and Lac concentrations decreased, during development. Lower thalamic Lac peak-area ratios are principally due to higher thalamic concentrations of Cho, Cr, and Naa rather than less Lac. The high thalamic Cho concentration may relate to active myelination; the high thalamic Naa concentration may be due to advanced gray-matter development including active myelination. Lac concentration is higher in neonatal than in adult brain.     

MR image segmentation and tissue metabolite contrast in 1H spectroscopic imaging of normal and aging brain.

The impact of image segmentation on 0.84-ml nominal voxel volume proton spectroscopic imaging in normal brain and in age-related cortical atrophy was investigated. Segmentation improved the gray matter-white matter (GM-WM) contrast for N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in normal brain, and for NAA/Cho and NAA/Cr in atrophic brain. NAA(GM/WM) (approximately 0.7), Cho(GM/WM) (approximately 0.8), and Cr(GM/WM) (approximately 1.3) in normal brain obtained with segmentation agreed with values obtained with quantitative magnetic resonance spectroscopy. Age-related cortical atrophy led to decreased cortical GM NAA/Cho and NAA/Cr; no changes were evident in WM or in NAA(GM/WM), Cho(GM/WM), or Cr(GM/WM). GM/WM metabolite analysis may be of limited use in conditions in which parallel metabolite changes occur in WM and GM.     

小儿正常小脑半球组织~1H-MRS研究

目的:测定和计算0～7岁小儿正常小脑半球组织代谢物比值,并观察各比值随年龄变化规律。方法:应用多体素2D1H-MRS点分辨波谱(PRESS)序列测定70例0～7岁小儿正常小脑半球组织的双侧灰质及白质区代谢物浓度,按年龄分为0-1岁,1-2岁,2-3岁,3-5岁,5-7岁五组,计算和分析NAA/Cr、Cho/Cr、NAA/Cho的比值。结果:正常小脑灰质区在各年龄组间NAA/Cho(P=0.0143)和NAA/Cr(P=0.0050);白质区的NAA/Cho和NAA/Cr均P<0.001;灰质和白质区的Cho/Cr(P=0.1195,P>0.05);灰质和白质区NAA/Cho值与年龄呈正相关(P<0.001,P<0.0001);NAA/Cr值与年龄呈正相关(P=0.0004,P<0.0001);灰质区Cho/Cr与年龄呈负相关(P=0.038),白质区与年龄呈负相关(P=0.568>0.05)。结论:0～7岁小儿正常小脑半球灰、白质的代谢物比值在不同年龄组会不同,灰质和白质区NAA/Cho、NAA/Cr值随年龄增长逐渐升高,而灰质区Cho/Cr值逐渐减小,白质区无明显变化,临床上应用MRS要考虑其年龄和部位的因素。     

Diffusion-weighted imaging and proton MR spectroscopy in the characterization of acute disseminated encephalomyelitis

Introduction Acute disseminated encephalomyelitis (ADEM) is usually a monophasic illness characterized by multiple lesions involving gray and white matter. Quantitative MR techniques were used to characterize and stage these lesions. Methods Eight patients (seven males and one female; mean age 19 years, range 5 to 36 years) were studied using conventional MRI (T2- and T1-weighted and FLAIR sequences), diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS). Apparent diffusion coefficient (ADC) values and MRS ratios were calculated for the lesion and for normal-appearing white matter (NAWM). Three patients were imaged in the acute stage (within 7 days of the onset of neurological symptoms) and five in the subacute stage (after 7 days from the onset of symptoms). Results ADC values in NAWM were in the range 0.7–1.24×10⁻³ mm/s² (mean 0.937 ± 0.17 mm/s²). ADC values of ADEM lesions in the acute stage were in the range 0.37–0.68×10⁻³ mm/s² (mean 0.56 ± 0.16 mm/s²) and 1.01–1.31×10⁻³ mm/s² (mean 1.24 ± 0.13 mm/s²) in the subacute stage. MRS ratios were obtained for all patients. NAA/Cho ratios were in the range 1.1–3.5 (mean 1.93 ± 0.86) in the NAWM. NAA/Cho ratios within ADEM lesions in the acute stage were in the range 0.63–1.48 (mean 1.18 ± 0.48) and 0.29–0.84 (mean 0.49 ± 0.22) in the subacute stage. The ADC values, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the acute and subacute stages (P < 0.001, P < 0.027, P < 0.047, respectively). ADC values were significantly different between lesions in the acute (P < 0.009) and subacute stages (P < 0.005) with NAWM. In addition, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the subacute stage and NAWM (P < 0.006, P < 0.007, respectively). Conclusion ADEM lesions were characterized in the acute stage by restricted diffusion and in the subacute stage by free diffusion and a decrease in NAA/Cho ratios. Restricted diffusion and progressive decrease in NAA/Cho ratios may help in staging the disease.     

Localised proton MR spectroscopy of brain metabolism changes in vegetative patients

We examined 14 vegetative brain-injured patients with proton magnetic resonance single-volume spectroscopy (¹H MRS) at 1.5 T to establish whether there were changes in relative concentrations of N -acetyl aspartate (NAA), choline (Cho) and creatine (CR) metabolites from those found in healthy brains. Spectra were obtained from two different (2 × 2 × 2 cm) volumes of interest in the left and in the right frontal cortex, normal on MRI. All spectra revealed abnormalities compared with normal spectra obtained from age-matched control subjects. Values outside the normal range for at least one of the metabolite ratios were observed in all patients. Cho/Cr was markedly higher and NAA/Cho and NAA/Cr were markedly lower than in the control subjects. At different times six patients regained awareness and the ability to obey commands, and four were re-examined; changes in metabolite ratios were observed, which were different in individual patients. The NAA/Cho ratio reaches statistical significance in discriminating between the patients with a poor outcome (death or prolonged vegetative state) and those who regained awareness; the dividing line appears to be at a value of about 1.6. Received: 10 January 1996 Accepted: 17 June 1996     

Developmental delay in children: assessment with proton MR spectroscopy

BACKGROUND AND PURPOSE: The cause of developmental delay frequently is unknown, and clinicians and families can be frustrated by the lack of neuroimaging correlation especially when considering therapeutic options and long-term prognosis. We sought to determine if proton MR spectroscopy can depict abnormalities in patients with developmental delay who have structurally normal brain MR images. METHODS: Children with developmental delay who were older than 2 years (mean age, 5.0 years; range, 3.0-10.0 years) and those aged 2 years or younger (mean age, 1.5 years; range, 0.5-2.0 years) and age-matched control subjects for each patient group underwent brain MR imaging and proton MR spectroscopy. A point-resolved spectroscopy sequence (2000/144 [TR/TE]) was used. Voxels (8 cm(3)) were placed in the subcortical white matter of the frontal and parieto-occipital lobes bilaterally. N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were assessed. RESULTS: All patients had normal brain MR images. In children with developmental delay who were aged 2 years or younger, no statistically significant differences were detected in the NAA/Cr or Cho/Cr ratios compared with those of the control subjects. In children with developmental delay who were older than 2 years, decreases in the NAA/Cr ratio were observed in frontal (P <.001) and parieto-occipital (P <.017) subcortical white matter, and elevations in the Cho/Cr ratio were detected in the frontal (P <.24) and parieto-occipital (P <.002) subcortical white matter compared with age-matched control subjects. CONCLUSIONS: In children with developmental delay who are older than 2 years, proton MR spectroscopy depicted abnormalities in the NAA/Cr and Cho/Cr ratios. Proton MR spectroscopy should be performed as part of the neuroimaging evaluation of developmental delay. Further studies will be needed to determine if abnormalities detected with proton MR spectroscopy can be used as a diagnostic tool and neuroimaging marker to assess long-term functional outcome.     

Proton magnetic resonance spectroscopy reflects cellular proliferative activity in astrocytomas

We examined whether proton magnetic resonance spectroscopy (MRS) could provide accurate information on histological grade and cell proliferation in astrocytomas. We studied 23 patients with astrocytomas: five grade II, 10 grade III and eight with grade IV (glioblastoma multiforme). We performed proton MRS and determined the Ki-67 labeling index (LI), a tumour proliferation marker, in the same areas of the astrocytomas, and examined the statistical relationship between proton MRS and Ki-67 LI. The N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline (Cho)-containing compound ratios were always significantly lower and the Cho/Cr ratios significantly higher than those for normal brain. The Cho/Cr ratio correlated positively and the NAA/Cho ratio inversely with Ki-67 LI. These findings suggest that the Cho signal in proton MRS reflects cellular proliferation. In Kaplan-Meier survival analysis, there was no significant difference between high (> 2.0, 14 cases) and low (< 2.0, 9 cases) Cho/cr ratio groups. Received: 24 December 1998/Accepted: 11 August 1999