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Adenylosuccinate lyase (ADSL) deficiency is a rare inborn error of metabolism resulting in accumulation of metabolites including succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in the brain and other tissues. Patients with ADSL have progressive psychomotor retardation, neonatal seizures, global developmental delay, hypotonia, and autistic features, although variable clinical manifestations may make the initial diagnosis challenging. Two cases of the severe form of the disease are reported here: an 18-month-old boy with global developmental delay, intractable neonatal seizures, progressive cerebral atrophy, and marked hypomyelination, and a 3-month-old girl presenting with microcephaly, neonatal seizures, and marked psychomotor retardation. In both patients in vivo proton magnetic resonance spectroscopy (MRS) showed the presence of S-Ado signal at 8.3 ppm, consistent with a prior report. Interestingly, SAICAr signal was also detectable at 7.5 ppm in affected white matter, which has not been reported in vivo before. A novel splice-site mutation, c.IVS12 + 1/G > C, in the ADSL gene was identified in the second patient. Our findings confirm the utility of in vivo proton MRS in suggesting a specific diagnosis of ADSL deficiency, and also demonstrate an additional in vivo resonance (7.5 ppm) of SAICAr in the cases of severe disease., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: To quantify and examine the distribution of brain metabolites in normal young adults using single voxel MR spectroscopy at 3 Tesla (T)., Materials and Methods: Short-echo time single-voxel PRESS technique was used to measure the apparent concentration of five metabolites at nine locations in the brains of young adults. Concentrations were estimated by means of an automated fitting method (LCModel) with reference to an unsuppressed water signal and were corrected for T(1) relaxation, T(2) relaxation, and cerebrospinal fluid partial volume. Analysis of variance with Tukey post hoc test was used to evaluate regional variations., Results: Statistically significant differences in regional concentrations were detected for each of the metabolites. The number of significant differences was greatest for total choline, whereas myo-inositol and the sum of glutamine and glutamate had the fewest. Magnitude of variation was greatest for total choline and least for the sum of N-acetyl aspartate and N-acetylaspartylglutamate., Conclusion: In agreement with previous studies at other field strengths, we found heterogeneous distribution of the major spectroscopically measurable brain metabolites. Although the most distinct differences are between tissue types, there is appreciable variation within a tissue type at different locations. The spectra and metabolite concentrations presented should provide a useful reference for both clinical and research MR spectroscopy studies performed at 3T.

Purpose: To investigate whether in vivo proton magnetic resonance spectroscopic imaging (MRSI) can differentiate between 1) tumors and nonneoplastic brain lesions, and 2) high- and low-grade tumors in children., Materials and Methods: Thirty-two children (20 males and 12 females, mean age = 10 +/- 5 years) with primary brain lesions were evaluated retrospectively. Nineteen patients had a neuropathologically confirmed brain tumor, and 13 patients had a benign lesion. Multislice proton MRSI was performed at TE = 280 msec. Ratios of N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr were evaluated in the lesion and the contralateral hemisphere. Normalized lesion peak areas (Cho(norm), Cr(norm), and NAA(norm)) expressed relative to the contralateral hemisphere were also calculated. Discriminant function analysis was used for statistical evaluation., Results: Considering all possible combinations of metabolite ratios, the best discriminant function to differentiate between nonneoplastic lesions and brain tumors was found to include only the ratio of Cho/Cr (Wilks' lambda, P = 0.012; 78.1% of original grouped cases correctly classified). The best discriminant function to differentiate between high- and low-grade tumors included the ratios of NAA/Cr and Cho(norm) (Wilks' lambda, P = 0.001; 89.5% of original grouped cases correctly classified). Cr levels in low-grade tumors were slightly lower than or comparable to control regions and ranged from 53% to 165% of the control values in high-grade tumors., Conclusion: Proton MRSI may have a promising role in differentiating pediatric brain lesions, and an important diagnostic value, particularly for inoperable or inaccessible lesions., (Published 2005 Wiley-Liss, Inc.)

Purpose: To evaluate variations in regional metabolite concentrations in the anterior mesial temporal lobe (ATL), and compare metabolite concentrations between the allocortex and neocortex using quantitative proton MR spectroscopic imaging (MRSI)., Materials and Methods: Metabolite concentrations and ratios were measured in 20 healthy young subjects with the use of a multislice spin-echo (SE) sequence (TR/TE=2300/280 msec). Quantitation of MRSI data was performed by means of the phantom replacement methodology., Results: The highest choline (Cho) concentration (4.1 +/- 1.1 mM) was found in the ATL (P=0.0015 compared to the middle mesial temporal lobe (MTL), and P=0.0008 compared to the posterior mesial temporal lobe (PTL)). The ATL also had a higher Cho/creatine (Cr) ratio and a lower N-acetyl aspartate (NAA)/Cho ratio compared to other examined regions (P <0.0001 and P < or = 0.052, respectively). In the allocortical regions, the average Cho concentration (3.5 +/- 0.8 mM) was 68% higher, and the NAA concentration (9.5 +/- 1.8 mM) was 13% lower than in the neocortex (P <10(-6) and P <0.008, respectively). Cho/Cr was 64% higher, NAA/Cr 14% lower, and NAA/Cho 47% lower in the allocortex than in the neocortex (P <10(-6), P=0.013, and P <10(-6), respectively)., Conclusion: The mesial temporal lobe shows high levels of Cho, which presumably reflect a difference in cellular composition between the allocortex and neocortex. Regional metabolite variations must be considered when pathological conditions involving the mesial temporal lobe are evaluated.

Normally, ventricular cerebrospinal fluid (CSF) contains low levels of all metabolite signals on proton magnetic resonance spectroscopic imaging (MRSI). We present here three cases (two with seizure disorders, one with a central nervous system lymphoma) who presented with unusually elevated CSF signals on MRSI. Based on chemical shifts and in vitro studies (in one case), the signals were assigned to propan-1,2-diol (PD), acetone, and lactate, respectively. These compounds were either exclusively, or more readily, detected in CSF than in brain. Proton MRSI conveniently screens both brain and CSF for abnormal metabolism simultaneously., (Copyright 2004 Wiley-Liss, Inc.)

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., (Copyright 2003 Wiley-Liss, Inc.)

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.

A variety of lesions may present as intraventricular masses in children. We report quantitative proton magnetic resonance spectroscopy (MRS) of two intraventricular tumors of the choroid plexus: choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP). Both lesions were characterized by high levels of choline-containing compounds and a complete absence of creatine and the neuronal/axonal marker N-acetyl aspartate. The CPC showed higher levels of choline compared to the CPP, and it also had elevated lactate. These preliminary results, if confirmed in a larger cohort of patients, indicate that proton MRS may have a role in the presurgical diagnosis of choroid plexus tumors in children, which may also have important implications for therapy and prognosis., (Copyright 2001 Wiley-Liss, Inc.)