Proton magnetic resonance spectroscopy imaging of the brain in childhood autism

Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, Los Angeles, California, USA.
Biological Psychiatry (Impact Factor: 10.26). 01/2004; 54(12):1355-66. DOI: 10.1016/S0006-3223(03)00688-7
Source: PubMed


Autism is a developmental disorder of unknown neurologic basis. Based on prior work, we used proton magnetic resonance spectroscopic imaging ((1)H- MRSI) to investigate brain structures, including cingulate and caudate, that we hypothesized would reveal metabolic abnormalities in subjects with autism.
In 22 children with autism, 5 to 16 years old, and 20 age-matched healthy control subjects, (1)H-MRSI assessed levels of N-acetyl compounds (NAA), choline compounds (Cho), and creatine plus phosphocreatine (Cr) at 272 msec echo-time and 1.5 T.
In subjects with autism compared with control subjects, Cho was 27.2% lower in left inferior anterior cingulate and 19.1% higher in the head of the right caudate nucleus; Cr was 21.1% higher in the head of the right caudate nucleus, but lower in the body of the left caudate nucleus (17.9%) and right occipital cortex (16.6%).
Results are consistent with altered membrane metabolism, altered energetic metabolism, or both in the left anterior cingulate gyrus, both caudate nuclei, and right occipital cortex in subjects with autism compared with control subjects.

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    • "Lethargy-social withdrawal score exhibited a negative correlation with the Ch/Cr ratio in the left ACG. There is a growing mass of evidence indicating a relationship between autism, and functional and structural ACG abnormalities [2]. Asperger syndrome has shown a correlation between raised prefrontal NAA and obsessive behaviors, and between raised prefrontal cholin level and reduced social functions [6]. "
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    ABSTRACT: To investigate any relation of behavior problems with cranial Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy (MRS) findings in autism spectrum disorders. A total of 20 males children (12 autistic patients and 8 healthy controls) was examined by cranial DTI and MRS. The Aberrant Behavior Checklist (ABC) was used to calculate the irritability, lethargy-social withdrawal, stereotypic behavior, hyperactivity, and speech disorder scores for each patient. The results of MRS and DTI were evaluated together with the ABC scores. Fractional anisotropy (FA) values demonstrated significant decreases in the left frontoparietal white matter, anterior limb of the right internal capsule, and left middle cerebellar peduncle as the behavior problem scores elevated (P < 0.05). With the exception of social withdrawal, as the behavior problem scores increased, metabolite levels increased, as well. The positive correlation between the MRS findings, behavior problem scores, and metabolite levels suggests the presence of a dysfunction leading to hypo and hyper neuronal function in various locations. Reduced FA values in DTI and negative correlation of behavior problems with FA values in the contralateral hemisphere, may indicate reduced myelination and abnormal axonal organization.
    International Journal of Clinical and Experimental Medicine 07/2015; 8(4):5621-30. · 1.28 Impact Factor
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    • "Previous studies investigating the thalamic metabolite concentrations in autism have presented conflicting results. Our results are concordant with one study that examined the metabolite concentrations of thalamus in children and adolescents (age range 5-16 years) with autism and reported no significant chemical abnormalities.18 Friedman et al.19 found significantly reduced NAA concentrations in the right, and reduced Cre and Cho concentrations in the left thalamus in a group of very young children with autism. "
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    ABSTRACT: Objective Thalamic abnormalities have been reported in people with pervasive developmental disorders (PDD) including Asperger's Disorder (ASP). The aim of the present study was to compare the volume and volume fraction of the thalamus and the metabolite concentrations in children and adolescents with ASP using the magnetic resonance imaging and proton magnetic resonance spectroscopy. Additionally, the relationships between thalamic abnormalities and clinical features were examined. Methods Volume and volume fractional and metabolic measurements of bilateral thalamus were collected from 15 boys with ASP with a total IQ over 70 (age range 7-18 years, mean age 11.6±3.79 years), and 15 healthy controls matching age, sex and IQ. The thalamic volumes, hemisphere volumes and total brain volumes (TBV) were estimated using the stereological methods on magnetic resonance images. Chemical metabolites of thalamus were evaluated by 1H spectroscopy. Results No differences in thalamic volumes, volume fractions and metabolites were observed between the groups. There were significant correlation between thalamic volume and total brain volume in both groups. The ASP group showed a significant left-minus-right thalamus difference as well as a significantly greater laterality index. In addition, a significant correlation between the laterality index and Autism Behavior Checklist language scores was observed. Conclusion Findings from this investigation point to a significant increase in laterality of the thalamus and a relationship with language problems in individuals with ASP. Our findings suggest that thalamic abnormalities may be related to mild language problems observed in ASP.
    Psychiatry investigation 07/2014; 11(3):237-42. DOI:10.4306/pi.2014.11.3.237 · 1.28 Impact Factor
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    • "Cr reduction in left frontal WM, left thalamus, left insula, anterior corpus callosum, left parietal WM Levitt et al., 2003 Autism = "
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    ABSTRACT: Proton magnetic resonance spectroscopy ((1) H-MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals with Autism Spectrum Disorders (ASD). Findings to date suggest ASD is associated with widespread reduction in N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol (mI), and glutamate plus glutamine plus gamma-Aminobutyric Acid (Glx); however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region-of-interest. Widespread reduction of NAA, Cr, Cho, mI, and Glx in ASD likely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate (1) H-MRS findings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between (1) H-MRS metabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated with ASD. Furthermore, more longitudinal (1) H-MRS studies are needed in both control and ASD subjects to attempt to standardize metabolite levels across different developmental periods in well-defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral-editing techniques capable of quantifying less-concentrated metabolites, (1) H-MRS will continue to be an important tool in ASD research. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 04/2013; 6(2). DOI:10.1002/aur.1273 · 4.33 Impact Factor
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