<sup>1</sup>H and <sup>31</sup>P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders

Knaap, Marjo S. van der; Grond, Jeroen van der; Luyten, Peter R.; Hollander, Jan A. den; Nauta, J. J. P.; Valk, Jacob

doi:10.1002/ana.410310211

Cited by 101 publications

(33 citation statements)

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“…The PME multicomponent comprises predominantly phosphoethanolamine and phosphocholine, as well as precursor and breakdown products of membrane PL. It is regarded as representing mainly the anabolic activity of PL (35). PDE consists of glycerol-3-phosphoethanolamine and -choline, as well as mobile PL, phosphorylized glycolipids, and glycoproteins.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Energy Metabolism in Phenylketonuria: Findings by Quantitative In Vivo 31P MR Spectroscopy

et al. 2003

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Both severe impairments of brain development in untreated infants and acute reversible neurotoxic effects on brain function are clinical features of phenylketonuria (PKU). For determining whether impairments of cerebral energy metabolism play a role in the pathophysiology of PKU, quantitative in vivo 31 P magnetic resonance spectroscopy (MRS) was performed in a supratentorial voxel of 11 adult PKU patients and controls. Peak areas of inorganic phosphate; phosphocreatine; ␣-, ␤-, and ␥-ATP; NAD; phosphomonoesters; phosphodiesters; and a broad phospholipid signal were converted to millimolar concentrations. Mg 2ϩ , pH, ADP, the phosphorylation potential, and the relative velocity of oxidative metabolism V/V max were derived. Clinical evaluation included mutation analysis, neurologic investigation, intelligence testing, magnetic resonance imaging, and concurrent plasma and brain phenylalanine (Phe), the last by 1 H-MRS. Phe loading was performed in five patients with an oral dose of 100 mg/kg body wt L-Phe monitored by spectral EEG analysis. Under steadystate conditions, 31 P-MRS revealed normal values for ATP, phosphocreatine, NAD, phosphomonoesters, phosphodiesters, Mg 2ϩ , and pH in PKU. ADP (ϩ11%) and the phosphorylation potential (ϩ22%) were increased. Peak areas of inorganic phosphate (Ϫ22%) and phospholipid (Ϫ8%) were decreased. ADP correlated with concurrent plasma (r ϭ 0.65) and brain (r ϭ 0.55) Phe. During the Phe load, blood Phe levels increased steeply.EEG revealed slowing of background activity. The phosphorylation potential decreased, whereas ADP and V/V max increased. In vivo31 P-MRS demonstrated subtle abnormalities of cerebral energy metabolism in PKU in steady-state conditions that were accentuated by a Phe load, indicating a link between Phe neurotoxicity and imbalances of cerebral energy metabolism. Abbreviations 1 H-MRS, proton magnetic resonance spectroscopy IDC, index of dietary control MPF, mean power frequency MRI, magnetic resonance imaging P I , inorganic phosphate PAH, phenylalanine hydroxylase PCr, phosphocreatine PDE, phosphodiesters Phe, phenylalanine PL, phospholipids PME, phosphomonoesters 31 P-MRS, phosphorus-31 magnetic resonance spectroscopy PKU, phenylketonuria PP, phosphorylation potential Phenylketonuria (PKU) is the most frequent inborn disorder of amino acid metabolism. PKU is caused by an autosomal recessively transmitted deficiency of hepatic phenylalanine (Phe) hydroxylase (PAH; enzyme commission 1.14.16.1). In untreated PKU patients, Phe accumulates to plasma levels exceeding 1500 M; normal plasma Phe in fasting adults is 60 M. The characteristics of untreated PKU result from disturbed brain development and include microcephaly, epilepsy, severe mental retardation, and behavior problems (1).Through the early start of a Phe-restricted diet, the phenotype of untreated PKU can be widely prevented. However, elevated plasma concentrations of Phe, which usually occur in adolescence because of a relaxed diet, are known to cause acute impairments of brain function. Reduced atten...

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Section: Discussionmentioning

confidence: 99%

Cerebral Energy Metabolism in Phenylketonuria: Findings by Quantitative In Vivo 31P MR Spectroscopy

et al. 2003

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“…94 Increased PME levels have been observed in the neonate brain, tumors, 36,107 and the regenerating liver. 108 In contrast, decreased PME levels, possibly reflecting a stagnation or halt of membrane synthesis, have been associated with chronic cerebral infarction, 35 severe demyelinating disorders, 12 anorexia nervosa, 109 and schizophrenia (particularly the negative symptoms thereof). 110,111 In consideration of the previously noted 1 H MRS findings of increased Cho and mI in bipolar subjects, it is important to recognize the partial inclusion of these metabolites within the PME peak.…”

Section: Impaired Phospholipid Metabolism In Bipolar Disordermentioning

confidence: 99%

“…In this way, NAA is hypothesized to play an integral role in the energetics of neuronal mitochondria ( Figure 2). 11 Consequently, although reductions in NAA concentration were formerly thought to indicate neuronal death, 12 recent research has suggested that decreased levels of NAA are more accurately consistent with impaired mitochondrial energy production. 8,13 For example, although traumatic brain injury (TBI) is associated with immediate reductions in NAA, several studies have reported that these levels appear to recover significantly with time, which could not occur if NAA levels were decreased by cell death alone.…”

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confidence: 99%

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

2005

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Magnetic resonance spectroscopy (MRS) affords a noninvasive window on in vivo brain chemistry and, as such, provides a unique opportunity to gain insight into the biochemical pathology of bipolar disorder. Studies utilizing proton ( 1 H) MRS have identified changes in cerebral concentrations of N-acetyl aspartate, glutamate/glutamine, choline-containing compounds, myo-inositol, and lactate in bipolar subjects compared to normal controls, while studies using phosphorus ( 31 P) MRS have examined additional alterations in levels of phosphocreatine, phosphomonoesters, and intracellular pH. We hypothesize that the majority of MRS findings in bipolar subjects can be fit into a more cohesive bioenergetic and neurochemical model of bipolar illness that is both novel and yet in concordance with findings from complementary methodological approaches. In this review, we propose a hypothesis of mitochondrial dysfunction in bipolar disorder that involves impaired oxidative phosphorylation, a resultant shift toward glycolytic energy production, a decrease in total energy production and/or substrate availability, and altered phospholipid metabolism. Molecular Psychiatry (2005) 10, 900-919.

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“…Previous studies have linked lowered NAA/Cr ratios to neuronal loss and decline in intellectual functioning. 10,13,17,18 Therefore, the lowered NAA/Cr ratio in MC is suggestive of significant neuronal loss in the region examined. There is no indication in MC's developmental history of any event other than lead exposure that would result in loss of brain neurons.…”

mentioning

confidence: 92%

“…16 The decrease in NAA is measured relative to the level of creatine, a stable metabolite that shows practically no change after neuronal loss. Van der Knapp et al 17 demonstrated that increased cerebral atrophy was accompanied by lower ratios of NAA to creatine (Cr) in patients with demyelination disorders. Applying the technique to children, Kimura and colleagues 18 reported abnormally low NAA/Cr ratios in neurologically delayed infants compared with children with no known developmental delays, and Grodd and coworkers 19 reported a marked decrease of NAA in children with focal or generalized demyelination.…”

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confidence: 99%

Magnetic Resonance Imaging and Spectroscopy of Regional Brain Structure in a 10-Year-Old Boy With Elevated Blood Lead Levels

1998

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ABSTRACT. Objective. The effects of elevated blood lead levels on the development of children have been examined only in the context of behavioral and neuropsychological evaluations. No studies have examined the effects of lead on brain metabolism in vivo or on structural and/or functional correlates of brain function in children. In the human brain, magnetic resonance spectroscopy (MRS) provides a noninvasive, risk-free method to monitor the biochemistry of acute and chronic stages of disease. The purpose of this study was to examine in vivo the use of MRS for the evaluation of the neurotoxic effects of lead on the nervous system, by detection of brain metabolism, especially N-acetylaspartate, a metabolite shown to decrease in processes that involve neuronal loss.Methodology. Two male cousins who live in the same household and share the same socioeconomic background and home environment were studied. The subject, a 10-year-old boy, had elevated blood lead levels. His cousin, a 9-year-old boy, was not exposed to lead. Both underwent a comprehensive neuropsychological evaluation and both were evaluated using the magnetic resonance imaging (MRI) and MRS at the University of Pennsylvania Medical Center. High-resolution MRI and MRS were performed using a 3-in surface coil. Localized proton spectra were obtained from contiguous 6 ؋ 6 ؋ 10-mm voxels using one-dimensional phase encoding, with a 2000-millisecond repetition time and a 31-millisecond echo time.Results. Neuropsychological evaluation demonstrated areas of impairment in the lead-exposed child, including difficulties in academic skills of reading, writing, and arithmetic, as well as deficient linguistic skills and attentional mechanism. By contrast, studies of the cousin, who was not exposed to lead, showed overall neuropsychological functioning within normal limits. Although both children had a normal MRI examination of the brain, studies of the lead-exposed boy showed a significant alteration in brain metabolites, with a reduction in the N-acetylaspartate:creatine ratio for both gray and white matter on the MRS examination, compared with his cousin.Conclusions. The present study is a first attempt to determine in vivo metabolic differences in the brain of a child exposed to lead compared with a healthy control subject. This is a unique case because these children were matched on a number of variables usually regarded as confounders in behavioral lead studies, and therefore can be regarded as matched controls. The present study demonstrates that MRS is a feasible, noninvasive technique for in vivo examination of the brains of children exposed to lead. We were able to obtain high-quality spectra from voxels as small as 0.36 cm at 1.5T. The spatial resolution used in the present study is sufficient to obtain spectra from voxels almost exclusively composed of gray matter. The one-dimensional phase-encoding approach used presents the advantage of obtaining several spectra simultaneously in a relatively short time. The present study has allowed us to examine the ...

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¹H and ³¹P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders

Cited by 101 publications

References 32 publications

Cerebral Energy Metabolism in Phenylketonuria: Findings by Quantitative In Vivo 31P MR Spectroscopy

Cerebral Energy Metabolism in Phenylketonuria: Findings by Quantitative In Vivo 31P MR Spectroscopy

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

Magnetic Resonance Imaging and Spectroscopy of Regional Brain Structure in a 10-Year-Old Boy With Elevated Blood Lead Levels

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1H and 31P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders

Cited by 101 publications

References 32 publications

Cerebral Energy Metabolism in Phenylketonuria: Findings by Quantitative In Vivo 31P MR Spectroscopy

Cerebral Energy Metabolism in Phenylketonuria: Findings by Quantitative In Vivo 31P MR Spectroscopy

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

Magnetic Resonance Imaging and Spectroscopy of Regional Brain Structure in a 10-Year-Old Boy With Elevated Blood Lead Levels

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¹H and ³¹P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders