Probable Alzheimer disease: diagnosis with proton MR spectroscopy.

Shonk, Truda; Moats, Rex; Gifford, P; Michaelis, Thomas; Mandigo, Jennifer C.; Izumi, Junichi; Ross, B D

doi:10.1148/radiology.195.1.7892497

Cited by 280 publications

(191 citation statements)

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“…Their advocates assume that due to the lack of detectable metabolites in the CSF (12,13), except for lactate, the effect of CSF contamination is simply to dilute all the concentrations by the same factor.…”

Section: Discussionmentioning

confidence: 99%

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

Guerrini

Belli

Mazzoni

et al. 2009

Magnetic Resonance Imaging

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Purpose:To investigate the impact of cerebrospinal fluid (CSF) contamination on metabolite evaluation in the superior cerebellar vermis with single-voxel 1 H-MRS in normal subjects and patients with degenerative ataxias. Materials and Methods:Twenty-nine healthy volunteers and 38 patients with degenerative ataxias and cerebellar atrophy were examined on a 1.5 Tesla scanner. Proton spectra of a volume of interest placed in the superior vermis were acquired using a four TE PRESS technique. We calculated N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and NAA/Cho ratios, T 2 relaxation times and concentrations of the same metabolites using the external phantom method. Finally, concentrations were corrected taking into account the proportion of nervous tissue and CSF, that was determined as Volume Fraction (VF). Results:In healthy subjects, a significant difference was observed between metabolite concentrations with and without correction for VF. As compared to controls, patients with ataxias showed significantly reduced NAA/Cr and NAA concentrations, while only corrected Cr concentration was significantly increased. The latter showed an inverse correlation with VF. Conclusion:CSF contamination has a not negligible effect on the estimation of brain metabolites. The increase of Cr concentration in patients with cerebellar atrophy presumably reflects the substitutive gliosis which takes place along with loss of neurons. EVALUATION IN VIVO of the amount of the brain metabolites with proton MR spectroscopy ( 1 H-MRS) is an important clinical tool in several diseases (1). This can be accomplished using a semiquantitative approach, in which metabolite ratios are computed by assuming that a reference metabolite, usually creatine (Cr), is constant, or using a quantitative approach in which the concentration of each brain metabolite is determined with several different techniques. These include external phantoms, reference to water signal, and compartmental analysis (2).A controversial issue in clinical 1 H-MRS of the brain is the evaluation of spectra obtained from volume of interest (VOI) containing cerebrospinal fluid (CSF). In particular, it is unclear the relevance of correction for the CSF contained in the VOI. In a prior study corrections from CSF inclusion were found to decrease the coefficient of variation of spectral data acquired in the hippocampus (3).The peripheral cerebellum is a region particularly suited to investigate the impact of CSF contamination on metabolite assessment. In fact, because of the thinness of the cerebellar folia, spectra of the peripheral cerebellum contain variable amounts of nervous tissue and CSF also in normal subjects. While spectra from the cerebellar hemispheres can be of suboptimal quality due to difficult shimming caused by the nearby skull and blood flow in the venous dural sinuses, good quality spectra are consistently obtained when the VOI is placed in the superior vermis (4).To investigate the impact of CSF contamination on the metabolite evaluation we examined the c...

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Section: Discussionmentioning

confidence: 99%

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

Guerrini

Belli

Mazzoni

et al. 2009

Magnetic Resonance Imaging

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“…Alzheimer disease-A reasonable working hypothesis, subsequently confirmed in myriad studies, suggests that regional reductions in NAA concentration and NAA-creatine ratio are to be found in individual patients and in patient groups who test positive for clinical dementia. Patients with Alzheimer disease consistently show a 15-20% reduction in NAA/Cr (or NAA concentration) in posterior cingulate gyrus gray matter Moats et al, 1994;Shonk et al, 1995;Waldman et al, 2002). The gray matter in the region of the posterior cingulate gyrus has been found to be the most reliable for the diagnosis of this and other dementias, rather than hippocampus, the region selected for PET diagnosis, and postmortem histological examination of Alzheimer disease.…”

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,209

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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“…NAA decreases in a variety of neurological disorders including AD. [17][18][19][20][21] The decrease of NAA or the NAA/creatine (Cr) ratio shows a regional variation in AD. [22][23][24] In patients with mild to moderate AD, NAA/Cr levels are lower than normal in the posterior cingulate gyrus, whereas they are normal in the medial occipital lobe, including in the visual cortex.…”

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confidence: 99%

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

Kantarci

Jack

2004

Neurotherapeutics

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Summary: Recent advances in understanding the molecular biology of Alzheimer's disease (AD) offer the promise of useful therapeutic intervention in the foreseeable future. Hence, improved methods for early diagnosis and noninvasive surrogates of disease severity in AD have become more imperative. Various quantitative magnetic resonance (MR) techniques that measure the anatomic, biochemical, microstructural, functional, and blood-flow changes are being evaluated as possible surrogate measures of disease progression. Cross-sectional and longitudinal studies indicate that MR-based volume measurements are potential surrogates of disease progression in AD, starting from the preclinical stages. The validity of MR-based volumetry as a surrogate marker for therapeutic efficacy in AD remains to be tested in a positive disease-modifying drug trial. Recent development of amyloid imaging tracers for positron emission tomography has been a major breakthrough in the field of imaging markers for AD. Efforts to image plaques are also underway in MR imaging. As with indirect MR measures, these approaches of directly imaging the pathological substrate will need to undergo a validation process with longitudinal studies to prove their usefulness as surrogate markers in AD.

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Probable Alzheimer disease: diagnosis with proton MR spectroscopy.

Abstract: Hydrogen-1 MR spectroscopy enables identification of mild to moderate AD with a specificity and sensitivity that suggest clinical utility.

Cited by 280 publications

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Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

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Probable Alzheimer disease: diagnosis with proton MR spectroscopy.

Abstract: Hydrogen-1 MR spectroscopy enables identification of mild to moderate AD with a specificity and sensitivity that suggest clinical utility.

Cited by 280 publications

References 0 publications

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

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Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias