Proton MR spectroscopic imaging of the striatum in Parkinson's disease

doi:10.1016/S0730-725X(97)00079-9

Magnetic Resonance Imaging

Volume 15, Issue 6, 1997, Pages 619-624

https://doi.org/10.1016/S0730-725X(97)00079-9 Get rights and content

Abstract

Assess the feasibility of proton MR spectroscopic imaging (¹H-MRSI) of the striatum (putamen and caudate nucleus) in patients with Parkinson's disease and evaluate striatal neuronal density. Proton MRSI of the striatum and thalamus with 2 cc spatial resolution was performed in 10 patients with Parkinson's disease, 1 patient with atypical parkinsonism, and 13 control subjects. Single voxel proton MR spectra with signals from choline metabolites (Cho), creatine metabolites (Cr), and the putative neuronal marker, N-acetylaspartate (NAA), were obtained from the putamen and thalamus, but not the caudate nucleus, of patients with parkinsonism and control subjects. Metabolite ratios in controls and patients were: in putamen NAA/Cho 1.70 ± 0.25 vrs 1.74 ± 0.32, NAA/Cr 2.80 ± 0.79 vrs 2.36 ± 0.42, Cho/Cr 1.63 ± 0.25 vrs 1.39 ± 0.3; in thalamus, NAA/Cho 1.78 ± 0.15 vrs 1.62 ± 0.22, NAA/Cr 2.78 ± 0.34 vrs 2.64 ± 0.41, Cho/Cr 1.57 ± 0.25 vrs 1.65 ± 0.28. There were no statistically significant differences between patients and controls. The putaminal NAA/Cho ratio of the single subject with atypical parkinsonism was lower than that of 9 of the 10 patients with classic Parkinson's disease and 11 of the 13 control subjects. Likewise, the putaminal NAA/Cr ratio in the single subject with atypical parkinsonism was lower than that of 7 of the patients with Parkinson's disease and 10 of the 13 control subjects. Proton MRSI, which allows retrospective imageguided selection of spectra from very smail brain volumes, is a technique that can be used to evaluate neuronal density in individual subcortical gray nuclei in the brains of patients with parkinsonism. Using this technique, we have shown that Parkinson's disease produces no change in relative levels of the neuronal marker, NAA, in the putamen.

References (34)

A.A. Maudsley et al.
Spatially resolved high resolution spectroscopy by “four dimensional” NMR
J. Magn. Reson.
(1983)
P. Christiansen et al.
The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium
Magn. Reson. Imaging
(1993)
A.A. Maudsley et al.
Spectroscopic imaging display and analysis
Magn. Reson. Imaging
(1992)
A.E. Kan
Striatonigral degeneration
Pathology
(1978)
E.G. Spokes et al.
Multiple system atrophy with autonomic failure: Clinical, histological and neurochemical observations on four cases
J. Neurol. Sci.
(1979)
C.W. Olanow
Magnetic resonance imaging in parkinsonism
Neurol. Clin.
(1992)
D. Eidelberg
Positron emission tomography studies in parkinsonism
Neurol. Clin.
(1992)
N. Quinn
Multiple system atrophy—the nature of the beast
J. Neurol. Neurosurg. Psychiatry special supplement
(1989)
T.R. Brown et al.
NMR chemical shift imaging in three dimensions
R.I. Grossman et al.
MR proton spectroscopy in multiple sclerosis
AJNR
(1992)

P.M. Matthews et al.

Proton magnetic resonance spectroscopy for metabolic characterization of plaques in multiple sclerosis [published erratum appears in Neurology 1991 Nov; 41 (11): 1828]

Neurology

(1991)

T.L. Richards

Proton MR spectroscopy in multiple sclerosis: Value in establishing diagnosis, monitoring progression, and evaluating therapy

AJR

(1991)

P. Gideon et al.

Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study

Stroke

(1992)

J.H. Duijn et al.

Human brain infarction: proton MR spectroscopy

Radiology

(1992)

S.R. Felber et al.

Combined magnetic resonance imaging and proton magnetic resonance spectroscopy of patients with acute stroke

Stroke

(1992)

M.D. Sappey et al.

Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities

Magn. Reson. Med.

(1992)

D.K. Menon et al.

Proton MR spectroscopy and imaging of the brain in AIDS: evidence of neuronal loss in regions that appear normal with imaging

J. Comput. Assist. Tomogr.

(1990)

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The in vivo differential diagnosis between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (PS), such as multiple system atrophy [MSA with a cerebellar (C) and parkinsonian (P) subtype] and progressive supranuclear palsy – Richardson's Syndrome (PSP-RS) is often challenging. Previous brain MR proton spectroscopy (¹H-MRS) studies showed biochemical alterations in PS, despite results are conflicting. Cerebellum plays a central role in motor control and its alterations has been already demonstrated in atypical PS. The main aim of this study was to evaluate diagnostic accuracy of cerebellar ¹H-MRS in the differential diagnosis between PD and atypical PS.
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Previous studies on PD found abnormal 1H-MRS spectra, by using long TE, in basal ganglia compared with control subjects [5–6,21–23,26–28]. However, no significant differences in metabolite profile between PD patients and control subjects, either in terms of metabolite ratios [29–30] or absolute concentrations [26,31], have also been reported. Many researchers showed significant changes of NAA and other metabolite levels in cortical regions involved in striatal circuit.
The aim of this study was to assess metabolic changes in the motor cortex in de novo Parkinson’s disease (PD) patients before and after therapy with ropinirole. Twenty de novo drug-naïve PD patients and 15 healthy controls underwent conventional magnetic resonance imaging and proton magnetic resonance spectroscopy imaging (¹H-MRSI). The resonance intensities of N-acetylaspartate (NAA) and choline (Cho) were normalized for the resonance intensities of creatine (Cr). At baseline, lower NAA/Cr and NAA/Cho ratios and higher Cho/Cr ratios were found in the motor cortex of PD patients compared with controls (p < 0.001). Ten months after ropinirole treatment, PD patients showed a significant clinical improvement in the UPDRS motor sub-scores (p < 0.001) and an increase of NAA/Cr and NAA/Cho ratios (p < 0.006 and p = 0.01, respectively). A highly significant correlation between NAA/Cr and NAA/Cho ratios and UPDRS motor sub-scores was observed (r = −0.981 and r = −0.983, respectively). We could argue that the ropinirole efficacy to improve the motor performances is the result of partial restoration of neuronal functions, due to the increase of NAA in motor cortex.
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However, some conflicting results have been reported in the clinical and preclinical PD research. Two clinical studies did not show any difference in NAA/Cr and NAA/Cho ratios between patients with PD and controls [49,50], and two preclinical studies observed no significant decreases in the NAA/Cr ratio in the striatum of MPTP-treated mice [29,30]. Another 1H-MRS study detected a lactate peak as an inverted doublet pattern at 1.33 ppm in all MPTP-treated cats, but not in the control or the pargyline+MPTP cats [46].
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication.
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Simultaneous determination method of N-acetyl-l-aspartyl-l-glutamate (NAAG), an endogenous agonist at type3 metabotropic glutamate receptor, and its degradation product, N-acetyl-l-aspartate (NAA) was developed by using reversed-phase high-performance liquid chromatography (HPLC) with pre-column fluorescence derivatization using 4-N,N-dimethylaminosulfonyl-7-N-(2-aminoethyl)amino-2,1,3-benzoxadiazole. The detection limits of NAAG and NAA were approximately 12 and 34 fmol on the column, respectively (signal to noise ratio 3). The proposed HPLC method was applied to determine NAAG and NAA simultaneously in the rat brain homogenate. Both concentrations of NAAG and NAA in the male rat cerebrum (13 weeks old) were 5.7 ± 0.30 and 2.1 × 10² ± 9.2 nmol/mg protein, respectively (n = 6), while those in the hippocampus were 6.8 ± 0.48 and 1.9 × 10² ± 8.5 nmol/mg protein, respectively (n = 5). Hippocampal NAA concentration was significantly increased in the ketamine-treated rats as compared to the control rats (p < 0.01).
Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease
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In this regard, imaging research activities for PD have focused on finding better means to assess nigrostriatal degeneration. Functional imaging including single photon emission computerized tomography (Benamer et al., 2000), positron emission tomography (Eidelberg et al., 1995; Morrish et al., 1996), proton magnetic resonance spectroscopic imaging (1H MRSI) (Cruz et al., 1997; Boska et al., 2005), and functional magnetic resonance imaging (Ceballos-Baumann, 2003) have all proved promising but not definitive. One promising and new approach that has gained attention for tracking age-related changes in human brain and for the diagnosis of neurodegenerative diseases is magnetic resonance diffusion tensor imaging (DTI) (McGraw et al., 2005).
Early diagnosis of Parkinson’s disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect > 50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p < 0.005) and decreased fractional anisotropy (p < 0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p ≤ 0.002) and correlated with the numbers of SN dopaminergic neurons (r = − 0.75, p = 0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.
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Phospholipase A₂ catalyzes the hydrolysis of membrane glycerophospholipids leading to the production of metabolites observable by both ¹H and ³¹P magnetic resonance spectroscopy. The signal of choline-containing compounds (Cho) observed by ¹H magnetic resonance spectroscopy is constituted of metabolites of phosphatidylcholine, especially phosphocholine (PCho) and glycerophosphocholine (GPCho). The phosphomonoester (PME) and phosphodiester (PDE) signals observed by ³¹P magnetic resonance spectroscopy are, respectively, precursors and catabolites of phospholipids. A large number of brain diseases have been reported to cause variations in the intensity of the Cho, PME and PDE signals. Changes in the activity of phospholipase A₂ have been measured in many brain diseases. In this review, the relationships between the results of ¹H and ³¹P magnetic resonance spectroscopy and the phospholipase A₂ assays are analyzed. In many brain diseases, the variation in the Cho signal intensity can be correlated with a stimulation or inhibition of the phospholipase A₂ activity.

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Original contributionProton MR spectroscopic imaging of the striatum in Parkinson's disease

Abstract

J. Magn. Reson.

Magn. Reson. Imaging

Magn. Reson. Imaging

Pathology

J. Neurol. Sci.

Neurol. Clin.

Neurol. Clin.

Multiple system atrophy—the nature of the beast

J. Neurol. Neurosurg. Psychiatry special supplement

NMR chemical shift imaging in three dimensions

MR proton spectroscopy in multiple sclerosis

AJNR

Proton magnetic resonance spectroscopy for metabolic characterization of plaques in multiple sclerosis [published erratum appears in Neurology 1991 Nov; 41 (11): 1828]

Neurology

Proton MR spectroscopy in multiple sclerosis: Value in establishing diagnosis, monitoring progression, and evaluating therapy

AJR

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Stroke

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Radiology

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Proton MR spectroscopy and imaging of the brain in AIDS: evidence of neuronal loss in regions that appear normal with imaging

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Original contribution
Proton MR spectroscopic imaging of the striatum in Parkinson's disease