François Nicoli

Metabolic Counterpart of Decreased Apparent Diffusion Coefficient During Hyperacute Ischemic Stroke: A Brain Proton Magnetic Resonance Spectroscopic Imaging Study

Background and Purpose— Recent studies have shown that the brain ischemic area defined by the map of decreased apparent diffusion coefficient (ADC) obtained by diffusion-weighted imaging (DWI) during the first hours of ischemic stroke includes a significant part of ischemic penumbra. We hypothesize that the misjudgment of the final infarct size by ADC mapping may be related to a restricted ability of DWI to capture variations in the intensity of cellular suffering. In an attempt to characterize metabolically the hypoperfused brain parenchyma, we studied the relationship between ADC values and brain metabolic parameters measured by proton MR spectroscopic imaging (SI). Methods— Six patients with hyperacute ischemic stroke were explored within the first 7 hours after onset with the use of a MR protocol including T2*-weighted MRI, DWI, SI, perfusion-weighted imaging, and MR angiography. Results— This study demonstrates, for the first time, a wide gradient of ischemia-related metabolic anomalies within the abnormal area delineated by DWI during hyperacute ischemic stroke. In the narrow range of decreased mean ADC values (0.60 to 0.40×10−9 m2 · s−1), a 33% decrease in mean ADC is associated with a 122% increase in lactate/ N-acetyl aspartate ratio. Mean ADC values never fall below 0.40×10−9 m2 · s−1 within the severely affected ischemic tissue, while SI still detects a large metabolic heterogeneity inside areas showing similar decreased mean ADC values close to this threshold. Conclusions— Our results indicate that the region of very low mean ADC values observed during hyperacute ischemic stroke contains areas of various tissue damage intensity characterized by SI in relation to different stages of cellular metabolic injury. This observation may explain why ADC mapping does not reliably predict final infarct size.

Grid-free interactive and automated data processing for MR chemical shift imaging data.

PurposeToday’s available chemical shift imaging (CSI) analysis tools are based on Fourier transform of the entire data set prior to interactive display. This strategy is associated with limitations particularly when arbitrary voxel positions within a 3D spatial volume are needed by the user. In this work, we propose and demonstrate a processing-resource-efficient alternative strategy for both interactive and automated CSI data processing up to three spatial dimensions.MethodsThis approach uses real-time voxel-shift by first-order phase manipulation as a basis and therefore allows grid-free voxel positioning within the 3D volume. The corresponding spectrum is extracted from the 4D data (3D spatial/1D spectral) at each time a voxel position is selected. The spatial response function and hence the exact voxel size and shape are calculated in parallel including the same processing parameters. Using this mechanism sequentially along with AMARES time-domain modeling, we also implemented automated quantitative and B0-insensitive metabolite mapping.ResultsMetabolite maps of N-acetyl aspartate, choline and creatine were generated using 1H-CSI data from the brain of healthy volunteers and patients with tumor and epilepsy. 31P-3D-CSI of the heart of a healthy volunteer is also shown.ConclusionThe calculated metabolite maps demonstrate good stability and accuracy of the algorithm in all situations tested. The suggested algorithm constitutes therefore an attractive alternative to existing CSI processing strategies.

Noninvasive diagnostic assessment of brain tumors using combined in vivo MR imaging and spectroscopy

To determine the potential value of multimodal MRI for the presurgical management of patients with brain tumors, we performed combined magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) in 164 patients who presented with tumors of various histological subtypes confirmed by surgical biopsy. Univariate statistical analysis of metabolic ratios carried out on the first 121 patients demonstrated significant differences in between‐group comparisons, but failed to provide sufficiently robust classification of individual cases. However, a multivariate statistical approach correctly classified the tumors using linear discriminant analysis (LDA) of combined MRI and MRS data. After initial separation of contrast‐enhancing and non‐contrast‐enhancing lesions, 91% of the former and 87% of the latter were correctly classified. The results were stable when this diagnostic strategy was tested on the additional 43 patients included for validation after the initial statistical analysis, with over 90% of correct classification. Combined MRI and MRS had superior diagnostic value compared to MRS alone, especially in the contrast‐enhancing group. This study shows the clinical value of a multivariate statistical analysis based on multimodal MRI and MRS for the noninvasive evaluation of intracranial tumors. Magn Reson Med, 2006.

Magnetic resonance spectroscopy study of glycine pathways in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia is a life-threatening disorder in neonates characterized by a deficiency of the glycine cleavage system. We report on four cases of the neonatal form of the disease, which were investigated by in vitro1H magnetic resonance spectroscopy of blood and cerebrospinal fluid, and in vivo1H magnetic resonance spectroscopy of brain. The existence of glycine disposal pathways leading to an increase in lactate in fluids and creatine in fluids and brain was demonstrated. This is the first observation of elevated creatine in brain in nonketotic hyperglycinemia. A recurrent decrease of glutamine and citrate was observed in cerebrospinal fluid, which might be related to abnormal glutamine metabolism in brain. Finally, the cerebral N-acetylaspartate to myo-inositol-glycine ratio was identified as a prognostic indicator of the disease.

Regional metabolite levels of the normal posterior fossa studied by proton chemical shift imaging

MR spectroscopy of the posterior fossa is pitted with numerous technical difficulties. It is, however, of great clinical interest in the study of the degenerative diseases and tumors of this area. We have developed a method to perform 2D CSI of this area, by using a sagittal slice and a careful positioning of outer volume saturation. We performed this acquisition in 30 healthy volunteers to determine the normal metabolic ratios in five voxels of this area (mesencephalon. pons. medulla oblongata, vermis, cerebellar white matter). The main technical difficulty was magnetic field inhomogeneity in the lower brainstem generated by dental alloys. However, 88% of the voxels were of sufficient quality to be analyzed. The statistically significant regional variations were a higher NAA/Cr ratio in the pons than in the medulla oblongata, higher Cho/Cr in the pons than in the mesencephalon and higher Cho/ Cr in the cerebellar white matter than in the vermis. We conclude that 2D CSI of the brainstem, although technically delicate can be performed in most patients.

High cerebral scyllo-inositol: a new marker of brain metabolism disturbances induced by chronic alcoholism

Cerebral metabolic changes that concur to motor and/or cognitive disorders in actively drinking alcoholics are not well established. We tested the hypothesis that chronic alcoholics exhibit profound alterations in the cerebral metabolism of scyllo-inositol. Brain metabolism was explored in nine actively drinking and 11 recently detoxified chronic alcoholics by in vivo brain 1H-MRS and in vitro1H-MRS of blood serum and cerebrospinal fluid. The cohort was composed of individuals with acute, subacute or chronic encephalopathy or without any clinical encephalopathy. Chronic alcoholism is associated with a hitherto unrecognized accumulation of brain scyllo-inositol. Our results suggest that scyllo-inositol is produced within the central nervous system and shows a diffuse but heterogenous distribution in brain where it can persist several weeks after detoxification. Its highest levels were observed in subjects with a clinically symptomatic alcohol-related encephalopathy. When detected, brain scyllo-inositol takes part in a metabolic encephalopathy since it is associated with reduced N-acetylaspartate and increased creatine. High levels of cerebral scyllo-inositol are correlated with altered glial and neuronal metabolism. Our findings suggest that the accumulation of scyllo-inositol may precede and take part in the development of symptomatic alcoholic metabolic encephalopathy.

Cerebral metabolic alterations in human immunodeficiency virus-related encephalopathy detected by proton magnetic resonance spectroscopy. Comparison between sequences using short and long echo times.

RATIONALE AND OBJECTIVES The aim of this study is to evaluate comparatively the metabolic information afforded by proton magnetic resonance (MR) spectroscopy with stimulated-echo acquisition mode (STEAM) (echo time [TE], 20 mseconds) and point-resolved spectroscopy sequence (PRESS) (TE, 135 mseconds) spectra in HIV-related encephalopathy. METHODS Sixty-three human immunodeficiency virus (HIV) patients and 8 controls were examined by single-voxel proton MR spectroscopy at 1.5 tesla, using both PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds) sequences performed during the same MR examination, in the same volume of interest. Cerebral atrophy was quantitated using bicaudate ratio (BCR) and bifrontal ratio (BFR). RESULTS With the STEAM (TE, 20 mseconds) spectra, mean N-acetylaspartate (NAA)/choline (Cho) and NAA/creatine and phosphocreatine (Cr-PCr) ratios are reduced in acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) patients but not in neuroasymptomatics. The proportion of inositol signal is increased, that of NAA decreased in ADC patients. NAA/Cho and NAA/ Cr-PCr mean values measured with PRESS (TE, 135 mseconds) spectra are significantly reduced in ADC and neuroasymptomatic patients. Bifrontal ratio only correlates with NAA/Cr-PCr and NAA/Cho measured on the PRESS spectrum. PRESS (TE, 135 mseconds) spectra allow a definition of different metabolic patterns in HIV-related encephalopathy. At last, no correlation has been found between the NAA raw signals measured on the PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds) spectra obtained in the same MR examination. CONCLUSIONS STEAM (TE, 20 mseconds) spectra provide more metabolic information-namely an evaluation of glial-neuronal status-than PRESS (TE, 135 mseconds) spectra, which afford a metabolic classification of the HIV-related encephalopathy. Because both sequences afford a similar diagnostic gain, MR spectroscopy examination probably requires spectrum acquisition with both sequences.

Familial, adult onset form of leukoencephalopathy with brain stem and spinal cord involvement: inconstant high brain lactate and very slow disease progression.

CHU de Clermont-Ferrand, INSERM UMR 384, Faculte de Medecine, Universite Clermont 1, Clermont-Ferrand , d Centre de Resonance Magnetique Biologique et Medicale, UMR-CNRS 6612, Faculte de Medecine, Universite de la Mediterranee, and Hopital de la Timone, e Service d’Urgences Neuro-vasculaires, CHU Timone, Marseille , f AP-HP, Service de Neuroradiologie, et Inserm UMR 788, CHU de Bicetre, Le Kremlin-Bicetre , and g Service de

Further assignment of resonances in 1H NMR spectra of cerebrospinal fluid (CSF)

A number of previously unidentified 1H NMR signals detected in CSF spectra of patients with various neurological and metabolic diseases are assigned to metabolites, drugs and drug excipients. Two‐dimensional 1H NMR spectroscopy (COSY and J‐resolved) is employed to resolve resonances which are hidden by superimposed peaks in one‐dimensional spectra. Assignments obtained by making use of 2‐D techniques, and of a 1‐D 1H NMR data base created for ca. 150 authentic compounds, enable us to clarify the nature of complex signal patterns found in crowded spectral regions of CSF such as the aliphatic methyl region at ca. 1.0 ppm.

Dominant form of vanishing white matter–like leukoencephalopathy

Leukoencephalopathy with vanishing white matter syndrome (childhood ataxia with central nervous system hypomyelination/vanishing white matter disease) is an autosomal recessive disorder characterized by the occurrence of acute episodes of deterioration after minor head trauma or infection, and symmetrical demyelination on magnetic resonance with cavitation aspects. Mutations in each of the five subunits of eIF2B have been identified. We report in an affected man and his mother an adult‐onset form of childhood ataxia with central nervous system hypomyelination/vanishing white matter disease–like disorder with no mutations in the EIF2B genes and normal guanine nucleotide exchange factor eIF2B activity, suggesting a new dominant inheritance of this syndrome that may involve other genes. Ann Neurol 2005