Patrick Viout

Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis.

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal‐appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT. Hum. Brain Mapping 24:216–228, 2005.

Assessment of Normal Fetal Brain Maturation In Utero by Proton Magnetic Resonance Spectroscopy

Cerebral maturation in the normal human fetal brain was investigated by in utero localized proton MR spectroscopy (1H MRS). Fifty‐eight subjects at 22–39 weeks of gestational age (GA) were explored. A combination of anterior body phased‐array coils (four elements) and posterior spinal coils (two to three elements) was used. Four sequences were performed (point‐resolved spectroscopy (PRESS) sequence with short and long TEs (30 and 135 ms), with and without water saturation). A significant reduction in myo‐inositol (myo‐Ins) and choline (Cho) levels, and an increase in N‐acetylaspartate (NAA) and creatine (Cr) content were observed with progressing age. A new finding is the detection of NAA as early as 22 weeks of GA. This result is probably related to the fact that oligodendrocytes (whether mature or not) express NAA, as demonstrated by in vitro studies. Cho and myo‐inositol were the predominant resonances from 22 to 30 weeks and decreased gradually, probably reflecting the variations in substrate needed for membrane synthesis and myelination. The normal MRS data for the second trimester of gestation (when fetal MRI is usually performed) reported here can help determine whether brain metabolism is altered or not, especially when subtle anatomic changes are observed on conventional images. Magn Reson Med, 2006.

Structure of WM bundles constituting the working memory system in early multiple sclerosis: A quantitative DTI tractography study

Working memory impairment is frequently observed in patients with early multiple sclerosis (MS). MRI and functional MRI studies have shown that working memory impairment is mostly due to diffuse white matter (WM) damage affecting the connectivity between distant cortical areas. However, working memory deficits in early MS patients can be either completely or partly masked by compensatory functional plasticity. It seems likely that concomitantly with the WM bundle injury resulting from pathological processes, the functional plasticity present in early MS patients may be accompanied by reactive structural WM plasticity. This structural plasticity may effectively compensate for connectivity disturbances and/or contribute to functional brain reorganization. The diffusion characteristics of WM bundles involved in working memory were assessed here by performing quantitative diffusion tensor imaging (DTI) tractography on 24 patients with early relapsing-remitting MS and 15 healthy control subjects. The DTI tractography findings showed that WM connections constituting the executive system of working memory were structurally impaired (the fractional anisotropy was lower than normal and the mean diffusivity, higher than normal). A significantly larger number of connections between the left and right thalami was concurrently observed in the MS patients than in the control subjects, which suggests that the WM is endowed with reactive structural plasticity.

Voxel‐based analysis of MTR images: A method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis

To determine whether voxel‐based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS).

Multiparametric differentiation of posterior fossa tumors in children using diffusion-weighted imaging and short echo-time 1H-MR spectroscopy.

To assess the combined value of diffusion‐weighted imaging (DWI) and proton magnetic resonance spectroscopy (1H‐MRS) in differentiating medulloblastoma, ependymoma, pilocytic astrocytoma, and infiltrating glioma in a pediatric population.

Distribution of Brain Sodium Accumulation Correlates with Disability in Multiple Sclerosis: A Cross-sectional 23Na MR Imaging Study

PURPOSE To quantify brain sodium accumulations and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing-remitting (RR) multiple sclerosis (MS) by using sodium 23 ((23)Na) magnetic resonance (MR) imaging. MATERIALS AND METHODS This study was approved by the local committee on ethics, and written informed consent was obtained from all participants. Three-dimensional (23)Na MR imaging data were obtained with a 3.0-T unit in two groups of patients with RR MS-14 with early RR MS (disease duration <5 years) and 12 with advanced RR MS (disease duration >5 years)-and 15 control subjects. Quantitative assessment of total sodium concentration (TSC) levels within compartments (MS lesions, white matter [WM], and gray matter [GM]) as well as statistical mapping analyses of TSC abnormalities were performed. RESULTS TSC was increased inside demyelinating lesions in both groups of patients, whereas increased TSC was observed in normal-appearing WM and GM only in those with advanced RR MS. In patients, increased TSC inside GM was correlated with disability (as determined with the Expanded Disability Status Scale [EDSS] score; P = .046, corrected) and lesion load at T2-weighted imaging (P = .003, corrected) but not with disease duration (P = .089, corrected). Statistical mapping analysis showed confined TSC increases inside the brainstem, cerebellum, and temporal poles in early RR MS and widespread TSC increases that affected the entire brain in advanced RR MS. EDSS score correlated with TSC increases inside motor networks. CONCLUSION TSC accumulation dramatically increases in the advanced stage of RR MS, especially in the normal-appearing brain tissues, concomitant with disability. Brain sodium MR imaging may help monitor the occurrence of tissue injury and disability.

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.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis. A two-year longitudinal MRI/MRSI study of corpus callosum.

Backgrounds Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. Goal and methods To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. Results Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. Conclusion These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

MRI/MRS of corpus callosum in patients with clinically isolated syndrome suggestive of multiple sclerosis

A trophy of corpus callosum (C C) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of C C are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (C ISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure C C volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/C ho) ratio, N-acetyl aspartate/total creatine (NA A/C r) ratio and C ho/C r ratio inside the C C of 46 C ISSMS patients and 24 sexand age-matched controls. No atrophy of C C was observed in the C ISSMS group. C C of patients was character ized by decreased MTR and increased MD. No change in the NA A/C r ratio was observed while the NA A/C ho ratio decreased and C ho/C r ratio increased in the splenium and the central anterio r part of C C. These abnormalities were present in patients with, but also without, macroscopic lesions inside the C C. O ur results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin patho logy, occur in the C C at the earliest stage of MS before any atrophy is detected.

Structural and functional surrogates of cognitive impairment at the very early stage of multiple sclerosis

Following our previous reports based on parametric MRI methods (T(2)-weighted MRI, statistical mapping analysis of magnetization transfer ratio images and functional MRI) applied to a population of 18 patients with clinically isolated syndrome suggestive of multiple sclerosis, we have reviewed the possible structural and functional surrogates of MS that could explain the subtle cognitive impairment related to attention and working memory deficits evaluated with paced auditory serial addition test (PASAT). We propose that the brain substrates underlying cognitive impairment observed at the very early stage of MS are multifactorial. Several components could influence PASAT performances in patients: i) the extent of diffuse white matter damage, ii) the location of visible and non visible lesions, iii) the connectivity efficiency between distant brain functional areas involved in working memory processes and iv) the cortical reorganization. Nevertheless, individually, each of these parameters may have few influences on PASAT performance in patients. Using a multiregression model built with independent MR parameters, a very good evaluation of PASAT scores has been obtained in this limited number of patients explaining 90% of the variance. In conclusion, the different aspects of tissue and functional pathological brain underpinnings must be accounted to monitor accurately new therapeutic strategies for the treatment of early cognitive deficits related to MS.