Quantitative assessment of sciatic nerve changes in Charcot-Marie-Tooth type 1A patients using magnetic resonance neurography.

BACKGROUND AND PURPOSE: Nerve tissue alterations have rarely been quantified in Charcot-Marie-Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables. METHODS: Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot-Marie-Tooth Neuropathy Score version 2, Charcot-Marie-Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot-Marie-Tooth examination scores. RESULTS: A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores. CONCLUSION: Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.

Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis.

BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated. RESULTS: The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio. CONCLUSIONS: The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.

Is brain maturation comparable in fetuses and premature neonates at term equivalent age?

BACKGROUND AND PURPOSE: Improved knowledge of brain maturation in fetuses and premature neonates is crucial for the early detection of pathologies and would help determine whether MR data from the premature brain might be used to evaluate fetal maturation. Using diffusion-weighted MR imaging and (1)H-MR spectroscopy, we compared cerebral microstructure and metabolism in normal in utero fetuses imaged near term and premature neonates imaged at term equivalent. MATERIALS AND METHODS: Forty-eight subjects were investigated: 24 in utero fetuses (mean gestational age, 37 ± 1 weeks) and 24 premature neonates (mean postconceptional age, 37 ± 1 weeks). ADC values were measured in cerebellum, pons, white matter, brain stem, basal ganglia, and thalamus. MR spectroscopy was performed in deep white matter. RESULTS: Mean ADC values from fetuses and premature neonates were comparable except for the pons and the parietal white matter. ADC values were lower in the pons of premature neonates, whereas greater values were found in their parietal white matter compared with fetuses. Proton MR spectroscopy showed higher levels of NAA/H(2)O, Glx/H(2)O, tCr/H(2)O, and mIns/H(2)O in premature neonates compared with fetuses. CONCLUSIONS: Our study provides evidence of subtle anomalies in the parietal white matter of healthy premature neonates. In addition, the reduced ADC values in the pons together with the increased levels of NAA/H(2)O, tCr/H(2)O, and Glx/H(2)O in the centrum semiovale suggest a more advanced maturation in some white matter regions. Our results indicate that MR data from the premature brain are not appropriate for the assessment of the fetal brain maturation.

[Imaging of brain tumors in children]. / Imagerie des tumeurs cérébrales de l'enfant.

Few studies exist in the literature on pediatric brain tumors examined with advances MRI techniques. The aim of this review is to try to find out some specific tissular characteristics of the main cerebral tumors encountered in children, especially through diffusion imaging, perfusion imaging and proton magnetic resonance spectroscopy (MRS). However, hemispheric cerebral tumors are not as common as in the adult population.

A MRS-MRI-fMRI exploration of the brain. Impact of long-lasting persistent vegetative state.

BACKGROUND: The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. However, very little is known about the actual degree of perception in these patients and the extent of progressive brain injury induced by very prolonged unawareness. METHODS: The authors have conducted a 2-year longitudinal study using a multimodal MRI-MRSI-fMRI protocol in four patients in long-lasting PVS (over 3 years at inclusion) characterized by various brain injuries. RESULTS: Although one subject showed initially preserved local brain metabolism and brain activity related to primary perception suggesting the presence of potential residual brain plasticity even in this critical stage, none of the four patients recovered to consciousness during the 2 years of the protocol. Moreover, significant deterioration of parameters related to brain atrophy, metabolism and functional excitability of primary cortices was observed in all patients during the follow-up. CONCLUSIONS: Heterogeneity of brain injury, consequences of long term minimal brain activity and potential factors that prevent recovery to consciousness are discussed.

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

PURPOSE: 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. MATERIALS AND METHODS: A total of 17 children with untreated posterior fossa tumors (seven medulloblastoma, four infiltrating glioma, two ependymoma, and four pilocytic astrocytoma), were investigated with conventional MRI, DWI, and MRS using a single-voxel technique. Within the nonnecrotic tumor core, apparent diffusion coefficient (ADC) values using a standardized region of interest (ROI) were retrieved. Quantification of water signal and analysis of metabolite signals from MRS measurements in the same tumorous area were reviewed using multivariant linear discriminant analysis. RESULTS: Combination of ADC values and metabolites, which were normalized using water as an internal standard, allowed discrimination between the four tumor groups with a likelihood below 1 x 10(-9). Positive predictive value was 1 in all cases. Tumors could not be discriminated when using metabolite ratios or ADC values alone, nor could they be differentiated using creatine (Cr) as an internal reference even in combination with ADC values. CONCLUSION: Linear discriminant analysis using DWI and MRS using water as internal reference, fully discriminates the four most frequent posterior fossa tumors in children.

Diffusion-weighted imaging in normal fetal brain maturation.

Diffusion-weighted imaging (DWI) provides information about tissue maturation not seen on conventional magnetic resonance imaging. The aim of this study is to analyze the evolution over time of the apparent diffusion coefficient (ADC) of normal fetal brain in utero. DWI was performed on 78 fetuses, ranging from 23 to 37 gestational weeks (GW). All children showed at follow-up a normal neurological evaluation. ADC values were obtained in the deep white matter (DWM) of the centrum semiovale, the frontal, parietal, occipital and temporal lobe, in the cerebellar hemisphere, the brainstem, the basal ganglia (BG) and the thalamus. Mean ADC values in supratentorial DWM areas (1.68 +/- 0.05 mm(2)/s) were higher compared with the cerebellar hemisphere (1.25 +/- 0.06 mm(2)/s) and lowest in the pons (1.11 +/- 0.05 mm(2)/s). Thalamus and BG showed intermediate values (1.25 +/- 0.04 mm(2)/s). Brainstem, cerebellar hemisphere and thalamus showed a linear negative correlation with gestational age. Supratentorial areas revealed an increase in ADC values, followed by a decrease after the 30th GW. This study provides a normative data set that allows insights in the normal fetal brain maturation in utero, which has not yet been observed in previous studies on premature babies.

Infratentorial pediatric brain tumors: the value of new imaging modalities.

The correct assessment of the four most frequent infratentorial brain tumors in children (medulloblastoma, ependymoma, pilocytic astrocytoma and infiltrating glioma) has always been problematic. They are known to often resemble one another on conventional magnetic resonance (MR) imaging. We tested the hypothesis whether the combined strength of diffusion-weighted imaging (DWI) and proton MR spectroscopy (MRS) could help differentiate these tumors. Seventeen children with untreated posterior fossa tumors were investigated between January 2005 and January 2006 with conventional MR imaging and combined DWI and MR spectroscopy using a single-voxel technique at short and long echo time (TE) of 30 ms and 135 ms respectively. Apparent diffusion coefficient (ADC) values were retrieved after regions of interest were manually positioned within non necrotic tumor core. Water signal was quantified and metabolite signals were compared and analyzed using linear discriminant analysis. When a combination of ADC values and normalized metabolites was used, all tumors could be discriminated against one other. This could only be achieved when metabolites were normalized using water as an internal standard. They could not be discriminated when using metabolite ratios or ADC values alone, nor could they be differentiated using creatine (Cr) as an internal reference even in combination with ADC values. In conclusion, linear discriminant analysis and multiparametric combination of DWI and MRS, although not replacing histology, fully discriminates the four most frequent posterior fossa tumors in children, but metabolites have to be normalized using water and not Cr signal as an internal reference.

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.

BACKGROUND: 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.

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 (1)H-MRS and in vitro(1)H-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.

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

Atrophy of corpus callosum (CC) 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 CC 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 (CISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure CC volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/Cho) ratio, N-acetyl aspartate/total creatine (NAA/Cr) ratio and Cho/Cr ratio inside the CC of 46 CISSMS patients and 24 sex- and age-matched controls. No atrophy of CC was observed in the CISSMS group. CC of patients was characterized by decreased MTR and increased MD. No change in the NAA/Cr ratio was observed while the NAA/Cho ratio decreased and Cho/Cr ratio increased in the splenium and the central anterior part of CC. These abnormalities were present in patients with, but also without, macroscopic lesions inside the CC. Our results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin pathology, occur in the CC at the earliest stage of MS before any atrophy is detected.

Multimodal magnetic resonance imaging of the central nervous system.

The physiological and biochemical properties of the diseased brain that can be explored with magnetic resonance imaging (MRI) are increasing. Progress in MR-based technology affords a large panel of MRI sequences that explore different phenomena and, thus, provide complementary informations. The diagnostic accuracy of MRI is improved by the combination of all MR modalities. However, this abundance of data requires an efficient multiparametric analysis to fully achieve the goal of the multimodal strategy. We will discuss the potential impact of this advanced MRI analysis in the clinical management and the therapeutical strategies of the most common brain pathologies (intracranial tumors, multiple sclerosis, stroke, epilepsy and dementia). This non-invasive approach is of utmost importance since it already improves the diagnosis and the therapeutic choice in the management of several central nervous system diseases.

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.

Magnetic resonance spectroscopy of serum and acute-phase proteins revisited: a multiparametric statistical analysis of metabolite variations in inflammatory, infectious and miscellaneous diseases.

Proton MR spectra and biochemical assays have been recorded on the sera of 40 patients and ten controls in order to document the correlation between spectroscopic and biochemical variations in selected pathologies (cancer, inflammatory and infectious diseases, diabetes). N-acetyl proton resonances are essentially generated by the N-acetyl residues of the glucidic moieties borne by the most abundant acute-phase proteins (alpha1-acid glycoprotein, alpha1-antitrypsin and haptoglobin). These resonances are not correlated to immunoglobulins A, G and M levels. Principal component analysis shows that variations in spectroscopic and biochemical data are independent markers of the inflammatory status of patients but no additional sensitivity or specificity is obtained when the two sets of data are combined.

Experimental protocol for clinical analysis of cerebrospinal fluid by high resolution proton magnetic resonance spectroscopy.

High resolution magnetic resonance spectroscopy (MRS) of cerebrospinal fluid (CSF) is a non-destructive analytical method which allows rapid and simultaneous detection of molecules involved in intermediary and oxidative metabolic pathways. We developed a protocol suitable for routine MRS analysis of lyophilized CSF samples. This procedure guarantees sample integrity, from CSF collection to spectrum acquisition. MRS analysis of blood serum was included in our protocol as a complementary method to CSF analysis. This protocol can contribute to establish MRS of CSF as a new analytical tool to better understand the metabolic processes involved in neurological diseases.

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.

Value of Doppler echocardiography in the detection of low-grade rejections after cardiac transplantation.

Modifications of the diastolic parameters pressure half-time (PHT) and isovolumic relaxation time (IVRT), recorded using cardiac Doppler echocardiography (CDE), were studied in 23 heart transplant recipients and compared to the results of 345 endomyocardial biopsies (EMB) performed on the same day. Two different protocols, analyzing respectively (1) a decrease of 20% or more in IVRT and/or PHT with respect to the mean and (2) a decrease of 20% or more in IVRT and/ or PHT with respect to its preceding value, were used to evaluate the efficiency of CDE in diagnosing mild and moderate rejections. When a mild rejection was detected by EMB, a statistically significant decrease was found in the average CDE parameter values of the patient population. However, these variations were weak and did not differ from the spontaneous variations observed in each patient in the absence of rejection. Thus, it is not surprising that the sensitivity of CDE in the detection of mild rejections was very low (45%) using the most sensitive protocol (variations of the parameters from their preceding value). We conclude that CDE alone does not seem to be sufficient to perform the noninvasive diagnosis of low-grade rejections and must be complemented by other noninvasive methods.

Rapid evaluation of ethanol content and metabolism in human plasma using quantitative proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy (MRS) was used to assay ethanol in plasma. Ethanol concentrations determined by MRS and conventional enzymatic methods are in excellent agreement. In addition to ethanol, acetone, acetate and beta-hydroxybutyrate can be quantified simultaneously in the same sample. Proton MRS of plasma offers a rapid evaluation of human ethanol metabolism and may be useful in screening for chronic alcoholism.

Analysis of plasma lipids by NMR spectroscopy: application to modifications induced by malignant tumors.

Lipid extracts of plasma were studied by 31P and 1H NMR spectroscopy at 9.4 T. Signals recorded on lipid mixtures were assigned to different lipid classes using a data base built with two-dimensional 1H COSY spectra of seven standard lipids. Signals unique to glycerophospholipids, sphingolipids, and triacylglycerols were identified. 31P and 1H NMR spectroscopy was used to study qualitative and quantitative modifications induced in plasma by malignant tumors. The results show a significant increase in triglyceride/phospholipid ratio and a concomitant decrease of total phospholipids in patients with cancer. In order to check for the possible presence of particular lipids such as glycolipids in these patients, 1H COSY spectra were recorded on the intact plasma and on extracts of plasma lipids in patients with cancer and in healthy subjects. Only in one case of ovarian cancer, a cross-peak at 1.35 and 4.15 ppm, corresponding to fucose residue in glycolipids, was detected.