New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study.

OBJECTIVE: In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions. METHODS: EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected). RESULTS: At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0-3] at Year 1 to 2.5 [range: 0-6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression. CONCLUSION: The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.

Multimodal MR imaging (diffusion, perfusion, and spectroscopy): is it possible to distinguish oligodendroglial tumor grade and 1p/19q codeletion in the pretherapeutic diagnosis?

BACKGROUND AND PURPOSE: Pretherapeutic determination of tumor grade and genotype in grade II and III oligodendroglial tumors is clinically important but is still challenging. Tumor grade and 1p/19q status are currently the 2 most important factors in therapeutic decision making for patients with these tumors. Histopathology and cMRI studies are still limited in some cases. In the present study, we were interested in determining whether the combination of PWI, DWI, and MR spectroscopy could help distinguish oligodendroglial tumors according to their histopathologic grade and genotype. MATERIALS AND METHODS: We retrospectively reviewed 50 adult patients with grade II and III oligodendrogliomas and oligoastrocytomas who had DWI, PWI, and MR spectroscopy at short and long TE data and known 1p/19q status. Univariate analyses and multivariate random forest models were performed to determine which criteria could differentiate between grades and genotypes. RESULTS: ADC, rCBV, rCBF, and rK2 were significantly different between grade II and III oligodendroglial tumors. DWI, PWI, and MR spectroscopy showed no significant difference between tumors with and without 1p/19q loss. Separation between tumor grades and genotypes with cMRI alone showed 31% and 48% misclassification rates, respectively. Multimodal MR imaging helps to determine tumor grade and 1p/19q genotype more accurately (misclassification rates of 17% and 40%, respectively). CONCLUSIONS: Although multimodal investigation of oligodendroglial tumors has a lower contribution to 1p/19q genotyping compared with cMRI alone, it greatly improves the accuracy of grading of these neoplasms. Use of multimodal MR imaging could thus provide valuable information that may assist clinicians in patient preoperative management and treatment decision making.

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.

Performance in recognition memory is correlated with entorhinal/perirhinal interictal metabolism in temporal lobe epilepsy.

In addition to the hippocampus, the entorhinal/perirhinal cortices are often involved in temporal lobe epilepsy (TLE). It has been proposed that these anterior parahippocampal structures play a key role in recognition memory. We studied the voxel-based PET correlation between number of correctly recognized targets in a new recognition memory paradigm and interictal cerebral metabolic rate for glucose, in 15 patients with TLE with hippocampal sclerosis. In comparison to healthy subjects, patients had decreased recognition of targets (P<0.001) and ipsilateral hypometabolism (relative to side of hippocampal sclerosis) of the hippocampus, entorhinal/perirhinal cortices, medial temporal pole, and middle temporal gyrus (P<0.05, corrected by false discovery rate method). Performance correlated with interictal metabolism of ipsilateral entorhinal/perirhinal cortices (P<0.005, Spearman's rank test), but this relationship was not significant in the hippocampus itself (P>0.18, Spearman's rank test). These findings highlight the preferential involvement of entorhinal/perirhinal cortices in recognition memory in patients with TLE, and suggest that recognition memory paradigms may be useful in assessing anterior parahippocampal functional status in TLE.

Efficiency of cognitive control recruitment in the very early stage of multiple sclerosis: a one-year fMRI follow-up study.

Functional magnetic resonance imaging (FMRI) studies have established that patients with multiple sclerosis show stronger activation in the lateral prefrontal cortices (LPFC) than healthy control subjects during effortful cognitive tasks. The aim of the present study was to assess the impact of these activation changes on cognitive performances. In addition to 19 controls, who were tested at a single time-point to define a standard pattern of fMRI activation during the performance of the Paced Auditory Serial Addition Task (PASAT), 13 patients with clinically isolated syndrome underwent a longitudinal fMRI examination while performing the PASAT at the beginning of the study (M0) and one year later (M12). Relative to the M0 scores, PASAT performances improved in eight patients (group A) and either decreased (n = 4) or remained unchanged (n = 1) (group B) in five patients at M12. Random effect analyses (SPM2; Wellcome Institute, London, England) were performed to compare intra-group time-related effects on brain activation (paired t-test between M0 and M12), and inter-group differences were also compared between the two groups of patients (analysis of covariance with PASAT performances as the covariate). Relative to group B, group A showed larger increase in activation between M0 and M12 in the right LPFC. In the whole group of patients, interaction analyses showed that the differences in the PASAT scores between M0 and M12 were correlated with the differences in activation observed in the right LPFC. This longitudinal study shows that in patients with early multiple sclerosis, the increased levels of activation in the right LPFC was associated with improved individual working memory and processing speed performances.

[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.

Profile of memory impairment and gray matter loss in amnestic mild cognitive impairment.

The present study assessed the patterns of cortical gray matter (GM) loss in patients with amnestic mild cognitive impairment (aMCI) with distinct profiles of memory impairment, i.e. aMCI patients failing on both recall and recognition memory vs. aMCI patients showing impaired recall but preserved recognition memory. This distinction is usually not taken into account in studies on aMCI and the aim of the present study was to assess whether this distinction is useful. Twenty-eight aMCI patients and 28 matched controls subjects were included. All aMCI patients failed a recall memory task (inclusion criteria). All underwent a visual recognition memory task (DMS48). However, 12 succeeded on this task while 16 failed. Relative gray matter (GM) loss was measured using voxel-based morphometry. When comparing aMCI patients to controls regardless of the profile of memory impairment, GM loss was found in temporal, parietal and frontal areas. However, in aMCI patients with preserved recognition (but impaired recall), GM loss was confined to frontal areas. This contrasted with GM loss in the right medial temporal lobe and bilateral temporo-parietal regions in aMCI patients with impaired recall and recognition memory, a pattern of GM loss usually described in early AD. We conclude that different profiles of memory impairment in aMCI patients are associated with distinct patterns of GM loss.

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.

MR imaging of brain maturation.

Magnetic resonance imaging (MRI) is the imaging tool of choice to evaluate brain maturation and especially brain myelination. Magnetic resonance imaging also provides functional insight through diffusion images and proton spectroscopy. In this review the MRI techniques are analyzed for both pre- and postnatal periods. The origin of MR signal changes is also detailed in order to understand normal myelination evolution and the consequences on brain maturation of the different pathologies encountered prior and after birth. Because MRI is "blind" in terms of signal on conventional sequences after 2 years of age, a particular attention is given to diffusion images and proton spectroscopy of the developing brain.

Neuroimaging of neonatal encephalopathies.

Neonatal brain disorders consist of a wide chapter including brain malformations, hypoxic-ischemic encephalopathy (HIE), intracranial infections, perinatal trauma and metabolic encephalopathy. We will focus here on HIE, intracranial infections (especially materno-fetal infection with or without prolonged and/or premature rupture of membranes) and metabolic encephalopathy, those three conditions being the most frequent so far in our experience. Neonatal stroke is also analyzed. Moreover minor perinatal events might be superimposed on an already damaged (infective, edematous, metabolically abnormal or maldeveloped) brain, highlighting the main role and potential benefits of neuroimaging during the neonatal period. The different methods of brain imaging are thus reported with their advantages and disadvantages.

[Indications for cerebral MR proton spectroscopy in 2007]. / Spectroscopie par résonance magnétique du proton. Quelles indications neurologiques en 2007?

Magnetic resonance spectroscopy (MRS) is being increasingly performed alongside the more conventional MRI sequences in the exploration of neurological disorders. It is however important to clearly differentiate its clinical applications aiming at improving the differential diagnosis or the prognostic evaluation of the patient, from the research protocols, when MRS can contribute to a better understanding of the pathophysiology of the disease or to the evaluation of new treatments. The most important applications in clinical practice are intracranial space occupying lesions (especially the positive diagnosis of intracranial abscesses and gliomatosis cerebri and the differential diagnosis between edema and tumor infiltration), alcoholic, hepatic, and HIV-related encephalopathies and the exploration of metabolic diseases. Among the research applications, MRS is widely used in multiple sclerosis, ischemia and brain injury, epilepsy and neuro degenerative diseases.

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.

[Brain magnetic resonance spectroscopy]. / Spectroscopie par résonance magnétique cérébrale.

MR spectroscopy (MRS) sequences allow noninvasive exploration of brain metabolism during a MRI examination. Their day-to-day use in a clinical setting has recently been improved by simple programming of sequences and automated quantification of metabolites. However, a few simple rules should be observed in the choice of sequences and the location of the voxels so as to obtain an informative, high-quality examination. The research applications of MR spectroscopy, where use of this examination seeks to better understand the pathophysiology of the disease, must be distinguished from its clinical indications, where MRS provides information that can be used directly in patient management. The most significant of the clinical uses are imaging intracranial tumors (positive and differential diagnosis, extension, treatment follow-up), diffuse brain injury, encephalopathies (especially hepatic and HIV-related), and the diagnosis of metabolic disorders.

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.

What is the significance of interictal water diffusion changes in frontal lobe epilepsies?

The aim of this study was to better understand the significance of interictal changes in water molecule diffusivity defined by diffusion-weighted imaging (DWI) in frontal lobe epilepsy (FLE), as well as to test the accuracy of interictal DWI in the definition of the epileptogenic zone (EZ). DWI was carried out in 14 patients with refractory FLE (9 negative-MRI) as well as in 25 controls. Statistical mapping analysis (SPM2) of diffusivity maps was used to detect, for each subject, significant diffusivity alterations. We then studied the relationships between diffusion and depth recorded electrical abnormalities. Clinical correlates of the extent of diffusivity changes were also tested. We found areas of significantly increased diffusivity (SID) in 13 patients. Eight had SID in the EZ, 9 within the irritative zone (IZ) and 12 outside, mainly in connected areas. We found a correlation between the extent of SID and the duration of epilepsy (p corrected=0.026, R=0.621). In addition, SID was significantly less widespread in negative-MRI patients (p=0.028). However, we found no significant differences concerning either seizure frequency (p=0.302), seizure generalization (p=0.841), history of status (p=0.396), or surgical outcome (p=0.606). We suggest that SID in normal appearing areas is not a specific signature of epileptogenicity in FLE, and is more likely to reflect multifactorial and potentially evolving neuro-glial injuries.

[MR spectroscopy of brain tumors]. / Spectroscopie par résonance magnétique des tumeurs cérébrales.

MR spectroscopy (MRS) can complement MRI in the evaluation of intracranial tumors. Before treatment, MRS can contribute to the differential diagnosis between tumor and non tumoral lesion (especially intracranial abscesses), to assess the aggressiveness of a glial tumor or to determine its extension to better delineate the surgical removal or the target volume of radiotherapy. During treatment follow-up, MRS helps differentiate recurrent tumor from radionecrosis or physiological post-surgical contrast enhancement. The current studies are trying to determine if the indications of MRS, alone or in association with other MR sequences can further be extended in the study of brain tumors, in particular the follow-up of lesions undergoing chemo or radiotherapy.

Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice.

AIMS/HYPOTHESIS: An important determinant of sensitivity to ischaemia is altered ion homeostasis, especially disturbances in intracellular Na(+) (Na(i)(+)) handling. As no study has so far investigated this in type 2 diabetes, we examined susceptibility to ischaemia-reperfusion in isolated hearts from diabetic db/db and control db/+ mice and determined whether and to what extent the amount of (Na(i)(+)) increase during a transient period of ischaemia could contribute to functional alterations upon reperfusion. METHODS: Isovolumic hearts were exposed to 30-min global ischaemia and then reperfused. (23)Na nuclear magnetic resonance (NMR) spectroscopy was used to monitor[Formula: see text] and (31)P NMR spectroscopy to monitor intracellular pH (pH(i)). RESULTS: A higher duration of ventricular tachycardia and the degeneration of ventricular tachycardia into ventricular fibrillation were observed upon reperfusion in db/db hearts. The recovery of left ventricular developed pressure was reduced. The increase in[Formula: see text] induced by ischaemia was higher in db/db hearts than in control hearts, and the rate of pH(i) recovery was increased during reperfusion. The inhibition of Na(+)/H(+) exchange by cariporide significantly reduced (Na(i)(+)) gain at the end of ischaemia. This was associated with a lower incidence of ventricular tachycardia in both heart groups, and with an inhibition of the degeneration of ventricular tachycardia into ventricular fibrillation in db/db hearts. CONCLUSIONS/INTERPRETATION: These findings strongly support the hypothesis that increased (Na(i)(+)) plays a causative role in the enhanced sensitivity to ischaemia observed in db/db diabetic hearts.

1H-MRS imaging in intractable frontal lobe epilepsies characterized by depth electrode recording.

Presurgical evaluation of frontal lobe epilepsy (FLE) remains a challenging issue and frequently requires invasive depth electrode recording. In this study, we aimed at evaluating the potential usefulness of a non-invasive technique such as proton magnetic resonance spectroscopic imaging ((1)H-MRSI) in the presurgical evaluation of FLE and at investigating the potential electrophysiological correlates of the metabolic disturbances as defined by (1)H-MRSI. We compared the distribution of (1)H-MRSI abnormalities with the electrophysiological abnormalities defined by stereo-electroencephalography (SEEG) recording in 12 patients presenting with several subtypes of FLE. We also used 12 control subjects in order to obtain normative (1)H-MRSI data. We used a multilevel (1)H-MRSI protocol to better sample the principal regions of the frontal lobe. We also applied a metabolic mapping technique allowing a visual display of metabolic data. A significant decrease of both N-acetyl-aspartate/phosphocreatine-creatine and N-acetyl-aspartate/(choline-compounds + phosphocreatine-creatine) ratios was observed in regions involved in the epileptogenic zone (EZ) and/or the irritative zone (IZ) compared to regions without electrical abnormalities in the same patients (P = 0.044 and P = 0.018, respectively), and also compared to controls (P = 0.004 and P = 0.0001, respectively). No significant differences in metabolic ratios were observed between those regions involved in the EZ and those involved in the IZ only. Our results suggest a link between the relative decrease of N-acetyl-aspartate and the EZ as well as the IZ in FLE. Thus, multilevel (1)H-MRSI protocol may add pertinent information during the non-invasive presurgical evaluation of FLE.