Biomedical subjects

Jean-Philippe Ranjeva

Publications and source records attributed to Jean-Philippe Ranjeva.

17 recordsLinked to original sources

PubMed2006

A branched-chain organic acid linked to multiple sclerosis: first identification by NMR spectroscopy of CSF.

(1)H NMR spectroscopy of cerebrospinal fluid (CSF) is currently being used to study metabolic profiles characteristic of distinct multiple sclerosis (MS) manifestations. For select MS patient groups, we have previously detected significantly increased concentrations of several identified metabolites and one unidentified compound. We now present, for the first time, the identification of the latter molecule, beta-hydroxyisobutyrate (BHIB). A combination of dedicated 1D and 2D (1)H NMR experiments was employed for signal assignment. To our knowledge, BHIB has not previously been identified in (1)H NMR spectra of biofluids or biological tissues. Our assignment suggests new biochemical pathways involved in specific MS pathologies.

Acids↗

PubMed2006

[Contribution of nuclear magnetic resonance imaging in multiple sclerosis].

Conventional MRI has become essential in the field of multiple sclerosis (MS). It reveals brain injury in visualising focal lesions of demyelination of the white matter, damage of the blood-brain barrier, and tissue loss within the lesions. These parameters are now used for an early diagnosis and for assessing the efficacy of new therapies. For years, neuroimaging research groups have been developing MRI techniques to get more sensitive and specific parameters of brain injury. Such techniques provide information on the extent of atrophy (volume, brain thickness), the metabolism (MR spectroscopy), the tissue structure (magnetization transfer and diffusion) and the compensation processes (functional MRI) of the brain. They lead to new approaches for analysing the pathophysiological processes at work in MS and their course in time.

Brain↗

PubMed2006

The right temporal lobe variant of frontotemporal dementia: cognitive and neuroanatomical profile of three patients.

The right temporal variant of frontotemporal lobar degeneration (Rtv-FTLD) is a focal degenerative condition affecting predominantly the right temporal lobe. The aim of this study was to further characterize the profile of cognitive impairment and the neuroanatomical basis of Rtv-FTLD patients without behavioural disturbances. A group of three patients with this syndrome had a detailed neuropsychological assessment, along with Voxel-Based Morphometry (VBM) of their brain to determine location of cortical atrophy. VBM analyses showed a pattern of atrophy that was predominant in the right hemisphere and concerned primarily the right anterior temporal lobe region. Patients carried out a test of famous people in which their ability to recognize, name and provide semantic information about famous persons from their faces, their voices and their names was investigated. They all showed a severe defect in recognizing, naming and identifying famous people irrespective of modality. Therefore, their inability to recognize famous people resulted from a multimodal defect (semantic). These results highlight the semantic nature of the defect, and suggest that the anterior right temporal lobe may have a prominent role in processing person-based semantic knowledge. This study helps in further understanding the neuropsychological profile of patients with Rtv-FTLD.

Aged↗

PubMed2006

Functional magnetic resonance imaging and cognition at the very early stage of MS.

Dysfunction of high controlled information processing is present in patients with multiple sclerosis (MS) right at the beginning of the disease. One hypothesis is that disruption of communication inside large-scale cortical networks, occurring as a consequence of white matter damage, may constitute the anatomical substrate of cognitive impairment at the very early stage of MS. Disturbance of interregional synchronization might be the main pathogenic factor in controlled information processing deficiency in early MS. Preliminary functional MRI studies (fMRI) have provided important clues to corroborate the connectivity hypotheses. First, brain connectivity assessed by fMRI has brought new data about the influence of diffuse white matter damage on connectivity efficiency inside large-scale networks. These studies have suggested that connectivity disturbances occur inside the working memory network in patients at the very early stage of MS and appear related to the extent of structural white matter damage. Also, fMRI studies have suggested that patients may partially compensate for connectivity impairment by a greater cognitive control. Such a compensatory mechanism could limit the determinant functional impact of diffuse white matter damage on high controlled information processing.

Age of Onset↗

PubMed2006

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.

Adult↗

PubMed2006

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.

Artificial Intelligence↗

PubMed2005

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.

Adult↗

PubMed2005

Altered functional connectivity related to white matter changes inside the working memory network at the very early stage of MS.

Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T(2) lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.

Acoustic Stimulation↗

PubMed2005

Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis.

BACKGROUND AND PURPOSE: In the early stage of Multiple Sclerosis (MS), conventional MR imaging parameters such as T2 lesion load fail to explain the clinical status of patients. In the present work, we aimed to determine the ability of magnification transfer imaging to better reflect the relationship between local tissue damage and functional status of MS patients. METHODS: We performed a comparative statistical mapping analysis on brain tissue magnetization transfer ratio (MTR) data measured in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) and 18 matched control subjects. RESULTS: In the patients with CISSMS, a pattern of significant low MTR values was observed in the white matter, corpus callosum, bilateral occipitofrontal fascicles, right fornix, right parietal white matter, external capsule, right superior longitudinal fasciculus (SLF), right inferior longitudinal fasciculus, optica radiata, parietal white matter, right cingulum, gray matter, bilateral thalamus, bilateral caudate, right insula, and left Brodmann area (BA) 8. No correlation was found between local MTR decrease and Expanded Disability Status Scale score. Significant correlations between MTR and MS Functional Composite scores (Spearman rank test, P <.05) were observed in the left BA40, right SLF, right frontal white matter, splenium, and anterior corpus callosum. Local MTR values correlated with Paced Auditory Serial Addition Test scores in the left BA40, right BA4, right SLF, and splenium. CONCLUSION: Statistical mapping analysis of brain MTR data provides valuable information on the relationship between the location of brain tissue damage and its functional impact in patients with MS, even in the earliest stage of the disease.

Activities of Daily Living↗

PubMed2004

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

PURPOSE: 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). MATERIALS AND METHODS: We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. RESULTS: A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. CONCLUSION: These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease.

Adult↗

PubMed2004

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter.

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-monthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P < 0.0001). Over the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. Although this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.

Adult↗

PubMed2003

Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS.

Recent functional magnetic resonance imaging (fMRI) studies have suggested that functional cortical changes seen in patients with early relapsing-remitting multiple sclerosis (MS) can have an adaptive role to limit the clinical impact of tissue injury. To determine whether cortical reorganization occurs during high cognitive processes at the earliest stage of multiple sclerosis (MS), we performed an fMRI experiment using the conventional Paced Auditory Serial Addition Test (PASAT) as paradigm in a population of ten patients with clinically isolated syndrome suggestive of multiple sclerosis (CISSMS). At the time of the fMRI exploration, mean disease duration was 6.8 +/- 3.3 months. We compared these results to those obtained in a group of ten education-, age-, and sex-matched healthy controls. Subjects were explored on a 1.5 T MRI system using single-shot gradient-echo EPI sequence. Performances of the two groups during PASAT recorded inside the MR scanner were not different. Statistical assessment of brain activation was based on the random effect analysis (between-group analysis two-sample t-test P < 0.005 confirmed by individual analyses performed in the surviving regions P < 0.05 Mann Whitney U-test). Compared to controls, patients showed significantly greater activation in the right frontopolar cortex, the bilateral lateral prefrontal cortices, and the right cerebellum. Healthy controls did not show greater activation compared to CISSMS patients. The present study argues in favor of the existence of compensatory cortical activations at the earliest stage of MS mainly located in regions involved in executive processing in patients performing PASAT. It also suggests that fMRI can evidence the active processes of neuroplasticity contributing to mask the clinical cognitive expression of brain pathology at the earliest stage of MS.

Adult↗

PubMed2003

Use of proton magnetic resonance spectroscopy of the brain to differentiate gliomatosis cerebri from low-grade glioma.

OBJECT: Gliomatosis cerebri (GC), a rare entity characterized by a widespread infiltration of brain by tumor, lacks objective and quantitative diagnostic criteria. Single-voxel spectroscopy and chemical shift imaging (two-dimensional proton magnetic resonance [MR] spectroscopy) were performed using both short (20- or 22-msec) and long (135-msec) echo times in nine patients suffering from GC, nine patients with low-grade gliomas (LGGs), and 25 healthy volunteers to establish the precise metabolic pattern of this uncommon brain neoplasm. METHODS: The gliomatosis infiltration was characterized by markedly elevated levels of creatine-phosphocreatine (Cr) and mvo-inositol (Ins), a reduced level of N-acetyl aspartate (NAA), and a moderately elevated level of choline-containing compounds (Cho). This pattern differs strikingly from LGGs, which are characterized by elevated levels of Cho and Ins, markedly reduced levels of NAA, and low-to-normal Cr concentrations. Although the distinction between GC and LGG, based on histological and MR imaging criteria, is a matter of debate, MR spectroscopy produces valuable information for the differentiation between these two entities and, hence, the choice of therapeutic strategy. It also provides new insight into the pathophysiology of GC because elevated Cr and Ins levels may be related to proliferation of glial elements or, more probably, activation of normal glia. Elevated levels of Cho reflect cellular proliferation and reduced NAA corresponds to reversible neuronal injury and/or focal invasion by the tumor process. CONCLUSIONS: Owing to the unfavorable clinical outcome associated with GC compared with that associated with LGG, the findings of this study illustrate the diagnostic and prognostic value of proton MR spectroscopy in the characterization of infiltrating gliomas.

Adolescent↗

PubMed2002

Objective and noninvasive metabolic characterization of donor hearts by phosphorous-31 magnetic resonance spectroscopy.

OBJECTIVE: The authors performed a multi-institutional, prospective, blind study on hearts from local donors to validate the feasibility and accuracy of the metabolic evaluation of human hearts by phosphorus-31 ( P) magnetic resonance spectroscopy (MRS) before transplantation. METHODS: Twenty-one hearts were separated into two groups according to a transplantation score (TS) on the basis of the current clinical and echocardiographic evaluation as follows: TS1 (n=7), grafts for United Network for Organ Sharing (UNOS) 1 patients only; and TS2 (n=14), grafts suitable for UNOS 2 patients. All hearts were cold preserved with Celsior and underwent ex situ P MRS to measure ratios of various high-energy phosphate metabolites and the intracellular pH (pHi). RESULTS: The total duration of the MRS procedure was 32 min, thereby not unacceptably increasing the total ischemic time for the transplanted grafts. Phosphocreatine (PCr) and inorganic phosphate (Pi ) was significantly different between the two groups (0.95+/-0.29 for TS1 and 2.05+/-0.74 for TS2). The difference in pHi was also significant (7.44+/-0.13 for TS1 and 7.64+/-0.19 for TS2). CONCLUSIONS: Determination of PCr-Pi and pHi as markers of ischemic injury before transplantation can be considered as an objective and accurate criterion for the decision to accept or refuse heart grafts for transplantation.

Adult↗

PubMed2002

Metabolic and electrophysiological alterations in subtypes of temporal lobe epilepsy: a combined proton magnetic resonance spectroscopic imaging and depth electrodes study.

PURPOSE: This study compared the metabolic regional alterations, characterized by proton magnetic spectroscopic imaging ((1)H-MRSI), with electrophysiological abnormalities recorded by using depth electrodes and with structural lesions, in patients with several subtypes of temporal lobe epilepsy (TLE). METHODS: Twenty-five subjects were investigated, including 15 controls and 10 patients with drug-resistant unilateral TLE, nine of whom had structural abnormalities identified by MRI. All patients underwent noninvasive presurgical evaluation and then stereoelectroencephalography (SEEG). We performed an original metabolic exploration combining two (1)H-MRS imaging acquisitions associated with two single-voxel acquisitions (temporal poles) to map the most informative regions of interest (ROIs) including mesial and neocortical localizations. The N-acetyl aspartate/(choline+creatine) ratio was chosen as a metabolic index. SEEG analysis allowed the classification of each ROI as electrically normal or abnormal (i.e., involved in ictal and/or interictal discharges). Groups were compared by using a nonparametric Mann-Whitney U test. RESULTS: N-Acetyl aspartate/(choline+creatine) was significantly lower in all regions involved in SEEG electrophysiological epileptic abnormalities than in controls (p < 0.05). In contrast, the regions without any electrophysiological abnormalities were not metabolically different from those in controls (p > 0.05) except in one ROI. No differences between the metabolic profiles of epileptogenic and irritative zones were found. The metabolic alterations included, but also extended beyond, the lesions. The presence of metabolic abnormalities in mesial structures was not specific for the mesial subtype and generally extended outside the mesial structures. CONCLUSIONS: These results indicate that metabolic abnormalities are linked to ictal and interictal epileptiform activities rather than to structural alterations in TLE.

Adolescent↗

PubMed2002

MR imaging and MR spectroscopy in rhizomelic chondrodysplasia punctata.

A case of rhizomelic chondrodysplasia punctata was investigated with MR imaging of the brain and hydrogen-1 MR spectroscopy of the brain and blood. Areas with abnormal signal hyperintensity on T2-weighted images or hypointensity on T1-weighted images were detected in the subcortical white matter. MR spectroscopy of the brain showed that normal-appearing white matter was characterized by increased levels of mobile lipids and myo-inositol, reduced levels of choline, and the presence of acetate. The importance of these metabolic anomalies is correlated to the deficiency in plasmalogen biosynthesis.

Acyltransferases↗

PubMed2002

[Contribution of magnetic resonance spectrometry to the diagnosis of intracranial tumors].

Magnetic resonance spectroscopy (MRS) is a method enabling the analysis of the tissue metabolic content. It may offer a more accurate diagnosis of the intracranial tumors than conventional MRI sequences. MRS of normal brain parenchyma displays 4 main metabolites: N-acetyl aspartate (neuronal marker), creatine (cellular density marker), choline (membrane activity marker) and myoinositol (glial marker); pathological processes lead to variations of the level of these metabolites and/or the appearance of abnormal metabolites (lactate), following different patterns according to pathological process involved: glioma, meningioma, metastasis, bacterial or toxoplasmic abscess, radionecrosis. The potential clinical use of this method includes positive, differential and etiological diagnosis of tumors, determination of the level of malignancy of gliomas, screening for tumor recurrence following treatment. Our laboratory has been performing MR spectroscopic explorations of brain tumors for many years. Based on this experience, we show how MRS can be routinely performed in the clinical setting, what are its limitations and potential, and what kind of information can be supplied to the clinician.

Aspartic Acid↗