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Daniel Pelletier

Publications and source records attributed to Daniel Pelletier.

17 recordsLinked to original sources
PubMed2006

TE-averaged two-dimensional proton spectroscopic imaging of glutamate at 3 T.

Glutamate and glutamine are important neurochemicals in the central nervous system and the neurotoxic properties of excess glutamate have been associated with several neurodegenerative diseases. The TE-Averaged PRESS technique has been shown by our group to detect an unobstructed glutamate signal at 3 T that is resolved from glutamine and NAA at 2.35 ppm. TE-Averaged PRESS therefore provides an unambiguous measurement of glutamate as well as other metabolites such as NAA, choline, creatine, and myo-inositol. In this study, we extend the single voxel TE-Averaged PRESS technique for two-dimensional (2D) spectroscopic imaging (TE-Averaged MRSI) to generate 2D glutamate maps. To facilitate TE-Averaged MRSI within a reasonable time, a fast encoding trajectory was used. This enabled rapid acquisition of TE-Averaged spectral arrays with good spectral bandwidth (977 Hz) and resolution (approximately 2 Hz). MRSI data arrays of 10 x 16 were acquired with 1.8 cm3 spatial resolution over a approximately 110 cm3 volume in a scan time of approximately 21 min. Two-dimensional metabolite maps were obtained with good SNR and clear differentiation in glutamate levels was observed between gray and white matter with significantly higher glutamate in gray matter relative to white matter as anticipated.

Aspartic Acid↗
PubMed2006

A temporal framework for understanding the effects of stressful life events on inflammation in patients with multiple sclerosis.

A growing literature reports that stressful life events are associated with exacerbation and the subsequent development of brain lesions in patients with multiple sclerosis (MS). The evolution an MS exacerbation occurs over a period of many months and involves many different biological processes that change over time. Likewise, the experience of stress also occurs over time, with an onset, a shift from acute to chronic in some cases, and resolution. Each of these phases is associated with unique biological features. Thus, the impact of stress on MS exacerbation may depend on the temporal trajectories of stress and MS exacerbation, and when the intersection between these two trajectories occurs. This paper presents a temporal model, along with three different temporal relationships and associated mechanisms by which stress may impact MS exacerbation. These include the onset of a stressor, which may be mediated by mast cell activation, the point that a stressor begins to become chronic, which may be mediated by glucocorticoid resistance in immune cells, and the resolution of the stressor, which may be mediated by a drop in cortisol. These three hypotheses are not necessarily mutually exclusive. Data on psychosocial mediators and moderators are also briefly reviewed and future research directions are discussed.

Acute Disease↗
PubMed2005

Measurement of in vivo multi-component T2 relaxation times for brain tissue using multi-slice T2 prep at 1.5 and 3 T.

The objective of this study was to implement a clinically relevant multi-slice multi-echo imaging sequence in order to quantify multi-component T2 relaxation times for normal volunteers at both 1.5 and 3 T. Multi-echo data were fitted using a nonnegative least square algorithm. Twelve echo data with nonlinear echo sampling were acquired using a receive-only eight-channel phased array coil and volume head coil for phantoms and normal volunteers, and compared to 32-echo data with linear echo sampling. It was observed that the performance of the 180 degrees refocusing trains was more spatially uniform for the receive-only eight-channel phased array coil than for the head coil, particularly at 3 T. The phantom study showed that the estimated T2 relaxation times were accurate and reproducible for both single- and multi-slice acquisition from a commercial phantom with known T2 relaxation times. Short T2 components (T2 <50 ms) were mainly observed within the white matter for normal volunteers, and the fraction of short T2 water components (i.e., myelin water) was 7-12% of total water. It was observed that the calculated myelin water fraction map from the nonlinearly sampled 12-echo data was comparable with that from the linearly sampled 32-echo data. Quantification of T2 relaxation times from multi-slice images was accomplished with a clinically acceptable scan times (16 min) for normal volunteers by using a nonselective T2 prep imaging sequence. The use of the eight-channel head coil involved more accurate quantification of T2 relaxation times particularly when the number of echoes was limited.

Adult↗
PubMed2005

Progressive multifocal leukoencephalopathy in a patient treated with natalizumab.

We describe the clinical course of a patient with multiple sclerosis in whom progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the central nervous system, developed during treatment with interferon beta-1a and a selective adhesion-molecule blocker, natalizumab. The first PML lesion apparent on magnetic resonance imaging was indistinguishable from a multiple sclerosis lesion. Despite treatment with corticosteroids, cidofovir, and intravenous immune globulin, PML progressed rapidly, rendering the patient quadriparetic, globally aphasic, and minimally responsive. Three months after natalizumab therapy was discontinued, changes consistent with an immune-reconstitution inflammatory syndrome developed. The patient was treated with systemic cytarabine, and two months later, his condition had improved.

Adult↗
PubMed2005

Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T.

Histopathological reports of multiple sclerosis and its animal models have shown evidence of a link between axonal injury in active lesions and impaired glutamate metabolism. Mature oligodendrocytes play a role in glutamate uptake to maintain glutamate homeostasis but in multiple sclerosis white matter the loss of expression of glutamate transporters in the lesion vicinity results in ineffective glutamate removal. Using a magnetic resonance spectroscopy technique that isolates the glutamate resonance at 3 T, we compared glutamate levels between normal subjects and multiple sclerosis patients in different brain areas. Metabolite concentrations (glutamate, glutamine, N-acetyl-aspartate, myo-inositol, choline, creatine) were derived from LCmodel and corrected for T1 relaxation time. Glutamate concentrations were found to be elevated in acute lesions (P = 0.02) and normal-appearing white matter (P = 0.03), with no significant elevation in chronic lesions (P = 0.77). The N-acetyl-aspartate level in chronic lesions was significantly lower (P < 0.001) than in acute lesions and normal-appearing white matter. The choline level in acute lesions was significantly higher (P < 0.001) than in chronic lesions. Evidence was also found for increased glial activity in multiple sclerosis, with significantly higher (P < 0.001) myo-inositol levels in acute lesions compared with control white matter. These in vivo results support the hypothesis that altered glutamate metabolism is present in brains of multiple sclerosis patients.

Acute Disease↗
PubMed2005

Seniors' views on the use of electronic health records.

In the Mauricie and Centre-du-Québec region of the province of Quebec, Canada, an integrated services network has been implemented for frail seniors. It combines three of the best practices in the field of integrated services, namely: single-entry point, case management and personalized care plan. A shared interdisciplinary electronic health record (EHR) system was set up in 1998. A consensus on the relevance of using EHRs is growing in Quebec, in Canada and around the world. However, technology has out-paced interest in the notions of confidentiality, informed consent and the impact perceived by the clientele. This study specifically examines how frail seniors perceive these issues related to an EHR. The conceptual framework is inspired by the DeLone and McLean model whose main attributes are: system quality, information quality, utilisation modes and the impact on organisations and individuals. This last attribute is the focus of this study, which is a descriptive with quantitative and qualitative component. Thirty seniors were surveyed. Positive information they provided falls under three headings: (i) being better informed; (ii) trust and consideration for professionals; and (iii) appreciation of innovation. The opinions of the seniors are generally favourable regarding the use of computers and the EHR in their presence. Improvements in EHR systems for seniors can be encouraged.

Aged↗
PubMed2004

Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis.

OBJECTIVE: To quantify the association between stressful life events and exacerbations of multiple sclerosis. DATA SOURCES: PubMed, PsychInfo, and Psychological Abstracts searched for empirical papers from 1965 to February 2003 with terms "stress", "trauma", and "multiple sclerosis". REVIEW METHODS: Three investigators independently reviewed papers for inclusion/exclusion criteria and extracted the relevant data, including methods, sample statistics, and outcomes. RESULTS: Of 20 studies identified, 14 were included. The meta-analysis showed a significant increase in risk of exacerbation in multiple sclerosis after stressful life events, with a weighted average effect size of d = 0.53 (95% confidence interval 0.40 to 0.65), P < 0.0001. The studies were homogenous, Q = 16.62, P = 0.22, I2 = 21.8%. Neither sampling nor study methods had any effect on study outcomes. CONCLUSIONS: There is a consistent association between stressful life events and subsequent exacerbation in multiple sclerosis. However these data do not allow the linking of specific stressors to exacerbations nor should they be used to infer that patients are responsible for their exacerbations. Investigation of the psychological, neuroendocrine, and immune mediators of stressful life events on exacerbation may lead to new behavioural and pharmacological strategies targeting potential links between stress and exacerbation.

Humans↗
PubMed2004

Corpus callosum axonal injury in multiple sclerosis measured by proton magnetic resonance spectroscopic imaging.

BACKGROUND: Axonal damage has been observed in normal-appearing white matter (NAWM) for patients with multiple sclerosis (MS). OBJECTIVES: To investigate changes in brain metabolite ratios in a region of normal-appearing corpus callosum (CC) for patients with MS and to test its relationship to changes in other regions of NAWM. DESIGN AND METHODS: Data were collected from 24 patients with MS and 15 control subjects. Two-dimensional proton magnetic resonance spectroscopic imaging was performed centered at the CC. Regions of interest from normal-appearing CC were manually segmented using anatomical images. The NAWM outside the CC region was segmented based on the signal intensity in T1- and T2-weighted images. RESULTS: The N-acetylaspartate-creatine-phosphocreatine ratio was lower in both regions for patients with secondary progressive MS compared with the controls; the N-acetylaspartate-creatine-phosphocreatine was lower only in the normal-appearing CC region for patients with relapsing-remitting MS (P<.001) compared with the controls. The ratio of choline-containing compound compared with the creatine-phosphocreatine ratio was also lower in the region of normal-appearing CC for patients with relapsing-remitting MS (P =.003) compared with the controls. There was a correlation between the N-acetylaspartate-creatine-phosphocreatine ratio in the normal-appearing CC and T1 lesions (r = -0.53, P =.01) for all patients. CONCLUSIONS: The CC was a more sensitive location for depicting axonal injury than other regions of NAWM. A correlation between the reduction of the N-acetylaspartate-creatine-phosphocreatine ratio in the normal-appearing CC and the T1 lesions may suggest that transection of axons in lesions may cause distant axonal damage and/or dysfunction that are expressed and more sensitively detectable in the CC.

Adult↗
PubMed2004

Measurement of brain glutamate using TE-averaged PRESS at 3T.

A method is introduced that provides improved in vivo spectroscopic measurements of glutamate (Glu), glutamine (Gln), choline (Cho), creatine (Cre), N-acetyl compounds (NAtot, NAA + NAAG), and the inositols (mI and sI). It was found that at 3T, TE averaging, the f1 = 0 slice of a 2D J-resolved spectrum, yielded unobstructed signals for Glu, Glu + Gln (Glx), mI, NA(tot), Cre, and Cho. The C4 protons of Glu at 2.35 ppm, and the C2 protons of Glx at 3.75 ppm were well resolved and yielded reliable measures of Glu/Gln stasis. Apparent T1/T2 values were obtained from the raw data, and metabolite tissue levels were determined relative to a readily available standard. A repeatibility error of <5%, and a coefficient of variation (CV) of <10% were observed for brain Glu levels in a study of six normal volunteers.

Adult↗
PubMed2004

Measurement of whole-brain atrophy in multiple sclerosis.

Brain atrophy reflects the net result of irreversible and destructive pathological processes in multiple sclerosis (MS). The gross morphological changes can be accurately quantified using standard magnetic resonance imaging (MRI) acquisitions and various image analysis tools. The current methods used to assess whole-brain atrophy in patients with MS can be classified into 2 groups based on their reliance on segmentation and registration. Segmentation-based methods employed to measure whole-brain atrophy in MS include the brain parenchymal fraction, the index of brain atrophy, the whole-brain ratio, the brain to intracranial capacity ratio, fuzzy connectedness/Udupa's method, 3DVIEWNIX, the Alfano method, and SIENAX. Current registration-based methods used to measure whole-brain atrophy in MS include the brain boundary shift integral, SIENA, statistical parametric mapping, template-driven seg mentation, and voxel-based morphometry. Most of the methods presented here are sensitive to subtle changes in brain structures and have been successfully applied to MS as measures of whole-brain atrophy. Yet comparative studies of these methods are limited and are complicated by the lack of a gold standard for image acquisition, a segmentation algorithm, an image analysis method, or a reproducibility measure. Overall, the measure of whole-brain atrophy from MRI contributes to an appreciation of the dynamics of MS pathology and its relationship to the clinical course of MS. Determination of the relative reproducibility, precision, sensitivity, and validity of these methods will promote the use of whole-brain atrophy measures as components of comprehensive MRI-based outcome assessment in MS clinical trials.

Atrophy↗
PubMed2004

Mitoxantrone as a potential therapy for primary progressive multiple sclerosis.

Mitoxantrone (Novantrone) was the first drug approved in western Europe and North America for treatment of secondary progressive multiple sclerosis (SPMS) and progressive relapsing MS (PRMS). Pharmacological properties of mitoxantrone, its role in SPMS, the study rational and design of an ongoing multi-centre, double blind, randomized, placebo-controlled phase 2 trial will be outlined in this article.

Humans↗
PubMed2004

The unique impact of changes in normal appearing brain tissue on cognitive dysfunction in secondary progressive multiple sclerosis patients.

OBJECTIVE: The purpose of this study was to examine the relationships between cognitive functioning, whole brain magnetic transfer ratio (MTR) imaging, supratentorial 1H-magnetic resonance spectroscopy imaging (1HMRSI), and conventional T1 and T2 imaging in a homogenous sample of SPMS patients. METHODS: Nineteen patients underwent a single 90-min imaging session that obtained T1-and T2-weighted images and MTR. 1HMRSI was obtained on 14 of these patients. Patients underwent a neuropsychological battery, which was used to create an integrated measure of cognitive impairment. Cognitive impairment was the dependent variable in two hierarchical multiple regression analyses in which T2 lesion load, T1 lesion load, and MTR or NAA/Cr were entered sequentially. RESULTS: MTR was significantly related to cognitive functioning (deltaR2 = 0.22, P = 0.02) after accounting for T2 lesion load (deltaR2 = 0.33, P = 0.01) and T1 lesion load (deltaR2 = 0.00, P = 0.98). NAA/Cr was not significantly related to cognitive functioning. CONCLUSIONS: Cognitive dysfunction may act as a clinical marker of normal appearing brain tissue pathology in multiple sclerosis.

Adult↗
PubMed2004

[Help and care participation of spouses and children of aged persons who return to homes for the aged and long term care facilities].

This study investigates the participation of family caregivers when an elderly relative is going to a nursing home. Twenty-two primary caregivers, whose relative, aged 60 years or older, had recently been admitted to a public nursing home, were interviewed. The content analysis reveals that caregivers worry about and do what is needed to ensure the physical, psychological, and social well-being of their elderly relative and take care of her/his belongings. Doing things for her/him gradually gives way to managing things. Caregivers carry out the duty of protecting their family members, stimulating them, and keeping a close watch on the work of the staff of the institution.

Adult↗
PubMed2003

Directional diffusion in relapsing-remitting multiple sclerosis: a possible in vivo signature of Wallerian degeneration.

PURPOSE: To examine the role of directional dependence of the apparent diffusion coefficients in the evaluation of normal-appearing brain regions of patients with relapsing-remitting multiple sclerosis. MATERIALS AND METHODS: The role of diffusion tensor eigenvalues was investigated in the normal-appearing brain regions for 18 patients with relapsing-remitting multiple sclerosis and 15 age-matched normal controls. RESULTS: The isotropic apparent diffusion was increased in all regions. However, reduced anisotropy was significant only in regions with high anisotropy, including the corpus callosum and the internal capsule, and was due to increased diffusion tensor eigenvalues corresponding to diffusion transverse to the fibers without significant increase along the fibers. This characteristic pattern of changes in diffusion tensor eigenvalues has been observed previously in cases of Wallerian degeneration. Low-anisotropy regions corresponded to gray matter and gray/white interface regions. Since fiber tract orientations are not determined for regions of low anisotropy, this characteristic pattern of diffusion change is not detectable in these regions. CONCLUSION: Examination of diffusion tensor eigenvectors may provide insight into the changes observed in diffusion and a signature of Wallerian degeneration in the normal-appearing white matter of relapsing-remitting multiple sclerosis patients.

Adult↗
PubMed2003

Standardized, reproducible, high resolution global measurements of T1 relaxation metrics in cases of multiple sclerosis.

BACKGROUND AND PURPOSE: We herein present a methodology for standardized and clinically applicable measurement of T1 relaxation maps with high resolution and volumetric coverage by using the commercially available 3D spoiled gradient-echo sequence. The reproducibility of the T1 metrics derived from these maps and their sensitivity to distinguish between control participants and patients with multiple sclerosis are evaluated. METHODS: Axial view 3D RF spoiled data sets with two flip angles were acquired at 1.5 T to generate the T1 maps, with all other imaging parameters (27/6 ms [TR/TE]; field of view, 180 x 240 x 186 mm(3); matrix, 192 x 256 x 124) kept identical between the two acquisitions. T1 maps were collected from 20 normal control participants and 32 patients with multiple sclerosis. An automated and operator-independent method was developed to segment the relaxation maps and define T1 metrics. RESULTS: We showed that the metrics derived from these maps to represent tissue characteristics were highly reproducible (coefficient of variation, approximately 1% to 4%) and were significantly different between normal control participants and patients with multiple sclerosis (P <.001) for the small cohort of patients in this study. CONCLUSION: The commercially accessible 3D spoiled gradient-echo sequence can be used to generate T1 relaxation maps with high resolution and volumetric coverage. The metrics derived from the relaxation maps are reproducible and have been shown to be sensitive to qualitative and quantitative differences between subgroups of patients with multiple sclerosis and control participants, with strong statistical significance. The use of a commercially available sequence enables the standardization and comparison of T1 metrics across different multiple sclerosis centers.

Artifacts↗
PubMed2002

Dissociating perceptual and conceptual implicit memory in multiple sclerosis patients.

Previous studies indicate that Multiple Sclerosis (MS) patients exhibit deficits in tests of explicit memory such as free recall, but show normal priming on implicit tests of memory such as word stem completion. However, the memory performance of patients with different MS disease subtypes has not been fully examined. In the current study, memory was assessed in Primary Progressive (PPMS), Relapsing Remitting (RRMS), and Secondary Progressive (SPMS) MS subgroups. Explicit memory as well as perceptual and conceptual implicit memory were examined using free recall, word fragment completion, and exemplar generation tests, respectively. All three groups of MS patients exhibited free recall deficits and normal priming on the exemplar generation test. However, the PPMS group exhibited a deficit in word fragment completion priming, whereas the RRMS and SPMS groups exhibited normal levels of priming on this task. Lesion load was assessed using magnetic resonance imaging and was negatively correlated with explicit memory performance, but it did not account for the observed deficits in perceptual implicit memory. The results indicate that PPMS patients exhibit a pattern of memory impairment that is distinct from that of the RRMS and SPMS groups. Moreover, the results indicate that perceptual implicit memory can be neurologically dissociated from conceptual implicit memory.

Adult↗