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Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis

Inglese, Matilde; Li, Belinda S Y; Rusinek, Henry; Babb, James S; Grossman, Robert I; Gonen, Oded
It is well known that multiple sclerosis (MS) pathogenesis continues even during periods of clinical silence. To quantify the metabolic characteristics of this activity we compared the absolute levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the normal-appearing white matter (NAWM) between relapsing-remitting (RR) MS patients and controls. Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3) volume-of-interest (VOI), centered on the corpus callosum of 11 MS patients and 9 matched controls. Gray/white-matter/cerebral-spinal-fluid (CSF) volumes were obtained from MRI segmentation. Patients' average VOI tissue volume (V(T)), 410.8 +/- 24.0 cm(3), and metabolite levels, NAA = 6.33 +/- 0.70, Cr = 4.67 +/- 0.52, Cho = 1.40 +/- 0.17 mM, were different from the controls by -8%, -9%, +22% and +32%. The Cho level was the only single metric differentiating patients from controls at 100% specificity and >90% sensitivity. Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation, gliosis, or de- and remyelination in the NAWM. Both metabolites are potential prognostic indicators of current disease activity, preceding NAA decline and atrophy
PMID: 12815694
ISSN: 0740-3194
CID: 39190

Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis

Filippi, M; Bozzali, M; Rovaris, M; Gonen, O; Kesavadas, C; Ghezzi, A; Martinelli, V; Grossman, R I; Scotti, G; Comi, G; Falini, A
Although axonal pathology is recognized as one of the major pathological features of multiple sclerosis, it is less clear how early in its course it occurs and how it correlates with MRI-visible lesion loads. To assess this early axonal pathology, we quantified the concentration of whole-brain N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical stage of the disease and compared the results with those from healthy controls. Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance spectroscopy were obtained from 31 patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis and paraclinical evidence of dissemination in space, and from 16 matched controls. An additional conventional MRI scan was obtained in all patients 4-6 months later to detect dissemination of lesions in time. The mean WBNAA concentration was significantly lower in patients compared with the controls (P < 0.0001). It was not significantly different between patients with and without enhancing lesions at the baseline MRI or between patients with and without lesion dissemination in time. No correlation was found between WBNAA concentrations and lesion volumes. Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis. This finding lessens the validity of the current concept that the axonal pathology of multiple sclerosis is the end-stage result of repeated inflammatory events, and argues strongly in favour of early neuroprotective intervention
PMID: 12538409
ISSN: 0006-8950
CID: 43794

Whole brain imaging of HIV-infected patients: quantitative analysis of magnetization transfer ratio histogram and fractional brain volume

Ge, Yulin; Kolson, Dennis L; Babb, James S; Mannon, Lois J; Grossman, Robert I
BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) histogram analysis and volumetric MR imaging are sensitive tools with which to quantify the tissue destructive effects in patients with white matter or neurodegenerative disease. Our purpose was to determine whether whole brain MTR and fractional brain parenchyma volume measurements are altered in HIV-1-infected patients who are neurologically symptomatic and in those who are asymptomatic. METHODS: We performed MR imaging and MTR studies of 15 neurologically symptomatic (seven patients) and asymptomatic (eight patients) HIV-1-seropositive patients and compared their findings with those of 10 seronegative normal control participants. MTR was computed on the basis of whole brain parenchyma segmented by using thin section dual echo MR images. RESULTS: The loss of brain tissue, indicated by fractional brain parenchyma volume, was more pronounced in neurologically symptomatic patients (P =.003) but not in asymptomatic patients (P =.23) when compared with control participants. As for whole brain MTR histogram analysis, both patient groups showed significant decrease in mean (P =.02) and median (P < or =.009) values, compared with normal control participants. There was a trend toward positive correlation (r > or = 0.56) between MTR histogram statistics and fractional brain parenchyma volume. CONCLUSION: Our results suggest that MTR histogram analysis is sensitive in detecting early involvement in neurologically asymptomatic patients with HIV and may, therefore, be used as a combined tool with volumetric measurement, which showed significant tissue loss only in symptomatic patients, to assess various stages of brain damage induced by HIV
PMID: 12533331
ISSN: 0195-6108
CID: 39325

Brain metabolite profiles of T1-hypointense lesions in relapsing-remitting multiple sclerosis

Li, Belinda S Y; Regal, Juleiga; Soher, Brian J; Mannon, Lois J; Grossman, Robert I; Gonen, Oded
BACKGROUND AND PURPOSE: Persistent T1-hypointense lesions ('black holes') are thought to represent permanent damage of brain parenchyma. We attempted to ascertain whether the metabolic profiles of these hypointense areas support this hypothesis and whether these profiles correlate with these hypointense findings. METHODS: Four patients with relapsing-remitting multiple sclerosis and four matched control volunteers underwent MR imaging and 3D proton MR spectroscopy. Absolute levels of N-acetylaspartate (NAA), creatine, and choline (Cho) were obtained in 0.19 cm(3) voxels containing 14 T1-hypointense lesions (average volume, 0.4 cm(3); range, 0.2-1.0 cm(3)) in patients. Metabolite levels were analyzed, by using Pearson correlation, against their respective lesions' hypointensity relative to the surrounding normal-appearing white matter. RESULTS: Moderate correlation, r = 0.56, was found between the NAA level and MR imaging hypointensity. Of the 14 lesions studied, 12 were deficient in NAA and 11 had excess Cho compared with corresponding brain regions in control volunteers. Only one lesion was significantly deficient in all three metabolites, indicative of total damage or matrix loss. CONCLUSION: No relationship was found between the hypointensity of the lesions and their metabolic profile. Specifically, lesions with the same hypointensity on T1-weighted MR images were metabolically variable (ie, displayed disparate metabolite levels and behavior). Also, although 86% of the lesions exhibited abnormally low NAA, 71% also had increased Cho. This indicates that although neuronal damage had already occurred (lower NAA), these lesions were still 'smoldering' with active membrane turnover (high Cho), most likely because of de- and remyelination, indicative of shadow plaques (remyelinated lesions). Consequently, relapsing-remitting hypointense lesions represent neither final-stage nor static pathologic abnormality
PMID: 12533329
ISSN: 0195-6108
CID: 39326

Neuroradiology : the requisites

Grossman RI; Yousem DM
Philadelphia : Mosby, 2003
Extent: 908 p. ; 29cm
ISBN: 032300508x
CID: 775

Global brain proton MR spectroscopy in MS

Chapter by: Gonen O; Grossman RI
in: New frontiers of MR-based techniques in multiple sclerosis by Filippi M; Comi G [Eds]
Milano ; New York : Springer, 2003
pp. 47-71
ISBN: 8847001986
CID: 3796

Proton magnetic resonance spectroscopic characteristics of hypo- and iso-intense T1 lesions versus normal-appearing white matter in relapsing-remitting multiple sclerosis patients [Meeting Abstract]

He, J; Li, BS; Regal, J; Babb, JS; Grossman, RI; Gonen, O
ISI:000178825102169
ISSN: 0033-8419
CID: 105106

Proton magnetic resonance spectroscopy of global metabolic variations as indicators of disease activity in relapsing remitting multiple sclerosis [Meeting Abstract]

Grossman, RI; Gonen, O
ISI:000178825101244
ISSN: 0033-8419
CID: 105101

Whole brain N-acetylaspartate proton MRS measurements in relapsing-remitting multiple sclerosis: Evidence for different clinical cohorts [Meeting Abstract]

Gonen, O; Li, BS; Babb, JS; He, J; Markowitz, CE; Grossman, RI
ISI:000178825101246
ISSN: 0033-8419
CID: 105102

Proton magnetic resonance spectroscopy evidence for early gray matter involvement in relapsing remitting MS [Meeting Abstract]

Inglese, M; Ge, Y; Filippi, M; Falini, A; Grossman, RI; Gonen, O
ISI:000178825101247
ISSN: 0033-8419
CID: 105103