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Contrast-enhanced T₁- and T₂-weighted MRI at 9.4 T and in-plane resolutions of 25 and 30 µm has been demonstrated to differentiate between neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. In T₁-weighted MRI of the olfactory bulb, hippocampus and cerebellum, contrast obtained by the intracranial administration of gadopentetate dimeglumine (Gd-DTPA) reflects the extra- and intracellular spaces of gray matter in agreement with histological data. General neuropil areas are highlighted, whereas other tissues present with lower signal intensities. The induced contrast is similar to that in plain T₂-weighted MRI, but offers a 16-30-fold higher contrast-to-noise ratio. Systemic administration of manganese chloride increases the signal-to-noise ratio in T₁-weighted MRI to a significantly greater extent in principal cell layers and specialized neuropil than in granule cell layers, whereas gadolinium-enhanced MRI indicates no larger intracellular spaces in these tissues. Granule cell layers are enhanced no more than general neuropil by manganese, whereas gadolinium-enhanced MRI indicates significantly larger intracellular spaces in the cell layers. These discrepancies suggest that the signal increase after manganese administration reflects cellular activity which is disproportionate to the intracellular space. As a result, principal cell layers and specialized neuropil become highlighted, whereas granule cell layers, general neuropil and white matter present with lower signal intensities.

Experimental autoimmune encephalomyelitis (EAE) induced by myelin-oligodendrocyte glycoprotein (MOG) in common marmosets (Callithrix jacchus) is a model for multiple sclerosis. Here, EAE was induced in four common marmosets by 250-300 microg recombinant rat MOG. In addition to a detailed disability scoring, T2- and T1-weighted high-resolution 3D MRI was performed to assess the onset and development of cerebral lesions. The findings were confirmed by histopathology in all animals. Although the animals exhibited a large heterogeneity with regard to onset and localization of lesions and also to disease duration and severity of disability signs, none of the animals revealed any evidence of recovery. A specification of the disability scoring system to account for different aspects of the disease led to a good concurrence of the first MRI-detectable lesion and the onset of central nervous system (CNS) symptoms. The results suggest that MRI monitoring of white matter lesions in conjunction with disability scores that focus on CNS symptoms may be a suitable method to evaluate novel therapeutic interventions even in the presence of pronounced interindividual heterogeneity., (2006 John Wiley & Sons, Ltd.)

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination., (Copyright 2005 John Wiley & Sons, Ltd)

This work presents three-dimensional MRI studies of rodent brain in vivo after focal and systemic administration of MnCl2. Particular emphasis is paid to the morphology and dynamics of Mn2+-induced MRI signal enhancements, and the physiological mechanisms underlying cerebral Mn2+ uptake and distribution. It turns out that intravitreal and intrahippocampal injections of MnCl2 emerge as useful tools for a delineation of major axonal connections in the intact central nervous system. Subcutaneous administrations may be exploited to highlight regions involved in fundamental brain functions such as the olfactory bulb, inferior colliculus, cerebellum and hippocampal formation. Specific insights into the processes supporting cerebral Mn2+ accumulation may be obtained by intraventricular MnCl2 injection as well as by pharmacologic modulation of, for example, hippocampal function. Taken together, Mn2+-enhanced MRI opens new ways for mapping functioning pathways in animal brain in vivo with applications ranging from assessments of transgenic animals to follow-up studies of animal models of human brain disorders., (Copyright 2004 John Wiley & Sons, Ltd.)

Proton magnetic resonance spectroscopy (MRS) was employed to determine the concentrations of N-acetylaspartate (NAA), total creatine (tCr), choline-containing compounds (Cho), myo-inositol (Ins), glucose (Glc), and lactate (Lac) in rat brain before and after 10 days of oral supplementation of 2.6 g Cr-monohydrate per kg body weight per day. Measurements were performed both in vitro (n = 16) and in vivo (n = 6). The neuroprotective potential of oral Cr was assessed by dynamically monitoring brain Glc and Lac in response to transient global ischemia (12 min). In comparison to controls the in vitro concentrations of Cr (13.1 +/- 9.3%) and Ins (12.7 +/- 14. 0%) were significantly increased in Cr-fed rats. Under in vivo conditions, the data revealed trends for elevated tCr (4.7%) and Ins (10.6%) which were enhanced in the concentration ratios of tCr:Cho (10.2%) and Ins:Cho (17.8%). Together with an increased Glc level (27.3%), the observation of a statistically significant decrease of brain Lac (-38.5 +/- 19.3%) in Cr-fed rats may reflect a shift of the energy metabolism from non-oxidative toward oxidative glycolysis. One hour after global ischemia most of the metabolic differences between Cr-fed rats and controls were retained. The increased Glc level (44.4 +/- 33.3%) reached statistical significance, but the accumulation of Lac and its time course during ischemia and early reperfusion showed no differences between Cr-fed rats and controls., (Copyright 1999 John Wiley & Sons, Ltd.)

Metabolic alterations in bovine brain homogenate were examined as a function of post mortem interval (PMI) using high-resolution proton NMR spectroscopy. In particular, while lactate, glutamate, glutamine, creatine and inositols as well as the total concentration of trimethyl-ammonium compounds remained constant, prominent changes due to the hydrolysis of N-acetylaspartate to acetate and aspartate as well as the decomposition of glycerophosphocholine into free choline and glycerol correlated linearly with the duration of PMI (3-195 h). The spectroscopic identification of the latter process was confirmed by proton NMR studies of model solutions as well as of extracts of mammalian brain showing high levels of free glycerol. Since the methylene resonances of glycerol overlap with the proton resonances of myo-inositol, care should be taken in the interpretation of both in vitro and in vivo brain spectra.

Scyllo-inositol has been identified in proton NMR spectra of mammalian brain in vitro and in vivo. In contrast to myo-inositol this isomer comprises six equivalent CH protons that yield a singlet resonance at a chemical shift of 3.35 ppm. 1-D and 2-D J-resolved proton NMR studies (7.0 T) of perchloric acid extracts of brain tissues revealed different amounts of scyllo-inositol in man, sheep, cow and rat. Absolute quantification of localized short-echo time proton NMR spectra (2.0 T) of human brain in vivo resulted in scyllo-inositol concentrations of 0.35 +/- 0.06 mM for white matter (n = 25), 0.43 +/- 0.11 mM for grey matter (n = 23) and 0.57 +/- 0.14 mM for cerebellum (n = 10). Evidence for a tight metabolic link to myo-inositol was supported by a simultaneous variation of myo- and scyllo-inositol in patients with various brain diseases.

Localized 1H NMR spectra of human brain in vivo are affected by signal overlap, strong spin-spin coupling, and complex J modulation, and therefore differ considerably from those obtained at higher magnetic fields. This paper deals with the assignment of 1H NMR resonances of cerebral metabolites under the experimental conditions used for human investigations. Conventional 7.0-T FID spectra and 2.0 T localized, short echo time STEAM spectra (TE = 20 ms) of aqueous metabolite solutions are compared to in vivo brain spectra of human volunteers and patients. In addition to singlet resonances from N-acetyl aspartate (NAA), creatines, and cholines, short echo time STEAM spectra exhibit multiplets due to the NAA aspartyl group, glutamate, taurine, and myo-inositol. Enhanced levels of cerebral glutamine are detected in patients with liver cirrhosis. For the first time elevated levels of brain glucose are observed in patients with diabetes mellitus.

Metabolites in brain and muscle of normal human volunteers have been studied by localized 1H and 31P NMR spectroscopy in vivo. Localization was achieved by means of stimulated echo (STEAM) sequences for both water-suppressed 1H NMR (TE = 20 ms) and 31P NMR (TE = 3 ms). Volumes-of-interest and measuring times selected for brain spectroscopy were 8 mL and 6.5 min for 1H NMR and 125 mL and 13 min for 31P NMR, respectively. General problems relating to spatial localization, spectral resolution, and quantitation of in vivo NMR data are discussed with respect to the nucleus and organs under investigation. They are correlated to studies of tissue extracts obtained at field strengths of 2.35 T (Bruker Biospec) and 7.0 T (Bruker MSL 300). Human studies were performed at 2.0 T on a whole-body research system (Siemens Magnetom).