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Biomedical subjects

J Frahm

Publications and source records attributed to J Frahm.

At least 73 records · Page 4Linked to original sources
PubMed1998

Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS.

The regional distribution of brain metabolites was studied in several cortical white and gray matter areas, cerebellum, and thalamus of young adults with use of quantitative single-voxel proton MRS at 2.0 T. Whereas the neuronal compound N-acetylaspartate is distributed homogeneously throughout the brain, N-acetylaspartylglutamate increases caudally and exhibits higher concentrations in white matter than in gray matter. Creatine, myo-inositol, glutamate, and glutamine are less concentrated in cortical white matter than in gray matter. The highest creatine levels are found in cerebellum, parallel to the distribution of creatine kinase and energy-requiring processes in the brain. Also myo-inositol has highest concentrations in the cerebellum. Choline-containing compounds exhibit a marked regional variability with again highest concentrations in cerebellum and lowest levels and a strong caudally decreasing gradient in gray matter. The present findings neither support a metabolic gender difference (except for a 1.3-fold higher myo-inositol level in parietal white matter of female subjects) nor a metabolic hemispheric asymmetry.

Adolescent↗
PubMed1998

Proton T2 relaxation of cerebral metabolites during transient global ischemia in rat brain.

Putative changes of metabolite T2 relaxation times were investigated before and after a 20-min period of global ischemia in rat brain in vivo (n = 10) using localized proton MRS at different echo times (2.35 T). Neither absolute T2 relaxation times (TE = 20-270 ms) nor time courses of T2-weighted metabolite signals (TE = 135 ms) revealed statistically significant changes during the occlusion or early reperfusion relative to pre-ischemic baseline. These findings are in line with reports of relaxation changes at much later stages and further demonstrate that altered T2 relaxation is not a confounding factor in diffusion-weighted long-TE proton MRS during early ischemic events.

Animals↗
PubMed1998

Temporal characteristics of oxygenation-sensitive MRI responses to visual activation in humans.

Series of single-shot blipped echo-planar images with spin-density weighting and T2* sensitivity (2.0 T, TR = 400 ms, TE = 54 ms, flip angle = 30 degrees) were used to study the temporal response profiles to repetitive visual activation (5 Hz, reversing black and white checkerboard versus darkness) for protocols comprising multiple cycles of a 1.6-s stimulus in conjunction with a 8.4-s or 90-s recovery phase and a 10-s stimulus with a 20-s or 90-s recovery phase. Analysis of the real-time data from all activated pixels resulted in a strong positive MRI response (mean values 3-6%) as well as a marked poststimulus undershoot (mean values 1-2%, duration 60-90 s) for all paradigms. Repetitive protocols with insufficient recovery periods of 8.4 s or 20 s gave rise to a wraparound effect when analyzing time-locked averages from multiple activation cycles. This problem may lead to an early signal decrease that originates from the ongoing undershoot of preceding activations folded back into the initial latency phase of a subsequent activation. When ensuring complete decoupling of responses to successive stimuli by using a 90-s recovery period, the wraparound effect vanished and an initial dip was observed in one of seven subjects for a 10-s/90-s protocol.

Adult↗
PubMed1998

Proton magnetic resonance spectroscopy of linear nevus sebaceus syndrome.

Cerebral metabolites of a patient with linear nevus sebaceus syndrome and hemimegalencephaly were determined at 18 and 30 months of age by localized proton magnetic resonance spectroscopy. Clinically, the patient suffered from hemiparesis and epileptic seizures. At 18 months of age, spectroscopy of the enlarged hemisphere revealed decreased N-acetylaspartate mainly in parietal white matter relative to the unaffected hemisphere. One year later, white matter studies indicated both reduced N-acetylaspartate and elevated myoinositol. In insular gray matter the previously normal concentrations of creatine, choline-containing compounds, myoinositol, and glutamine were increased. The findings are consistent with mild neuroaxonal loss or damage (white matter) and glial proliferation (cortical gray and white matter) of the affected hemisphere. The metabolic disturbances indicate disease progression but are less pronounced than in older patients with hemimegalencephaly.

Aspartic Acid↗
PubMed1998

Quantitative proton magnetic resonance spectroscopy of childhood adrenoleukodystrophy.

Cerebral metabolic disturbances in patients with childhood adrenoleukodystrophy (ALD) were assessed by quantitative localized proton MRS. Patient monitoring by follow-up MRS studies served to identify putative markers for disease onset and progression. Whereas normal-appearing white matter of neurologically asymptomatic patients is characterized by slightly elevated concentrations of choline-containing compounds (Cho), an increase of both Cho and myo-inositol (Ins) seems to indicate the onset of demyelination. Markedly elevated concentrations of Cho, Ins, and glutamine in affected white matter reflect active demyelination and glial proliferation. A simultaneous reduction of the concentrations of N-acetylaspartate and glutamate is consistent with neuronal damage or loss. The observation of elevated lactate is in line with inflammation and/or macrophage infiltration. The more severe metabolic disturbances in cerebral ALD correspond to progressive demyelination, neuroaxonal loss and gliosis leading to clinical deterioration and eventually death. The detection of MRS abnormalities before the onset of neurological symptoms may help in the selection of patients for bone marrow transplantation (BMT). Stabilization and partial reversal of metabolic abnormalities is demonstrated in a patient after BMT.

Adolescent↗
PubMed1997

Differential distribution of NAA and NAAG in human brain as determined by quantitative localized proton MRS.

Quantitative proton magnetic resonance spectroscopy was performed in frontal, parietal and occipital white and gray matter of young adults with use of a fully relaxed, short-echo time stimulated echo acquisition mode localization sequence at 2.0 T. Separate concentrations of the neuronal compounds N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) were obtained by user-independent spectral analysis (LCModel). Except for occipital gray matter in which an NAA concentration of 10.1 +/- 1.0 mM correlated with enhanced neuronal density in visual cortex, NAA was found to be homogeneously distributed throughout cortical white and gray matter at a concentration of 8.0-8.9 mM. NAAG concentrations of 1.5-2.7 mM were higher in white matter than levels of 0.6-1.5 mM found in gray matter, contributing up to 25% of total N-acetyl-containing compounds. The frontal to parieto-occipital increase of both gray and white matter NAAG levels is also reflected in the distribution of total NAA.

Adolescent↗
PubMed1997

Equivalent responses to lexical and nonlexical visual stimuli in occipital cortex: a functional magnetic resonance imaging study.

Stimulus-related changes in cerebral blood oxygenation were measured using high-resolution functional magnetic resonance imaging sequentially covering visual occipital areas in contiguous sections. During dynamic imaging, healthy subjects silently viewed pseudowords, single false fonts, or length-matched strings of the same false fonts. The paradigm consisted of a sixfold alternation of an activation and a control task. With pseudowords as activation vs single false fonts as control, responses were seen mainly in medial occipital cortex. These responses disappeared when pseudowords were alternated with false font strings as the control and reappeared when false font strings instead of pseudowords served as activation and were alternated with single false fonts. The string-length contrast alone, therefore, is sufficient to account for the activation pattern observed in medial visual cortex when word-like stimuli are contrasted with single characters.

Adult↗
PubMed1997

Dynamic NMR studies of perfusion and oxidative metabolism during focal brain activation.

Together, the present results on oxygenation, flow, and metabolism indicate that the prevalence of nonoxidative glycolysis and associated lactate production during the initial phase of activation is replaced by the upregulation of oxidative glucose consumption (see sketches in Fig. 5). Following rapid circulatory changes the gap between oxygen availability and oxygen consumption gradually closes until a recoupling of perfusion and oxidative metabolism is achieved a few minutes after switching the state of neural activity. While brain glucose and lactate concentrations reflect an initial prevalence of anaerobic glycolysis, the changes in blood oxygenation suggest that the rapid adjustment of blood flow (enhanced oxygen delivery) is followed by a slower upregulation of oxidative metabolism (enhanced oxygen consumption). The physiological uncoupling of perfusion and oxidative metabolism emerges as a transient phenomenon in response to both onset and end of stimulation. Recoupling at enhanced cerebral metabolic rates of oxygen (CMRO2) and glucose occurs a few minutes after switching the state of neural activity. Since glycolysis takes place primarily in astrocytes, the stimulus-related increase and decrease of lactate seen here may reflect a transfer of astrocytic lactate to neurons where it is converted into pyruvate and channelled into oxidative phosphorylation. This model of metabolic responses to functional activation is supported by a recently detected pathway for glutamate-stimulated glycolysis in astrocytes that provides a simple mechanism linking astrocytic glucose utilization to neuronal activity (Pellerin and Magistretti, 1994). In summary, evidence has accumulated that the physiological uncoupling of perfusion and oxidative metabolism associated with the onset of functional activation is a transient phenomenon leading to an only temporal mismatch of oxygen delivery and consumption. Recoupling at enhanced though balanced levels of glucose and oxygen consumption is most remarkably documented by the pronounced "negative" uncoupling at the end of stimulation.

Blood Flow Velocity↗
PubMed1997

Cystic leukoencephalopathy in a megalencephalic child: clinical and magnetic resonance imaging/magnetic resonance spectroscopy findings.

A neurodegenerative disorder characterized by megalencephaly since early infancy and slowly progressive symptoms of cerebellar, pyramidal, and extrapyramidal dysfunction, pseudobulbar signs, and epilepsy was detected in an 8-year-old girl with severe neuromotor handicap but preservation of mental and sensory functions. Cranial computed tomography and magnetic resonance imaging revealed brain swelling as well as severe abnormalities of frontal, temporal, and parietal white matter, with an extended cystlike appearance isointense to cerebrospinal fluid. Localized proton magnetic resonance spectroscopy of affected cystic white matter showed a loss of all metabolites, in accordance with a complete disintegration of neuroaxonal and glial tissue. This case is likely a severe variant of a recently described megalencephalic leukoencephalopathy with swelling and discrepantly mild clinical course.

Brain↗
PubMed1997

Somatotopy in the human motor cortex hand area. A high-resolution functional MRI study.

Fine-scale somatotopic encoding in brain areas devoted to sensorimotor processing has recently been questioned by functional neuroimaging studies which suggested its absence within the hand area of the human primary motor cortex. We re-examined this issue by addressing somatotopy both in terms of functional segregation and of cortical response preference using oxygenation-sensitive magnetic resonance imaging at high spatial resolution. In a first step, spatial representations of self-paced isolated finger movements were mapped by using motor rest as a control state. A subsequent experimental design studied the predominance of individual finger movements by using contrasting finger movements as the control task. While the first approach confirmed previous reports of extensive overlap in spatial representations, the second approach revealed foci of differential activation which displayed an orderly mediolateral progression in accordance with the classical cortical motor homunculus. We conclude that somatotopy within the hand area of the primary motor cortex does not present as qualitative functional segregation but as quantitative predominance of certain movement or digit representation embedded in an overall joint hand area.

Adult↗
PubMed1996

Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism.

BACKGROUND: The creatine/creatine-phosphate system is essential for the storage and transmission of phosphate-bound energy in muscle and brain. In infants, inefficiency or failure of this metabolic pathway can impair the development of motor control and mentation. METHODS: We studied and treated an infant with extrapyramidal signs who was shown--by assay for urinary creatinine and by analysis of brain metabolites with use of nuclear magnetic resonance spectra--to have depletion of body and brain creatine, due to inborn deficiency of guanidinoacetate methyltransferase (GAMT). FINDINGS: Long-term oral administration of creatine-monohydrate (4-8 g per day) to this index patient resulted in substantial clinical improvement, disappearance of magnetic resonance (MRI) signal abnormalities in the globus pallidus, and normalisation of slow background activity on the electroencephalogram (EEG). During the 25-month treatment period, both brain and total body creatine concentrations became normal. INTERPRETATION: Oral creatine replacement has proved to be effective in one child with an inborn error of GAMT. It may well be effective in the treatment of other disorders of creatine synthesis.

Basal Ganglia Diseases↗
PubMed1996

Metabolic alterations in brain autopsies: proton NMR identification of free glycerol.

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.

Animals↗
PubMed1996

Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man.

Changes in glucose consumption, lactate production, and blood oxygenation were measured during prolonged neuronal activation (4-6 min) in human primary visual cortex using dynamic magnetic resonance spectroscopy and imaging. A decrease of steady-state glucose by 40% because of enhanced use by 21% was accompanied by a transient accumulation of lactate with a peak value of 170% 2.5 min after stimulation onset. Rapid blood hyperoxygenation indicating "uncoupling" of blood flow and oxidative metabolism was followed by a return to basal levels over 3 min. Thus, initial nonoxidative glucose consumption during functional activation is gradually complemented by a slower adjustment of oxidative phosphorylation that "recouples" perfusion and oxygen consumption at a new equilibrium.

Adult↗
PubMed1996

Dynamic MRI sensitized to cerebral blood oxygenation and flow during sustained activation of human visual cortex.

Changes in cerebral blood oxygenation and flow during prolonged activation of human visual cortex (6-min video projection) were monitored using high-resolution T2*- and T1-weighted gradient-echo MRI in identical sessions. Oxygenation-sensitive recordings displayed an initial signal increase (oxygenation "overshoot"), a subsequent signal decrease extending over 4-5 min (relative deoxygenation), and a signal drop after the end of stimulation that mirrored the initial response (oxygenation "undershoot"). Flow-sensitive MRI demonstrated that the inflow effect remained elevated during the entire period of stimulation. The observation of gradually decreasing cerebral blood oxygenation, despite persisting elevation of blood flow, may be understood to be an accumulation of deoxyhemoglobin due to the progressive up-regulation of oxidative phosphorylation. The present findings support a concept in which transitions between functional states lead to an uncoupling of perfusion (oxygen delivery) from oxidative metabolism (oxygen consumption) whereas steady-state activity achieves their recoupling.

Adult↗
PubMed1996

Functional mapping of color processing by magnetic resonance imaging of responses to selective P- and M-pathway stimulation.

Magnetic resonance imaging sensitized to activity-related changes in cerebral blood oxygenation was performed to map responses to selective stimulation of the parvo- and magnocellular visual pathways in calcarine and adjacent ventral occipital cortex of human subjects. In a repetitive stimulation protocol isoluminant chromatic or isochromatic luminance modulation was alternated with steady light of the same mean chromaticity and luminance as a reference condition. While no significant effects were observed for diffuse luminance modulation, two consistent cortical foci responded to isoluminant chromatic stimulation. A strong response was obtained in calcarine cortex at both 2 and 10 Hz, and even for selective S-cone stimulation. A second weaker color-sensitive response was seen bilaterally in the collateral sulcus. Thus, the data not only confirm color-sensitive activation in the collateral sulcus elicited in previous studies by selective cognitive tasks, but additionally demonstrate color-sensitive activation in primary visual cortex. With stimuli defined according to electrophysiological response properties of early visual processing stages, this study complements phenomenological or cognitive approaches in functional mapping of the human visual system.

Adult↗
PubMed1996

Localized proton magnetic resonance spectroscopy of a cerebellar tumor in a two-year-old child.

Noninvasive localized proton magnetic resonance spectroscopy (MRS) was used for differential diagnosis of a focal brain lesion in a 2.5-year-old girl. The clinical signs were a mild head tilt and neck pain. Magnetic resonance imaging (MRI) revealed a lesion in the right hemisphere of the cerebellum, but its nature remained obscure. In this lesion quantitative determinations of cerebral metabolites by fully relaxed, short-echo-time proton MRS revealed markedly lowered N-acetylaspartate (NAA) and pronounced elevations of choline-containing compounds (Cho) and myo-inositol (Ins), whereas metabolite concentrations in cortical gray matter and white matter were within normal ranges. The metabolite pattern of the lesion indicated loss of vital neuroaxonal tissue (low NAA) and enhanced glial proliferation (high Cho and Ins), which, together with the MRI morphology, suggested a brain tumor. The diagnosis was established by neurosurgical exploration and total extirpation of the tumor. Histology confirmed an astrocytoma (WHO II). After 2 weeks' recovery the child was discharged with no neurological signs.

Astrocytoma↗
PubMed1996

Arrested cerebral adrenoleukodystrophy: a clinical and proton magnetic resonance spectroscopy study in three patients.

We report three unrelated boys with X-linked adrenoleukodystrophy with onset of typical neurological symptoms of cerebral adrenoleukodystrophy between the age of 7 and 11 years. In contrast to the expected rapid progression, these patients showed an apparent arrest of initial neurological deterioration for subsequent periods of 5-12 years. Repeated neuroimaging revealed no progression of demyelination. Despite regional variability of demyelination, proton magnetic resonance spectroscopy revealed a specific metabolic pattern in all patients, with only moderate reduction of N-acetylaspartate, normal or reduced choline-containing compounds, normal or enhanced myo-inositol and no detectable lactate, which differs from findings in progressive cerebral adrenoleukodystrophy which usually exhibits a severe reduction of N-acetylaspartate and marked increases of choline-containing compounds, myo-inositol, and lactate. The ability to identify this newly described subgroup of patients with cerebral adrenoleukodystrophy is important for medical advice and planning of therapy.

Aspartic Acid↗