Biomedical subjects

J Frahm

Publications and source records attributed to J Frahm.

At least 55 records · Page 3Linked to original sources

PubMed1999

Does stimulus quality affect the physiologic MRI responses to brief visual activation?

We studied the effect of stimulus quality on the basic physiological response characteristics of oxygenation-sensitive MRI signals. Paradigms comprised a contrast-reversing checkerboard vs. darkness or vs. gray light as well as gray light vs. darkness in a 2 s/52 s protocol (nine subjects). MRI was performed at 2.0 T using single-shot gradient-echo EPI (TR/TE = 500/54 ms, flip angle 30 degrees). All paradigms elicited almost identical signal intensity time courses comprising a latency period (1-2s), an activation-induced signal increase (4-4.5% at about 6-7 s after stimulus onset) and a post-stimulus signal undershoot (-1%) that slowly recovered to baseline (about 50 s). Thus, in contrast to findings for sustained stimulation, brief presentations of distinct visual stimuli exhibit similar physiological response characteristics that support the use of a uniform response profile for the evaluation of event related paradigms.

Adult↗

PubMed1999

Telemedicine.

Explore the source record for details and available documents.

Humans↗

PubMed1999

Effects of sedation, stimulation, and placebo on cerebral blood oxygenation: a magnetic resonance neuroimaging study of psychotropic drug action.

The effects of pharmacologic depression and stimulation of cerebral activity were investigated in seven healthy young volunteers using blood oxygenation-sensitive MRI at 2.0 T. Dynamic gradient-echo imaging (7 min) was performed before, during and after the intravenous application of 10 mg diazepam and 15 mg metamphetamine as well as of the corresponding drug placebos (isotonic saline) in a brain section covering frontotemporal gray matter, subcortical gray matter structures, and cerebellum. The MRI responses were significantly different for the two drugs applied (p = 0.01). Relative to signal strength during injection, metamphetamine elicited a signal increase of 0.97 +/- 0.03% (mean +/- SD, p = 0.02) within the whole section 4-5 min after injection. Similarly, both placebo conditions led to a small signal increase, i.e. 0.50 +/- 0. 03% (n.s.) for the metamphetamine placebo and 0.40 +/- 0.07% (p = 0. 03) for the diazepam placebo. Diazepam abolished this signal increase. A topographic analysis revealed the metamphetamine-induced signal increase to be more pronounced in subcortical gray matter structures (p = 0.01) and cerebellum (p = 0.02) than in frontotemporal cortical gray matter (p = 0.04). This finding is in agreement with the hypothesis that pertinent responses not only reflect global cerebral hemodynamic adjustments, but also localized perfusion changes coupled to alterations in synaptic activity. The occurrence of a placebo response is best explained by expectancy and may provide a confounding factor in the design of functional activation experiments.

Adult↗

PubMed1999

Proton MRS of oral creatine supplementation in rats. Cerebral metabolite concentrations and ischemic challenge.

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.

Administration, Oral↗

PubMed1999

Magnetization transfer attenuation of creatine resonances in localized proton MRS of human brain in vivo.

To assess putative magnetization transfer effects on the proton resonances of cerebral metabolites in human brain, we performed quantitative proton magnetic resonance spectroscopy (2.0 T, STEAM, TR/TE/TM = 6000/40/10 ms, LCModel data evaluation) of white matter (7.68 mL, 10 healthy young subjects) in the absence and presence of fast repetitive off-resonance irradiation (2.1 kHz from the water resonance) using a train of 100 Gaussian-shaped RF pulses (12.8 ms duration, 120 Hz nominal bandwidth, 40 ms repetition period, 1080 degrees nominal flip angle). A comparison of pertinent metabolite concentrations revealed a magnetization transfer attenuation factor of the methyl and methylene resonances of creatine and phosphocreatine of 0.87 +/- 0.05 (p < 0.01). No attenuation was observed for the resonances of N-acetylaspartate and N-acetylaspartylglutamate, glutamate and glutamine, choline-containing compounds, and myo-inositol. The finding for total creatine is in excellent agreement with data reported for rat brain. The results are consistent with the hypothesis of a chemical exchange of mobile creatine or phosphocreatine molecules with a small immobilized or 'bound' pool.

Adult↗

PubMed1999

Localized proton MRS of the human hippocampus: metabolite concentrations and relaxation times.

Absolute concentrations and proton relaxation times of major metabolites in the human hippocampus were determined with use of fully relaxed, short-echo time STEAM localization sequences at 2.0 T (20 normal adults). Mean metabolite concentrations were 7.6+/-0.9 mM for total Nacetylaspartate (tNAA), 6.9+/-0.8 mM for total creatine (tCr), 2.1+/-0.3 mM for choline-containing compounds (Cho), and 6.2+/-0.9 mM for myo-inositol (Ins). The observation of relatively low tNAA and high Cho and Ins levels compared with cortical gray and white matter corresponds to a lower neuronal density and higher glial density than in the neocortex, in agreement with histologic findings. The data do not support a lateralization of metabolites. T1 and T2 relaxation times were in the range of 1400-1730 and 140-330 msec, respectively, similar to those in other brain regions.

Adult↗

PubMed1999

Diffusion-weighted single-shot line scan imaging of the human brain.

Single-shot line scan imaging (LSI) was adapted to diffusion-weighted (DW) MRI by replacing the initial 90 degrees radiofrequency pulse of the underlying high-speed stimulated echo sequence by a DW spin-echo preparation period. Implementation on a 2. 0 T whole-body MRI system yielded DW images of the human brain with b factors of 750 s mm(-2) and total imaging times of about 500 ms either for a single slice at 1.5 x 3.0 x 6 mm(3) resolution or simultaneously for up to seven slices at 3.75 x 3.75 x 8 mm(3) resolution. Isotropic DW images and maps of the trace of the diffusion tensor were calculated from four scans with different combinations of three orthogonal diffusion gradients. DW LSI combines high speed with robustness against image artifacts caused by motion (no phase ghosting) and tissue susceptibility differences (no signal losses, no geometric distortions). Because the latter is an important advantage over echo-planar imaging, DW LSI may find useful applications despite a limited signal-to-noise ratio. Magn Reson Med 42:772-778, 1999.

Brain↗

PubMed1999

Brain water diffusion in normal and creatine-supplemented rats during transient global ischemia.

Brain water diffusion in response to transient global ischemia (12 min), reperfusion (60 min), and cardiac arrest was monitored by localized proton magnetic resonance spectroscopy. The trace of the apparent diffusion coefficient tensor (ADC(Av)) was determined at high temporal resolution (10 sec) to assess the putative neuroprotective potential of oral creatine (Cr) in rats that received 2.2 g Cr-monohydrate per kg body weight per day for 10 days (n = 8) relative to controls (n = 9). Cr-fed rats revealed a statistically significant increase of the cerebral concentration ratio of Cr to choline-containing compounds (20%). The decrease of the ADC(Av) value during acute ischemia showed a three-phasic behavior in line with energy depletion, cytotoxic edema, and brain cooling. In Cr-fed rats, slightly less severe and mildly delayed diffusion changes during ischemia and similar beneficial trends during early reperfusion did not reach statistical significance. Magn Reson Med 42:798-802, 1999.

Animals↗

PubMed1999

Single-shot line scan imaging using stimulated echoes.

A new high-speed MRI method is described for single-shot line scan imaging (LSI) based on stimulated echoes (STE). To allow for multislice imaging, the technique comprises a series of slice-selective preparation pulses (each corresponding to the first RF pulse of a STE sequence), a slab-selective refocusing pulse (second RF pulse), and multiple line-selective read pulses (third RF pulses). An alternative version employs packages of two slice-selective pulses followed by multiple line-selective read pulses. Experimental applications deal with human brain imaging on a clinical MRI system at 2.0 T. The technique offers user-selectable trade-offs between volume coverage (1-15 sections) and in-plane spatial resolution (1-5 mm linear pixel dimension) within total acquisition times of less than 500 ms. Although LSI yields a lower signal-to-noise ratio than Fourier imaging, single-shot LSI with STEs is free from resonance offset effects (e.g., magnetic field inhomogeneities and susceptibility differences) that are typical for echo-planar imaging. Moreover, the technique exhibits considerable robustness against motion and provides access to arbitrary fields-of-view, i.e., localized imaging of inner volumes without aliasing artifacts due to phase wrapping.

Adult↗

PubMed1999

MRI of functional deactivation: temporal and spatial characteristics of oxygenation-sensitive responses in human visual cortex.

Magnetic resonance imaging (MRI) of neuronal "activation" relies on the elevation of blood flow and oxygenation and a related increase of the blood oxygenation level-dependent (BOLD) MRI signal. Because most cognitive paradigms involve both switches from a low degree of activity to a high degree of activity and vice versa, we have undertaken a baseline study of the temporal and spatial characteristics of positive and negative BOLD MRI responses in human visual cortex. Experiments were performed at 2.0 T using a multislice gradient-echo EPI sequence (TR = 1 s, mean TE = 54 ms, flip angle 50 degrees) at 2x2-mm2 spatial resolution. Activation and "deactivation" processes were accomplished by reversing the order of stimulus presentations in paradigms using homogeneous gray light and an alternating checkerboard as distinct functional states. For sustained stimulation (> or = 60 s) the two conditions resulted in markedly different steady-state BOLD MRI signal strengths. The transient responses to brief stimulation (< or = 18 s) differed insofar as activation processes temporally separate positive BOLD and negative undershoot effects by about 10 s, whereas negative BOLD effects and undershoot contributions overlap for deactivation processes. Apart from differences in stimulus features (e.g., motion) the used activation and deactivation protocols revealed similar maps of neuronal activity changes.

Adult↗

PubMed1999

Temporal and spatial MRI responses to subsecond visual activation.

The temporal and spatial characteristics of oxygenation-sensitive MRI responses to very brief visual stimuli (five Hz reversing black and white checkerboard pattern versus darkness) were investigated (nine subjects) by means of serial single-shot gradient-echo echo-planar imaging (2.0 T, TR=400 ms, mean TE=54 ms, flip angle 30 degrees). The use of a 0.2-s stimulus and a 90-s control phase resulted in an initial latency phase (about 2 s, no signal change), a positive MRI response (2.5% signal increase peaking at 5 s after stimulus onset), and a post-stimulus undershoot (1% signal decrease peaking at 15 s after stimulus onset) lasting for about 50-60 s. The finding that a subsecond visual stimulus elicits both a strong positive MRI response and a long-lasting undershoot provides further evidence for the neuronal origin of slow signal fluctuations seen in the absence of functional challenge and their utility for mapping functional connectivity. The additional observation that a reduction of the inter-stimulus control phase from 90 s to 9.8 s does not seem to affect the spatial extent of cortical activation in pertinent maps is of major relevance for the design and analysis of "event-related" MRI studies.

Adult↗

PubMed1999

Quantitative proton magnetic resonance spectroscopy of cerebral metabolic disturbances in patients with MELAS.

Four patients with clinically and genetically defined MELAS were examined using quantitative localized proton magnetic resonance spectroscopy of the brain. Acute and chronic lesions were located in the occipital lobe and mostly characterized by strongly elevated concentrations of lactate (Lac) and glucose (GIc) as well as severely reduced concentrations of total N-acetylaspartyl compounds (tNAA, neuroaxonal markers), glutamate (Glu), and total creatine. These findings indicate a high degree of nonoxidative glycolysis reflecting either impaired oxidative energy metabolism or the use of anaerobic metabolism by infiltrating macrophages as well as damage or loss of viable neuroaxonal tissue. In contrast, glial cell populations, in particular astrocytes, seem to remain unaffected as evidenced by unchanged concentrations of myo-inositol (glial marker). In addition, all patients including one who never experienced a stroke-like episode showed elevated Lac and Glc as well as reduced tNAA and Glu in tissues appearing normal on MRI. These disturbances were stronger in cortical gray matter and cerebellum than in white matter and indicate that neuroaxonal damage is not restricted to structural lesions. The steady presence of Lac is consistent with a reduced capacity of the mitochondrial oxidative energy metabolism resulting from impaired respiratory chain function.

Adolescent↗

PubMed1999

Increase of total creatine in human brain after oral supplementation of creatine-monohydrate.

The effect of oral creatine supplementation on brain metabolite concentrations was investigated in gray matter, white matter, cerebellum, and thalamus of healthy young volunteers by means of quantitative localized proton magnetic resonance spectroscopy in vivo (2.0 T, stimulated echo acquisition mode sequence; repetition time = 6,000 ms, echo time = 20 ms, middle interval = 10 ms, automated spectral evaluation). Oral consumption of 4 x 5 g creatine-monohydrate/day for 4 wk yielded a statistically significant increase (8.7% corresponding to 0.6 mM, P < 0.001) of the mean concentration of total creatine (tCr) when averaged across brain regions and subjects (n = 6). The data revealed considerable intersubject variability (3.5-13.3%), with the smallest increases observed for the two male volunteers with the largest body weights. A regional analysis resulted in significant increases of tCr in gray matter (4.7%), white matter (11.5%), and cerebellum (5.4%) and was most pronounced in thalamus (14.6% corresponding to 1.0 mM). Other findings were significant decreases of N-acetyl-containing compounds in cerebellum and thalamus as well as of choline-containing compounds in thalamus. All cerebral metabolic alterations caused by oral Cr were reversible, as evidenced by control measurements at least 3 mo after the diet. This work demonstrates that excess consumption of Cr yields regionally dependent increases of the tCr concentration in human brain over periods of several weeks.

Administration, Oral↗

PubMed1999

Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS.

Regional changes of metabolite concentrations during human brain development were assessed by quantitative localized proton magnetic resonance spectroscopy in vivo. Apart from measurements in young healthy adults, the study was based on regional spectra from 97 children who were either healthy or suffered from mental retardation, movement disorders, epilepsies, neoplasm, or vascular malformation. Metabolite quantitation focused on cortical gray and white matter, cerebellum, thalamus, and basal ganglia in six age groups from infancy to adulthood. During infancy and childhood, the concentration of the neuroaxonally located N-acetylasparate increased in gray matter, cerebellum, and thalamus, whereas a constant level was detected in white matter. These findings are in line with regional differences in the formation of synaptic connections during early development and suggest a role of N-acetylaspartate as a marker of functioning neuroaxonal tissue rather than of the mere presence of nerve cells. This view is further supported by high concentrations of taurine in gray matter and cerebellum during infancy, because taurine is also believed to be involved in the process of synapse formation. Remarkably, in basal ganglia both N-acetylaspartate and taurine remain constant at relatively high concentrations. Other metabolite changes during maturation include increases of N-acetylaspartylglutamate, especially in thalamus and white matter, and a decrease of glutamine in white matter. Despite regional differences and some small changes during the first year of life, the concentrations of creatine, phosphocreatine, choline-containing compounds, myoinositol, and glutamate remain constant afterward. The creatine to phosphocreatine concentration ratio yields 2:1 throughout the human brain irrespective of region or age. The observed increase of the proton resonance line-width with age is most pronounced in basal ganglia and corresponds to the age-related and tissue-dependent increase of brain iron.

Adolescent↗

PubMed1999

Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy.

BACKGROUND AND PURPOSE: The mechanisms behind the demyelination that is characteristic of multiple sclerosis (MS) are still poorly understood. The purpose of this study was to compare immunopathologic findings in demyelinating lesions of three patients with in vivo assessments obtained by quantitative proton MR spectroscopy (MRS). METHODS: Between four and seven stereotactic needle brain biopsies were performed in three young adults with diagnostically equivocal findings for MS. Axonal density, gliosis, blood brain-barrier breakdown, and demyelinating activity of lesions were determined. Combined MR/MRS studies were performed (T1-weighted fast low-angle shot and single-voxel stimulated-echo acquisition mode), and absolute metabolite levels were obtained with a user-independent fitting routine. Metabolite control values were obtained from a group of age-matched healthy volunteers (n = 40, age range, 20-25 years old). Alterations of metabolite levels of control subjects were considered significant when exceeding two standard deviations. RESULTS: There were parallel decreases of N-acetylaspartate (21%-82%) and reductions of axonal density (44%-74%) in demyelinating plaques. Concomitant increases of choline (75%-152%) and myo-inositol (84%-160%) corresponded to glial proliferation. Elevated lactate was associated with inflammation. CONCLUSION: The present data suggest that in vivo MRS indicates key pathologic features of demyelinating lesions.

Adult↗

PubMed1998

Physiologic aspects of event related paradigms in magnetic resonance functional neuroimaging.

In order to substantiate event related paradigms in magnetic resonance functional neuroimaging, we assessed the temporal and spatial characteristics of oxygenation-sensitive MRI responses to 1 s periods of visual activation in repetitive protocols. A main finding is a reduction of the functional contrast between conditions (reversing checkerboard vs. darkness) for decreasing interstimulus intervals yielding 4.5% signal change for 89 s, 4% for 9 s, 3% for 6 s, and 1% for 3 s, respectively. Although rapid repetitions of identical stimuli preclude the development of the full positive and negative MRI signal deflections, pertinent responses leave the spatial pattern of activated brain regions unaffected and result in identical maps. These findings suggest the use of interstimulus intervals of the order of the response time from stimulus onset to maximum signal strength (5-6 s in the visual system). The resulting distinction in time will allow for separate mapping of stimulus-related responses with spatially overlapping cortical representations.

Adult↗

PubMed1998

No visual responses in denervated V1: high-resolution functional magnetic resonance imaging of a blindsight patient.

Following severe cranio-cerebral trauma that affected the optic radiation, patient FS suffers from an incomplete macula-splitting hemianopia. Within the hemianopic field, FS exhibits blindsight, i.e. he detects and discriminates visual stimuli he cannot (consciously) see. We performed functional magnetic resonance imaging (fMRI) at high spatial resolution using a large flickering stimulus field to assess visual responsiveness of deafferented V1. Contrasting strong activation of the normal contralesional visual cortex, ipsilesional V1 displayed no stimulus-related MRI signal changes. However, activation was observed in ipsilesional extrastriate cortex. We conclude that blindsight does not depend on functional islands of tissue preserved within the deafferented striate cortex.

Adult↗

PubMed1998

Stimulus dependence of oxygenation-sensitive MRI responses to sustained visual activation.

Oxygenation-sensitive MRI responses to repetitive and sustained visual activation were compared for stimuli with different temporal, spatial, and luminance contrasts, i.e. reversing checkerboard, flashing diffuse red light, and stationary diffuse gray light with darkness as a control. All paradigms elicited an initial oxygenation 'overshoot' as well as a post-stimulus 'undershoot'. However, whereas flashing and stationary diffuse light resulted in more than a 50% decrease of the initial signal response after 6 min of stimulation, checkerboard responsed remained largely unaffected (less than 20% signal attenuation). The demonstration of a stimulus dependence for sustained visual activation reconciles apparently contradictory reports for stimuli involving checkerboards as opposed to goggles, flickerlight, and movies. It may be caused by stimulus-dependent adjustments of neuronal activity, oxygen consumption, blood flow, or blood volume.

Adult↗