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Jens Frahm

Publications and source records attributed to Jens Frahm.

At least 37 records · Page 2Linked to original sources

Use of phased array coils for a determination of absolute metabolite concentrations.

This work describes the use of phased array coils for a quantification of absolute metabolite concentrations. The method is demonstrated for single-voxel localized proton MRS of human brain with an eight-element receive-only head coil. It is based on the transmitter reference amplitude of the body coil used for RF transmission. A relative sensitivity of every element of the phased array coil is derived from a combination of two reference scans without water suppression that correspond to either the body coil in transmit-receive mode or the phased array coil in conjunction with body coil excitation. Experimental results were obtained at 2.9 T for both phantoms and 12 human subjects in different locations of gray and white matter. The data demonstrate that the procedure is technically robust and without a penalty in measuring time. Moreover, it takes full advantage of the signal-to-noise gain for quantitative proton MRS and may be extended to other phased array coils without the need for a recalibration.

Adult↗

Diffusion tensor imaging using partial Fourier STEAM MRI with projection onto convex subsets reconstruction.

Diffusion-weighted single-shot STEAM MRI allows for diffusion mapping of the human brain without sensitivity to resonance offset effects. In order to compensate for its inherently lower SNR and speed than echo-planar imaging, this work describes the use of partial Fourier encoding in combination with image reconstruction by the projection onto convex subsets algorithm. The method overcomes phase distortions in diffusion-weighted partial Fourier acquisitions that disturb the conjugate complex symmetry of k-space and preclude the use of respective reconstruction techniques. In comparison with full Fourier encoding and a static flip angle for the STEAM readout pulses, experimental results at 2.9 T demonstrate a gain in relative SNR per unit time by 20% for 5/8 phase encoding with optimized variable flip angles. Simultaneously, the imaging time is reduced from about 670 ms (80 echoes) to 440 ms (50 echoes). Current implementations at 2 x 2 mm2 in-plane resolution comprise a protocol for clinical anisotropy studies (12 diffusion-encoding gradient directions at 1000 s mm(-2)) covering 18 sections of 4-mm thickness within a measurement time of 8.5 min (5 averages) and a version optimized for fiber tracking using 24 gradient directions and 38 sections of 2-mm thickness yielding a measurement time of 29.5 min (4 averages).

Anisotropy↗

Multicontrast MRI of remyelination in the central nervous system.

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.

Animals↗

Simultaneous recordings of visual evoked potentials and BOLD MRI activations in response to visual motion processing.

Visual motion processing in humans was studied by simultaneous 32-channel electroencephalography (EEG) recordings of visual evoked potentials and BOLD MRI activations at 2.9 T. The paradigms compared three different random dot patterns (12 s duration) with stationary random dots (18 s) or with each other. The stimuli represented pattern reversal (500 ms switches between two stationary patterns), motion onset (200 ms of starfield motion followed by 1000 ms of stationary dots) and motion reversal (reversal of moving starfield directions every 1000 ms). Whereas motion-evoked visual potentials, and in particular the N2 component in occipito-temporal channels, were most prominent for motion onset, the most extended BOLD MRI activations and strongest signal changes in V5/MT+ were obtained in response to motion reversal. These apparently contradictory findings most likely reflect different physiological aspects of the neural activity associated with visual motion processing. For example, desynchronized activity of subpopulations of cortical neurons inside V5/MT+ is expected to attenuate visual evoked potentials in scalp recordings while continuously driving metabolic demands that lead to sustained BOLD MRI responses. The understanding of the physiological correlates and neural processes underlying either technique is fundamental to exploring fully the potential of combined EEG-MRI for studying human brain function at both high temporal and spatial resolution.

Adult↗

Echo train shifted multi-echo FLASH for functional MRI of the human brain at ultra-high spatial resolution.

This paper describes the development of a novel technique for functional MRI of the human brain at 0.135 microL resolution for a whole brain section. In comparison with conventional studies at 3 mm isotropic resolution or 27 microL voxel size, the method yields an improvement by a factor of 200. To achieve optimum image quality, the approach is based on a multi-echo fast low-angle shot (FLASH) sequence with unipolar traversals of k-space in the frequency-encoding dimension and echo train shifting to avoid amplitude discontinuities in the phase-encoding dimension. These strategies ensure a smooth point-spread function and eliminate image ghosting artifacts without the need for any phase correction or other post-processing. Signal-to-noise losses due to the considerably reduced voxel sizes are compensated for by single slice acquisitions, optimized bandwidths and an experimental four-channel shoulder coil matched to the posterior portion of the head. Multi-echo FLASH studies of the human brain (2.9 T, seven echoes, 200 Hz/pixel bandwidth, effective echo time 36 ms, acquisition time 6 s) at 300 microm resolution (no interpolation) and 1.5 mm slice thickness revealed robust activations in primary visual areas in response to binocular stimulation. The new method holds promise for refined studies of the columnar organization of specific brain systems and for functional assessments of the gray matter at laminar resolution.

Animals↗

Functional mapping of neural pathways in rodent brain in vivo using manganese-enhanced three-dimensional magnetic resonance imaging.

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.

Animals↗

Is the human primary motor cortex involved in motor imagery?

Participation of the primary motor cortex (M1) in motor imagery was addressed using functional magnetic resonance imaging at 2.0 T and 2 x 2 x 4 mm3 resolution in six right-handed subjects. Paradigms comprised visually cued execution and imagination of a sequential finger-to-thumb opposition task (12 s) contrasted with motor rest and visual imagery (18 s), respectively. Motor execution activated M1 as well as other parts of the motor system including supplementary motor area (SMA) and premotor areas (PM). In contrast, motor imagery did not lead to activations in M1 except for 1/6 subjects but involved SMA and PM bilaterally as well as the anterior intraparietal cortex. Moreover, a region-of-interest analysis revealed a weak initial MRI signal increase in M1 in 4/6 subjects. This novel finding of a transient response reflecting the onset of imagination which does not lead to sustained M1 activation may explain previous contradictory reports.

Adult↗

In vivo 3D MRI staining of the mouse hippocampal system using intracerebral injection of MnCl2.

The morphology and function of the hippocampal system of C57BL/6J mice (n = 8) was studied in vivo using T1-weighted 3D magnetic resonance imaging (MRI) (117 microm isotropic resolution) after bilateral injection of MnCl(2) (0.25 microl, 5 or 200 mM) into the posterior hippocampal formation. The neuronal uptake of the T1-shortening Mn(2+) ions resulted in a pronounced MRI signal enhancement within the CA3 subfield and dentate gyrus with milder increases in CA1 and subiculum. This finding is in line with differences in the excitability of hippocampal neurons previously reported using electrophysiologic recordings. The subsequent axonal transport of Mn(2+) highlighted the principal extrinsic projections from the posterior hippocampal formation via the fimbria and the precommissural fornix to the dorsal part of the lateral septal nucleus. A strong MRI signal enhancement was also observed in the ventral hippocampal commissure. A time-course analysis revealed unsaturated conditions of Mn(2+) accumulation at about 2 h after injection and optimal contrast-to-noise ratios at about 6 h after injection. The present results using Mn(2+)-enhanced 3D MRI open new ways for studying the role of the hippocampal system in specific aspects of learning and memory in normal and mutant mice.

Animals↗

Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits.

Recent studies indicate that the cortical effects of transcranial magnetic stimulation (TMS) may not be localized to the site of stimulation, but spread to other distant areas. Using echo-planar imaging with blood-oxygenation-level-dependent (BOLD) contrast at 3 Tesla, we measured MRI signal changes in cortical and subcortical motor regions during high-frequency (3.125 Hz) repetitive TMS (rTMS) of the left sensorimotor cortex (M1/S1) at intensities above and below the active motor threshold in healthy humans. The supra- and subthreshold nature of the TMS pulses was confirmed by simultaneous electromyographic monitoring of a hand muscle. Suprathreshold rTMS activated a network of primary and secondary cortical motor regions including M1/S1, supplementary motor area, dorsal premotor cortex, cingulate motor area, the putamen and thalamus. Subthreshold rTMS elicited no MRI-detectable activity in the stimulated M1/S1, but otherwise led to a similar activation pattern as obtained for suprathreshold stimulation though at reduced intensity. In addition, we observed activations within the auditory system, including the transverse and superior temporal gyrus, inferior colliculus and medial geniculate nucleus. The present findings support the notion that re-afferent feedback from evoked movements represents the dominant input to the motor system via M1 during suprathreshold stimulation. The BOLD MRI changes in motor areas distant from the site of subthreshold stimulation are likely to originate from altered synaptic transmissions due to induced excitability changes in M1/S1. They reflect the capability of rTMS to target both local and remote brain regions as tightly connected constituents of a cortical and subcortical network.

Adult↗

Functional somatotopy of finger representations in human primary motor cortex.

To assess the degree of fine-scale somatotopy within the hand area of the human primary motor cortex (M1), functional mapping of individual movements of all fingers was performed in healthy young subjects (n = 7) using MRI at 0.8 x 0.8 mm2 resolution and 4 mm section thickness. The experimental design comprised both a direct paradigm contrasting single digit movements vs. motor rest and multiple differential paradigms contrasting single digit movements vs. the movement of another digit. Direct mapping resulted in largely overlapping activations. A somatotopic arrangement was only recognizable when considering the mean center-of-mass coordinates of individual digit representations averaged across subjects. In contrast, differential paradigms revealed more segregated and somatotopically ordered activations in single subjects. The use of center-of-mass coordinates yielded inter-digit distances ranging from 2.0 to 16.8 mm, which reached statistical significance for pairs of more distant digits. For the middle fingers, the functional somatotopy obtained by differential mapping was dependent on the choice of the digit used for control. These results confirm previous concepts that finger somatotopy in the human M1 hand area emerges as a functional predominance of individual digit representations sharing common areas in a distributed though ordered network.

Adult↗

On the synchronization of transcranial magnetic stimulation and functional echo-planar imaging.

PURPOSE: To minimize artifacts in echo-planar imaging (EPI) of human brain function introduced by simultaneous transcranial magnetic stimulation (TMS). MATERIALS AND METHODS: Distortions due to TMS pulses (0.25 msec, 2.0 T) were studied at 2.0 T before and during EPI. RESULTS: Best results were obtained if both the EPI section orientation and the frequency-encoding gradient were parallel to the plane of the TMS coil. Under these conditions, a TMS pulse caused image distortions when preceding the EPI sequence by less than 100 msec. Recordings with a magnetic field gradient pick-up coil revealed transient magnetic fields after TMS, which are generated by eddy currents in the TMS coil. TMS during image acquisition completely spoiled all transverse magnetizations and induced disturbances ranging from image corruption to mild image blurring, depending on the affected low and high spatial frequencies. Simultaneous TMS and radio-frequency (RF) excitation gave rise to T1-dependent signal changes that lasted for several seconds and yielded pronounced false-positive activations during functional brain mapping. CONCLUSION: To ensure reliable and robust combinations, TMS should be applied at least 100 msec before EPI while completely avoiding any pulses during imaging.

Artifacts↗

Localized proton MRS of cerebral metabolite profiles in different mouse strains.

Localized proton MR spectroscopy (MRS) was used to quantify cerebral metabolite concentrations in NMRI (n = 8), BALB/c (n = 7), and C57BL/6 (n = 8) mice in vivo and 1 hr after global irreversible ischemia (2.35 T, STEAM, TR/TE/TM = 6000/20/10 ms, 4 x 3 x 4 mm(3) volume, corrections for cerebrospinal fluid). Anatomical MRI and proton MRS revealed significant differences of the C57BL/6 strain in comparison with both BALB/c and NMRI mice. While MRI volumetry yielded larger ventricular spaces of the C57BL/6 strain, proton MRS resulted in elevated concentrations of N-acetylaspartate (tNAA), creatine and phosphocreatine (tCr), choline-containing compounds (Cho), glucose (Glc), and lactate (Lac) relative to BALB/c mice and elevated Glc relative to NMRI mice. Apart from the expected decrease of Glc and increase of Lac 1 hr post mortem, C57BL/6 mice presented with significant reductions of tNAA, tCr, and Cho, whereas these metabolites remained unchanged in BALB/c and NMRI mice. The results support the hypothesis that the more pronounced vulnerability of C57BL/6 mice to brain ischemia is linked to strain-dependent differences of the cerebral energy metabolism.

Animals↗

Cerebral proton magnetic resonance spectroscopy in infantile Alexander disease.

Alexander disease (AD) is a rare genetic disorder of the central nervous system due to a dysfunction of astrocytes. The most common infantile form presents as a progressive leukodystrophy with macrocephalus. Recently, heterozygous de novo mutations in the gene encoding glial fibrillary acidic protein (GFAP) have been demonstrated to be associated with AD. We used localized proton magnetic resonance spectroscopy (MRS) to assess metabolic abnormalities in grey and white matter, basal ganglia, and cerebellum of 4 patients with infantile AD and GFAP mutations. Strongly elevated concentrations of myo-inositol in conjunction with normal or increased choline-containing compounds in all regions investigated point to astrocytosis and demyelination. Neuroaxonal degeneration, as reflected by a reduction of N-acetylaspartate, was most pronounced in cerebral and cerebellar white matter. The accumulation of lactate in affected white matter is in line with infiltrating macrophages. Metabolic alterations demonstrated by in vivo proton MRS are in excellent agreement with known neuropathological features of AD.

Alexander Disease↗

Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS.

To elucidate changes in human brain activity evoked by repetitive transcranial magnetic stimulation (rTMS), sub- and suprathreshold rTMS (4 Hz, 10 s) over the left primary sensorimotor cortex (M1/S1) was interleaved with blood-oxygenation-level-dependent (BOLD) echo-planar imaging of primary and secondary motor areas. Suprathreshold rTMS over left M1/S1 caused marked increases in BOLD signal in the stimulated area and SMA-proper in seven of eight subjects. By contrast, we found no change in BOLD signal in the stimulated M1/S1, when rTMS was given at intensities that were subthreshold for inducing motor responses in the contralateral hand. However, five of eight subjects showed consistent increases in BOLD MRI signal in the SMA-proper and, to a lesser extent, in bilateral lateral premotor cortex (LPMC) during subthreshold rTMS. A decrease in BOLD MRI signal was found in contralateral (right) M1/S1 in 6/8 subjects across all conditions. No significant changes were observed in the pre-SMA. The results support the notion that BOLD MRI responses to suprathreshold rTMS over M1/S1 are dominated by neuronal activity related to reafferent processing of TMS-induced hand movements. At subthreshold intensity, a short train of high-frequency rTMS seems to predominantly modulate activity of corticocortical connections which link the stimulated area with remote frontal premotor areas.

Adult↗

Cerebral proton magnetic resonance spectroscopy of a patient with giant axonal neuropathy.

Magnetic resonance imaging of a girl with giant axonal neuropathy revealed a progressive white matter disease. In close agreement with histopathological features reported previously, localized proton magnetic resonance spectroscopy at 9 and 12 years of age indicated a specific damage or loss of axons (reduced N-acetylaspartate and N-acetylaspartylglutamate) accompanied by acute demyelination (elevated choline-containing compounds, myo-inositol, and lactate) in white matter as well as a generalized proliferation of glial cells (elevated choline-containing compounds and myo-inositol) in both gray and white matter.

Axons↗

Characterization of the human visual V6 complex by functional magnetic resonance imaging.

Magnetoencephalography of a visual area along the human parieto-occipital sulcus suggested that this region represents the human homologue of the monkey visual area V6 complex (visual area V6/visuomotor area V6A) involved in the integration of visual and somatomotor information. We used functional magnetic resonance imaging at 2.0 T and 2 x 2 x 3 mm3 resolution (16 sections) to characterize visual areas along the parieto-occipital sulcus in five healthy human subjects. Paradigms comprised a full-field checkerboard stimulation, a full-field luminance flicker as well as a foveal and peripheral luminance flicker using both a direct and differential design for comparing functional states. Along the parieto-occipital sulcus, and in contrast to primary visual areas, luminance stimulation evoked much larger activation volumes than checkerboard stimulation. Moreover, based on anatomic landmarks, luminance stimulation identified two functionally distinct regions of parieto-occipital sulcus activations: an inferior part (supposedly visual area V6) and a superior portion (supposedly visuomotor area V6A). With these assignments, foveal vs. peripheral luminance stimulation revealed a weaker foveal overrepresentation in visual area V6/visuomotor area V6A than in early visual areas, and only a mild tendency for a retinotopic organization in visual area V6. Further analyses of the functional coding of the human visual area V6 complex require functional magnetic resonance imaging at even higher spatial resolution.

Adult↗