Biomedical subjects

Jens Frahm

Publications and source records attributed to Jens Frahm.

At least 19 recordsLinked to original sources

PubMed2006

Quantitative proton MRS of cerebral metabolites in laminin alpha2 chain deficiency.

Congenital muscular dystrophy (CMD) due to merosin (laminin alpha2 chain) deficiency is an autosomal recessively inherited disorder characterized by severe muscular weakness and hypotonia from birth on. Brain involvement is the rule and characterized by variable T2 hyperintensities of white matter which appears swollen on cranial MRI. The pathophysiology of these white matter changes is not clear. In five patients with laminin alpha2 deficient CMD we performed short-echo time localized proton MRS with determination of absolute metabolite concentrations in grey and white matter. In affected white matter, a consistent pattern of metabolites was detected comprising reduced concentrations of N-acetylaspartate and N-acetylaspartylglutamate, creatine, and phosphocreatine, and to a milder degree of choline-containing compounds. In contrast, concentrations of myo-inositol were in the normal range. Spectra of cortical and subcortical grey matter were normal. The observed metabolite profile is consistent with white matter edema, that is reduced cellular density, and relative astrocytosis. This interpretation is in line with the hypothesis that laminin alpha2 deficiency results in leakage of fluids across the blood-brain barrier and a histopathological report of astrocytic proliferation in CMD.

Adolescent↗

PubMed2006

High-field diffusion tensor imaging of mouse brain in vivo using single-shot STEAM MRI.

Information about the microstructural organization of cerebral white matter that is accessible by magnetic resonance diffusion tensor imaging (DTI) gains increasing importance for studies of animal brain. Particular challenges occur for in vivo conditions as well as at high magnetic fields. Here, we have employed a diffusion-weighted (DW) single-shot STEAM MRI sequence for DTI of mouse brain in vivo at 7 T. The approach exploits the increased longitudinal magnetization and prolonged T1 relaxation times of water protons at higher magnetic field strengths without suffering from susceptibility-induced artifacts. When compared to studies at 2.35 T, half Fourier DW STEAM MRI at 7 T yielded a substantial gain in signal-to-noise ratio (SNR) that could be invested either in a reduction of the measurement time or an increase of the spatial resolution. Thus, for a measurement time of 3h, DTI with a voxel size of 117 microm x 117 microm x 720 microm not only resulted in high-quality maps of the fractional anisotropy and main diffusion direction (MDD), but also allowed for fiber tracking of major mouse brain structures in vivo.

Animals↗

PubMed2006

Manganese-enhanced 3D MRI of established and disrupted synaptic activity in the developing insect brain in vivo.

The antennal lobe of the sphinx moth Manduca sexta serves as a model for the development of the olfactory system. Here, the establishment of the glomerular synaptic network formed by the olfactory receptor axons and antennal lobe neurons at pupal stage P12 was followed by transection of the right antenna and - within 24 h - by injection of MnCl2 into the hemolymph. In vivo 3D MRI at 100 and 60 microm isotropic resolution was then performed at P13 to P17. Whereas the left antennal lobe revealed a pronounced increase of the signal-to-noise ratio (SNR) reflecting normal synaptic activity, the observation of only a small SNR increase within the right antennal lobe indicated the disruption of pertinent activity after antennal transection. The accumulation of manganese in the intact antennal system became observable within 3 h and lasted for at least 2 days after injection. Intra-individual comparisons between the right and left side yielded a statistically significant differential SNR increase in the left antennal lobe. Because such an effect was not observed in younger animals studied at pupal stages P10/P11, the MRI findings confirm the development of functional synapses in the antennal lobe of Manduca sexta by P13.

Animals↗

PubMed2006

Cerebral metabolic and structural alterations in hereditary spastic paraplegia with thin corpus callosum assessed by MRS and DTI.

INTRODUCTION: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a complicated form of autosomal-recessive hereditary spastic paraplegia. Characteristic clinical features comprise progressive spastic gait, cognitive impairment, and ataxia. Diagnostic MRI findings include thinning of the corpus callosum and non-progressive white matter (WM) alterations. METHODS: To study the extent of axonal involvement, we performed localized proton magnetic resonance spectroscopy (MRS) of the cerebral WM and cortical grey matter (GM) in a patient with HSP-TCC at 20 and 25 years of age. The second investigation included diffusion tensor imaging (DTI). RESULTS: While MRS of the GM was normal, affected WM was characterized by major metabolic alterations such as reduced concentrations of N-acetylaspartate and N-acetylaspartyl-glutamate, creatine and phosphocreatine, and choline-containing compounds as well as elevated levels of myo-inositol. These abnormalities showed progression over a period of 5 years. DTI revealed increased mean diffusivity as well as reduced fractional anisotropy in periventricular WM. The metabolic and structural findings are consistent with progressive neuroaxonal loss in the WM accompanied by astrocytic proliferation-histopathological changes known to occur in HSP-TCC. CONCLUSION: Our results are in agreement with the hypothesis that the primary pathological process in HSP-TCC affects the axon, possibly due to impaired axonal trafficking.

Adult↗

PubMed2006

Topography of the human corpus callosum revisited--comprehensive fiber tractography using diffusion tensor magnetic resonance imaging.

Several tracing studies have established a topographical distribution of fiber connections to the cortex in midsagittal cross-sections of the corpus callosum (CC). The most prominent example is Witelson's scheme, which defines five vertical partitions mainly based on primate data. Conventional MRI of the human CC does not reveal morphologically discernable structures, although microscopy techniques identified myelinated axons with a relatively small diameter in the anterior and posterior third of the CC as opposed to thick fibers in the midbody and posterior splenium. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to gain cortical connectivity information of the CC in individual subjects. With DTI-based tractography, we distinguished five vertical segments of the CC, containing fibers projecting into prefrontal, premotor (and supplementary motor), primary motor, and primary sensory areas as well as into parietal, temporal, and occipital cortical areas. Striking differences to Witelson's classification were recognized in the midbody and anterior third of the CC. In particular, callosal motor fiber bundles were found to cross the CC in a much more posterior location than previously indicated. Differences in water mobility were found to be in qualitative agreement with differences in the microstructure of transcallosal fibers yielding the highest anisotropy in posterior regions of the CC. The lowest anisotropy was observed in compartments assigned to motor and sensory cortical areas. In conclusion, DTI-based fiber tractography of healthy human subjects suggests a modification of the widely accepted Witelson scheme and a new classification of vertical CC partitions.

Adult↗

PubMed2006

Task- and EEG-correlated analyses of BOLD MRI responses to eyes opening and closing.

Variations of a subject's vigilance may pose a severe confound during functional brain mapping. Here, we focused on BOLD MRI responses to eyes opening and closing in complete darkness and the associated changes in the EEG's alpha frequency band (Berger's effect) as a possible approach to this problem. In awake subjects, BOLD MRI activation patterns were positively correlated to eyes opening and negatively to alpha power. In contrast, activation patterns of subjects with diminished wakefulness as determined by alpha band analysis were negatively correlated to eyes opening. We conclude that a control of the subjects' state of wakefulness must be of prime concern for functional MRI, especially for paradigms which allow for a free shift of vigilance.

Adult↗

PubMed2006

Mapping of the habenulo-interpeduncular pathway in living mice using manganese-enhanced 3D MRI.

This magnetic resonance imaging (MRI) study describes mapping of the habenulo-interpeduncular pathway in living mice based on manganese-induced contrast. Six hours after intracerebroventricular microinjection of MnCl2, T1-weighted 3D MRI (2.35 T) at 117 mum isotropic resolution revealed a continuous pattern of anterograde labeling from the habenula via the fasciculus retroflexus to the interpeduncular nucleus. Alternatively, the less invasive systemic administration of MnCl2 allowed for monitoring of the dynamic uptake pattern of respective neural components with even higher reproducibility across animals. Time courses covered the range from 42 min to 24 h after injection. In conclusion, manganese-enhanced MRI may open new ways for functional assessments of the habenulo-interpeduncular system in animal models with cognitive impairment.

Animals↗

PubMed2006

Gradient and stimulated echo (GRASTE) imaging.

As a modification of single-shot stimulated echo acquisition mode (STEAM) MRI, a gradient and stimulated echo (GRASTE) sequence is presented that acquires multiple gradient echoes in addition to each stimulated echo. While "contiguous" GRASTE exploits all stimulated echoes for the central part of k-space and the gradient echoes for outer lines, "interleaved" GRASTE assigns all echoes of a particular readout interval to directly neighboring lines. Phase distortions may be corrected by the reference signals of a single readout interval without phase encoding. Experimental results obtained for the human brain demonstrate that contiguous GRASTE yields up to 30% better SNR per acquisition time than conventional single-shot STEAM due to a better efficiency and maintains most of its robustness. Interleaved GRASTE can improve the SNR by a factor of 2 because of the possibility of using larger flip angles in the readout interval. However, its more pronounced sensitivity to off-resonance effects requires short echo trains.

Brain Mapping↗

PubMed2006

Chromium(VI) as a novel MRI contrast agent for cerebral white matter: preliminary results in mouse brain in vivo.

This work demonstrates that intraventricular microinjections of a low dose of potassium dichromate (0.4 microL of 10 mM solution) yield a specific contrast enhancement of white matter (WM) tracts in T1-weighted 3D MRI of mouse brain in vivo. Pronounced and persistent signal increases (40-100% at 24 hr after injection) were observed in the corpus callosum, anterior commissure, fornix, and stria medullaris, as well as in the mammillothalamic tract and fasciculus retroflexus. These results suggest that the extracellular diffusion of diamagnetic chromium(VI) (Cr(VI)) after injection is followed by a tissue-specific reduction to paramagnetic Cr(V) and (III), which relies predominantly on the oxidation of myelin lipids. Because Cr(VI)-induced contrast leads to only a mild unspecific enhancement (10-20%) of gray matter (GM) structures, such as the hippocampal formation, the method reveals novel information that differs from that obtainable using other paramagnetic ions, such as manganese.

Animals↗

PubMed2006

Monitoring of EAE onset and progression in the common marmoset monkey by sequential high-resolution 3D MRI.

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.

Animals↗

PubMed2006

Magnetic resonance imaging and proton magnetic resonance spectroscopy of megalencephaly and dilated Virchow-Robin spaces.

Megalencephaly with dilated Virchow-Robin spaces has been suggested to represent a new clinical entity. This report describes two males and a female who have been monitored from pregnancy. The patients manifest a relatively normal psychomotor development with some minor neurologic symptoms such as mild muscle hypotonia and clumsy motor performance. Biochemical and electrophysiologic tests were normal. In the white matter of the brain, a prominent dilatation of the Virchow-Robin spaces with some adjacent signal alterations could be demonstrated by magnetic resonance imaging. Magnetic resonance spectroscopy revealed normal metabolite concentrations in the cortical and deep gray matter and normal-appearing white matter. Affected white matter was characterized by mildly reduced to normal levels of myo-inositol and a decrease of all other metabolites including total N-acetyl moieties, choline-containing compounds, and total creatine. These data indicate that the dilatation of Virchow-Robin spaces reflects an underlying brain pathology causing neuroaxonal damage. Possible differential diagnoses are discussed.

Aspartic Acid↗

PubMed2005

The cost of parallel imaging in functional MRI of the human brain.

While the advantages of parallel acquisition techniques for echo-planar imaging (EPI) are well documented for studies affected by magnetic field inhomogeneities, this work focuses on the costs in functional MRI of brain regions without artifacts due to susceptibility effects. For a visual stimulation paradigm and relative to conventional EPI (2.9 T; TR/TE=2000/36 ms), the use of parallel acquisition at a reduction factor of 2 decreased the mean number of activated voxels by 21% at 2 x 2 x 2-mm(3) resolution (n=6) and by 15% at 3 x 3 x 3-mm(3) resolution (n=6). The loss of sensitivity reflects both a decreased signal-to-noise ratio of the native images due to a lower number of contributing gradient echoes and a decreased BOLD MRI sensitivity due to the coverage of a smaller range of TEs.

Adolescent↗

PubMed2005

Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin.

In humans, neurotrauma is suspected to cause brain atrophy and accelerate slowly progressive neurodegenerative disorders, such as Alzheimer's disease or schizophrenia. However, a direct link between brain injury and subsequent delayed global neurodegeneration has remained elusive. Here we show that juvenile (4-week-old) mice that are given a discrete unilateral lesion of the parietal cortex, develop to adulthood without obvious clinical symptoms. However, when monitored 3 and 9 months after lesioning, using high-resolution three-dimensional MRI and behavioural testing, the same mice display global neurodegenerative changes. Surprisingly, erythropoietin, a haematopoietic growth factor with potent neuroprotective activity, prevents behavioural abnormalities, cognitive dysfunction and brain atrophy when given for 2 weeks after acute brain injury. This demonstrates that a localized brain lesion is a primary cause of delayed global neurodegeneration that can be efficiently counteracted by neuroprotection.

Acute Disease↗

PubMed2005

BOLD MRI responses to repetitive TMS over human dorsal premotor cortex.

Functional magnetic resonance imaging (fMRI) studies in humans have hitherto failed to demonstrate activity changes in the direct vicinity of transcranial magnetic stimulation (TMS) that cannot be attributed to re-afferent somatosensory feedback or a spread of excitation. In order to investigate the underlying activity changes at the site of stimulation as well as in remote connected regions, we applied short trains of high-intensity (110% of resting motor threshold) and low-intensity (90% of active motor threshold) repetitive TMS (rTMS; 3 Hz, 10 s duration) over the presumed location of the left dorsal premotor cortex (PMd) during fMRI. Signal increases in the direct vicinity of the stimulated PMd were observed during rTMS at 110% RMT. However, positive BOLD MRI responses were observed with rTMS at both 90% and 110% RMT in connected brain regions such as right PMd, bilateral PMv, supplementary motor area, somatosensory cortex, cingulate motor area, left posterior temporal lobe, cerebellum, and caudate nucleus. Responses were generally smaller during low-intensity rTMS. The results indicate that short trains of TMS can modify local hemodynamics in the absence of overt motor responses. In addition, premotor rTMS cannot only effectively stimulate cortico-cortical but also cortico-subcortical connections even at low stimulation intensities.

Adult↗

PubMed2005

Essential role of protein kinase B gamma (PKB gamma/Akt3) in postnatal brain development but not in glucose homeostasis.

Protein kinase B is implicated in many crucial cellular processes, such as metabolism, apoptosis and cell proliferation. In contrast to Pkb(alpha) and Pkb(beta)-deficient mice, Pkb(gamma)(-/-) mice are viable, show no growth retardation and display normal glucose metabolism. However, in adult Pkb(gamma)mutant mice, brain size and weight are dramatically reduced by about 25%. In vivo magnetic resonance imaging confirmed the reduction of Pkb(gamma)(-/-) brain volumes with a proportionally smaller ventricular system. Examination of the major brain structures revealed no anatomical malformations except for a pronounced thinning of white matter fibre connections in the corpus callosum. The reduction in brain weight of Pkb(gamma)(-/-) mice is caused, at least partially, by a significant reduction in both cell size and cell number. Our results provide novel insights into the physiological role of Pkb(gamma) and suggest a crucial role in postnatal brain development.

Animals↗

PubMed2005

Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression.

RATIONALE: Substance P antagonists have been proposed as candidates for a new class of antidepressant compounds. OBJECTIVES: We examined the effects of SLV-323, a novel neurokinin 1 receptor (NK1R) antagonist, in the chronic psychosocial stress paradigm of adult male tree shrews. METHODS: Animals were subjected to a 7 day period of psychosocial stress before being treated daily with SLV-323 (20 mg kg(-1) day(-1)). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy. Norepinephrine excretion was monitored from daily urine samples, and serum testosterone concentrations were measured at the end of the experiment. All animals were videotaped daily to analyze scent-marking behavior and locomotor activity. Cell proliferation in the dentate gyrus and hippocampal volume were measured postmortem. RESULTS: Stress significantly decreased cerebral concentrations of N-acetyl-aspartate, total creatine, and choline-containing compounds in vivo and resulted in an increase of urinary norepinephrine and decrease of serum testosterone concentrations. Moreover, stressed animals displayed decreased scent-marking behavior and locomotor activity. The proliferation rate of the granule precursor cells in the dentate gyrus was reduced, and hippocampal volume was mildly decreased. The stress-induced alterations in the central nervous system were partially prevented by concomitant administration of SLV-323, while drug treatment had only a minor effect on the stress-induced behavioral changes. CONCLUSIONS: The novel NK1R antagonist SLV-323 has certain antidepressant-like effects in a valid animal model of depression.

Animals↗

PubMed2005

In vivo 3D MRI of insect brain: cerebral development during metamorphosis of Manduca sexta.

High-resolution 3D MRI of male pupae of Manduca sexta was performed at 2.35 T in order to evaluate its potential for an in vivo characterization of insect brain during metamorphosis. T1-weighted 3D FLASH (TR/TE = 20/7.8 ms, 25 degrees flip angle) and T2-weighted 3D fast SE MRI data sets (TR/TEeff = 3000/100 ms) were acquired at different developmental stages with an isotropic resolution of 100 microm. Both T1- and T2-weighted 3D MRI allowed for the identification of cerebral structures such as the antennal nerve, antennal and optical lobe, and central brain. Pronounced developmental alterations of the morphology were observed during metamorphosis. The results demonstrate the feasibility of 3D MRI at nanoliter resolution to identify major brain systems of M. sexta and respective changes during pupal development from caterpillar to sphinx moth. Together with the use of suitable contrast agents, this approach may provide new ways for studying the axonal connectivity and neural function of the developing insect brain.

Animals↗

PubMed2005

Spiral imaging: a critical appraisal.

In view of recent applications in cardiovascular and functional brain imaging, this work revisits the basic performance characteristics of spiral imaging in direct comparison to echo-planar imaging (EPI) and conventional rapid gradient-echo imaging. Using both computer simulations and experiments on phantoms and human subjects at 2.9 T, the study emphasizes single-shot applications and addresses the design of a suitable trajectory, the choice of a gridding algorithm, and the sensitivity to experimental inadequacies. As a general result, the combination of a spiral trajectory with regridding of the k-space data poses no principle obstacle for high-quality imaging. On the other hand, experimental difficulties such as gradient deviations, resonance offset contributions, and concomitant field effects cause more pronounced and even less acceptable image artifacts than usually obtained for EPI. Moreover, when ignoring parallel imaging strategies that are also applicable to EPI, improvements of image quality via reduced acquisition periods are only achievable by interleaved multishot spirals because partial Fourier sampling and rectangular fields of view (FOVs) cannot be exploited for non-Cartesian trajectories. Taken together, while spiral imaging may find its niche applications, most high-speed imaging needs are more easily served by EPI.

Algorithms↗