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Biomedical subjects

G Krüger

Publications and source records attributed to G Krüger.

At least 19 recordsLinked to original sources

C6 peptide ELISA test in the serodiagnosis of Lyme borreliosis in Sweden.

The aim of this study was to evaluate the synthetic C6 peptide test as a first-line test in a two-tiered scheme for Borrelia serology in a clinically well-characterized population of patients with Lyme borreliosis in Kalmar County, Sweden. The study population consisted of a prospective group (n = 200), a control group (n = 255), and a retrospective group (n = 29). The test panel consisted of the Immunetics Quick ELISA C6 Borrelia assay kit (Immunetics, Cambridge, MA, USA), the Virotech Borrelia burgdorferi ELISA (Genzyme Virotech, Rüsselsheim, Germany), and the Liaison Borrelia CLIA (DiaSorin, Saluggia, Vercelli, Italy). Seroprevalence among 200 healthy blood donors was significantly lower in the C6 test (8%) compared to the Virotech ELISA (14%) and the Liaison CLIA (12%). In convalescent sera (2-3 months and 6 months post infection) from 158 patients with erythema migrans, the seropositivity in the C6 test was also significantly lower compared to both the Virotech ELISA and the Liaison CLIA. Serosensitivity in the acute phase of erythema migrans and other clinical manifestations of borreliosis did not differ significantly between the C6 test and the Virotech ELISA or the Liaison CLIA. Overall, a positive C6 test seems to correlate well with acute borreliosis. Cross-reactivity was lower in the C6 test in sera positive for Epstein-Barr virus infection as compared to the Virotech ELISA. This study supports the use of the C6 test as a screening test for borreliosis, in endemic areas.

Adolescent↗

Neuroimaging at 1.5 T and 3.0 T: comparison of oxygenation-sensitive magnetic resonance imaging.

Noise properties, the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and signal responses were compared during functional activation of the human brain at 1.5 and 3.0 T. At the higher field spiral gradient-echo (GRE) brain images revealed an average gain in SNR of 1.7 in fully relaxed and 2.2 in images with a repetition time (TR) of 1.5 sec. The tempered gain at longer TRs reflects the fact that the physiological noise depends on the signal strength and becomes a larger fraction of the total noise at 3.0 T. Activation of the primary motor and visual cortex resulted in a 36% and 44% increase of "activated pixels" at 3.0 T, which reflects a greater sensitivity for the detection of activated gray matter at the higher field. The gain in the CNR exhibited a dependency on the underlying tissue, i.e., an increase of 1.8x in regions of particular high activation-induced signal changes (presumably venous vessels) and of 2.2x in the average activated areas. These results demonstrate that 3.0 T provides a clear advantage over 1.5 T for neuroimaging of homogeneous brain tissue, although stronger physiological noise contributions, more complicated signal features in the proximity of strong susceptibility gradients, and changes in the intrinsic relaxation times may mediate the enhancement. Magn Reson Med 45:595-604, 2001.

Brain↗

Physiological noise in oxygenation-sensitive magnetic resonance imaging.

The physiological noise in the resting brain, which arises from fluctuations in metabolic-linked brain physiology and subtle brain pulsations, was investigated in six healthy volunteers using oxygenation-sensitive dual-echo spiral MRI at 3.0 T. In contrast to the system and thermal noise, the physiological noise demonstrates a signal strength dependency and, unique to the metabolic-linked noise, an echo-time dependency. Variations of the MR signal strength by changing the flip angle and echo time allowed separation of the different noise components and revealed that the physiological noise at 3.0 T (1) exceeds other noise sources and (2) is significantly greater in cortical gray matter than in white matter regions. The SNR in oxygenation-sensitive MRI is predicted to saturate at higher fields, suggesting that noise measurements of the resting brain at 3.0 T and higher may provide a sensitive probe of functional information.

Adult↗

Degradation of poly(D,L)lactide implants with or without addition of calciumphosphates in vivo.

The study was aimed at examining the in vivo degradation of pure poly(D,L)lactide (PDLLA) or PDLLA with an admixture of calciumphosphates. One rod (20 x 3 x 2 mm) and one cube (3 x 2 x 2 mm) of pure PDLLA, PDLLA with tricalciumphosphate (PDLLA + TCP) or PDLLA with calciumhydrogenphosphate (PDLLA + CHP), respectively, were implanted into the dorsal muscles of 50 male Wistar Albino rats. After definite intervals (from 2nd to 72nd week), pH measurements were performed in the environment of the implants. Afterwards, the cubes with their surrounding tissues were excised for histological examinations, measurements of the outer dimensions and mechanical analyses of the explanted rods were performed. No drop of more than 0.1 pH units was detectable in the tissue surrounding any type of implants. No advantageous effect of the calciumphosphates could be proved. A mild foreign body reaction could be observed around PDLLA implants. After 72 weeks, pure PDLLA had been totally resorbed from the extracellular space, the degradation of calciumphosphate-enriched PDLLA was still in progress. A large amount of inflammations occurred in the tissues surrounding PDLLA with an admixture of slowly degrading TCP or CHP, leading to two abscesses and four fistulas at PDLLA + TCP, and two abscesses and three fistulas at PDLLA + CHP implantation site. Bending strength of pure PDLLA was constant up to the 4th week post-implantation and reduced to 60% of the initial value up to the 12th week. No traces of crystallinity could be observed during the degradation of PDLLA. As a conclusion of the study, complete resorption from the extracellular space and tissue tolerance of pure PDLLA is proved. An admixture of small calciumphosphate particles is not suitable to improve the biocompatibility of PDLLA but leads to a decrease in the mechanical characteristics.

Animals↗

Assessment of cerebrovascular reactivity with functional magnetic resonance imaging: comparison of CO(2) and breath holding.

Cerebral blood flow (CBF) and oxygenation changes following both a simple breath holding test (BHT) and a CO(2) challenge can be detected with functional magnetic resonance imaging techniques. The BHT has the advantage of not requiring a source of CO(2) and acetazolamide and therefore it can easily be performed during a routine MR examination. In this study we compared global hemodynamic changes induced by breath holding and CO(2) inhalation with blood oxygenation level dependent (BOLD) and CBF sensitized fMRI techniques. During each vascular challenge BOLD and CBF signals were determined simultaneously with a combined BOLD and flow-sensitive alternating inversion recovery (FAIR) pulse sequence. There was a good correlation between the global BOLD signal intensity changes during breath holding and CO(2) inhalation supporting the notion that the BHT is equivalent to CO(2) inhalation in evaluating the hemodynamic reserve capacity with BOLD fMRI. In contrast, there was no correlation between relative CBF changes during both vascular challenges, which was probably due to the reduced temporal resolution of the combined BOLD and FAIR pulse sequence.

Adult↗

Simultaneous monitoring of dynamic changes in cerebral blood flow and oxygenation during sustained activation of the human visual cortex.

Functional neuroimaging was used to investigate the effect of cerebral blood flow (CBF) adjustments on the blood oxygenation level dependent (BOLD) signal during visual stimulation. Temporal responses from both oxygenation- and perfusion-sensitized MRI revealed almost identical features during onset and ongoing activation, i.e. an activation-induced signal rise, and a gradual signal decrease during prolonged activation (overshoot). However, the post-stimulus responses exhibited a pronounced BOLD signal drop below prestimulus baseline (undershoot), but a rather rapid normalisation of the related CBF signal. Thus, an activation-induced initial BOLD signal rise and a gradual signal decrease reflect a coarse upregulation of CBF, which is followed by fine-tuning adjustments of flow. Regulations of other involved physiological parameters, including blood volume and oxidative metabolism give rise to a negative post-stimulus BOLD signal response.

Adult↗

The -3.9 kb DNaseI hypersensitive site of the chicken lysozyme locus harbours an enhancer with unusual chromatin reorganizing activity.

Tissue specific regulation of the chicken lysozyme locus is achieved by a combination of positive and negative cis-regulatory elements. Here we describe the molecular characterization of a newly discovered enhancer element located -3.9kb upstream of the transcription start. The -3.9kb enhancer is activated early in macrophage differentiation, as indicated by chromatin reorganization in macrophage precursor cells. Interestingly, enhancer activation leads to nucleosome phasing. Tissue specificity of expression is achieved by a combination of 5'-sequences with ubiquitous enhancer activity and 3'-flanking sequences. The 5'-half contains binding sites for members of the nuclear factor I transcription family and a yet unknown protein. We could show by in vivo footprinting that the ubiquitously expressed factors occupy their binding sites only in lysozyme expressing cells. We conclude that a specific chromatin architecture may be responsible for the differential activity of the enhancer.

Animals↗

Relationship between cerebral blood flow changes during visual stimulation and baseline flow levels investigated with functional MRI.

Using fMRI, the relationship between regional cerebral blood flow (rCBF) changes during visual stimulation and the prevailing baseline global and regional flow levels was evaluated in 22 volunteers. The absolute increase in rCBF was not correlated with baseline rCBF values (r = 0.01, p = 0.8); however, the percentage change in rCBF showed a negative correlation (r=-0.78, p<0.001). Both absolute and relative changes in rCBF were independent of baseline global CBF values. These results indicate that caution should be exercised when comparing relative flow changes during focal brain activation, especially in functional neuroimaging studies dealing with altered baseline flow values.

Adult↗

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↗

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↗

Assessment of cerebral oxidative metabolism with breath holding and fMRI.

Carbon dioxide inhalation can be used to map changes in cerebral metabolic rate of oxygen (CMRO(2)) during neuronal activation with functional MRI (fMRI). A hypercapnic stress also can be achieved with a simple breath-holding test. Using this test as means of manipulating cerebral blood flow (CBF) independent of CMRO(2), we assessed changes in CMRO(2) during visual stimulation. With this task, CBF increased by 61 +/- 7%, whereas CMRO(2) changed by 2.43 +/- 4.97%. These results are in good agreement with previous positron emission tomographic (PET) data, indicating that changes in oxidative metabolism during focal neuronal activity can potentially be determined with the breath-holding test. This test could easily be performed during a routine MRI examination. Magn Reson Med 42:608-611, 1999.

Blood Volume↗

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↗

Regional variability of cerebral blood oxygenation response to hypercapnia.

In functional magnetic resonance imaging studies changes in blood oxygenation level-dependent (BOLD) signal intensities during task activation are related to multiple physiological parameters such as cerebral blood flow, volume, and oxidative metabolism, as well as to the regional microvascular anatomy. Consequently, the magnitude of activation-induced BOLD signal changes may vary regionally and between subjects. The aim of this study was to use a uniform global stimulus such as hypercapnia to quantitatively investigate the regional BOLD response in the human brain. In 10 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 9 min during alternating periods of breath holding for 30 s after expiration and self-paced normal breathing for 60 s. Hypercapnia-induced BOLD signal changes in the sensorimotor cortex, frontal cortex, basal ganglia, visual cortex, and cerebellum were significantly different (P < 0.001) and varied from 1.8 to 5.1%. The highest BOLD signal changes were found in the cerebellum and visual cortex, whereas the lowest BOLD signal increase was observed in the frontal cortex. These results demonstrate a regional dependence of the BOLD signal changes during breath hold-induced hypercapnia, indirectly supporting the notion of regional different sensitivities of BOLD responses to task activation.

Adult↗

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↗

Gender differences in cerebral blood flow and oxygenation response during focal physiologic neural activity.

Using functional magnetic resonance imaging techniques CBF and oxygenation changes were measured during sustained checkerboard stimulation in 38 right-handed healthy volunteers (18 men and 20 women). The average blood oxygenation level dependent (BOLD) contrast technique signal intensity change was 1.67 +/- 0.6% in the group of male volunteers and 2.15 +/- 0.6% in the group of female volunteers (P < .05). Baseline regional CBF (rCBF) values in activated gray matter areas within the visual cortex were 57 +/- 10 mL x 100 g(-1) x min(-1) in women and 50 +/- 12 mL x 100 g(-1) x min(-1) in men, respectively (P = .09). Despite a broad overlap between both groups the rCBF increase was significantly higher in women compared to men (33 +/- 5 mL x 100 g(-1) x min(-1) versus 28 +/- 4 mL x 100 g(-1) x min(-1), P < .01). The increase of rCBF was not correlated with the baseline rCBF (mL x 100 g(-1) x min(-1)) (r(s) = 0.01, P = .9). Moreover, changes of rCBF were not correlated with changes in BOLD signal intensities (r(s) = 0.1, P = .7). Enhanced rCBF response in women during visual stimulation could be related to gender differences in visual physiology or may reflect gender differences in the vascular response to focal neuronal activation. Gender differences must be considered when interpreting the results of functional magnetic resonance imaging studies.

Adult↗