Biomedical subjects

Frank Seifert

Publications and source records attributed to Frank Seifert.

13 recordsLinked to original sources

PubMed2007

Abnormal hippocampal neurochemistry in smokers: evidence from proton magnetic resonance spectroscopy at 3 T.

OBJECTIVE: In animals, nicotine, the primary psychoactive constituent of tobacco smoke, reduces neurogenesis and increases cell loss in both hippocampus and cortex. Accordingly, tobacco smoking has been linked to reduced performance on cognitive paradigms requiring attention and working memory in humans. However, few prior studies have tested for evidence of structural brain alterations in human tobacco smokers. In this study, proton magnetic resonance spectroscopy was used to assess the effects of chronic smoking on neuronal integrity of the hippocampus and anterior cingulate cortex (ACC). METHODS: Absolute concentrations of N-acetylaspartate, total choline (tCho), and total creatine were measured in the left hippocampus and ACC in 13 chronic tobacco smokers and 13 nonsmokers matched for age, sex, and education. RESULTS: The N-acetylaspartate concentration was significantly reduced in smokers relative to nonsmokers in the left hippocampus but not in the ACC. There were no group differences in the tCho and total creatine concentrations in either voxel. However, ACC tCho concentration was positively correlated with magnitude of lifetime exposure to tobacco smoke (pack-years). CONCLUSION: The results are consistent with prior observations of hippocampal neuronal damage in rodents receiving nicotine and working memory deficits in human tobacco smokers. The positive relationship between tCho and lifetime tobacco exposure suggests that a component of tobacco smoke, presumably nicotine, may increase cortical membrane turnover or modify cell density. Together, these results add to growing evidence that nicotine exerts neurotoxic effects in human brain, although an a priori nature of the findings cannot be ruled out.

Adult↗

PubMed2006

Laser power stabilization for second-generation gravitational wave detectors.

We present results on the power stabilization of a Nd:YAG laser in the frequency band from 1 Hz to 100 kHz. High-power, low-noise photodetectors are used in a dc-coupled control loop to achieve relative power fluctuations down to 5 x 10(-9) Hz(-1/2) at 10 Hz and 3.5 x 10(-9) Hz(-1/2) up to several kHz, which is very close to the shot-noise limit for 80 mA of detected photocurrent on each detector. We investigated and eliminated several noise sources such as ground loops and beam pointing. The achieved stability level is close to the requirements for the Advanced LIGO gravitational wave detector.

Journal Article↗

PubMed2006

Metabolic alterations in the dorsolateral prefrontal cortex after treatment with high-frequency repetitive transcranial magnetic stimulation in patients with unipolar major depression.

Neuroimaging studies suggest a specific role of anterior cingulate cortex (ACC) and left dorsolateral prefrontal cortex (DLPFC) in major depression. Stimulation of the latter by means of repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the past. The objective of the present study was to examine in vivo neurochemical alterations in both brain regions in 17 patients with unipolar major depression before and after 10 days of high-frequency (20Hz) rTMS of the left DLPFC using 3-tesla proton magnetic resonance spectroscopy. Six out of seventeen patients were treatment responders, defined as a 50% reduction of the Hamilton depression rating scale. No neurochemical alterations in the ACC were detected after rTMS. As compared to the non-responders, responders had lower baseline concentrations of DLPFC glutamate which increased after successful rTMS. Correspondingly, besides a correlation between clinical improvement and an increase in glutamate concentration, an interaction between glutamate concentration changes and stimulation intensity was observed. Our results indicate that metabolic, state-dependent changes within the left DLPFC in major depressive disorder involve the glutamate system and can be reversed in a dose-dependent manner by rTMS.

Adult↗

PubMed2006

Smoking and structural brain deficits: a volumetric MR investigation.

Growing evidence from animal studies indicates brain-damaging properties of nicotine exposure. Investigations in humans found a wide range of functional cerebral effects of nicotine and cigarette smoking, but studies focusing on brain damage are sparse. In 22 smokers and 23 never-smokers possible differences of the cerebral structures were investigated using magnetic resonance imaging and voxel-based morphometry. Significantly smaller grey matter volume and lower grey matter density (P = 0.05, corrected) were observed in the frontal regions (anterior cingulate, prefrontal and orbitofrontal cortex), the occipital lobe and the temporal lobe including parahippocampal gyrus, in smokers than in never-smokers. Group differences of either grey matter volume or grey matter density were also found in the thalamus, cerebellum and substantia nigra, among other regions. Smokers did not show greater volumes than never-smokers in any cerebral region. Magnitude of lifetime exposure to tobacco smoke (pack-years) was inversely correlated with volume of frontal and temporal lobes and cerebellum (P = 0.001, uncorrected). The data indicate structural deficits of several cortical and subcortical regions in smokers relative to never-smokers. The topographic profile of the group differences show some similarities to brain networks known to mediate drug reinforcement, attention and working memory processing. The present findings may explain in part the frequently reported cognitive dysfunctions in chronic cigarette consumers.

Adult↗

PubMed2005

Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene.

Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli. We further present convergent behavioral and electrophysiological evidence that the variable responses to noxious heat are due to strain-dependence of CGRP expression and sensitivity. Strain differences in behavioral response to noxious heat could be abolished by peripheral injection of CGRP, blockade of cutaneous and spinal CGRP receptors, or long-term inactivation of CGRP with a CGRP-binding Spiegelmer. Linkage mapping supports the contention that the genetic variant determining variable heat pain sensitivity across mouse strains affects the expression of the Calca gene that codes for CGRPalpha.

Animals↗

PubMed2005

TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol.

The aim of this study was to evaluate the psychophysical effects of both TRPA1 and TRPM8 activation in humans by application of either cinnamaldehyde or menthol. We applied 10% cinnamaldehyde or 40% menthol solutions on the forearm in 10 study participants. Quantitative sensory testing and laser Doppler imaging was performed before and after exposure to the compounds. Cinnamaldehyde evoked significant spontaneous pain and induced heat and mechanical hyperalgesia, cold hypoalgesia and a neurogenic axon reflex erythema. In contrast, TRPM8 activation by menthol produced no axon reflex reaction and resulted in cold hyperalgesia. We conclude that agonists of TRPA1 and TRPM8 channels produce strikingly different psychophysical patterns.

Acrolein↗

PubMed2005

Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety.

The impact of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) on anxiety-related behavior and related cerebral activation has facilitated the understanding of neurobiological mechanisms of anxiety. However, the influence of the 5-HTTLPR genotype on hippocampal neuronal development and neurochemistry, which is relevant to anxiety behavior, has not been investigated. In 38 healthy subjects, absolute concentrations of N-acetylaspartate (NAA) were measured as a main surrogate parameter for hippocampal neurochemistry on a 3-T scanner. A significantly lower hippocampal NAA concentration in s allele carriers was observed as compared to l/l genotype. Other metabolites (choline, creatine + phosphocreatine, glutamate) were unaffected by genotype. The hippocampal NAA concentration was negatively correlated with trait anxiety scores (STAI). Metabolites measured in the anterior cingulate cortex (reference region) were not associated with genotype. The results are in accordance with the recently reported relationship between hippocampal neuronal development and anxiety behavior in adult animals and show an association between human limbic neurochemistry and genetically driven serotonergic neurotransmission relevant to anxiety.

Alleles↗

PubMed2005

Quantitative magnetic resonance spectroscopy: semi-parametric modeling and determination of uncertainties.

A semi-parametric approach for the quantitative analysis of magnetic resonance (MR) spectra is proposed and an uncertainty analysis is given. Single resonances are described by parametric models or by parametrized in vitro spectra and the baseline is determined nonparametrically by regularization. By viewing baseline estimation in a reproducing kernel Hilbert space, an explicit parametric solution for the baseline is derived. A Bayesian point of view is adopted to derive uncertainties, and the many parameters associated with the baseline solution are treated as nuisance parameters. The derived uncertainties formally reduce to Cramér-Rao lower bounds for the parametric part of the model in the case of a vanishing baseline. The proposed uncertainty calculation was applied to simulated and measured MR spectra and the results were compared to Cramér-Rao lower bounds derived after the nonparametrically estimated baselines were subtracted from the spectra. In particular, for high SNR and strong baseline contributions the proposed procedure yields a more appropriate characterization of the accuracy of parameter estimates than Crémer-Rao lower bounds, which tend to overestimate accuracy.

Bayes Theorem↗

PubMed2005

Experimental analysis of parallel excitation using dedicated coil setups and simultaneous RF transmission on multiple channels.

An experimental implementation and first performance analysis of parallel spatially selective excitation with an array of transmit coils and simultaneous transmission of individual waveforms on multiple channels is presented. This technique, also known as Transmit SENSE, uses the basic idea of parallel imaging to shorten the k-space trajectories that accompany multidimensional excitation pulses, and hence shorten the duration of such pulses. So far, this concept has only been presented in simulations and semi-experimental studies since no hardware setup had been available for a full experimental realization. In this study, a hardware solution, in combination with a dedicated coil setup, is presented to overcome this limitation, and in several experiments of localized excitation and transmit field inhomogeneity compensation the practical feasibility of Transmit SENSE is demonstrated and a first performance analysis is given.

Equipment Design↗

PubMed2004

Dynamic NMR spectroscopy of hyperpolarized (129)Xe in human brain analyzed by an uptake model.

Hyperpolarized (129)Xe (HpXe) NMR not only holds promise for functional lung imaging, but for measurements of tissue perfusion as well. To investigate human brain perfusion, several time-series of (129)Xe MR spectra were recorded from one healthy volunteer after HpXe inhalation. The time-dependent amplitudes of the MR spectra were analyzed by using a compartment model for xenon uptake modified to account for the loss of (129)Xe polarization due to RF-excitation and for the breathhold technique used in the experiments. This analysis suggests that the resonances detected at 196.5 +/- 1 ppm and 193 +/- 1 ppm originate from HpXe dissolved in gray and white matter, respectively, and that T(1) relaxation times of HpXe are different in gray and white matter (T(1g) > T(1w)).

Algorithms↗

PubMed2004

Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla.

A method for quantitative determination of the glutamate (Glu) concentration in human brain using PRESS-based single voxel MR spectroscopy (MRS) at 3 T has been developed and validated by repeatedly analyzing voxels comprising the anterior cingulate cortex (acc) and the left hippocampus (hc) in 40 healthy volunteer brains. At an optimum echo time of 80 ms, the C4 resonance of Glu appears well resolved and separated from major interferents, that is, glutamine and N-acetylaspartate. As a complementary method, a multiple quantum coherence filter sequence for Glu was employed. For quantification of Glu and the principal MRS-visible metabolites as well as for an estimate of the glutamine level, analysis of both types of in vivo spectra was carried out by a time domain-frequency domain method involving prior knowledge obtained from phantom spectra. Using PRESS, coefficients of variation (CV) for Glu concentration were of the order of 10%. When the concentrations were corrected by individual cerebrospinal fluid fractions obtained by segmentation using spm, CVs tended to increase and the correlation coefficients for the two MRS sessions tended to decrease, indicating that this type of correction adds uncertainty to the data. The concentrations of Glu in the two voxels studied were found to be significantly different (11.6 mmol/l in acc, 10.9 mmol/l in hc, P = 0.023) and decrease with age (P < 0.04). These concentrations agreed well with those determined using the quantum coherence filter method although the uncertainty of the latter limits reliable analysis.

Adult↗

PubMed2002

Serial 1H-MRS in relapsing-remitting multiple sclerosis: effects of interferon-beta therapy on absolute metabolite concentrations.

To assess the applicability of magnetic resonance spectroscopy (MRS) for long-term follow-up of neurological diseases a longitudinal 1H-MRS study at 3 T was carried out on ten patients having relapsing-remitting multiple sclerosis (MS) who, after baseline examination, received interferon-beta (IFN) 1b. At 8-20 examinations within up to 34 months absolute concentrations of N-acetylaspartate (NAA), total creatine (tG), and choline-containing compounds (tCho) were determined in a large non-enhancing lesion and contralateral normal appearing white matter (NAWM). MR spectra were analyzed using a novel time domain-frequency domain method including non-parametric background characterization. For comparison at baseline, ten healthy controls were examined. The concentrations of tCho and tCr were found to be higher in MS brain than in control brain. Besides a non-significantly lower NAA concentration in lesions there were no concentration differences between lesions and NAWM. Over the follow-up period the measured metabolite concentrations exhibited a high variability. Most concentrations remained within this scatter, and statistical tests revealed significant fluctuations in the levels of metabolites in one case only. This stability of the metabolite concentrations over time might result from IFN therapy as for the spontaneous course of relapsing-remitting MS decreasing metabolite (NAA/tCr) ratios have been reported. The results further suggest that future treatment trials intending to use metabolite concentrations as a secondary outcome indicator use even longer observation periods and, besides group analysis of large cohorts, investigate the time behavior of selected single cases. The biochemical abnormalities found in NAWM emphasize the importance of analyzing both lesion and NAWM.

Adult↗

PubMed2002

Combined coronary artery bypass and carotid endarterectomy: long-term results.

PURPOSE: We determined late survival, freedom from late stroke, and freedom from late cardiac events in patients treated by combined coronary artery bypass and carotid endarterectomy (CAB/CEA). METHODS: All patients who underwent CAB/CEA in our institution between January 1994 and December 1999 were identified. Follow-up data were obtained from office records and telephone interviews. Endpoints included death from any cause, stroke, and non-fatal cardiac events (MI, CHF, percutaneous transluminal angioplasty with stenting, redo CAB). Data were expressed in life table format. RESULTS: Over a 6-yr period 154 patients had combined CAB/CEA with a 3.9% postoperative stroke rate. Six patients (3.9%) died, leaving 148 patients for follow-up. Average follow-up was 38 +/- 23 months (range: 1-82 months). During the follow-up period two patients (1.4%) had late strokes and 17 patients (11%) had late non-fatal cardiac events. The late mortality rate was 13% (19 patients). Of the late mortalities, four were related to cardiac disease and one to stroke. Using Kaplan-Meier analysis, the 5-yr survival probability was 80 +/- 4.3%. The freedom from late ipsilateral neurologic events was 98 +/- 1.3% at 5 yr. The freedom from late cardiac events was 82 +/- 4.6% at 5 yr. CONCLUSIONS: The large majority of patients with combined coronary and carotid artery disease can be expected to live for greater than 5 yr. Therefore, these patients should be considered candidates for prophylactic CEA for stroke prevention, even when their carotid lesions are asymptomatic. Successful CAB/CEA provides good long-term survival and freedom from late cardiac events, as well as excellent freedom from late stroke. Further reduction in perioperative events will make this operative approach even more attractive in patients with combined disease.

Aged↗