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N Lange

Publications and source records attributed to N Lange.

At least 37 records · Page 2Linked to original sources

Plurality and resemblance in fMRI data analysis.

We apply nine analytic methods employed currently in imaging neuroscience to simulated and actual BOLD fMRI signals and compare their performances under each signal type. Starting with baseline time series generated by a resting subject during a null hypothesis study, we compare method performance with embedded focal activity in these series of three different types whose magnitudes and time courses are simple, convolved with spatially varying hemodynamic responses, and highly spatially interactive. We then apply these same nine methods to BOLD fMRI time series from contralateral primary motor cortex and ipsilateral cerebellum collected during a sequential finger opposition study. Paired comparisons of results across methods include a voxel-specific concordance correlation coefficient for reproducibility and a resemblance measure that accommodates spatial autocorrelation of differences in activity surfaces. Receiver-operating characteristic curves show considerable model differences in ranges less than 10% significance level (false positives) and greater than 80% power (true positives). Concordance and resemblance measures reveal significant differences between activity surfaces in both data sets. These measures can assist researchers by identifying groups of models producing similar and dissimilar results, and thereby help to validate, consolidate, and simplify reports of statistical findings. A pluralistic strategy for fMRI data analysis can uncover invariant and highly interactive relationships between local activity foci and serve as a basis for further discovery of organizational principles of the brain. Results also suggest that a pluralistic empirical strategy coupled formally with substantive prior knowledge can help to uncover new brain-behavior relationships that may remain hidden if only a single method is employed.

Brain↗

Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study.

Exogenous administration of 5-aminolaevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of protoporphyrin IX (PpIX) in photodynamic therapy (PDT) and fluorescence photodetection (PD). Recently, results have shown that the chemical modification of ALA into its more lipophilic esters circumvents limitations of ALA-induced PpIX like shallow penetration depth into deep tissue layers and inhomogeneous biodistribution and enhances the total PpIX formation. The present clinical pilot study assesses the feasibility and the advantages of a topical ALA ester-based fluorescence photodetection in the human bladder. In this preliminary study 5-aminolaevulinic acid hexylester (h-ALA) solutions, containing concentrations ranging from 4 to 16 mM, were applied intravesically to 25 patients. Effects of time and drug dose on the resulting PpIX fluorescence level were determined in vivo with an optical fibre-based spectrofluorometer. Neither local nor systemic side-effects were observed for the applied conditions. All conditions used yielded a preferential PpIX accumulation in the neoplastic tissue. Our clinical investigations indicate that with h-ALA a twofold increase of PpIX fluorescence intensity can be observed using 20-fold lower concentrations as compared to ALA.

Aged↗

Optimisation of the formation and distribution of protoporphyrin IX in the urothelium: an in vitro approach.

PURPOSE: To optimize conditions for photodynamic detection (PDD) and photodynamic therapy (PDT) of bladder carcinoma, urothelial accumulation of protoporphyrin IX (PpIX) and conditions leading to cell photodestruction were studied. MATERIALS AND METHODS: Porcine and human bladder mucosae were superfused with derivatives of 5-aminolevulinic acid (ALA). PpIX accumulation and distribution across the mucosa was studied by microspectrofluorometry. Cell viability and structural integrity were assessed by using vital dyes and microscopy. RESULTS: ALA esters, especially hexyl-ALA, accelerated and regularized urothelial PpIX accumulation and allowed for necrosis upon illumination. CONCLUSIONS: hexyl-ALA used at micromolar concentrations is the most efficient PpIX precursor for PDD and PDT.

Aminolevulinic Acid↗

D-serine added to antipsychotics for the treatment of schizophrenia.

BACKGROUND: Hypofunction of N-methyl-D-aspartate (NMDA) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. D-serine is a full agonist of the glycine site of NMDA receptor, an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor. Supplementation of D-serine may improve the symptoms of schizophrenia. METHODS: Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-serine (30 mg/kg/day), which was added to their stable antipsychotic regimens. Of these, 28 completed the trial. Measures of clinical efficacy, side effects, and serum levels of amino acids and D-serine were determined every other week. Wisconsin Card Sorting Test (WCST) was performed at the beginning and end of the trial. RESULTS: Patients who received D-serine treatment revealed significant improvements in their positive, negative, and cognitive symptoms as well as some performance in WCST. D-serine levels at week 4 and 6 significantly predicted the improvements. D-serine was well tolerated and no significant side effects were noted. CONCLUSIONS: The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia. Given the effects of D-serine on positive symptoms, a trial of D-serine alone in schizophrenia should be considered.

Adult↗

Reduction in BOLD fMRI response to primary visual stimulation following alcohol ingestion.

The physiology of alcohol's effects on brain function is poorly understood. Emission tomographic imaging has revealed both acute and chronic alterations in resting cerebral hemodynamics and metabolism following alcohol ingestion. However, cerebral functional integrity under these conditions has received less attention. Functional magnetic resonance imaging (fMRI) offers a non-invasive method for assessing brain functional activation. In order to assess its utility for studying the effect of alcohol on brain function, we performed fMRI with photic stimulation before and after administration of either 0.7 mg/kg alcohol (N = 12) or placebo (N = 5), resulting in peak breath alcohol levels averaging 0.069 g/dl. We found that the amplitude of visual cortical activation in response to photic stimulation was significantly reduced by approximately 33% following alcohol administration (4.0 +/- 1.7% vs. 2.7 +/- 1.3%, P = 0.02), but not following placebo (4.2 +/- 1.5% vs. 4.1 +/- 1.4%, P = 0.7). The results also suggest that the baseline right hemispheric predominance of activation in response to photic stimulation may be reduced following alcohol, suggesting a greater effect on the right hemisphere, consistent with previous studies and alcohol's known effects on visuospatial processing. In addition, through the course of each activation session, there was a progressive reduction in response following alcohol. These data demonstrate that the cerebral effects of alcohol intoxication can be studied with fMRI, and that the effects on brain function of even moderate alcohol intoxication may be widespread, may be lateralized, and may include the visual system.

Adult↗

Cocaine-induced cerebral vasoconstriction detected in humans with magnetic resonance angiography.

CONTEXT: Clinical observations and case reports suggest that there are important cerebrovascular complications of cocaine use, but no studies have documented a direct link. OBJECTIVE: To determine whether low-dose cocaine administration induces cerebral vasoconstriction in healthy cocaine users. DESIGN: Randomized controlled trial. SUBJECTS: Twenty-four healthy and neurologically normal men (mean age, 29 years) reporting median cocaine use of 8 lifetime exposures (range, 3 to >40). INTERVENTION: Double-blind intravenous administration of cocaine (0.4 or 0.2 mg/kg) or placebo, with cerebral magnetic resonance angiography performed at baseline and 20 minutes following infusion. MAIN OUTCOME MEASURE: Cocaine-induced angiographic change indicative of vasoconstriction, as independently and concordantly rated by 2 reviewers blind to treatment condition. RESULTS: Cocaine-induced cerebral vasoconstriction in a dose-related fashion (P=.03), with angiograms indicative of vasoconstriction found in 5 of 8 and 3 of 9 subjects receiving 0.4- and 0.2-mg/kg cocaine, respectively, compared with 1 of 7 subjects administered placebo. Outcome stratification by frequency of self-reported lifetime cocaine use (3-10 times, 11-40 times, or >40 times) revealed a statistically stronger dose-related effect (P<.001), suggesting that greater lifetime cocaine use was associated with a greater likelihood of vasoconstriction. CONCLUSIONS: Cocaine administration induced dose-related cerebral vasoconstriction on magnetic resonance angiograms. These changes occurred at low cocaine doses and in the absence of other risk factors, including polydrug abuse, hypertension, or cerebrovascular disease. Outcome stratification by prior cocaine use statistically strengthened the relationship between cocaine administration and vasoconstriction, suggesting that cocaine may have a cumulative residual effect in promoting cerebrovascular dysfunction.

Adult↗

Gyri of the human neocortex: an MRI-based analysis of volume and variance.

This magnetic resonance imaging (MRI)-based morphometric analysis of cortical topography in the human brain is based upon the segmentation and parcellation of volumetric T1-weighted MRI data for a set of 20 young adult brains including 10 males and 10 females. For the most part, each parcellation unit (PU) of the neocortex corresponds to a single or a portion of a single gyrus. The volumes of each PU were computed for each brain. Subsets of PUs were also grouped so as to represent the neocortex for the frontal, temporal, parietal and occipital lobes. The coefficient of variation of the mean volume of total neocortex and that of the neocortex assigned to individual lobes cluster around 10%, whereas that of neocortex assigned to the individual gyri (PU) is more than twice that value. Approximately 80% of the total variance in gyral volume arises from determinants interactive for individual and specific gyri, while only approximately 10% of the total variance appears to be a reflection of uniform scaling to total neocortical volume. Sexual dimorphism contributes a pervasive though relatively small component of this variance. These results have implications for the study of structure-function correlation, and the proper statistical methods of handling volumetric data in morphometric studies. In addition, the nature of the covariance structure of the data will lead to future hypotheses regarding the relationships between the various potential genetic and epigenetic gyral influencing factors.

Adult↗

Variability of human brain structure size: ages 4-20 years.

Understanding variability of human brain structure sizes during development is important for the design and interpretation of pediatric neuroimaging studies. In this study we analyze the effects of hemisphere, sex and age on size variability of the total cerebrum, cerebellum, lateral ventricles, temporal lobe, amygdala, hippocampus, superior temporal gyrus, corpus callosum, caudate, putamen, and globus pallidus in 115 healthy children and adolescents, ages 4-20 years. Variability differed significantly across structures, with the lateral ventricles demonstrating the highest coefficient of variation and the putamen the lowest. Males varied significantly more than females in the left cerebrum and left superior temporal gyrus, whereas females varied more than males in the right caudate and right putamen. Age effects were seen in increased variability after puberty for the lateral ventricles, hippocampus and superior temporal gyrus. These variances are important determinants of minimum sample sizes required to detect group differences in both cross-sectional and longitudinal studies.

Adolescent↗

Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4-18 years.

The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders.

Adolescent↗

Statistical approaches to human brain mapping by functional magnetic resonance imaging.

Proper use of functional neuro-imaging through effective experimental design and modern statistical analysis provides new insights in current brain research. This tutorial has two aims: to describe aspects of this technology to applied statisticians and to provide some statistical ideas to neuroscientists unfamiliar with quantitative analytic methods that accommodate randomness. Introductory background material and ample references to current literature on the physics of magnetic resonance imaging, Fourier methods for image reconstruction and measures of image quality are included. Two of the statistical approaches mentioned here are extensions of established methods for longitudinal data analysis to the frequency domain. A recent case study provides real-world instances of approaches, problems and open questions encountered in current functional neuro-imaging research and an introduction to the analysis of spatial time series in this context.

Algorithms↗

Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder.

BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. METHODS: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. RESULTS: Subjects with ADHD had a 4.7% smaller total cerebral volume (P = .02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P = .006), smaller right globus pallidus (P = .005), smaller right anterior frontal region (P = .02), smaller cerebellum (P = .05), and reversal of normal lateral ventricular asymmetry (P = .03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. CONCLUSION: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.

Adolescent↗

Visualizing cortical activation during mental calculation with functional MRI.

Cortical activation during arithmetic calculation (silent subtraction by sevens) was compared to that observed during a control condition for which subjects were required to count forward by ones. Nine normal subjects underwent 1.5-T functional magnetic resonance imaging while performing these tasks. All subjects showed bilateral premotor, posterior parietal, and prefrontal cortex activation during serial calculation. There was a large degree of individual variation in activation outside of these areas. These results confirm the role of posterior parietal cortex in arithmetic calculation and implicate other regions, including prefrontal cortex.

Adult↗

[The effect of a low molecular weight synthetic humic substance on selected reproductive parameters of male rats].

Influences of the low molecular humic substance HS 1500 on parameters of organs (testis weight, epididymis weight), FSH-, and LH-levels in plasma as well as on the spermatogenesis of male rats were studied. After a daily oral application of 1000 mg/kg b.w. and 2000 mg/kg b.w., respectively over a period of 60 days (40th to 100th day of life) only 2 animals of the high dose group were observed with bilateral testicular atrophy. Despite of the two animals with testicular atrophy no significant differences between treated and control rats were observed with respect to testis morphology and spermatogenesis. There is no evidence whether the differences between the hormone levels and the testicular atrophy revealed is regarded to a HS 1500-effect or not. But otherwise a direct influence of HS 1500 can be ruled out with high certainty. Possibly because of the thin covering layer on the gastrointestinal mucous membrane formed by HS 1500, the absorption of nutritive substances is inhibited. Therefore the growth of sensitive organs like testis and epididymis, in the development period, can be decreased. Nevertheless, even after long time application the spermatogenesis is not influenced.

Administration, Oral↗

[The effect of a low molecular weight synthetic humic substance on pre- and postnatal development in rats].

The influence of a low molecular synthetic humic substance (HS 1500) on pre- and postnatal development of rats was investigated. After oral application of 1000 mg/kg and 2000 mg/kg b. w. HS 1500 during the period of organogenesis (6th to 15th day p. c.) and from 16th day p. c. up to weaning neither adverse effects in the mothers nor in the fetuses were reported. The occurrence of a single malformation (gastroschisis) after application of 1000 mg/kg b. w. from day 6 to 15 of pregnancy, few ossifications of phalanges and differences in swimming behaviour are not regarded as the effect of the substance. In conclusion, the oral use of HS 1500 in the treatment of gastrointestinal diseases in animals during pregnancy is regarded to be riskless.

Administration, Oral↗

[The resorptive behavior of a low-molecular weight humic substance after a single oral administration to the rat].

By labeling HS 1500 with a radioactive 14C, it was proven that after oral application and under certain circumstances, low amounts of low molecular humic acids are for a short time absorbed from the gastrointestinal tract. But the biological availability of the substance is very low (less than 0.1% of the applied high doses). The plasma concentration curve assumes a first order kinetic for invasion and excretion. After oral application of 500 mg/kg b.w. HS 1500 the half life period was 1.5 hours and maximum plasma concentration was 3 micrograms/ml. The result obtained indicate that HS 1500 is toxicological riskless after oral administration. Taking into account the pharmacokinetic data, residues of the substance in animal tissues can be ruled out with high significance.

Administration, Oral↗

Human postmortem interval estimation from vitreous potassium: an analysis of original data from six different studies.

The investigation of the postmortem interval (PMI) by determining potassium levels in the vitreous humor (KV) has been a subject of forensic pathology research for more than a quarter of a century. The numerous studies to date have yielded a variety of linear or piecewise-linear relationships between KV and PMI, i.e., different estimated intercepts and slopes of regression line(s) as well as different reliabilities of these estimates. This lack of agreement is due in part to the variable numbers of cases reported from study to study, differing observed ranges of KV and PMI, and the unaccommodated effects of factors on potassium concentration, including age of subject, amount of urea nitrogen, ambient temperature, and presence of illness. Original data from six of these studies, for a total of 790 cases, are reanalyzed together. The relationship between KV and PMI is not completely linear, and the residual variability of KV as a function of PMI is not constant. Thus, two main assumptions of the simple linear model, linearity and constant variance, are not supported by the data. It is clearly problematic to report statistical summaries such as the slope of an estimated regression line and the reliability of that estimate based on a model with faulty assumptions. Yet even after rescaling the data in an attempt to achieve linearity in the KV-PMI relationship and to stabilize residual variation, the relationship continues to be non-linear and its variability unstable. A new approach is developed for modeling KV and PMI that accommodates non-linearities and changing residual variability. A local regression model, specifically a loess smooth curve, is fitted separately to the data from each of the six studies. The loess smooth curve adapts locally to the changing and possibly non-linear relationship between KV and PMI across their observed ranges. The data from all six studies are then combined to yield a single loess curve with 95% confidence bands. The estimated loess curve and confidence bands are used in an inverse prediction method to construct low, middle and high PMI estimates at given values of KV. The reliability of estimated PMI decreases as KV increases. Although the confidence bands surrounding the overall curve widen in the extreme high end due to there being fewer available data in that region, PMI estimates are more precise over the entire range of KV and PMI than those obtained from any single study alone. A cross-validation procedure provides an independent check of the predictive performance of the method.

Age Factors↗