Fiber tracking from DTI using linear state space models: detectability of the pyramidal tract.

Diffusion tensor imaging (DTI) is an emerging and promising tool to provide information about the course of white matter fiber tracts in the human brain. Based on specific acquisition schemes, diffusion tensor data resemble local fiber orientations allowing for a reconstruction of the fiber bundles. Current techniques to calculate fascicles range from simple heuristic tracking solutions to Bayesian and differential equations approaches. Most methods are based only on local diffusion information, often resulting in bending or kinking fiber paths in voxels with reduced diffusion properties. In this article we present a new tracking approach based on linear state space models encompassing an inherent smoothness criterion to avoid too wiggly tracked fiber bundles. The new technique will be described formally and tested on simulated and real data. The performance tests are focused on the pyramidal tract, where we employed a test-retest study and a group comparison in healthy subjects. Anatomical course was confirmed in a patient with selective degeneration of the pyramidal tract. The potential of the presented technique for improved neurosurgical planning is demonstrated by visualization of a tumor-induced displacement of the motor pathways. The paper closes with a thorough discussion of perspectives and limitations of the new tracking approach.

Bayesian analysis of logistic regression with an unknown change point and covariate measurement error.

We discuss Bayesian estimation of a logistic regression model with an unknown threshold limiting value (TLV). In these models it is assumed that there is no effect of a covariate on the response under a certain unknown TLV. The estimation of these models in a Bayesian context by Markov chain Monte Carlo (MCMC) methods is considered with focus on the TLV. We extend the model by accounting for measurement error in the covariate. The Bayesian solution is compared with the likelihood solution proposed by Küchenhoff and Carroll using a data set concerning the relationship between dust concentration in the working place and the occurrence of chronic bronchitis.

Improved analysis of 1H-MR spectra in the presence of mobile lipids.

Focal brain lesions can be associated with proton magnetic resonance spectra (1H-MRS)-detectable mobile lipids, reflecting severe tissue degradation and necrosis. However, advanced fitting procedures, such as the LCModel, fail to adequately fit spectra in the presence of lipid resonances. To overcome this, different approaches to generate lipid model spectra were compared using a phantom, real in vivo data, and simulated data. Twenty-six in vivo short-echo time (TE) 1H-MRS from 21 malignant gliomas, four infections, and one ischemia were analyzed to evaluate the performance of the modified LCModel fit. Adding simulated aliphatic resonances at 1.3 and 0.9 ppm improved the overall fitting quality remarkably and allowed good separation of lactate and alanine. Also, a better differentiation of glioblastomas and anaplastic gliomas was achieved. In conclusion, we propose a simple way to efficiently include lipid resonances in the LCModel, allowing a better fit of in vivo short-TE 1H-MRS, and demonstrate the diagnostic potential of quantitative assessment of mobile lipids in brain tumors.

Blood pressure changes induced by arterial blood withdrawal influence bold signal in anesthesized rats at 7 Tesla: implications for pharmacologic mri.

Functional magnetic resonance imaging (fMRI) using the blood oxygenation level-dependent (BOLD) contrast is now increasingly applied for measuring drug effects on brain activity. A possible confound in pharmacologic fMRI (phMRI) is that the BOLD signal may be sensitive to systemic cardiovascular or respiratory parameters, which can themselves be modulated by a drug. To assess whether abrupt changes in arterial blood pressure (BP) as may be observed in phMRI experiments influence the BOLD signal, a hemorrhage model was studied in anesthesized rats at 7 T using spin-echo EPI. BP and BOLD signal time courses were found to be significantly correlated (P < 0.01). This effect was detected under the three different anesthetic regimens employed (isoflurane, halothane, and propofol). The regional pattern of BP-BOLD correlations was heterogeneous and may reflect vascular density. In physiological terms, a BOLD decrease during a decrease in BP may result from an increase in mostly venous cerebral blood volume (CBV) as an autoregulatory response to maintain cerebral blood flow (CBF) during decreased perfusion pressure. The observed influence of BP on BOLD may complicate qualitative and quantitative description of drug effects.

Bayesian modeling of the hemodynamic response function in BOLD fMRI.

In functional magnetic resonance imaging (fMRI), modeling the complex link between neuronal activity and its hemodynamic response via the neurovascular coupling requires an elaborate and sensitive response model. Methods based on physiologic assumptions as well as direct, descriptive models have been proposed. The focus of this study is placed on such a direct approach that allows for a robust pixelwise determination of hemodynamic characteristics, such as time to peak or the poststimulus undershoot. A Bayesian procedure is presented that can easily be adapted to different hemodynamic properties in question and can be estimated without numerical problems known from nonlinear optimization algorithms. The usefulness of the model is demonstrated by thorough analyzes of the poststimulus undershoot in visual and acoustic stimulation paradigms. Further, we show the capability of this approach to improve analysis of fMRI data in altered hemodynamic conditions.

Frequency dependence and gender effects in visual cortical regions involved in temporal frequency dependent pattern processing.

Neural response to flickering stimuli has been shown to be frequency dependent in the primary visual cortex. Controversial gender differences in blood oxygen level dependent (BOLD) amplitude upon 6 and 8 Hz visual stimulation have been reported. In order to analyze frequency and gender effects in early visual processing we employed a passive graded task paradigm with a dartboard stimulus combining eight temporal frequencies from 0 to 22 Hz in one run. Activation maps were calculated within Statistical Parametric Mapping, and BOLD amplitudes were estimated for each frequency within the striate and extrastriate visual cortex. The BOLD amplitude was found to steadily rise up to 8 Hz in BA 17 and 18 with an activation plateau at higher frequencies. In addition, we observed a laterality effect in the striate cortex with higher BOLD contrasts in the right hemisphere in men and in women. BOLD response rises similarly in men and women up to 8 Hz but with lower amplitudes in women at 4, 8, and 12 Hz (30% lower). No frequency effect above 1 Hz was found in the extrastriate visual cortex. There was also a regional specific gender difference. Men activated more in the right lingual gyrus (BA 18) and the right cerebellum compared with women, whereas women showed more activation in the right inferior temporal gyrus (BA 17). The study indicates that frequency dependent processing at the cortical level is limited to the striate cortex and may be associated with a more global information processing (right hemisphere dominance), particularly in men. The finding of significantly lower BOLD amplitudes in women despite previously shown larger VEP (visual evoked potential) amplitudes might suggest gender differences in cerebral hemodynamics (baseline rCBV, rCBF, or neurovascular coupling). The regional distinction points at additional differences in psychological processing even when using a simple visual stimulus.

Bayesian spatiotemporal inference in functional magnetic resonance imaging.

Mapping of the human brain by means of functional magnetic resonance imaging (fMRI) is an emerging field in cognitive and clinical neuroscience. Current techniques to detect activated areas of the brain mostly proceed in two steps. First, conventional methods of correlation, regression, and time series analysis are used to assess activation by a separate, pixelwise comparison of the fMRI signal time courses to the reference function of a presented stimulus. Spatial aspects caused by correlations between neighboring pixels are considered in a separate second step, if at all. The aim of this article is to present hierarchical Bayesian approaches that allow one to simultaneously incorporate temporal and spatial dependencies between pixels directly in the model formulation. For reasons of computational feasibility, models have to be comparatively parsimonious, without oversimplifying. We introduce parametric and semiparametric spatial and spatiotemporal models that proved appropriate and illustrate their performance applied to visual fMRI data.

Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison.

PURPOSE: To differentiate lesion patterns in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from those in patients with sporadic subcortical arteriosclerotic encephalopathy (sSAE). MATERIALS AND METHODS: Magnetic resonance (MR; T2-weighted and fluid-attenuated inversion-recovery) images obtained in 28 patients with CADASIL were compared with images obtained in 24 patients with sSAE by using an automated pixel-based group comparison with statistical parametric mapping and regional semiquantitative rating. RESULTS: Visual rating showed higher lesion scores for CADASIL in the temporal and temporopolar white matter (WM). Statistical parametric mapping group analysis independently revealed more extensive bilateral involvement of the anterior temporal and superior frontal WM in CADASIL. There were bilateral signal intensity reductions within the dentate nucleus, deep cerebellar WM, crus cerebri, and thalamus. Lesions extended remarkably more often into arcuate fibers in the temporopolar and paramedian superior frontal lobes in CADASIL. Linear discriminant analysis was used to classify 96% (50 of 52) of the cases correctly, with temporopolar WM and arcuate fiber involvement contributing most to the discrimination function. CONCLUSION: The presented MR imaging criteria are useful in the diagnostic work-up in patients with leukoencephalopathy and help to differentiate CADASIL from sSAE. The observed pattern of vulnerability in CADASIL suggests future directions for research in the pathophysiology of this disorder. In addition, the study demonstrates the potential of automated image analysis to explore MR imaging lesion patterns.

Dynamic models in fMRI.

Most statistical methods for assessing activated voxels in fMRI experiments are based on correlation or regression analysis. In this context, the main assumptions are that the baseline can be described by a few known basis functions or variables and that the effect of the stimulus, i.e., the activation, stays constant over time. As these assumptions are in many cases neither necessary nor correct, a new dynamic approach that does not depend on those assumptions will be presented. This allows for simultaneous nonparametric estimation of the baseline and, as an important feature, of time-varying effects of stimulation. This method of estimating the stimulus related areas of the brain furthermore provides the possibility to analyze the temporal and spatial evolution of the activation within an fMRI experiment.

Characterization of human insulin-like growth factor-binding proteins by two-dimensional polyacrylamide gel electrophoresis and Western ligand blot analysis.

The insulin-like growth factor (IGF)-binding proteins (IGFBPs) from adult human serum, amniotic fluid, and cerebrospinal fluid were analyzed by a modified two-dimensional gel electrophoresis followed by Western ligand blotting. The samples were subjected to immobilized pH gradient isoelectric focusing in the first dimension, followed by nondenaturing SDS-PAGE in the second dimension and autoradiography after ligand blotting with [125I]IGF-I or [125I]IGF-II. The identity of the binding proteins was confirmed by immunoblotting and immunoprecipitation with specific antibodies. Using this method, all six human high affinity IGFBPs could be clearly separated from each other according to their molecular mass and isoelectric points (pI). All IGFBPs exhibited a variety of specific pI isoforms, which presumably represent posttranslational modifications. In adult human serum, glycosylated IGFBP-3 is found as a broad band of spots with molecular masses of 41 and 45 kDa and a pI in the range of 4.8-8.2. The two IGFBP-3 bands could be reduced to a single 36-kDa band after deglycosylation (pI 6-9). Furthermore, the specific spots for IGFBP-2 (33 kDa; pI 6.2-7.1) and deglycosylated IGFBP-4 (24 kDa; pI 6.3, 6.5, and 6.8) were found with their expected molecular masses. Additionally, the diffuse bands around 30 kDa, found in one-dimensional Western ligand blotting, could be clearly separated into distinct groups of specific spots representing IGFBP-1 (30 kDa; pI 4.0-4.8), IGFBP-6 (30 kDa; pI 4.8-5.8), glycosylated IGFBP-4 (29 kDa; pI 6.1 and 6.3), and IGFBP-5 (30/31 kDa; pI 6.4-8). As expected, IGFBP-6 was visible only when IGF-II was used as radioligand. In conclusion, two-dimensional gel electrophoresis followed by Western ligand blotting allows identification of all six high affinity IGFBPs with their isoforms on the basis of their characteristic molecular masses and pI, especially in the range of 30 kDa. This technique can be rapidly performed with small amounts of complex biological fluids and is a powerful tool for the detection and analysis of posttranslational modifications of IGFBPs.

Sarcoidosis associated with interferon-alpha therapy for chronic hepatitis C.

BACKGROUND/AIMS: Pulmonary side effects of interferon-alpha therapy of chronic hepatitis C seem to be rare. So far, only two cases of sarcoidosis in association with interferon-alpha treatment of chronic hepatitis C have been described. METHODS/CASES: We report on three patients who were treated with recombinant interferon-alpha2a for chronic hepatitis C, two of them in combination with ribavirin. These patients developed pulmonary sarcoidosis 12, 20 and 21 weeks, respectively, after beginning interferon therapy, one patient with Löfgren's syndrome. In one patient sarcoidosis emerged only after discontinuation of interferon therapy because of treatment failure. Clinical symptoms of sarcoidosis in the three patients were suggestive of side effects of interferon-alpha. Interferon therapy was discontinued and spontaneous remission was observed in all three cases 5, 6, and 8 months, respectively, after the onset of symptoms. CONCLUSION: The occurrence of sarcoidosis in association with interferon-alpha therapy for chronic hepatitis C may have been underestimated so far. This could be due to the fact that symptoms of sarcoidosis and common side effects of interferon are similar, and sarcoidosis may occur after the end of interferon therapy. We hypothesize that interferon-alpha as a potent stimulator for T-helper 1 (Th1) immune responses may trigger the compartmentalized Th1 reaction that has been shown to take place in sarcoidosis.