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PubMed2006

The NIH MRI study of normal brain development.

MRI is increasingly used to study normal and abnormal brain development, but we lack a clear understanding of "normal". Previous studies have been limited by small samples, narrow age ranges and few behavioral measures. This multi-center project conducted epidemiologically based recruitment of a large, demographically balanced sample across a wide age range, using strict exclusion factors and comprehensive clinical/behavioral measures. A mixed cross-sectional and longitudinal design was used to create a MRI/clinical/behavioral database from approximately 500 children aged 7 days to 18 years to be shared with researchers and the clinical medicine community. Using a uniform acquisition protocol, data were collected at six Pediatric Study Centers and consolidated at a Data Coordinating Center. All data were transferred via a web-network into a MYSQL database that allowed (i) secure data transfer, (ii) automated MRI segmentation, (iii) correlation of neuroanatomical and clinical/behavioral variables as 3D statistical maps and (iv) remote interrogation and 3D viewing of database content. A population-based epidemiologic sampling strategy minimizes bias and enhances generalizability of the results. Target accrual tables reflect the demographics of the U.S. population (2000 Census data). Enrolled subjects underwent a standardized protocol to characterize neurobehavioral and pubertal status. All subjects underwent multi-spectral structural MRI. In a subset, we acquired T1/T2 relaxometry, diffusion tensor imaging, single-voxel proton spectroscopy and spectroscopic imaging. In the first of three cycles, successful structural MRI data were acquired in 392 subjects aged 4:6-18:3 years and in 72 subjects aged 7 days to 4:6 years. We describe the methodologies of MRI data acquisition and analysis, using illustrative results. This database will provide a basis for characterizing healthy brain maturation in relationship to behavior and serve as a source of control data for studies of childhood disorders. All data described here will be available to the scientific community from July, 2006.

Adolescent↗
PubMed2006

Distributed brain sites for the g-factor of intelligence.

The general factor of intelligence (g) results from the empirical fact that almost all cognitive tests are positively correlated with one another. Individual tests can be classified according to the degree to which they involve g. Here, regional brain volumes associated with g are investigated by means of structural magnetic resonance imaging and voxel-based morphometry. First, individual differences in the amount of regional gray matter volumes across the entire brain were correlated with eight cognitive tests showing distinguishable g-involvement. Results show that increasing g-involvement of individual tests was associated with increased gray matter volume throughout the brain. Second, it is shown that two prototypical measures of verbal and non-verbal g (i.e., vocabulary and block design) correlate with the amount of regional gray matter across frontal, parietal, temporal, and occipital lobes, suggesting that the general factor of intelligence relates to areas distributed across the brain as opposed to the view that g derives exclusively from the frontal lobes.

Adolescent↗
PubMed2003

Estimation of general linear model coefficients for real-time application.

An algorithm using an orthogonalization procedure to estimate the coefficients of general linear models (GLM) for functional magnetic resonance imaging (fMRI) calculations is described. The idea is to convert the basis functions or explanatory variables of a GLM into orthogonal functions using the usual Gram-Schmidt orthogonalization procedure. The coefficients associated with the orthogonal functions, henceforth referred to as auxiliary coefficients, are then easily estimated by applying the orthogonality condition. The original GLM coefficients are computed from these estimates. With this formulation, the estimates can be updated when new image data become available, making the approach applicable for real-time estimation. Since the contribution of each image data is immediately incorporated into the estimated values, storing the data in memory during the estimation process becomes unnecessary, minimizing the memory requirements of the estimation process. By employing Cholesky decomposition, the algorithm is a factor of two faster than the standard recursive least-squares approach. Results of the analysis of an fMRI study using this approach showed the algorithm's potential for real-time application.

Algorithms↗
PubMed2003

Statistical tests for fMRI based on experimental randomization.

Statistical parametric mapping (SPM) analysis of fMRI data requires specifying correctly the temporal and spatial noise covariance structure. This is a difficult if not impossible task. When these assumptions are not satisfied, statistical inference can be invalid or inefficient. Permutation tests are free of strong assumptions on the distribution of signal noise. We propose permutation tests of fMRI data based on experimental randomization of the stimulus sequences. Smooth hemodynamic response curves are estimated using quadratic B-splines. We study fMRI data obtained from event-related potential (ERP) oddball paradigm. Tests of two-tone and three-tone stimulus sequences are conducted to illustrate the application of the proposed method. Comparisons of the SPM and proposed method show that a permutation test is more specific and less susceptible to artifacts.

Arousal↗
PubMed2003

Interindividual functional mapping: a nonlinear local approach.

Within the scope of three-dimensional brain imaging, we propose an interindividual fusion scheme to register functional activations according to anatomical cortical structures, the sulci. This paper is based on the assumption that an important part of functional intersubject variability is encoded in anatomical variability. The aim of this paper is therefore to propose a generic framework to register functional activations according to the relevant anatomical landmarks. Compared to "classical" interindividual fusion schemes, this approach is local. It relies on a statistical sulci shape model accounting for the interindividual variability of a population of subjects and providing deformation modes relative to a reference shape (a mean sulcus). The deformation field obtained between a given sulcus and the reference sulcus is extended to a neighborhood of the given sulcus by using the thin-plate spline interpolation. It is then applied to functional activations located in the vicinity of this sulcus. This approach is compared with rigid and nonrigid registration methods. In this paper, we present results on MEG somatosensory data acquired on 18 subjects. We show that the nonlinear local fusion scheme significantly reduces the observed functional variability.

Adult↗
PubMed2003

Region of interest based analysis of functional imaging data.

fMRI analysis techniques are presented that test functional hypotheses at the region of interest (ROI) level. An SPM-compatible Matlab toolbox has been developed that allows the creation of subject-specific ROI masks based on anatomical markers and the testing of functional hypotheses on the regional response using multivariate time-series analysis techniques. The combined application of subject-specific ROI definition and region-level functional analysis is shown to appropriately compensate for intersubject anatomical variability, offering finer localization and increased sensitivity to task-related effects than standard techniques based on whole-brain normalization and voxel or cluster-level functional analysis, while providing a more direct link between discrete brain region hypotheses and the statistical analyses used to test them.

Artifacts↗
PubMed1994

High-resolution structure of an engineered biologically potent insulin monomer, B16 Tyr-->His, as determined by nuclear magnetic resonance spectroscopy.

Site-directed mutagenesis is used in conjunction with 1H nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy in order to find an insulin species amenable for structure determination in aqueous solution by NMR spectroscopy. A successful candidate in this respect, i.e., B16 Tyr-->His mutant insulin, is identified and selected for detailed characterization by two-dimensional 1H NMR. This mutant species retains 43% biological potency and native folding stability, but in contrast to human insulin it remains monomeric at millimolar concentration in aqueous solution at pH 2.4. The resulting homogeneous sample allows high-quality 2D NMR spectra to be recorded. The NMR studies result in an almost complete assignment of the 1H resonance signals as well as identification of NOE cross peaks. NOE-derived distance restraints in conjunction with torsion restraints based on measured coupling constants, 3JHNH alpha, are used for structure calculations using the hybrid method of distance geometry and simulated annealing. The calculated structures show that the major part of the insulin monomer is structurally well-defined with an average rms deviation between the 20 calculated structures and the mean coordinates of 0.89 A for all backbone atoms, 0.46 A for backbone atoms (A2-A19 and B4-B28), and 1.30 A for all heavy atoms. The structure of the A-chain is composed of two helices from A2 to A7 and from A12 to A19 connected by a short extended strand. The B-chain consists of a loop, B1-B8, an alpha-helix, B9-B19, a beta-turn, B20-B23, and an extended strand from B24 to B30.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2006

Paper or plastic? Data equivalence in paper and electronic diaries.

Concern has been raised about the lack of participant compliance in diary studies that use paper-and-pencil as opposed to electronic formats. Three studies explored the magnitude of compliance problems and their effects on data quality. Study 1 used random signals to elicit diary reports and found close matches to self-reported completion times, matches that could not plausibly have been fabricated. Studies 2 and 3 examined the psychometric and statistical equivalence of data obtained with paper versus electronic formats. With minor exceptions, both methods yielded data that were equivalent psychometrically and in patterns of findings. These results serve to at least partially mollify concern about the validity of paper diary methods.

Adolescent↗
PubMed2004

Tackling the challenges of interdisciplinary bioscience.

The ultimate goal for biology is to become a science that formulates our understanding of subcellular, cellular and multicellular systems in terms of quantitative, holistic models that are underpinned by the rigorous principles of the physical sciences and mathematics. This can only be achieved through interdisciplinary research that draws heavily on the expertise and technologies of the physical sciences, engineering, computation and mathematics. Here, I discuss the benefits and challenges (both intellectual and practical) of interdisciplinary bioscience.

Biological Science Disciplines↗
PubMed2001

[Clinical investigations: innovative management of data. Electronic Data Capture: IOStudy Office].

In the future clinical trials will increasingly be conducted using "electronic data capture EDC" in place of documentation on paper. The utilization of computer systems and special software programs will make quality optimization possible while speeding up the documentation and data processing. In the publication the software system IOStudy Office and its modules are presented. The facilitation of the data capturing process (physician), data monitoring (monitor), and project managment are discussed in detail.

Clinical Trials as Topic↗
PubMed2003

[Assessment of the optical image quality of the eye using raytracing technique of corneal topography data].

BACKGROUND: Optical aberrations in the optical system may downgrade image quality and cannot be fully compensated by spherocylindrical glasses. The subjectively evaluated visual acuity may be significantly reduced. The purpose of this study was to calculate the image forming properties of the eye using a spotlight source or alternatively extended objects. METHODS: A convex and first derivative continuous (C1) surface from the rough height data of the anterior corneal surface (TMS-1, Tomey, Erlangen) or the anterior and posterior corneal surface (Orbscan, Orbtec, USA) was calculated by means of an interpolating subdivision scheme (modified Butterfly algorithm). The characteristics of the residual refractive surfaces were used according to Navarro's eye model. The focal distance was calculated from the exact raytracing calculation (Snellius' law) of the point-spread function by minimising the variance of the point-spread function. The diffraction property of the aperture stop was implemented with a transmission characteristic according to a radially symmetrical Bessel function within the entrance pupil. The algorithm was realised with a C code on the LINUX platform and applied to a normal eye (example 1, TMS-1), an eye with severe keratoconus (example 2, TMS-1) and an eye with corneal scars (example 3, Orbscan). RESULTS: The focal distance in example 1 (22.5 mm, 22.6 mm, and 22.8 mm) increased with the pupil diameter (2 mm, 3 mm, and 5 mm). The variance of the approximately radially symmetrical point-spread function in the focal plane attained a minimum value with a pupil size of 3 mm (0.164, 0.104, and 0.230). In example 2, the focal distance changed inconclusively (21.1 mm, 21.0 mm, and 21.3 mm) with the pupil size (2 mm, 3 mm, and 5 mm). The variance of the markedly asymmetrical point-spread function in the focal plane was systematically higher compared to the values of example 1 and reached a minimum value with a pupil size of 3 mm (0.255, 0.224, and 0.371). The imaging of the sinus-modulated pattern is anisotropic due to the asymmetry of the point-spread function. In example 3, the focal distance (22.3 mm, 22.3 mm, and 22.5 mm) did not change systematically with the pupil size (2 mm, 3 mm, and 5 mm). The variance of the nearly radially symmetrical point-spread function changed only marginally between pupil sizes of 2 mm and 3 mm (0.231, 0.239, and 0.338). CONCLUSIONS: Raytracing of corneal topography height data based on refined eye models with the option of auto-focussing has the potential to trace the optical resolution of the eye for arbitrary objects. Further studies on contrast sensitivity and the conversion of the real image to a perceived image by the retina and brain are required for complete modeling of subjective visual acuity.

Adult↗
PubMed2004

[Correlation between glaucomatous hemifield scotomas in white-on-white perimetry and blue-on-yellow perimetry using the oculus twinfield perimeter].

INTRODUCTION: The "Twinfield Perimeter" can be used for white-on-white and blue-on-yellow perimetry. Since the normative database which is used fort the calculation of the visual field indices for both strategies is based on data from white-on-white perimetric evaluations of normal persons using the "Tübinger Automatikperimeter", the validity of this approach may be questioned. In the study presented here we compared the correlation of white-on-white (W/W) and blue-on-yellow (B/Y) visual fields in glaucoma patients with a hemifield scotoma. PATIENTS AND METHODS: One eye each from 40 normal persons and from 40 glaucoma patients was included in the study. Both W/W-perimetry and B/Y-perimetry was performed using the "Twinfield Perimeter" (Oculus, Modell 56 900, Wetzlar, Germany). From the sensitivity values determined with the 30/2 strategy, we calculated the mean sensitivity (MS), mean deviation (MD) of the total field and of both hemifields (HMS bzw. HMD) separately. Normal values derived from the normal persons of the present study were compared with the normal values used by the Twinfield Perimeter. To determine the strength of the association of B/Y- and W/W-hemifield scotoma, we calculated the linear correlation coefficient (Pearson's R) between the HMD of B/Y und W/W-hemifields. RESULTS: MS of both glaucoma patients and normal persons were determined to be significantly higher for B/Y visual fields (14.17 +/- 4.15 and 20.97 +/- 3.56) when compared with W/W-visual fields (10.70 +/- 3.19 or 15.98 +/- 3.3). When normal values from the Twinfield Perimeter were applied, the MD for normal persons was calculated to be - 4.69 +/- 3.22 compared with 0 +/- 3.6 when the MD was calculated with the normal values from the study. For both normal values we confirm a strong correlation between HMD-values of W/W- and B/Y-visual fields. CONCLUSIONS: Since the mean sensitivity of B/Y visual fields is higher than the mean sensitivity of W/W visual fields, calculations of the MD of B/Y visual fields of glaucoma patients should be based on normative databases which are derived from B/Y visual fields of normal persons.

Aged↗
PubMed2004

[Development of a database system for multicentric ENT tumor documentation].

BACKGROUND: Multicentric clinical studies have a great impact on progress in diagnostics and therapy in oncology. However, multicentric retrospective clinical trials require a common documentation standard. METHODS: A network enabled tumor documentation program based on a relational database system was developed for the management of multicentric clinical studies. This system is designed for the documentation of treatment and follow-up. CONCLUSION: The use of a computer-supported documentation system minimizes documentation effort and error frequency. However, communication with cancer registries is still an unsolved problem.

Clinical Trials as Topic↗
PubMed1994

Maximum likelihood estimation of quantitative trait loci parameters with the aid of genetic markers using a standard statistical package.

Consistent parameter estimates of quantitative trait loci linked to genetic markers can be derived by maximum likelihood methodology. For many experimental designs of interest, parameter estimates and their standard errors can be obtained by program LE of BMDP, which uses the Newton-Raphson method of iteration. Program LE was tested on data simulated for a backcross between two inbred lines. A single quantitative trait locus linked to either one or two genetic markers was simulated. Convergence was rapid, and computing and programming time were insignificant. All parameter estimates were within the expected bounds. Many different designs can be readily analyzed.

Algorithms↗
PubMedDate not supplied

Assessment of shape variation of the levator ani with optimal scan planning and statistical shape modeling.

OBJECTIVE: To capture 3D shape variation of the levator ani during straining with open access MR imaging. METHODS: Optimal scan-planning based on statistical shape modeling is developed for recovering the entire 3D structure of the levator ani from a limited number of 2D imaging planes. Statistical shape modeling ensures optimum material correspondence, and Subspace Reprojection is used to identify the optimum orientation of the imaging plans. The accuracy of the method in using limited 2D imaging planes to instantiate the dynamic structure of the levator ani is assessed with data acquired from 10 asymptomatic subjects. RESULTS: Leave-one-out analysis was performed whereby a model based on a training set consisting of all but one surface was used to instantiate the dynamic surface structure from the corresponding optimal planes. The mean surface distance error for the proposed Subspace Reprojection method is 3.989 +/- 0.790 mm, which is significantly smaller than other approaches. CONCLUSIONS: Surfaces of the levator ani may be instantiated using a limited number of imaging planes as well as a statistical shape model based on a training set of subjects. The proposed technique offers a new way forward for studying dynamic shape changes of 3D structures where complete volumetric imaging is prohibited by the inherent temporal resolution of the scanning technique.

Adult↗
PubMed1994

On time delay estimation of epileptic EEG.

The present study deals with comparative evaluation of various methods for time delay estimations applied to multichannel seizure EEG. The different methods included block algorithms, both in time and frequency domains (such as General Crosscorrelation, FFT, AR), and a new method for time delay estimation based on adaptive least-squares filtering. The various time delay estimators were tested on simulated signals and on real multichannel EEG recorded from rats having generalized seizures with focal onset. The adaptive least-squares filtering (the lattice-ladder type) has been found as the most efficient for time delay estimation.

Algorithms↗
PubMed1988

Epicardial coronary blood flow including the presence of stenoses and aorto-coronary bypasses--II: Experimental comparison and parametric investigations.

This article is the second in a series which presents a computer model of the left coronary arteries. The first article discussed the geometry, the governing equations, and the numerical method employed. This paper details an acute canine experiment used to validate the approach as well as the systematic investigation of several important parameters governing the left coronary circulation. These parameters include peripheral resistance, wall properties, and altered geometric properties through various stenosis/bypass configurations. With appropriate selection of parameters, the model reproduces an in vivo waveform very closely. The model also predicts many clinical phenomena, such as the "critical" value of stenosis, the dramatic reduction in flow through a stenosis when bypassed, and the restorative effect of the bypass upon flow to the distal bed. The model also is used to show that the autonomic state of the animal profoundly affects the influence of various factors, e.g., the critical value of a stenosis is much higher under resting conditions than under hyperemic conditions.

Algorithms↗
PubMed2003

Shortening MR image acquisition time for volumetric interpolated breath-hold examination with a recently developed parallel imaging reconstruction technique: clinical feasibility.

A recently developed parallel magnetic resonance (MR) imaging technique, parallel imaging with an augmented radius in k space, was used to accelerate the volumetric interpolated breath-hold examination (VIBE) performed in 20 patients referred for clinical liver imaging. Nonaccelerated MR images were also acquired in these patients. A five-point scale was used to score the quality of the images. The acceleration resulted in reduced image quality: The nonaccelerated images had a significantly higher (P <.05) mean score--3.8 +/- 0.3 (SD), indicating good quality--than the accelerated images--3.0 +/- 0.3, indicating acceptable quality. However, for three patients who could not hold their breath for the duration necessary for nonaccelerated imaging, less severe breathing artifacts on the accelerated images resulted in improved quality compared with the quality of the nonaccelerated images. Parallel MR imaging-accelerated VIBE may be beneficial for patients who have difficulty sustaining a breath hold for the duration necessary to perform nonaccelerated imaging.

Adult↗