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Biomedical subjects

C Windischberger

Publications and source records attributed to C Windischberger.

17 recordsLinked to original sources

Optimized 3 T EPI of the amygdalae.

The optimum parameters for single-shot gradient-recalled (GR) EPI-based fMRI studies of the limbic region are systematically established at 3 T via their ability to mitigate intravoxel dephasing-measured via SNR and T2* in the amygdalae-and their implications for temporal resolution (or brain coverage). Conventional imaging parameters (64 x 64 matrix size and 4-6 mm thick slices) are confirmed to be inadequate for functional studies at 3 T. Measurements of main magnetic field variations across the amygdalae suggest that such variations are equal in the craniocaudal and anterior-posterior directions, and slightly lower in the mediolateral direction, with this and other considerations leading us to conclude an oblique axial orientation to be most suitable. In-plane resolution of approximately 1.7 mm was sufficient to recover signal in the area of the amygdalae. SNR was found to peak at a slice thickness of between 2.0 and 2.5 mm, dependent on the subject. T2* time in the amygdalae was measured with a standard EPI protocol to be 22 +/- 3 ms. Using the optimized (high resolution) EPI protocol proposed here, the measured T2* time increased to 48 +/- 2 ms (compared with 43 +/- 3 ms for a reference FLASH scan), only slightly lower than the cortex (49 +/- 2 ms measured with optimized EPI and 52 +/- 2 ms with FLASH). The FLASH measurement of 43 ms is taken to be a suitable effective echo time (TE(eff)) to achieve maximum BOLD sensitivity in the amygdalae. Time series data acquired with these parameters showed a 60% increase in SNR in the amygdala over that obtained with a standard low-resolution protocol and suggest sufficient SNR and BOLD sensitivity to make functional studies feasible. Arteries, but no substantial draining veins, were found in high-resolution BOLD venograms of the region. Our results indicate that EPI protocols need to be carefully optimized for structures of interest if reliable results from single subjects are to be established in this brain region.

Adult↗

The preparation and execution of self-initiated and externally-triggered movement: a study of event-related fMRI.

Studies of functional brain imaging in humans and single cell recordings in monkeys have generally shown preferential involvement of the medially located supplementary motor area (SMA) in self-initiated movement and the lateral premotor cortex in externally cued movement. Studies of event-related cortical potentials recorded during movement preparation, however, generally show increased cortical activity prior to self-initiated movements but little activity at early stages prior to movements that are externally cued at unpredictable times. In this study, the spatial location and relative timing of activation for self-initiated and externally triggered movements were examined using rapid event-related functional MRI. Twelve healthy right-handed subjects were imaged while performing a brief finger sequence movement (three rapid alternating button presses: index-middle-index finger) made either in response to an unpredictably timed auditory cue (between 8 to 24 s after the previous movement) or at self-paced irregular intervals. Both movement conditions involved similar strong activation of medial motor areas including the pre-SMA, SMA proper, and rostral cingulate cortex, as well as activation within contralateral primary motor, superior parietal, and insula cortex. Activation within the basal ganglia was found for self-initiated movements only, while externally triggered movements involved additional bilateral activation of primary auditory cortex. Although the level of SMA and cingulate cortex activation did not differ significantly between movement conditions, the timing of the hemodynamic response within the pre-SMA was significantly earlier for self-initiated compared with externally triggered movements. This clearly reflects involvement of the pre-SMA in early processes associated with the preparation for voluntary movement.

Adult↗

Dissociation of supplementary motor area and primary motor cortex in human subjects when comparing index and little finger movements with functional magnetic resonance imaging.

This study provides the first investigation of supplementary motor area (SMA) and primary motor cortex (MI) activation with similar movements differing only in subjective difficulty of motor control. Brain activation with simple tapping of the right index finger (well trained during daily life and easy to perform) was compared with tapping of the little finger (less trained and difficult to perform) using functional magnetic resonance imaging at 3 Tesla. Due to optimised movement standardisation, extrinsic influences on activation levels such as movement complexity, amplitude and frequency were minimised. Fifth finger tapping significantly increased the number of activated SMA voxels by 450% whereas MI activation showed no significant difference between fingers. We conclude that with similar movements the degree of subjective difficulty specifically modifies SMA but not MI activation.

Adult↗

Finger somatotopy in human motor cortex.

Although qualitative reports about somatotopic representation of fingers in the human motor cortex exist, up to now no study could provide clear statistical evidence. The goal of the present study was to reinvestigate finger motor somatotopy by means of a thorough investigation of standardized movements of the index and little finger of the right hand. Using high resolution fMRI at 3 Tesla, blood oxygenation level-dependent (BOLD) responses in a group of 26 subjects were repeatedly measured to achieve reliable statistical results. The center of mass of all activated voxels within the primary motor cortex was calculated for each finger and each run. Results of all runs were averaged to yield an individual index and little finger representation for each subject. The mean center of mass localizations for all subjects were then submitted to a paired t test. Results show a highly significant though small scale somatotopy of fingerspecific activation patterns in the order indicated by Penfields motor homunculus. In addition, considerable overlap of finger specific BOLD responses was found. Comparing various methods of analysis, the mean center of mass distance for the two fingers was 2--3 mm with overlapping voxels included and 4--5 mm with overlapping voxels excluded. Our data may be best understood in the context of the work of Schieber (1999) who recently described overlapping somatotopic gradients in lesion studies with humans.

Adult↗

Evidence for premotor cortex activity during dynamic visuospatial imagery from single-trial functional magnetic resonance imaging and event-related slow cortical potentials.

A strong correspondence has been repeatedly observed between actually performed and mentally imagined object rotation. This suggests an overlap in the brain regions involved in these processes. Functional neuroimaging studies have consistently revealed parietal and occipital cortex activity during dynamic visuospatial imagery. However, results concerning the involvement of higher-order cortical motor areas have been less consistent. We investigated if and when premotor structures are active during processing of a three-dimensional cube comparison task that requires dynamic visuospatial imagery. In order to achieve a good temporal and spatial resolution, single-trial functional magnetic resonance imaging (fMRI) and scalp-recorded event-related slow cortical potentials (SCPs) were recorded from the same subjects in two separate measurement sessions. In order to reduce inter-subject variability in brain activity due to individual differences, only male subjects (n = 13) with high task-specific ability were investigated. Functional MRI revealed consistent bilateral activity in the occipital (Brodmann area BA18/19) and parietal cortex (BA7), in lateral and medial premotor areas (BA6), the dorsolateral prefrontal cortex (BA9), and the anterior insular cortex. The time-course of SCPs indicated that task-related activity in these areas commenced approximately 550-650 ms after stimulus presentation and persisted until task completion. These results provide strong and consistent evidence that the human premotor cortex is involved in dynamic visuospatial imagery.

Adult↗

Co-registration of EEG and MRI data using matching of spline interpolated and MRI-segmented reconstructions of the scalp surface.

Accurate co-registration of MRI and EEG data is indispensable for the correct interpretation of EEG maps or source localizations in relation to brain anatomy derived from MRI. In this study, a method for the co-registration of EEG and MRI data is presented. The method consists of an iterative matching of EEG-electrode based reconstructions of the scalp surface to scalp-segmented MRIs. EEG-electrode based surface reconstruction is achieved via spline interpolation of individually digitized 3D-electrode coordinates. In contrast to other approaches, neither fiducial determination nor any additional provisions (such as bite bars, other co-registration devices or head shape digitization) are required, and co-registration errors associated with inaccurate fiducial determination are avoided. The accuracy of the method was estimated by calculating the root-mean-square (RMS) deviation of spline interpolated and MRI-segmented surface reconstructions in 20 subjects. In addition, the distance between co-registered and genuine electrode coordinates was assessed via a simulation study, in which surface reconstruction was based on virtual electrodes determined on the scalp surface of a high-resolution MRI data set. The mean RMS deviation of surface reconstructions was 2.43 mm, and the maximal distance between any two matched surface points was 5.06 mm. The simulated co-registration revealed a mean deviation of genuine and co-registered electrode coordinates of 0.61 mm. It is concluded that surface matching using spline interpolated reconstructions of scalp surfaces is a precise and highly practicable method to co-register EEG and MRI data.

Adult↗

Spatial distribution of prostate cancers undetected on initial needle biopsies.

OBJECTIVES: The spatial distribution of cancer foci of prostate carcinomas with negative initial biopsies was compared to that of prostate carcinomas with positive initial biopsies to detect areas in which carcinomas were more frequently located when the initial biopsy was negative. METHODS: Twenty patients with prostate cancer and a negative initial biopsy trial were detected among 218 patients with preceding systematic biopsies (9.2%) in our hospital. Analysis of the prostatectomy specimens regarding cancer distribution, multifocality, tumour size, Gleason score, and stage was performed using pathohistological techniques and three-dimensional computer reconstruction. RESULTS: Prostatectomy specimens with negative initial biopsies showed more frequently cancer foci in apical (p<0.0001) and dorsal (p<0.02) prostatic compartments, higher incidence of multifocality (p<0.01), and smaller size of carcinoma foci (p<0.00003) compared to carcinomas in 81 stage-matched prostatectomy specimens with positive initial biopsies. Comparing both groups, no significant differences were noted in Gleason score of preoperative biopsies and prostatectomies, prostate weight, prostate-specific antigen (PSA) level, digital rectal examination, and patients age. CONCLUSIONS: Missing the cancer in clinically significant prostate carcinomas by current systematic biopsy techniques may also be due to an apico-dorsal cancer location, particularly in combination with multifocality and small size of carcinoma foci in large prostates. In case of reasonable clinical suspicion of prostate cancer and negative initial biopsy, an early repeat biopsy with special emphasis on the apico-dorsal peripheral zone should be envisaged.

Biopsy, Needle↗

Improvement of presurgical patient evaluation by generation of functional magnetic resonance risk maps.

Recent functional magnetic resonance imaging (FMRI) replication studies show a high variability of active voxels within subjects and across runs - a potentially harmful situation for clinical applications. We tried to reduce these uncertainties inherent in current presurgical FMRI. For this, a new high quality head fixation device was used to detect reliably activated voxels over repeated measurements. In addition high correlation thresholds were applied to define the areas with highest probability of activation. The results show a focussing of such functional high risk areas to only a few voxels which localized close to intraoperative cortical stimulation. The generation of such FMRI risk maps may improve validity of clinical localization and facilitate the development of currently missing standards for maximized but still safe tumor resection.

Adult↗

Quantification of fMRI artifact reduction by a novel plaster cast head holder.

In light of artifact-induced high variability of activation in fMRI repeat studies, we developed and tested a clinically useful plaster cast head holder (PCH) with improved immobilization, repositioning, and comfort. With PCH, there were considerably lower levels of translational and rotational head motion components compared to head fixation with conventional restraining straps (CRS). Rotational components cannot be fully compensated by realignment and lead to "false activations." In addition, task-correlated head motion, which highly increases the risk of artifacts, was considerably reduced with PCH, especially in a motion prone subject. Compared with PCH, head motion was 133% larger with CRS in a highly cooperative subject. With a motion prone subject, head motion range was increased by 769% (PCH: 0.9 mm, CRS: 7.8 mm), which may indicate the usefulness of PCH for restless patients. In functional activation maps, PCH alone yielded fewer residual motion artifacts than CRS + image registration. Subject tolerance of the head holder during the long measurement times of up to 2.5 hr was good, and slice orientation on different days confirmed the quality of repositioning.

Adult↗

Supplementary motor area activation preceding voluntary movement is detectable with a whole-scalp magnetoencephalography system.

Despite the fact that the knowledge about the structure and the function of the supplementary motor area (SMA) is steadily increasing, the role of the SMA in the human brain, e.g., the contribution of the SMA to the Bereitschaftspotential, still remains unclear and controversial. The goal of this study was to contribute further to this discussion by taking advantage of the increased spatial information of a whole-scalp magnetoencephalography (MEG) system enabling us to record the magnetic equivalent of the Bereitschaftspotential 1, the Bereitschaftsfeld 1 (BF 1) or readiness field 1. Five subjects performed a complex, and one subject a simple, finger-tapping task. It was possible to record the BF 1 for all subjects. The first appearance of the BF 1 was in the range of -1.9 to -1.7 s prior to movement onset, except for the subject performing the simple task (-1 s). Analysis of the development of the magnetic field distribution and the channel waveforms showed the beginning of the Bereitschaftsfeld 2 (BF 2) or readiness field 2 at about -0.5 s prior to movement onset. In the time range of BF 1, dipole source analysis localized the source in the SMA only, whereas dipole source analysis containing also the time range of BF 2 resulted in dipole models, including dipoles in the primary motor area. In summary, with a whole-head MEG system, it was possible for the first time to detect SMA activity in healthy subjects with MEG.

Adult↗

Spatial resolution in echo planar imaging: shifting the acquisition window in k-space.

Single-shot echo planar imaging (EPI) is one of the most suitable techniques for very fast image acquisition, especially in functional MRI. In standard EPI schemes the k-space center is sampled in the middle of the acquisition train. This leads to longer echo times for higher spatial resolutions, as well as reduced signal intensity and signal-to-noise ratio. Therefore, echo shifting to lower echo times is often used. After a brief overview on the theoretical background of various point-spread-functions (PSF) computational simulations are presented, which quantify the modulation amplitude of a binary test object sampled with either standard, zero-filled or shifted k-space acquisition. The results suggest that echo-shifting with zero-filling is not advantageous, not even with small matrix sizes, and that echo-shifting with additional acquisition of outer k-space lines decreases the modulation amplitude only slightly. Simulations were also performed on noise-corrupted test objects, indicating that the use of the echo-shifted scheme causes resolution loss of up to 30% compared to the standard scheme for a 128 by 128 pixel matrix at a noise level of 20%. Finally, in vivo experiments using different echo shifts are presented and the characteristics of signal and noise with varying TE are quantified.

Echo-Planar Imaging↗

Wavelet domain de-noising of time-courses in MR image sequences.

Magnetic resonance images acquired with high temporal resolution often exhibit large noise artifacts, which arise from physiological sources as well as from the acquisition hardware. These artifacts can be detrimental to the quality and interpretation of the time-course data in functional MRI studies. A class of wavelet-domain de-noising algorithms estimates the underlying, noise-free signal by thresholding (or 'shrinking') the wavelet coefficients, assuming the underlying temporal noise of each pixel is uncorrelated and Gaussian. A Wiener-type shrinkage algorithm is developed in this paper, for de-noising either complex- or magnitude-valued image data sequences. Using the de-correlation properties of the wavelet transform, as elucidated by Johnstone and Silverman, the assumption of i.i.d. Gaussian noise can be abandoned, opening up the possibility of removing colored noise. Both wavelet- and wavelet-packet based algorithms are developed, and the Wiener method is compared to the traditional Hard and Soft wavelet thresholding methods of Donoho and Johnstone. The methods are applied to two types of data sets. In the first, an artificial set of complex-valued images was constructed, in which each pixel has a simulated bimodal time-course. Gaussian noise was added to each of the real and imaginary channels, and the noise removed from the complex image sequence as well as the magnitude image sequence (where the noise is Rician). The bias and variance between the original and restored paradigms was estimated for each method. It was found that the Wiener method gives better balance in bias and variance than either Hard or Soft methods. Furthermore, de-noising magnitude data provides comparable accuracy of the restored images to that obtained from de-noising complex data. In the second data set, an actual in vivo complex image sequence containing unknown physiological and instrumental noise was used. The same bimodal paradigm as in the first data set was added to pixels in a small localized region of interest. For the paradigm investigated here, the smooth Daubechies wavelets provide better de-noising characteristics than the discontinuous Haar wavelets. Also, it was found that wavelet packet de-noising offers no significant improvement over the computationally more efficient wavelet de-noising methods. For the in vivo data, it is desirable that the groups of "activated" time-courses are homogeneous. It was found that the internal homogeneity of the group of time-courses increases when de-noising is applied. This suggests using de-noising as a pre-processing tool for both exploratory and inferential data analysis methods in fMRI.

Journal Article↗

A wavelet-based method for improving signal-to-noise ratio and contrast in MR images.

Magnetic resonance (MR) images acquired with fast measurement often display poor signal-to-noise ratio (SNR) and contrast. With the advent of high temporal resolution imaging, there is a growing need to remove these noise artifacts. The noise in magnitude MR images is signal-dependent (Rician), whereas most de-noising algorithms assume additive Gaussian (white) noise. However, the Rician distribution only looks Gaussian at high SNR. Some recent work by Nowak employs a wavelet-based method for de-noising the square magnitude images, and explicitly takes into account the Rician nature of the noise distribution. In this article, we apply a wavelet de-noising algorithm directly to the complex image obtained as the Fourier transform of the raw k-space two-channel (real and imaginary) data. By retaining the complex image, we are able to de-noise not only magnitude images but also phase images. A multiscale (complex) wavelet-domain Wiener-type filter is derived. The algorithm preserves edges better when the Haar wavelet rather than smoother wavelets, such as those of Daubechies, are used. The algorithm was tested on a simulated image to which various levels of noise were added, on several EPI image sequences, each of different SNR, and on a pair of low SNR MR micro-images acquired using gradient echo and spin echo sequences. For the simulated data, the original image could be well recovered even for high values of noise (SNR approximately 0 dB), suggesting that the present algorithm may provide better recovery of the contrast than Nowak's method. The mean-square error, bias, and variance are computed for the simulated images. Over a range of amounts of added noise, the present method is shown to give smaller bias than when using a soft threshold, and smaller variance than a hard threshold; in general, it provides a better bias-variance balance than either hard or soft threshold methods. For the EPI (MR) images, contrast improvements of up to 8% (for SNR = 33 dB) were found. In general, the improvement in contrast was greater the lower the original SNR, for example, up to 50% contrast improvement for SNR of about 20 dB in micro-imaging. Applications of the algorithm to the segmentation of medical images, to micro-imaging and angiography (where the correct preservation of phase is important for flow encoding to be possible), as well as to de-noising time series of functional MR images, are discussed.

Algorithms↗

Fractal analysis: an objective method for identifying atypical nuclei in dysplastic lesions of the cervix uteri.

OBJECTIVES: Fractal geometry is a tool used to characterize irregularly shaped and complex figures. It can be used not only to generate biological structures (e.g., the human renal artery tree), but also to derive parameters such as the fractal dimension in order to quantify the shapes of structures. As such, it allows user-independent evaluation and does not rely on the experience level of the examiner. METHODS: We applied a box-counting algorithm to determine the fractal dimension of atypical nuclei in dysplastic cervical epithelium. An automatic algorithm was used to determine the fractal dimension of nuclei in order to prevent errors from manual segmentation. Four groups of patients (CIN 1-3 and control) with 10 subjects each were examined. In total, the fractal dimensions of 1200 nuclei were calculated. RESULTS: We found that the fractal dimensions of the nuclei increased as the degree of dysplasia increased. There were significant differences between control and atypical nuclei found by an analysis of variance. Atypical nuclei associated with CIN 1, CIN 2, and CIN 3 also differed significantly among these groups. CONCLUSION: We conclude that the fractal dimension is a valuable tool for detecting irregularities in atypical nuclei of the cervix uteri and thus allows objective nuclear grading.

Cell Nucleus↗

Quantification in functional magnetic resonance imaging: fuzzy clustering vs. correlation analysis.

The potential of functional MRI (fMRI) data analysis using the paradigm independent fuzzy cluster analysis (FCA) applied in the time domain compared to frequently used paradigm based correlation analysis (CA) was studied with simulated and in vivo fMRI data. The performance of FCA and CA was investigated in a typical contrast-to-noise range for fMRI, ranging from 1.33 to 3.33. Using simulated fMRI data the methods were quantitatively compared in terms of generation of true positives, false positives, and the corresponding signal enhancement. Even without prior knowledge about the stimulation paradigm and the actual hemodynamic response function the performance of FCA was comparable to that of CA where extensive prior knowledge has to be added. Furthermore, discrimination of nonanticipated hemodynamic responses by FCA, such as different levels of activation and delayed response, are demonstrated in simulated and in vivo fMRI data. We demonstrate that using CA one cannot differentiate between these responses at least without extensive prior knowledge, i.e., FCA yields a more particular description of fMRI data. This may be worthwhile for analysis and optimization of data quality in fMRI as well as in the final data analysis.

Adult↗

[Fractal analysis of a breast carcinoma--presentation of a modern morphometric method].

Fractal analysis techniques are common tools in physics and image processing. In the past few years they have gained increasing attention in medical sciences, e.g., cardiology, pathology and radiology, respectively. This article intends to describe this new technique by applying fractal analysis to the instant of a breast carcinoma. One of the advantages of fractal analysis is the ability to describe an irregular and complex object by a measureable value, called the fractal dimension. The fractal dimension can be determined by using the box-counting method. We applied this technique to the mammography as well as to the histologic section of a breast carcinoma. The application of fractal analysis provides a specific measureable value of the growth pattern of a tumor. Thus, the fractal dimension serves in addition to the common used metric diameter.

Aged↗

Characterization of BOLD activation in multi-echo fMRI data using fuzzy cluster analysis and a comparison with quantitative modeling.

A combination of multiple gradient-echo imaging and exploratory data analysis (EDA), i.e. fuzzy cluster analysis (FCA), is proposed for separation and characterization of BOLD activation in single-shot spiral functional magnetic resonance imaging (fMRI) experiments at 3 T. Differentiation of functional activation using FCA is performed by clustering pixel signal changes (DeltaS) as a function of echo time (TE). Further vascular classification is supported by the localization of activation and the comparison with a single-exponential decay model. In some subjects, an additional indication for large vessels within a voxel was found as oscillation of the fMRI signal difference vs echo time (TE). Such large vessels may be separated from small vessel activation and, therefore, our proposed procedure might prove useful if a more specific functional localization is desired in fMRI. In addition to the signal change DeltaS, DeltaT(2)*/T(2)* is significantly different between activated regions. Averaged over all eight subjects DeltaT(2)* is 1.7 +/- 0.2 ms in ROIs with the highest signal change characterized as containing large vessels, whereas in ROIs corresponding to microvascular environment average DeltaT(2)* values are 0.8 +/- 0.1 ms.

Brain↗