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Biomedical subjects

Ewald Moser

Publications and source records attributed to Ewald Moser.

At least 19 recordsLinked to original sources

Proton magnetic resonance spectroscopic imaging in brain tumor diagnosis.

The current state of standard tumor diagnostics using contrast-enhanced MRI and biopsy is assessed in this review, and the progress of proton magnetic resonance spectroscopy (MRS) over the last 15 years is discussed. We summarize MRS basics and describe a typical magnetic resonance session for noninvasive routine tumor diagnostics at 1.5 T, including two-dimensional magnetic resonance spectroscopic imaging (MRSI). The results that can be obtained from such procedures are illustrated with clinical examples. Attention is turned to cutting-edge methodologic and clinical research at 3 T, with examples using high-resolution or very short echo-time three-dimensional MRSI. The current status and limitations in proton MRSI are discussed, and we look to the potential of faster data collection and even higher field strength.

Adult↗

Proton magnetic resonance spectroscopic imaging integrated into image-guided surgery: correlation to standard magnetic resonance imaging and tumor cell density.

OBJECTIVE: In this study, we attempted to improve the delineation of the infiltration zone in gliomas using proton magnetic resonance spectroscopic imaging (1H MRSI). In conventional magnetic resonance imaging (MRI), the boundaries of gliomas sometimes are underestimated. 1H MRSI is a noninvasive tool that can be used to investigate the spatial distribution of metabolic changes in brain lesions. The purpose was to correlate tumor cell density from histopathological specimens with metabolic levels and the coregistered metabolic maps. METHODS: We developed a method to integrate spectroscopic data depicted as metabolic maps of biochemically pathological tissue into frameless stereotaxy. In seven patients harboring gliomas, we performed 1H MRSI with high spatial resolution and evaluated the spectral data. An algorithm was developed for user-independent calculation of pathological voxels and for visualization as metabolic maps. These maps were integrated into a three-dimensional MRI data set used for frameless stereotaxy. Stereotactic biopsies were taken from three different areas in and around the tumor involving the maximum pathological change, the border zone, and an area from outside the spectroscopically suspicious area. These specimens were correlated to the exact voxel positions in the stereotactic image space and evaluated histopathologically. RESULTS: In all cases, the implementation of the metabolic maps into frameless stereotaxy was successful, and stereotactic biopsies were acquired by use of the spectral data. A relation could be demonstrated between the metabolic changes and tumor cell density ranging from 60 to 100% in the maximum pathological area to 5 to 15% in the border zone. Interestingly, the tumor areas defined by the metabolic maps and histopathologically confirmed by biopsy exceeded the T2-weighted signal change in all cases, ranging from 6 to 32% in the examined volume. CONCLUSION: Our preliminary data suggest that 1H MRSI may be useful in combination with frameless stereotaxy to define more exactly the tumor infiltration zone in glioma surgery compared with conventional anatomic MRI alone.

Algorithms↗

Robust field map generation using a triple-echo acquisition.

PURPOSE: To establish a fast and robust technique for generating magnetic field maps for the correction of geometric distortions in echo-planar magnetic resonance (MR) images. MATERIALS AND METHODS: Multislice gradient-echo (GE) images were acquired at echo times of 6, 6.5, and 7.5 msec in order to cover a field shift range of +/-666 Hz in the resulting B0 maps. To account for possible phase wrap scenarios, seven phase triples were calculated for each pixel. Linear regression of the phase vs. echo time was performed for each set. The slope of the set with the minimum fitting error was taken as the true magnetic field in the respective pixel. RESULTS: Based on the fitting error distribution, the technique is shown to be feasible and effective for assessing the field distribution in the brain at 3 T, especially in inferior brain areas (amygdalae, hippocampus). Examples of echo-planar images distortion corrected using the calculated field maps are shown. CONCLUSION: The approach presented yields robust estimation of magnetic field maps and requires under a minute of additional acquisition time and only seconds of computational time. As such, it is easily possible to apply image distortion correction in routine functional MR imaging (fMRI) studies, enabling improved coregistration of brain activation maps with structures on anatomical images.

Algorithms↗

A quantitative comparison of functional MRI cluster analysis.

The aim of this work is to compare the efficiency and power of several cluster analysis techniques on fully artificial (mathematical) and synthesized (hybrid) functional magnetic resonance imaging (fMRI) data sets. The clustering algorithms used are hierarchical, crisp (neural gas, self-organizing maps, hard competitive learning, k-means, maximin-distance, CLARA) and fuzzy (c-means, fuzzy competitive learning). To compare these methods we use two performance measures, namely the correlation coefficient and the weighted Jaccard coefficient (wJC). Both performance coefficients (PCs) clearly show that the neural gas and the k-means algorithm perform significantly better than all the other methods using our setup. For the hierarchical methods the ward linkage algorithm performs best under our simulation design. In conclusion, the neural gas method seems to be the best choice for fMRI cluster analysis, given its correct classification of activated pixels (true positives (TPs)) whilst minimizing the misclassification of inactivated pixels (false positives (FPs)), and in the stability of the results achieved.

Algorithms↗

Wavelet-based multifractal analysis of fMRI time series.

Functional magnetic resonance imaging (fMRI) time series are investigated with a multifractal method based on the Wavelet Modulus Maxima (WTMM) method to extract local singularity ("fractal") exponents. The spectrum of singularity exponents of each fMRI time series is quantified by spectral characteristics including its maximum and the corresponding dimension. We found that the range of Hölder exponents in voxels with activation is close to 1, whereas exponents are close to 0.5 in white matter voxels without activation. The maximum dimension decreases going from white matter to gray matter, and is lower still for activated time series. The full-width-at-half-maximum of the spectra is higher in activated areas. The proposed method becomes particularly effective when combining these spectral characteristics into a single parameter. Using these multifractal parameters, it is possible to identify activated areas in the human brain in both hybrid and in vivo fMRI data sets without knowledge of the stimulation paradigm applied.

Brain↗

Improved delineation of brain tumors: an automated method for segmentation based on pathologic changes of 1H-MRSI metabolites in gliomas.

In this study, we developed a method to improve the delineation of intrinsic brain tumors based on the changes in metabolism due to tumor infiltration. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) with a nominal voxel size of 0.45 cm(3) was used to investigate the spatial distribution of choline-containing compounds (Cho), creatine (Cr) and N-acetyl-aspartate (NAA) in brain tumors and normal brain. Ten patients with untreated gliomas were examined on a 1.5 T clinical scanner using a MRSI sequence with PRESS volume preselection. Metabolic maps of Cho, Cr, NAA and Cho/NAA ratios were calculated. Tumors were automatically segmented in the Cho/NAA images based on the assumption of Gaussian distribution of Cho/NAA values in normal brain using a limit for normal brain tissue of the mean + three times the standard deviation. Based on this threshold, an area was calculated which was delineated as pathologic tissue. This area was then compared to areas of hyperintense signal caused by the tumor in T2-weighted MRI, which were determined by a region growing algorithm in combination with visual inspection by two experienced clinicians. The area that was abnormal on (1)H-MRSI exceeded the area delineated via T2 signal changes in the tumor (mean difference 24%) in all cases. For verification of higher sensitivity of our spectroscopic imaging strategy we developed a method for coregistration of MRI and MRSI data sets. Integration of the biochemical information into a frameless stereotactic system allowed biopsy sampling from the brain areas that showed normal T2-weighted signal but abnormal (1)H-MRSI changes. The histological findings showed tumor infiltration ranging from about 4-17% in areas differentiated from normal tissue by (1)H-MRSI only. We conclude that high spatial resolution (1)H-MRSI (nominal voxel size = 0.45 cm(3)) in combination with our segmentation algorithm can improve delineation of tumor borders compared to routine MRI tumor diagnosis.

Adult↗

Integration of biochemical images of a tumor into frameless stereotaxy achieved using a magnetic resonance imaging/magnetic resonance spectroscopy hybrid data set.

OBJECT: It is often difficult to delineate the extent of invasion of high- and low-grade gliomas into normal brain tissue by using conventional T1- and T2-weighted magnetic resonance (MR) imaging. Knowledge of the relationship between the tumor infiltration zone and normal brain, however, is one of the prerequisites for performing as radical a tumor resection as possible. Proton MR spectroscopy allows noninvasive measurements of the concentrations and spatial distributions of brain metabolites and, therefore, may provide biochemical information in vivo, that is useful in distinguishing pathological from normal areas of the brain. The authors have developed a method to use the properties of MR spectroscopy to investigate intraoperatively pathological changes in the spatial distribution of choline (Cho)-containing compounds, total creatine, and N-acetylaspartate (NAA) in brain tumors with the aid of frameless stereotaxy. METHODS: Maps of the Cho/NAA ratio were calculated and automatic segmentation of the tumors was performed. Spectroscopic images of the segmented tumor were matched to an anatomical three-dimensional (3D) MR imaging set by applying a fully automated mutual-information algorithm. The resulting 3D MR image can be used subsequently for neurosurgical planning, transfer to a frameless stereotactic system, and display in the navigation microscope during surgery leading to 1H-MR spectroscopy-guided navigation. CONCLUSIONS: This method may allow better intraoperative identification of tumor border zones based on metabolic changes due to tumor infiltration.

Brain Neoplasms↗

Automated unwrapping of MR phase images applied to BOLD MR-venography at 3 Tesla.

PURPOSE: To improve the diagnostic value of BOLD MR-Venography by removing artifacts related to phase wrapping, particularly in regions of large background susceptibilities at high magnetic field strengths. MATERIALS AND METHODS: High resolution, T(2)(*)-weighted, single echo images were acquired on a 3 T system (Medspec 30/80 Avance, Bruker Medical, Ettlingen, Germany) with a three-dimensional, first order velocity compensated gradient echo sequence using a quadrature transmit/receive birdcage head coil. Data of nine healthy subjects and 19 patients were evaluated (age range: 27 to 76 years). To achieve improved MR-venograms, a fully automated region-growing phase unwrapping algorithm and subsequent high pass filtering were applied to phase images prior to the computation of minimum intensity projections. RESULTS: Considerably improved visualization of venous structures in regions of large background susceptibility-induced field inhomogeneities is demonstrated in healthy subjects and patients with brain tumors. CONCLUSION: BOLD MR venograms are improved compared to previous post-processing algorithms. It is now feasible to obtain high-resolution images also in inhomogeneous regions, which increases the clinical potential of BOLD MR-Venography.

Adult↗

High-resolution 3D proton spectroscopic imaging of the human brain at 3 T: SNR issues and application for anatomy-matched voxel sizes.

In a systematic study on the interdependence of linewidth, signal-to-noise ratio (SNR), and spatial resolution in 3D proton spectroscopic imaging ((1)H-SI) at 3 T, we demonstrate reduced linewidths with increased spatial resolution due to reduced magnetic inhomogeneity within the brain. High-precision quantitative data (0.75-0.094 cm(3)) were obtained for all resolutions, enabling the creation of metabolic maps that display details such as the ventricles, sulci, and gyri. High-resolution (1)H-SI allows differences in metabolic ratios to be estimated for anatomically defined regions in gray (GM) and white matter (WM). Seven distinct regions in a healthy brain were anatomically segmented and their metabolic ratios were compared quantitatively. Data from a tumor patient are also presented to demonstrate potential clinical applications. Because of the high resolution, the metabolite ratios could be determined for distinct pathologic regions within the tumor and its surroundings. The method was additionally applied to a patient with patchy Pelizaeus Merzbacher disease (PMD), and compared to single-voxel spectroscopy performed in the same session. High-resolution SI data were demonstrated in our study to allow the direct matching of anatomic and metabolic images. This may enhance the clinical value of (1)H-SI.

Adult↗

Relaxation times of 31P-metabolites in human calf muscle at 3 T.

Localized (31)P-STEAM experiments were performed at 3 T to estimate relaxation times of phosphorus-containing metabolites in the human calf muscle in vivo. T(1) and T(2) times of PCr, P(i), and NTPs were measured in the resting calf muscle of healthy subjects by varying TR and TE. The localization performance of the (31)P-STEAM sequence was evaluated on a test object, resulting in a relative selection efficiency of 78 +/- 1% and contamination from outside the voxel of 0 +/- 2% under fully relaxed conditions. T(1) relaxation times (+/-SD, n = 5) of P(i), PCr, gamma-NTP, alpha-NTP, and beta-NTP obtained at 3 T are 5.2 +/- 1.0 s, 6.4 +/- 0.2 s, 4.5 +/- 0.3 s, 2.6 +/- 0.9 s, and 3.5 +/- 1.1 s, respectively. T(2) relaxation times (+/-SD, n = 6) of these metabolites are 148 +/- 17 ms, 334 +/- 30 ms, 78 +/- 13 ms, 55 +/- 7 ms, and 55 +/- 10 ms, respectively. Spin-lattice relaxation times established at 3 T are consistent with literature data at lower field strengths, whereas spin-spin relaxation times are lower. Several methodological considerations are discussed which may help improve quantification of metabolite concentrations in the human (calf) muscle in vivo by using localized noninvasive (31)P-MRS at 3 T, which is currently being tested for routine clinical applications.

Adult↗

Fuzzy cluster analysis of high-field functional MRI data.

Functional magnetic resonance imaging (fMRI) based on blood-oxygen level dependent (BOLD) contrast today is an established brain research method and quickly gains acceptance for complementary clinical diagnosis. However, neither the basic mechanisms like coupling between neuronal activation and haemodynamic response are known exactly, nor can the various artifacts be predicted or controlled. Thus, modeling functional signal changes is non-trivial and exploratory data analysis (EDA) may be rather useful. In particular, identification and separation of artifacts as well as quantification of expected, i.e. stimulus correlated, and novel information on brain activity is important for both, new insights in neuroscience and future developments in functional MRI of the human brain. After an introduction on fuzzy clustering and very high-field fMRI we present several examples where fuzzy cluster analysis (FCA) of fMRI time series helps to identify and locally separate various artifacts. We also present and discuss applications and limitations of fuzzy cluster analysis in very high-field functional MRI: differentiate temporal patterns in MRI using (a) a test object with static and dynamic parts, (b) artifacts due to gross head motion artifacts. Using a synthetic fMRI data set we quantitatively examine the influences of relevant FCA parameters on clustering results in terms of receiver-operator characteristics (ROC) and compare them with a commonly used model-based correlation analysis (CA) approach. The application of FCA in analyzing in vivo fMRI data is shown for (a) a motor paradigm, (b) data from multi-echo imaging, and (c) a fMRI study using mental rotation of three-dimensional cubes. We found that differentiation of true "neural" from false "vascular" activation is possible based on echo time dependence and specific activation levels, as well as based on their signal time-course. Exploratory data analysis methods in general and fuzzy cluster analysis in particular may help to identify artifacts and add novel and unexpected information valuable for interpretation, classification and characterization of functional MRI data which can be used to design new data acquisition schemes, stimulus presentations, neuro(physio)logical paradigms, as well as to improve quantitative biophysical models.

Artifacts↗

Human motor cortex activity during mental rotation.

The functional role of human premotor and primary motor cortex during mental rotation has been studied using functional MRI at 3 T. Fourteen young, male subjects performed a mental rotation task in which they had to decide whether two visually presented cubes could be identical. Exploratory Fuzzy Cluster Analysis was applied to identify brain regions with stimulus-related time courses. This revealed one dominant cluster which included the parietal cortex, premotor cortex, and dorsolateral prefrontal cortex that showed signal enhancement during the whole stimulus presentation period, reflecting cognitive processing. A second cluster, encompassing the contralateral primary motor cortex, showed activation exclusively after the button press response. This clear separation was possible in 3 subjects only, however. Based on these exploratory results, the hypothesis that primary motor cortex activity was related to button pressing only was tested using a parametric approach via a random-effects group analysis over all 14 subjects in SPM99. The results confirmed that the stimulus response via button pressing causes activation in the primary motor cortex and supplementary motor area while parietal cortex and mesial regions rostral to the supplementary motor area are recruited for the actual mental rotation process.

Adult↗

The preparation and readiness for voluntary movement: a high-field event-related fMRI study of the Bereitschafts-BOLD response.

Activity within motor areas of the cortex begins to increase 1 to 2 s prior to voluntary self-initiated movement (termed the Bereitschaftspotential or readiness potential). There has been much speculation and debate over the precise source of this early premovement activity as it is important for understanding the roles of higher order motor areas in the preparation and readiness for voluntary movement. In this study, we use high-field (3-T) event-related fMRI with high temporal sampling (partial brain volumes every 250 ms) to specifically examine hemodynamic response time courses during the preparation, readiness, and execution of purely self-initiated voluntary movement. Five right-handed healthy volunteers performed a rapid sequential finger-to-thumb movement performed at self-determined times (12-15 trials). Functional images for each trial were temporally aligned and the averaged time series for each subject was iteratively correlated with a canonical hemodynamic response function progressively shifted in time. This analysis method identified areas of activation without constraining hemodynamic response timing. All subjects showed activation within frontal mesial areas, including supplementary motor area (SMA) and cingulate motor areas, as well as activation in left primary sensorimotor areas. The time courses of hemodynamic responses showed a great deal of variability in shape and timing between subjects; however, four subjects clearly showed earlier relative hemodynamic responses within SMA/cingulate motor areas compared with left primary motor areas. These results provide further evidence that the SMA and cingulate motor areas are major contributors to early stage premovement activity and play an important role in the preparation and readiness for voluntary movement.

Adult↗

Bone homogeneity factor: an advanced tool for the assessment of osteoporotic bone structure in high-resolution magnetic resonance images.

RATIONALE AND OBJECTIVES: Osteoporosis is characterized by low bone mass and inferior structural competence. In this study we introduce the bone homogeneity factor (BHF) as a quantitative measurement of bone structure, which could be equally important as bone mineral density. METHODS: BHF represents an advanced texture analysis tool based on the spatial autocorrelation function calculated in 9 different directions. These calculations were performed on high-resolution magnetic resonance images of the calcaneus at 3.0 T and compared with dual-energy x-ray absorptiometry measurements of the femoral neck. RESULTS: The quality and resolution of the high-resolution magnetic resonance images is sufficient for reliably calculating BHF. The mean BHF of the control group (n = 5, mean BHF = 525,0) with normal bone is significantly (P = 0.009, Mann-Whitney U test) higher than in the osteoporotic group (n = 7, mean BHF = 137,8). The BHF correlates with the DXA measurements of the femoral neck (correlation coefficient = 0.75). CONCLUSIONS: By calculating the BHF, it was possible to distinguish between osteoporotic and nonosteoporotic bone structure. Hence, BHF could be a possible candidate for noninvasive assessment of osteoporotic bone structure giving additional information to routinely used bone mineral densitometry.

Absorptiometry, Photon↗

Diffusivity- and T2 imaging at 3 Tesla for the detection of degenerative changes in human-excised tissue with high resolution: atherosclerotic arteries.

RATIONALE AND OBJECTIVES: We investigated whether it is possible to investigate degenerative changes in human tissue on a sub-100-microm resolution scale not only on special high-field small-bore MR-microscopy systems but also on a 3T whole-body MR-scanner. METHODS: Spin-spin relaxation, proton density, and diffusion microimaging were investigated in studying human atherosclerotic arteries. Strong diffusion weighting and high spatial resolution was achieved by means of a strong dedicated gradient system and a small birdcage radiofrequency resonator. RESULTS: Quantitative parameter maps were obtained at voxel sizes down to 73 x 73 x 600 microm3. The morphologic structure and pathology connected to lipid deposits, plaques, small thrombi, and bifurcations were well visualized. CONCLUSION: High-resolution parameter-weighted and parameter-imaging at sub-100-microm pixel resolution can be achieved for excised tissue on a 3.0 T whole body MR system. Perspectives for the characterization of atherosclerotic plaques imply not only cost advantages but also equivalence of contrast, especially as to T(2), for in vivo and high-resolution ex vivo investigations on the same MR scanner.

Aged↗

Quantification of metabolic differences in the frontal brain of depressive patients and controls obtained by 1H-MRS at 3 Tesla.

RATIONALE AND OBJECTIVES: This study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla. METHODS: Short-echo-time stimulated echo acquisition mode (TE/TM/TR=20/30/6000 milliseconds) was applied in the prefrontal region of 17 depressed patients and 17 age- and sex-matched controls. Metabolic ratios, ie, N-acetyl-aspartate/creatine (Cr), choline/Cr, and myo-inositol/Cr, and absolute concentrations (using internal water as a reference together with LCModel-based spectra fitting) were calculated and compared between groups and published reference data. RESULTS: Metabolic ratios showed significantly lower N-acetyl-aspartate/Cr (P = 0.016/0.006, left/right), choline/Cr (P = n.s./0.016), and myo-inositol/Cr (P = 0.022/0.026) for depressive patients versus controls. However, depressive patients showed significantly higher absolute concentrations of Cr (P = 0.017/0.0004) compared with controls with no differences in all other metabolites estimated. CONCLUSIONS: The authors demonstrate that absolute quantification of metabolite concentration is essential in properly identifying pathologic differences of brain metabolites in depression.

Adult↗

High-resolution diffusivity imaging at 3.0 T for the detection of degenerative changes: a trypsin-based arthritis model.

RATIONALE AND OBJECTIVES: To establish whether it is possible to quantitatively characterize the degenerative changes in cartilage that typify arthritis on a sub-150-microm resolution scale using a 3.0 T whole body MR-scanner with a reasonable measurement time. MATERIALS AND METHODS: This problem is addressed through diffusion-microimaging investigations on an arthritis model based on the enzymatic destruction of the proteoglycans in cartilage specimen. A 35-mm birdcage resonator made high spatial resolution possible, and diffusion-micro-imaging was achieved with the use of a strong gradient system. RESULTS: Diffusion-weighted and quantitative parameter maps were acquired with 117 x 234 microm2 pixel resolution in less than 9 minutes. Diffusivity profiles and parameter images exhibit an increase in diffusivity in degenerated tissue. CONCLUSION: In a trypsin-based arthritis model, the spatial localization and quantification of damaged areas have been shown to be possible on a whole body 3.0 T MR system. Measurement times achieved for these high spatial resolution studies make in vivo investigations feasible.

Animals↗