Biomedical subjects

Josef Pfeuffer

Publications and source records attributed to Josef Pfeuffer.

14 recordsLinked to original sources

PubMed2006

Combined passive and active shimming for in vivo MR spectroscopy at high magnetic fields.

The use of high magnetic fields increases the sensitivity and spectral dispersion in magnetic resonance spectroscopy (MRS) of brain metabolites. Practical limitations arise, however, from susceptibility-induced field distortions, which are increased at higher magnetic field strengths. Solutions to this problem include optimized shimming, provided that active, i.e., electronic, shimming can operate over a sufficient range. To meet our shim requirements, which were an order of magnitude greater than the active shim capacity of our 7T MR system, we developed a combined passive and active shim approach. Simple geometries of ferromagnetic shim elements were derived and numerically optimized to generate a complete set of second-order spherical harmonic shim functions in a modular manner. The major goals of the shim design were maximization of shim field accuracy and ease of practical implementation. The theoretically optimized ferro-shim geometries were mounted on a cylindrical surface and placed inside the magnet bore, surrounding the subject's head and the RF coil. Passive shimming generated very strong shim fields and eliminated the worst of the field distortions, after which the field was further optimized by flexible and highly accurate active shimming. Here, the passive-shimming procedure was first evaluated theoretically, then applied in phantom studies and subsequently validated for in vivo 1H MRS in the macaque visual cortex. No artifacts due to the passive shim setup were observed; adjustments were reproducible between sessions. The modularity and the reduction to two pieces per shim term in this study is an important simplification that makes the method applicable also for passive shimming within single sessions. The feasibility of very strong, flexible and high-quality shimming via a combined approach of passive and active shimming is of great practical relevance for MR imaging and spectroscopy at high field strengths where shim power is limited or where shimming of specific anatomical regions inherently requires strong shim fields.

Algorithms↗

PubMed2005

High-resolution (1)H chemical shift imaging in the monkey visual cortex.

Functionally distinct anatomic subdivisions of the brain can often be only a few millimeters in one or more dimensions. The study of metabolic differences in such structures by means of localized in vivo MR spectroscopy is therefore challenging, if not impossible. In fact, the spatial resolution of chemical shift imaging (CSI) in humans is typically in the range of centimeters. The aim of the present study was to optimize (1)H CSI in monkeys and demonstrate the feasibility of high spatial resolutions up to 1.4 x 2 x 1.4 mm(3). The obtained spatial resolution permitted the segregation of gray and white matter in the visual cortex based on the concentration of different metabolites and neurotransmitters like N-acetylaspartate, glutamate, and creatine. Concentration ratios of white matter versus gray matter tissue as well as between metabolites matched those reported in the literature from healthy human brain, demonstrating the consistency and reliability of the procedure.

Animals↗

PubMed2005

Detection of intracellular lactate with localized diffusion {1H-13C}-spectroscopy in rat glioma in vivo.

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of (13)C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). (13)C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, {(1)H-(13)C}-lactate and {(1)H-(13)C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {(1)H-(13)C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/microm(2)). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, (1)H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([(13)C] lactate) originates from an intracellular compartment.

Alanine↗

PubMed2004

High-field localized 1H NMR spectroscopy in the anesthetized and in the awake monkey.

Localized cerebral in vivo 1H NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cm MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than 1 mM, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr-Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6-10 cerebral metabolites of 1-ml volumes.

Anesthesia, General↗

PubMed2004

Anatomical and functional MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup.

Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75x150x300 microm3 and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and -2.4%, respectively. Finally, the first high-resolution (500 microm in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity.

Animals↗

PubMed2004

Region and volume dependencies in spectral line width assessed by 1H 2D MR chemical shift imaging in the monkey brain at 7 T.

High magnetic fields increase the sensitivity and spectral dispersion in magnetic resonance spectroscopy (MRS). In contrast, spectral peaks are broadened in vivo at higher field strength due to stronger susceptibility-induced effects. Strategies to minimize the spectral line width are therefore of critical importance. In the present study, 1H 2D chemical shift imaging at short echo times was performed in the macaque monkey brain at 7 T. Large brain coverage was obtained at high spatial resolution with voxel sizes down to 50 microl being able to quantify up to nine metabolites in vivo with good reliability. Measured line widths of metabolites decreased from 14.2 to 7.6 Hz with voxel volumes of 3.14 ml to 50 microl (at increased spatial resolution). The line width distribution of the metabolites (7.6+/-1.6 Hz, ranging from 5.5 to 10 Hz) was considerably smaller compared to that of water (10.6+/-2.4 Hz) and was also smaller than reported in 1H MRS at 7 T in the human brain. Our study showed that even in well-shimmed areas assumed to have minimal macroscopic susceptibility variations, spectral line widths are tissue-specific exhibiting considerable regional variation. Therefore, an overall improvement of a gross spectral line width--directly correlated with improved spectral quality--can only be achieved when voxel volumes are significantly reduced. Our line width optimization was sufficient to permit clear glutamate (Glu)-glutamine separation, yielding distinct Glu maps for brain areas including regions of greatly different Glu concentration (e.g., ventricles vs. surrounding tissue).

Animals↗

PubMed2004

On the nature of the BOLD fMRI contrast mechanism.

Since its development about 15 years ago, functional magnetic resonance imaging (fMRI) has become the leading research tool for mapping brain activity. The technique works by detecting the levels of oxygen in the blood, point by point, throughout the brain. In other words, it relies on a surrogate signal, resulting from changes in oxygenation, blood volume and flow, and does not directly measure neural activity. Although a relationship between changes in brain activity and blood flow has long been speculated, indirectly examined and suggested and surely anticipated and expected, the neural basis of the fMRI signal was only recently demonstrated directly in experiments using combined imaging and intracortical recordings. In the present paper, we discuss the results obtained from such combined experiments. We also discuss our current knowledge of the extracellularly measured signals of the neural processes that they represent and of the structural and functional neurovascular coupling, which links such processes with the hemodynamic changes that offer the surrogate signal that we use to map brain activity. We conclude by considering applications of invasive MRI, including injections of paramagnetic tracers for the study of connectivity in the living animal and simultaneous imaging and electrical microstimulation.

Animals↗

PubMed2003

Spatial dependence of the nonlinear BOLD response at short stimulus duration.

Most functional magnetic resonance imaging studies use linear models to predict the measured response by convolution of an impulse response with the stimulus profile. Using very short visual presentation times (<2 s), deviation from the linear model in the measured BOLD data from the human brain was found for the response integral, amplitude, and width. In this study, high temporal and spatial resolution were used to quantify nonlinear effects and investigate the spatial dependence. Data at 4 Tesla showed at short stimulus duration a nonlinearity, i.e., deviation from a linear model, with an index up to 400%, whereas data at 7 Tesla exhibited a nonlinearity index up to 40%. The effect was more pronounced for response amplitude than for response area. A reduced width and sharpening of responses at shorter stimulus duration was also found. A voxel-based analysis of 7 Tesla data with 1.2 x 1.2 x 2 mm(3) resolution revealed a correlation between response onset and nonlinearity index. This suggests that the nonlinearity effects are a tissue-specific phenomenon and are likely to be more localized to the site of neuronal activity. The observed magnetic field dependence and the demonstrated nonlinearity in the response width support the hypothesis that the source of the nonlinearity at short stimulus duration has a considerable hemodynamic contribution. The nonlinearity was modeled as a "switch"-type initial hemodynamic response onset. Understanding these nonlinearities in the BOLD response is important for design and the analysis of rapid event-related fMRI experiments with brief stimulus presentations.

Brain Mapping↗

PubMed2002

Sustained negative BOLD, blood flow and oxygen consumption response and its coupling to the positive response in the human brain.

Most fMRI studies are based on the detection of a positive BOLD response (PBR). Here, we demonstrate and characterize a robust sustained negative BOLD response (NBR) in the human occipital cortex, triggered by stimulating part of the visual field. The NBR was spatially adjacent to but segregated from the PBR. It depended on the stimulus and thus on the pattern of neuronal activity. The time courses of the NBR and PBR were similar, and their amplitudes covaried both with increasing stimulus duration and increasing stimulus contrast. The NBR was associated with reductions in blood flow and with decreases in oxygen consumption. Our findings support the contribution to the NBR of (1) a significant component of reduction in neuronal activity and (2) possibly a component of hemodynamic changes independent of the local changes in neuronal activity.

Adult↗

PubMed2002

Correction of physiologically induced global off-resonance effects in dynamic echo-planar and spiral functional imaging.

In functional magnetic resonance imaging, a rapid method such as echo-planar (EPI) or spiral is used to collect a dynamic series of images. These techniques are sensitive to changes in resonance frequency which can arise from respiration and are more significant at high magnetic fields. To decrease the noise from respiration-induced phase and frequency fluctuations, a simple correction of the "dynamic off-resonance in k-space" (DORK) was developed. The correction uses phase information from the center of k-space and a navigator echo and is illustrated with dynamic scans of single-shot and segmented EPI and, for the first time, spiral imaging of the human brain at 7 T. Image noise in the respiratory spectrum was measured with an edge operator. The DORK correction significantly reduced respiration-induced noise (image shift for EPI, blurring for spiral, ghosting for segmented acquisition). While spiral imaging was found to exhibit less noise than EPI before correction, the residual noise after the DORK correction was comparable. The correction is simple to apply and can correct for other sources of frequency drift and fluctuations in dynamic imaging.

Adult↗

PubMed2002

Respiration-induced B0 fluctuations and their spatial distribution in the human brain at 7 Tesla.

In functional magnetic resonance imaging (fMRI), it is known that physiological influences such as cardiac pulsation, respiration, and brain motion can induce fluctuations in signal intensity and phase. Some of the mechanisms potentially involved in those phenomena are expected to be amplified at higher magnetic fields. This study addresses the issue of B(0) fluctuations induced by susceptibility changes during respiration attributed to movements of chest and diaphragm, and variations in the oxygen concentration. It is demonstrated that respiration-induced resonance offsets (RIROs) are significant at 7T. Data were acquired with an RF pulse (no gradients), multislice echo-planar imaging (EPI), and dynamic 3D fast low-angle shot (3D- FLASH) imaging. Three main observations summarize the experimental findings. First, in FIDs measured after a single RF pulse, a RIRO with a large amplitude was consistently detected, although the average amplitude varied between subjects from 1.45 Hz to 4 Hz. Second, in transverse EPI images obtained in the occipital lobe, the RIRO amplitude showed a monotonic increase along the z axis toward the lungs. Third, a more detailed spatial analysis with 3D-FLASH phase maps revealed that a previously published analytical model can accurately describe the spatial distribution of RIRO. Consequential apparent motions in the EPI series, as well as the implications of slice orientation for correction strategies are discussed.

Brain↗

PubMed2002

Perfusion-based high-resolution functional imaging in the human brain at 7 Tesla.

Perfusion-based MRI measures cerebral blood flow (CBF) at the capillary level and can be used for functional studies based on the tight spatial coupling between brain activity and blood flow. Obtaining functional CBF maps with high spatial resolution is a major challenge because the CBF signal is intrinsically low and the SNR is critical. In the present work, CBF-based functional imaging was performed at a considerably smaller voxel size than previously reported in humans. High-resolution CBF maps were obtained with voxel sizes as small as 0.9 x 0.9 x 1.5 mm(3) in the human brain. High sensitivity was made possible by signal-to-noise gains at the high magnetic field of 7 T and by using a novel RF combination coil design. In addition, a reduction of the field-of-view was critical to achieve 0.9-mm in-plane resolution with gradient-echo echo-planar imaging in a single shot. Functional CBF data were compared with functional BOLD data to reveal that, for CBF, large contrast- to-noise gains were obtained at high spatial resolution, indicating that the functional CBF response was more localized. High-resolution functional CBF imaging is significant for neuroscience research because it provides better localization and more specific information than BOLD for monitoring brain function.

Cerebrovascular Circulation↗

PubMed2002

Zoomed functional imaging in the human brain at 7 Tesla with simultaneous high spatial and high temporal resolution.

Functional neuroimaging in the human brain using noninvasive magnetic resonance methods has the potential of providing highly resolved maps of neuronal activation. Decreasing the voxel size and obtaining simultaneously high temporal resolution is a major challenge and is mainly limited by sensitivity. Here, signal-to-noise gains at high magnetic fields (7 Tesla) and an optimized surface coil setup are combined with a novel approach for zoomed functional imaging in the visual cortex. For echoplanar imaging, the acquisition time and segmentation was shortened fourfold by using a reduced field-of-view. An adiabatic outer-volume suppression method, BISTRO, was used to obliterate signal outside the area-of-interest achieving effective suppression even for inhomogeneous B1-fields. A single-shot acquisition was performed at submillimeter resolution in the human brain, while simultaneously maintaining a high temporal resolution of 125 ms. Functional studies with and without field-of-view reduction were performed. Activation and percent change maps were compared with respect to spatial extent, t values and percentage changes of the BOLD contrast. The detection of functional activation was found to be equal within the inter-series variability for the two acquisition schemes. Thus, single-trial BOLD responses were detected for the first time robustly at a 500 x 500 microm2 in plane and 250 ms temporal resolution, significantly expanding the possibilities of event-related functional imaging in the human brain. The magnetization transfer effect induced by the outer-volume suppression pulses was investigated and found to be increased during neuronal activity.

Algorithms↗

PubMedDate not supplied

A new class of Gd-based DO3A-ethylamine-derived targeted contrast agents for MR and optical imaging.

Synthetic bifunctional probes based on [4,7-bis-carboxymethyl-10-(2-aminoethyl)-1,4,7,10-tetraaza-cyclododec-1-yl]-acetic acid (DO3A-ethylamine) preloaded with gadolinium were prepared for applications in targeted magnetic resonance imaging (MRI) and optical imaging. A convenient route of synthesis is reported, which allowed conjugation of this probe with biomolecules for the preparation of model MR contrast agents for targeted imaging. The conjugated probes have the following interesting properties: GdDO3A-ethylamido-biotin (Gd-9) can be used for targeted imaging using an avidin-biotin system. The fluorescent probe GdDO3A-ethylthiourea-fluorescein (Gd-12) is a bimodal compound, which can be used for both MR and optical imaging. The precursors, DO3A-ethylamidopropyl-maleimide and DO3A-ethyl-isothiocyanate contain a highly reactive moiety, which can interact with free SH-terminals and N-terminals of biological molecules, respectively. In vitro MR relaxivity studies were performed at 300 MHz using different concentrations and chemical environments. MR relaxivity for ligand Gd-9 at pH 7.4, r1 was (3.32 +/- 0.03) s(-1) mM(-1) and r2 was (5.02 +/- 0.14) s(-1) mM(-1). For the mixture of Gd-9 with avidin, at pH 7.4, relaxivity increased linearly with the avidin concentration. A relaxivity enhancement of 45% for r1 and more than 400% for r2 with respect to the unbound biotinylated Gd3+ complex was found at a ratio of 4:1. MR relaxivity for ligand Gd-12, r1 was (5.36 +/- 0.05) s(-1) mM(-1) at pH 7.4. Fluorescence microscopy and spectroscopy of Gd-12-labeled 3T3 mouse fibroblasts showed a concentration-dependent intracellular uptake, accompanied by a slight dose-dependent increase in toxicity up to 150 microM. MR studies on labeled cells indicated a contrast enhancement in both T1- and T2-weighted images by the internalized compound, with the effect being more pronounced in T2-weighted images. Our results indicate that DO3A-ethylamine is a multipurpose precursor, from which various targeted contrast agents can be synthesized after a single-step conjugation with organic/bioorganic molecules.

Animals↗