Biomedical subjects

O Bieri

Publications and source records attributed to O Bieri.

10 recordsLinked to original sources

PubMed2007

Effect of diffusion in inhomogeneous magnetic fields on balanced steady-state free precession.

In this work, the effects of susceptibility variation from dilute, micron-sized spherical field perturbers and diffusion on balanced steady-state free precession (bSSFP) are analyzed. Predictions from Monte Carlo simulations are in good agreement with experiments and reveal that, for diffusing protons, susceptibility variation becomes apparent as a reduction in the overall bSSFP signal intensity. This reduction depends on microsphere parameters (radius and susceptibility difference), as well as on sequence-related parameters (repetition time and flip angle) and on relaxation times. Specific Monte Carlo results from one set of parameter values can be extrapolated to another set of values by means of a scaling law and a substitution model. The scaling law, derived from the Bloch-Torrey equation, captures the dependencies of bSSFP signal reduction on susceptibility and diffusion-related changes and on repetition time, whereas the substitution model describes those on flip angle and relaxation times.

Algorithms↗

PubMed2006

Balanced alternating steady-state elastography.

A conventional balanced steady-state free precession (b-SSFP) sequence scheme was modified such that the dynamic equilibrium becomes very sensitive to small cyclic displacements, generating two distinct and alternating steady states. This novel technique is proposed for the visualization of propagating transverse acoustic shear waves, as used in MR elastography (MRE) to determine the mechanical properties of materials or in vivo soft tissue. Experiments with tissue-like agarose gel phantoms and simulations demonstrate that the novel sequence offers an increase in phase sensitivity by about one order in magnitude compared to standard motion-encoding methods. In addition, the new method benefits from the very short acquisition times achieved by b-SSFP protocols.

Artifacts↗

PubMed2006

On the origin of apparent low tissue signals in balanced SSFP.

Balanced steady-state free precession (bSSFP) has become increasingly important in clinical applications. Its signal properties have been investigated over several years by many groups, and various critical factors for bSSFP signal intensity and stability, such as off-resonances, flow, and eddy currents, have been identified. It is generally accepted that bSSFP signal intensity is a function of relaxation times, excitation angles, and spin densities only. While this is true for simple phantoms, it appears that signals from tissues are significantly less intense than predicted by theory. This work demonstrates that the molecular origin of this apparent signal reduction is due to on-resonance magnetization transfer (MT). High flip angles in combination with very short repetition times (TRs), as commonly used for bSSFP, lead to a considerable saturation in the fraction of macromolecular (MM) pool protons. As a result, bSSFP signal is strongly attenuated by up to a factor of 2 in the human brain compared to the signal expected from theory.

Algorithms↗

PubMed2005

Analysis and compensation of eddy currents in balanced SSFP.

Balanced steady-state free precession (SSFP) completely compensates for all gradients within each repetition time (TR), and is thus very sensitive to any magnetic field imperfection that disturbs the perfectly balanced acquisition scheme. It is demonstrated that balanced SSFP is especially sensitive to changing eddy currents that are induced by stepwise changing phase-encoding (PE) gradients. In contrast to the linear k-space trajectory, which has small variations between consecutive encoding steps, other encoding schemes (e.g., centric, random, or segmented orderings) exhibit significant jumps in k-space between adjacent PE steps, and consequently induce rapidly changing eddy currents. The resulting disturbances induce significant image artifacts, such that compensation strategies are essential when nonlinear PE schemes are applied. Although direct annihilation of the induced eddy currents by additional, opposing magnetic fields has been investigated, it is limited by uncertainty regarding the time evolution of induced eddy currents. A generic (and thus system-unrelated) compensation strategy is proposed that consists of "pairing" of consecutive PE steps. Another approach is based on partial dephasing along the slice direction that annihilates eddy-current-induced signal oscillations. Both pairing of the PE steps and "through-slice equilibration" are easy to implement and allow the use of arbitrary k-space trajectories for balanced SSFP.

Algorithms↗

PubMed2005

Double average parallel steady-state free precession imaging: optimized eddy current and transient oscillation compensation.

Balanced steady-state free precession (SSFP) imaging is sensitive to off-resonance effects, which can lead to considerable artifacts during a transient phase following magnetization preparation or steady-state interruption. In addition, nonlinear k-space encoding is required if contrast-relevant k-space regions need to be acquired at specific delays following magnetization preparation or for transient artifact reduction in cardiac-gated k-space segmented CINE imaging. Such trajectories are problematic for balanced SSFP imaging due to nonconstant eddy current effects and resulting disruption of the steady state. In this work, a novel acquisition strategy for balanced SSFP imaging is presented that utilizes scan time reduction by parallel imaging for optimized "double average" eddy current compensation and artifact reduction during the transient phase following steady-state storage and magnetization preparation. Double average parallel SSFP imaging was applied to k-space segmented CINE SSFP tagging as well as nongated centrically encoded SSFP imaging. Phantom and human studies exhibit substantial reduction in steady-state storage and eddy current artifacts while maintaining spatial resolution, signal-to-noise ratio, and similar total scan time of a standard SSFP acquisition. The proposed technique can easily be extended to other acquisition schemes that would benefit from nonlinear reordering schemes and/or rely on interruption of the balanced SSFP steady state.

Algorithms↗

PubMed2005

Flow compensation in balanced SSFP sequences.

In balanced steady-state free precession (b-SSFP) sequences, uncompensated first-order moments of encoding gradients induce a nonconstant phase evolution for moving spins within the excitation train, resulting in signal loss and image artifacts. To restore these flow-related phase perturbations, "pairing" of consecutive phase-encoding (PE) steps is compared with a fully flow-compensated sequence using compensating gradient waveforms along all three encoding directions. In volunteer studies, the quality of images acquired with the "pairing" technique was comparable to that of images obtained with the fully flow-compensated technique, regardless of the selected view-ordering scheme used for data acquisition. Nevertheless, the results of phantom experiments indicate that the pairing technique becomes ineffective at flow velocities exceeding roughly 0.5-1 m/s. Consequently, the additional scan time required to null the first gradient moments in a flow-compensated b-SSFP sequence makes the "pairing" technique preferable for applications in which slow to moderate flow velocities can be expected.

Algorithms↗

PubMed2001

Origin of apparent fast and non-exponential kinetics of lysozyme folding measured in pulsed hydrogen exchange experiments.

Folding of lysozyme at pH 5.2 is a complex processes. After rapid collapse (<1 ms) kinetic partitioning into a slow and fast folding pathway occurs. The fast pathway leads directly to the native structure (N), whereas the slow pathway goes through a partially folded intermediate (I(1)) with native-like secondary structure in the alpha-domain. This mechanism is in agreement with data from a large number of spectroscopic probes, from changes in the radius of gyration and from measurements on the time-course of the populations of the different species. Results from pulsed hydrogen exchange experiments, in contrast, revealed that the secondary structure of I(1) and of N is formed significantly faster than changes in spectroscopic properties occur and showed large variations in the protection kinetics of individual amide sites. We investigated the molecular origin of the rapid amide protection by quantitatively simulating all kinetic processes during the pulse-labeling experiments. Absorbance and fluorescence-detected folding kinetics showed that the early events in lysozyme folding are accelerated under exchange conditions (pH 9.2) and that a change in folding mechanism occurs due to the transient population of an additional intermediate (I(2)). This leads to kinetic competition between exchange and folding during the exchange pulse and to incomplete labeling of amide sites with slow intrinsic exchange rates. As a result, apparently faster and non-exponential kinetics of amide protection are measured in the labeling experiments. Our results further suggest that collapsed lysozyme (C) and I(1) have five and ten-times reduced free exchange rates, respectively, due to limited solvent accessibility.

Amides↗

PubMed1999

A salt-induced kinetic intermediate is on a new parallel pathway of lysozyme folding.

Lysozyme folds through two competing pathways. A fast pathway leads directly from a collapsed state to the native protein, whereas folding on a slow pathway proceeds through a partially folded intermediate (I(1)). At NaCl concentrations above 100 mM, a second transient intermediate (I(2)) is induced as judged by the appearance of an additional apparent rate constant in the refolding kinetics. Monitoring the time course of native molecules and of both intermediates shows that the NaCl-induced state (I(2)) is located on neither of the two folding pathways observed at low-salt concentrations. These results suggest that I(2) is a metastable high-energy intermediate at low-ionic strength and is located on a third folding pathway. The folding landscape of lysozyme seems to be complex with several high-energy intermediates located on parallel folding routes. However, the experiments show no evidence for partially folded states on the fast direct pathway.

Animals↗

PubMed1999

The speed limit for protein folding measured by triplet-triplet energy transfer.

A direct measure of intramolecular chain diffusion is obtained by the determination of triplet-triplet energy-transfer rates between a donor and an acceptor chromophore attached at defined points on a polypeptide chain. Single exponential kinetics of contact formation are observed on the nanosecond time scale for polypeptides in which donor and acceptor are linked by repeating units of glycine and serine residues. The rates depend on the number of peptide bonds (N) separating donor and acceptor and show a maximum for the shortest peptides (N = 3) with a time constant (tau = 1/k) of 20 ns. This sets an upper limit for the speed of formation of the first side-chain contacts during protein folding.

Energy Transfer↗

PubMedDate not supplied

Elementary steps in protein folding.

The mechanism of protein folding is under intense theoretical and experimental investigation. From stopped-flow mixing experiments we have detailed knowledge of processes slower than about 1 ms, but until recently little was known about folding and unfolding reactions on the microsecond to nanosecond time scale. The use of novel techniques allowed to explore the elementary steps in protein folding, such as intrachain diffusion and formation of alpha-helices, beta-hairpins and loop structures. This brief review discusses the time scales of these early elementary events which are crucial for the understanding of how proteins fold.

Protein Conformation↗