Thies H. Jochimsen

Quantifying the intra‐ and extravascular contributions to spin‐echo fMRI at 3 T

Functional MRI (fMRI) by means of spin‐echo (SE) techniques provides an interesting alternative to gradient‐echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level‐dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion‐weighting gradient schemes which are either flow‐compensated, or will maximally dephase moving spins. Second, contributions from the intra‐ and extravascular space are selectively suppressed by combining flow‐weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra‐ and extravascular compartments at TE ≈ 80 ms and 3 T. Combining these results, there is evidence that at least one‐half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow‐compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma. Magn Reson Med 52:724–732, 2004.

Perfusion mapping with multiecho multishot parallel imaging EPI

Echo‐planar imaging (EPI) is the standard technique for dynamic susceptibility‐contrast (DSC) perfusion MRI. However, EPI suffers from well‐known geometric distortions, which can be reduced by increasing the k‐space phase velocity. Moreover, the long echo times (TEs) used in DSC lead to signal saturation of the arterial input signal, and hence to severe quantitation errors in the hemodynamic information. Here, through the use of interleaved shot acquisition and parallel imaging (PI), rapid volumetric EPI is performed using pseudo‐single‐shot (ss)EPI with the effective T  *2 blur and susceptibility distortions of a multishot EPI sequence. The reduced readout lengths permit multiple echoes to be acquired with temporal resolution and spatial coverage similar to those obtained with a single‐echo method. Multiecho readouts allow for unbiased R  *2 mapping to avoid incorrect estimation of tracer concentration due to signal saturation or T1 shortening effects. Multiecho perfusion measurement also mitigates the signal‐to‐noise ratio (SNR) reduction that results from utilizing PI. Results from both volunteers and clinical stroke patients are presented. This acquisition scheme can aid most rapid time‐series acquisitions. The use of this method for DSC addresses the problem of signal saturation and T1 contamination while it improves image quality, and is a logical step toward better quantitative MR PWI. Magn Reson Med 58:70–81, 2007.

Efficiency of flow-driven adiabatic spin inversion under realistic experimental conditions: a computer simulation.

Continuous arterial spin labeling (CASL) using adiabatic inversion is a widely used approach for perfusion imaging. For the quantification of perfusion, a reliable determination of the labeling efficiency is required. A numerical method for predicting the labeling efficiency in CASL experiments under various experimental conditions, including spin relaxation, is demonstrated. The approach is especially useful in the case of labeling at the carotid artery with a surface coil, as consideration of the experimental or theoretical profile of the B1 field is straightforward. Other effects that are also accounted for include deviations from a constant labeling gradient, and variations in the blood flow velocity due to the cardiac cycle. Assuming relevant experimental and physiological conditions, maximum inversion efficiencies of about 85% can be obtained. Magn Reson Med 51:1187–1193, 2004.

Whole-brain mapping of venous vessel size in humans using the hypercapnia-induced BOLD effect.

Measuring the morphology of the cerebral microvasculature by vessel-size imaging (VSI) is a promising approach for clinical applications, such as the characterization of tumor angiogenesis and stroke. Despite the great potential of VSI, this method has not yet found widespread use in practice due to the lack of experience in testing it on healthy humans. Since this limitation derives mainly from the need for an invasive injection of a contrast agent, this work explores the possibility to employ instead the easily accessible blood oxygenation level dependent (BOLD) effect for VSI of the venous microstructure. It is demonstrated that BOLD-VSI in humans can be realized by a hypercapnic challenge using a fast gradient-echo (GE) and spin-echo (SE) sequence at 7T. Reproducible maps of the mean venous vessel radius, based on the BOLD-induced changes in GE and SE relaxation rates, could be obtained within a scan time of 10min. Moreover, the method yields maps of venous blood volume and vessel density. Owing to its non-invasive character, BOLD-VSI provides a low-risk method to analyze the venous microstructure, which will not only be useful in clinical applications, but also provide a better understanding of BOLD effect.

Increasing specificity in functional magnetic resonance imaging by estimation of vessel size based on changes in blood oxygenation

Detecting neuronal activity by functional magnetic resonance imaging (fMRI) based on the blood oxygenation level dependent (BOLD) contrast can be problematic since the contrast reflects changes in blood oxygenation which can be distant from the activated site, e.g. in the presence of large veins. In this work, a novel approach is presented to increase specificity, i.e. to confine the origin of the BOLD contrast to the microvasculature, by predicting the average venous vessel radius in activated voxels, and to filter out those voxels whose contrast is dominated by large veins. The average vessel radius is derived from the combined change in transverse relaxation rates upon activation which are measured by a parallel-imaging, single-shot, multi-gradient-echo sampling of spin echo sequence. Due to the high temporal and spatial resolution, this sequence is suitable for routine fMRI applications. In addition, the technique provides additional insight into the origin of the BOLD contrast, such as the impact of the significance threshold on the macrovascular contribution to the fMRI signal.

Functional magnetic resonance imaging with intermolecular double‐quantum coherences at 3 T

Functional magnetic resonance imaging (fMRI) based on the selection of intermolecular double‐quantum coherences (iDQC) was performed with a standard birdcage coil at 3 T in a group of normal human volunteers. Suppression of spurious signal contributions from unwanted coherence‐transfer pathways was achieved by combining a two‐step phase cycle and a long repetition time of 5 s. A gradient‐recalled echo iDQC sequence (echo time, TE = 80 ms) yielded robust activation with a visual paradigm. Maximum z‐scores were about half of those observed with conventional blood‐oxygen level dependent fMRI, whereas the functional signal change increased by more than a factor of 5. No activation was obtained with a spin‐echo iDQC sequence (TE = 160 ms), in which dephasing accumulated during the evolution period was fully rephased by an appropriate delay time. It is hypothesized that substantial inherent diffusion weighting of the iDQC technique efficiently suppresses intravascular contributions to the functional contrast. A consistent quantitative explanation of the observed amount of signal change currently remains speculative. Magn Reson Med 53:1402–1408, 2005.

Is there a change in water proton density associated with functional magnetic resonance imaging

In a recent series of studies (see, for example, Stroman et al. Magn Reson Imag 2001; 19:827–831), an increase of water proton density has been suggested to correlate with neuronal activity. Owing to the significant implications of such a mechanism for other functional experiments, the functional signal changes in humans at very short echo times were re‐examined by spin‐echo EPI at 3 T. The results do not confirm the previous hypothesis of a significant increase in extravascular proton density at TE = 0. Instead, an alternative explanation of the effect is offered: The use of a low threshold to identify activated voxels may generate an artificial offset in functional contrast due to the inclusion of false‐positives in the analysis. Magn Reson Med 53:470–473, 2005.

BOLD background gradient contributions in diffusion-weighted fMRI-comparison of spin-echo and twice-refocused spin-echo sequences

The interaction (‘cross terms’) between diffusion‐weighting gradients and susceptibility‐induced background gradient fields around vessels has an impact on apparent diffusion coefficient (ADC) measurements and diffusion‐weighted functional magnetic resonance imaging (DFMRI) experiments. Monte‐Carlo (MC) simulations numerically integrating the Bloch equations for a large number of random walks in a vascular model were used to investigate to what extent such interactions would influence the extravascular signal change as well as the ADC change observed in DFMRI experiments. The vascular model consists of a set of independent, randomly oriented, infinite cylinders whose internal magnetic susceptibility varies as the state changes between rest and activation. In such a network, the cross terms result in the observation of a functional increase in ADC accompanied by a descending percent signal change with increasing diffusion weighting. It is shown that the twice‐refocused spin‐echo sequence permits sufficient yet not total suppression of such effects compared to the standard Stejskal‐Tanner spin‐echo diffusion weighting under experimentally relevant conditions. Copyright

Functional magnetic resonance imaging using PROPELLER-EPI.

Periodically rotated overlapping parallel lines with enhanced reconstruction‐echo‐planar imaging (PROPELLER‐EPI) is a multishot technique that samples k‐space by acquisition of narrow blades, which are subsequently rotated until the entire k‐space is filled. It has the unique advantage that the center of k‐space, and thus the area containing the majority of functional MRI signal changes, is sampled with each shot. This continuous refreshing of the k‐space center by each acquired blade enables not only sliding‐window but also keyhole reconstruction. Combining PROPELLER‐EPI with a fast gradient‐echo readout scheme allows for high spatial resolutions to be achieved while maintaining a temporal resolution, which is suitable for functional MRI experiments. Functional data acquired with a novel interlaced sequence that samples both single‐shot EPI and blades in an alternating fashion suggest that PROPELLER‐EPI can achieve comparable functional MRI results. PROPELLER‐EPI, however, features different spatiotemporal characteristics than single‐shot EPI, which not only enables keyhole reconstruction but also makes it an interesting alternative for many functional MRI applications. Magn Reson Med, 2012.

Single-shot curved slice imaging

The feasibility of imaging a curved slice with a single-shot technique so that the reconstructed image shows an un-warping of the slice is examined. This could be of practical importance when the anatomical structures of interest can be more efficiently covered with curved slices than with a series of flat planes. One possible example of such a structure is the cortex of the human brain. Functional imaging would especially benefit from this technique because several planar images can be replaced by a few curved slice images. A method is introduced that is based on multidimensional pulses to excite the desired curved slice profile. A GRASE imaging sequence is then applied that is tailored to the k-space representation of the curved slice. This makes it possible to capture the in-plane information of the slice with a single-shot technique. The method presented is limited to slices that are straight along one axis and can be approximated by a polygon. Reconstruction is performed using a simple numeric Fourier integration along the curved slice. This leads to an image that shows the desired un-warped representation of the slice. Experimental results obtained with this method from healthy volunteers are presented and demonstrate the feasibility of the proposed technique.