Myelin bilayer mapping in the human brain in vivo.

PURPOSE: To quantitatively map the myelin lipid-protein bilayer in the live human brain. METHODS: This goal was pursued by integrating a multi-TE acquisition approach targeting ultrashort T2 signals with voxel-wise fitting to a three-component signal model. Imaging was performed at 3 T in two healthy volunteers using high-performance RF and gradient hardware and the HYFI sequence. The design of a suitable imaging protocol faced substantial constraints concerning SNR, imaging volume, scan time, and RF power deposition. Model fitting to data acquired using the proposed protocol was made feasible through simulation-based optimization, and filtering was used to condition noise presentation and overall depiction fidelity. RESULTS: A multi-TE protocol (11 TEs of 20-780 µs) for in vivo brain imaging was developed in adherence with applicable safety regulations and practical scan time limits. Data acquired using this protocol produced accurate model fitting results, validating the suitability of the protocol for this purpose. Structured, grainy texture of myelin bilayer maps was observed and determined to be a manifestation of correlated image noise resulting from the employed acquisition strategy. Map quality was significantly improved by filtering to uniformize the k-space noise distribution and simultaneously extending the k-space support. The final myelin bilayer maps provided selective depiction of myelin, reconciling competitive resolution (1.4 mm) with adequate SNR and benign noise texture. CONCLUSION: Using the proposed technique, quantitative maps of the myelin bilayer can be obtained in vivo. These maps offer unique information content with potential applications in basic research, diagnosis, disease monitoring, and drug development.

Retrospective correction of second-order concomitant fields in 3D axial stack-of-spirals imaging on a high-performance gradient system.

PURPOSE: MRI using 3D stack-of-spirals (SoS) readout on a high-performance gradient system is subject to strong second-order, spatially varying concomitant fields, which can lead to signal dropout and blurring artifacts that become more significant at locations farther from the gradient isocenter. A method for compensating for second-order concomitant fields in 3D axial SoS image reconstruction is described. METHODS: We retrospectively correct for second-order concomitant field-induced phase error in the 3D SoS data by slice-dependent k-space phase compensation based on the nominal spiral readout trajectories. The effectiveness of the method was demonstrated in phantom and healthy volunteer scans in which 3D pseudo-continuous arterial spin labeling imaging was performed with SoS fast spin-echo readout at 3 T. RESULTS: Substantial reduction in blurring was observed with the proposed method. In phantom scans, blurring was reduced by about 53% at 98 mm from the gradient isocenter. In the in vivo 3D pseudo-continuous arterial spin labeling scans, differences of up to 10% were observed at 78 mm from the isocenter, especially around the white-matter and gray-matter interfaces, between the corrected and uncorrected proton density images, perfusion-weighted images, and cerebral blood flow maps. CONCLUSIONS: The described retrospective correction method provides a means to correct erroneous phase accruals due to second-order concomitant fields in 3D axial stack-of-spirals imaging.

On the correction of spiral trajectories on a preclinical MRI scanner with a high-performance gradient insert.

This study aimed to examine different trajectory correction methods for spiral imaging on a preclinical scanner with high-performance gradients with respect to image quality in a phantom and in vivo. The gold standard method of measuring the trajectories in a separate experiment is compared to an isotropic delay-correction, a correction using the gradient system transfer function (GSTF), and a combination of the two. Three different spiral trajectories, with 96, 16, and three interleaves, are considered. The best image quality is consistently achieved when determining the trajectory in a separate phantom measurement. However, especially for the spiral with 96 interleaves, the other correction methods lead to almost comparable results. Remaining imperfections in the corrected gradient waveforms and trajectories are attributed to asymmetrically occurring undulations in the actual, generated gradients, suggesting that the underlying assumption of linearity is violated. In conclusion, images of sufficient quality can be acquired on preclinical small-animal scanners using spiral k-space trajectories without the need to carry out separate trajectory measurements each time. Depending on the trajectory, a simple isotropic delay-correction or a GSTF-based correction can provide images of similar quality.

Frequency-dependent diffusion kurtosis imaging in the human brain using an oscillating gradient spin echo sequence and a high-performance head-only gradient.

Measuring the time/frequency dependence of diffusion MRI is a promising approach to distinguish between the effects of different tissue microenvironments, such as membrane restriction, tissue heterogeneity, and compartmental water exchange. In this study, we measure the frequency dependence of diffusivity (D) and kurtosis (K) with oscillating gradient diffusion encoding waveforms and a diffusion kurtosis imaging (DKI) model in human brains using a high-performance, head-only MAGNUS gradient system, with a combination of b-values, oscillating frequencies (f), and echo time that has not been achieved in human studies before. Frequency dependence of diffusivity and kurtosis are observed in both global and local white matter (WM) and gray matter (GM) regions and characterized with a power-law model ∼Λ*fθ. The frequency dependences of diffusivity and kurtosis (including changes between fmin and fmax, Λ, and θ) vary over different WM and GM regions, indicating potential microstructural differences between regions. A trend of decreasing kurtosis over frequency in the short-time limit is successfully captured for in vivo human brains. The effects of gradient nonlinearity (GNL) on frequency-dependent diffusivity and kurtosis measurements are investigated and corrected. Our results show that the GNL has prominent scaling effects on the measured diffusivity values (3.5∼5.5% difference in the global WM and 6∼8% difference in the global cortex) and subsequently affects the corresponding power-law parameters (Λ, θ) while having a marginal influence on the measured kurtosis values (<0.05% difference) and power-law parameters (Λ, θ). This study expands previous OGSE studies and further demonstrates the translatability of frequency-dependent diffusivity and kurtosis measurements to human brains, which may provide new opportunities to probe human brain microstructure in health and disease.

Mapping the myelin bilayer with short-T2 MRI: Methods validation and reference data for healthy human brain.

PURPOSE: To explore the properties of short-T2 signals in human brain, investigate the impact of various experimental procedures on these properties and evaluate the performance of three-component analysis. METHODS: Eight samples of non-pathological human brain tissue were subjected to different combinations of experimental procedures including D2 O exchange and frozen storage. Short-T2 imaging techniques were employed to acquire multi-TE (33-2067 µs) data, to which a three-component complex model was fitted in two steps to recover the properties of the underlying signal components and produce amplitude maps of each component. For validation of the component amplitude maps, the samples underwent immunohistochemical myelin staining. RESULTS: The signal component representing the myelin bilayer exhibited super-exponential decay with T2,min of 5.48 µs and a chemical shift of 1.07 ppm, and its amplitude could be successfully mapped in both white and gray matter in all samples. These myelin maps corresponded well to myelin-stained tissue sections. Gray matter signals exhibited somewhat different components than white matter signals, but both tissue types were well represented by the signal model. Frozen tissue storage did not alter the signal components but influenced component amplitudes. D2 O exchange was necessary to characterize the non-aqueous signal components, but component amplitude mapping could be reliably performed also in the presence of H2 O signals. CONCLUSIONS: The myelin mapping approach explored here produced reasonable and stable results for all samples. The extensive tissue and methodological investigations performed in this work form a basis for signal interpretation in future studies both ex vivo and in vivo.

Evaluating diffusion dispersion across an extended range of b-values and frequencies: Exploiting gap-filled OGSE shapes, strong gradients, and spiral readouts.

PURPOSE: To address the long echo times and relatively weak diffusion sensitization that typically limit oscillating gradient spin-echo (OGSE) experiments, an OGSE implementation combining spiral readouts, gap-filled oscillating gradient shapes providing stronger diffusion encoding, and a high-performance gradient system is developed here and utilized to investigate the tradeoff between b-value and maximum OGSE frequency in measurements of diffusion dispersion (i.e., the frequency dependence of diffusivity) in the in vivo human brain. In addition, to assess the effects of the marginal flow sensitivity introduced by these OGSE waveforms, flow-compensated variants are devised for experimental comparison. METHODS: Using DTI sequences, OGSE acquisitions were performed on three volunteers at b-values of 300, 500, and 1000 s/mm2 and frequencies up to 125, 100, and 75 Hz, respectively; scans were performed for gap-filled oscillating gradient shapes with and without flow sensitivity. Pulsed gradient spin-echo DTI acquisitions were also performed at each b-value. Upon reconstruction, mean diffusivity (MD) maps and maps of the diffusion dispersion rate were computed. RESULTS: The power law diffusion dispersion model was found to fit best to MD measurements acquired at b = 1000 s/mm2 despite the associated reduction of the spectral range; this observation was consistent with Monte Carlo simulations. Furthermore, diffusion dispersion rates without flow sensitivity were slightly higher than flow-sensitive measurements. CONCLUSION: The presented OGSE implementation provided an improved depiction of diffusion dispersion and demonstrated the advantages of measuring dispersion at higher b-values rather than higher frequencies within the regimes employed in this study.

High-resolution MRI of mummified tissues using advanced short-T2 methodology and hardware.

PURPOSE: Evolutionary medicine aims to study disease development from a long-term perspective, and through the analysis of mummified tissue, timescales of several thousand years are unlocked. Due to the status of mummies as ancient relics, noninvasive techniques are preferable, and, currently, CT imaging is the most widespread method. However, CT images lack soft-tissue contrast, making complementary MRI data desirable. Unfortunately, the dehydrated nature and short T2 times of mummified tissues render them practically invisible to standard MRI techniques. Specialized short-T2 approaches have therefore been used, but currently suffer severe resolution limitations. The purpose of the present study is to improve resolution in MRI of mummified tissues. METHODS: The zero-TE-based hybrid filling technique, together with a high-performance magnetic field gradient, was used to image three ancient Egyptian mummified human body parts: a hand, a foot, and a head. A similar pairing has already been shown to increase resolution and image quality in MRI of short-T2 tissues. RESULTS: MRI images of yet unparalleled image quality were obtained for all samples, reaching isotropic resolutions of 0.6 mm and SNR values above 100. The same general features as present in CT images were depicted but with different contrast, particularly for regions containing embalming substances. CONCLUSION: Mummy MRI is a potentially valuable tool for (paleo)pathological studies, as well as for investigations into ancient mummification processes. The results presented here show sufficient improvement in the depiction of mummified tissues to clear new paths for the exploration of this field.

Advances in MRI of the myelin bilayer.

Myelin plays a key role in the function of the central nervous system and is involved in many neurodegenerative diseases. Hence, depiction of myelin is desired for both research and diagnosis. However, MRI of the lipid bilayer constituting the myelin membrane is hampered by extremely rapid signal decay and cannot be accomplished with conventional sequences. Dedicated short-T2 techniques have therefore been employed, yet with extended sequence timings not well matched to the rapid transverse relaxation in the bilayer, which leads to signal loss and blurring. In the present work, capture and encoding of the ultra-short-T2 signals in the myelin bilayer is considerably improved by employing advanced short-T2 methodology and hardware, in particular a high-performance human-sized gradient insert. The approach is applied to tissue samples excised from porcine brain and in vivo in a human volunteer. It is found that the rapidly decaying non-aqueous components in the brain can indeed be depicted with MRI at useful resolution. As a considerable fraction of these signals is related to the myelin bilayer, the presented approach has strong potential to contribute to myelin research and diagnosis.

Highly efficient head-only magnetic field insert gradient coil for achieving simultaneous high gradient amplitude and slew rate at 3.0T (MAGNUS) for brain microstructure imaging.

PURPOSE: To develop a highly efficient magnetic field gradient coil for head imaging that achieves 200 mT/m and 500 T/m/s on each axis using a standard 1 MVA gradient driver in clinical whole-body 3.0T MR magnet. METHODS: A 42-cm inner diameter head-gradient used the available 89- to 91-cm warm bore space in a whole-body 3.0T magnet by increasing the radial separation between the primary and the shield coil windings to 18.6 cm. This required the removal of the standard whole-body gradient and radiofrequency coils. To achieve a coil efficiency ~4× that of whole-body gradients, a double-layer primary coil design with asymmetric x-y axes, and symmetric z-axis was used. The use of all-hollow conductor with direct fluid cooling of the gradient coil enabled ≥50 kW of total heat dissipation. RESULTS: This design achieved a coil efficiency of 0.32 mT/m/A, allowing 200 mT/m and 500 T/m/s for a 620 A/1500 V driver. The gradient coil yielded substantially reduced echo spacing, and minimum repetition time and echo time. In high b = 10,000 s/mm2 diffusion, echo time (TE) < 50 ms was achieved (>50% reduction compared with whole-body gradients). The gradient coil passed the American College of Radiology tests for gradient linearity and distortion, and met acoustic requirements for nonsignificant risk operation. CONCLUSIONS: Ultra-high gradient coil performance was achieved for head imaging without substantial increases in gradient driver power in a whole-body 3.0T magnet after removing the standard gradient coil. As such, any clinical whole-body 3.0T MR system could be upgraded with 3-4× improvement in gradient performance for brain imaging.