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 T$_{2}$ 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

Increased cerebral blood volume in small arterial vessels is a correlate of amyloid-β-related cognitive decline

The protracted accumulation of amyloid-β (Aβ) is a major pathologic hallmark of Alzheimer's disease and may trigger secondary pathological processes that include neurovascular damage. This study was aimed at investigating long-term effects of Aβ burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aβ burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years]. After 2 years, inflow-based vascular space occupancy at ultra-high field strength of 7-Tesla was administered for measuring CBVa, and neuropsychological testing for cognitive decline. Crushing gradients were incorporated during MR-imaging to suppress signals from fast-flowing blood in large arteries, and thereby sensitize inflow-based vascular space occupancy to CBVa in pial arteries and arterioles. CBVa was significantly elevated in MCI compared to cognitively normal controls and regional CBVa related to local Aβ deposition. For both MCI and controls, Aβ burden and follow-up CBVa in several brain regions synergistically predicted cognitive decline over 2 years. Orbitofrontal CBVa was positively associated with apolipoprotein E e4 carrier status. Increased CBVa may reflect long-term effects of region-specific pathology associated with Aβ deposition. Additional studies are needed to clarify the role of the arteriolar system and the potential of CBVa as a biomarker for Aβ-related vascular downstream pathology

BOLD PSF: Impact of k-space sampling on T2* contrast

The timing of BOLD-fMRI is typically chosen such that TE matches T2*. This assumes contrast being exclusively elicited by signal differences at TE. While sensible for short or TE-symmetric readouts, such as EPIs, it oversimplifies contrast generation for longer or TE-asymmetric trajectories, such as spirals. We propose the concept of a BOLD PSF for a more comprehensive perspective on the imaging characteristics of a functional experiment. Our findings indicate that TE can be reduced for spiral-out without sacrificing BOLD-sensitivity when compared to EPI. Furthermore, we characterize the intrinsic trade-off between specificity and resolution of the BOLD response under varying TE

Motion-compensated diffusion encoding in multi-shot human brain acquisitions: Insights using high-performance gradients

Purpose: To evaluate the utility of up to second-order motion-compensated diffusion encoding in multi-shot human brain acquisitions. Methods: Experiments were performed with high-performance gradients using three forms of diffusion encoding motion-compensated through different orders: conventional zeroth-order–compensated pulsed gradients (PG), first-order–compensated gradients (MC1), and second-order–compensated gradients (MC2). Single-shot acquisitions were conducted to correlate the order of motion compensation with resultant phase variability. Then, multi-shot acquisitions were performed at varying interleaving factors. Multi-shot images were reconstructed using three levels of shot-to-shot phase correction: no correction, channel-wise phase correction based on FID navigation, and correction based on explicit phase mapping (MUSE). Results: In single-shot acquisitions, MC2 diffusion encoding most effectively suppressed phase variability and sensitivity to brain pulsation, yielding residual variations of about 10° and of low spatial order. Consequently, multi-shot MC2 images were largely satisfactory without phase correction and consistently improved with the navigator correction, which yielded repeatable high-quality images; contrarily, PG and MC1 images were inadequately corrected using the navigator approach. With respect to MUSE reconstructions, the MC2 navigator-corrected images were in close agreement for a standard interleaving factor and considerably more reliable for higher interleaving factors, for which MUSE images were corrupted. Finally, owing to the advanced gradient hardware, the relative SNR penalty of motion-compensated diffusion sensitization was substantially more tolerable than that faced previously. Conclusion: Second-order motion-compensated diffusion encoding mitigates and simplifies shot-to-shot phase variability in the human brain, rendering the multi-shot acquisition strategy an effective means to circumvent limitations of retrospective phase correction methods.ISSN:0740-3194ISSN:1522-259

Mapping the myelin bilayer with short-T2_{2} MRI: Methods validation and reference data for healthy human brain

PURPOSE To explore the properties of short-T$_{2}$ 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 D$_{2}$ O exchange and frozen storage. Short-T$_{2}$ 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 T$_{2,min}$ 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. D$_{2}$ O exchange was necessary to characterize the non-aqueous signal components, but component amplitude mapping could be reliably performed also in the presence of H$_{2}$ 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

Probing neuronal activation by functional quantitative susceptibility mapping under a visual paradigm: A group level comparison with BOLD fMRI and PET

Dynamic changes of brain-tissue magnetic susceptibility provide the basis for functional MR imaging (fMRI) via T2*-weighted signal-intensity modulations. Promising initial work on a detection of neuronal activity via quantitative susceptibility mapping (fQSM) has been published but consistently reported on ill-understood positive and negative activation patterns (Balla et al., 2014; Chen and Calhoun, 2015a). We set out to (i) demonstrate that fQSM can exploit established fMRI data acquisition and processing methods and to (ii) better describe aspects of the apparent activation patterns using fMRI and PET as standards of reference. Under a standardized visual-stimulation paradigm PET and 3-T gradient-echo EPI-based fQSM, fMRI data from 9 healthy volunteers were acquired and analyzed by means of Independent Component Analysis (ICA) at subject level and, for the first time, at group level. Numbers of activated (z-score>2.0) voxels were counted and their mean z-scores calculated in volumes of interest (occipital lobe (Nocc_lobe), segmented occipital gray-matter (NGM_occ_lobe), large veins (Nveins)), and in occipital-lobe voxels commonly activated in fQSM and fMRI component maps. Common but not entirely congruent regions of apparent activation were found in the occipital lobe in z-score maps from all modalities, fQSM, fMRI and PET, with distinct BOLD-negatively correlated regions in fQSM data. At subject-level, Nocc_lobe, NGM_occ_lobe and their mean z-scores were significantly smaller in fQSM than in fMRI, but their ratio, NGM_occ_lobe/Nocc_lobe, was comparable. Nveins did not statistically differ and the ratio Nveins/NGM_occ_lobe as well as the mean z-scores were higher for fQSM than for fMRI. In veins and immediate vicinity, z-score maps derived from both phase and fQSM-data showed positive and negative lobes resembling dipole shapes in simulated field and phase maps with no correlate in fMRI or PET data. Our results show that standard fMRI tools can directly be used for fQSM processing, and suggest that fQSM may have the potential to detect gray-matter activation distant from large veins, to improve detection of veins with stimulus-induced venous oxygen saturation (SvO2) variations, and to better localize areas of activation. However, our results seem to clearly expose issues that phenomenologically resemble an incomplete dipolar inversion and that need to be subject to further investigation

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

A comprehensive approach for correcting voxel‐wise b‐value errors in diffusion MRI

PURPOSE: In diffusion MRI, the actual b-value played out on the scanner may deviate from the nominal value due to magnetic field imperfections. A simple image-based correction method for this problem is presented. METHODS: The apparent diffusion constant (ADC) of a water phantom was measured voxel-wise along 64 diffusion directions at b = 1000 s/mm2 . The true diffusion constant of water was estimated, considering the phantom temperature. A voxel-wise correction factor, providing an effective b-value including any magnetic field deviations, was determined for each diffusion direction by relating the measured ADC to the true diffusion constant. To test the method, the measured b-value map was used to calculate the corrected voxel-wise ADC for additionally acquired diffusion data sets on the same water phantom and data sets acquired on a small water phantom at three different positions. Diffusion tensor was estimated by applying the measured b-value map to phantom and in vivo data sets. RESULTS: The b-value-corrected ADC maps of the phantom showed the expected spatial uniformity as well as a marked improvement in consistency across diffusion directions. The b-value correction for the brain data resulted in a 5.8% and 5.5% decrease in mean diffusivity and angular differences of the primary diffusion direction of 2.71° and 0.73° inside gray and white matter, respectively. CONCLUSION: The actual b-value deviates significantly from its nominal setting, leading to a spatially variable error in the common diffusion outcome measures. The suggested method measures and corrects these artifacts