A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene.

Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) was significantly (P=7 × 10(-8)) associated with verbal memory performance in a cognitively healthy cohort from Switzerland (n=1073) and was replicated in a second cohort from Serbia (n=524; P=0.003). Gene expression studies showed CTNNBL1 genotype-dependent differences in beta-catenin-like protein 1 mRNA levels in the human cortex. Functional magnetic resonance imaging in 322 subjects detected CTNNBL1 genotype-dependent differences in memory-related brain activations. Converging evidence from independent experiments and different methodological approaches suggests a role for CTNNBL1 in human memory.

Feasibility of in vivo myelin water imaging using 3D multigradient-echo pulse sequences.

Quantitative myelin water imaging is able to show demyelinating processes and, therefore, provides insight into the pathology of white matter diseases such as multiple sclerosis. So far, mapping of the myelin water fraction most often was performed using single-slice multiecho spin-echo sequences. Recently, a different approach using two-dimensional multigradient-echo pulse sequences was suggested. In this work, a solution to three-dimensional in vivo myelin water fraction imaging is presented that applies multigradient-echo pulse sequences and uses non-negative least squares algorithms to analyze the multicomponent T*(2) decay. The suggested method offers not only whole brain coverage but also clinically practicable acquisition times. The obtained myelin water fraction values are low (6.9% for white matter) but are able to detect demyelination in multiple sclerosis lesions. However, the clinical application of the proposed method remains questionable, because further measurements that clarify the possibility of detecting ongoing processes in lesions are needed.

The Restless Spinal Cord in Degenerative Cervical Myelopathy.

BACKGROUND AND PURPOSE: The spinal cord is subject to a periodic, cardiac-related movement, which is increased at the level of a cervical stenosis. Increased oscillations may exert mechanical stress on spinal cord tissue causing intramedullary damage. Motion analysis thus holds promise as a biomarker related to disease progression in degenerative cervical myelopathy. Our aim was characterization of the cervical spinal cord motion in patients with degenerative cervical myelopathy. MATERIALS AND METHODS: Phase-contrast MR imaging data were analyzed in 55 patients (37 men; mean age, 56.2 [SD,12.0] years; 36 multisegmental stenoses) and 18 controls (9 men, P = .368; mean age, 62.2 [SD, 6.5] years; P = .024). Parameters of interest included the displacement and motion pattern. Motion data were pooled on the segmental level for comparison between groups. RESULTS: In patients, mean craniocaudal oscillations were increased manifold at any level of a cervical stenosis (eg, C5 displacement: controls [n = 18], 0.54 [SD, 0.16] mm; patients [n = 29], monosegmental stenosis [n = 10], 1.86 [SD, 0.92] mm; P < .001) and even in segments remote from the level of the stenosis (eg, C2 displacement: controls [n = 18], 0.36 [SD, 0.09] mm; patients [n = 52]; stenosis: C3, n = 21; C4, n = 11; C5, n = 18; C6, n = 2; 0.85 [SD, 0.46] mm; P < .001). Motion at C2 differed with the distance to the next stenotic segment and the number of stenotic segments. The motion pattern in most patients showed continuous spinal cord motion throughout the cardiac cycle. CONCLUSIONS: Patients with degenerative cervical myelopathy show altered spinal cord motion with increased and ongoing oscillations at and also beyond the focal level of stenosis. Phase-contrast MR imaging has promise as a biomarker to reveal mechanical stress to the cord and may be applicable to predict disease progression and the impact of surgical interventions.

Limitations of rapid myelin water quantification using 3D bSSFP.

OBJECT: Imaging of the myelin water fraction (MWF) is conventionally performed using a multi-echo spin-echo sequence. This technique requires long acquisition times and therefore often suffers from a lack of volume coverage. In this work, the application of 3D balanced steady-state free precession (bSSFP) sequences to extract high-resolution myelin water maps is discussed. MATERIALS AND METHODS: Based on a two-pool water exchange model, an approximate bSSFP signal equation is derived and applied to fit the flip angle dependence of the in vivo bSSFP signal. Thereby, the MWF and signal amplitude are fitted, while a priori assumptions are made for the other parameters of the two-pool system. RESULTS: The effects of magnetization transfer, finite RF pulses, B (0) and B (1) inhomogeneities, as well as variation of the constant fit parameters, are investigated. Acquisition and calculation of quantitative, high-resolution MWF maps from white matter of healthy volunteers based on bSSFP is feasible and averaged MWF fit results agree with literature. However, results from numerical simulations indicate a severe dependence of the derived MWF values on the constant two-pool parameters. CONCLUSION: The demonstrated dependence of the MWF on the two-pool parameters considerably impairs the applicability of the proposed method.

Functional MRI of the human motor cortex using single-shot, multiple gradient-echo spiral imaging.

In this study, we combined the advantages of a fast multi-slice spiral imaging approach with a multiple gradient-echo sampling scheme at high magnetic field strength to improve quantification of BOLD and inflow effects and to estimate T2* relaxation times in functional brain imaging. Eight echoes are collected with echo time (TE) ranging from 5 to 180 ms. Acquisition time per slice and echo time is 25 ms for a nominal resolution of 4 x 4 x 4 mm3. Evaluation of parameter images during rest and stimulation yields no significant activation on the inflow sensitive spin-density images (rho or I0-maps) whereas clear activation patterns in primary human motor cortex (M1) and supplementary motor area (SMA) are detected on BOLD sensitive T2*-maps. The calculation of relaxation times and rates of the activated areas over all subjects yields an average T2* +/- standard deviation (SD) of 46.1+/-4.5 ms (R2* of 21.8+/-2.2 s(-1)) and an average increase (deltaT2* +/- SD) of 0.93+/-0.47 ms (deltaR2* of -0.4+/-0.14 s(-1)). Our findings demonstrate the usefulness of a multiple gradient echo data acquisition approach in separating various vascular contributions to brain activation in fMRI.

In vivo magnetic resonance micro-imaging of the human toe at 3 Tesla.

The feasibility of in vivo high-resolution magnetic resonance micro-imaging of fine anatomic structures of human toes was tested. Five healthy subjects were investigated on an experimental 3 Tesla whole body scanner, using standard 3D gradient echo sequences. A radio-frequency surface coil was used for signal detection. Feet, toes and surface coil were comfortably fixed using a home built device for positioning and reduction of motion artifacts. The spatial resolution of 117 x 313 x 375 microm(3) allowed detailed visualization of anatomic structures like skin layers, vessels and nerves. In addition, oval structures with diameters ranging from 500 to 1000 microm were observed in all subjects, which could represent the sensory nerve endings of Vater-Pacinian bodies. Thus, high resolution MR micro-imaging at 3 Tesla may provide improved morphologic information in distal extremities of humans in vivo.

Characterization of BOLD activation in multi-echo fMRI data using fuzzy cluster analysis and a comparison with quantitative modeling.

A combination of multiple gradient-echo imaging and exploratory data analysis (EDA), i.e. fuzzy cluster analysis (FCA), is proposed for separation and characterization of BOLD activation in single-shot spiral functional magnetic resonance imaging (fMRI) experiments at 3 T. Differentiation of functional activation using FCA is performed by clustering pixel signal changes (DeltaS) as a function of echo time (TE). Further vascular classification is supported by the localization of activation and the comparison with a single-exponential decay model. In some subjects, an additional indication for large vessels within a voxel was found as oscillation of the fMRI signal difference vs echo time (TE). Such large vessels may be separated from small vessel activation and, therefore, our proposed procedure might prove useful if a more specific functional localization is desired in fMRI. In addition to the signal change DeltaS, DeltaT(2)*/T(2)* is significantly different between activated regions. Averaged over all eight subjects DeltaT(2)* is 1.7 +/- 0.2 ms in ROIs with the highest signal change characterized as containing large vessels, whereas in ROIs corresponding to microvascular environment average DeltaT(2)* values are 0.8 +/- 0.1 ms.

High-resolution blood flow velocity measurements in the human finger.

MR phase contrast blood flow velocity measurements in the human index finger were performed with triggered, nontriggered, and cine acquisition schemes. A strong (G(max) = 200 mT/m), small bore (inner diameter 12 cm) gradient system inserted in a whole body 3 Tesla MR scanner allowed high-resolution imaging at short echo times, which decreases partial volume effects and flow artifacts. Arterial blood flow velocities ranging from 4.9-19 cm/sec were measured, while venous blood flow was significantly slower at 1.5-7.1 cm/sec. Taking into account the corresponding vessel diameters ranging from 800 microm to 1.8 mm, blood flow rates of 3.0-26 ml/min in arteries and 1.2-4.8 ml/min in veins are obtained. The results were compared to ultrasound measurements, resulting in comparable blood flow velocities in the same subjects. Magn Reson Med 45:716-719, 2001.

High-resolution MR venography at 3.0 Tesla.

PURPOSE: The aim of this study was to investigate the visualization of small venous vessels in the normal human brain at a field strength of 3 Tesla. METHODS: T2*-weighted, three-dimensional gradient-echo images were acquired by exploiting the magnetic susceptibility difference between oxygenated and deoxygenated hemoglobin in the vasculature and microvasculature. The spatial resolution was 0.5 x 0.5 x 1 mm3, and sequence parameters were varied to obtain good vessel delineation. Improved visibility of venous vessels was obtained by creating phase mask images from the magnetic resonance phase images and multiplying these by the magnitude images. Venograms were created by performing a minimum intensity projection over targeted volumes. RESULTS: Highly detailed visualization of venous structures deep in the brain and in the superficial cortical areas were obtained without administration of an exogenous contrast agent; compared with similar studies performed at 1.5 T, the echo time could be reduced from typically 40-50 ms to 17-28 ms. CONCLUSION: Imaging at high-field strength offers the possibility of improved resolution and the delineation of smaller vessels compared with lower field strengths.