Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry.

In Parkinson's disease, the depletion of iron-rich dopaminergic neurons in nigrosome 1 of the substantia nigra precedes motor symptoms by two decades. Methods capable of monitoring this neuronal depletion, at an early disease stage, are needed for early diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue microstructure and in particular, to iron. However, the exact mechanisms of MRI contrast in the substantia nigra are not well understood, hindering the development of powerful biomarkers. In the present report, we illuminate the contrast mechanisms in gradient and spin echo MR images in human nigrosome 1 by combining quantitative 3D iron histology and biophysical modeling with quantitative MRI on post mortem human brain tissue. We show that the dominant contribution to the effective transverse relaxation rate (R2*) in nigrosome 1 originates from iron accumulated in the neuromelanin of dopaminergic neurons. This contribution is appropriately described by a static dephasing approximation of the MRI signal. We demonstrate that the R2* contribution from dopaminergic neurons reflects the product of cell density and cellular iron concentration. These results demonstrate that the in vivo monitoring of neuronal density and iron in nigrosome 1 may be feasible with MRI and provide directions for the development of biomarkers for an early detection of dopaminergic neuron depletion in Parkinson's disease.

hMRI - A toolbox for quantitative MRI in neuroscience and clinical research.

Neuroscience and clinical researchers are increasingly interested in quantitative magnetic resonance imaging (qMRI) due to its sensitivity to micro-structural properties of brain tissue such as axon, myelin, iron and water concentration. We introduce the hMRI-toolbox, an open-source, easy-to-use tool available on GitHub, for qMRI data handling and processing, presented together with a tutorial and example dataset. This toolbox allows the estimation of high-quality multi-parameter qMRI maps (longitudinal and effective transverse relaxation rates R1 and R2⋆, proton density PD and magnetisation transfer MT saturation) that can be used for quantitative parameter analysis and accurate delineation of subcortical brain structures. The qMRI maps generated by the toolbox are key input parameters for biophysical models designed to estimate tissue microstructure properties such as the MR g-ratio and to derive standard and novel MRI biomarkers. Thus, the current version of the toolbox is a first step towards in vivo histology using MRI (hMRI) and is being extended further in this direction. Embedded in the Statistical Parametric Mapping (SPM) framework, it benefits from the extensive range of established SPM tools for high-accuracy spatial registration and statistical inferences and can be readily combined with existing SPM toolboxes for estimating diffusion MRI parameter maps. From a user's perspective, the hMRI-toolbox is an efficient, robust and simple framework for investigating qMRI data in neuroscience and clinical research.

Cortical lamina-dependent blood volume changes in human brain at 7 T.

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans.

Anatomical brain imaging at 7T using two-dimensional GRASE.

PURPOSE: Specific absorption rate is a serious problem at high field strengths, especially for sequences involving many high power radiofrequency pulses, such as turbo spin echo (TSE). GRASE (gradient and spin echo) may overcome this problem by omitting a certain number of refocusing pulses of a TSE sequence, and replacing them with segmented echo-planar imaging readouts. METHODS: GRASE and TSE were compared using similar sequence parameters at a field strength of 7T. The signal-to-noise ratio (SNR) per unit time, contrast, and point spread function (PSF) were determined. High-resolution human brain images were acquired and the implementation of an inversion recovery preparation for T(1) weighting was evaluated. RESULTS: TSE and GRASE images at 7T showed very similar SNR and contrast. The slightly worse PSF for GRASE is balanced by a significant reduction in scan time or increase in spatial coverage compared with TSE. Furthermore, implementing an additional inversion recovery preparation enables the acquisition of T(1)-weighted images with high SNR per unit time. CONCLUSION: GRASE is highly suitable for structural scanning at ultra-high field strengths and is a valid alternative to the commonly used TSE sequence.

Fast accurate MR thermometry using phase referenced asymmetric spin-echo EPI at high field.

PURPOSE: A novel highly accurate method for MR thermometry, effective at high field, is introduced and validated, which corrects for slow and fast field fluctuations by means of reference images. METHODS: An asymmetric spin-echo echo planar imaging sequence was made frequency-selective to water or a reference substance by controlling the slice-select gradient polarity and the duration of the excitation and refocusing radiofrequency pulses. Images were acquired pairwise, and the temperature-sensitive water images were corrected for field fluctuations using the reference images. In a phantom radiofrequency heating experiment, dissolved dimethyl sulfoxide was used as a reference substance. Temperature stability was tested in vivo on the human brain, referenced using subcutaneous scalp fat. Water and fat phase images were acquired only 50 ms apart. Bloch simulations validated the frequency selection accuracy. RESULTS: Asymmetric spin-echo imaging using a simple frequency selection method provides highly accurate referenced MR thermometry in phantoms and in vivo at 7 T. Effects of field fluctuations caused by field drift, breathing, and heart beat were corrected. The technique is highly robust against B1 inhomogeneities. CONCLUSION: Frequency selection using gradient-reversal can enable fast accurate referenced in vivo MR thermometry, assisting thermal characterization of radiofrequency coils and possibly in vivo SAR monitoring.

Effects of air susceptibility on proton resonance frequency MR thermometry.

OBJECT: The temperature dependence of the proton resonance frequency (PRF) is often used in MR thermometry. However, this method is prone to even very small changes in local magnetic field strength. Here, we report on the effects of susceptibility changes of surrounding air on the magnetic field inside an object and their inferred effect on the measured MR temperature. MATERIALS AND METHODS: MR phase thermometry was performed on spherical agar phantoms enclosed in cylindrical containers at 7 T. The air susceptibility inside the cylindrical container was changed by both heating the air and changing the gas composition. RESULTS: Changing the temperature of surrounding air from 23 to 69°C caused an apparent MR temperature error of 2 K. When ambient air was displaced by 100% oxygen, the MR temperature error increased to 40 K. The magnetic field shift and therefore error in inferred MR temperature scales linearly with volume susceptibility change and has a strong and nontrivial dependence on the experimental configuration. CONCLUSION: Air susceptibility changes associated with oxygen concentration changes greatly affect PRF MR thermometry measurements. Air temperature changes can also affect these measurements, but to a smaller degree. For uncalibrated MR thermometry, air susceptibility changes may be a significant source of error.

An embedded optical tracking system for motion-corrected magnetic resonance imaging at 7T.

OBJECT: Prospective motion correction using data from optical tracking systems has been previously shown to reduce motion artifacts in MR imaging of the head. We evaluate a novel optical embedded tracking system. MATERIALS AND METHODS: The home-built optical embedded tracking system performs image processing within a 7 T scanner bore, enabling high speed tracking. Corrected and uncorrected in vivo MR volumes are acquired interleaved using a modified 3D FLASH sequence, and their image quality is assessed and compared. RESULTS: The latency between motion and correction of the slice position was measured to be (19 ± 5) ms, and the tracking noise has a standard deviation no greater than 10 µm/0.005° during conventional MR scanning. Prospective motion correction improved the edge strength by 16 % on average, even though the volunteers were asked to remain motionless during the acquisitions. CONCLUSION: Using a novel method for validating the effectiveness of in vivo prospective motion correction, we have demonstrated that prospective motion correction using motion data from the embedded tracking system considerably improved image quality.

Parcellation of human amygdala in vivo using ultra high field structural MRI.

Histological studies show that human amygdala is subdivided into several nuclei with specific connections to other brain areas. One such study has been recently used as the basis of a probabilistic amygdala map, to enable in vivo identification of specifically located functions within the amygdala and connections to it. The involvement of the amygdala in cognition, emotion and action, which may underlie several psychiatric disorders, points to a need for discrimination of these nuclei in living human brains using different techniques. Structural MRI scans of the human amygdala at standard field strengths (≤3 T) have shown a region of generally featureless gray matter. Apparently homogeneous regions may reveal internal structure, however, when improved imaging strategies and better SNR are available. The goal of this study is the in vivo anatomical segmentation of the amygdala using high resolution structural MR data. The use of different MRI tissue contrast mechanisms at high field strengths has been little explored so far. Combining two different contrasts, and using cutting-edge image analysis, the following study provides a robust clustering of three amygdala components in vivo using 7 T structural imaging.

Diffusion tensor imaging segments the human amygdala in vivo.

The amygdala plays an important role in emotion, learning, and memory. It would be highly advantageous to understand more precisely its internal structure and connectivity for individual human subjects in vivo. Earlier cytoarchitectural research in post-mortem human and animal brains has revealed multiple subdivisions and connectivity patterns, probably related to different functions. With standard magnetic resonance imaging (MRI) techniques, however, the amygdala appears as an undifferentiated area of grey matter. Using high-quality diffusion tensor imaging (DTI) at 3 Tesla, we show diffusion anisotropy in this grey matter area. Such data allowed us to subdivide the amygdala for the first time in vivo. In 15 living subjects, we applied a spectral clustering algorithm to the principal diffusion direction in each amygdala voxel and found a consistent subdivision of the amygdala into a medial and a lateral region. The topography of these regions is in good agreement with the fibre architecture visible in myelin-stained sections through the amygdala of a human post-mortem brain. From these in vivo results we derived a probabilistic map of amygdalar fibre orientations. This segmentation technique has important implications for functional studies in the processing of emotions, cognitive function, and psychiatric disorders and in studying morphometry and volumetry of amygdala subdivisions.

Example dataset for the hMRI toolbox.

The hMRI toolbox is an open-source toolbox for the calculation of quantitative MRI parameter maps from a series of weighted imaging data, and optionally additional calibration data. The multi-parameter mapping (MPM) protocol, incorporating calibration data to correct for spatial variation in the scanner's transmit and receive fields, is the most complete protocol that can be handled by the toolbox. Here we present a dataset acquired with such a full MPM protocol, which is made freely available to be used as a tutorial by following instructions provided on the associated toolbox wiki pages, which can be found at http://hMRI.info, and following the theory described in: hMRI - A toolbox for quantitative MRI in neuroscience and clinical research [1].

Blame it on the bossa nova: Transfer of perceived sexiness from music to touch.

Emotion elicited through music transfers to subsequent processing of facial expressions. Music may accordingly function as a social technology by promoting social bonding. Here, we investigated whether music would cross-modally influence the perception of sensual touch, a behavior related to mating. A robot applied precisely controlled gentle touch to a group of healthy participants while they listened to music that varied with respect to its perceived sexiness. As the perceived sexiness of the music increased, so did the subjective sexiness of the touch stimulations. In short, the perception of sexiness transferred from music to touch. Because sensual touch is key to mating behavior and relates to procreation, this association has implications for the universality and evolutionary significance of music. (PsycINFO Database Record