Improving T2*-weighted human cortico-spinal acquisitions with a dedicated algorithm for region-wise shimming.

Cortico-spinal fMRI acquisitions aim to investigate direct interactions between brain and spinal cord, e.g. during motor output or pain processing, by covering both regions in a single measurement. Due to their large distance and location in the body, a dynamic shim update of constant and linear shim terms is required when using echo-planar imaging (EPI) to achieve reasonable image quality in both target regions. A previously presented approach with region-wise shim settings is based on a standard single-region shim algorithm and suffers from (i) non-optimal shim settings because it combines linear and second-order shim terms optimized for different volumes, and (ii) significant user interactions making it rather cumbersome, time consuming, and error-prone. Here, a dedicated ("CoSpi") shim algorithm for cortico-spinal fMRI is presented that performs joint optimization of static second-order shim terms and one set of linear and constant shim terms for each region in a single run and with minimal user interaction. Field map and T2*-weighted EPI measurements were performed on a clinical 3 T whole-body MR system in water phantoms and five healthy volunteers using the conventional region-wise and CoSpi shim settings as well as "gold standard" shim settings optimized for one of the target regions only. With CoSpi shim settings, (i) overall field inhomogeneity was reduced by about 65% / 75% (brain / spinal cord volume) compared to the conventional region-wise approach and in vivo was within 5% of the values obtained with the single-volume shim settings, (ii) geometric distortions derived from voxel displacement maps were reduced on average by about 35% / 70%, (iii) the temporal SNR determined from an EPI time series that may reflect the impact of through-slice dephasing, was increased by about 17% / 10%, and (iv) the variation of the mean field between slices, a measure targeting the predisposition to insufficient fat saturation and GRAPPA-related ghosting artifacts, was reduced by about 90% / 45%. Thus, the presented algorithm not only speeds up and simplifies the shim procedure considerably, but also provides a better field homogeneity and image quality, which both could help to significantly improve the applicability of cortico-spinal fMRI.

Reliability of resting-state functional connectivity in the human spinal cord: Assessing the impact of distinct noise sources.

The investigation of spontaneous fluctuations of the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord, where it has stimulated interest from a clinical perspective. A number of resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated robust functional connectivity between the time series of BOLD fluctuations in bilateral dorsal horns and between those in bilateral ventral horns, in line with the functional neuroanatomy of the spinal cord. A necessary step prior to extension to clinical studies is assessing the reliability of such resting-state signals, which we aimed to do here in a group of 45 healthy young adults at the clinically prevalent field strength of 3T. When investigating connectivity in the entire cervical spinal cord, we observed fair to good reliability for dorsal-dorsal and ventral-ventral connectivity, whereas reliability was poor for within- and between-hemicord dorsal-ventral connectivity. Considering how prone spinal cord fMRI is to noise, we extensively investigated the impact of distinct noise sources and made two crucial observations: removal of physiological noise led to a reduction in functional connectivity strength and reliability - due to the removal of stable and participant-specific noise patterns - whereas removal of thermal noise considerably increased the detectability of functional connectivity without a clear influence on reliability. Finally, we also assessed connectivity within spinal cord segments and observed that while the pattern of connectivity was similar to that of whole cervical cord, reliability at the level of single segments was consistently poor. Taken together, our results demonstrate the presence of reliable resting-state functional connectivity in the human spinal cord even after thoroughly accounting for physiological and thermal noise, but at the same time urge caution if focal changes in connectivity (e.g. due to segmental lesions) are to be studied, especially in a longitudinal manner.

Association between activity in the ventral premotor cortex and spinal cord activation during force generation-A combined cortico-spinal fMRI study.

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is associated with the activity in the cerebral primary motor and premotor areas is poorly understood. Here, we conducted combined cortico-spinal functional magnetic resonance imaging during a simple visually guided isometric force generation task in 20 healthy young subjects. Activation was localized in the right cervical spinal cord and left primary motor and premotor areas. The main finding is that spinal activation was negatively correlated with ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation, while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding that extends our understanding of human motor function beyond the animal literature.

Simultaneous multislice imaging with slice-specific z-shim.

PURPOSE: To implement slice-specific z-shim in simultaneous multislice (SMS) imaging in order to minimize signal losses in slice-accelerated T2 *-weighted acquisitions, such as for spinal cord functional neuroimaging. METHODS: The RF envelopes of the individual slice bands are temporally shifted on the plateau of the slice-selection gradient pulse before being combined to the multiband RF envelope. Thus, optimum z-shims can be realized for each slice of an SMS excitation, which is in contrast to conventional z-shimming. EPI with 2-fold SMS acceleration was performed on a 3T whole-body MR system in phantoms and the cervical spinal cord of healthy volunteers (i) without z-shim, (ii) with conventional z-shim using the average value of the slices of the SMS excitation, and (iii) with optimal, slice-specific z-shims for each slice using envelope shifts. RESULTS: Phantom experiments demonstrate the equivalence of the envelope shift and conventional z-shimming for non-SMS excitations. With SMS, the best image quality is obtained with "mixed" z-shim, where only the z-shim differences of the slices of an SMS excitation are implemented by an envelope shift while their mean z-shim is applied conventionally with a gradient pulse after the echoes acquired for N/2 ghost correction. In phantoms and in vivo, this setup outperforms the approaches without slice-specific z-shim with respect to signal amplitude and temporal SNR at the expense of slight TE differences (<1 ms) between the slices. CONCLUSION: With RF envelope shifts, slice-specific z-shims can be combined with SMS imaging, which could improve slice-accelerated functional neuroimaging in the spinal cord.

Resting-state brain and spinal cord networks in humans are functionally integrated.

In the absence of any task, both the brain and spinal cord exhibit spontaneous intrinsic activity organised in a set of functionally relevant neural networks. However, whether such resting-state networks (RSNs) are interconnected across the brain and spinal cord is unclear. Here, we used a unique scanning protocol to acquire functional images of both brain and cervical spinal cord (CSC) simultaneously and examined their spatiotemporal correspondence in humans. We show that the brain and spinal cord activities are strongly correlated during rest periods, and specific spinal cord regions are functionally linked to consistently reported brain sensorimotor RSNs. The functional organisation of these networks follows well-established anatomical principles, including the contralateral correspondence between the spinal hemicords and brain hemispheres as well as sensory versus motor segregation of neural pathways along the brain-spinal cord axis. Thus, our findings reveal a unified functional organisation of sensorimotor networks in the entire central nervous system (CNS) at rest.

Brain-spinal cord interaction in long-term motor sequence learning in human: An fMRI study.

The spinal cord is important for sensory guidance and execution of skilled movements. Yet its role in human motor learning is not well understood. Despite evidence revealing an active involvement of spinal circuits in the early phase of motor learning, whether long-term learning engages similar changes in spinal cord activation and functional connectivity remains unknown. Here, we investigated spinal-cerebral functional plasticity associated with learning of a specific sequence of visually-guided joystick movements (sequence task) over six days of training. On the first and last training days, we acquired high-resolution functional images of the brain and cervical cord simultaneously, while participants practiced the sequence or a random task while electromyography was recorded from wrist muscles. After six days of training, the subjects' motor performance improved in the sequence compared to the control condition. These behavioral changes were associated with decreased co-contractions and increased reciprocal activations between antagonist wrist muscles. Importantly, early learning was characterized by activation in the C8 level, whereas a more rostral activation in the C6-C7 was found during the later learning phase. Motor sequence learning was also supported by increased spinal cord functional connectivity with distinct brain networks, including the motor cortex, superior parietal lobule, and the cerebellum at the early stage, and the angular gyrus and cerebellum at a later stage of learning. Our results suggest that the early vs. late shift in spinal activation from caudal to rostral cervical segments synchronized with distinct brain networks, including parietal and cerebellar regions, is related to progressive changes reflecting the increasing fine control of wrist muscles during motor sequence learning.

Automated slice-specific z-shimming for functional magnetic resonance imaging of the human spinal cord.

Functional magnetic resonance imaging (fMRI) of the human spinal cord faces many challenges, such as signal loss due to local magnetic field inhomogeneities. This issue can be addressed with slice-specific z-shimming, which compensates for the dephasing effect of the inhomogeneities using a slice-specific gradient pulse. Here, we aim to address outstanding issues regarding this technique by evaluating its effects on several aspects that are directly relevant for spinal fMRI and by developing two automated procedures in order to improve upon the time-consuming and subjective nature of manual selection of z-shims: one procedure finds the z-shim that maximizes signal intensity in each slice of an EPI reference-scan and the other finds the through-slice field inhomogeneity for each EPI-slice in field map data and calculates the required compensation gradient moment. We demonstrate that the beneficial effects of z-shimming are apparent across different echo times, hold true for both the dorsal and ventral horn, and are also apparent in the temporal signal-to-noise ratio (tSNR) of EPI time-series data. Both of our automated approaches were faster than the manual approach, lead to significant improvements in gray matter tSNR compared to no z-shimming and resulted in beneficial effects that were stable across time. While the field-map-based approach performed slightly worse than the manual approach, the EPI-based approach performed as well as the manual one and was furthermore validated on an external corticospinal data-set (N > 100). Together, automated z-shimming may improve the data quality of future spinal fMRI studies and lead to increased reproducibility in longitudinal studies.

DTI of chronic spinal cord injury in children without MRI abnormalities (SCIWOMR) and with pathology on MRI and comparison to severity of motor impairment.

STUDY DESIGN: This investigation was a cohort study that included: 36 typically developing (TD) children and 19 children with spinal cord lesions who underwent spinal cord MRI. OBJECTIVES: To investigate diffusion tensor imaging (DTI) cervical and thoracic spinal cord changes in pediatric patients that have clinically traumatic and non-traumatic spinal cord injury (SCI) without MR (SCIWOMR) abnormalities. SETTING: Thomas Jefferson University, Temple University, Shriners Hospitals for Children all in Philadelphia, USA. METHODS: 36 TD children and 19 children with spinal cord lesions that represent either a chronic traumatic acquired SCI or chronic non-traumatic SCI (≥6 months post injury), age range, 6-16 years who underwent cervical and thoracic spinal cord MRI in 2014-2017. Additionally DTI was correlated to clinical American Spinal Injury Association Impairment Scale (AIS). RESULTS: Both SCIWOMR and MRI positive (+) groups showed abnormal FA and RD DTI values in the adjacent MRI-normal appearing segments of cephalad and caudal spinal cord compared to TD. The FA values demonstrated perilesional abnormal DTI findings in the middle and proximal segments of the cephalad and caudal cord in the SCIWOMR AIS A/B group compared to SCIWOMR AIS C/D group. CONCLUSIONS: We found DTI changes in children with SCIWOMR with different causes of spinal lesions. We also investigated the relationship between DTI and clinical AIS scores. This study further examined the potential diagnostic value of DTI and should be translatable to adults with spinal cord lesions.

Detection of microscopic diffusion anisotropy in human cortical gray matter in vivo with double diffusion encoding.

PURPOSE: To detect microscopic diffusion anisotropy in human cortical gray matter in vivo with double diffusion encoding experiments. METHODS: Double diffusion encoding experiments were performed on a 3 T whole-body MR system using echo-planar imaging. Angular double diffusion encoding measurements were acquired with 8 × 8 and 12 × 12 planar direction combinations and were analyzed in three regions of interest containing white matter, mostly cortical gray matter, and one having significant contributions from cerebrospinal fluid. Inversion with variable recovery times served to estimate and eliminate white matter partial volume effects. To investigate the influence of magnetic field inhomogeneities, experiments with gradient offsets and cross-term compensated diffusion weightings were performed. The MA index, a rotationally invariant measure of the microscopic diffusion anisotropy, was determined from measurements with 96 direction combinations. RESULTS: The angular signal modulation in the gray matter region of interest has two components, one being consistent, inter alia, with cross terms with field inhomogeneities while the other represents a signal difference between parallel/antiparallel and orthogonal direction combinations, ie, the fingerprint of microscopic diffusion anisotropy. Based on the amplitudes and their dependency on the inversion time, white matter partial volumes can be excluded as the sole source for this modulation, providing strong evidence for the detection of microscopic diffusion anisotropy in cortical gray matter. MA maps of healthy volunteers show considerably lower values in cortical gray matter compared with white matter. CONCLUSION: Microscopic diffusion anisotropy can be measured in human cortical brain matter, which could help to characterize the microstructure of healthy and pathological tissue.

Investigating resting-state functional connectivity in the cervical spinal cord at 3T.

The study of spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord. Two ultra-high field functional magnetic resonance imaging (fMRI) studies in humans have provided evidence for reproducible resting-state connectivity between the dorsal horns as well as between the ventral horns, and a study in non-human primates has shown that these resting-state signals are impacted by spinal cord injury. As these studies were carried out at ultra-high field strengths using region-of-interest (ROI) based analyses, we investigated whether such resting-state signals could also be observed at the clinically more prevalent field strength of 3T. In a reanalysis of a sample of 20 healthy human participants who underwent a resting-state fMRI acquisition of the cervical spinal cord, we were able to observe significant dorsal horn connectivity as well as ventral horn connectivity, but no consistent effects for connectivity between dorsal and ventral horns, thus replicating the human 7T results. These effects were not only observable when averaging along the acquired length of the spinal cord, but also when we examined each of the acquired spinal segments separately, which showed similar patterns of connectivity. Finally, we investigated the robustness of these resting-state signals against variations in the analysis pipeline by varying the type of ROI creation, temporal filtering, nuisance regression and connectivity metric. We observed that - apart from the effects of band-pass filtering - ventral horn connectivity showed excellent robustness, whereas dorsal horn connectivity showed moderate robustness. Together, our results provide evidence that spinal cord resting-state connectivity is a robust and spatially consistent phenomenon that could be a valuable tool for investigating the effects of pathology, disease progression, and treatment response in neurological conditions with a spinal component, such as spinal cord injury.

Combining rheology and MRI: Imaging healthy and tumorous brains based on mechanical properties.

PURPOSE: It is well known that pathological changes in tissue alter its mechanical properties. This holds also true for brain tissue. In case of the brain, however, obtaining information about these properties is hard due to the surrounding cranial bone. In this paper a novel technique to create an imaging contrast based on the aforementioned properties is presented. METHODS: The method is based on an excitation of the brain induced by a short fall. The response of the brain tissue is measured using a motion sensitive MRI sequence. RESULTS: The new method is tested by measurements on phantom material as well as on healthy volunteers. In a proof of principle experiment the capability of the approach to identify local alterations in the mechanical properties is shown by means of measurements on meningioma patients. CONCLUSION: The presented results show the feasibility of the novel method. Even in this early state of the proposed method, comparisons of measurements on meningioma patients with intraoperative palpation suggest that meningioma tissue responds differently to the excitation depending on their mechanical properties. Magn Reson Med 78:930-940, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Intrinsically organized resting state networks in the human spinal cord.

Spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signals of the brain have repeatedly been observed when no task or external stimulation is present. These fluctuations likely reflect baseline neuronal activity of the brain and correspond to functionally relevant resting-state networks (RSN). It is not known however, whether intrinsically organized and spatially circumscribed RSNs also exist in the spinal cord, the brain's principal sensorimotor interface with the body. Here, we use recent advances in spinal fMRI methodology and independent component analysis to answer this question in healthy human volunteers. We identified spatially distinct RSNs in the human spinal cord that were clearly separated into dorsal and ventral components, mirroring the functional neuroanatomy of the spinal cord and likely reflecting sensory and motor processing. Interestingly, dorsal (sensory) RSNs were separated into right and left components, presumably related to ongoing hemibody processing of somatosensory information, whereas ventral (motor) RSNs were bilateral, possibly related to commissural interneuronal networks involved in central pattern generation. Importantly, all of these RSNs showed a restricted spatial extent along the spinal cord and likely conform to the spinal cord's functionally relevant segmental organization. Although the spatial and temporal properties of the dorsal and ventral RSNs were found to be significantly different, these networks showed significant interactions with each other at the segmental level. Together, our data demonstrate that intrinsically highly organized resting-state fluctuations exist in the human spinal cord and are thus a hallmark of the entire central nervous system.

Spinal cord-midbrain functional connectivity is related to perceived pain intensity: a combined spino-cortical FMRI study.

The dynamic interaction between ascending spinocortical nociceptive signaling and the descending control of the dorsal horn (DH) by brain regions such as the periaqueductal gray matter (PAG) plays a critical role in acute and chronic pain. To noninvasively investigate the processing of nociceptive stimuli in humans, previous fMRI studies either focused exclusively on the brain or, more recently, on the spinal cord. However, to relate neuronal responses in the brain to responses in the spinal cord and to assess the functional interplay between both sites in normal and aberrant conditions, fMRI of both regions within one experiment is necessary. Employing a new MRI acquisition protocol with two separate slice stacks, individually adapted resolutions and parameter settings that are dynamically updated to the optimized settings for the respective region we assessed neuronal activity in the spinal cord and in the brain within one measurement at 3 T. Using a parametric pain paradigm with thermal stimulation to the left radial forearm, we observed BOLD responses in the ipsilateral DH of the spinal segment C6 and corresponding neuronal responses in typical pain-processing brain regions. Based on correlations of adjusted time series, we are able to reveal functional connectivity between the spinal C6-DH and the thalamus, primary somatosensory cortex, bilateral insula, bilateral striatum, and key structures of the descending pain-modulatory system such as the PAG, the hypothalamus, and the amygdala. Importantly, the individual strength of the spinal-PAG coupling predicted individual pain ratings highlighting the functional relevance of this system during physiological pain signaling.

Microscopic diffusion anisotropy in the human brain: Age-related changes.

The fractional anisotropy (FA) that can be derived from diffusion tensor imaging (DTI), is ambiguous because it not only depends on the tissue microstructure but also on the axon or fiber orientation distribution within a voxel. Measures of the microscopic diffusion anisotropy, like the microscopic anisotropy index (MA) that can be determined with so-called double-wave-vector (DWV) or double diffusion encoding (DDE) imaging, are independent of this orientation distribution and, thus, offer a more direct and undisguised access to the tissue structure on a cellular or microscopic scale. In this study, FA and MA measurements were performed in a group of aged (>60y), healthy volunteers and compared to the data obtained recently for a group of young (<33y), healthy volunteers to reveal age-related differences. The coefficients-of-variation (CV) determined for the aged group were considerably lower for MA than for FA in average and in most of the 16 ROIs analyzed due to lower between-subject variations of MA. FA differences between the young and the aged group were in line with previous DTI studies. MA was also decreased in the aged group but in more of the 16 ROIs and with a higher significance. Furthermore, MA differences were also observed in frontal brain regions containing fiber crossings that did not reveal significant FA differences, i.e. MA seems to provide a better sensitivity to detect microstructural changes in such regions. In some non-cortical gray matter structures like the putamen, FA was increased but MA was decreased in the aged group which could indicate a coherent fiber orientation in the aged group related to the loss of crossing or fanning fibers. In conclusion, MA not only could improve the detectability of differences of the tissue microstructure but, in conjunction with FA, could also help to identify the underlying changes.

TOWERS: T-One with Enhanced Robustness and Speed.

PURPOSE: A new T1 mapping method is proposed that is accurate, rapid, and robust to motion. Considering these features, the method is dubbed "T-One with Enhanced Robustness and Speed (TOWERS)." METHODS: TOWERS is composed of inversion recovery (IR) and saturation recovery (SR) acquisitions. In the IR acquisitions, a slice reordering scheme is used to sample all slices in an efficient manner, whereas the SR acquisitions serve as references for motion estimation. Furthermore, as opposed to the usual way of running generalized autocalibrating partially parallel acquisitions (GRAPPA) calibration only once at the beginning, GRAPPA coefficients are updated in the middle and at the end, and are later used for retrospectively correcting for motion artifacts. Finally, sub-voxel magnetization tracking is deployed to account for motion-induced signal evolution changes. RESULTS: Whole-brain T1 mapping data with a spatial resolution of 1.56 × 1.56 × 2.00 mm can be collected within 2.5 min. TOWERS and the gold-standard IR method agree well in phantom, while high reproducibility is achieved in vivo. High-quality T1 maps in the presence of severe motion show the robustness of the method. CONCLUSION: The proposed method, TOWERS, is shown to be rapid, accurate, and robust. Multiple GRAPPA calibrations and sub-voxel magnetization tracking make TOWERS unique. Magn Reson Med 76:118-126, 2016. © 2015 Wiley Periodicals, Inc.

Experimental considerations for fast kurtosis imaging.

PURPOSE: The clinical use of kurtosis imaging is impeded by long acquisitions and postprocessing. Recently, estimation of mean kurtosis tensor W¯ and mean diffusivity ( D¯) was made possible from 13 distinct diffusion weighted MRI acquisitions (the 1-3-9 protocol) with simple postprocessing. Here, we analyze the effects of noise and nonideal diffusion encoding, and propose a new correction strategy. We also present a 1-9-9 protocol with increased robustness to experimental imperfections and minimal additional scan time. This refinement does not affect computation time and also provides a fast estimate of fractional anisotropy (FA). THEORY AND METHODS: 1-3-9/1-9-9 data are acquired in rat and human brains, and estimates of D¯, FA, W¯ from human brains are compared with traditional estimates from an extensive diffusion kurtosis imaging data set. Simulations are used to evaluate the influence of noise and diffusion encodings deviating from the scheme, and the performance of the correction strategy. Optimal b-values are determined from simulations and data. RESULTS: Accuracy and precision in D¯ and W¯ are comparable to nonlinear least squares estimation, and is improved with the 1-9-9 protocol. The compensation strategy vastly improves parameter estimation in nonideal data. CONCLUSION: The framework offers a robust and compact method for estimating several diffusion metrics. The protocol is easily implemented. Magn Reson Med 76:1455-1468, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Conventions and nomenclature for double diffusion encoding NMR and MRI.

Stejskal and Tanner's ingenious pulsed field gradient design from 1965 has made diffusion NMR and MRI the mainstay of most studies seeking to resolve microstructural information in porous systems in general and biological systems in particular. Methods extending beyond Stejskal and Tanner's design, such as double diffusion encoding (DDE) NMR and MRI, may provide novel quantifiable metrics that are less easily inferred from conventional diffusion acquisitions. Despite the growing interest on the topic, the terminology for the pulse sequences, their parameters, and the metrics that can be derived from them remains inconsistent and disparate among groups active in DDE. Here, we present a consensus of those groups on terminology for DDE sequences and associated concepts. Furthermore, the regimes in which DDE metrics appear to provide microstructural information that cannot be achieved using more conventional counterparts (in a model-free fashion) are elucidated. We highlight in particular DDE's potential for determining microscopic diffusion anisotropy and microscopic fractional anisotropy, which offer metrics of microscopic features independent of orientation dispersion and thus provide information complementary to the standard, macroscopic, fractional anisotropy conventionally obtained by diffusion MR. Finally, we discuss future vistas and perspectives for DDE.

Microscopic diffusion anisotropy in the human brain: reproducibility, normal values, and comparison with the fractional anisotropy.

Human neuroimaging of tissue microstructure, such as axonal density and integrity, is key in clinical and neuroscience research. Most studies rely on diffusion tensor imaging (DTI) and the measures derived from it, most prominently fractional anisotropy (FA). However, FA also depends on fiber orientation distribution, a more macroscopic tissue property. Recently introduced measures of so-called microscopic diffusion anisotropy, diffusion anisotropy on a cellular or microscopic level, overcome this limitation because they are independent of the orientation distributions of axons and fibers. In this study, we evaluate the feasibility of two measures of microscopic diffusion anisotropy I(MA) and MA indices, for human neuroscience and clinical research. Both indices reflect the eccentricity of the cells but while I(MA) also depends on the cell size, MA is independent of the cell size and, like FA, scaled between 0 and 1. In whole-brain measurements of a group of 19 healthy volunteers, we measured average values and variability, evaluated their reproducibility, both within and between sessions, and compared MA to FA values in selected regions-of-interest (ROIs). The within- and between-session comparison did not show substantial differences but the reproducibility was much better for the MA than I(MA) (coefficient of variation between sessions 10.5% vs. 28.9%). The reproducibility was less for MA than FA overall, but comparable in the defined ROIs and the average group sizes required for between-group comparisons was similar (about 60 participants for a relative difference of 5%). Group-averaged values of MA index were generally larger and showed less variation across white-matter brain ROIs than FA (mean ± standard deviation of seven ROIs 0.83 ± 0.10 vs. 0.58 ± 0.13). Even in some gray-matter ROIs, MA values comparable to those of white matter ROIs were observed. Furthermore, the within-group variation of the values in white matter ROIs was lower for the MA compared to the FA (mean standard deviation over volunteers 0.038 vs. 0.049) which could be due to significant variability in the distribution of fiber orientation contributing to FA. These results indicate that MA (i) should be preferred to I(MA), (ii) has a reproducibility and group-size requirements comparable to those of FA; (iii) is less sensitive to the fiber orientation distribution than FA; and (iv) could be more sensitive to differences or changes of the tissue microstructure than FA. R1.1.

Simultaneous functional MRI acquisition of distributed brain regions with high temporal resolution using a 2D-selective radiofrequency excitation.

PURPOSE: To perform simultaneous functional MRI of multiple, distributed brain regions at high temporal resolution using a 2D-selective radiofrequency (2DRF) excitation. METHODS: A tailored 2DRF excitation is used to excite several, small regions-of-interest distributed in the brain. They are acquired in a single projection image with an appropriately chosen orientation such that the different regions-of-interest can be discriminated by their position in the projection plane. Thus, they are excited and acquired simultaneously with a temporal resolution comparable to that of a single-slice measurement. The feasibility of this approach for functional neuroimaging (in-plane resolution 2 × 2 mm(2) ) at high temporal resolution (80 ms) is demonstrated in healthy volunteers for regions-of-interest in the visual and motor system using checkerboard and finger tapping block-design paradigms. RESULTS: Task-related brain activation could be observed in both the visual and the motor system simultaneously with a high temporal resolution. For an onset shift of 240 ms for half of the checkerboard, a delay of the hemodynamic response in the corresponding hemisphere of the visual cortex could be detected. CONCLUSION: Limiting the excited magnetization to the desired target regions with a 2DRF excitation reduces the imaging sampling requirements which can improve the temporal resolution significantly.

Mapping measures of microscopic diffusion anisotropy in human brain white matter in vivo with double-wave-vector diffusion-weighted imaging.

PURPOSE: To demonstrate that rotationally invariant measures of the diffusion anisotropy on a microscopic scale can be mapped in human brain white matter in vivo. METHODS: Echo-planar imaging experiments (resolution 3.0 × 3.0 × 3.0 mm(3) ) involving two diffusion-weighting periods (δ = 22 ms, Δ = 25 ms) in the same acquisition, so-called double-wave-vector or double-pulsed-field-gradient diffusion-weighting experiments, were performed on a 3 T whole-body magnetic resonance system with a long mixing time ( τm=45 ms) between the two diffusion weightings. RESULTS: The disturbing influences of background gradient fields, eddy currents, and the finite mixing time can be minimized using 84 direction combinations based on nine directions and their antipodes. In healthy volunteers, measures of the microscopic diffusion anisotropy ( IMA and MA indexes) could be mapped in white matter across the human brain. The measures were independent (i) of the absolute orientation of the head and of the diffusion directions and (ii) of the predominant fiber orientation. Compared to the fractional anisotropy derived from the conventional diffusion tensor, the double-wave-vector indexes exhibit a narrower distribution, which could reflect their independence of the fiber orientation distribution. CONCLUSIONS: Mapping measures of the microscopic diffusion anisotropy in human brain white matter is feasible in vivo and could help to characterize tissue microstructure in the healthy and pathological brain.