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Purpose Slice-wise shimming can improve field homogeneity, but suffers from large noise propagation in the shim calculation. Here, we propose a robust shim current optimization for higher-order dynamic shim updating, based on Tikhonov regularization with a variable regularization parameter, 𝜆. Theory and Methods 𝜆 was selected for each slice separately in a fully automatic procedure based on a combination of boundary constraints and an L-curve search algorithm. Shimming performance was evaluated for second order slice-wise shimming of the brain at 7T, by simulation on a database of field maps from 143 subjects, and by direct measurements in 8 subjects. Results Simulations yielded on average 36% reduction in the shim current norm for just 0.4 Hz increase in residual field SD as compared to unconstrained unregularized optimization. In vivo results yielded on average 34.0 Hz residual field SD as compared to 34.3 Hz with a constrained unregularized optimization, while simultaneously reducing the shim current norm to 2.8 A from 3.9 A. The proposed regularization also reduced the average step in the shim current between slices. Conclusion Slice-wise variable Tikhonov regularization yielded reduced current norm and current steps to a negligible cost in field inhomogeneity. The method holds promise to increase the robustness, and thereby the utility, of higher-order shim updating.

Background High tibial osteotomy (HTO) re-aligns the weight-bearing axis (WBA) of the lower limb. The surgery reduces medial load (reducing pain and slowing progression of cartilage damage) while avoiding overloading the lateral compartment. The optimal correction has not been established. This study investigated how different WBA re-alignments affected load distribution in the knee, to consider the optimal post-surgery re-alignment. Methods We collected motion analysis and seven Tesla MRI data from three healthy subjects, and combined this data to create sets of subject-specific finite element models (total = 45 models). Each set of models simulated a range of potential post-HTO knee re-alignments. We shifted the WBA from its native alignment to between 40% and 80% medial–lateral tibial width (corresponding to 2.8°–3.1° varus and 8.5°–9.3° valgus), in three percent increments. We then compared stress/pressure distributions in the models. Results Correcting the WBA to 50% tibial width (0° varus–valgus) approximately halved medial compartment stresses, with minimal changes to lateral stress levels, but provided little margin for error in undercorrection. Correcting the WBA to a more commonly-used 62%–65% tibial width (3.4°–4.6° valgus) further reduced medial stresses but introduced the danger of damaging lateral compartment tissues. To balance optimal loading environment with that of the historical risk of under-correction, we propose a new target: WBA correction to 55% tibial width (1.7°–1.9° valgus), which anatomically represented the apex of the lateral tibial spine. Conclusions Finite element models can successfully simulate a variety of HTO re-alignments. Correcting the WBA to 55% tibial width (1.7°–1.9° valgus) optimally distributes medial and lateral stresses/pressures.

Increasing numbers of 7 tesla (7T) magnetic resonance imaging (MRI) scanners are in research and clinical use. 7T MRI can increase the scanning speed, spatial resolution and contrast-to-noise-ratio of many neuroimaging protocols, but technical challenges in implementation have been addressed in a variety of ways across sites. In order to facilitate multi-centre studies and ensure consistency of findings across sites, it is desirable that 7T MRI sites implement common high-quality neuroimaging protocols that can accommodate different scanner models and software versions. With the installation of several new 7T MRI scanners in the United Kingdom, the UK7T Network was established with an aim to create a set of harmonized structural and functional neuroimaging sequences and protocols. The Network currently includes five sites, which use three different scanner platforms, provided by two different vendors. Here we describe the harmonization of functional and anatomical imaging protocols across the three different scanner models, detailing the necessary changes to pulse sequences and reconstruction methods. The harmonized sequences are fully described, along with implementation details. Example datasets acquired from the same subject on all Network scanners are made available. Based on these data, an evaluation of the harmonization is provided. In addition, the implementation and validation of a common system calibration process is described. Keywords 7 tesla; MRI; Harmonization; anatomical; functional; Scanner calibration

Introduction: We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's “Travelling Heads” study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5–3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. Methods: Ten healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each “home” site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. Results and Discussion: Mean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001–0.005 ppm (χ) and 0.0005–0.001 ms−1 (R2*). For χ this is 2.1–4.8 fold better than 3T reports, and 1.1–3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. Conclusion: The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

Magnetic resonance imaging and spectroscopy of the spinal cord stand to benefit greatly from the increased signal-to-noise ratio of ultra-high field. However, ultra-high field also poses considerable technical challenges, especially related to static and dynamic B0 fields. Breathing causes the field to fluctuate with the respiratory cycle, giving rise to artifacts such as ghosting and apparent motion in images. We here investigated the spatial and temporal characteristics of breathing-induced B0 fields in the cervical spinal cord at 7T. We analyzed the magnitude and spatial profile of breathing-induced fields during breath-holds in an expired and inspired breathing state. We also measured the temporal field evolution during free breathing by acquiring a time series of fast phase images, and a principal component analysis was performed on the measured field evolution. In all subjects, the field shift was largest around the vertebral level of C7 and lowest at the top of the spinal cord. At C7, we measured peak-to-peak field fluctuations of 36 Hz on average during normal free breathing; increasing to on average 113 Hz during deep breathing. The first principal component could explain more than 90% of the field variations along the foot-head axis inside the spinal cord in all subjects. We further implemented a proof-of-principle shim correction, demonstrating the feasibility of using the shim system to compensate for the breathing-induced fields inside the spinal cord. Effective correction strategies will be crucial to unlock the full potential of ultra-high field for spinal cord imaging., Highlights • The B0 field in the spinal cord fluctuates with the breathing cycle. • Average peak-to-peak ΔB0 of 36/113 Hz at C7 during normal/deep breathing at 7T. • The first principal component explains more than 90% of the field variance. • Respiratory trace correlates well with field fluctuations during normal breathing. • Proof-of-principle correction using 2nd-order shims was demonstrated.

Purpose In typical MRI protocols, time is spent acquiring a field map to calculate the shim settings for best image quality. We propose a fast template‐based field map prediction method that yields near‐optimal shims without measuring the field. Methods The template‐based prediction method uses prior knowledge of the B0 distribution in the human brain, based on a large database of field maps acquired from different subjects, together with subject‐specific structural information from a quick localizer scan. The shimming performance of using the template‐based prediction is evaluated in comparison to a range of potential fast shimming methods. Results Static B0 shimming based on predicted field maps performed almost as well as shimming based on individually measured field maps. In experimental evaluations at 7 T, the proposed approach yielded a residual field standard deviation in the brain of on average 59 Hz, compared with 50 Hz using measured field maps and 176 Hz using no subject‐specific shim. Conclusions This work demonstrates that shimming based on predicted field maps is feasible. The field map prediction accuracy could potentially be further improved by generating the template from a subset of subjects, based on parameters such as head rotation and body mass index. Magn Reson Med 80:171–180, 2018. © 2017 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.

Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices. However, there is relatively little evidence for such cortical reorganisation over the short-term. Using human somatosensory cortex as a model, we investigated the effects of a 24 hr gluing manipulation in which the right index and right middle fingers (digits 2 and 3) were adjoined with surgical glue. Somatotopic representations, assessed with two 7 tesla fMRI protocols, revealed rapid off-target reorganisation in the non-manipulated fingers following gluing, with the representation of the ring finger (digit 4) shifted towards the little finger (digit 5) and away from the middle finger (digit 3). These shifts were also evident in two behavioural tasks conducted in an independent cohort, showing reduced sensitivity for discriminating the temporal order of stimuli to the ring and little fingers, and increased substitution errors across this pair on a speeded reaction time task. DOI: http://dx.doi.org/10.7554/eLife.17280.001, eLife digest The areas of the brain that receive inputs from our senses have a map-like structure. In an area called the visual cortex this map represents our field of vision; in the auditory cortex, it represents the range of different tones we can hear. The sense of touch is processed in the somatosensory cortex: an area of the brain that is organised around a map of the body, with adjacent regions of the cortex representing adjacent regions of the body. The clear structure of these brain regions makes them ideal for exploring how the organisation of the brain changes over time. How quickly can changes to the touch inputs that the brain receives cause the map in the somatosensory cortex to reorganise? Can these effects be produced in just 24 hours? And would this remapping affect how we perceive touch? To investigate these questions, Kolasinski et al. glued together the right index and right middle fingers of healthy human volunteers. This separated the middle and ring fingers: a pair that usually move together due to the anatomical structure of the hand. Functional magnetic resonance imaging of the brain’s activity revealed that within 24 hours of the gluing, the brain’s representation of the ring finger moved away from that of the middle finger, and towards the representation of the little finger. A perceptual judgment task mirrored this finding: after 24 hours of gluing, the participants became better at distinguishing between the middle and ring fingers and worse at distinguishing between the ring and little fingers. This is a powerful demonstration of the human brain’s potential to adapt and reorganise rapidly to changes to sensory inputs. The sense of touch declines gradually with age and may also be reduced as a result of disease such as stroke. A long-term challenge is to understand how the sensory regions of the brain change during this loss of sensation. Further research could then investigate how to maintain the structure of the cortical map to prolong or restore high quality touch sensation. DOI: http://dx.doi.org/10.7554/eLife.17280.002

Publisher Summary This chapter describes the magnetic resonance imaging (MRI) of the brain function. The rapid development of methods for noninvasive brain mapping has led to exciting advances in understanding of the human brain. Functional MRI relies on detecting the small changes in image brightness on MRI scans, associated with the hemodynamic changes in the brain, in response to a specific external stimulus or internal cognitive process. Carrying out an fMRI experiment, therefore, consists of three primary components, including presenting or otherwise cueing the stimulus, scanning the brain rapidly using MRI, and analyzing the MRI scans to detect changes in image intensity. The complex physiological processes that give rise to the signal changes observed in fMRI mean that there are a number of reasons for caution in interpreting the experimental results. The most common fast imaging method used for fMRI is echo planar imaging. This method is able to collect data from a single slice through the brain in less than 100 ms. It is found that functional MRI has been used to demonstrate the cortical changes that occur upon rehabilitation after stoke.

Visual area MT is a model of choice in primate neurophysiological and human imaging research of visual perception, due to its considerable sensitivity to moving stimuli and the strong direction selectivity of its neurons. While the location of MT(V5) in the non-human primate is easily identifiable based on gross anatomy and appears consistent between animals, this is less the case in human subjects. Functional localisation of human MT. + with moving stimuli can identify a group of motion-sensitive regions, but defining MT proper has proved more challenging. In this review we consider approaches to studying the cyto- and myleoarchitecture of this cortical area that may, in the future, allow identification of human MT in vivo based on anatomy. © 2013 Elsevier Inc.

Background: The Whitehall II (WHII) study of British civil servants provides a unique source of longitudinal data to investigate key factors hypothesized to affect brain health and cognitive ageing. This paper introduces the multi-modal magnetic resonance imaging (MRI) protocol and cognitive assessment designed to investigate brain health in a random sample of 800 members of the WHII study. Methods/design: A total of 6035 civil servants participated in the WHII Phase 11 clinical examination in 2012–2013. A random sample of these participants was included in a sub-study comprising an MRI brain scan, a detailed clinical and cognitive assessment, and collection of blood and buccal mucosal samples for the characterisation of immune function and associated measures. Data collection for this sub-study started in 2012 and will be completed by 2016. The participants, for whom social and health records have been collected since 1985, were between 60–85 years of age at the time the MRI study started. Here, we describe the pre-specified clinical and cognitive assessment protocols, the state-of-the-art MRI sequences and latest pipelines for analyses of this sub-study. Discussion: The integration of cutting-edge MRI techniques, clinical and cognitive tests in combination with retrospective data on social, behavioural and biological variables during the preceding 25 years from a well-established longitudinal epidemiological study (WHII cohort) will provide a unique opportunity to examine brain structure and function in relation to age-related diseases and the modifiable and non-modifiable factors affecting resilience against and vulnerability to adverse brain changes.

The relationship between neocortical structure and function is a key area of research in neuroscience. Most studies of neural function, whether using neurophysiology or neuroimaging methods, are interpreted with relation to the underlying cortical myelo‐ and cytoarchitecture. For functional neuroimaging studies this often means using cytoarchitectonic maps based on the study of a limited number of brains, despite evidence for substantial interindividual variation. Improvements in MR technology, resulting in wider availability of high‐field MRI systems, have led to an increase in the achievable resolution in MR scans. Several groups have reported the in vivo detection of myelination patterns within the cortex, consistent with those observed in postmortem tissue. This leads to the possibility of predefining areas for fMRI analysis based on the cortical architecture. To do this it is essential to know, in a quantitative way, how reliably myeloarchitectonic areas and boundaries can be detected using MRI. Here we investigate the striate cortex, known to be coincident with V1, to assess the detectability of the stria of Gennari across V1 and across subjects. Under optimal conditions, 80% of the stria of Gennari was visualized using our methodology, although there was considerable variability in the level of detection across subjects. We discuss the limitations of the methodology and propose ways to improve the detection level of cortical myeloarchitecture more generally. Hum. Brain Mapping, 2005. © 2005 Wiley‐Liss, Inc.

Associative learning is thought to depend on detecting mismatches between actual and expected experiences. With functional magnetic resonance imaging (FMRI), we studied brain activity during different types of mismatch in a paradigm where contrasting-colored lights signaled the delivery of painful heat, nonpainful warmth, or no stimulation. When painful heat stimulation was unexpected, there was increased FMRI signal intensity in areas of the hippocampus, superior frontal gyrus, cerebellum, and superior parietal gyrus that was not found with mismatch between expectation and delivery of nonpainful warmth stimulation. When painful heat stimulation was unexpectedly omitted, the FMRI signal intensity decreased in the left superior parietal gyrus and increased in the other regions. These contrasting activation patterns correspond to two different mismatch concepts in theories of associative learning (Rescorla-Wagner, temporal difference vs. Pearce-Hall, Mackintosh). Searching for interventions to specifically modulate activation of these brain regions therefore offers an approach to identifying new treatments for chronic pain, which often has a substantial associative learning component.

Room temperature (RT) shims are used routinely in MRI to remove global and local B0 field inhomogeneity introduced by the subject. Most clinical scanners use only second-order spherical harmonic terms, but with the increasing availability of very high field systems, third- and fourth-order terms are a serious consideration. However, choosing appropriate coil strengths is of critical importance in shim coil design since overspecification of the shim strengths can lead to a variety of problems, including shim coil self-resonance. In this study B0 field map data collected over a period of 6 months (over 400 brain volumes) were analyzed to find the characteristic B-fields required to shim these brains. These data can be used to specify the coil requirements to effectively shim the human brain. Magn Reson Med, 2006. © 2005 Wiley-Liss, Inc.

It is common clinical experience that anxiety about pain can\ud exacerbate the pain sensation. Using event-related functional\ud magnetic resonance imaging (FMRI), we compared activation\ud responses to noxious thermal stimulation while perceived pain\ud intensity was manipulated by changes in either physical intensity\ud or induced anxiety. One visual signal, which reliably predicted\ud noxious stimulation of moderate intensity, came to\ud evoke low anxiety about the impending pain. Another visual\ud signal was followed by the same, moderate-intensity stimulation\ud on most of the trials, but occasionally by discriminably\ud stronger noxious stimuli, and came to evoke higher anxiety. We\ud found that the entorhinal cortex of the hippocampal formation\ud responded differentially to identical noxious stimuli, dependent\ud on whether the perceived pain intensity was enhanced by\ud pain-relevant anxiety. During this emotional pain modulation,\ud entorhinal responses predicted activity in closely connected,\ud affective (perigenual cingulate), and intensity coding (midinsula)\ud areas. Our finding suggests that accurate preparatory\ud information during medical and dental procedures alleviates\ud pain by disengaging the hippocampus. It supports the proposal\ud that during anxiety, the hippocampal formation amplifies aversive\ud events to prime behavioral responses that are adaptive to\ud the worst possible outcome.

Functional magnetic resonance image (fMRI) experiments rely on the ability to detect subtle signal changes in magnetic resonance image time series. Any areas of signal change that correlate with the neurological stimulus can then be identified and compared with a corresponding high‐resolution anatomical scan. This report reviews some of the several artefacts that are frequently present in fMRI data, degrading their quality and hence their interpretation. In particular, the effects of magnetic field inhomogeneities are described, both on echo planar imaging (EPI) data and on spiral imaging data. The modulation of these distortions as the subject moves in the magnet is described. The effects of gradient coil nonlinearities and EPI ghost correction schemes are also discussed. Hum. Brain Mapping 8:80–85, 1999. © 1999 Wiley‐Liss, Inc.

Purpose To study arterial spin labeling (ASL) MRI techniques and to investigate various problematic issues that still hinder the accurate and robust quantitative analysis of ASL data. Materials and Methods A pulsed-ASL (PASL) sequence was implemented on a 3-T imaging system and a protocol was developed for the measurement of perfusion based on fitting to a standard kinetic model. Both numerical simulations and multi-inversion time MRI data were analyzed. The effect of fitting a kinetic curve to a large region of interest (ROI) with a distribution of arterial transit times was compared to a pixel-by-pixel (PBP) method. Results It was found that a significant underestimation of perfusion of approximately 17 ± 6% (P < 0.001) occurs in gray matter, when comparing an ROI with a PBP analysis over a group of 12 healthy subjects. Conclusion Analysis of ASL data based on a large ROI may suffer from inaccuracies arising from a distribution of transit times, implying that averaging of ASL kinetic data over such regions should therefore be avoided. When possible, a PBP fit should be performed. J. Magn. Reson. Imaging 2005;21:676–682. © 2005 Wiley-Liss, Inc.

Highlights • Healthy adults performed movements while receiving neurofeedback from real-time fMRI. • Two experiments were performed, one with younger and one with older adults. • Neurofeedback (NF) represented the laterality of activation in the motor cortices. • The NF groups produced more lateralized activity than the sham group., Neurofeedback training involves presenting an individual with a representation of their brain activity and instructing them to alter the activity using the feedback. One potential application of neurofeedback is for patients to alter neural activity to improve function. For example, there is evidence that greater laterality of movement-related activity is associated with better motor outcomes after stroke; so using neurofeedback to increase laterality may provide a novel route for improving outcomes. However, we must demonstrate that individuals can control relevant neurofeedback signals. Here, we performed two proof-of-concept studies, one in younger (median age: 26 years) and one in older healthy volunteers (median age: 67.5 years). The purpose was to determine if participants could manipulate laterality of activity between the motor cortices using real-time fMRI neurofeedback while performing simple hand movements. The younger cohort trained using their left and right hand, the older group trained using their left hand only. In both studies participants in a neurofeedback group were able to achieve more lateralized activity than those in a sham group (younger adults: F(1,23) = 4.37, p

Purpose Blood oxygen level dependent (BOLD) brain activity, measured using functional MRI (fMRI), is dependent on the echo time (TE) and the reversible spin–spin relaxation time constant ( T2*) that describes the decay of transverse magnetization. Use of the optimal TE during fMRI experiments allows maximal sensitivity to BOLD to be achieved. Reports that T2* values are longer in infants (due to higher water concentrations and lower lipid content) have led to the use of longer TEs during infant fMRI experiments; however, the optimal TE has not been established. Methods In this study, acute experimental mildly noxious stimuli were applied to the heel in 12 term infants (mean gestational age = 40 weeks, mean postnatal age = 3 days); and the percentage change in BOLD activity was calculated across a range of TEs, from 30 to 70 ms, at 3 Tesla. In addition, T2* maps of the whole brain were collected in seven infants. Results The maximal change in BOLD occurred at a TE of 52 ms, and the average T2* across the whole brain was 99 ms. Conclusion A TE of approximately 50 ms is recommended for use in 3T fMRI investigations in term infants. Magn Reson Med 78:625–631, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Echo-planar diffusion-weighted images can display significant geometric distortions due to eddy current fields. Several preparation schemes have been proposed, which can null eddy currents with a single time constant. The aim of this work was to compare the performance of three such pulse sequences in the presence of multiple components and investigate whether affine registration is capable of correcting for the resulting distortions. A magnetic resonance imaging simulator was used to eliminate potential confounding factors. The doubly refocused sequences showed substantially reduced effects. Applying affine registration to the single spin-echo images leads to reduced residuals, but not to the level observed for the doubly refocused sequences. Modified versions of the standard single spin-echo and doubly refocused sequences performed better than their original counterparts. Affine registration is not sufficient to correct for strong eddy current effects, which should therefore be minimized at source. When the use of a doubly refocused sequence is not possible, a modified single spin-echo sequence should be considered.

Limited understanding of infant pain has led to its lack of recognition in clinical practice. While the network of brain regions that encode the affective and sensory aspects of adult pain are well described, the brain structures involved in infant nociceptive processing are less well known, meaning little can be inferred about the nature of the infant pain experience. Using fMRI we identified the network of brain regions that are active following acute noxious stimulation in newborn infants, and compared the activity to that observed in adults. Significant infant brain activity was observed in 18 of the 20 active adult brain regions but not in the infant amygdala or orbitofrontal cortex. Brain regions that encode sensory and affective components of pain are active in infants, suggesting that the infant pain experience closely resembles that seen in adults. This highlights the importance of developing effective pain management strategies in this vulnerable population. DOI: http://dx.doi.org/10.7554/eLife.06356.001, eLife digest Doctors long believed that infants do not feel pain the way that older children and adults do. Instead, they believed that the infants' responses to discomfort were reflexes. Based on these beliefs, it was a routine practice to perform surgery on infants without suitable pain relief up until the late 1980s. Even now, infants may receive less than ideal pain relief. For example, a review found that although newborns in intensive care units undergo 11 painful procedures per day on average, more than half of the babies received no pain medications. Some guidelines continue to emphasize that for infants cuddling and feeding are more important sources of comfort than pain-relieving drugs. There is growing support for better pain control for infants. Doctors and nurses now routinely observe behaviour and physiological responses—such as heart rate—to assess whether infants are experiencing pain. When an infant shows signs of pain, medical staff may give the infant sugar water or other interventions aimed at reducing their distress. However, recordings of brain activity suggest that infants may experience pain without exhibiting physical signs and that sugar water may reduce the behaviours associated with pain but not the pain itself. More objective measurements of infant pain would be useful, but to create such measurements scientists must first understand how infants experience pain. So Goksan et al. used a technique called functional magnetic resonance imaging (fMRI) to compare the brain responses of adults and newborns to the same stimulus—a sharp poke of the foot. The adults were also asked about the pain they experienced, and whether the infants pulled their foot away when poked was documented. The fMRI results revealed that pain increased activity in 20 regions in the adults' brains, and 18 of the same regions in the infants' brains. The brain regions activated in the infants' brains in response to a poke on the foot are involved in processing sensations and emotions. The two regions that did not activate in the infant brains—the amygdala and the orbitofrontal cortex—help individuals interpret the stimuli. Goksan et al. therefore conclude that infants experience pain in similar ways to adults, though they may not experience all the emotions that adults have when they are in pain. It is, therefore, important to give infants suitable pain relief during potentially painful procedures. DOI: http://dx.doi.org/10.7554/eLife.06356.002

The medial geniculate body (MGB) of the thalamus is a key component of the auditory system. It is involved in relaying and transforming auditory information to the cortex and in top-down modulation of processing in the midbrain, brainstem, and ear. Functional imaging investigations of this region in humans, however, have been limited by the difficulty of distinguishing MGB from other thalamic nuclei. Here, we introduce two methods for reliably delineating MGB anatomically in individuals based on conventional and diffusion MRI data. The first uses high-resolution proton density weighted scanning optimized for subcortical grey-white contrast. The second uses diffusion-weighted imaging and probabilistic tractography to automatically segment the medial and lateral geniculate nuclei from surrounding structures based on their distinctive patterns of connectivity to the rest of the brain. Both methods produce highly replicable results that are consistent with published atlases. Importantly, both methods rely on commonly available imaging sequences and standard hardware, a significant advantage over previously described approaches. In addition to providing useful approaches for identifying the MGB and LGN in vivo, our study offers further validation of diffusion tractography for the parcellation of grey matter regions on the basis of their connectivity patterns.

Previous studies have established the clinical relevance of hypointense lesions ("black holes") on T1-weighted MRI as a surrogate marker for pathological change [36]. In contrast to measuring the volume of "black holes", the direct measurement of T1 values allows an objective assessment of the changes contributing to hypointensity both in the focal lesions and in the normal appearing white matter (NAWM). The aims of this study were first, to determine the relationship between T1 values in the NAWM and in discrete lesions, second, to test the relationship between white matter T1 changes and measures of disability and third, to determine whether pathology leading to T1 change occurred in thalamic grey matter of patients with multiple sclerosis. 24 patients with clinically definite multiple sclerosis (13 with relapsing-remitting multiple sclerosis and 11 with secondary progressive multiple sclerosis) and 11 controls participated. White matter T1 histograms and mean T1 values for the thalamus were generated from whole brain T1 relaxation time maps measured using a novel echo-planar imaging based MRI sequence at 3Tesla. Tissue segmentation based on T2- and T1-weighted images allowed independent study of changes in lesions and NAWM. White matter T1 histograms from the patient group showed a reduced peak height and a shift towards higher T1 values (p = 0.028) relative to controls. The mean thalamic T1 was greater for secondary progressive patients than for healthy controls (p = 0.03). Mean white matter T1 values correlated significantly with disability (r = 0.48, p = 0.02). The mean T1 value in the T1-hypointense lesions correlated strongly with the mean T1 value in the NAWM (r = 0.80, p < 0.001). No significant relationship was found between mean white matter T1 value and cerebral volume (r = -0.23, p = 0.31). The T1 measurements extend previous observations suggesting that changes in the NAWM occur in parallel with pathology in lesions of MS. T1 measurements of either the total or NAWM therefore may provide a potentially observer- and scanner- independent marker of pathology relevant to disability in MS.

The effect of poor B(1) homogeneity on MRI images not only affects the appearance of the images, but produces difficulty in automated segmentation and in certain quantification methods. While improved RF coil design is the first line in reducing such artifact, compensation methods can significantly improve the quality of images. Existing methods of compensation typically apply a filter during the image reconstruction. Here a method is presented that compensates for part of the inhomogeneity by actively modulating the RF transmit power as a function of slice position. The method is demonstrated both quantitatively on a phantom and qualitatively on a human brain.

An optimal sampling schedule strategy based on the Fisher information matrix and the D-optimality criterion has previously been proposed as a formal framework for optimizing inversion time scheduling for multi-inversion-time arterial spin labeling experiments. Optimal sampling schedule possesses the primary advantage of improving parameter estimation precision but requires a priori estimation of plausible parameter distributions that may not be available in all situations. An adaptive sequential design approach addresses this issue by incorporating the optimal sampling schedule strategy into an adaptive process that iteratively updates the parameter estimates and adjusts the optimal sampling schedule accordingly as data are acquired. In this study, the adaptive sequential design method was experimentally implemented with a real-time feedback scheme on a clinical MRI scanner and was tested in six normal volunteers. Adapted schedules were found to accommodate the intrinsically prolonged arterial transit times in the occipital lobe of the brain. Simulation of applying the adaptive sequential design approach on subjects with pathologically reduced perfusion was also implemented. Simulation results show that the adaptive sequential design approach is capable of incorporating pathologic parameter information into an optimal arterial spin labeling scheduling design within a clinically useful experimental time.

For centuries scientists have been fascinated with the question of how the brain works. Investigators have looked at both where different functions are localized and how the anatomical microstructure varies across the brain surface. Here we discuss how advances in magnetic resonance imaging (MRI) have allowed in vivo visualization of the fine structure of the brain that was previously only visible in post-mortem brains. We present data showing the correspondence between definitions of the primary visual cortex defined anatomically using very high-resolution MRI and functionally using functional MRI. We consider how this technology can be applied to allow the investigation of brains that differ from normal, and what this ever-evolving technology may be able to reveal about in vivo brain structure in the next few years.

OBJECTIVE: To test the sensitivity of whole-brain T1 relaxometry to the evolution of pathological changes in multiple sclerosis (MS). BACKGROUND: T1-weighted hypointense lesion load in the brains of patients with MS is associated with axonal loss. Other work has shown that T1 measurements may provide information complementary to existing imaging techniques, such as magnetization transfer imaging. METHODS: The authors studied 14 MS patients twice over a median time interval of 19.5 months (range, 14-22 months). Structural images and whole-brain T1 maps using a novel rapid-scanning technique (3 min/study) were performed at 3 T. Analysis focused on defining changes separately in the lesional and normal-appearing white matter (NAWM) and in the cortical gray matter. RESULTS: At baseline, there was an inverse relationship between disease duration and the NAWM T1 histogram peak height (r = -0.75, P = .03). The total white matter T1 histogram peak height decreased over time (P < .001). This could be accounted for by changes in the NAWM (P < .03). There also was a decrease (6%) in the mean (11 of 14 patients, P = .004) and in the median (7%) (13 of 14 patients, P < .001) neocortical gray matter T1 over the follow-up period. CONCLUSIONS: Brain T1 maps can be generated quickly and are sensitive to pathological changes over time. T1 values in both the gray and the white matter at the baseline visit were related to disease duration, suggesting that the T1 changes are clinically relevant. Although the absolute values will be different, it is likely that similar changes will be able to be detected at 1.5 T. The role of T1 measurement as a magnetic resonance imaging outcome measure in clinical trials now should be explored.

Current clinical and experimental literature strongly supports the phenomenon of reduced pain perception whilst attention is distracted away from noxious stimuli. This study used functional MRI to elucidate the underlying neural systems and mechanisms involved. An analogue of the Stroop task, the counting Stroop, was used as a cognitive distraction task whilst subjects received intermittent painful thermal stimuli. Pain intensity scores were significantly reduced when subjects took part in the more cognitively demanding interference task of the counting Stroop than in the less demanding neutral task. When subjects were distracted during painful stimulation, brain areas associated with the affective division of the anterior cingulate cortex (ACC) and orbitofrontal regions showed increased activation. In contrast, many areas of the pain matrix (i.e. thalamus, insula, cognitive division of the ACC) displayed reduced activation, supporting the behavioural results of reduced pain perception.

Summary Functional magnetic resonance imaging was used to study fetal brain activity. This activity was in response to an auditory stimulus.

Demonstration that contrast in magnetic resonance images can be generated based on differences in blood oxygenation has led to an explosion of interest in so-called functional magnetic resonance imaging (FMRI). FMRI can be used to map increases in blood flow that accompany local synaptic activity in the brain. The technique has proved remarkably sensitive and has been used to map a broad range of cognitive, motor and sensory processes in the brain entirely non-invasively. More recently, efforts have been made to extend this technique to the analysis of clinical problems. A major application is for presurgical localization of cerebral functions, e.g. in the surgical treatment of epilepsy. The technique also is beginning to provide information on functional consequences of abnormal brain development. Perhaps most exciting are applications to neurological impairments that are not associated with structural abnormalities, such as learning problems, dyslexia and movement disorders. It is possible that useful applications of FMRI may be found for directly mapping sites of action of CNS-active drugs. Although the extent of the potential clinical applications of this new brain mapping technique is not clear, the widespread availability of MRI scanners suggests that the technique should in some form soon become a routine tool in major neuroradiological centres.

The experience of pain is subjectively different from the fear and anxiety caused by threats of pain. Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation. Expectation of pain activated sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to, locations mediating pain experience itself. Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients. Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain.

Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.

Conventional functional imaging paradigms use periods of repetitive task performance to generate sustained functional signal changes. We have developed a technique of imaging the small, transient signal changes that occur after single cognitive events. The technique uses echo-planar imaging at 3 T to generate functional images of the whole brain with a temporal resolution of 3 seconds. It uses a signal averaging technique to create time sweeps of functional activity. After a single cognitive event, widely distributed patterns of brain activation can be detected and their time course measured. This technique enables the individual cognitive tasks that constitute a paradigm to be analyzed separately and compared. We describe the application of this new technique to separate the cognitive elements in a simple "go/no-go" motor paradigm. Comparison of activation patterns during "go" and "no-go" responses reveals hierarchical subdivision of the medial premotor cortex into an anterior region (presupplementary motor area) involved in movement decision making and a posterior region (supplementary motor area proper) directly involved in motor execution.

Pain is an unpleasant sensory and emotional experience usually triggered by stimulation of peripheral nerves and often associated with actual or potential tissue damage. It is well known that pain perception for patients and normal subjects can be modulated by psychological factors, such as attention, stress, and arousal. Our understanding of how this modulation occurs at a neuroanatomical level is poor. Here we neuroanatomically defined a key area in the network of brain regions active in response to pain that is modulated by attention to the painful stimulus. High-resolution functional magnetic resonance imaging was used to define brain activation to painful heat stimulation applied to the hand of nine normal subjects within the periaqueductal gray region. Subjects were asked to either focus on or distract themselves from the painful stimuli, which were cued using colored lights. During the distraction condition, subjects rated the pain intensity as significantly lower compared with when they attended to the stimulus. Activation in the periaqueductal gray was significantly increased during the distraction condition, and the total increase in activation was predictive of changes in perceived intensity. This provides direct evidence supporting the notion that the periaqueductal gray is a site for higher cortical control of pain modulation in humans.

The cerebral cortex has both anatomical and functional specialization, but the level of correspondence between the two in the human brain has remained largely elusive. Recent successes in high-resolution magnetic resonance imaging of myeloarchitecture patterns in the cortex suggest that it may now be possible to compare directly human anatomy and function in vivo. We independently investigated the anatomical and functional borders between primary and secondary human visual areas (V1 and V2) in vivo. Functional borders were mapped with functional magnetic resonance imaging (fMRI) using a narrow, vertical bla ck and white contrast-reversing wedge. In three separate scanning sessions, anatomical images were collected at three different slice orientations (300 µm x 300 µm, slice thickness, 1.5 mm). The anatomical signature of V1 was determined by the presence of a hypointense band in the middle of the cortical gray matter. The band was identified in between 81% and 33% (mean 57%) of V1 defined using fMRI, and less than 5% of the identified band was in cortex outside V1. Intensity profiles taken through the gray matter on the V1 and V2 sides of the functional border indicate a measurable difference in the size of the hypointense band for all subjects. This is the first demonstration that the definition of V1 by fMRI closely matches the anatomically defined striate cortex in the human brain. The development of very high-resolution structural MRI may permit the definition of cortical areas based on myeloarchitecture when functional definition is not possible. Keywords: primary visual cortex, high-resolution MRI, myeloarchitecture, stria of Gennari