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Amplitudes of 2-hydroxyglutarate (2-HG) signal for density matrix simulation of pulse acquire and semi-LASER at TE = 110 ms (TE1 =11 ms, TE2 = 65 ms and TE3 = 34 ms) acquisitions.

Legends for Supplementary Figures S1-S5.

Description of additional methods and procedures used in the study. Also includes Supplementary References.

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.

Whilst considerable progress has been made in using ultra-high field fMRI to study brain function at fine spatial resolution, methods are generally optimized at a single site and do not translate to studies where multiple sites are required for sufficient subject recruitment. With a recent increase in installations of human 7 T systems, there is now the opportunity to establish a framework for multi-site 7 T fMRI studies. However, an understanding of the inter-site variability of fMRI measurements is required for datasets to be combined across sites. To address this, we employ a hand digit localization task and compare across-site and within-site reproducibility of 7 T fMRI to a hand digit localization task which requires fine spatial resolution to resolve individual digit representations. As part of the UK7T Network “Travelling Heads” study, 10 participants repeated the same hand digit localization task at five sites with whole-body 7T MRI systems to provide a measure of inter-site variability. A subset of the participants (2 per site) performed repeated sessions at each site for measurement of intra-site reproducibility. Dice’s overlap coefficient was used to assess reproducibility, with hand region inter-site Dice = 0.70±0.04 significantly lower than intrasite Dice = 0.76±0.06, with similar trends for the individual digit maps. Although slightly lower than intra-site reproducibility, the inter-site reproducibility results are consistent with previous single site reproducibility measurements, providing evidence that multi-site 7 T fMRI studies are feasible. These results can be used to inform sample size calculations for future multi-site somatomotor mapping studies.

Background: Immune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)–targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate cortex, prefrontal cortex, and insula regions; and 2) explore the relationship between cerebral TSPO binding and peripheral blood C-reactive protein (CRP) concentration. Methods: A total of 51 depressed subjects with Hamilton Depression Rating Scale score >13 (median 17; interquartile range, 16–22) and 25 healthy control subjects underwent dynamic brain 11C-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (2 p = .09; F 1,71 = 6.97, p = .01), which was not influenced by body mass index. The case-control difference was greatest in the anterior cingulate cortex (d = 0.49; t 74 = 2.00, p = .03) and not significant in the prefrontal cortex or insula (d = 0.27 and d = 0.36, respectively). Following CRP stratification, significantly higher TSPO binding was observed in low-CRP depression compared with controls (d = 0.53; t 54 = 1.96, p = .03). These effect sizes are comparable to prior major depressive disorder case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures. Conclusions: Consistent with previous findings, there is a modest increase in TSPO binding in depressed patients compared with healthy control subjects. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or body mass index poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.

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.MethodsTen 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 1x Philips, 2x Siemens Magnetom, and 2x 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 DiscussionMean 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.ConclusionThe 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.

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 The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists. Methods EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization. Results The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials. Discussion The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration.

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acids, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional1H MRS-detectable differences between IDH1 and IDH2 mutations, and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 37 ± 11, 13 males) were recruited for magnetic resonance spectroscopy (MRS) using semi-localization by adiabatic selective refocusing pulse sequence at an ultra-high-field (7T). For 20 patients, the tumor mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n= 15) and IDH2 (n= 5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 ± 1.01vs.0.72 ± 0.38,Pc< 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51,Pc= 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show the improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

PurposeSpinal cord MRI at ultra-high field is hampered by time-varying magnetic fields associated with the breathing cycle, giving rise to ghosting artifacts in multi-shot acquisitions. Here, we suggest a correction approach based on linking the signal from a respiratory bellows to field changes inside the spinal cord. The information is used to correct the data at the image reconstruction level.MethodsThe correction was demonstrated in the context of multi-shot T2*-weighted imaging of the cervical spinal cord at 7T. A respiratory trace was acquired during a high-resolution multi-echo gradient-echo sequence, used for structural imaging and quantitative T2* mapping, and a multi-shot EPI time series, as would be suitable for fMRI. The coupling between the trace and the breathing-induced fields was determined by a short calibration scan in each individual. Images were reconstructed with and without trace-based correction.ResultsIn the multi-echo GRE, breathing-induced fields caused severe ghosting in the long echo time images, which led to a systematic underestimation of T2* in the spinal cord. The trace-based correction reduced the ghosting and increased the estimated T2* values. Breathing-related ghosting was also observed in the multi-shot EPI images. The correction largely removed the ghosting, thereby improving the temporal signal-to-noise ratio of the time series.ConclusionsTrace-based retrospective correction of breathing-induced field variations can reduce ghosting and improve quantitative metrics in multi-shot structural and functional T2*-weighted imaging of the spinal cord. The method is straightforward to implement and does not rely on sequence modifications or additional hardware beyond a respiratory bellows.

The aim of this study was to acquire high-quality in vivo (1) H spectra concurrently from two voxels at ultra-high field (7 T) without specialized hardware. To this end, an acquisition scheme was developed in which first-order shims and flip angles are dynamically updated to acquire spectra from both of the brain's motor cortices in an alternating fashion. To validate this acquisition scheme, separate, static, single-voxel acquisitions were also performed for comparison. Six subjects were examined using semi-LASER spectroscopy at 7 T. Barium titanate pads were used to increase the extent of the effective transmit field (B1 (+) ). Spectra were obtained from the hand area of both motor cortices for both acquisition schemes. LCModel was used to determine neurochemical profiles in order to examine variations between acquisition schemes and volumes of interest. The dynamic two-voxel acquisition protocol produced water linewidths (full width at half-maximum between 11.6 and 12.8 Hz) and signal-to-noise ratios similar to those from static single-voxel measurements. The concentrations of 13 individual and 3 combined metabolites with Cramer-Rao lower bounds below 30% were reliably detected for both acquisition schemes, and agreed well with previous postmortem assay and spectroscopy studies. The results show that high spectral quality from two voxels can be acquired concurrently without specialized hardware. This practical technique can be applied to many neuroscience applications.

Abnormally high levels of the 'oncometabolite' 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field (≥7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection. Long echo time (long-TE) semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) is a promising method for improved 2-HG detection in vivo at either 3 or 7 T owing to the use of broad-band adiabatic localization. Using previously published semi-LASER methods at 3 and 7 T, this study directly compares the detectability of 2-HG in phantoms and in vivo across nine patients. Cramér-Rao lower bounds (CRLBs) of 2-HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild-type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2-HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ-aminobutyric acid (GABA) and 2-HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2-HG detection using long-TE acquisition at 7 T may allow for more rapid estimation of 2-HG (within a few spectral averages) together with other associated metabolic markers in glioma.

Significance statementFunctional topography is present throughout the cerebral cortex, often in the form of columns or clusters of neurons with similar functional properties within identified cortical regions. Most of the evidence for these structures comes from work with non-human species. Using high-field strength magnetic resonance imaging in living human cortex, the search for this structure is frustrated by the presence of a background of local spatial correlations in the signal across the cortical surface. This structured background, which we term ‘neural dust’, is a form of noise that imposes a fundamental limit on the detection of clustering and topography. We apply a novel analysis approach that quantifies the background of spatial correlations, so that we achieve reliable identification of high-signal clusters of activation in the human cortex at a scale previously only visible with invasive optical imaging in animals. We searched specifically in visual cortex for correlates of binocular stereoscopic depth. We show both that signals for stereoscopic depth are clustered into specific zones within the cortex and that these signals occur within spatially extended cortical domains, which have similar preferences for the stereoscopic depth. The revealed structures are reliably identified in all subjects tested and in repeated testing of individual subjects. Our methods provide an objective approach for defining the size and locations of clusters of activation within functional images of neural activity.AbstractA characteristic principle of the organization of cerebral neocortex is the presence of clusters or columns of neurons with similar functional properties. Animals with forward-facing eyes exploit slight differences between the images in the two eyes to determine binocular depth using stereopsis. Evidence for an organized structure in human visual cortex for the representation of stereoscopic depth has proved elusive. Using 7-tesla functional MRI, with gradient-echo echo-planar imaging at 0.75 mm isotropic resolution and a novel analytical approach based on geospatial mapping methods, we find that clustered responses for disparity-defined depth can be clearly segregated from a background of spatially correlated signals in all subjects tested. High-signal clusters are associated with cortical domains as large as 12-15mm across the cortical surface, in which nearby points in the cortical map tend to respond to the same stereoscopic depth. These domains are found predominantly within visual cortical area V3A.

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

A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate.

Determination of neurological pathology in white matter disease can be made in a semiquantitative way from T(1)- or T(2)-weighted images. A higher level of quantification based on measured T(1) or T(2) values has been either limited to specific regions of interest or to low-resolution maps. Higher-resolution T(1) maps have proved difficult to obtain due to the excessively long scan times required using conventional techniques. In this study, clinically acceptable images are obtained by using single-shot echo planar imaging (EPI) with an acquisition scheme that maximizes signal-to-noise while minimizing the scan time. Magn Reson Med 45:630-634, 2001.

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.

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.

Early visual areas can be defined using fMRI on the basis of their retinotopic organisation. Recently, very high-resolution images of the human brain in vivo have identified areas of myelination within the grey matter, corresponding to the striate cortex (Barbier et al. 2002; Clare et al. 2002). This myelination has traditionally been understood to correspond to the human primary visual cortex (V1). To test this correspondence, we compared the location of visually identified striate in high resolution images with the location of functionally defined V1. For imaging the myeloarchitecture, a magnetisation prepared 3D FLASH sequence was used as described in Clare et al. (2002). The resulting images had a resolution of 0.3×0.3×1.5 mm. Functional MRI was performed at a lower resolution of 3×3×1.5 mm using single shot EPI at the same 16 slice locations as the structural scan. Retinotopy data were collected using expanding ring and rotating wedge stimuli. The data were transformed onto a segmented (mrGray) and flattened (mrFlatMesh) T1-weighted scan (1×1×1mm). V1 was defined by locating the upper and lower field V1/V2 borders from the rotating wedge phase map. From the high-resolution myeloarchitecture images, striate cortex was conservatively determined as those regions where a stripe was identified within the grey matter. These observer drawn maps of striate cortex were then transformed into flattened space to allow comparison with the functional data. A good level of correspondence was found between the striate cortex determined in the structural MRI and V1 determined by fMRI. While the striate cortex was not identified as a continuous band, it is hoped that more striate will be revealed by using multiple slice orientations in the same subjects. In the future these very high-resolution structural images will offer the opportunity to combine the study of myeloarchitecture with functional architecture in the living human cortex.

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.