Search

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.

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.

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.

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.

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.

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

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.

The most common design of a functional MRI (fMRI) experiment is a block design. The use of rapid imaging, however, and carefully designed paradigms makes the separation of cognitive events possible. Such experiments make use of event-related paradigms, in which a task involving several cognitive processes is repeated. In analyzing data from such experiments, existing methods often prove inadequate, because the prediction of the exact shape or timing of the time course is difficult. Here we present an analysis of variance (ANOVA) method for analyzing fMRI data that does not require any assumptions about the shape of the activation time course. Consequently, this method can simultaneously detect brain areas showing a variety of stimulus-locked time courses in the same experiment. The utility of this technique is demonstrated by the analysis of data from two event-related paradigms in which regions of activation are detected that correspond to a variety of distinct neural processes, yielding significantly different temporal signal changes. Magn Reson Med 42:1117‐1122, 1999. r 1999 Wiley-Liss, Inc.

Patient motion during the acquisition of a magnetic resonance image can cause blurring and ghosting artifacts in the image. This paper presents a new post-processing strategy that can reduce artifacts due to in-plane, rigid-body motion in times comparable to that required to re-scan a patient. The algorithm iteratively determines unknown patient motion such that corrections for this motion provide the best image quality, as measured by an entropy-related focus criterion. The new optimization strategy features a multi-resolution approach in the phase-encode direction, separate successive one-dimensional searches for rotations and translations, and a novel method requiring only one re-gridding calculation for each rotation angle considered. Applicability to general rigid-body in-plane rotational and translational motion and to a range of differently weighted images and k-space trajectories is demonstrated. Motion artifact reduction is observed for data from a phantom, volunteers, and patients.

Single-shot techniques have preferentially been adopted for diffusion-weighted imaging due to their reduced sensitivity to bulk motion. However, the limited spatial resolution achievable results in orientational signal averaging within voxels containing a distribution of fibers. This leads to impaired performance of tracking algorithms. To combat partial volume effects, high-resolution multishot techniques can be used but, being more sensitive to motion, require phase correction to obtain artifact-free images. While separately acquiring 2D navigator echoes is an effective approach, it is not very efficient as the navigators do not contribute signal to the final image. Here a self-navigated interleaved echo planar imaging (EPI) sequence based on EPI with keyhole (EPIK) is proposed. The refocusing reconstruction method is successfully adapted to EPIK and compared to the standard linear approach. The resultant improvement in resolution is shown to lead to a significant increase in anisotropy in fiber-branching areas and can potentially offer a superior ability to detect fine tract splits.

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.

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.

Post-mortem diffusion imaging of whole, human brains has potential to provide data for validation or high-resolution anatomical investigations. Previous work has demonstrated improvements in data acquired with diffusion-weighted steady-state free precession (DW-SSFP) compared with conventional diffusion-weighted spin echo at 3 T. This is due to the ability of DW-SSFP to overcome signal-to-noise and diffusion contrast losses brought about by tissue fixation related decreases in T2 and ADC. In this work, data of four post-mortem human brains were acquired at 3 T and 7 T, using DW-SSFP with similar effective b-values (beff ~ 5150 s/mm2) for inter-field strength comparisons; in addition, DW-SSFP data were acquired at 7 T with higher beff (~ 8550 s/mm2) for intra-field strength comparisons. Results demonstrate that both datasets acquired at 7 T had higher SNR and diffusion contrast than data acquired at 3 T, and data acquired at higher beff had improved diffusion contrast than at lower beff at 7 T. These results translate to improved estimates of secondary fiber orientations leading to higher fidelity tractography results compared with data acquired at 3 T. Specifically, tractography streamlines of cortical projections originating from the corpus callosum, corticospinal tract, and superior longitudinal fasciculus were more successful at crossing the centrum semiovale and projected closer to the cortex. Results suggest that DW-SSFP at 7 T is a preferential method for acquiring diffusion-weighted data of post-mortem human brain, specifically where the primary region of interest involves crossing white matter tracts., Highlights • Diffusion weighted SSFP imaging of post-mortem human brain at 7 T is compared to 3 T. • Both SNR and diffusion contrast are improved at 7 T. • 7 T data show improved crossing fiber estimates and accompanying tractography. • Including B1 map in 7 T data analysis brings diffusion metrics in line with 3 T data.