Category Archives: Magnetic Resonance

Primates brain shape

We have published one more paper on the morphology of the precuneus, this time featuring a sample of non-human primates, in collaboration with James Rilling and Todd Preuss from the Emory University (Atlanta, USA). Modern humans have a much larger precuneus than chimpanzees both in absolute and relative size. Taking into account the large brain size in our species, we investigated the midsagittal morphology in non-human primates as to test whether precuneus proportions are influenced by allometric factors. We did a geometric morphometric analysis on a total of 42 MRIs from the National chimpanzee brain resource database, including 5 species of apes and 4 species of monkeys. A first analysis, conducted on the species averages, showed that the main pattern of midsagittal variation involves the general shape of the braincase, which might be due to cranial constraints rather than to changes in proportions of specific brain regions. This main shape pattern separates monkeys from apes, as the former display flatter, elongated brains (with capuchins being the flattest), while the latter exhibit rounder brains with frontal bulging (especially orangutans). This morphological variation correlates with brain size, except for gorillas (which brain is large but elongated), and gibbons (which have smaller but round brains). A second analysis was conducted only on chimpanzees and macaques, to compare two species with different brain size. In neither case the proportions of the precuneus displayed major differences between species or size-related changes. However, as in humans, precuneus size is very variable within each species, suggesting a remarkable plasticity. Overall, the results suggest that precuneus expansion in modern humans is a species-specific characteristic of our species, rather than a simple consequence of increase in brain size. Further studies should address the histological and functional processes involved in this morphological change.

Sofia Pedro

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Vessels and neurosurgery

obrMagnetic Resonance Imaging (MRI) methods has a primary use in medicine, especially in diagnosis and image-guided surgery. In neuroscience, attention is mainly focused on the brain, and vessels are not always a target of the imaging procedures. The crucial aspect of using imaging during surgery concerns the correspondence with the real physical structures. This correspondence is affected by a displacement of the brain during surgery called brain shift, which can result in 5 – 10 mm difference from the MRI data. Several technical procedures are used in order to avoid this mismatch. Since intraoperative MRI devices are not always available, using local markers for orientation and navigation could be a plausible alternative. In a recent paper, Grabner and colleagues suggest to use the system of veins on the surface of the cerebral cortex as reference landmarks. These veins are well visible during the surgery, and can potentially improve navigation. The study is focused on developing a non-invasive MRI technique for the visualization of the superficial cortical veins and validation of that method by comparing MR images with high resolution photographs of human cadavers.

Considering Magnetic Resonance Angiography (MRA), the main concern of using this method is the use of a contrast agent, and the possibility of overlooking the superficial cortical veins because of the slow blood flow. Alternatively, the authors suggest to use Susceptibility-Weighted Imaging (SWI), which is a blood-oxygen-level dependent technique of MRI with an ability to image vessels smaller than a voxel. Gradient-echo based T2-weighted imaging was performed in this study using a 7 Tesla MRI scanner. Image processing relied on automated vessel segmentation and overlaid on anatomical MRI. The results showed high correlation between segmented veins in MRI and actual venous anatomy of the sample, and therefore surface venograms could serve as alternative navigation system for neurosurgery.

Reliable methods of imaging and segmentation of vessels are valuable also in theoretical fields, where those methods could contribute to the investigation of the function of the endocranial venous system. The importance of the veins is usually estimated according to their size, although functional information on these vessels is still scanty, and methodological research to improve craniovascular studies can be beneficial in both anthropology and medicine.

Stáňa Eisová


Microgravity and sensorimotor function

Space missions can have adverse effects on astronauts, such as the already-mentioned vision deterioration and cognitive impairment. Spending a long time on space can also impact sensorimotor function. Koppelmans et al. have recently investigated the influence of microgravity environment on sensorimotor performance and brain structure. They conducted a longitudinal study with a group of male subjects remaining in a 6-degrees head down tilt bed rest (HDBR) position, an analog environment to study the effects of spaceflight microgravity, during 70 days. MR images were collected before, during, and after HDBR, to explore changes in gray matter (GM) volume, and functional mobility and postural equilibrium tests were conducted pre- and post-HDBR, to check sensorimotor performance. For control, they used data from other subjects who had completed the same measurements at four different times over 90 days for another study, not being exposed to HDBR. Relative to controls, the HDBR subjects showed widespread changes in GM volume, as the percent of brain volume, from pre- to the last assessment during HDBR. More specifically, GM volume increased in the posterior parietal region and decreased in the fronto-temporal regions, and these changes are strongly correlated. The sensorimotor performance was decreased in HDBR subjects from pre- to post-HDBR, as they needed more time to complete the test, while controls showed no difference in performance. Following the HDBR period, both GM volume and sensorimotor changes started to recover, though not totally 12 days later. Regarding the association between brain and behavior, researchers found that larger increases in GM volume in precuneus and pre- and postcentral gyri correlated with better balance performance, though not significantly after Bonferroni correction. They propose these changes in GM volume might reflect cortical plasticity as an adaptive response to alterations in somatosensory input caused by HDBR position. The observed patterns of GM change could also be explained by alterations in intracranial fluids distribution and pressure due to posture, though this hypothesis would need further examination. The authors conclude their findings match the sensorimotor deterioration observed in astronauts, but are also of interest for individuals who are temporarily or permanently confined to a bed and will probably experience the same GM and sensorimotor alterations.

Sofia Pedro


Cortical and scalp development

In a recent study, Tsuzuki and colleagues analysed the co-development of the brain and head surfaces during the first two years of life using a sample of 16 infant MRIs, aged from 3 to 22 months. First, they digitized a set of cortical landmarks defined by the major sulci. Then they determined the position of cranial landmarks according to the 10-10 system, a standard method to place electrodes for electroencephalography, using  nasion, inion, and the pre-auriculars as a reference. Besides analysing the spatial variability of the cortical and scalp landmarks with age, they compared the variability of the cortical landmarks to the 10-10 positions, in order to evaluate the validity of the scalp system as a reference for brain development. For that, they transferred a given cortical landmark to the head surface by expressing its position as a composition of vectors in reference to the midpoint between the two pre-auriculars and to the three neighbor 10-10 points. The scalp-transferred landmarks were then transformed to the scalp template of a 12-month-old infant and depicted in reference to the 10-10 system.

Age-related changes in the cortical landmarks were most obvious in the prefrontal and parietal regions. As the brain elongates, the frontal lobe shifts anteriorly and the precentral gyri widen. In addition, the intraparietal sulci and the posterior part of the left Sylvian fissure move forward, suggesting relative enlargement of the parietal region in the anterior direction. The same result was obtained by our team by analyzing cranial and brain landmarks in adults: larger brain size is associated with a relative forward position of the parietal lobe. The scalp showed relative anteroposterior elongation and lateral narrowing with growth. Regarding the contrast between the cortical landmarks and the 10-10 system, the authors observed that the variability in the position of the former was much smaller than the area defined by 10-10 landmarks, indicating this system can be useful to predict the underlying cortical structures. Hence, they conclude that the changes in brain shape during development are well described by cortical landmarks and that the relative scalp positioning based on the 10-10 system can adjust to preserve the correspondence between the scalp and the cortical surfaces.

 

Sofia Pedro


What the brain’s wiring looks like

The world’s most detailed scan of the brain’s internal wiring has been produced by scientists at Cardiff University. The MRI machine reveals the fibres which carry all the brain’s thought processes. It’s been done in Cardiff, Nottingham, Cambridge and Stockport, as well as London England and London Ontario. Doctors hope it will help increase understanding of a range of neurological disorders and could be used instead of invasive biopsies …

[keep on reading this article by Fergus Walsh on BBC News]


Structural MRI artifacts

Magnetic resonance imaging (MRI) is a valuable and increasingly used method for studying brain anatomy as it allows large-scale, high-quality in vivo analyses. However, some artifacts might influence the digital results, and thus require cautious interpretation. In a recent review, these issues are addressed along with possible solutions. First, we need to keep in mind that the images acquired are not mere photographs of the brain, but reflect some biophysical properties of the tissues, by measuring the radio-frequency signals emitted by hydrogen atoms (present in water and fat) after being excited by magnetic waves. Thus, MRI is an indirect analysis of the brain anatomy and depends greatly on specific tissue properties. Second, researchers can choose from a variety of methods, depending on the aim of the survey. Macrostructure, i.e. the size and shape across voxels, can be studied through manual volumetry or automatic segmentation, voxel- or deformation-based morphometry, surface- based algorithms, or diffusion tractography. Microstructure, i.e. within-voxel contents, is usually analyzed through diffusion MRI, but also magnetization transfer imaging, or quantitative susceptibility mapping.

When making inferences on the biological significance of the outputs, the researcher must account for the possible digital artifacts. These can occur both during image acquisition and processing and can be subject-related and methodological-related. A common problem is subject motion, which might contaminate or influence the results, as the amount of motion varies with other factors influencing brain changes (age, sex, and disease status), or can even correlate with a specific effect being studied. For instance, motion induces gray matter reduction, which might be perceived as brain atrophy. Subject motion is unavoidable, but its influence can be reduced by using a motion detector during acquisition, or by estimating the amount of motion allowing statistical adjustments, also useful to  detect outliers. The difficulty in manipulating the magnetic and radio-frequency fields might also introduce deformation. The main magnetic field should be spatially uniform, but it is dispersed by brain tissue while concentrated by air. This can be partially compensated by applying additional fields. The radiofrequency field is not homogeneous, which affects MRI contrast and intensity. Combining multiple transmit coils might help reduce this caveat, although the contribution and sensitivity of each coil must be taken into account when processing the image.

A particular case that can affect estimates of cortical volume and thickness is the difficulty in discriminating the dura and gray matter due to the similar intensity and anatomical proximity. In this case,  MRI parameters can be manipulated in order to increase the contrast between these tissues, without reducing the contrast between gray and white matter. Individual variability in folding patterns is a further major issue in voxel-based morphometry studies because it complicates the mapping of correspondences between subjects. Registration might be enhanced by analyzing regions with larger variation to find possible anatomical alterations, aligning cortical folding patterns to locate corresponding areas, and mapping sulcal changes to improve sulci identification. Finally, researchers should continuously keep track of the constant advances and innovations in the field. The authors conclude acknowledging the importance of structural MRI when coupled with other biological information, like genetic expression (Allen Brain Atlas), cytoarchitecture (JuBrain), and cognitive associations (Neurosynth).

Sofia Pedro


fMRI Failure? Or a Replication Crisis?

fmri brain

In a recent study,  Eklund et al. sparked an ongoing international debate when it highlighted systemic failures in cluster-based analysis of functional magnetic resonance imaging (fMRI). The fMRI method has been used for decades to investigate correlations between brain region inactivation and task performance. Active regions in the brain are assigned by two methods: voxel-wise and cluster-wise inferences. Voxel-wise inference assigns activity to brain regions based on association of specific voxels.  Meanwhile, cluster-wise inference assigns activity based on correlation between specific clusters of voxels usually associated by size. The occurrence of false-positives is controlled in the most commonly used fMRI software packages (SPM, FSL and AFNI) by a function known as the Family-wise error (FWE). The Eklund et al. study examined the reliability of the five FWE analysis tools offered by the main software packages. The results showed that for the FWE in cluster-wise inference, parametric studies gave extremely high false-positives but were within range for the voxel-wise inference. To analyze the data using a nonparametric test, Eklund et al. utilized a permutation test which gave results for the FWE within the boundaries for both cluster-wise and voxel-wise inferences.

An independent post examined the assumptions behind the comparison of the five different FWE tools based on the differences between voxel-wise and cluster-wise thresholds. In short, voxel-wise thresholding relies on making a decision about ‘active’ brain regions at a specific voxel-level, whereas cluster-wise thresholding relies on this decision made about adjacent ‘clusters’ of voxels and is specific to the spatial distribution or size of the clusters. Eklund et al. also examined the in-built auto-correlation functions in the software packages which assign activity to a brain region based on the cluster representing a squared exponential. This is the basic assumption made by the auto-correlation algorithm but in testing this functionality, Eklund et al. found the assumption of spatial smoothness did not follow a Gaussian distribution or was not normally distributed across the entire brain. The lack of spatial smoothness lead the auto-correlation function to incorrectly calculate clusters and in turn, force a false-positive finding.

With the Eklund et al. research actively calling into question the fMRI studies of the past two decades, a heated debate arose around the validity of such a statement and the methods used in the research. Subsequently, the statement was retracted and redefined but this did not go unnoticed. Unfortunately, it does appear that the issue at the heart of this debate has been overlooked and somewhat downplayed which is the matter of reproducibility affecting neuroscience and all science in general. The replication of all results are essential to removing incorrect inferences and misassumptions that lead discoveries to be meaningless without validation. While the debate over the ‘failure’ of fMRI continues to evolve the premise holds that without validation of scientific hypotheses there will never be an opportunity for these to graduate into scientific theories.

Alannah Pearson


Precuneus: folding and metrics

Pereira-Pedro and Bruner 2016_1 This month we have published a study featuring the cortical extension and anatomy of the precuneus, dealing with its metrics as well as with its sulcal pattern. The analysis was based on a MRI sample of 50 adult humans from both sexes. Our previous works concerned the variation, position, and surface, as well as the phylogenetic differences in the midsagittal plane. Instead, in this survey metrics was assessed on the coronal plane, “cutting” the precuneus in its anterior, middle and posterior sections, taking into account its curvature. The lateral (inner) extension of the precuneus was measured along the subparietal sulcus and its height was measured from the subparietal sulcus to the endocranial wall. Then a set of 10 two dimensional landmarks were digitized on the middle section along the outline of the parietal lobe, to analyze the correlation between outer brain profile and inner precuneus dimensions. We found that, on average, the precuneus extends 14 mm laterally and 36 mm vertically. It is wider on the anterior and middle sections, and usually larger on the right hemisphere, possibly due to the length of the fold (surface area) rather than to the thickness of the grey matter. The precuneus height influences the outer brain morphology (vertical stretching), but the subparietal size apparently has no influence on the external outline. Therefore, at least the former trait could be investigated in paleoneurology, by indirect inference on the inner dimensions as evaluated through their external effects. The lateral (parasagittal) surface of the upper parietal lobules seems to be unrelated to the size of the precuneus. Therefore, when a change of these areas is detected (like in Neandertals) the intraparietal sulcus is a better candidate as the cortical element involved in the morphological variations.

Pereira-Pedro and Bruner 2016_2

The sulcal pattern was analyzed on the average density projection of the 5 most sagittal stacks (5 mm of the cortex), a thickness which displays most of the sulcal features. Three characteristics were taken into consideration: the connections of the subparietal sulcus, the connections of other sulci in the precuneus, and the general sulcal scheme. Some of these features have been analyzed in other surveys, but  the consideration of other folds beyond the subparietal one is specific of this study. Roughly half of the precuneus sulci that reach the external surface are not linked to the subparietal sulcus. Contrary to other studies which found higher frequencies of an H-like pattern of the subparietal sulcus, we found a larger proportion of an inverted-T pattern (subparietal sulcus connected with one precuneus sulcus). The differences between studies might be due to random effects of the samples, because of the relevant individual variability of these traits. The left hemisphere displays more sulci reaching the external surface while the right hemisphere displays deeper folding. The anterior area shows more sulcal complexity than the posterior one. There seems to be no relationship between the size of the subparietal sulcus and its folding pattern, and these characteristics might be hence influenced by genetics or folding biomechanics.

Sofia Pedro


Chimp brains

NCBSDear colleagues,
We are very pleased to announce the launch of the National Chimpanzee Brain Resource (NCBR) website. The NCBR is supported by the National Institute of Neurological Disorders and Stroke. We encourage you to browse the site, where you will find information about MRI datasets and tissue samples that are available by request to researchers. The NCBR website also serves as a data repository for studies that include chimpanzee brains. In the near future, the NCBR website will grow with the addition of a searchable database of behavioral and cognitive tasks, pedigrees, rearing history, neuroimaging data, and postmortem brain samples; chimpanzee brain atlas tools; and educational information about chimpanzee neuroscience. We invite you to make a request for MRI data or tissue. Please contribute your datasets that include chimpanzee brains to the repository. Our aim is for the NCBR to facilitate research advancement through the distribution of chimpanzee brain resources and dissemination of information, promoting the value of chimpanzees as a comparative reference to better understand the structure, function, and evolution of the human brain.

NCBR Directors
Chet Sherwood, Bill Hopkins, Todd Preuss


Brain gyrification and simulations

The advantages of brain gyrification are well established, but the mechanisms behind this process are yet matter of discussion. However, early this month, a group of researchers published two models for brain gyrification based on the mechanical stress generated by the differential growth of the cortical layer. They created a physical model of a brain in three steps: (1) 3D printing a plastic replica from a MRI of a smooth fetal brain; (2) build a silicon negative mould to cast the core of a gel brain, which would represent the white matter; and after cooled, (3)  deposited the same gel polymer in the surface of the core to form the cortical layer. These polymer layers act as elastic solids. The mimicking of fetal brain growth was accomplished by placing the gel brain in a substrate of hexanes that would cause swelling and differential growth of the outer cortical layer, in respect to the core of the model. Starting from the same MRI, they also built a numerical model based on finite element and parameters like cortical thickness, brain growth and tissue stiffness, creating functions for folding and unfolding simulations. The combined results of the physical and numerical simulations showed that the pattern of gyrification depends on the overall shape of the brain, and the primary sulci are formed perpendicularly to the largest compressive stress. Their models are robust and reproducible, capturing the main gyral scheme and even account for variability and hemispherical differences. Furthermore, when comparing the simulated brain to a real one, they were able to find a correspondence with all the primary folds.

Sofia Pedro