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  • Comparison of cerebral blood flow acquired by simultaneous [15O]water positron emission tomography and arterial spin labeling magnetic resonance imaging.

    24 October 2018

    Until recently, no direct comparison between [(15)O]water positron emission tomography (PET) and arterial spin labeling (ASL) for measuring cerebral blood flow (CBF) was possible. With the introduction of integrated, hybrid magnetic resonance (MR)-PET scanners, such a comparison becomes feasible. This study presents results of CBF measurements recorded simultaneously with [(15)O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [(15)O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant (P<0.05) correlation was observed between the two modalities; the whole-brain CBF values determined with PET and pCASL were 43.3±6.1 mL and 51.9±7.1 mL per 100 g per minute, respectively. The gray/white matter (GM/WM) ratio of CBF was 3.0 for PET and 3.4 for pCASL. A paired t-test revealed differences in regional CBF between ASL and PET with higher ASL-CBF than PET-CBF values in cortical areas. Using an integrated, hybrid MR-PET a direct simultaneous comparison between ASL and [(15)O]water PET became possible for the first time so that temporal, physiologic, and functional variations were avoided. Regional and individual differences were found despite the overall similarity between ASL and PET, requiring further detailed investigations.

  • Validation of planning-free vessel-encoded pseudo-continuous arterial spin labeling MR imaging as territorial-ASL strategy by comparison to super-selective p-CASL MRI.

    24 October 2018

    PURPOSE: Vessel-encoded (VE) pseudo-continuous arterial spin labeling (p-CASL) is a territorial ASL (T-ASL) technique to identify the perfusion territories of cerebral arteries. The aim of this study was to validate the output of three Vessel-encoded p-CASL image processing methods, k-means clustering with and without subsequent linear analysis and a Bayesian framework, by comparison with the perfusion maps acquired with super-selective p-CASL. METHODS: The comparison was done quantitatively using the Hausdorff distance and Dice similarity coefficient in the territories of the right and left internal carotid arteries, the basilar artery, and the right and left vertebral arteries. A qualitative comparison was done in the areas of the anterior and posterior circulation, and the deep gray matter. RESULTS: The overall agreement between the Vessel-encoded p-CASL image processing methods and super-selective p-CASL was good; with the difference that the linear analysis and the Bayesian framework were able to detect mixed perfusion. CONCLUSION: Planning-free Vessel-encoded p-CASL with k-means clustering appears suitable as a general purpose T-ASL strategy, but to determine mixed perfusion a combination with linear analysis, or the Bayesian framework is preferable, which are superior in this regard. To accurately determine the perfusion territory of a single vessel, super-selective p-CASL is still recommended.

  • Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging.

    24 October 2018

    The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.

  • Lacunar infarction associated with anabolic steroids and polycythemia: a case report.

    24 October 2018

    Lacunar infarction is traditionally ascribed to lipohyalinosis or microatheroma. We report the case of 40-year-old man, without traditional risk factors for ischemic stroke, who presented to the Emergency Department with recurrent episodes of transient right-sided weakness and paresthesia. Lacunar infarction was confirmed on diffusion-weighted MRI and blood tests showed a marked polycythemia. Quantitative magnetic resonance perfusion imaging demonstrated dramatically abnormal perfusion throughout both cerebral hemispheres, and transcranial Doppler revealed reduced cerebral artery velocities, both consistent with the proposed mechanism of hyperviscosity. His symptoms settled with treatment of the polycythemia and workup did not find another cause of ischemic stroke. We propose that hyperviscosity secondary to steroid-induced polycythemia caused ischemia in this case and not lipohyalinosis or microatheroma, to which lacunar disease is commonly attributed.

  • An Optimized Encoding Scheme for Planning Vessel-Encoded Pseudocontinuous Arterial Spin Labeling.

    24 October 2018

    PURPOSE: Vessel-encoded pseudocontinuous arterial spin labeling allows the acquisition of vessel-selective angiograms and vascular territory perfusion maps. The technique generates a periodic variation in inversion efficiency across space that can be manipulated to encode specific combinations of vessels. Currently, the choice of these encodings is limited to scenarios with few vessels and may not optimize the signal-to-noise ratio (SNR). Here we present an automated, rapid method for calculating a minimal number of SNR optimal encodings for any number and arrangement of vessels. THEORY AND METHODS: The proposed optimized encoding scheme (OES) is a Fourier-based method that finds SNR optimized encodings to best match the ideal encodings for a set of vessels. For nine or fewer vessels, the calculation takes less than 3 s. RESULTS: In simulations, the OES method produces encodings for a range of vessel geometries that, on average, have an SNR efficiency 37% greater than that for random encoding. When labeling vessels in the neck in healthy subjects, the OES encodings result in images with higher SNR than other encoding methods. CONCLUSION: The OES results in a minimal number of encodings with a higher SNR efficiency than other encoding methods, regardless of the number or geometry of the vessels.

  • Antibodies to heteromeric glycolipid complexes in Guillain-Barré syndrome.

    24 October 2018

    Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barré syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on the cis interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 heterodimeric glycolipid complexes). Serum samples of 181 patients from a geographically defined, Western European cohort of GBS cases were analysed, along with 161 control sera. Serum IgG binding to single gangliosides was observed in 80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating electrophysiology. The inclusion of glycolipid complexes increased the positivity rate in demyelinating disease to 62.4%. There were 40 antigens with statistically significantly increased binding intensities in GBS as compared to healthy control sera. Of these, 7 complex antigens and 1 single ganglioside also produced statistically significantly increased binding intensities in GBS versus neurological disease controls. The detection of antibodies against specific complexes was associated with particular clinical features including disease severity, requirement for mechanical ventilation, and axonal electrophysiology. This study demonstrates that while antibodies against single gangliosides are often found in cases with axonal-type electrophysiology, antibodies against glycolipid complexes predominate in cases with demyelinating electrophysiology, providing a more robust serum biomarker than has ever been previously available for such cases. This work confirms the activation of the humoral immune system in the dysimmune disease process in GBS, and correlates patterns of antigen recognition with different clinical features.

  • Primate comparative neuroscience using magnetic resonance imaging: promises and challenges.

    24 October 2018

    Primate comparative anatomy is an established field that has made rich and substantial contributions to neuroscience. However, the labor-intensive techniques employed mean that most comparisons are often based on a small number of species, which limits the conclusions that can be drawn. In this review we explore how new developments in magnetic resonance imaging have the potential to apply comparative neuroscience to a much wider range of species, allowing it to realize an even greater potential. We discuss (1) new advances in the types of data that can be acquired, (2) novel methods for extracting meaningful measures from such data that can be compared between species, and (3) methods to analyse these measures within a phylogenetic framework. Together these developments will allow researchers to characterize the relationship between different brains, the ecological niche they occupy, and the behavior they produce in more detail than ever before.

  • A neural circuit covarying with social hierarchy in macaques.

    24 October 2018

    Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

  • A model for extra-axonal diffusion spectra with frequency-dependent restriction.

    24 October 2018

    PURPOSE: In the brain, there is growing interest in using the temporal diffusion spectrum to characterize axonal geometry in white matter because of the potential to be more sensitive to small pores compared to conventional time-dependent diffusion. However, analytical expressions for the diffusion spectrum of particles have only been derived for simple, restricting geometries such as cylinders, which are often used as a model for intra-axonal diffusion. The extra-axonal space is more complex, but the diffusion spectrum has largely not been modeled. We propose a model for the extra-axonal space, which can be used for interpretation of experimental data. THEORY AND METHODS: An empirical model describing the extra-axonal space diffusion spectrum was compared with simulated spectra. Spectra were simulated using Monte Carlo methods for idealized, regularly and randomly packed axons over a wide range of packing densities and spatial scales. The model parameters are related to the microstructural properties of tortuosity, axonal radius, and separation for regularly packed axons and pore size for randomly packed axons. RESULTS: Forward model predictions closely matched simulations. The model fitted the simulated spectra well and accurately estimated microstructural properties. CONCLUSIONS: This simple model provides expressions that relate the diffusion spectrum to biologically relevant microstructural properties.

  • Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys.

    24 October 2018

    In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.