Static and dynamic BOLD fMRI components along white matter fibre tracts and their dependence on the orientation of the local diffusion tensor axis relative to the B0-field.

Recent studies have reported functional MRI (fMRI) activation within cerebral white matter (WM) using blood-oxygenation-level-dependent (BOLD) contrast. Many blood vessels in WM run parallel to the fibre bundles, and other studies observed dependence of susceptibility contrast-based measures of blood volume on the local orientation of the fibre bundles relative to the magnetic field or B0 axis. Motivated by this, we characterized the dependence of gradient-echo BOLD fMRI on fibre orientation (estimated by the local diffusion tensor) relative to the B0 axis to test whether the alignment between bundles and vessels imparts an orientation dependence on resting-state BOLD fluctuations in the WM. We found that the baseline signal level of the T2*-weighted data is 11% higher in voxels containing fibres parallel to B0 than those containing perpendicular fibres, consistent with a static influence of either fibre or vessel orientation on local T2* values. We also found that BOLD fluctuations in most bundles exhibit orientation effects expected from oxygenation changes, with larger amplitudes from voxels containing perpendicular fibres. Different magnitudes of this orientation effect were observed across the major WM bundles, with inferior fasciculus, corpus callosum and optic radiation exhibiting 14-19% higher fluctuations in voxels containing perpendicular compared to parallel fibres.

Imaging of the pial arterial vasculature of the human brain in vivo using high-resolution 7T time-of-flight angiography.

The pial arterial vasculature of the human brain is the only blood supply to the neocortex, but quantitative data on the morphology and topology of these mesoscopic arteries (diameter 50-300 µm) remains scarce. Because it is commonly assumed that blood flow velocities in these vessels are prohibitively slow, non-invasive time-of-flight magnetic resonance angiography (TOF-MRA)-which is well suited to high 3D imaging resolutions-has not been applied to imaging the pial arteries. Here, we provide a theoretical framework that outlines how TOF-MRA can visualize small pial arteries in vivo, by employing extremely small voxels at the size of individual vessels. We then provide evidence for this theory by imaging the pial arteries at 140 µm isotropic resolution using a 7 Tesla (T) magnetic resonance imaging (MRI) scanner and prospective motion correction, and show that pial arteries one voxel width in diameter can be detected. We conclude that imaging pial arteries is not limited by slow blood flow, but instead by achievable image resolution. This study represents the first targeted, comprehensive account of imaging pial arteries in vivo in the human brain. This ultra-high-resolution angiography will enable the characterization of pial vascular anatomy across the brain to investigate patterns of blood supply and relationships between vascular and functional architecture.

Sexual dimorphism in the cerebrovascular network: Brain MRI shows lower arterial density in women.

BACKGROUND AND PURPOSE: Accumulating evidence suggests that there is a sexual dimorphism in brain health, with women exhibiting greater disability following strokes of comparable size and having a higher prevalence of cognitive impairment later in life. Despite the critical implication of the cerebrovascular architecture in brain perfusion and brain health, it remains unclear whether structural differences in vessel density exist across the sexes. METHODS: In this study, we used high-density MRI imaging to characterize the intracerebral arterial and venous density of 28 (14 women) sex-matched healthy young volunteers in vivo. Using an in-house vessel segmentation algorithm, we quantified and compared these vascular features across the cortical and subcortical deep gray matter, white matter, and periventricular white matter. RESULTS: We found that, on average, women have reduced intracerebral arterial density in comparison to men (F 2.34 ± 0.48%, M 2.67 ± 0.39%; p<.05). This difference was most pronounced in the subcortical deep gray matter (F 1.78 ± 0.53%, M 2.38 ± 0.82%; p<.05) and periventricular white matter (F 0.68 ± 0.15%, M 1.14 ± 0.33%; p<.0005), indicating a potential sex-specific vulnerability to hypoperfusion in areas critical to core cerebral functions. In contrast, venous density did not exhibit a significant difference between sexes. CONCLUSIONS: While this research remains exploratory, it raises important pathophysiological considerations for brain health, adverse cerebrovascular events, and dementia across the sexes. Our findings also highlight the need to take into account sex differences when investigating cerebral characteristics in humans.

Arterial tortuosity syndrome causing recurrent transient ischemic attacks in young adult: a case report.

BACKGROUND: Arterial Tortuosity Syndrome (ATS) is a rare autosomal recessive disorder characterized by elongated and tortuous arteries. Although ATS showed a significant clinical and pathophysiological overlap with other syndromes involving connective tissues, only few cases of cerebrovascular events related to this syndrome have been described so far. CASE PRESENTATION: We report the case of a 33-years-old male diagnosed with ATS since childhood, that experienced three sudden episodes of expressive aphasia and right hemiparesis with spontaneous resolution. He was treated with recombinant tissue plasminogen activator (r-TPA) at a dosage of 0.9 mg/kg with a complete recovery. Brain Magnetic Resonance Imaging (MRI) showed the absence of acute ischemic lesions and the patient was diagnosed with recurrent transient ischemic attacks (TIA). Intracranial and supra-aortic trunks Magnetic Resonance Angiography (MRA) and Angio-CT scan of the thoracic and abdominal aorta showed marked vessel tortuosity without stenosis. To our knowledge, this is the first reported case of an ATS patient with TIA in young age that was treated with intravenous thrombolysis with recombinant plasminogen activator. CONCLUSION: Our report strengthens the relationship between ATS and juvenile cerebrovascular events, suggesting that an extensive study of body vessels in order to detect potential stenoses or occlusions in these cases is needed. The greater predisposition to cerebrovascular events in ATS could benefit from a more aggressive primary and secondary prevention therapy.

A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment.

INTRODUCTION: Unlike for glucose, uptake of the brain's main alternative fuel, ketones, remains normal in mild cognitive impairment (MCI). Ketogenic medium chain triglycerides (kMCTs) could improve cognition in MCI by providing the brain with more fuel. METHODS: Fifty-two subjects with MCI were blindly randomized to 30 g/day of kMCT or matching placebo. Brain ketone and glucose metabolism (quantified by positron emission tomography; primary outcome) and cognitive performance (secondary outcome) were assessed at baseline and 6 months later. RESULTS: Brain ketone metabolism increased by 230% for subjects on the kMCT (P < .001) whereas brain glucose uptake remained unchanged. Measures of episodic memory, language, executive function, and processing speed improved on the kMCT versus baseline. Increased brain ketone uptake was positively related to several cognitive measures. Seventy-five percent of participants completed the intervention. DISCUSSION: A dose of 30 g/day of kMCT taken for 6 months bypasses a significant part of the brain glucose deficit and improves several cognitive outcomes in MCI.

The morphology of the human cerebrovascular system.

While several methodologies exist for quantifying gray and white matter properties in humans, relatively little is known regarding the spatial organization and the intersubject variability of cerebral vessels. To resolve this, we developed a fast, open-source processing algorithm using advanced vessel segmentation schemes and iterative nonlinear registration to isolate, extract, and quantify cerebral vessels in susceptibility weighting imaging (SWI) and time-of-flight angiography (TOF-MRA) datasets acquired in a large cohort (n = 42) of healthy individuals. From this, whole-brain venous and arterial probabilistic maps were generated along with the computation of regional densities and diameters within regions based on popular anatomical and functional atlases. The results show that cerebral vasculature is highly heterogeneous, displaying disproportionally large vessel densities in brain areas such as the anterior and posterior cingulate, cuneus, precuneus, parahippocampus, insula, and temporal gyri. On average, venous densities were slightly higher and less variable across subjects than arterial. Moreover, regional variations in both venous and arterial density were significantly correlated to cortical thickness (R = 0.42). This publicly available new atlas of the human cerebrovascular system provides a first step toward quantifying morphological changes in the diseased brain and serving as a potential regression tool in fMRI analysis.

The Effectiveness of Transcranial Direct Current Stimulation as an Add-on Modality to Graded Motor Imagery for Treatment of Complex Regional Pain Syndrome: A Randomized Proof of Concept Study.

BACKGROUND: The efficacy of Graded Motor Imagery (GMI) for the management of Complex Regional Pain Syndrome (CRPS) is supported by evidence, but its treatment effect remains generally modest. Transcranial Direct Current Stimulation (tDCS) has been advocated as an adjunct intervention to enhance the effect of motor imagery approaches in pain populations. OBJECTIVE: The purpose of this study was to investigate the effectiveness of GMI+active tDCS compared with the GMI+sham tDCS in the treatment of CRPS type I. METHODS: A total of 22 patients (n=11/group) were randomly assigned to the experimental (GMI+tDCS) or placebo (GMI+sham tDCS) group. GMI treatments lasted 6 weeks; anodal tDCS was applied over the motor cortex for 5 consecutive days during the first 2 weeks and once a week thereafter. Changes in pain perception, quality of life, kinesiophobia, pain catastrophizing, anxiety and mood were monitored after 6 weeks of treatment (T1) and 1-month posttreatment (T2). RESULTS: GMI+tDCS induced no statistically significant reduction in pain compared with GMI+sham tDCS. Although we observed significant group differences in kinesiophobia (P=0.012), pain catastrophizing (P=0.049), and anxiety (P=0.046) at T1, these improvements were not maintained at T2 and did not reached a clinically significant difference. DISCUSSION: We found no added value of tDCS combined with GMI treatments for reducing pain in patients with chronic CRPS. However, given that GMI+sham tDCS induced no significant change, further studies comparing GMI+tDCS and tDCS alone are needed to further document tDCS's effect in CRPS.

Stimulus-evoked changes in cerebral vessel diameter: A study in healthy humans.

The high metabolic demand of neuronal tissue, coupled with its relatively low energy storage capacity, requires that increases in neuronal activation are quickly matched with increased blood flow to ensure efficient supply of oxygen and nutrients to the tissue. For this to occur, dilation of nearby arterioles must be coordinated with the dilation of larger upstream feeding arteries. As it stands, the exact spatial extent of such dilation in humans is unknown. Using non-invasive time-of-flight magnetic resonance angiography in healthy participants, we developed an automatic methodology for reconstructing cerebral arterial vessels and quantifying their diameter on a voxel-by-voxel basis. Specifically, we isolated the posterior cerebral artery (PCA) supplying each occipital lobe and quantified its vasodilation induced by visual stimulation. Stimulus-induced changes were strongest (∼30%) near primary visual cortex and progressively decreased in a non-linear fashion as a function of distance. Surprisingly, weak - albeit significant - changes (∼2%) were observed ∼70 mm from the visual cortex. This demonstrates that visual stimulation modulates vascular tone along the bulk of the PCA segment, and thus may have important implications for our understanding of functional hyperemia in healthy and diseased states.

On the Origin of Individual Functional Connectivity Variability: The Role of White Matter Architecture.

Fingerprint patterns derived from functional connectivity (FC) can be used to identify subjects across groups and sessions, indicating that the topology of the brain substantially differs between individuals. However, the source of FC variability inferred from resting-state functional magnetic resonance imaging remains unclear. One possibility is that these variations are related to individual differences in white matter structural connectivity (SC). However, directly comparing FC with SC is challenging given the many potential biases associated with quantifying their respective strengths. In an attempt to circumvent this, we employed a recently proposed test-retest approach that better quantifies inter-subject variability by first correcting for intra-subject nuisance variability (i.e., head motion, physiological differences in brain state, etc.) that can artificially influence FC and SC measures. Therefore, rather than directly comparing the strength of FC with SC, we asked whether brain regions with, for example, low inter-subject FC variability also exhibited low SC variability. From this, we report two main findings: First, at the whole-brain level, SC variability was significantly lower than FC variability, indicating that an individual's structural connectome is far more similar to another relative to their functional counterpart even after correcting for noise. Second, although FC and SC variability were mutually low in some brain areas (e.g., primary somatosensory cortex) and high in others (e.g., memory and language areas), the two were not significantly correlated across all cortical and sub-cortical regions. Taken together, these results indicate that even after correcting for factors that may differently affect FC and SC, the two, nonetheless, remain largely independent of one another. Further work is needed to understand the role that direct anatomical pathways play in supporting vascular-based measures of FC and to what extent these measures are dictated by anatomical connectivity.

Graph cut-based method for segmenting the left ventricle from MRI or echocardiographic images.

In this paper, we present a fast and interactive graph cut method for 3D segmentation of the endocardial wall of the left ventricle (LV) adapted to work on two of the most widely used modalities: magnetic resonance imaging (MRI) and echocardiography. Our method accounts for the fundamentally different nature of both modalities: 3D echocardiographic images have a low contrast, a poor signal-to-noise ratio and frequent signal drop, while MR images are more detailed but also cluttered and contain highly anisotropic voxels. The main characteristic of our method is to work in a 3D Bezier coordinate system instead of the original Euclidean space. This comes with several advantages, including an implicit shape prior and a result guarantied not to have any holes in it. The proposed method is made of 4 steps. First, a 3D sampling of the LV cavity is made based on a Bezier coordinate system. This allows to warp the input 3D image to a Bezier space in which a plane corresponds to an anatomically plausible 3D Euclidean bullet shape. Second, a 3D graph is built and an energy term (which is based on the image gradient and a 3D probability map) is assigned to each edge of the graph, some of which being given an infinite energy to ensure the resulting 3D structure passes through key anatomical points. Third, a max-flow min-cut procedure is executed on the energy graph to delineate the endocardial surface. And fourth, the resulting surface is projected back to the Euclidean space where a post-processing convex hull algorithm is applied on every short axis slice to remove local concavities. Results obtained on two datasets reveal that our method takes between 2 and 5s to segment a 3D volume, it has better results overall than most state-of-the-art methods on the CETUS echocardiographic dataset and is statistically as good as a human operator on MR images.

Spatial distribution of resting-state BOLD regional homogeneity as a predictor of brain glucose uptake: A study in healthy aging.

Positron emission tomography using [18F]-fluorodeoxyglucose (PET-FDG) is the primary imaging modality used to measure glucose metabolism in the brain (CMRGlu). CMRGlu has been used as a biomarker of brain aging and neurodegenerative diseases, but the complexity and invasive nature of PET often limits its use in research. There is therefore great interest in developing non-invasive metrics for estimating brain CMRGlu. We therefore investigated resting state fMRI metrics such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and regional global connectivity (Closeness) with multiple analytical approaches to determine their relationship to CMRGlu. We investigated this relation in two distinct cognitively healthy populations separated by age (27 young adults and 35 older adults). Overall, we found that both regionally and across participants, ReHo strongly correlated with CMRGlu in healthy young and older adults. Moreover, ReHo demonstrated the same age-related differences as CMRGlu throughout all cortical regions, particularly in the default network and frontal areas.

Practices of Return-to-Work Coordinators Working in Large Organizations.

Purpose Although the role of return-to-work coordinators (RTW coordinators) is associated with reducing long-term disabilities, little has been written about their practices. The objective of this study was to clearly identify their tasks and activities and the stakeholders with whom they collaborate. Methods A cross-sectional survey was conducted using a web-based self-administered questionnaire. Participant inclusion criteria were as follows: (1) working for a large organization with 500 or more employees; (2) being responsible for managing disabilities and coordinating the return-to-work process; and (3) having been involved in coordinating the return to work of at least one person in the past year. Results 195 RTW coordinators completed the questionnaire. The three tasks or activities rated as most important were applying laws, policies, and regulations related to work absences and return to work; contacting the absent worker; and planning the return to work. A nursing or occupational health and safety training background significantly influenced the RTW coordinators' practices. In addition, RTW coordinators collaborated mainly with workers and their supervisors. Conclusion Despite a wide variety of contexts and diverging definitions of competencies, a set of common RTW coordination practices appears to exist across industrialized countries. RTW coordinators with a training background in the health field seem better able to assimilate the various dimensions of work disability. Moreover, concerted action was found to be minimal and a far cry from recommendations. The practices defined could serve as a benchmark for describing RTW coordinators' responsibilities in greater detail and allow for cross-organization and cross-country comparisons.

Semi-Automatic Segmentation of Optic Radiations and LGN, and Their Relationship to EEG Alpha Waves.

At rest, healthy human brain activity is characterized by large electroencephalography (EEG) fluctuations in the 8-13 Hz range, commonly referred to as the alpha band. Although it is well known that EEG alpha activity varies across individuals, few studies have investigated how this may be related to underlying morphological variations in brain structure. Specifically, it is generally believed that the lateral geniculate nucleus (LGN) and its efferent fibres (optic radiation, OR) play a key role in alpha activity, yet it is unclear whether their shape or size variations contribute to its inter-subject variability. Given the widespread use of EEG alpha in basic and clinical research, addressing this is important, though difficult given the problems associated with reliably segmenting the LGN and OR. For this, we employed a multi-modal approach and combined diffusion magnetic resonance imaging (dMRI), functional magnetic resonance imaging (fMRI) and EEG in 20 healthy subjects to measure structure and function, respectively. For the former, we developed a new, semi-automated approach for segmenting the OR and LGN, from which we extracted several structural metrics such as volume, position and diffusivity. Although these measures corresponded well with known morphology based on previous post-mortem studies, we nonetheless found that their inter-subject variability was not significantly correlated to alpha power or peak frequency (p >0.05). Our results therefore suggest that alpha variability may be mediated by an alternative structural source and our proposed methodology may in general help in better understanding the influence of anatomy on function such as measured by EEG or fMRI.

Increased BOLD activation in the left parahippocampal cortex after 1 year of medical school: an association with cumulative verbal memory learning.

Although several studies have shown left-right hippocampus asymmetry during learning, it is unclear whether such asymmetry also exists for the parahippocampal cortex, a structure within the limbic system that is also involved in memory and learning. Using a common mental navigation task known to activate the bilateral parahippocampal cortex, this study aimed at determining how BOLD activation in these two areas changes after 1 year of medical school, a program characterized by intensive verbal learning. Fifteen first-year medical students participated in this study and underwent two sessions of functional MRI, at a 1-year interval. In the first session, we observed marginal differences between left and right parahippocampal cortex activity. However, 1 year later, left parahippocampal activation significantly increased (+4.7%), whereas the right remained stable. These results bring new information as to how intensive learning can modify regional metabolism in the human brain and how the left parahippocampal region is particularly important for cumulative verbal memory.

3D interactive tractography-informed resting-state fMRI connectivity.

In the past decade, the fusion between diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) has opened the way for exploring structure-function relationships in vivo. As it stands, the common approach usually consists of analysing fMRI and dMRI datasets separately or using one to inform the other, such as using fMRI activation sites to reconstruct dMRI streamlines that interconnect them. Moreover, given the large inter-individual variability of the healthy human brain, it is possible that valuable information is lost when a fixed set of dMRI/fMRI analysis parameters such as threshold values are assumed constant across subjects. By allowing one to modify such parameters while viewing the results in real-time, one can begin to fully explore the sensitivity of structure-function relations and how they differ across brain areas and individuals. This is especially important when interpreting how structure-function relationships are altered in patients with neurological disorders, such as the presence of a tumor. In this study, we present and validate a novel approach to achieve this: First, we present an interactive method to generate and visualize tractography-driven resting-state functional connectivity, which reduces the bias introduced by seed size, shape and position. Next, we demonstrate that structural and functional reconstruction parameters explain a significant portion of intra- and inter-subject variability. Finally, we demonstrate how our proposed approach can be used in a neurosurgical planning context. We believe this approach will promote the exploration of structure-function relationships in a subject-specific aspect and will open new opportunities for connectomics.

Using fMRI non-local means denoising to uncover activation in sub-cortical structures at 1.5 T for guided HARDI tractography.

In recent years, there has been ever-increasing interest in combining functional magnetic resonance imaging (fMRI) and diffusion magnetic resonance imaging (dMRI) for better understanding the link between cortical activity and connectivity, respectively. However, it is challenging to detect and validate fMRI activity in key sub-cortical areas such as the thalamus, given that they are prone to susceptibility artifacts due to the partial volume effects (PVE) of surrounding tissues (GM/WM interface). This is especially true on relatively low-field clinical MR systems (e.g., 1.5 T). We propose to overcome this limitation by using a spatial denoising technique used in structural MRI and more recently in diffusion MRI called non-local means (NLM) denoising, which uses a patch-based approach to suppress the noise locally. To test this, we measured fMRI in 20 healthy subjects performing three block-based tasks : eyes-open closed (EOC) and left/right finger tapping (FTL, FTR). Overall, we found that NLM yielded more thalamic activity compared to traditional denoising methods. In order to validate our pipeline, we also investigated known structural connectivity going through the thalamus using HARDI tractography: the optic radiations, related to the EOC task, and the cortico-spinal tract (CST) for FTL and FTR. To do so, we reconstructed the tracts using functionally based thalamic and cortical ROIs to initiates seeds of tractography in a two-level coarse-to-fine fashion. We applied this method at the single subject level, which allowed us to see the structural connections underlying fMRI thalamic activity. In summary, we propose a new fMRI processing pipeline which uses a recent spatial denoising technique (NLM) to successfully detect sub-cortical activity which was validated using an advanced dMRI seeding strategy in single subjects at 1.5 T.

Structural network underlying visuospatial imagery in humans.

INTRODUCTION: Several neuroimaging studies have shown that visuospatial imagery is associated with a multitude of activation nodes spanning occipital, parietal, temporal and frontal brain areas. However, the anatomical connectivity profile linking these areas is not well understood. Specifically, it is unknown whether cortical areas activated during visuospatial imagery are directly connected to one another, or whether few act as hubs which facilitate indirect connections between distant sites. Addressing this is important since mental imagery tasks are commonly used in clinical settings to assess complex cognitive functions such as spatial orientation. METHODS: We recorded functional magnetic resonance imaging (fMRI) data while participants (N = 18) performed a visuospatial imagery task. In the same subjects, we acquired diffusion MRI (dMRI) and used state-of-the-art tractography robust to fiber crossings to reconstruct the white matter tracts linking the fMRI activation sites. For each pair of these sites, we then computed the fraction of subjects showing a connection between them. RESULTS: Robust fMRI activation was observed in cortical areas spanning the dorsal (extrastriate, parietal and prefrontal areas) and ventral (temporal and lingual areas) pathways, as well as moderate deactivation in striate visual cortex. In over 80% of subjects, striate cortex showed anatomical connectivity with extrastriate (medial occipital) and lingual (posterior cingulate cortex-PCC) sites with the latter showing divergent connections to ventral (parahippocampus) and dorsal (BA7) activation areas. CONCLUSION: Our results demonstrate that posterior cingulate cortex is not only activated by visuospatial imagery, but also serves as an anatomical hub linking activity in occipital, parietal and temporal areas. This finding adds to the growing body of evidence pointing to PCC as a connector hub which may facilitate integration across widespread cortical areas.

Regional variations in vascular density correlate with resting-state and task-evoked blood oxygen level-dependent signal amplitude.

Functional magnetic resonance imaging (fMRI) has become one of the primary tools used for noninvasively measuring brain activity in humans. For the most part, the blood oxygen level-dependent (BOLD) contrast is used, which reflects the changes in hemodynamics associated with active brain tissue. The main advantage of the BOLD signal is that it is relatively easy to measure and thus is often used as a proxy for comparing brain function across population groups (i.e., control vs. patient). However, it is particularly weighted toward veins whose structural architecture is known to vary considerably across the brain. This makes it difficult to interpret whether differences in BOLD between cortical areas reflect true differences in neural activity or vascular structure. We therefore investigated how regional variations of vascular density (VAD) relate to the amplitude of resting-state and task-evoked BOLD signals. To address this issue, we first developed an automated method for segmenting veins in images acquired with susceptibility-weighted imaging, allowing us to visualize the venous vascular tree across the brain. In 19 healthy subjects, we then applied voxel-based morphometry (VBM) to T1-weighted images and computed regional measures of gray matter density (GMD). We found that, independent of spatial scale, regional variations in resting-state and task-evoked fMRI amplitudes were better correlated to VAD compared to GMD. Using a general linear model (GLM), it was observed that the bulk of regional variance in resting-state activity could be modeled by VAD. Cortical areas whose resting-state activity was most suppressed by VAD correction included Cuneus, Precuneus, Culmen, and BA 9, 10, and 47. Taken together, our results suggest that resting-state BOLD signals are significantly related to the underlying structure of the brain vascular system. Calibrating resting BOLD activity by venous structure may result in a more accurate interpretation of differences observed between cortical areas and/or individuals.