High Angular Resolution Diffusion MRI Research Articles

Adolescents with ADHD and co-occurring motor difficulties show a distinct pattern of maturation within the corticospinal tract from those without: A longitudinal fixel-based study.

It is well documented that attention-deficit hyperactivity disorder (ADHD) often presents with co-occurring motor difficulties. However, little is known about the biological mechanisms that explain compromised motor skills in approximately half of those with ADHD. To provide insight into the neurobiological basis of poor motor outcomes in ADHD, this study profiled the development of white matter organization within the cortico-spinal tract (CST) in adolescents with ADHD with and without co-occurring motor problems, as well as non-ADHD control children with and without motor problems. Participants were 60 children aged 9-14 years, 27 with a history of ADHD and 33 controls. All underwent high-angular resolution diffusion MRI data at up to three time points (115 in scans total). We screened for motor impairment in all participants at the third time point (≈14 years) using the Developmental Coordination Disorder Questionnaire (DCD-Q). Following pre-processing of diffusion MRI scans, fixel-based analysis was performed, and the bilateral CST was delineated using TractSeg. Mean fiber density (FD) and fiber cross-section (FC) were extracted for each tract at each time-point. To investigate longitudinal trajectories of fiber development, linear mixed models were performed separately for the left and right CST, controlling for nuisance variables. To examine possible variations in fiber development between groups, we tested whether the inclusion of group and the interaction between age and group improved model fit. At ≈10 years, those with ADHD presented with lower FD within the bilateral CST relative to controls, irrespective of their prospective motor status. While these microstructural abnormalities persisted into adolescence for individuals with ADHD and co-occurring motor problems, they resolved for those with ADHD alone. Divergent maturational pathways of motor networks (i.e., the CST) may, at least partly, explain motor problems individuals with ADHD.

Olfactory Loss and Brain Connectivity after COVID-19: Structural Follow-Up at One Year.

The structural connectivity from the primary olfactory cortex to the main secondary olfactory areas was previously reported as relatively increased in the medial orbitofrontal cortex in a cohort of 27 recently SARS-CoV-2-infected (COV+) subjects, of which 23/27 had clinically confirmed olfactory loss, compared to 18 control (COV-) normosmic subjects, who were not previously infected. To complement this finding, here we report the outcome of an identical high angular resolution diffusion MRI analysis on follow-up data sets collected in 18/27 COV+ subjects (10 males, mean age ± SD: 38.7 ± 8.1 years) and 10/18 COV- subjects (5 males, mean age ± SD: 33.1 ± 3.6 years) from the previous samples who repeated both the olfactory functional assessment and the MRI examination after ~1 year. By comparing the newly derived subgroups, we observed that the increase in the structural connectivity index of the medial orbitofrontal cortex was not significant at follow-up, despite 10/18 COV+ subjects were still found hyposmic after ~1 year from SARS-CoV-2 infection. We concluded that the relative hyperconnectivity of the olfactory cortex to the medial orbitofrontal cortex could be, at least in some cases, an acute or reversible phenomenon linked to the recent SARS-CoV-2 infection with associated olfactory loss.

Spatiotemporal Developmental Gradient of Thalamic Morphology, Microstructure, and Connectivity fromthe Third Trimester to Early Infancy.

Thalamus is a critical component of the limbic system that is extensively involved in both basic and high-order brain functions. However, how the thalamic structure and function develops at macroscopic and microscopic scales during the perinatal period development is not yet well characterized. Here, we used multishell high-angular resolution diffusion MRI of 144 preterm-born and full-term infants in both sexes scanned at 32-44 postmenstrual weeks (PMWs) from the Developing Human Connectome Project database to investigate the thalamic development in morphology, microstructure, associated connectivity, and subnucleus division. We found evident anatomic expansion and linear increases of fiber integrity in the lateral side of thalamus compared with the medial part. The tractography results indicated that thalamic connection to the frontal cortex developed later than the other thalamocortical connections (parieto-occipital, motor, somatosensory, and temporal). Using a connectivity-based segmentation strategy, we revealed that functional partitions of thalamic subdivisions were formed at 32 PMWs or earlier, and the partition developed toward the adult pattern in a lateral-to-medial pattern. Collectively, these findings revealed faster development of the lateral thalamus than the central part as well as a posterior-to-anterior developmental gradient of thalamocortical connectivity from the third trimester to early infancy.SIGNIFICANCE STATEMENT This is the first study that characterizes the spatiotemporal developmental pattern of thalamus during the third trimester to early infancy. We found that thalamus develops in a lateral-to-medial pattern for both thalamic microstructures and subdivisions; and thalamocortical connectivity develops in a posterior-to-anterior gradient that thalamofrontal connectivity appears later than the other thalamocortical connections. These findings may enrich our understanding of the developmental principles of thalamus and provide references for the atypical brain growth in neurodevelopmental disorders.

Longitudinal developmental trajectories of inhibition and white-matter maturation of the fronto-basal-ganglia circuits

Response inhibition refers to the cancelling of planned (or restraining of ongoing) actions and is required in much of our everyday life. Response inhibition appears to improve dramatically in early development and plateau in adolescence. The fronto-basal-ganglia network has long been shown to predict individual differences in the ability to enact response inhibition. In the current study, we examined whether developmental trajectories of fiber-specific white matter properties of the fronto-basal-ganglia network was predictive of parallel developmental trajectories of response inhibition. 138 children aged 9–14 completed the stop-signal task (SST). A subsample of 73 children underwent high-angular resolution diffusion MRI data for up to three time points. Performance on the SST was assessed using a parametric race modelling approach. White matter organization of the fronto-basal-ganglia circuit was estimated using fixel-based analysis. Contrary to predictions, we did not find any significant associations between maturational trajectories of fronto-basal-ganglia white matter and developmental improvements in SST performance. Findings suggest that the development of white matter organization of the fronto-basal-ganglia and development of stopping performance follow distinct maturational trajectories.

White matter variability in auditory callosal pathways contributes to variation in the cultural transmission of auditory symbolic systems.

The cultural transmission of spoken language and music relies on human capacities for encoding and recalling auditory patterns. In this experiment, we show that interindividual differences in this ability are associated with variation in the organization of cross-callosal white matter pathways. First, high-angular resolution diffusion MRI (dMRI) data were analyzed in a large participant sample (N = 51). Subsequently, these participants underwent a behavioral test that models in the laboratory the cultural transmission of auditory symbolic systems: the signaling game. Cross-callosal and intrahemispheric (arcuate fasciculus) pathways were reconstructed and analyzed using conventional diffusion tensor imaging (DTI) as well as a more advanced dMRI technique: fixel-based analysis (FBA). The DTI metric of fractional anisotropy (FA) in auditory callosal pathways predicted-weeks after scanning-the fidelity of transmission of an artificial tone system. The ability to coherently transmit auditory signals in one signaling game, irrespective of the signals learned during the previous game, was predicted by morphological properties of the fiber bundles in the most anterior portions of the corpus callosum. The current study is the first application of dMRI in the field of cultural transmission, and the first to connect individual characteristics of callosal pathways to core behaviors in the transmission of auditory symbolic systems.

The connections of the insular VEN area in great apes: A histologically-guided ex vivo diffusion tractography study.

We mapped the connections of the insular von Economo neuron (VEN) area in ex vivo brains of a bonobo, an orangutan and two gorillas with high angular resolution diffusion MRI imaging acquired in 36 h imaging sessions for each brain. The apes died of natural causes without neurological disorders. The localization of the insular VEN area was based on cresyl violet-stained histological sections from each brain that were coregistered with structural and diffusion images from the same individuals. Diffusion MRI tractography showed that the insular VEN area is connected with olfactory, gustatory, visual and other sensory systems, as well as systems for the mediation of appetite, reward, aversion and motivation. The insular VEN area in apes is most strongly connected with frontopolar cortex, which could support their capacity to choose voluntarily among alternative courses of action particularly in exploring for food resources. The frontopolar cortex may also support their capacity to take note of potential resources for harvesting in the future (prospective memory). All of these faculties may support insight and volitional choice when contemplating courses of action as opposed to rule-based decision-making.

Regionconnect: Rapidly extracting standardized brain connectivity information in voxel-wise neuroimaging studies

Reporting white matter findings in voxel-wise neuroimaging studies typically lacks specificity in terms of brain connectivity. Therefore, the purpose of this work was to develop an approach for rapidly extracting standardized brain connectivity information for white matter regions with significant findings in voxel-wise neuroimaging studies. The new approach was named regionconnect and is based on precalculated average healthy adult brain connectivity information stored in standard space in a fashion that allows fast retrieval and integration. Towards this goal, the present work first generated and evaluated the white matter connectome of the IIT Human Brain Atlas v.5.0. It was demonstrated that the edges of the atlas connectome are representative of those of individual participants of the Human Connectome Project in terms of the spatial organization of streamlines and spatial patterns of track-density. Next, the new white matter connectome was used to develop multi-layer, connectivity-based labels for each white matter voxel of the atlas, consistent with the fact that each voxel may contain axons from multiple connections. The regionconnect algorithm was then developed to rapidly integrate information contained in the multi-layer labels across voxels of a white matter region and to generate a list of the most probable connections traversing that region. Usage of regionconnect does not require high angular resolution diffusion MRI or any MRI data. The regionconnect algorithm as well as the white matter tractogram and connectome, multi-layer, connectivity-based labels, and associated resources developed for the IIT Human Brain Atlas v.5.0 in this work are available at www.nitrc.org/projects/iit. An interactive, online version of regionconnect is also available at www.iit.edu/~mri.

Understanding motor difficulties in children with ADHD: A fixel-based analysis of the corticospinal tract

AimsChildren with attention deficit hyperactivity disorder (ADHD) often present with deficits in fine motor control. The cortico-spinal tract (CST) is critical for voluntary motor control. Although neuroimaging work has identified anomalous microstructural properties in the CST in ADHD, no study to date has attempted to investigate the link between deficits in fine motor performance and microstructural properties of the CST in children with ADHD. This study aimed to address this gap using a novel fixel-based analysis (FBA). MethodsParticipants were 50 right-handed medication naïve children with a history of ADHD and 56 non-ADHD controls aged 9–11 years. Fine motor control was assessed using the Grooved Pegboard task. Children underwent high angular resolution diffusion MRI. Following pre-processing, FBA was performed and the semi-automated deep-learning TractSeg was used to delineate the CST bilaterally. Fibre density (FD), fibre cross-section (FC-log), and fibre density/cross-section (FDC) were extracted for each tract. ResultsChildren with ADHD performed significantly worse than non-ADHD children on the Grooved Pegboard task when using their non-dominant hand. They also demonstrated widespread significantly lower diffusion metrics in both CSTs compared to non-ADHD controls. However, no correlations were observed between Grooved Pegboard performance and diffusion metrics for the CST in either hemisphere. ConclusionsWhile we failed to detect a significant relationship between fine motor skill and FBA metrics in either group, this paper extends previous work by showing that children with ADHD and reduced fine motor competence demonstrate atypical microstructure within the CST relative to non-ADHD controls.

Reduced fine motor competence in children with ADHD is associated with atypical microstructural organization within the superior longitudinal fasciculus.

Recent work in healthy adults suggests that white matter organization within the superior longitudinal fasciculus (SLF) may, at least partly, explain individual differences in fine motor skills. The SLF is also often implicated in the neurobiology underlying attention deficit hyperactivity disorder (ADHD) as part of the attention network connecting frontal and parietal regions. While ADHD is primarily characterized by inattention, impulsivity and/or hyperactivity, atypical fine motor control is a common comorbid feature. This study aimed to investigate the association between reduced fine motor skills in ADHD and microstructural properties within the SLF. Participants were 55 right-handed children with ADHD and 61 controls aged 9-11years. Fine motor control was assessed using the Grooved Pegboard task. Children underwent high angular resolution diffusion MRI. Following pre-processing, constrained spherical deconvolution tractography was performed to delineate the three SLF branches bilaterally. Children with ADHD showed significantly poorer fine motor performance relative to controls in the non-dominant hand, indicated by significantly slower left handed Grooved Pegboard task performance. This slower response time for the non-dominant (left) hand was significantly associated with reduced apparent fibre density within the right SLF I, and reduced right SLF I, II and III volume. This finding was independent of spatial attention performance. These data support previous reports indicating that children with ADHD have poorer fine motor performance than controls in their non-dominant hand, and indicates that the neurobiological basis for impaired fine motor control may involve white matter properties within the contralateral SLF. This suggests that white matter properties in fronto-parietal areas may have broader implications than attention.

Insight into the fundamental trade-offs of diffusion MRI from polarization-sensitive optical coherence tomography in ex vivo human brain

In the first study comparing high angular resolution diffusion MRI (dMRI) in the human brain to axonal orientation measurements from polarization-sensitive optical coherence tomography (PSOCT), we compare the accuracy of orientation estimates from various dMRI sampling schemes and reconstruction methods. We find that, if the reconstruction approach is chosen carefully, single-shell dMRI data can yield the same accuracy as multi-shell data, and only moderately lower accuracy than a full Cartesian-grid sampling scheme. Our results suggest that current dMRI reconstruction approaches do not benefit substantially from ultra-high b-values or from very large numbers of diffusion-encoding directions. We also show that accuracy remains stable across dMRI voxel sizes of 1 ​mm or smaller but degrades at 2 ​mm, particularly in areas of complex white-matter architecture. We also show that, as the spatial resolution is reduced, axonal configurations in a dMRI voxel can no longer be modeled as a small set of distinct axon populations, violating an assumption that is sometimes made by dMRI reconstruction techniques. Our findings have implications for in vivo studies and illustrate the value of PSOCT as a source of ground-truth measurements of white-matter organization that does not suffer from the distortions typical of histological techniques.

Reduced structural connectivity in cortico-striatal-thalamic network in neonates with congenital heart disease

Impaired brain development has been observed in newborns with congenital heart disease (CHD). We performed graph theoretical analyses and network-based statistics (NBS) to assess global brain network topology and identify subnetworks of altered connectivity in infants with CHD prior to cardiac surgery. Fifty-eight infants with critical/serious CHD prior to surgery and 116 matched healthy controls as part of the developing Human Connectome Project (dHCP) underwent MRI on a 3T system and high angular resolution diffusion MRI (HARDI) was obtained. Multi-tissue constrained spherical deconvolution, anatomically constrained probabilistic tractography (ACT) and spherical-deconvolution informed filtering of tractograms (SIFT2) was used to construct weighted structural networks. Network topology was assessed and NBS was used to identify structural connectivity differences between CHD and control groups. Structural networks were partitioned into core and peripheral nodes, and edges classed as core, peripheral, or feeder. NBS identified one subnetwork with reduced structural connectivity in CHD infants involving basal ganglia, amygdala, hippocampus, cerebellum, vermis, and temporal and parieto-occipital lobe, primarily affecting core nodes and edges. However, we did not find significantly different global network characteristics in CHD neonates. This locally affected sub-network with reduced connectivity could explain, at least in part, the neurodevelopmental impairments associated with CHD.

The role of the fornix in human navigational learning

Experiments on rodents have demonstrated that transecting the white matter fibre pathway linking the hippocampus with an array of cortical and subcortical structures - the fornix - impairs flexible navigational learning in the Morris Water Maze (MWM), as well as similar spatial learning tasks. While diffusion magnetic resonance imaging (dMRI) studies in humans have linked inter-individual differences in fornix microstructure to episodic memory abilities, its role in human spatial learning is currently unknown. We used high-angular resolution diffusion MRI combined with constrained spherical deconvolution-based tractography, to ask whether inter-individual differences in fornix microstructure in healthy young adults would be associated with spatial learning in a virtual reality navigation task. To efficiently capture individual learning across trials, we adopted a novel curve fitting approach to estimate a single index of learning rate. We found a statistically significant correlation between learning rate and the microstructure (mean diffusivity) of the fornix, but not that of a comparison tract linking occipital and anterior temporal cortices (the inferior longitudinal fasciculus, ILF). Further, this correlation remained significant when controlling for both hippocampal volume and participant gender. These findings extend previous animal studies by demonstrating the functional relevance of the fornix for human spatial learning in a virtual reality environment, and highlight the importance of a distributed neuroanatomical network, underpinned by key white matter pathways, such as the fornix, in complex spatial behaviour.

Structural core of the executive control network: A high angular resolution diffusion MRI study.

Executive function (EF) is a set of cognitive capabilities considered essential for successful daily living, and is negatively affected by ageing and neurodegenerative conditions. Underpinning EF performance are functional nodes in the executive control network (ECN), while the structural connectivity underlying this network is not well understood. In this paper, we evaluated the structural white matter tracts that interconnect the ECN and investigated their relationship to the EF performance. Using high‐angular resolution diffusion MRI data, we performed tractography analysis of structural connectivity in a cognitively normal cohort (n = 140), specifically targeting the connectivity between ECN nodes. Our data revealed the presence of a strongly‐connected “structural core” of the ECN comprising three components: interhemispheric frontal connections, a fronto‐parietal subnetwork and fronto‐striatal connections between right dorsolateral prefrontal cortex and right caudate. These pathways were strongly correlated with EF performance (p = .003). Post‐hoc analysis of subregions within the significant ECN connections showed that these effects were driven by a highly specific subset of interconnected cortical regions. The structural core subnetwork of the functional ECN may be an important feature crucial to a better future understanding of human cognition and behaviour.

High Angular Resolution Diffusion MRI Reveals Conserved and Deviant Programs in the Paths that Guide Human Cortical Circuitry.

Diffusion magnetic resonance (MR) tractography represents a novel opportunity to investigate conserved and deviant developmental programs between humans and other species such as mice. To that end, we acquired high angular resolution diffusion MR scans of mice [embryonic day (E) 10.5 to postnatal week 4] and human brains [gestational week (GW) 17-30] at successive stages of fetal development to investigate potential evolutionary changes in radial organization and emerging pathways between humans and mice. We compare radial glial development as well as commissural development (e.g., corpus callosum), primarily because our findings can be integrated with previous work. We also compare corpus callosal growth trajectories across primates (i.e., humans and rhesus macaques) and rodents (i.e., mice). One major finding is that the developing cortex of humans is predominated by pathways likely associated with a radial glial organization at GW 17-20, which is not as evident in age-matched mice (E 16.5, 17.5). Another finding is that, early in development, the corpus callosum follows a similar developmental timetable in primates (i.e., macaques and humans) as in mice. However, the corpus callosum grows for an extended period of time in primates compared with rodents. Taken together, these findings highlight deviant developmental programs underlying the emergence of cortical pathways in the human brain.

Lateralisation of the white matter microstructure associated with the hemispheric spatial attention dominance.

ObjectivesHealthy people have a slight leftward bias of spatial attention as measured on the Landmark task. Former studies indicated that lateralisation of brain activation contributes to this attentional bias. In this study we hypothesised that if the spatial bias was consistent over several measurements there would be structural background of it.MethodsReproducibility of the spatial bias of visuo-spatial attention was measured in twenty healthy subject in a Landmark task over three consecutive days. In order to evaluate the correlation between the spatial attentional bias and the white matter microstructure high angular resolution diffusion MRI was acquired for each subjects. The Track Based Spatial Statistics method was used to measure the hemispheric differences of the white matter microstructure. Probabilistic tractography was used to reveal the connection of the identified regions.ResultsThe analysis showed correlation between the behavioural scores and the lateralisation of the white matter microstructure in the parietal white matter (p<0.05, corrected for multiple correlations). Higher FA values on the left are associated to rightward bias. The parietal cluster showed connectivity along the superior longitudinal fascicle on one end to posterior parietal cortex and anteriorly to the putative frontal eye field. From the frontal eye field some of the fibres run towards the nodes of the dorsal attention network to the intraparietal suclus, while some of the fibres travelled toward to ventral attention network to the temporo-parietal junction.ConclusionsThese results indicate that the structural integrity dorsal fronto-parietal network and the connection between the dorsal and ventral attention networks are responsible for the attentional bias in normal healthy controls.

Neurite orientation dispersion and density imaging of mouse brain microstructure.

Advanced biophysical models like neurite orientation dispersion and density imaging (NODDI) have been developed to estimate the microstructural complexity of voxels enriched in dendrites and axons for both in vivo and ex vivo studies. NODDI metrics derived from high spatial and angular resolution diffusion MRI using the fixed mouse brain as a reference template have not yet been reported due in part to the extremely long scan time required. In this study, we modified the three-dimensional diffusion-weighted spin-echo pulse sequence for multi-shell and undersampling acquisition to reduce the scan time. This allowed us to acquire several exhaustive datasets that would otherwise not be attainable. NODDI metrics were derived from a complex 8-shell diffusion (1000-8000s/mm2) dataset with 384 diffusion gradient-encoding directions at 50µm isotropic resolution. These provided a foundation for exploration of tradeoffs among acquisition parameters. A three-shell acquisition strategy covering low, medium, and high b values with at least angular resolution of 64 is essential for ex vivo NODDI experiments. The good agreement between neurite density index (NDI) and the orientation dispersion index (ODI) with the subsequent histochemical analysis of myelin and neuronal density highlights that NODDI could provide new insight into the microstructure of the brain. Furthermore, we found that NDI is sensitive to microstructural variations in the corpus callosum using a well-established demyelination cuprizone model. The study lays the ground work for developing protocols for routine use of high-resolution NODDI method in characterizing brain microstructure in mouse models.

The Contribution of Various MRI Parameters to Clinical and Cognitive Disability in Multiple Sclerosis.

Next to the disseminated clinical symptoms, cognitive dysfunctions are common features of multiple sclerosis (MS). Over the recent years several different MRI measures became available representing the various features of the pathology, but the contribution to various clinical and cognitive functions is not yet fully understood. In this multiparametric MRI study we set out to identify the set of parameters that best predict the clinical and cognitive disability in MS. High resolution T1 weighted structural and high angular resolution diffusion MRI images were measured in 53 patients with relapsing remitting MS and 53 healthy controls. Clinical disability was inflicted by EDSS and cognitive functions were evaluated with the BICAMS tests. The contribution of lesion load, partial brain, white matter, gray matter and subcortical volumes as well as the diffusion parameters in the area of the lesions and the normal appearing white matter were examined by model free, partial least square (PLS) approach. Significance of the predictors was tested with Variable Importance in the Projection (VIP) score and 1 was used for threshold of significance. The PLS analysis indicated that the axial diffusivity of the NAWM contributed the most to the clinical disability (VIP score: 1.979). For the visuo-spatial working memory the most critical contributor was the size of the bilateral hippocampi (VIP scores: 1.183 and 1.2 left and right respectively). For the verbal memory the best predictors were the size of the right hippocampus (VIP score: 1.972), lesion load (VIP score: 1.274) and the partial brain volume (VIP score: 1.119). In case of the information processing speed the most significant contribution was from the diffusion parameters (fractional anisotropy, mean and radial diffusivity, VIP scores: 1.615, 1.321 respectively) of the normal appearing white matter. Our results indicate that various MRI measurable factors of MS pathology contribute differently to clinical and cognitive disability. These results point out the importance of the volumetry of the subcortical structures and the diffusion measures of the white matter in understanding the disability progression.

Characterizing Structural Changes With Devolving Remyelination Following Experimental Demyelination Using High Angular Resolution Diffusion MRI and Texture Analysis.

Changes in myelin integrity are associated with the pathophysiology of many neurological diseases, including multiple sclerosis. However, noninvasive measurement of myelin injury and repair remains challenging. Advanced MRI techniques including diffusion tensor imaging (DTI), neurite orientation dispersion and density index (NODDI), and texture analysis have shown promise in quantifying subtle abnormalities in white matter structure. To determine whether and how these advanced imaging methods help understand remyelination changes after demyelination using a mouse model. Prospective, longitudinal. Demyelination was induced in the thoracic spinal cord of 21 mice using the chemical toxin lysolecithin. 9.4T ASSESSMENT: Imaging was done at day 7 (demyelination) and days 14 to 35 (ongoing remyelination) postsurgery, followed by histology. Image analysis focused on both lesions and peri-lesional areas where remyelination began. In histology, we quantified the complexity of tissue alignment using angular entropy, in addition to staining area. Two-way analysis of variance was performed for assessing differences between tissue types and across timepoints, followed by post-hoc analysis to correct for multiple comparisons (P < 0.05). All diffusion and texture parameters were worse in lesions than the control tissue (P < 0.05) except orientation dispersion index (ODI) and neurite density index (NDI) over late remyelination. Longitudinally, ODI decreased and NDI increased persistently in both lesions and peri-lesion regions (P < 0.05). Fractional anisotropy showed a mild decrease at day 35 after increase, when lesion texture heterogeneity showed a trend to decrease (P > 0.05). Both lesion size and angular entropy decreased over time, and no change in any measure in the control tissue. Diffusion and MRI texture metrics may provide compensatory information on myelin repair and ODI and NDI could be sensitive measures of evolving remyelination, deserving further validation. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1750-1759.

Angular Upsampling in Infant Diffusion MRI Using Neighborhood Matching in x-q Space.

Diffusion MRI requires sufficient coverage of the diffusion wavevector space, also known as the q-space, to adequately capture the pattern of water diffusion in various directions and scales. As a result, the acquisition time can be prohibitive for individuals who are unable to stay still in the scanner for an extensive period of time, such as infants. To address this problem, in this paper we harness non-local self-similar information in the x-q space of diffusion MRI data for q-space upsampling. Specifically, we first perform neighborhood matching to establish the relationships of signals in x-q space. The signal relationships are then used to regularize an ill-posed inverse problem related to the estimation of high angular resolution diffusion MRI data from its low-resolution counterpart. Our framework allows information from curved white matter structures to be used for effective regularization of the otherwise ill-posed problem. Extensive evaluations using synthetic and infant diffusion MRI data demonstrate the effectiveness of our method. Compared with the widely adopted interpolation methods using spherical radial basis functions and spherical harmonics, our method is able to produce high angular resolution diffusion MRI data with greater quality, both qualitatively and quantitatively.

Optimal deep brain stimulation site and target connectivity for chronic cluster headache.

Objective:To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area.Methods:Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of ≥30% in headache load.Results:There was no surgical morbidity. Average follow-up was 34 ± 14 months. Patients showed reductions of 76 ± 33% in headache load, 46 ± 41% in attack severity, 58 ± 41% in headache frequency, and 51 ± 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas.Conclusions:We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.