High-resolution microscopic diffusion anisotropy imaging in the human hippocampus at 3T

Purpose Several neurological conditions are associated with microstructural changes in the hippocampus that can be observed using DWI. Imaging studies often use protocols with whole-brain coverage, imposing limits on image resolution and worsening partial-volume effects. Also, conventional single-diffusion-encoding methods confound microscopic diffusion anisotropy with size variance of microscopic diffusion environments. This study addresses these issues by implementing a multidimensional diffusion-encoding protocol for microstructural imaging of the hippocampus at high resolution. Methods The hippocampus of 8 healthy volunteers was imaged at 1.5-mm isotropic resolution with a multidimensional diffusion-encoding sequence developed in house. Microscopic fractional anisotropy (µFA) and normalized size variance (CMD) were estimated using q-space trajectory imaging, and their values were compared with DTI metrics. The overall scan time was 1 hour. The reproducibility of the protocol was confirmed with scan–rescan experiments, and a shorter protocol (14 minutes) was defined for situations with time constraints. Results Mean µFA (0.47) was greater than mean FA (0.20), indicating orientation dispersion in hippocampal tissue microstructure. Mean CMD was 0.17. The reproducibility of q-space trajectory imaging metrics was comparable to DTI, and microstructural metrics in the healthy hippocampus are reported. Conclusion This work shows the feasibility of high-resolution microscopic anisotropy imaging in the human hippocampus at 3 T and provides reference values for microstructural metrics in a healthy hippocampus

Estimating brain volume loss after radiation therapy in children treated for posterior fossa tumors (Corpus callosum and whole brain volume changes following radiotherapy in children).

Background More than half of pediatric tumors of central nervous system (CNS) primarily originate in the posterior fossa and are conventionally treated with radiation therapy (RT).Objectives The objective of this study was to establish whether corpus callosum volumes (CCV) and whole brain volumes (WBV) are correlated and to determine the impact of whole-brain lowvs high-dose RT on brain parenchymal volume loss as assessed using each technique.Material and methods Of the 30 identified children (6-12 years) with newly diagnosed posterior fossa tumors treated with cranial RT, including focal and whole-brain RT, suitable imaging was obtained for 23. Radiotherapy regimens were the following: no whole-brain RT (Group 1, n = 7), low-dose whole-brain RT (30 Gy, Group 3, n = 7) in addition to focal boost. Magnetic resonance images (MRIs) were analyzed at baseline and follow-up (median 14 months). The CCVs were manually segmented on midline sagittal slice (n = 23), while WBVs were segmented semi-automatically using Freesurfer (n = 15). This was done twice (6-month interval) for all baseline CCV measurements and 5 randomly selected WBV measurements to establish measurement reproducibility. Correlations between CCV and WBV were investigated and percentage of children demonstrating reduction in CCV or WBV noted.Results Correlation between baseline CCV and WBV was not significant (p = 0.37). Measurement reproducibility was from 6% to -9% for CCV and from 4.8% to -1.2% for WBV. Among the children studied, 30.4% (7/23) had >9% reduction in CCV at follow-up, while 33.3% (5/15) had >1.2% reduction in WBV. Five of 7 patients with CCV loss were not picked up by WBV measurements. Similarly, 3 of 5 patients with WBV loss were not picked up by CCV measurements.Conclusions The CCV and the WBV are unrelated and may indicate different brain parenchymal losses following RT. Up to a third of posterior fossa tumors treated with RT have measurable CCV or WBV loss; incidence was equivalent in lowvs high-dose whole-brain RT

White matter microstructure correlates with autism trait severity in a combined clinical-control sample of high-functioning adults

Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical-neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits

Reduced ventral cingulum integrity and increased behavioral problems in children with isolated optic nerve hypoplasia and mild to moderate or no visual impairment.

To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process

Building connectomes using diffusion MRI: why, how and but

Why has diffusion MRI become a principal modality for mapping connectomes in vivo? How do different image acquisition parameters, fiber tracking algorithms and other methodological choices affect connectome estimation? What are the main factors that dictate the success and failure of connectome reconstruction? These are some of the key questions that we aim to address in this review. We provide an overview of the key methods that can be used to estimate the nodes and edges of macroscale connectomes, and we discuss open problems and inherent limitations. We argue that diffusion MRI-based connectome mapping methods are still in their infancy and caution against blind application of deep white matter tractography due to the challenges inherent to connectome reconstruction. We review a number of studies that provide evidence of useful microstructural and network properties that can be extracted in various independent and biologically-relevant contexts. Finally, we highlight some of the key deficiencies of current macroscale connectome mapping methodologies and motivate future developments

Incomplete initial nutation diffusion imaging: An ultrafast, single‐scan approach for diffusion mapping

PURPOSE: Diffusion MRI is confounded by the need to acquire at least two images separated by a repetition time, thereby thwarting the detection of rapid dynamic microstructural changes. The issue is exacerbated when diffusivity variations are accompanied by rapid changes in T2 . The purpose of the present study is to accelerate diffusion MRI acquisitions such that both reference and diffusion-weighted images necessary for quantitative diffusivity mapping are acquired in a single-shot experiment. METHODS: A general methodology termed incomplete initial nutation diffusion imaging (INDI), capturing two diffusion contrasts in a single shot, is presented. This methodology creates a longitudinal magnetization reservoir that facilitates the successive acquisition of two images separated by only a few milliseconds. The theory behind INDI is presented, followed by proof-of-concept studies in water phantom, ex vivo, and in vivo experiments at 16.4 and 9.4 T. RESULTS: Mean diffusivities extracted from INDI were comparable with diffusion tensor imaging and the two-shot isotropic diffusion encoding in the water phantom. In ex vivo mouse brain tissues, as well as in the in vivo mouse brain, mean diffusivities extracted from conventional isotropic diffusion encoding and INDI were in excellent agreement. Simulations for signal-to-noise considerations identified the regimes in which INDI is most beneficial. CONCLUSIONS: The INDI method accelerates diffusion MRI acquisition to single-shot mode, which can be of great importance for mapping dynamic microstructural properties in vivo without T2 bias. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine

Sexual Dimorphism in White Matter Developmental Trajectories Using Tract-Based Spatial Statistics

Increasing evidence is emerging for sexual dimorphism in the trajectory of white matter development in children assessed using volumetric magnetic resonance imaging (MRI) and more recently diffusion MRI. Recent studies using diffusion MRI have examined cohorts with a wide age range (typically between 5 and 30 years) showing focal regions of differential diffusivity and fractional anisotropy (FA) and have implicated puberty as a possible contributory factor. To further investigate possible dimorphic trajectories in a young cohort, presumably closer to the expected onset of puberty, we used tract-based spatial statistics to investigate diffusion metrics. The cohort consisted of 23 males and 30 females between the ages of 8 and 16 years. Differences in diffusion metrics were corrected for age, total brain volume, and full scale IQ. In contrast to previous studies showing focal differences between males and females, widespread sexually dimorphic trajectories in structural white matter development were observed. These differences were characterized by more advanced development in females compared to males indicated by lower mean diffusivity, radial and axial diffusivity, and higher FA in females. This difference appeared to be larger at lower ages (8-9 years) with diffusion measures from males and females tending to converge between 10 and 14 years of age. Males showed a steeper slope for age-diffusion metric correlations compared to females, who either did not correlate with age or correlated in fewer regions. Further studies are now warranted to determine the role of hormones on the observed differences, particularly in 8-9-year-old children