Identifying sources of human interictal discharges with travelling wave and white matter propagation.

Interictal epileptiform discharges have been shown to propagate from focal epileptogenic sources as travelling waves or through more rapid white matter conduction. We hypothesize that both modes of propagation are necessary to explain interictal discharge timing delays. We propose a method that, for the first time, incorporates both propagation modes to identify unique potential sources of interictal activity. We retrospectively analysed 38 focal epilepsy patients who underwent intracranial EEG recordings and diffusion-weighted imaging for epilepsy surgery evaluation. Interictal discharges were detected and localized to the most likely source based on relative delays in time of arrival across electrodes, incorporating travelling waves and white matter propagation. We assessed the influence of white matter propagation on distance of spread, timing and clinical interpretation of interictal activity. To evaluate accuracy, we compared our source localization results to earliest spiking regions to predict seizure outcomes. White matter propagation helps to explain the timing delays observed in interictal discharge sequences, underlying rapid and distant propagation. Sources identified based on differences in time of receipt of interictal discharges are often distinct from the leading electrode location. Receipt of activity propagating rapidly via white matter can occur earlier than more local activity propagating via slower cortical travelling waves. In our cohort, our source localization approach was more accurate in predicting seizure outcomes than the leading electrode location. Inclusion of white matter in addition to travelling wave propagation in our model of discharge spread did not improve overall accuracy but allowed for identification of unique and at times distant potential sources of activity, particularly in patients with persistent postoperative seizures. Since distant white matter propagation can occur more rapidly than local travelling wave propagation, combined modes of propagation within an interictal discharge sequence can decouple the commonly assumed relationship between spike timing and distance from the source. Our findings thus highlight the clinical importance of recognizing the presence of dual modes of propagation during interictal discharges, as this may be a cause of clinical mislocalization.

A novel framework for in-vivo diffusion tensor distribution MRI of the human brain.

Neural tissue microstructure plays an important role in developmental, physiological and pathophysiological processes. Diffusion tensor distribution (DTD) MRI helps probe subvoxel heterogeneity by describing water diffusion within a voxel using an ensemble of non-exchanging compartments characterized by a probability density function of diffusion tensors. In this study, we provide a new framework for acquiring multiple diffusion encoding (MDE) images and estimating DTD from them in the human brain in vivo. We interfused pulsed field gradients (iPFG) in a single spin echo to generate arbitrary b-tensors of rank one, two, or three without introducing concomitant gradient artifacts. Employing well-defined diffusion encoding parameters we show that iPFG retains salient features of a traditional multiple-PFG (mPFG/MDE) sequence while reducing the echo time and coherence pathway artifacts thereby extending its applications beyond DTD MRI. Our DTD is a maximum entropy tensor-variate normal distribution whose tensor random variables are constrained to be positive definite to ensure their physicality. In each voxel, the second-order mean and fourth-order covariance tensors of the DTD are estimated using a Monte Carlo method that synthesizes micro-diffusion tensors with corresponding size, shape, and orientation distributions to best fit the measured MDE images. From these tensors we obtain the spectrum of diffusion tensor ellipsoid sizes and shapes, and the microscopic orientation distribution function (µODF) and microscopic fractional anisotropy (µFA) that disentangle the underlying heterogeneity within a voxel. Using the DTD-derived µODF, we introduce a new method to perform fiber tractography capable of resolving complex fiber configurations. The results revealed microscopic anisotropy in various gray and white matter regions and skewed MD distributions in cerebellar gray matter not observed previously. DTD MRI tractography captured complex white matter fiber organization consistent with known anatomy. DTD MRI also resolved some degeneracies associated with diffusion tensor imaging (DTI) and elucidated the source of diffusion heterogeneity which may help improve the diagnosis of various neurological diseases and disorders.

Multiple parietal pathways are associated with rTMS-induced hippocampal network enhancement and episodic memory changes.

Repetitive transcranial magnetic stimulation (rTMS) of the inferior parietal cortex (IPC) increases resting-state functional connectivity (rsFC) of the hippocampus with the precuneus and other posterior cortical areas and causes proportional improvement of episodic memory. The anatomical pathway(s) responsible for the propagation of these effects from the IPC is unknown and may not be direct. In order to assess the relative contributions of candidate pathways from the IPC to the MTL via the parahippocampal cortex and precuneus, to the effects of rTMS on rsFC and memory improvement, we used diffusion tensor imaging to measure the extent to which individual differences in fractional anisotropy (FA) in these pathways accounted for individual differences in response. FA in the IPC-parahippocampal pathway and several MTL pathways predicted changes in rsFC. FA in both parahippocampal and hippocampal pathways was related to changes in episodic, but not procedural, memory. These results implicate pathways to the MTL in the enhancing effect of parietal rTMS on hippocampal rsFC and memory.

Improved reproducibility of diffusion MRI of the human brain with a four-way blip-up and down phase-encoding acquisition approach.

PURPOSE: To assess the effects of blip-up and -down echo planar imaging (EPI) acquisition designs, with different choices of phase-encoding directions (PEDs) on the reproducibility of diffusion MRI (dMRI)-derived metrics in the human brain. METHODS: Diffusion MRI data in seven subjects were acquired five times, each with five different protocols. The base design included 64 diffusion directions acquired with anterior-posterior (AP) PED, the first and second protocols added reverse phase-encoded b=0s/mm2 posterior-anterior (PA) PED images. The third one included 32 directions all with PED acquisitions with opposite polarity (AP and PA). The fourth protocol, also with 32 unique directions used four PEDs (AP, PA, right-left (RL), and left-right (LR)). The scan time was virtually identical for all protocols. The variability of diffusion MRI metrics for each subject and each protocol was computed across the different sessions. RESULTS: The highest reproducibility for all dMRI metrics was obtained with protocol four (AP/PA-RL/LR, ie, four-way PED). Protocols that used only b=0s/mm2 for distortion correction, which are the most widely used designs, had the lowest reproducibility. CONCLUSIONS: An acquisition design with four PEDs, including all DWIs in addition to b=0s/mm2 images should be used to achieve high reproducibility in diffusion MRI studies.

Evaluating effects of sex and age on white matter microstructural alterations in alcohol use disorder: A diffusion tensor imaging study.

BACKGROUND: Alterations in white matter microstructure associated with chronic alcohol use have been demonstrated in previous diffusion tensor imaging (DTI) research. However, there is conflicting evidence as to whether such differences are influenced by an individual's biological sex. The purpose of the present study was to investigate the prevalence of sex differences in the white matter microstructure of the brains of individuals with alcohol use disorder (AUD) and healthy controls. METHODS: One hundred participants with AUD (38 female, aged 21 to 68) participating in the National Institute on Alcohol Abuse and Alcoholism's inpatient treatment program and 98 healthy control participants (52 female) underwent a diffusion-weighted scan. Images collected were processed for each subject individually, and voxelwise, tract-based spatial statistics analysis was conducted to test for differences in the DTI measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: A 2-way, between-subjects ANCOVA that tested for differences by group and sex revealed widespread differences between AUD and control subjects, but no interaction between group and sex. Additional analyses exploring demographic and alcohol use variables showed significant impacts of age on white matter microstructure that were more pronounced in individuals with AUD. Plots of FA by age, sex, and group in major white matter tracts suggest a need to explore higher order interactions in larger samples. CONCLUSIONS: These results bolster recent findings of similar microstructural properties in men and women with AUD but provide a rationale for the consideration of age when investigating the impacts of chronic alcohol use on the brain's white matter.

White matter microstructure in youth with and at risk for bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) and familial risk for BD have been associated with aberrant white matter (WM) microstructure in the corpus callosum and fronto-limbic pathways. These abnormalities might constitute trait or state marker and have been suggested to result from aberrant maturation and to relate to difficulties in emotion regulation. METHODS: To determine whether WM alterations represent a trait, disease or resilience marker, we compared youth at risk for BD (n = 36 first-degree relatives, REL) to youth with BD (n = 36) and healthy volunteers (n = 36, HV) using diffusion tensor imaging. RESULTS: Individuals with BD and REL did not differ from each other in WM microstructure and, compared to HV, showed similar aberrations in the superior corona radiata (SCR)/corticospinal tract (CST) and the body of the corpus callosum. WM microstructure of the anterior CC showed reduced age-related in-creases in BD compared to REL and HV. Further, individuals with BD and REL showed in-creased difficulties in emotion regulation, which were associated with the microstructure of the anterior thalamic radiation. DISCUSSION: Alterations in the SCR/CST and the body of the corpus callosum appear to represent a trait marker of BD, whereas changes in other WM tracts seem to be a disease state marker. Our findings also support the role of aberrant developmental trajectories of WM microstructure in the risk architecture of BD, although longitudinal studies are needed to confirm this association. Finally, our findings show the relevance of WM microstructure for difficulties in emotion regulation-a core characteristic of BD.

Measuring non-parametric distributions of intravoxel mean diffusivities using a clinical MRI scanner.

We measure spectra of water mobilities (i.e., mean diffusivities) from intravoxel pools in brain tissues of healthy subjects with a non-parametric approach. Using a single-shot isotropic diffusion encoding (IDE) preparation, we eliminate signal confounds caused by anisotropic diffusion, including microscopic anisotropy, and acquire in vivo diffusion-weighted images (DWIs) over a wide range of diffusion sensitizations. We analyze the measured IDE signal decays using a regularized inverse laplace transform (ILT) to derive a probability distribution of mean diffusivities of tissue water in each voxel. Based on numerical simulations we assess the sensitivity and accuracy of our ILT analysis and optimize an experimental protocol for use with clinical MRI scanners. In vivo spectra of intravoxel mean diffusivities measured in healthy subjects generally show single-peak distributions throughout the brain parenchyma, with small differences in peak location and shape among white matter, cortical and subcortical gray matter, and cerebrospinal fluid. Mean diffusivity distributions (MDDs) with multiple peaks are observed primarily in voxels at tissue interfaces and are likely due to partial volume contributions. To quantify tissue-specific MDDs with improved statistical power, we average voxel-wise normalized MDDs in corresponding regions-of-interest (ROIs). This non-parametric, rotation-invariant assessment of isotropic diffusivities of tissue water may reflect important microstructural information, such as cell packing and cell size, and active physiological processes, such as water transport and exchange, which may enhance biological specificity in the clinical diagnosis and characterization of ischemic stroke, cancer, neuroinflammation, and neurodegenerative disorders and diseases.

Apparent diffusion coefficient changes in human brain during sleep - Does it inform on the existence of a glymphatic system?

The role of sleep in brain physiology is poorly understood. Recently rodent studies have shown that the glymphatic system clears waste products from brain more efficiently during sleep compared to wakefulness due to the expansion of the interstitial fluid space facilitating entry of cerebrospinal fluid (CSF) into the brain. Here, we studied water diffusivity in the brain during sleep and awake conditions, hypothesizing that an increase in water diffusivity during sleep would occur concomitantly with an expansion of CSF volume - an effect that we predicted based on preclinical findings would be most prominent in cerebellum. We used MRI to measure slow and fast components of the apparent diffusion coefficient (ADC) of water in the brain in 50 healthy participants, in 30 of whom we compared awake versus sleep conditions and in 20 of whom we compared rested-wakefulness versus wakefulness following one night of sleep-deprivation. Sleep compared to wakefulness was associated with increases in slow-ADC in cerebellum and left temporal pole and with decreases in fast-ADC in thalamus, insula, parahippocampus and striatal regions, and the density of sleep arousals was inversely associated with ADC changes. The CSF volume was also increased during sleep and was associated with sleep-induced changes in ADCs in cerebellum. There were no differences in ADCs with wakefulness following sleep deprivation compared to rested-wakefulness. Although we hypothesized increases in ADC with sleep, our findings uncovered both increases in slow ADC (mostly in cerebellum) as well as decreases in fast ADC, which could reflect the distinct biological significance of fast- and slow-ADC values in relation to sleep. While preliminary, our findings suggest a more complex sleep-related glymphatic function in the human brain compared to rodents. On the other hand, our findings of sleep-induced changes in CSF volume provide preliminary evidence that is consistent with a glymphatic transport process in the human brain.

Evaluating corrections for Eddy-currents and other EPI distortions in diffusion MRI: methodology and a dataset for benchmarking.

PURPOSE: To propose a methodology for assessment of algorithms that correct distortions due to motion, eddy-currents, and echo planar imaging in diffusion weighted images (DWIs). METHODS: The proposed method evaluates correction performance by measuring variability across datasets of the same object acquired with images having distortions in different directions, thereby overcoming the unavailability of ground-truth, undistorted DWIs. A comprehensive diffusion MRI dataset, collected using a suitable experimental design, is made available to the scientific community, consisting of three DWI shells (Bmax = 5000 s/mm2 ), 30 gradient directions, a replicate set of antipodal gradient directions, four phase-encoding directions, and three different head orientations. The proposed methodology was tested using the TORTOISE diffusion MRI processing pipeline. RESULTS: The median variability of the original distorted data was 123% higher for DWIs, 100-168% higher for tensor-derived metrics and 28-111% higher for MAPMRI metrics, than in the corrected versions. EPI distortions induced substantial variability, nearly comparable to the contribution of eddy-current distortions. CONCLUSIONS: The dataset and the evaluation strategy proposed herein enable quantitative comparison of different methods for correction of distortions due to motion, eddy-currents, and other EPI distortions, and can be useful in benchmarking newly developed algorithms.

Impact of time-of-day on diffusivity measures of brain tissue derived from diffusion tensor imaging.

Diurnal fluctuations in MRI measures of structural and functional properties of the brain have been reported recently. These fluctuations may have a physiological origin, since they have been detected using different MRI modalities, and cannot be explained by factors that are typically known to confound MRI measures. While preliminary evidence suggests that measures of structural properties of the brain based on diffusion tensor imaging (DTI) fluctuate as a function of time-of-day (TOD), the underlying mechanism has not been investigated. Here, we used a longitudinal within-subjects design to investigate the impact of time-of-day on DTI measures. In addition to using the conventional monoexponential tensor model to assess TOD-related fluctuations, we used a dual compartment tensor model that allowed us to directly assess if any change in DTI measures is due to an increase in CSF/free-water volume fraction or due to an increase in water diffusivity within the parenchyma. Our results show that Trace or mean diffusivity, as measured using the conventional monoexponential tensor model tends to increase systematically from morning to afternoon scans at the interface of grey matter/CSF, most prominently in the major fissures and the sulci of the brain. Interestingly, in a recent study of the glymphatic system, these same regions were found to show late enhancement after intrathecal injection of a CSF contrast agent. The increase in Trace also impacts DTI measures of diffusivity such as radial and axial diffusivity, but does not affect fractional anisotropy. The dual compartment analysis revealed that the increase in diffusivity measures from PM to AM was driven by an increase in the volume fraction of CSF-like free-water. Taken together, our findings provide important insight into the likely physiological origins of diurnal fluctuations in MRI measurements of structural properties of the brain.

Efficient experimental designs for isotropic generalized diffusion tensor MRI (IGDTI).

PURPOSE: We propose a new generalized diffusion tensor imaging (GDTI) experimental design and analysis framework for efficiently measuring orientationally averaged diffusion-weighted images (DWIs), which remove bulk signal modulations attributed to diffusion anisotropy and quantify isotropic higher-order diffusion tensors (HOT). We illustrate how this framework accelerates the clinical measurement of rotation-invariant tissue microstructural parameters derived from HOT, such as the HOT-Trace and the mean t-kurtosis. THEORY AND METHODS: For a large range of b-values, we compare orientationally averaged DWIs measured with high angular resolution diffusion imaging to those obtained with the proposed isotropic GDTI (IGDTI) experimental design. We compare rotation-invariant microstructural parameters measured with IGDTI to those derived from HOTs measured explicitly with GDTI. RESULTS: In both fixed-brain microimaging and in vivo clinical experiments, IGDTI accurately quantifies mean apparent diffusion coefficient (mADC)-weighted DWIs over a wide range of b-values and allows efficient computation of HOT-derived scalar tissue parameters from a small number of DWIs. CONCLUSIONS: IGDTI provides direct and accurate estimates of orientationally averaged tissue water mobilities over a wide range of b-values. This efficient method may enable new, sensitive, and quantitative assessments for clinical applications in which changes in mADC can be observe,d such as detecting and characterizing stroke, cancers, and neurodegenerative diseases. Magn Reson Med 79:180-194, 2018. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Clinical feasibility of using mean apparent propagator (MAP) MRI to characterize brain tissue microstructure.

Diffusion tensor imaging (DTI) is the most widely used method for characterizing noninvasively structural and architectural features of brain tissues. However, the assumption of a Gaussian spin displacement distribution intrinsic to DTI weakens its ability to describe intricate tissue microanatomy. Consequently, the biological interpretation of microstructural parameters, such as fractional anisotropy or mean diffusivity, is often equivocal. We evaluate the clinical feasibility of assessing brain tissue microstructure with mean apparent propagator (MAP) MRI, a powerful analytical framework that efficiently measures the probability density function (PDF) of spin displacements and quantifies useful metrics of this PDF indicative of diffusion in complex microstructure (e.g., restrictions, multiple compartments). Rotation invariant and scalar parameters computed from the MAP show consistent variation across neuroanatomical brain regions and increased ability to differentiate tissues with distinct structural and architectural features compared with DTI-derived parameters. The return-to-origin probability (RTOP) appears to reflect cellularity and restrictions better than MD, while the non-Gaussianity (NG) measures diffusion heterogeneity by comprehensively quantifying the deviation between the spin displacement PDF and its Gaussian approximation. Both RTOP and NG can be decomposed in the local anatomical frame for reference determined by the orientation of the diffusion tensor and reveal additional information complementary to DTI. The propagator anisotropy (PA) shows high tissue contrast even in deep brain nuclei and cortical gray matter and is more uniform in white matter than the FA, which drops significantly in regions containing crossing fibers. Orientational profiles of the propagator computed analytically from the MAP MRI series coefficients allow separation of different fiber populations in regions of crossing white matter pathways, which in turn improves our ability to perform whole-brain fiber tractography. Reconstructions from subsampled data sets suggest that MAP MRI parameters can be computed from a relatively small number of DWIs acquired with high b-value and good signal-to-noise ratio in clinically achievable scan durations of less than 10min. The neuroanatomical consistency across healthy subjects and reproducibility in test-retest experiments of MAP MRI microstructural parameters further substantiate the robustness and clinical feasibility of this technique. The MAP MRI metrics could potentially provide more sensitive clinical biomarkers with increased pathophysiological specificity compared to microstructural measures derived using conventional diffusion MRI techniques.

PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc.

Improvement of temporal signal-to-noise ratio of GRAPPA accelerated echo planar imaging using a FLASH based calibration scan.

PURPOSE: To demonstrate that the temporal signal-to-noise ratio (SNR) of generalized autocalibrating partially parallel acquisitions (GRAPPA) accelerated echo planar imaging (EPI) can be enhanced and made more spatially uniform by using a fast low angle shot (FLASH) based calibration scan. METHODS: EPI of a phantom and human brains were acquired at 3 Tesla without and with GRAPPA acceleration factor of 2. The GRAPPA accelerated data were reconstructed using calibration scans acquired with EPI and FLASH acquisition schemes. The increase in temporal signal fluctuation due to GRAPPA reconstruction was quantified and compared. Simulated g-factor maps were also created for different calibration scans. RESULTS: GRAPPA accelerated phantom data exhibited areas with high g values when using the EPI based calibration for reconstruction. The g-factor maps were uniform when using the FLASH calibration scan. g was greater than 1.1 in 74% of pixels in 64 × 64 data reconstructed with the EPI calibration compared with only 15% when using the FLASH calibration scan. Human data also showed abnormally high g regions when using the EPI calibration but not when using the FLASH calibration scan. Use of the FLASH calibration scan increased the whole brain temporal SNR by ∼12% without affecting the image quality. Experimental observations were confirmed by simulations. CONCLUSION: A calibration scan based on a FLASH acquisition scheme can be used to improve the temporal SNR of GRAPPA accelerated EPI time series. Magn Reson Med 75:2362-2371, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

DR-BUDDI (Diffeomorphic Registration for Blip-Up blip-Down Diffusion Imaging) method for correcting echo planar imaging distortions.

We propose an echo planar imaging (EPI) distortion correction method (DR-BUDDI), specialized for diffusion MRI, which uses data acquired twice with reversed phase encoding directions, often referred to as blip-up blip-down acquisitions. DR-BUDDI can incorporate information from an undistorted structural MRI and also use diffusion-weighted images (DWI) to guide the registration, improving the quality of the registration in the presence of large deformations and in white matter regions. DR-BUDDI does not require the transformations for correcting blip-up and blip-down images to be the exact inverse of each other. Imposing the theoretical "blip-up blip-down distortion symmetry" may not be appropriate in the presence of common clinical scanning artifacts such as motion, ghosting, Gibbs ringing, vibrations, and low signal-to-noise. The performance of DR-BUDDI is evaluated with several data sets and compared to other existing blip-up blip-down correction approaches. The proposed method is robust and generally outperforms existing approaches. The inclusion of the DWIs in the correction process proves to be important to obtain a reliable correction of distortions in the brain stem. Methods that do not use DWIs may produce a visually appealing correction of the non-diffusion weighted images, but the directionally encoded color maps computed from the tensor reveal an abnormal anatomy of the white matter pathways.

Investigation of vibration-induced artifact in clinical diffusion-weighted imaging of pediatric subjects.

It has been reported that mechanical vibrations of the magnetic resonance imaging scanner could produce spurious signal dropouts in diffusion-weighted images resulting in artifactual anisotropy in certain regions of the brain with red appearance in the Directionally Encoded Color maps. We performed a review of the frequency of this artifact across pediatric studies, noting differences by scanner manufacturer, acquisition protocol, as well as weight and position of the subject. We also evaluated the ability of automated and quantitative methods to detect this artifact. We found that the artifact may be present in over 50% of data in certain protocols and is not limited to one scanner manufacturer. While a specific scanner had the highest incidence, low body weight and positioning were also associated with appearance of the artifact for both scanner types evaluated, making children potentially more susceptible than adults. Visual inspection remains the best method for artifact identification. Software for automated detection showed very low sensitivity (10%). The artifact may present inconsistently in longitudinal studies. We discuss a published case report that has been widely cited and used as evidence to set policy about diagnostic criteria for determining vegetative state. That report attributed longitudinal changes in anisotropy to white matter plasticity without considering the possibility that the changes were caused by this artifact. Our study underscores the need to check for the presence of this artifact in clinical studies, analyzes circumstances for when it may be more likely to occur, and suggests simple strategies to identify and potentially avoid its effects.

The Variegation of Human Brain Vulnerability to Rare Genetic Disorders and Convergence With Behaviorally Defined Disorders.

BACKGROUND: Diverse gene dosage disorders (GDDs) increase risk for psychiatric impairment, but characterization of GDD effects on the human brain has so far been piecemeal, with few simultaneous analyses of multiple brain features across different GDDs. METHODS: Here, through multimodal neuroimaging of 3 aneuploidy syndromes (XXY [total n = 191, 92 control participants], XYY [total n = 81, 47 control participants], and trisomy 21 [total n = 69, 41 control participants]), we systematically mapped the effects of supernumerary X, Y, and chromosome 21 dosage across a breadth of 15 different macrostructural, microstructural, and functional imaging-derived phenotypes (IDPs). RESULTS: The results revealed considerable diversity in cortical changes across GDDs and IDPs. This variegation of IDP change underlines the limitations of studying GDD effects unimodally. Integration across all IDP change maps revealed highly distinct architectures of cortical change in each GDD along with partial coalescence onto a common spatial axis of cortical vulnerability that is evident in all 3 GDDs. This common axis shows strong alignment with shared cortical changes in behaviorally defined psychiatric disorders and is enriched for specific molecular and cellular signatures. CONCLUSIONS: Use of multimodal neuroimaging data in 3 aneuploidies indicates that different GDDs impose unique fingerprints of change in the human brain that differ widely depending on the imaging modality that is being considered. Embedded in this variegation is a spatial axis of shared multimodal change that aligns with shared brain changes across psychiatric disorders and therefore represents a major high-priority target for future translational research in neuroscience.

In vivo detection of microscopic anisotropy using quadruple pulsed-field gradient (qPFG) diffusion MRI on a clinical scanner.

We report our design and implementation of a quadruple pulsed-field gradient (qPFG) diffusion MRI pulse sequence on a whole-body clinical scanner and demonstrate its ability to non-invasively detect restriction-induced microscopic anisotropy in human brain tissue. The microstructural information measured using qPFG diffusion MRI in white matter complements that provided by diffusion tensor imaging (DTI) and exclusively characterizes diffusion of water trapped in microscopic compartments with unique measures of average cell geometry. We describe the effect of white matter fiber orientation on the expected MR signal and highlight the importance of incorporating such information in the axon diameter measurement using a suitable mathematical framework. Integration of qPFG diffusion-weighted images (DWI) with fiber orientations measured using high-resolution DTI allows the estimation of average axon diameters in the corpus callosum of healthy human volunteers. Maps of inter-hemispheric average axon diameters reveal an anterior-posterior variation in good topographical agreement with anatomical measurements reported in previous post-mortem studies. With further technical refinements and additional clinical validation, qPFG diffusion MRI could provide a quantitative whole-brain histological assessment of white and gray matter, enabling a wide range of neuroimaging applications for improved diagnosis of neurodegenerative pathologies, monitoring neurodevelopmental processes, and mapping brain connectivity.

Effects of image distortions originating from susceptibility variations and concomitant fields on diffusion MRI tractography results.

In this work we investigate the effects of echo planar imaging (EPI) distortions on diffusion tensor imaging (DTI) based fiber tractography results. We propose a simple experimental framework that would enable assessing the effects of EPI distortions on the accuracy and reproducibility of fiber tractography from a pilot study on a few subjects. We compare trajectories computed from two diffusion datasets collected on each subject that are identical except for the orientation of phase encode direction, either right-left (RL) or anterior-posterior (AP). We define metrics to assess potential discrepancies between RL and AP trajectories in association, commissural, and projection pathways. Results from measurements on a 3 Tesla clinical scanner indicated that the effects of EPI distortions on computed fiber trajectories are statistically significant and large in magnitude, potentially leading to erroneous inferences about brain connectivity. The correction of EPI distortion using an image-based registration approach showed a significant improvement in tract consistency and accuracy. Although obtained in the context of a DTI experiment, our findings are generally applicable to all EPI-based diffusion MRI tractography investigations, including high angular resolution (HARDI) methods. On the basis of our findings, we recommend adding an EPI distortion correction step to the diffusion MRI processing pipeline if the output is to be used for fiber tractography.

Robust fat suppression at 3T in high-resolution diffusion-weighted single-shot echo-planar imaging of human brain.

Single-shot echo-planar imaging is the most common acquisition technique for whole-brain diffusion tensor imaging (DTI) studies in vivo. Higher field MRI systems are readily available and advantageous for acquiring DTI due to increased signal. One of the practical issues for DTI with single-shot echo-planar imaging at high-field is incomplete fat suppression resulting in a chemically shifted fat artifact within the brain image. Unsuppressed fat is especially detrimental in DTI because the diffusion coefficient of fat is two orders of magnitude lower than that of parenchyma, producing brighter appearing fat artifacts with greater diffusion weighting. In this work, several fat suppression techniques were tested alone and in combination with the goal of finding a method that provides robust fat suppression and can be used in high-resolution single-shot echo-planar imaging DTI studies. Combination of chemical shift saturation with slice-select gradient reversal within a dual-spin-echo diffusion preparation period was found to provide robust fat suppression at 3 T.