PEAR: PEriodic And fixed Rank separation for fast fMRI

In functional MRI (fMRI), faster acquisition via undersampling of data can improve the spatial-temporal resolution trade-off and increase statistical robustness through increased degrees-of-freedom. High quality reconstruction of fMRI data from undersampled measurements requires proper modeling of the data. We present an fMRI reconstruction approach based on modeling the fMRI signal as a sum of periodic and fixed rank components, for improved reconstruction from undersampled measurements. We decompose the fMRI signal into a component which a has fixed rank and a component consisting of a sum of periodic signals which is sparse in the temporal Fourier domain. Data reconstruction is performed by solving a constrained problem that enforces a fixed, moderate rank on one of the components, and a limited number of temporal frequencies on the other. Our approach is coined PEAR - PEriodic And fixed Rank separation for fast fMRI. Experimental results include purely synthetic simulation, a simulation with real timecourses and retrospective undersampling of a real fMRI dataset. Evaluation was performed both quantitatively and visually versus ground truth, comparing PEAR to two additional recent methods for fMRI reconstruction from undersampled measurements. Results demonstrate PEAR's improvement in estimating the timecourses and activation maps versus the methods compared against at acceleration ratios of R=8,16 (for simulated data) and R=6.66,10 (for real data). PEAR results in reconstruction with higher fidelity than when using a fixed-rank based model or a conventional Low-rank+Sparse algorithm. We have shown that splitting the functional information between the components leads to better modeling of fMRI, over state-of-the-art methods

The effect of realistic geometries on the susceptibility-weighted MR signal in white matter

Purpose: To investigate the effect of realistic microstructural geometry on the susceptibility-weighted magnetic resonance (MR) signal in white matter (WM), with application to demyelination. Methods: Previous work has modeled susceptibility-weighted signals under the assumption that axons are cylindrical. In this work, we explore the implications of this assumption by considering the effect of more realistic geometries. A three-compartment WM model incorporating relevant properties based on literature was used to predict the MR signal. Myelinated axons were modeled with several cross-sectional geometries of increasing realism: nested circles, warped/elliptical circles and measured axonal geometries from electron micrographs. Signal simulations from the different microstructural geometries were compared to measured signals from a Cuprizone mouse model with varying degrees of demyelination. Results: Results from simulation suggest that axonal geometry affects the MR signal. Predictions with realistic models were significantly different compared to circular models under the same microstructural tissue properties, for simulations with and without diffusion. Conclusion: The geometry of axons affects the MR signal significantly. Literature estimates of myelin susceptibility, which are based on fitting biophysical models to the MR signal, are likely to be biased by the assumed geometry, as will any derived microstructural properties.Comment: Accepted March 4 2017, in publication at Magnetic Resonance in Medicin

Detecting microstructural properties of white matter based on compartmentalization of magnetic susceptibility

AbstractThe microscopic structure of neuronal tissue is crucial to brain function, with axon diameter, axonal density and myelination directly influencing signal conduction in the white matter. There is increasing evidence that these microstructural properties alter signal in magnetic resonance imaging (MRI) driven by magnetic susceptibility of different compartments (e.g., myelin sheaths and iron-laden cells). To explain these observations, we have developed a multi-compartmental geometric model of whitematter microstructure. Using a single set of literature parameters, this forward model predicts experimentally observed orientation dependence and temporal evolution of the MRI signal. Where previous models have aimed to explain only the orientation dependence of signal phase, the proposed approach encapsulates the full repertoire of signal behavior. The frequency distribution underlying signal behavior is predicted to be a rich source of microstructural information with relevance to neuronal pathology

Group-PCA for very large fMRI datasets

Increasingly-large datasets (for example, the resting-state fMRI data from the Human Connectome Project) are demanding analyses that are problematic because of the sheer scale of the aggregate data. We present two approaches for applying group-level PCA; both give a close approximation to the output of PCA applied to full concatenation of all individual datasets, while having very low memory requirements regardless of the number of datasets being combined. Across a range of realistic simulations, we find that in most situations, both methods are more accurate than current popular approaches for analysis of multi-subject resting-state fMRI studies. The group-PCA output can be used to feed into a range of further analyses that are then rendered practical, such as the estimation of group-averaged voxelwise connectivity, group-level parcellation, and group-ICA. (C) 2014 Elsevier Inc. All rights reserved.Peer reviewe

Scan time reduction for readout-segmented EPI using simultaneous multislice acceleration: Diffusion-weighted imaging at 3 and 7 Tesla

Purpose: Readout‐segmented echo‐planar imaging (rs‐EPI) can provide high quality diffusion data because it is less prone to distortion and blurring artifacts than single‐shot echo‐planar imaging (ss‐EPI), particularly at higher resolution and higher field. Readout segmentation allows shorter echo‐spacing and echo train duration, resulting in reduced image distortion and blurring, respectively, in the phase‐encoding direction. However, these benefits come at the expense of longer scan times because the segments are acquired in multiple repetitions times (TRs). This study shortened rs‐EPI scan times by reducing the TR duration with simultaneous multislice acceleration. Methods: The blipped‐CAIPI method for slice acceleration with reduced g‐factor SNR loss was incorporated into the diffusion‐weighted rs‐EPI sequence. The rs‐ and ss‐EPI sequences were compared at a range of resolutions at both 3 and 7 Tesla in terms of image fidelity and diffusion postprocessing results. Results: Slice‐accelerated clinically useful trace‐weighted images and tractography results are presented. Tractography analysis showed that the reduced artifacts in rs‐EPI allowed better discrimination of tracts than ss‐EPI. Conclusion: Slice acceleration reduces rs‐EPI scan times providing a practical alternative to diffusion‐weighted ss‐EPI with reduced distortion and high resolution. Magn Reson Med 74:136–149, 2015

Diffusion Tensor Imaging of Dolphin Brains Reveals Direct Auditory Pathway to Temporal Lobe

The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes’ auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this position induced by expansion of ‘associative0 regions in lateral and caudal directions. However, the precise location of the auditory cortex and its connections are still unknown. Here, we used a novel diffusion tensor imaging (DTI) sequence in archival post-mortem brains of a common dolphin (Delphinus delphis) and a pantropical dolphin (Stenella attenuata) to map their sensory and motor systems. Using thalamic parcellation based on traditionally defined regions for the primary visual (V1) and auditory cortex (A1), we found distinct regions of the thalamus connected to V1 and A1. But in addition to suprasylvian-A1, we report here, for the first time, the auditory cortex also exists in the temporal lobe, in a region near cetacean-A2 and possibly analogous to the primary auditory cortex in related terrestrial mammals (Artiodactyla). Using probabilistic tract tracing, we found a direct pathway from the inferior colliculus to the medial geniculate nucleus to the temporal lobe near the sylvian fissure. Our results demonstrate the feasibility of postmortem DTI in archival specimens to answer basic questions in comparative neurobiology in a way that has not previously been possible and shows a link between the cetacean auditory system and those of terrestrial mammals. Given that fresh cetacean specimens are relatively rare, the ability to measure connectivity in archival specimens opens up a plethora of possibilities for investigating neuroanatomy in cetaceans and other species

Hybrid-space reconstruction with add-on distortion correction for simultaneous multi-slab diffusion MRI

Purpose: This study aims to propose a model-based reconstruction algorithm for simultaneous multi-slab diffusion MRI acquired with blipped-CAIPI gradients (blipped-SMSlab), which can also incorporate distortion correction. Methods: We formulate blipped-SMSlab in a 4D k-space with kz gradients for the intra-slab slice encoding and km (blipped-CAIPI) gradients for the inter-slab encoding. Because kz and km gradients share the same physical axis, the blipped-CAIPI gradients introduce phase interference in the z-km domain while motion induces phase variations in the kz-m domain. Thus, our previous k-space-based reconstruction would need multiple steps to transform data back and forth between k-space and image space for phase correction. Here we propose a model-based hybrid-space reconstruction algorithm to correct the phase errors simultaneously. Moreover, the proposed algorithm is combined with distortion correction, and jointly reconstructs data acquired with the blip-up/down acquisition to reduce the g-factor penalty. Results: The blipped-CAIPI-induced phase interference is corrected by the hybrid-space reconstruction. Blipped-CAIPI can reduce the g-factor penalty compared to the non-blipped acquisition in the basic reconstruction. Additionally, the joint reconstruction simultaneously corrects the image distortions and improves the 1/g-factors by around 50%. Furthermore, through the joint reconstruction, SMSlab acquisitions without the blipped-CAIPI gradients also show comparable correction performance with blipped-SMSlab. Conclusion: The proposed model-based hybrid-space reconstruction can reconstruct blipped-SMSlab diffusion MRI successfully. Its extension to a joint reconstruction of the blip-up/down acquisition can correct EPI distortions and further reduce the g-factor penalty compared with the separate reconstruction.Comment: 10 figures+tables, 8 supplementary figure

Biallelic GINS2 variant p.(Arg114Leu) causes Meier-Gorlin syndrome with craniosynostosis

Contains fulltext : 284813.pdf (Publisher’s version ) (Open Access)INTRODUCTION: Replication of the nuclear genome is an essential step for cell division. Pathogenic variants in genes coding for highly conserved components of the DNA replication machinery cause Meier-Gorlin syndrome (MGORS). OBJECTIVE: Identification of novel genes associated with MGORS. METHODS: Exome sequencing was performed to investigate the genotype of an individual presenting with prenatal and postnatal growth restriction, a craniofacial gestalt of MGORS and coronal craniosynostosis. The analysis of the candidate variants employed bioinformatic tools, in silico structural protein analysis and modelling in budding yeast. RESULTS: A novel homozygous missense variant NM_016095.2:c.341G>T, p.(Arg114Leu), in GINS2 was identified. Both non-consanguineous healthy parents carried this variant. Bioinformatic analysis supports its classification as pathogenic. Functional analyses using yeast showed that this variant increases sensitivity to nicotinamide, a compound that interferes with DNA replication processes. The phylogenetically highly conserved residue p.Arg114 localises at the docking site of CDC45 and MCM5 at GINS2. Moreover, the missense change possibly disrupts the effective interaction between the GINS complex and CDC45, which is necessary for the CMG helicase complex (Cdc45/MCM2-7/GINS) to accurately operate. Interestingly, our patient's phenotype is strikingly similar to the phenotype of patients with CDC45-related MGORS, particularly those with craniosynostosis, mild short stature and patellar hypoplasia. CONCLUSION: GINS2 is a new disease-associated gene, expanding the genetic aetiology of MGORS

Confound modelling in UK Biobank brain imaging

© 2020 Dealing with confounds is an essential step in large cohort studies to address problems such as unexplained variance and spurious correlations. UK Biobank is a powerful resource for studying associations between imaging and non-imaging measures such as lifestyle factors and health outcomes, in part because of the large subject numbers. However, the resulting high statistical power also raises the sensitivity to confound effects, which therefore have to be carefully considered. In this work we describe a set of possible confounds (including non-linear effects and interactions that researchers may wish to consider for their studies using such data). We include descriptions of how we can estimate the confounds, and study the extent to which each of these confounds affects the data, and the spurious correlations that may arise if they are not controlled. Finally, we discuss several issues that future studies should consider when dealing with confounds

Abrogated Response to Cellular Stress Identifies DCIS Associated with Subsequent Tumor Events and Defines Basal-like Breast Tumors

SummaryApproximately 15%–30% of women diagnosed with ductal carcinoma in situ (DCIS) develop a subsequent tumor event within 10 years after surgical lumpectomy. To date, little is known about the molecular pathways that confer this differential risk for developing subsequent disease. In this study, we demonstrate that expression of biomarkers indicative of an abrogated response to cellular stress predicts DCIS with worse outcome and is a defining characteristic of basal-like invasive tumors. Mechanistic studies identify the Rb pathway as a key regulator of this response. Conversely, biomarkers indicative of an intact response to cellular stress are strongly associated with a disease-free prognosis. Assessment of these biomarkers in DCIS begins to allow prediction of tumor formation years before it actually occurs