Rotating single-shot acquisition (RoSA) with composite reconstruction for fast high-resolution diffusion imaging

PURPOSE: To accelerate high-resolution diffusion imaging, rotating single-shot acquisition (RoSA) with composite reconstruction is proposed. Acceleration was achieved by acquiring only one rotating single-shot blade per diffusion direction, and high-resolution diffusion-weighted (DW) images were reconstructed by using similarities of neighboring DW images. A parallel imaging technique was implemented in RoSA to further improve the image quality and acquisition speed. RoSA performance was evaluated by simulation and human experiments. METHODS: A brain tensor phantom was developed to determine an optimal blade size and rotation angle by considering similarity in DW images, off-resonance effects, and k-space coverage. With the optimal parameters, RoSA MR pulse sequence and reconstruction algorithm were developed to acquire human brain data. For comparison, multishot echo planar imaging (EPI) and conventional single-shot EPI sequences were performed with matched scan time, resolution, field of view, and diffusion directions. RESULTS: The simulation indicated an optimal blade size of 48 × 256 and a 30 ° rotation angle. For 1 × 1 mm2 in-plane resolution, RoSA was 12 times faster than the multishot acquisition with comparable image quality. With the same acquisition time as SS-EPI, RoSA provided superior image quality and minimum geometric distortion. CONCLUSION: RoSA offers fast, high-quality, high-resolution diffusion images. The composite image reconstruction is model-free and compatible with various diffusion computation approaches including parametric and nonparametric analyses. Magn Reson Med 79:264-275, 2018. © 2017 International Society for Magnetic Resonance in Medicine

Parcellation of Human Amygdala Subfields Using Orientation Distribution Function and Spectral K-means Clustering

Amygdala plays an important role in fear and emotional learning, which are critical for human survival. Despite the functional relevance and unique circuitry of each human amygdaloid subnuclei, there has yet to be an efficient imaging method for identifying these regions in vivo. A data-driven approach without prior knowledge provides advantages of efficient and objective assessments. The present study uses high angular and high spatial resolution diffusion magnetic resonance imaging to generate orientation distribution function, which bears distinctive microstructural features. The features were extracted using spherical harmonic decomposition to assess microstructural similarity within amygdala subfields are identified via similarity matrices using spectral k-mean clustering. The approach was tested on 32 healthy volunteers and three distinct amygdala subfields were identified including medial, posterior-superior lateral, and anterior-inferior lateral

GRASP-Pro: imProving GRASP DCE‐MRI through self-calibrating subspace-modeling and contrast phase automation

Purpose: To propose a highly accelerated, high-resolution dynamic contrast-enhanced MRI (DCE-MRI) technique called GRASP-Pro (golden-angle radial sparse parallel imaging with imProved performance) through a joint sparsity and self-calibrating subspace constraint with automated selection of contrast phases. Methods: GRASP-Pro reconstruction enforces a combination of an explicit low-rank subspace-constraint and a temporal sparsity constraint. The temporal basis used to construct the subspace is learned from an intermediate reconstruction step using the low-resolution portion of radial k-space, which eliminates the need for generating the basis using auxiliary data or a physical signal model. A convolutional neural network was trained to generate the contrast enhancement curve in the artery, from which clinically relevant contrast phases are automatically selected for evaluation. The performance of GRASP-Pro was demonstrated for high spatiotemporal resolution DCE-MRI of the prostate and was compared against standard GRASP in terms of overall image quality, image sharpness, and residual streaks and/or noise level. Results: Compared to GRASP, GRASP-Pro reconstructed dynamic images with enhanced sharpness, less residual streaks and/or noise, and finer delineation of the prostate without prolonging reconstruction time. The image quality improvement reached statistical significance (P < 0.05) in all the assessment categories. The neural network successfully generated contrast enhancement curves in the artery, and corresponding peak enhancement indexes correlated well with that from the manual selection. Conclusion: GRASP-Pro is a promising method for rapid and continuous DCE-MRI. It enables superior reconstruction performance over standard GRASP and allows reliable generation of artery enhancement curve to guide the selection of desired contrast phases for improving the efficiency of GRASP MRI workflow

Bifurcated topological optimization for IVIM

In this work, we shed light on the issue of estimating Intravoxel Incoherent Motion (IVIM) for diffusion and perfusion estimation by characterizing the objective function using simplicial homology tools. We provide a robust solution via topological optimization of this model so that the estimates are more reliable and accurate. Estimating the tissue microstructure from diffusion MRI is in itself an ill-posed and a non-linear inverse problem. Using variable projection functional (VarPro) to fit the standard bi-exponential IVIM model we perform the optimization using simplicial homology based global optimization to better understand the topology of objective function surface. We theoretically show how the proposed methodology can recover the model parameters more accurately and consistently by casting it in a reduced subspace given by VarPro. Additionally we demonstrate that the IVIM model parameters cannot be accurately reconstructed using conventional numerical optimization methods due to the presence of infinite solutions in subspaces. The proposed method helps uncover multiple global minima by analyzing the local geometry of the model enabling the generation of reliable estimates of model parameters.The National Institute of Biomedical Imaging And Bioengineering (NIBIB) of the National Institutes of Health (NIH); University of Washington’s Royalty Research Fund; NIH grants; the German Research Foundation (DFG) and a grant from the Alfred P. Sloan Foundation and the Gordon & Betty Moore Foundation to the University of Washington eScience Institute Data Science Environment.http://www.frontiersin.org/Neuroscienceam2022Chemical Engineerin

Tau-related white-matter alterations along spatially selective pathways

Progressive accumulation of tau neurofibrillary tangles in the brain is a defining pathologic feature of Alzheimer's disease (AD). Tau pathology exhibits a predictable spatiotemporal spreading pattern, but the underlying mechanisms of this spread are poorly understood. Although AD is conventionally considered a disease of the gray matter, it is also associated with pronounced and progressive deterioration of the white matter (WM). A link between abnormal tau and WM degeneration is suggested by findings from both animal and postmortem studies, but few studies demonstrated their interplay in vivo. Recent advances in diffusion magnetic resonance imaging and the availability of tau positron emission tomography (PET) have made it possible to evaluate the association of tau and WM degeneration (tau-WM) in vivo. In this study, we explored the spatial pattern of tau-WM associations across the whole brain to evaluate the hypothesis that tau deposition is associated with WM microstructural alterations not only in isolated tracts, but in continuous structural connections in a stereotypic pattern. Sixty-two participants, including 22 cognitively normal subjects, 22 individuals with subjective cognitive decline, and 18 with mild cognitive impairment were included in the study. WM characteristics were inferred by classic diffusion tensor imaging (DTI) and a complementary diffusion compartment model - neurite orientation dispersion and density imaging (NODDI) that provides a proxy for axonal density. A data-driven iterative searching (DDIS) approach, coupled with whole-brain graph theory analyses, was developed to continuously track tau-WM association patterns. Without applying prior knowledge of the tau spread, we observed a distinct spatial pattern that resembled the typical propagation of tau pathology in AD. Such association pattern was not observed between diffusion and amyloid-β PET signal. Tau-related WM degeneration is characterized by an increase in the mean diffusivity (with a dominant change in the radial direction) and a decrease in the intra-axonal volume fraction. These findings suggest that cortical tau deposition (as measured in tau PET) is associated with a lower axonal packing density and greater diffusion freedom. In conclusion, our in vivo findings using a data-driven method on cross-sectional data underline the important role of WM alterations in the AD pathological cascade with an association pattern similar to the postmortem Braak staging of AD. Future studies will focus on longitudinal analyses to provide in vivo evidence of tau pathology spreads along neuroanatomically connected brain areas

Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations

Global diversity and biogeography of bacterial communities in wastewater treatment plants

Microorganisms in wastewater treatment plants (WWTPs) are essential for water purification to protect public and environmental health. However, the diversity of microorganisms and the factors that control it are poorly understood. Using a systematic global-sampling effort, we analysed the 16S ribosomal RNA gene sequences from ~1,200 activated sludge samples taken from 269 WWTPs in 23 countries on 6 continents. Our analyses revealed that the global activated sludge bacterial communities contain ~1 billion bacterial phylotypes with a Poisson lognormal diversity distribution. Despite this high diversity, activated sludge has a small, global core bacterial community (n = 28 operational taxonomic units) that is strongly linked to activated sludge performance. Meta-analyses with global datasets associate the activated sludge microbiomes most closely to freshwater populations. In contrast to macroorganism diversity, activated sludge bacterial communities show no latitudinal gradient. Furthermore, their spatial turnover is scale-dependent and appears to be largely driven by stochastic processes (dispersal and drift), although deterministic factors (temperature and organic input) are also important. Our findings enhance our mechanistic understanding of the global diversity and biogeography of activated sludge bacterial communities within a theoretical ecology framework and have important implications for microbial ecology and wastewater treatment processes

Longitudinal white-matter abnormalities in sports-related concussion: A diffusion MRI study

Objective To study longitudinal recovery trajectories of white matter after sports-related concussion (SRC) by performing diffusion tensor imaging (DTI) on collegiate athletes who sustained SRC. Methods Collegiate athletes (n = 219, 82 concussed athletes, 68 contact-sport controls, and 69 non–contact-sport controls) were included from the Concussion Assessment, Research and Education Consortium. The participants completed clinical assessments and DTI at 4 time points: 24 to 48 hours after injury, asymptomatic state, 7 days after return-to-play, and 6 months after injury. Tract-based spatial statistics was used to investigate group differences in DTI metrics and to identify white-matter areas with persistent abnormalities. Generalized linear mixed models were used to study longitudinal changes and associations between outcome measures and DTI metrics. Cox proportional hazards model was used to study effects of white-matter abnormalities on recovery time. Results In the white matter of concussed athletes, DTI-derived mean diffusivity was significantly higher than in the controls at 24 to 48 hours after injury and beyond the point when the concussed athletes became asymptomatic. While the extent of affected white matter decreased over time, part of the corpus callosum had persistent group differences across all the time points. Furthermore, greater elevation of mean diffusivity at acute concussion was associated with worse clinical outcome measures (i.e., Brief Symptom Inventory scores and symptom severity scores) and prolonged recovery time. No significant differences in DTI metrics were observed between the contact-sport and non–contact-sport controls. Conclusions Changes in white matter were evident after SRC at 6 months after injury but were not observed in contact-sport exposure. Furthermore, the persistent white-matter abnormalities were associated with clinical outcomes and delayed recovery tim

Integration of Advanced Diffusion Acquisition and Analysis Techniques to Improve Treatment Management of Brain Tumor

Diffusion MRI is a technique that is capable of providing unique contrast that is sensitive to molecular displacement motion at cellular and sub-cellular length scales. By sensitizing MR signal to the random motion of water molecule protons at a microscopic level (of the order of 5-20um), it is able to probe tissue microstructures in the brain such as axons, dendrites, glial cells, and extra-cellular spaces, in a manner that may provide valuable insights into tumor physiology. Diffusion imaging is routinely acquired as part of the MR protocol for patients with brain tumors. However, the implications of the parameters being used are often not appreciated by the oncology community. This is especially true when applied to patients with high-grade glioma, where the lesion is highly heterogeneous and changes in diffusion parameters are due to a combination of treatment effects, edema and tumor infiltration. Although advanced diffusion models that aim to distinguish between different types of tissue have the potential for providing information that is complementary to conventional MR imaging, their application has been very limited due to their relatively long acquisition time. These challenges have become the motivation for this thesis. We first explored the value of standard diffusion imaging methods in characterizing tumor response to therapy. By applying different ways of evaluating changes in the apparent diffusion coefficient (ADC) and examining their association with patient outcomes in clinical trials, we hoped to gain a better understanding of the physiological process behind the patterns of changes that occur, and improve the interpretation of the data obtained. The next step was to bridge the gap between advanced diffusion models and their clinical applications by using fast diffusion imaging techniques. This was achieved by optimizing the protocol for acquiring multiband diffusion data at 7T and the post-processing pipeline for such data. The quality of the 7T multiband data was evaluated qualitatively and quantitatively in comparison with data obtained at 3T. The acquisition of multiband two shell diffusion data allowed us to apply neurite orientation dispersion and density imaging (NODDI) to patients with glioma and to evaluate its performance in distinguishing between different types of tissue. The results of this dissertation suggest that diffusion imaging plays an important role in assessing gliomas. These are very important steps towards improving the assessment of residual disease and distinguishing between tumor and treatment effects for patients with brain tumors