Head-and-neck multichannel B1+ mapping and RF shimming of the carotid arteries using a 7T parallel-transmit head coil.

PURPOSE: Neurovascular MRI suffers from a rapid drop in B1 + into the neck when using transmit head coils at 7 T. One solution to improving B1 + magnitude in the major feeding arteries in the neck is to use custom RF shims on parallel-transmit head coils. However, calculating such shims requires robust multichannel B1 + maps in both the head and the neck, which is challenging due to low RF penetration into the neck, limited dynamic range of multichannel B1 + mapping techniques, and B0 sensitivity. We therefore sought a robust, large-dynamic-range, parallel-transmit field mapping protocol and tested whether RF shimming can improve carotid artery B1 + magnitude in practice. METHODS: A pipeline is presented that combines B1 + mapping data acquired using circularly polarized (CP) and CP2-mode RF shims at multiple voltages. The pipeline was evaluated by comparing the predicted and measured B1 + for multiple random transmit shims, and by assessing the ability of RF shimming to increase B1 + in the carotid arteries. RESULTS: The proposed method achieved good agreement between predicted and measured B1 + in both the head and the neck. The B1 + magnitude in the carotid arteries can be increased by 43% using tailored RF shims or by 37% using universal RF shims, while also improving the RF homogeneity compared with CP mode. CONCLUSION: B1 + in the neck can be increased using RF shims calculated from multichannel B1 + maps in both the head and the neck. This can be achieved using universal phase-only RF shims, facilitating easy implementation in existing sequences.

Accelerated 3D multi-channel B 1 + mapping at 7 T for the brain and heart.

PURPOSE: To acquire accurate volumetric multi-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps in under 14 s whole-brain or 23 heartbeats whole-heart for parallel transmit (pTx) applications at 7 T. THEORY AND METHODS: We evaluate the combination of three recently proposed techniques. The acquisition of multi-channel transmit array B 1 + $$ {\mathrm{B}}_1^{+} $$ maps is accelerated using transmit low rank (TxLR) with absolute B 1 + $$ {\mathrm{B}}_1^{+} $$ mapping (Sandwich) acquired in a B 1 + $$ {\mathrm{B}}_1^{+} $$ time-interleaved acquisition of modes (B1TIAMO) fashion. Simulations using synthetic body images derived from Sim4Life were used to test the achievable acceleration for small scan matrices of 24 × 24. Next, we evaluated the method by retrospectively undersampling a fully sampled B 1 + $$ {\mathrm{B}}_1^{+} $$ library of nine subjects in the brain. Finally, Cartesian undersampled phantom and in vivo images were acquired in both the brain of three subjects (8Tx/32 receive [Rx]) and the heart of another three subjects (8Tx/8Rx) at 7 T. RESULTS: Simulation and in vivo results show that volumetric multi-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps can be acquired using acceleration factors of 4 in the body, reducing the acquisition time to within 23 heartbeats, which was previously not possible. In silico heart simulations demonstrated a RMS error to the fully sampled native resolution ground truth of 4.2° when combined in first-order circularly polarized mode (mean flip angle 66°) at an acceleration factor of 4. The 14 s 3D B 1 + $$ {\mathrm{B}}_1^{+} $$ maps acquired in the brain have a RMS error of 1.9° to the fully sampled (mean flip angle 86°). CONCLUSION: The proposed method is demonstrated as a fast pTx calibration technique in the brain and a promising method for pTx calibration in the body.

Dynamic Nuclear Polarization Illuminates Key Protein-Lipid Interactions in the Native Bacterial Cell Envelope.

Elucidating the structure and interactions of proteins in native environments is a fundamental goal of structural biology. Nuclear magnetic resonance (NMR) spectroscopy is well suited for this task but often suffers from low sensitivity, especially in complex biological settings. Here, we use a sensitivity-enhancement technique called dynamic nuclear polarization (DNP) to overcome this challenge. We apply DNP to capture the membrane interactions of the outer membrane protein Ail, a key component of the host invasion pathway of Yersinia pestis. We show that the DNP-enhanced NMR spectra of Ail in native bacterial cell envelopes are well resolved and enriched in correlations that are invisible in conventional solid-state NMR experiments. Furthermore, we demonstrate the ability of DNP to capture elusive interactions between the protein and the surrounding lipopolysaccharide layer. Our results support a model where the extracellular loop arginine residues remodel the membrane environment, a process that is crucial for host invasion and pathogenesis.

Rapid 3D absolute B1 + mapping using a sandwiched train presaturated TurboFLASH sequence at 7 T for the brain and heart.

PURPOSE: To shorten the acquisition time of magnetization-prepared absolute transmit field (B1 + ) mapping known as presaturation TurboFLASH, or satTFL, to enable single breath-hold whole-heart 3D B1 + mapping. METHODS: SatTFL is modified to remove the delay between the reference and prepared images (typically 5 T1 ), with matching transmit configurations for excitation and preparation RF pulses. The new method, called Sandwich, is evaluated as a 3D sequence, measuring whole-brain and gated whole-heart B1 + maps in a single breath-hold. We evaluate the sensitivity to B1 + and T1 using numerical Bloch, extended phase graph, and Monte Carlo simulations. Phantom and in vivo images were acquired in both the brain and heart using an 8-channel transmit 7 Tesla MRI system to support the simulations. A segmented satTFL with a short readout train was used as a reference. RESULTS: The method significantly reduces acquisition times of 3D measurements from 360 s to 20 s, in the brain, while simultaneously reducing bias in the measured B1 + due to T1 and magnetization history. The mean coefficient of variation was reduced by 81% for T1 s of 0.5-3 s compared to conventional satTFL. In vivo, the reproducibility coefficient for flip angles in the range 0-130° was 4.5° for satTFL and 4.7° for our scheme, significantly smaller than for a short TR satTFL sequence, which was 12°. The 3D sequence measured B1 + maps of the whole thorax in 26 heartbeats. CONCLUSION: Our adaptations enable faster B1 + mapping, with minimal T1 sensitivity and lower sensitivity to magnetization history, enabling single breath-hold whole-heart absolute B1 + mapping.

A Cluster of Ocular Syphilis Cases with a Common Sex Partner - Southwest Michigan, 2022.

Untreated syphilis can lead to ocular syphilis, otosyphilis, and neurosyphilis, conditions resulting from Treponema pallidum infection of the eye, inner ear, or central nervous system. During March-July 2022, Michigan public health officials identified a cluster of ocular syphilis cases. The public health response included case investigation, partner notification, dissemination of health alerts, patient referral to a public health clinic for diagnosis and treatment, hospital care coordination, and specimen collection for T. pallidum molecular typing. Five cases occurred among southwest Michigan women, all of whom had the same male sex partner. The women were aged 40-60 years, HIV-negative, and identified as non-Hispanic White race; the disease was staged as early syphilis, and all patients were hospitalized and treated with intravenous penicillin. The common male sex partner was determined to have early latent syphilis and never developed ocular syphilis. No additional transmission was identified after the common male partner's treatment. Due to lack of genetic material in limited specimens, syphilis molecular typing was not possible. A common heterosexual partner in an ocular syphilis cluster has not been previously documented and suggests that an unidentified strain of T. pallidum might have been associated with increased risk for systemic manifestations of syphilis. A high index of clinical suspicion and thorough sexual history are critical to diagnosing ocular syphilis, otosyphilis, and neurosyphilis. Coordination of disease surveillance with disease intervention specialist investigation and treatment referral can interrupt syphilis transmission.

Calcium and hydroxyapatite binding site of human vitronectin provides insights to abnormal deposit formation.

The human blood protein vitronectin (Vn) is a major component of the abnormal deposits associated with age-related macular degeneration, Alzheimer's disease, and many other age-related disorders. Its accumulation with lipids and hydroxyapatite (HAP) has been demonstrated, but the precise mechanism for deposit formation remains unknown. Using a combination of solution and solid-state NMR experiments, cosedimentation assays, differential scanning fluorimetry (DSF), and binding energy calculations, we demonstrate that Vn is capable of binding both soluble ionic calcium and crystalline HAP, with high affinity and chemical specificity. Calcium ions bind preferentially at an external site, at the top of the hemopexin-like (HX) domain, with a group of four Asp carboxylate groups. The same external site is also implicated in HAP binding. Moreover, Vn acquires thermal stability upon association with either calcium ions or crystalline HAP. The data point to a mechanism whereby Vn plays an active role in orchestrating calcified deposit formation. They provide a platform for understanding the pathogenesis of macular degeneration and other related degenerative disorders, and the normal functions of Vn, especially those related to bone resorption.

fMRIPrep: a robust preprocessing pipeline for functional MRI.

Preprocessing of functional magnetic resonance imaging (fMRI) involves numerous steps to clean and standardize the data before statistical analysis. Generally, researchers create ad hoc preprocessing workflows for each dataset, building upon a large inventory of available tools. The complexity of these workflows has snowballed with rapid advances in acquisition and processing. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for fMRI data. fMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing without manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection. Additionally, fMRIPrep introduces less uncontrolled spatial smoothness than observed with commonly used preprocessing tools. fMRIPrep equips neuroscientists with an easy-to-use and transparent preprocessing workflow, which can help ensure the validity of inference and the interpretability of results.

Correlating the Structure and Activity of Y. pestis Ail in a Bacterial Cell Envelope.

Understanding microbe-host interactions at the molecular level is a major goal of fundamental biology and therapeutic drug development. Structural biology strives to capture biomolecular structures in action, but the samples are often highly simplified versions of the complex native environment. Here, we present an Escherichia coli model system that allows us to probe the structure and function of Ail, the major surface protein of the deadly pathogen Yersinia pestis. We show that cell surface expression of Ail produces Y. pestis virulence phenotypes in E. coli, including resistance to human serum, cosedimentation of human vitronectin, and pellicle formation. Moreover, isolated bacterial cell envelopes, encompassing inner and outer membranes, yield high-resolution solid-state NMR spectra that reflect the structure of Ail and reveal Ail sites that are sensitive to the bacterial membrane environment and involved in the interactions with human serum components. The data capture the structure and function of Ail in a bacterial outer membrane and set the stage for probing its interactions with the complex milieu of immune response proteins present in human serum.

Hippocampal acidity and volume are differentially associated with spatial navigation in older adults.

The hippocampus is negatively affected by aging and is critical for spatial navigation. While there is evidence that wayfinding navigation tasks are especially sensitive to preclinical hippocampal deterioration, these studies have primarily used volumetric hippocampal imaging without considering microstructural properties or anatomical variation within the hippocampus. T1ρ is an MRI measure sensitive to regional pH, with longer relaxation rates reflecting acidosis as a marker of metabolic dysfunction and neuropathological burden. For the first time, we investigate how measures of wayfinding including landmark location learning and delayed memory in cognitively normal older adults (N = 84) relate to both hippocampal volume and T1ρ in the anterior and posterior hippocampus. Regression analyses revealed hippocampal volume was bilaterally related to learning, while right lateralized T1ρ was related to delayed landmark location memory and bilateral T1ρ was related to the delayed use of a cognitive map. Overall, results suggest hippocampal volume and T1ρ relaxation rate tap into distinct mechanisms involved in preclinical cognitive decline as assessed by wayfinding navigation, and laterality influenced these relationships more than the anterior-posterior longitudinal axis of the hippocampus.

Notes from the Field: Cluster of Lymphogranuloma Venereum Cases Among Men Who Have Sex with Men - Michigan, August 2015-April 2016.

Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) caused by infection with invasive Chlamydia trachomatis serovars L1-L3 (1). LGV is characterized by inguinal and/or femoral lymphadenopathy, typically following a transient, self-limited genital ulcer or papule that might go unnoticed. Rectal infection can result in proctocolitis that can present with mucoid and/or hemorrhagic rectal discharge, anal pain, constipation, fever, and tenesmus, and signs of granulomas and/or ulcerations on anoscopy (1,2). LGV can be an invasive, systemic infection, and if it is not treated early, LGV proctocolitis can lead to chronic colorectal fistulas and strictures (2). In Europe, outbreaks of LGV have been reported among men who have sex with men (MSM), often in association with human immunodeficiency virus (HIV) coinfection (3-5). The prevalence of LGV in the United States is unknown (1), because diagnostic tests to differentiate LGV from non-LGV Chlamydia trachomatis are not widely available (6), and providers might not know that they should report cases that are presumptively treated.

Migration distorts surveillance estimates of engagement in care: results of public health investigations of persons who appear to be out of HIV care.

BACKGROUND: Prevention and clinical efforts are increasingly focused on improving the HIV care cascade, the sequential steps from diagnosis to engagement in care and viral suppression. Monitoring of this cascade is largely dependent on HIV laboratory surveillance data. However, little is known about the completeness of these data or the true care status of individuals for whom no data are reported. METHODS: We investigated people presumed to be living with HIV/AIDS in King County, WA, who had no laboratory results reported to HIV surveillance for at least 1 year between 2006 and 2010. We determined whether each person had relocated, died, or remained in the county. RESULTS: Of 7379 HIV-infected people presumed living in King County, 2545 (35%) had 1 or more 12-month gap in laboratory reporting. Among these individuals, 47% had relocated, 7% died, and 38% remained in King County; we were unable to determine the status of 8%. Of individuals remaining in the area, 91% had evidence of returning to or being in HIV care. Case investigations reduced the proportion of individuals thought to be out of care in 2011 from 27% to 16%. CONCLUSIONS: Investigations of individuals without laboratory results reported to HIV surveillance identified large numbers of people who are no longer living in the area. Our findings suggest that current estimates of the HIV care cascade may be too pessimistic and that individual case investigations are required to accurately define the size and composition of the population of people living with HIV in local areas.

Integrative genomic reconstruction of carbohydrate utilization networks in bifidobacteria: global trends, local variability, and dietary adaptation.

Bifidobacteria are among the earliest colonizers of the human gut, conferring numerous health benefits. While multiple Bifidobacterium strains are used as probiotics, accumulating evidence suggests that the individual responses to probiotic supplementation may vary, likely due to a variety of factors, including strain type(s), gut community composition, dietary habits of the consumer, and other health/lifestyle conditions. Given the saccharolytic nature of bifidobacteria, the carbohydrate composition of the diet is one of the primary factors dictating the colonization efficiency of Bifidobacterium strains. Therefore, a comprehensive understanding of bifidobacterial glycan metabolism at the strain level is necessary to rationally design probiotic or synbiotic formulations that combine bacterial strains with glycans that match their nutrient preferences. In this study, we systematically reconstructed 66 pathways involved in the utilization of mono-, di-, oligo-, and polysaccharides by analyzing the representation of 565 curated metabolic functional roles (catabolic enzymes, transporters, transcriptional regulators) in 2973 non-redundant cultured Bifidobacterium isolates and metagenome-assembled genomes (MAGs). Our analysis uncovered substantial heterogeneity in the predicted glycan utilization capabilities at the species and strain level and revealed the presence of a yet undescribed phenotypically distinct subspecies-level clade within the Bifidobacterium longum species. We also identified Bangladeshi isolates harboring unique gene clusters tentatively implicated in the breakdown of xyloglucan and human milk oligosaccharides. Predicted carbohydrate utilization phenotypes were experimentally characterized and validated. Our large-scale genomic analysis considerably expands the knowledge of carbohydrate metabolism in bifidobacteria and provides a foundation for rationally designing single- or multi-strain probiotic formulations of a given bifidobacterial species as well as synbiotic combinations of bifidobacterial strains matched with their preferred carbohydrate substrates.

Exercise effects on brain health and learning from minutes to months: The brain EXTEND trial.

Despite evidence that aerobic exercise benefits the aging brain, in particular the hippocampus and memory, controlled clinical trials have not comprehensively evaluated effects of aerobic exercise training on human memory in older adults. The central goal of this study was to determine chronic effects of moderate-to-vigorous intensity aerobic exercise on the hippocampus and memory in non-demented, inactive adults ages 55-80 years. We determine effects of aerobic exercise training with a 6-month randomized controlled trial (RCT) comparing 150 min/week of home-based, light intensity exercise with progressive moderate-to-vigorous intensity aerobic exercise. For the first time in a large trial, we examined temporal mechanisms by determining if individual differences in the rapid, immediate effects of moderate intensity exercise on hippocampal-cortical connectivity predict chronic training-related changes over months in connectivity and memory. We examined physiological mechanisms by testing the extent to which chronic training-related changes in cardiorespiratory fitness are a critical factor to memory benefits. The Exercise Effects on Brain Connectivity and Learning from Minutes to Months (Brain-EXTEND) trial is conceptually innovative with advanced measures of hippocampal-dependent learning and memory processes combined with novel capture of the physiological changes, genetic components, and molecular changes induced by aerobic exercise that change hippocampal-cortical connectivity. Given that hippocampal connectivity deteriorates with Alzheimer's and aerobic exercise may contribute to reduced risk of Alzheimer's, our results could lead to an understanding of the physiological mechanisms and moderators by which aerobic exercise reduces risk of this devastating and costly disease.

Dynamic nuclear polarization illuminates key protein-lipid interactions in the native bacterial cell envelope.

Elucidating the structure and interactions of proteins in native environments has become a fundamental goal of structural biology. Nuclear magnetic resonance (NMR) spectroscopy is well suited for this task but often suffers from low sensitivity, especially in complex biological settings. Here, we use a sensitivity-enhancement technique called dynamic nuclear polarization (DNP) to overcome this challenge. We apply DNP to capture the membrane interactions of the outer membrane protein Ail, a key component of the host invasion pathway of Yersinia pestis . We show that the DNP-enhanced NMR spectra of Ail in native bacterial cell envelopes are well resolved and enriched in correlations that are invisible in conventional solid-state NMR experiments. Furthermore, we demonstrate the ability of DNP to capture elusive interactions between the protein and the surrounding lipopolysaccharide layer. Our results support a model where the extracellular loop arginine residues remodel the membrane environment, a process that is crucial for host invasion and pathogenesis.

Two Classes of DNA Gyrase Inhibitors Elicit Distinct Evolutionary Trajectories Toward Resistance in Gram-Negative Pathogens.

Comprehensive knowledge of mechanisms driving the acquisition of antimicrobial resistance is essential for the development of new drugs with minimized resistibility. To gain this knowledge, we combine experimental evolution in a continuous culturing device, the morbidostat, with whole genome sequencing of evolving cultures followed by characterization of drug-resistant isolates. Here, this approach was used to assess evolutionary dynamics of resistance acquisition against DNA gyrase/topoisomerase TriBE inhibitor GP6 in Escherichia coli and Acinetobacter baumannii. The evolution of GP6 resistance in both species was driven by a combination of two classes of mutational events: (i) amino acid substitutions near the ATP-binding site of the GyrB subunit of the DNA gyrase target; and (ii) various mutations and genomic rearrangements leading to upregulation of efflux pumps, species-specific (AcrAB/TolC in E. coli and AdeIJK in A. baumannii) and shared by both species (MdtK). A comparison with the experimental evolution of resistance to ciprofloxacin (CIP), previously performed using the same workflow and strains, revealed fundamental differences between these two distinct classes of compounds. Most notable were non-overlapping spectra of target mutations and distinct evolutionary trajectories that, in the case of GP6, were dominated by upregulation of efflux machinery prior to (or even in lieu) of target modification. Most of efflux-driven GP6-resistant isolates of both species displayed a robust cross-resistance to CIP, while CIP-resistant clones showed no appreciable increase in GP6-resistance.

Methods for decoding cortical gradients of functional connectivity.

Macroscale gradients have emerged as a central principle for understanding functional brain organization. Previous studies have demonstrated that a principal gradient of connectivity in the human brain exists, with unimodal primary sensorimotor regions situated at one end and transmodal regions associated with the default mode network and representative of abstract functioning at the other. The functional significance and interpretation of macroscale gradients remains a central topic of discussion in the neuroimaging community, with some studies demonstrating that gradients may be described using meta-analytic functional decoding techniques. However, additional methodological development is necessary to fully leverage available meta-analytic methods and resources and quantitatively evaluate their relative performance. Here, we conducted a comprehensive series of analyses to investigate and improve the framework of data-driven, meta-analytic methods, thereby establishing a principled approach for gradient segmentation and functional decoding. We found that a two-segment solution determined by a k-means segmentation approach and an LDA-based meta-analysis combined with the NeuroQuery database was the optimal combination of methods for decoding functional connectivity gradients. Finally, we proposed a method for decoding additional components of the gradient decomposition. The current work aims to provide recommendations on best practices and flexible methods for gradient-based functional decoding of fMRI data.

Neuroscout, a unified platform for generalizable and reproducible fMRI research.

Functional magnetic resonance imaging (fMRI) has revolutionized cognitive neuroscience, but methodological barriers limit the generalizability of findings from the lab to the real world. Here, we present Neuroscout, an end-to-end platform for analysis of naturalistic fMRI data designed to facilitate the adoption of robust and generalizable research practices. Neuroscout leverages state-of-the-art machine learning models to automatically annotate stimuli from dozens of fMRI studies using naturalistic stimuli-such as movies and narratives-allowing researchers to easily test neuroscientific hypotheses across multiple ecologically-valid datasets. In addition, Neuroscout builds on a robust ecosystem of open tools and standards to provide an easy-to-use analysis builder and a fully automated execution engine that reduce the burden of reproducible research. Through a series of meta-analytic case studies, we validate the automatic feature extraction approach and demonstrate its potential to support more robust fMRI research. Owing to its ease of use and a high degree of automation, Neuroscout makes it possible to overcome modeling challenges commonly arising in naturalistic analysis and to easily scale analyses within and across datasets, democratizing generalizable fMRI research.