The CALIPR framework for highly accelerated myelin water imaging with improved precision and sensitivity.

Quantitative magnetic resonance imaging (MRI) techniques are powerful tools for the study of human tissue, but, in practice, their utility has been limited by lengthy acquisition times. Here, we introduce the Constrained, Adaptive, Low-dimensional, Intrinsically Precise Reconstruction (CALIPR) framework in the context of myelin water imaging (MWI); a quantitative MRI technique generally regarded as the most rigorous approach for noninvasive, in vivo measurement of myelin content. The CALIPR framework exploits data redundancy to recover high-quality images from a small fraction of an imaging dataset, which allowed MWI to be acquired with a previously unattainable sequence (fully sampled acquisition 2 hours:57 min:20 s) in 7 min:26 s (4.

Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD.

Rationale: Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms.

Nonaqueous magnetization following adiabatic and selective pulses in brain: T1 and cross-relaxation dynamics.

Inversion pulses are commonly employed in MRI for -weighted contrast and relaxation measurements. In the brain, it is often assumed that adiabatic pulses saturate the nonaqueous magnetization. We investigated this assumption using solid-state NMR to monitor the nonaqueous signal directly following adiabatic inversion and compared this with signals following hard and soft inversion pulses.

Myelin biomarkers in the healthy adult brain: Correlation, reproducibility, and the effect of fiber orientation.

Purpose: We investigated the correlation, reproducibility, and effect of white matter fiber orientation for three myelin-sensitive MRI techniques: magnetization transfer ratio (MTR), inhomogeneous magnetization transfer ratio (ihMTR), and gradient and spin echo-derived myelin water fraction (MWF).

Methods: We measured the three metrics in 17 white and three deep grey matter regions in 17 healthy adults at 3 T.

Results: We found a strong correlation between ihMTR and MTR (r = 0.

AAV5-miHTT-mediated huntingtin lowering improves brain health in a Huntington's disease mouse model.

Huntingtin (HTT)-lowering therapies show great promise in treating Huntington's disease. We have developed a microRNA targeting human HTT that is delivered in an adeno-associated serotype 5 viral vector (AAV5-miHTT), and here use animal behaviour, MRI, non-invasive proton magnetic resonance spectroscopy and striatal RNA sequencing as outcome measures in preclinical mouse studies of AAV5-miHTT. The effects of AAV5-miHTT treatment were evaluated in homozygous Q175FDN mice, a mouse model of Huntington's disease with severe neuropathological and behavioural phenotypes.

Inhomogeneous magnetization transfer imaging: Concepts and directions for further development.

Off-resonance radio frequency irradiation can induce the ordering of proton spins in the dipolar fields of their neighbors, in molecules with restricted mobility. This dipolar order decays with a characteristic relaxation time, T , that is very different from the T and T relaxation of the nuclear alignment with the main magnetic field. Inhomogeneous magnetization transfer (ihMT) imaging is a refinement of magnetization transfer (MT) imaging that isolates the MT signal dependence on dipolar order relaxation times within motion-constrained molecules.

Orientation dependence of inhomogeneous magnetization transfer and dipolar order relaxation rate in phospholipid bilayers.

Inhomogeneous magnetization transfer (ihMT) is a novel MRI technique used to measure white matter myelination in the brain and spinal cord. In the brain, ihMT has a strong orientation dependence which is likely to arise from the anisotropy of dipolar couplings between protons on oriented lipids in the myelin bilayers. We measured the orientation dependence of the second moment (M) of the lineshape, dipolar order relaxation rate (R), and ihMT ratio (ihMTR) in an oriented phospholipid bilayer at 9.

A data-driven T relaxation analysis approach for myelin water imaging: Spectrum analysis for multiple exponentials via experimental condition oriented simulation (SAME-ECOS).

Purpose: The decomposition of multi-exponential decay data into a T spectrum poses substantial challenges for conventional fitting algorithms, including non-negative least squares (NNLS). Based on a combination of the resolution limit constraint and machine learning neural network algorithm, a data-driven and highly tailorable analysis method named spectrum analysis for multiple exponentials via experimental condition oriented simulation (SAME-ECOS) was proposed.

Theory And Methods: The theory of SAME-ECOS was derived.

Rare variant contribution to human disease in 281,104 UK Biobank exomes.

Genome-wide association studies have uncovered thousands of common variants associated with human disease, but the contribution of rare variants to common disease remains relatively unexplored. The UK Biobank contains detailed phenotypic data linked to medical records for approximately 500,000 participants, offering an unprecedented opportunity to evaluate the effect of rare variation on a broad collection of traits. Here we study the relationships between rare protein-coding variants and 17,361 binary and 1,419 quantitative phenotypes using exome sequencing data from 269,171 UK Biobank participants of European ancestry.

Water content changes in new multiple sclerosis lesions have a minimal effect on the determination of myelin water fraction values.

Background And Purpose: Myelin water fraction (MWF) is a histopathologically validated in vivo myelin marker. As MWF is the proportion of water with a short T relative to the total water, increases in water from edema and inflammation may confound MWF determination in multiple sclerosis (MS) lesions. Total water content (TWC) measurement enables calculation of absolute myelin water content (MWC) and can be used to distinguish edema/inflammation from demyelination.

Early human impacts and ecosystem reorganization in southern-central Africa.

Modern engage in substantial ecosystem modification, but it is difficult to detect the origins or early consequences of these behaviors. Archaeological, geochronological, geomorphological, and paleoenvironmental data from northern Malawi document a changing relationship between forager presence, ecosystem organization, and alluvial fan formation in the Late Pleistocene. Dense concentrations of Middle Stone Age artifacts and alluvial fan systems formed after ca.

Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study.

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper-extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel.

Myelin water fraction decrease in individuals with chronic mild traumatic brain injury and persistent symptoms.

The diffuse and continually evolving secondary changes after mild traumatic brain injury (mTBI) make it challenging to assess alterations in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic mTBI and persistent symptoms and measured their cognitive status using the NIH Toolbox Cognitive Battery. Fifteen adults with mTBI with persistent symptoms and twelve age, gender and education matched healthy controls took part in this study.

Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain.

Purpose: The promise of inhomogeneous magnetization transfer (ihMT) as a new myelin imaging method was studied in ex vivo human brain tissue and in relation to myelin water fraction (MWF). The temperature dependence of both methods was characterized, as well as their correspondence with a histological measure of myelin content. Unfiltered and filtered ihMT protocols were studied by adjusting the saturation scheme to preserve or attenuate signal from tissue with short dipolar relaxation time T.

Identification of a missense variant in SPDL1 associated with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite substantial progress, the genetic determinants of this disease remain incompletely defined. Using whole genome and whole exome sequencing data from 752 individuals with sporadic IPF and 119,055 UK Biobank controls, we performed a variant-level exome-wide association study (ExWAS) and gene-level collapsing analyses.

Exploring the Contribution of Myelin Content in Normal Appearing White Matter to Cognitive Outcomes in Cerebral Small Vessel Disease.

Background: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood.

Understanding aqueous and non-aqueous proton T relaxation in brain.

A full picture of longitudinal relaxation in complex heterogeneous environments like white matter brain tissue remains elusive. In tissue, successive approximations, from the solvation layer model to the two pool model, have highlighted how longitudinal magnetization evolution depends on both inter-compartmental exchange and spin-lattice relaxation. In white matter, however, these models fail to capture the behaviour of the two distinct aqueous pools, myelin water and intra/extra-cellular water.

Comparison of multi echo T relaxation and steady state approaches for myelin imaging in the central nervous system.

The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T relaxation data to calculate the myelin water fraction (MWF). A fundamentally different approach, abbreviated "mcDESPOT", uses a more efficient steady-state acquisition to generate an equivalent metric (f). Although previous studies have demonstrated inherent instability and bias in the complex mcDESPOT analysis procedure, f has often been used as a surrogate for MWF.

An atlas for human brain myelin content throughout the adult life span.

Myelin water imaging is a quantitative neuroimaging technique that provides the myelin water fraction (MWF), a metric highly specific to myelin content, and the intra-/extra-cellular T (IET2), which is related to water and iron content. We coupled high-resolution data from 100 adults with gold-standard methodology to create an optimized anatomical brain template and accompanying MWF and IET2 atlases. We then used the MWF atlas to characterize how myelin content relates to demographic factors.

Myelin Water Imaging Demonstrates Lower Brain Myelination in Children and Adolescents With Poor Reading Ability.

Magnetic resonance imaging (MRI) provides a means to non-invasively investigate the neurological links with dyslexia, a learning disability that affects one's ability to read. Most previous brain MRI studies of dyslexia and reading skill have used structural or diffusion imaging to reveal regional brain abnormalities. However, volumetric and diffusion MRI lack specificity in their interpretation at the microstructural level.

Patient-Reported Outcomes (PROs) in COPD Clinical Trials: Trends and Gaps.

Key characteristics of chronic obstructive pulmonary disease (COPD) that significantly affect health-related quality of life (HRQoL) include chest symptoms, dyspnea, cough, sputum production, and exacerbations. Additional areas of impact are sleep, fatigue, emotional well-being, social functioning, and coping. Patient-reported outcomes (PROs) are essential to evaluate symptoms, impact of symptoms on activities of daily living, and treatment response.

Multi-spin echo T relaxation imaging with compressed sensing (METRICS) for rapid myelin water imaging.

Purpose: Myelin water imaging (MWI) provides a valuable biomarker for myelin, but clinical application has been restricted by long acquisition times. Accelerating the standard multi-echo T acquisition with gradient echoes (GRASE) or by 2D multi-slice data collection results in image blurring, contrast changes, and other issues. Compressed sensing (CS) can vastly accelerate conventional MRI.

Brain Myelin Water Fraction and Diffusion Tensor Imaging Atlases for 9-10 Year-Old Children.

Background And Purpose: Myelin water imaging (MWI) and diffusion tensor imaging (DTI) provide information about myelin and axon-related brain microstructure, which can be useful for investigating normal brain development and many childhood brain disorders. While pediatric DTI atlases exist, there are no pediatric MWI atlases available for the 9-10 years old age group. As myelination and structural development occurs throughout childhood and adolescence, studies of pediatric brain pathologies must use age-specific MWI and DTI healthy control data.