Biology subjects

Fripp, J.

Publications and source records attributed to Fripp, J..

7 recordsLinked to original sources

bioRxiv2024

Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux

Waste from the brain is cleared via a cerebrospinal fluid (CSF) exchange pathway, the dysfunction of which is suggested to underlie the pathogenesis of many brain conditions. Coherent cerebrovascular oscillation that couples with pulsatile CSF inflow is suggested to drive the fluid flux. However, how this coupling is regulated, whether it mediates waste clearance, and why fluid flux is impaired in disease status remain unclear. Here we show that vascular-CSF coupling correlates with cortical cholinergic activity in non-demented aged humans. The causal role of basal forebrain cholinergic neurons that project to the cortex is then verified by specific lesioning in mice, revealing correlated changes in vascular-CSF coupling, arterial pulsation and glymphatic flux, which can be altered by an acetylcholinesterase inhibitor. These results suggest a neurovascular mechanism by which CSF/glymphatic flux is modulated by cholinergic neuronal activity, thereby providing a conceptual basis for the development of diagnostics and treatments for glymphatic dysfunction.

neuroscience↗

bioRxiv2022

Genetic, clinical underpinnings of subtle early brain change along Alzheimer's dimensions

Alzheimers disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised clustering technique known as Surreal-GAN, through which we identified two dominant dimensions of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the "diffuse-AD" (R1) dimension shows widespread brain atrophy, and the "MTL-AD" (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE {varepsilon}4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained model in the general population and two cognitively unimpaired cohorts of asymptomatic participants. In the general population, genome-wide association studies found 77 genes unrelated to APOE differentially associated with R1 and R2. Functional analyses revealed that these genes were overrepresented in differentially expressed gene sets in organs beyond the brain (R1 and R2), including the heart (R1) and the pituitary gland, muscle, and kidney (R2). These genes were enriched in biological pathways implicated in dendritic cells (R2), macrophage functions (R1), and cancer (R1 and R2). Several of them were "druggable genes" for cancer (R1), inflammation (R1), cardiovascular diseases (R1), and diseases of the nervous system (R2). The longitudinal progression showed that APOE {varepsilon}4, amyloid, and tau were associated with R2 at early asymptomatic stages, but this longitudinal association occurs only at late symptomatic stages in R1. Our findings deepen our understanding of the multifaceted pathogenesis of AD beyond the brain. In early asymptomatic stages, the two dimensions are associated with diverse pathological mechanisms, including cardiovascular diseases, inflammation, and hormonal dysfunction - driven by genes different from APOE - which may collectively contribute to the early pathogenesis of AD.

bioengineering↗

bioRxiv2022

A snapshot of brain and cognition in healthy mid-life and older adults

Deficits in memory are seen as a canonical sign of ageing and a prodrome to dementia in older adults. However, the nature of cognitive and brain changes across a wider aperture of adulthood is not well known. We quantify the relationship between cognitive function and brain morphology from mid-life to older adulthood, and the influence of age, sex, amyloid and genetic risk for dementia. We analyzed three observational cohorts (PISA, AIBL, ADNI) with cognitive, genetic and neuroimaging measures comprising a total of 1570 healthy mid-life and older adults (mean age 72, range 49-90 years, 1330 males) and 1365 age- and sex-matched adults with mild cognitive impairment or Alzheimers disease. Among healthy adults, we find robust modes of co-variation between regional sulcal width and multidomain cognitive function that change from mid-life to the older age range. The most prominent cortical changes in mid-life are predominantly associated with changes in executive functions, whereas they are most strongly associated with poorer memory function in older age. These cognitive changes are accompanied by an age-dependent pattern of sulcal widening. Amyloid exerts a weak, but significant, influence on cognition, but not on sulcal width. The APOE {varepsilon}4 allele also exerts a weak influence on cognition, but only significantly in the (larger and older) AIBL cohort. These findings provide new insights into brain and cognition in mid-life and older adults, suggesting that cognitive screening in mid-life cohorts should encompass executive functions as well as memory.

neuroscience↗

bioRxiv2021

Multi T1-weighted contrast imaging and T1 mapping with Compressed sensing FLAWS at 3T

The Fluid And White matter Suppression (FLAWS) MRI sequence allows for the acquisition of multiple T1-weighted contrasts in a single sequence acquisition. However, its acquisition time is prohibitive for use in clinical practice when the k-space is linearly downsampled and reconstructed using the Generalized Autocalibrating Partially Parallel Acquisition (GRAPPA) technique. This study proposes a FLAWS sequence optimization tailored to allow for the acquisition of FLAWS images with a Cartesian phyllotaxis k-space undersampling and compressed sensing (CS) reconstruction at 3T. The CS FLAWS sequence parameters were determined using a method previously employed to optimize FLAWS imaging at 1.5T and 7T. In-vivo experiments show that the proposed CS FLAWS optimization allows to reduce the FLAWS sequence acquisition time from 8 mins to 6 mins without decreasing the FLAWS image quality. In addition, this study demonstrates for the first time that T1-weighted imaging with low B1 sensitivity and T1 mapping can be performed with the FLAWS sequence at 3T for both GRAPPA and CS reconstructions. The FLAWS T1 mapping was validated using in-silico, in-vitro and in-vivo experiments with comparison against the inversion recovery turbo spin echo and MP2RAGE T1 mappings. These new results suggest that the recent advances in FLAWS imaging allow to combine the MP2RAGE imaging benefits (T1-weigthed imaging with low B1 sensitivity and T1 mapping) and with the previous version of FLAWS imaging benefits (multi T1-weighted contrast imaging) in a single 6 mins sequence acquisition. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

neuroscience↗

bioRxiv2021

Avoiding Data Loss: Synthetic MRIs Generated from Diffusion Imaging Can Replace Corrupted Structural Acquisitions For Freesurfer-Seeded Tractography

1Magnetic Resonance Imaging (MRI) motion artefacts frequently complicate structural and diffusion MRI analyses. While diffusion imaging is easily scrubbed of motion affected volumes, the same is not true for structural images. Structural images are critical to most diffusion-imaging pipelines thus their corruption can lead to disproportionate data loss. To enable diffusion-image processing when structural images have been corrupted, we propose a means by which synthetic structural images can be generated from diffusion MRI. This technique combines multi-tissue constrained spherical deconvolution, which is central to many existing diffusion analyses, with the Bloch equations which allow simulation of MRI intensities given scanner parameters and magnetic resonance (MR) tissue properties. We applied this technique to 32 scans, including those acquired on different scanners, with different protocols and with pathology present. The resulting synthetic T1w and T2w images were visually convincing and exhibited similar tissue contrast to acquired structural images. These were also of sufficient quality to drive a Freesurfer-based tractographic analysis. In this analysis, probabilistic tractography connecting the thalamus to the primary sensorimotor cortex was delineated with Freesurfer, using either real or synthetic structural images. Tractography for real and synthetic conditions was largely identical in terms of both voxels encountered (Dice 0.88 - 0.95) and mean fractional anisotropy (intrasubject absolute difference 0.00 - 0.02). We provide executables for the proposed technique in the hope that these may aid the community in analysing datasets where structural image corruption is common, such as studies of children or cognitively impaired persons. HighlightsO_LIWe propose a simple means of synthesizing T1w and T2w images from diffusion data C_LIO_LIThe proposed method worked well for a variety of acquisitions C_LIO_LISynthetic images showed tissue contrast akin to acquired images C_LIO_LISynthetic images were high enough quality to be used for Freesurfer seeded diffusion tractography C_LIO_LIThis method enables analysis of datasets where motion has corrupted acquired structural MRIs C_LI

neuroscience↗

bioRxiv2019

Harmonization of large multi-site imaging datasets: Application to 10,232 MRIs for the analysis of imaging patterns of structural brain change throughout the lifespan

As medical imaging enters its information era and presents rapidly increasing needs for big data analytics, robust pooling and harmonization of imaging data across diverse cohorts with varying acquisition protocols have become critical. We describe a comprehensive effort that merges and harmonizes a large-scale dataset of 10,232 structural brain MRI scans from participants without known neuropsychiatric disorder from 18 different studies that represent geographic diversity. We use this dataset and multi-atlas-based image processing methods to obtain a hierarchical partition of the brain from larger anatomical regions to individual cortical and deep structures and derive normative age trends of brain structure through the lifespan (3 to 96 years old). Critically, we present and validate a methodology for harmonizing this pooled dataset in the presence of nonlinear age trends. We provide a web-based visualization interface to generate and present the resulting age trends, enabling future studies of brain structure to compare their data with this normative reference of brain development and aging, and to examine deviations from normative ranges, potentially related to disease.

bioinformatics↗

bioRxiv2019

Non-Linear Realignment Improves Hippocampus Subfield Segmentation

Participant movement can deleteriously affect MR image quality. Further, for the visualization and segmentation of small anatomical structures, there is a need to improve image quality, specifically signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), by acquiring multiple anatomical scans consecutively. We aimed to ameliorate movement artefacts and increase SNR in a high-resolution turbo spin-echo (TSE) sequence acquired thrice using non-linear realignment in order to improve segmentation consistency of the hippocampus subfields. We assessed the method in young healthy participants, Motor Neurone Disease patients, and age matched controls. Results show improved image segmentation of the hippocampus subfields when comparing template-based segmentations with individual segmentations with Dice overlaps N=51; ps < 0.001 (Friedmans test) and higher sharpness ps < 0.001 in non-linearly realigned scans as compared to linearly, and arithmetically averaged scans.

neuroscience↗