ORCID Profile
0000-0002-9133-5951
Current Organisation
University of Oxford
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Publisher: Cold Spring Harbor Laboratory
Date: 21-05-2018
DOI: 10.1101/327205
Abstract: White matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model. In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework. We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, ided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease. On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of 7.27 × 10 −5 , which was lower than the MSE value reported in the literature, with the advantage of being robust and computationally efficient. In the UK Biobank data, we found that the lesion probabilities are higher for the hypertension group compared to the non-hypertension group and further verified this finding using a statistical t-test. Finally, when applying our method on patients with vascular disease, we observed that the overall probability of lesions is significantly higher in later age groups, which is in line with the current literature.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2020
DOI: 10.1161/STROKEAHA.119.027544
Abstract: Periventricular white matter hyperintensities (WMH PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 ( NBEAL ), 10q23.1 ( TSPAN14/FAM231A ), and 10q24.33 ( SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 ( NOS3 ) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.
Publisher: Cold Spring Harbor Laboratory
Date: 19-05-2021
DOI: 10.1101/2021.05.19.21257316
Abstract: SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study. The protocol acquires high resolution T 1 , T 2 -FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 minutes. The automated imaging pipeline derives 1575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, these quantitative measures were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed that recovered COVID-19 patients had a decrease in frontal grey matter volumes, an increased burden of white matter hyperintensities, and reduced mean diffusivity in the total and normal appearing white matter in the posterior thalamic radiation and sagittal stratum, relative to controls. These differences were generally more prominent in patients who received organ support. Increased T 2 * in the thalamus was also observed in recovered COVID-19 patients, with a more prominent increase for non-critical patients. This initial evidence of brain changes in COVID-19 survivors prompts the need for further investigations. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in large-scale studies. The pipeline is widely applicable and will contribute to new analyses to hopefully clarify the medium to long-term effects of COVID-19. UK Biobank brain MRI protocol and pipeline was adapted for multiorgan MRI of COVID-19 High-quality brain MRI data from 5 modalities are acquired in 17 minutes Analysis pipeline derives 1575 IDPs of brain anatomy, perfusion, and microstructure Evidence of brain changes in COVID-19 survivors was found in the C-MORE study This MRI protocol is now being used in multiple large-scale studies on COVID-19
Publisher: Elsevier BV
Date: 2021
Publisher: Cold Spring Harbor Laboratory
Date: 27-06-2019
DOI: 10.1101/683367
Abstract: We conducted a genome-wide association meta-analysis of two ischemic white matter disease subtypes in the brain, periventricular and deep white matter hyperintensities (PVWMH and DWMH). In 26,654 participants, we found 10 independent genome-wide significant loci only associated with PVWMH, four of which have not been described previously for total WMH burden (16q24.2, 17q21.31, 10q23.1, 7q36.1). Additionally, in both PVWMH and DWMH we observed the previous association of the 17q25.1 locus with total WMH. We found that both phenotypes have shared but also distinct genetic architectures, consistent with both different underlying and related pathophysiology. PVWMH had more extensive genetic overlap with small vessel ischemic stroke, and unique associations with several loci implicated in ischemic stroke. DWMH were characterized by associations with loci previously implicated in vascular as well as astrocytic and neuronal function. Our study confirms the utility of these phenotypes and identifies new candidate genes associated only with PVWMH.
Publisher: Cold Spring Harbor Laboratory
Date: 24-04-2017
DOI: 10.1101/130385
Abstract: UK Biobank is a large-scale prospective epidemiological study with all data accessible to researchers worldwide. It is currently in the process of bringing back 100,000 of the original participants for brain, heart and body MRI, carotid ultrasound and low-dose bone/fat x-ray. The brain imaging component covers 6 modalities (T1, T2 FLAIR, susceptibility weighted MRI, Resting fMRI, Task fMRI and Diffusion MRI). Raw and processed data from the first 10,000 imaged subjects has recently been released for general research access. To help convert this data into useful summary information we have developed an automated processing and QC (Quality Control) pipeline that is available for use by other researchers. In this paper we describe the pipeline in detail, following a brief overview of UK Biobank brain imaging and the acquisition protocol. We also describe several quantitative investigations carried out as part of the development of both the imaging protocol and the processing pipeline.
Publisher: Public Library of Science (PLoS)
Date: 09-03-2017
Publisher: Elsevier BV
Date: 10-2018
Publisher: Cold Spring Harbor Laboratory
Date: 04-10-2016
DOI: 10.1101/079145
Abstract: The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness richness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a erse set of commonly used neuroimaging algorithms. Magnetic Resonance Imaging (MRI) is a non-invasive way to measure human brain structure and activity that has been used for over 25 years. There are thousands MRI studies performed every year generating a substantial amount of data. At the same time, many new data analysis methods are being developed every year. The potential of using new analysis methods on the variety of existing and newly acquired data is hindered by difficulties in software deployment and lack of support for standardized input data. Here we propose to use container technology to make deployment of a wide range of data analysis techniques easy. In addition, we adapt the existing data analysis tools to interface with data organized in a standardized way. We hope that this approach will enable researchers to access a wider range of methods when analyzing their data which will lead to accelerated progress in human neuroscience.
Publisher: Cold Spring Harbor Laboratory
Date: 19-06-2023
DOI: 10.1101/2023.06.16.545260
Abstract: Despite the huge potential of magnetic resonance imaging (MRI) in mapping and exploring the brain, MRI measures can often be limited in their consistency, reproducibility and accuracy which subsequently restricts their quantifiability. Nuisance nonbiological factors, such as hardware, software, calibration differences between scanners, and post-processing options can contribute to, or drive trends in, neuroimaging features to an extent that interferes with biological variability. Such lack of consistency, known as lack of harmonisation, across neuroimaging datasets poses a great challenge for our capabilities in quantitative MRI. Here, we build a new resource for comprehensively mapping the extent of the problem and objectively evaluating neuroimaging harmonisation approaches. We use a travelling-heads paradigm consisting of multimodal MRI data of 10 travelling subjects, each scanned at 5 different sites on 6 different 3T scanners from all the 3 major vendors and using 5 neuroimaging modalities, providing more comprehensive coverage than before. We also acquire multiple within-scanner repeats for a subset of subjects, setting baselines for multi-modal scan-rescan variability. Having extracted hundreds of image-derived features, we compare three forms of variability: (i) between-scanner, (ii) within-scanner (within-subject), and (iii) biological (between-subject). We characterise the reliability of features across scanners and use our resource as a testbed to enable new investigations that until now have been relatively unexplored. Specifically, we identify optimal pipeline processing steps that minimise between-scanner variability in extracted features (implicit harmonisation). We also test the performance of post-processing harmonisation tools (explicit harmonisation) and specifically check their efficiency in reducing between-scanner variability against baseline standards provided by our data. Our explorations allow us to come up with good practice suggestions on processing steps and sets of features where results are more consistent, while our publicly-released datasets establish references for future studies in this field.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Fidel Alfaro-Almagro.