Jonathan Clayden PhD

Jonathan D. Clayden


Publications:
2017
  Improved reference tracts for unsupervised brain white matter tractography
Muñoz Maniega, S, Bastin, M, Deary, I, Wardlaw, J & Clayden, JD 2017, Improved reference tracts for unsupervised brain white matter tractography. in Medical Image Understanding and Analysis: 21st Annual Conference, MIUA 2017, Edinburgh, UK, July 11–13, 2017, Proceedings. Communications in Computer and Information Science, pp. 425-435. DOI: 10.1007/978-3-319-60964-5_37
Neighbourhood tractography aims to automatically segment equivalent brain white matter tracts from diffusion magnetic resonance imaging (dMRI) data in different subjects by using a “reference tract” as a prior for the shape and length of each tract of interest. In the current work we present a means of improving the technique by using references tracts derived from dMRI data acquired from 80 healthy volunteers aged 25–64 years. The reference tracts were tested on the segmentation of 16 major white matter tracts in 50 healthy older people, aged 71.8 (±0.4) years. We found that datagenerated reference tracts improved the automatic white matter tract segmentations compared to results from atlas-generated reference tracts. We also obtained higher percentages of visually acceptable segmented tracts and lower variation in water diffusion parameters using this approach.
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Muñoz Maniega, Susana, Bastin, Mark, Deary, Ian, Wardlaw, Joanna & Clayden, Jonathan D..
Pages: 425-435
Publication Date: 22 Jun 2017
Publication Information
Category: Conference contribution
Original Language: English
DOIs: 10.1007/978-3-319-60964-5_37
2015
  White matter hyperintensities and normal-appearing white matter integrity in the ageing brain
Munoz-Maniega, S, Valdes Hernandez, M, Clayden, JD, Royle, N, Murray, C, Morris, Z, Aribisala, B, Gow, A, Starr, J, Bastin, M, Deary, I & Wardlaw, J 2015, 'White matter hyperintensities and normal-appearing white matter integrity in the ageing brain' Neurobiology of Aging, vol 36, no. 2, pp. 909-918. DOI: 10.1016/j.neurobiolaging.2014.07.048
White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain MRI of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss and rarefaction, often attributed to ischaemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported, but have not yet been fully characterized. Here we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from MRI that collectively reflect white matter integrity, myelination and brain water content. Fractional anisotropy (FA) and magnetisation transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10-9 m2 s-1 (area under curve 0.982, 95% CI 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared to surrounding NAWM, and that MD provides the best discriminator between the two tissue classes even within the mild range of WMH severity, while FA, MTR and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe.
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Munoz-Maniega, Susana, Valdes Hernandez, Maria, Clayden, Jonathan D., Royle, Natalie, Murray, Catherine, Morris, Zoe, Aribisala, Benjamin, Gow, Alan, Starr, John, Bastin, Mark, Deary, Ian & Wardlaw, Joanna.
Pages: 909-918
Publication Date: Feb 2015
Publication Information
Category: Article
Journal: Neurobiology of Aging
Volume: 36
Issue number: 2
ISSN: 0197-4580
Original Language: English
DOIs: 10.1016/j.neurobiolaging.2014.07.048
2013
  Probabilistic Neighborhood Tractography in the Preterm Neonatal Brain at 3 T
Anblagan, D, Bastin, M, Kershaw, L, Munoz-Maniega, S, Clayden, JD, Piyasena, C, Wilkinson, G, Roberts, N, Semple, S, Norman, J & Boardman, J 2013, 'Probabilistic Neighborhood Tractography in the Preterm Neonatal Brain at 3 T' The International Society for Magnetic Resonance in Medicine, Salt Lake City, United States, 20/04/13 - 26/04/13, .
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Anblagan, Devasuda, Bastin, Mark, Kershaw, Lucy, Munoz-Maniega, Susana, Clayden, Jonathan D., Piyasena, Chinthika, Wilkinson, Graham, Roberts, Neil , Semple, Scott, Norman, Jane & Boardman, James.
Publication Date: 2013
Publication Information
Category: Abstract
Original Language: English
  Probabilistic Neighbourhood Tractography in the Developing Brain
Anblagan, D, Bastin, M, Kershaw, L, Munoz-Maniega, S, Clayden, JD, Piyasena, C, Wilkinson, G, Semple, S, Roberts, N, Norman, J & Boardman, J 2013, 'Probabilistic Neighbourhood Tractography in the Developing Brain' Pediatric Academic Societies, United States, 4/05/13 - 7/05/13, .
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Anblagan, Devasuda, Bastin, Mark, Kershaw, Lucy, Munoz-Maniega, Susana, Clayden, Jonathan D., Piyasena, Chinthika, Wilkinson, Graham, Semple, Scott, Roberts, Neil , Norman, Jane & Boardman, James.
Publication Date: 2013
Publication Information
Category: Abstract
Original Language: English
  Probabilistic Neighbourhood Tractography in the Preterm Neonatal Brain
Anblagan, D, Bastin, M, Kershaw, L, Munoz-Maniega, S, Clayden, JD, Piyasena, C, Wilkinson, G, Roberts, N, Semple, S, Norman, J & Boardman, J 2013, 'Probabilistic Neighbourhood Tractography in the Preterm Neonatal Brain' Organization for Human Brain Mapping, Seattle, United States, 16/06/13 - 20/06/13, .
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Anblagan, Devasuda, Bastin, Mark, Kershaw, Lucy, Munoz-Maniega, Susana, Clayden, Jonathan D., Piyasena, Chinthika, Wilkinson, Graham, Roberts, Neil , Semple, Scott, Norman, Jane & Boardman, James.
Publication Date: 2013
Publication Information
Category: Abstract
Original Language: English
2011
  TractoR: Magnetic Resonance Imaging and Tractography with R
Clayden, JD, Maniega, SM, Storkey, AJ, King, MD, Bastin, ME & Clark, CA 2011, 'TractoR: Magnetic Resonance Imaging and Tractography with R' Journal of statistical software, vol 44, no. 8, pp. 1-18.

Statistical techniques play a major role in contemporary methods for analyzing magnetic resonance imaging (MRI) data. In addition to the central role that classical statistical methods play in research using MRI, statistical modeling and machine learning techniques are key to many modern data analysis pipelines. Applications for these techniques cover a broad spectrum of research, including many preclinical and clinical studies, and in some cases these methods are working their way into widespread routine use.

In this manuscript we describe a software tool called TractoR (for "Tractography with R"), a collection of packages for the R language and environment, along with additional infrastructure for straightforwardly performing common image processing tasks. TractoR provides general purpose functions for reading, writing and manipulating MR images, as well as more specific code for fitting signal models to diffusion MRI data and performing tractography, a technique for visualizing neural connectivity.


General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Clayden, Jonathan D., Maniega, Susana Munoz, Storkey, Amos J., King, Martin D., Bastin, Mark E. & Clark, Chris A..
Keywords: (diffusion, MODEL, BRAIN, MRI, tractography, R, machine learning, image processing, magnetic resonance imaging, DIFFUSION TENSOR, , , . )
Number of pages: 18
Pages: 1-18
Publication Date: Oct 2011
Publication Information
Category: Article
Journal: Journal of statistical software
Volume: 44
Issue number: 8
ISSN: 1548-7660
Original Language: English
  Brain Ageing, Cognition in Youth and Old Age, and Vascular Disease in the Lothian Birth Cohort 1936: Rationale, Design and Methodology of the Imaging Protocol
Wardlaw, JM, Bastin, ME, Valdes Hernandez, M, Muñoz Maniega, S, Royle, NA, Morris, Z, Clayden, JD, Sandeman, EM, Eadie, E, Murray, C, Starr, JM & Deary, IJ 2011, 'Brain Ageing, Cognition in Youth and Old Age, and Vascular Disease in the Lothian Birth Cohort 1936: Rationale, Design and Methodology of the Imaging Protocol' International Journal of Stroke, vol 6, no. 6, pp. 547-559. DOI: 10.1111/j.1747-4949.2011.00683.x.
Rationale: As the population of the world ages, age-related cognitive decline is becoming an ever-increasing problem. However, the changes in brain structure that accompany normal ageing, and the role they play in cognitive decline, remain to be fully elucidated. Aims: This study aims to characterize changes in brain structure in old age, and to investigate relationships between brain ageing and cognitive decline using the Lothian Birth Cohort 1936 (LBC1936). Here, we report the rationale, design and methodology of the brain and neurovascular imaging protocol developed to study this cohort. Design: An observational, longitudinal study of the LBC1936, which comprises 1091 relatively healthy individuals now in their 70's and living in the Edinburgh area. They are surviving participants of the Scottish Mental Survey 1947, which involved a test of general intelligence taken at age 11 years. At age 70 years the LBC1936 undertook detailed cognitive, medical and genetic testing, and provided social, family, nutritional, quality of life and physical activity information. At mean age 73 years they are undergoing detailed brain MRI and neurovascular ultrasound imaging, repeat cognitive and other testing. The MRI protocol is designed to provide qualitative and quantitative measures of grey and white matter atrophy, severity and location of white matter lesions, enlarged perivascular spaces, brain mineral deposits, microbleeds and integrity of major white matter tracts. The neurovascular ultrasound imaging provides velocity, stenosis and intima-media thickness measurements of the carotid and vertebral arteries. Study: This valuable imaging dataset will be used to determine which changes in brain structural parameters have the largest effects on cognitive ageing. Analysis will include multimodal image analysis and multivariate techniques, such as factor analysis and structural equation modelling. Especially valuable is the ability within this sample to examine the influence that early life intelligence has on brain structural parameters in old age, and the role of genetic, vascular, educational and lifestyle factors. Outcomes: Final outcomes include associations between early and late life cognition and integrity of key white matter tracts, volume of grey and white matter, myelination, brain water content, and visible abnormalities such as white matter lesions and mineral deposits; and influences of vascular risk factors, diet, environment, social metrics, education and genetics on healthy brain ageing. It is intended that this information will help to inform and develop strategies for successful cognitive ageing.
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Wardlaw, Joanna M., Bastin, Mark E., Valdes Hernandez, Maria, Muñoz Maniega, Susana, Royle, Natalie A., Morris, Zoe, Clayden, Jonathan D., Sandeman, Elaine M., Eadie, Elizabeth, Murray, Catherine, Starr, John M. & Deary, Ian J..
Keywords: (cognition, aeging, Lothian Birth Cohort, vascular disease, brain imaging. )
Number of pages: 13
Pages: 547-559
Publication Date: Dec 2011
Publication Information
Category: Article
Journal: International Journal of Stroke
Volume: 6
Issue number: 6
ISSN: 1747-4930
Original Language: English
DOIs: 10.1111/j.1747-4949.2011.00683.x.
2010
  White Matter Integrity in the Splenium of the Corpus Callosum is Related to Successful Cognitive Aging and Partly Mediates the Protective Effect of an Ancestral Polymorphism in ADRB2
Penke, L, Maniega, SM, Houlihan, LM, Murray, C, Gow, AJ, Clayden, JD, Bastin, ME, Wardlaw, JM & Deary, IJ 2010, 'White Matter Integrity in the Splenium of the Corpus Callosum is Related to Successful Cognitive Aging and Partly Mediates the Protective Effect of an Ancestral Polymorphism in ADRB2' Behavior Genetics, vol 40, no. 2, pp. 146-156. DOI: 10.1007/s10519-009-9318-4
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Penke, Lars, Maniega, Susana Muñoz, Houlihan, Lorna M., Murray, Catherine, Gow, Alan J., Clayden, Jonathan D., Bastin, Mark E., Wardlaw, Joanna M. & Deary, Ian J..
Keywords: (, , . )
Pages: 146-156
Publication Date: 1 Mar 2010
Publication Information
Category: Article
Journal: Behavior Genetics
Volume: 40
Issue number: 2
ISSN: 0001-8244
Original Language: English
DOIs: 10.1007/s10519-009-9318-4
  A General Factor of Brain White Matter Integrity Predicts Information Processing Speed in Healthy Older People
Penke, L, Maniega, SM, Murray, C, Gow, AJ, Valdes Hernandez, M, Clayden, JD, Starr, J, Wardlaw, JM, Bastin, ME & Deary, IJ 2010, 'A General Factor of Brain White Matter Integrity Predicts Information Processing Speed in Healthy Older People' The Journal of Neuroscience, vol 30, no. 22, pp. 7569-7574. DOI: 10.1523/JNEUROSCI.1553-10.2010
Human white matter integrity has been related to information processing speed, but it is unknown whether impaired integrity results from localized processes or is a general property shared across white matter tracts. Based on diffusion MRI scans of 132 healthy individuals with a narrow age range around 72 years, the integrity of eight major white matter tracts was quantified using probabilistic neighborhood tractography. Principal component analyses (PCAs) were conducted on the correlations between the eight tracts, separately for four tract-averaged integrity parameters: fractional anisotropy, mean diffusivity, and radial and axial diffusivity. For all four parameters, the PCAs revealed a single general factor explaining ?45% of the individual differences across all eight tracts. Individuals' scores on a general factor that captures the common variance in white matter integrity had significant associations with a general factor of information processing speed for fractional anisotropy (r = ?0.24, p = 0.007) and radial diffusivity (r = 0.21, p = 0.016), but not with general intelligence or memory factors. Individual tracts showed no associations beyond what the common integrity factor explained. Just as different types of cognitive ability tests share much of their variance, these novel findings show that a substantial amount of variance in white matter integrity is shared between different tracts. Therefore, impaired cortical connection is substantially a global process affecting various major tracts simultaneously. Further studies should investigate whether these findings relate more to the role of tract integrity and information processing speed in nonpathological cognitive aging or in lifelong-stable processes.
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Penke, L., Maniega, S. M., Murray, C., Gow, A. J., Valdes Hernandez, Maria, Clayden, J. D., Starr, John, Wardlaw, J. M., Bastin, M. E. & Deary, I. J..
Keywords: (, , . )
Pages: 7569-7574
Publication Date: 2 Jun 2010
Publication Information
Category: Article
Journal: The Journal of Neuroscience
Volume: 30
Issue number: 22
ISSN: 0270-6474
Original Language: English
DOIs: 10.1523/JNEUROSCI.1553-10.2010
  Quantifying the effects of normal ageing on white matter structure using unsupervised tract shape modelling
Bastin, ME, Maniega, SM, Ferguson, KJ, Brown, LJ, Wardlaw, JM, MacLullich, AMJ & Clayden, JD 2010, 'Quantifying the effects of normal ageing on white matter structure using unsupervised tract shape modelling' NeuroImage, vol 51, no. 1, pp. 1-10. DOI: 10.1016/j.neuroimage.2010.02.036
Quantitative tractography may provide insights into regional heterogeneity of changes in white matter structure in normal ageing. Here we examine how brain atrophy and white matter lesions affect correlations between tract shape, tract integrity and age in a range of frontal and non-frontal tracts in 90 non-demented subjects aged over 65 years using an enhanced version of probabilistic neighbourhood tractography. This novel method for automatic single seed point placement employs unsupervised learning and streamline selection to provide reliable and accurate tract segmentation, whilst also indicating how the shape of an individual tract compares to that of a predefined reference tract. There were significant negative correlations between tract shape similarity to reference tracts derived from a young brain white matter atlas and age in genu and splenium of corpus callosum. Controlling for intracranial and lateral ventricle volume, the latter of which increased significantly with age, attenuated these correlations by 40% and 84%, respectively, indicating that this age-related change in callosal tract topology is significantly mediated by global atrophy and ventricular enlargement. In accordance with the "frontal ageing" hypothesis, there was a significant positive correlation between mean diffusivity (D) and age, and a significant negative correlation between fractional anisotropy (FA) and age in corpus callosum genu; correlations not seen in splenium. Significant positive correlations were also observed between D and age in bilateral cingulum cingulate gyri, uncinate fasciculi and right corticospinal tract. This pattern of correlations was not, however, reproduced when those subjects with significant white matter lesion load were analyzed separately from those without. These data therefore suggest that brain atrophy and white matter lesions play a significant role in driving regional patterns of age-related changes in white matter tract shape and integrity.
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Bastin, Mark E, Maniega, Susana Muñoz, Ferguson, Karen J, Brown, Laura J, Wardlaw, Joanna M, MacLullich, Alasdair M J & Clayden, Jonathan D..
Keywords: (ageing, white matter, magnetic resonance imaging, water diffusion tensor, tractography, , , . )
Number of pages: 10
Pages: 1-10
Publication Date: May 2010
Publication Information
Category: Article
Journal: NeuroImage
Volume: 51
Issue number: 1
ISSN: 1053-8119
Original Language: English
DOIs: 10.1016/j.neuroimage.2010.02.036
2009
  The Relationship of Anterior Thalamic Radiation Integrity to Psychosis Risk Associated Neuregulin-1 Variants
Sprooten, E, Lymer, GK, Maniega, SM, McKirdy, J, Clayden, JD, Bastin, ME, Porteous, D, Johnstone, EC, Lawrie, SM, Hall, J & McIntosh, AM 2009, 'The Relationship of Anterior Thalamic Radiation Integrity to Psychosis Risk Associated Neuregulin-1 Variants' Biological Psychiatry, vol 65, no. 8, pp. 202S-203S.
General Information
Organisations: Centre for Genomic and Experimental Medicine.
Authors: Sprooten, Emma, Lymer, G. Katherine, Maniega, Susana Munoz, McKirdy, James, Clayden, Jonathan D., Bastin, Mark E., Porteous, David, Johnstone, Eve C., Lawrie, Stephen M., Hall, Jeremy & McIntosh, Andrew M..
Number of pages: 2
Pages: 202S-203S
Publication Date: 15 Apr 2009
Publication Information
Category: Meeting abstract
Journal: Biological Psychiatry
Volume: 65
Issue number: 8
ISSN: 0006-3223
Original Language: English
  The relationship of anterior thalamic radiation integrity to psychosis risk associated neuregulin-1 variants
Sprooten, E, Lymer, GK, Maniega, SM, McKirdy, J, Clayden, JD, Bastin, ME, Porteous, D, Johnstone, EC, Lawrie, SM, Hall, J & McIntosh, AM 2009, 'The relationship of anterior thalamic radiation integrity to psychosis risk associated neuregulin-1 variants' Molecular Psychiatry, vol 14, no. 3, pp. 237-238. DOI: 10.1038/mp.2008.136
General Information
Organisations: Centre for Genomic and Experimental Medicine.
Authors: Sprooten, E., Lymer, G. K., Maniega, S. M., McKirdy, J., Clayden, J. D., Bastin, M. E., Porteous, D., Johnstone, E. C., Lawrie, S. M., Hall, Jeremy & McIntosh, A. M..
Keywords: (, , . )
Number of pages: 2
Pages: 237-238
Publication Date: Mar 2009
Publication Information
Category: Letter
Journal: Molecular Psychiatry
Volume: 14
Issue number: 3
ISSN: 1359-4184
Original Language: English
DOIs: 10.1038/mp.2008.136
  Reproducibility of tract segmentation between sessions using an unsupervised modelling-based approach
Clayden, JD, Storkey, AJ, Maniega, SM & Bastin, ME 2009, 'Reproducibility of tract segmentation between sessions using an unsupervised modelling-based approach' NeuroImage, vol 45, no. 2, pp. 377-385. DOI: 10.1016/j.neuroimage.2008.12.010
This work describes a reproducibility analysis of scalar water diffusion parameters, measured within white matter tracts segmented using a probabilistic shape modelling method. In common with previously reported neighbourhood tractography (NT) work, the technique optimises seed point placement for fibre tracking by matching the tracts generated using a number of candidate points against a reference tract, which is derived from a white matter atlas in the present study. No direct constraints are applied to the fibre tracking results. An Expectation–Maximisation algorithm is used to fully automate the procedure, and make dramatically more efficient use of data than earlier NT methods. Within-subject and between-subject variances for fractional anisotropy and mean diffusivity within the tracts are then separated using a random effects model. We find test–retest coefficients of variation (CVs) similar to those reported in another study using landmark-guided single seed points; and subject to subject CVs similar to a constraint-based multiple ROI method. We conclude that our approach is at least as effective as other methods for tract segmentation using tractography, whilst also having some additional benefits, such as its provision of a goodness-of-match measure for each segmentation.
General Information
Organisations: Deanery of Clinical Sciences.
Authors: Clayden, J. D., Storkey, A. J., Maniega, S. M. & Bastin, M. E..
Keywords: (, , . )
Number of pages: 9
Pages: 377-385
Publication Date: Apr 2009
Publication Information
Category: Article
Journal: NeuroImage
Volume: 45
Issue number: 2
ISSN: 1053-8119
Original Language: English
DOIs: 10.1016/j.neuroimage.2008.12.010
  Diffusion tensor and magnetization transfer MRI measurements of periventricular white matter hyperintensities in old age
Bastin, M, Clayden, J, Pattie, A, Gerrish, I, Wardlaw, J & Deary, I 2009, 'Diffusion tensor and magnetization transfer MRI measurements of periventricular white matter hyperintensities in old age' Neurobiology of Aging, vol 30, no. 1, pp. 125-136. DOI: 10.1016/j.neurobiolaging.2007.05.013
Regions of diffuse periventricular white matter hyperintensities (PVWMH) are a common finding on T2-weighted MRI scans of older subjects, but their aetiology remains unclear. The aim of this study was to characterize differences in water diffusion and magnetization transfer MRI parameters between macroscopically normal-appearing white matter (NAWM) and PVWMH in a cohort of normal older subjects. Forty-two non-demented 83-year olds underwent structural, diffusion tensor and magnetization transfer MRI. Mean diffusivity (<D>), fractional anisotropy (FA), axial (?ax) and radial (?rad) diffusivity, and magnetization transfer ratio (MTR) were measured in both NAWM and PVWMH in frontal and parieto-occipital white matter, and centrum semiovale. For all three regions, PVWMH had greater <D>, ?ax and ?rad than NAWM, while FA and MTR were significantly reduced compared with normal tissue (p 0.01). For PVWMH, MTR was significantly correlated (Spearman's ? in the range ?0.93 to 0.70; p < 0.01) with <D>, FA, ?ax and ?rad in all three regions. Conversely, for NAWM, the only significant correlation between MTR and a water diffusion parameter was for ?rad in parieto-occipital white matter (? = ?0.40; p < 0.05), with all other correlations close to the ? = 0 level. These data indicate that in normal white matter, characterized by structurally coherent cell membranes, the degree of water molecule diffusion and myelination are held within relatively tight limits. However, within PVWMH, MTR correlates strongly with water diffusion parameters probably because of the pathologically associated neuronal loss, demyelination and gliosis.
General Information
Organisations: Deanery of Molecular, Genetic and Population Health Sciences.
Authors: Bastin, M, Clayden, J, Pattie, A, Gerrish, I, Wardlaw, J & Deary, I.
Keywords: (ageing , white matter , magnetic resonance imaging , water diffusion tensor , magnetization transfer, , , . )
Number of pages: 12
Pages: 125-136
Publication Date: Jan 2009
Publication Information
Category: Article
Journal: Neurobiology of Aging
Volume: 30
Issue number: 1
ISSN: 0197-4580
Original Language: English
DOIs: 10.1016/j.neurobiolaging.2007.05.013
2008
  Evidence of shared white matter disruption in bipolar disorder and sschizophrenia
McIntosh, AM, Sussmann, J, Lymer, GKS, Munoz-Maniega, S, Bastin, M, Hall, J, Lawrie, S, Johnstone, E, Clayden, J, Job, D & Moorhead, TWJ 2008, 'Evidence of shared white matter disruption in bipolar disorder and sschizophrenia' European Psychiatry, vol 23, pp. S43-S43.
General Information
Organisations: Neuroinformatics DTC.
Authors: McIntosh, A. M., Sussmann, J., Lymer, G. K. S., Munoz-Maniega, Susana, Bastin, M., Hall, J., Lawrie, S., Johnstone, E., Clayden, J., Job, D. & Moorhead, T. W. J..
Number of pages: 1
Pages: S43-S43
Publication Date: Apr 2008
Publication Information
Category: Meeting abstract
Journal: European Psychiatry
Volume: 23
ISSN: 0924-9338
Original Language: English
  White Matter Tractography in Bipolar Disorder and Schizophrenia
McIntosh, AM, Maniega, SM, Lymer, GKS, McKirdy, J, Hall, J, Sussmann, JED, Bastin, ME, Clayden, JD, Johnstone, EC & Lawrie, SM 2008, 'White Matter Tractography in Bipolar Disorder and Schizophrenia' Biological Psychiatry, vol 64, no. 12, pp. 1088-1092. DOI: 10.1016/j.biopsych.2008.07.026

Background: Abnormalities of white matter integrity have been repeatedly demonstrated in both schizophrenia and bipolar disorder with voxel based methods. Because these methods are limited in their ability to localize deficits to specific tracts, we sought to investigate alterations in fractional anisotropy (FA) in the uncinate fasciculus and anterior thalamic radiation with probabilistic tractography.

Methods: Individuals with schizophrenia (n = 25) or bipolar disorder (n = 40) were recruited from families with two or more affected members and age-matched to a control group (n = 49). All participants underwent diffusion tensor magnetic resonance imaging that was subsequently analyzed with probabilistic tractography. Mean FA was calculated bilaterally for the uncinate and anterior thalamic radiation and compared between groups with repeated measures analysis of variance.

Results: Patients with schizophrenia or bipolar disorder showed common reductions in the uncinate fasciculus and anterior thalamic radiation. These reductions were unrelated to age, duration of illness, current medication, or current psychiatric symptoms in all patients or the lifetime presence of psychotic symptoms in bipolar subjects.

Conclusions: Patients with schizophrenia or bipolar disorder show common abnormalities in the uncinate fasciculus and anterior thalamic radiation that fail to respect traditional diagnostic boundaries. These deficits might be related to shared risk factors and disease mechanisms common to both disorders.


General Information
Organisations: Neuroinformatics DTC.
Authors: McIntosh, Andrew M., Maniega, Susana Munoz, Lymer, G. Katherine S., McKirdy, James, Hall, Jeremy, Sussmann, Jessika E. D., Bastin, Mark E., Clayden, Jonathan D., Johnstone, Eve C. & Lawrie, Stephen M..
Keywords: (, , . )
Number of pages: 5
Pages: 1088-1092
Publication Date: 15 Dec 2008
Publication Information
Category: Article
Journal: Biological Psychiatry
Volume: 64
Issue number: 12
ISSN: 0006-3223
Original Language: English
DOIs: 10.1016/j.biopsych.2008.07.026
  Tract shape modelling provides evidence of topological change in corpus callosum genu during normal ageing
Bastin, ME, Piatkowski, JP, Storkey, AJ, Brown, LJ, MacLullich, AMJ & Clayden, JD 2008, 'Tract shape modelling provides evidence of topological change in corpus callosum genu during normal ageing' NeuroImage, vol 43, no. 1, pp. 20-28. DOI: 10.1016/j.neuroimage.2008.06.047

Understanding how ageing affects brain structure is an important challenge for medical science. By allowing segmentation of fasciculi-of-interest front diffusion magnetic resonance imaging (dMRI) data, tractography provides a promising tool for assessing white matter connectivity in old age. However, the output from tractography algorithms is usually strongly dependent on the subjective location of user-specified seed points, with the result that it can be both difficult and time consuming to identify the same tract reliably in cross-sectional Studies. Here we investigate whether a novel method for automatic single seed point placement based on tract shape modelling, termed probabilistic model-based neighbourhood tractography (PNT), can reliably segment the same tract from subject to subject in a non-demented cohort aged over 65 years. For the fasciculi investigated (genu and splenium of corpus callosum, cingulum cingulate gyri, corticospinal tracts and uncinate fasciculi), PNT was able to provide anatomically plausible representations of the tract in question in 70 to 90% of subjects compared with 2.5 to 60% if single seed points were simply transferred directly from standard to native space. In corpus callosum germ there was a significant negative correlation between a PNT-derived measure Of tract shape similarity to a young brain reference tract and age, and a trend towards a significant negative correlation between tract-averaged fractional anisotropy and age; results that are consistent with previous dMRI studies of normal ageing. These data show that it is possible automatically to segment Comparable tracts in the brains of older subjects using single seed point tractography, if the seed point is carefully chosen. (C) 2008 Elsevier Inc. All rights reserved.


General Information
Organisations: Neuroinformatics DTC.
Authors: Bastin, Mark E., Piatkowski, Jakub P., Storkey, Amos J., Brown, Laura J., MacLullich, Alasdair M. J. & Clayden, Jonathan D..
Keywords: (, , . )
Number of pages: 9
Pages: 20-28
Publication Date: 15 Oct 2008
Publication Information
Category: Article
Journal: NeuroImage
Volume: 43
Issue number: 1
ISSN: 1053-8119
Original Language: English
DOIs: 10.1016/j.neuroimage.2008.06.047
2007
  Fine-grained comparison of anisotropy differences between groups of white matter tracts
Clayden, JD, Zhang, S, Correia, S & Laidlaw, DH 2007, Fine-grained comparison of anisotropy differences between groups of white matter tracts. in ISMRM-ESMRMB Joint Annual Meeting, Berlin.
General Information
Organisations: Neuroinformatics DTC.
Authors: Clayden, Jonathan D., Zhang, S., Correia, S. & Laidlaw, D. H..
Publication Date: 2007
Publication Information
Category: Conference contribution
Original Language: English
  A Probabilistic Model-Based Approach to Consistent White Matter Tract Segmentation
Clayden, JD, Storkey, AJ & Bastin, ME 2007, 'A Probabilistic Model-Based Approach to Consistent White Matter Tract Segmentation' IEEE Transactions on Medical Imaging, vol 26, no. 11, pp. 1555-1561. DOI: 10.1109/TMI.2007.905826
Since the invention of diffusion magnetic resonance imaging (dMRI), currently the only established method for studying white matter connectivity in a clinical environment, there has been a great deal of interest in the effects of various pathologies on the connectivity of the brain. As methods for in vivo tractography have been developed, it has become possible to track and segment specific white matter structures of interest for particular study. However, the consistency and reproducibility of tractography-based segmentation remain limited, and attempts to improve them have thus far typically involved the imposition of strong constraints on the tract reconstruction process itself. In this work we take a different approach, developing a formal probabilistic model for the relationships between comparable tracts in different scans, and then using it to choose a tract, a posteriori, which best matches a predefined reference tract for the structure of interest. We demonstrate that this method is able to significantly improve segmentation consistency without directly constraining the tractography algorithm.
General Information
Organisations: Centre for Clinical Brain Sciences.
Authors: Clayden, J.D , Storkey, A. J. & Bastin, M. E. .
Number of pages: 7
Pages: 1555-1561
Publication Date: 1 Nov 2007
Publication Information
Category: Article
Journal: IEEE Transactions on Medical Imaging
Volume: 26
Issue number: 11
ISSN: 0278-0062
Original Language: English
DOIs: 10.1109/TMI.2007.905826
  DTI and MTI parameters correlate in periventricular white matter hyperintensities in old age
Bastin, M, Clayden, JD & Wardlaw, J 2007, DTI and MTI parameters correlate in periventricular white matter hyperintensities in old age. in ISMRM-ESMRMB Joint Annual Meeting, Berlin.
General Information
Organisations: Neuroinformatics DTC.
Authors: Bastin, Mark, Clayden, Jonathan D. & Wardlaw, Joanna.
Publication Date: 2007
Publication Information
Category: Conference contribution
Original Language: English
2006
  Automated assessment of tract similarity in group diffusion MRI data
Clayden, JD, Bastin, M & Storkey, A 2006, Automated assessment of tract similarity in group diffusion MRI data. in Proceedings of the ISMRM, 14th Scientific Meeting Exhibition, Seattle.
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: Clayden, Jonathan D., Bastin, Mark & Storkey, Amos.
Publication Date: 2006
Publication Information
Category: Conference contribution
Original Language: English
  Neighbourhood tractography: a new approach to seed point placement for fibre tracking
Clayden, JD, Bastin, M & Storkey, A 2006, Neighbourhood tractography: a new approach to seed point placement for fibre tracking. in Proceedings of the British Chapter of the ISMRM, Guildford, UK.
One area in which diffusion MRI (dMRI) based fibre tracking techniques have strong potential is in the segmentation of individual white matter structures (tracts) from dMRI images. The segmented areas can be used as regions of interest (ROIs) for studying tract specific effects of pathology [1]. This kind of tractography based segmentation is advantageous over more established ROI methods because the regions are calculated algorithmically, removing observer subjectivity; and because the regions can be arbitrarily shaped in three dimensions, matching the anatomy of the underlying fasciculus.
However, fibre tracking algorithms typically require as input a seed point, a location in dMRI space from which the algorithm begins to reconstruct a tract. The resultant segmentation can be very strongly dependent on the exact location of this point. This sensitivity can be problematic when trying to consistently segment a specific tract from several brain volumes. In this work we demonstrate the inconsistency of segmentations derived from registration based seed point placement, and describe an alternative approach that is based on maximising output similarity to a reference tract within a seeding neighbourhood in native image space.
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: Clayden, Jonathan D., Bastin, Mark & Storkey, Amos.
Publication Date: 2006
Publication Information
Category: Conference contribution
Original Language: English
  Improved segmentation reproducibility in group tractography using a quantitative tract similarity measure
Clayden, JD, Bastin, ME & Storkey, AJ 2006, 'Improved segmentation reproducibility in group tractography using a quantitative tract similarity measure' NeuroImage, vol 33, no. 2, pp. 482-92. DOI: 10.1016/j.neuroimage.2006.07.016
The field of tractography is rapidly developing, and many automatic or semiautomatic algorithms have now been devised to segment and visualize neural white matter fasciculi in vivo. However, these algorithms typically need to be given a starting location as input, and their output can be strongly dependent on the exact location of this "seed point". No robust method has yet been devised for placing these seed points so as to segment a comparable tract in a group of subjects. Here, we develop a measure of tract similarity, based on the shapes and lengths of the two tracts being compared, and apply it to the problem of consistent seed point placement and tract segmentation in group data. We demonstrate that using a single seed point transferred from standard space to each native space produces considerable variability in tractography output between scans. However, by seeding in a group of nearby candidate points and choosing the output with the greatest similarity to a reference tract chosen in advance--a method we refer to as neighborhood tractography--this variability can be significantly reduced.
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: Clayden, Jonathan D, Bastin, Mark E & Storkey, Amos J.
Number of pages: 11
Pages: 482-92
Publication Date: 2006
Publication Information
Category: Article
Journal: NeuroImage
Volume: 33
Issue number: 2
ISSN: 1053-8119
Original Language: English
DOIs: 10.1016/j.neuroimage.2006.07.016
  White matter integrity and cognition in childhood and old age
Deary, IJ, Bastin, ME, Pattie, A, Clayden, JD, Whalley, LJ, Starr, J & Wardlaw, JM 2006, 'White matter integrity and cognition in childhood and old age' Neurology, vol 66, no. 4, pp. 505-512.

Objective: To test the hypothesis that white matter integrity, as measured by diffusion tensor and magnetization transfer MRI is significantly associated with cognitive ability measured in youth and old age. Methods: Forty, nondemented, surviving participants of the Scottish Mental Survey of 1932 underwent brain MRI and a battery of psychometric tests covering major cognitive domains and tests of information processing efficiency. IQ scores were available from age 11. Mean diffusivity, fractional anisotropy (FA), and magnetization transfer ratio (MTR) were measured in frontal and parieto-occipital white matter and centrum semiovale. Results: Centrum semiovale FA correlated (r = 0.36 to 0.56; p < 0.02) with contemporaneous (age 83) scores on psychometric tests of nonverbal reasoning, working memory, executive function, and information processing efficiency. Centrum semiovale FA also correlated with IQ at age 11 (r = 0.37; p = 0.02). Controlling for IQ at age 11 and information processing at age 83 attenuated the association between centrum semiovale FA and general cognitive ability by approximately 85%. MTR, largely, did not show significant correlations with cognitive test scores. Conclusions: These data support the information processing efficiency hypothesis of cognitive aging and suggest one foundation for individual differences in processing efficiency. They also suggest that studies of imaging and cognition in the elderly should take into account prior mental ability rather than assuming that any associations between imaging parameters and cognitive test scores are the result of age-related changes.


General Information
Organisations: Deanery of Molecular, Genetic and Population Health Sciences.
Authors: Deary, I J , Bastin, M E , Pattie, A , Clayden, J D, Whalley, L J , Starr, John & Wardlaw, J M .
Keywords: (REMITTING MULTIPLE-SCLEROSIS, DIFFUSION-TENSOR, MAGNETIZATION-TRANSFER, ALZHEIMERS-DISEASE, PROCESSING-SPEED, WATER DIFFUSION, NERVOUS-SYSTEM, BRAIN, IMPAIRMENT, ABNORMALITIES. )
Number of pages: 8
Pages: 505-512
Publication Date: 28 Feb 2006
Publication Information
Category: Article
Journal: Neurology
Volume: 66
Issue number: 4
ISSN: 0028-3878
Original Language: English
2005
  Cognitive ageing and white matter integrity: a diffusion tensor and magnetisation transfer MRI study
Bastin, M, Clayden, JD & Wardlaw, J 2005, Cognitive ageing and white matter integrity: a diffusion tensor and magnetisation transfer MRI study. in Proceedings of the ISMRM, 13th Scientific Meeting Exhibition, Miami, USA.
Retaining the integrity of the brain’s white matter might be important for successful cognitive ageing [1]. There are associations between the number of white matter lesions (e.g. Fazekas scores) and cognitive test scores [2]. Diffusion tensor MRI (DT-MRI) can provide more sensitive indicators of the state of cerebral white matter. Mean diffusivity () and fractional anisotropy (FA) are found to correlate significantly with cognitive ability in old age, especially with tests of executive function [3]. On the other hand, one study suggested that DT- MRI parameters correlate with life-long cognitive traits rather than cognitive ability in old age specifically [4]. Here we test the hypothesis that white matter integrity as measured by DT-MRI and magnetisation transfer MRI (MT-MRI) is related to cognitive ability in youth and old age [5]. In MT-MRI, a saturation pulse is used to selectively saturate the bound proton pool, giving rise to contrast that reflects differences in the resonant properties of free and bound protons. The magnetisation transfer ratio (MTR) , which expresses the magnitude of this effect, therefore reflects the amount and nature of macromolecular structures in a given brain volume, and can indicate white matter structural damage resulting from myelin loss. DT-MRI and MT-MRI are therefore complementary imaging modalities in that they provide measures of white matter tract integrity.
General Information
Organisations: Neuroinformatics DTC.
Authors: Bastin, Mark, Clayden, Jonathan D. & Wardlaw, Joanna.
Publication Date: 2005
Publication Information
Category: Conference contribution
Original Language: English
  Towards an automated method for white matter integrity comparison between populations
Clayden, JD, Marjoram, DKS, Bastin, M, Johnstone, E & Lawrie, S 2005, 'Towards an automated method for white matter integrity comparison between populations'.
General Information
Organisations: Centre for Clinical Brain Sciences.
Authors: Clayden, Jonathan D., Marjoram, Dominic K. S., Bastin, Mark, Johnstone, Eve & Lawrie, Stephen.
Publication Date: 2005
Publication Information
Category: Poster
Original Language: English
  White matter integrity and cognition in childhood and old age: a diffusion tensor MRI study, Methods for Quantitative MRI of Human Brain
Bastin, M, Clayden, JD, Starr, JM & Wardlaw, J 2005, White matter integrity and cognition in childhood and old age: a diffusion tensor MRI study, Methods for Quantitative MRI of Human Brain. in ISMRM Workshop.
General Information
Organisations: Neuroinformatics DTC.
Authors: Bastin, Mark, Clayden, Jonathan D., Starr, J. M. & Wardlaw, Joanna.
Publication Date: 2005
Publication Information
Category: Conference contribution
Original Language: English

Projects:
Developing advanced diffusion MR imaging (dMRI) methods (PhD)

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