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Stuart M. Grieve

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

9 papers

1 author row

YNICL Journal 2021 Journal Article

Diffusion kurtosis imaging detects subclinical white matter abnormalities in Phenylketonuria

Sarah C. Hellewell
Thomas Welton
Kate Eisenhuth
Michel C. Tchan
Stuart M. Grieve

OBJECTIVE: Phenylketonuria (PKU) is an autosomal recessive disorder whereby deficiencies in phenylalanine metabolism cause progressive neurological dysfunction. Managing PKU is challenging, with disease monitoring focussed on short-term phenylalanine control rather than measures of neuronal damage. Conventional imaging lacks sensitivity, however diffusion kurtosis imaging (DKI), a new MRI method may reveal subclinical white matter structural changes in PKU. METHODS: ratio). We then tested this metric in a Replication cohort (PKU = 20; controls = 43). RESULTS: provided clear separation by diagnosis in the Replication cohort (p < 0.001 in periventricular, deep and pericortical compartments). The ratio also correlated negatively with attention (r = -0.51 & -0.50, p < 0.05) and positively with 3-year mean Phe (r = 0.45 & 0.58, p < 0.01). CONCLUSION: ratio) was sensitive to cognitive impairment and PKU control over the medium term and may provide a meaningful subclinical biomarker of end-organ damage.

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YNICL Journal 2020 Journal Article

Characteristic patterns of white matter tract injury in sport-related concussion: An image based meta-analysis

Sarah C. Hellewell
Vy P.B. Nguyen
Ruchira N. Jayasena
Thomas Welton
Stuart M. Grieve

Sports-related concussion (SRC) is sustained by millions of people per year, yet the spatiotemporal patterns of white matter (WM) injury remain poorly understood. Several SRC studies have implemented the standardised approach Tract-Based Spatial Statistics (TBSS). The aim of this image-based meta-analysis was to identify consensus patterns of SRC-related WM injury across TBSS studies. We included studies comparing the diffusion MRI measurement fractional anisotropy (FA) in SRC or subconcussive injury vs. controls using TBSS, as FA is the most frequently examined diffusion tensor imaging metric. Authors of eligible studies were contacted to request unthresholded statistical map outputs from TBSS, and image-based meta-analyses were performed using Seed-Based d-Mapping. Eight studies contributed to our meta-analyses, comprising 174 SRC or subconcussive injury participants and 160 controls. Our primary meta-analysis (n = 8), encompassing subjects with acute SRC (n = 2), chronic SRC (n = 4) and subconcussive injuries (n = 2) revealed dominant bilateral increased FA in the superior longitudinal fasciculus (SLF) and internal capsule. Subconcussive injury was associated with small clusters of increased and decreased FA in the arcuate fasciculus compared to control. In acute SRC, we found diffuse foci of raised FA at WM/grey matter border-zone associated with the bilateral SLF and right inferior fronto-occipital fasciculus. In contrast, chronic SRC had a pattern of deep WM alteration, asymmetrically located in the right optic radiations and arcuate fasciculus. Our findings represent the most powerful analysis of TBSS data in SRC, supporting the use of this approach to analyse diffusion data. TBSS is sensitive to WM abnormalities resulting from SRC or subconcussive injury over a range of temporal and clinical scenarios. Our data show spatially concordant patterns of WM injury unique to subconcussive, acute and chronic phases, highlighting the future utility of diffusion MRI for concussion diagnosis.

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YNICL Journal 2019 Journal Article

Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis

Thomas Welton
Jerome J. Maller
R. Marc Lebel
Ek T. Tan
Dominic B. Rowe
Stuart M. Grieve

OBJECTIVE: To construct a clinical diagnostic biomarker using state-of-the-art microstructural MRI in the motor cortex of people with amyotrophic lateral sclerosis (ALS). METHODS: Clinical and MRI data were obtained from 21 ALS patients (aged 54 ± 14 years, 33% female) and 63 age- and gender-matched controls (aged 48 ± 18 years, 43% female). MRI was acquired at 3T and included T1-weighted scan (for volumetrics), arterial spin labelling (for cerebral blood flow), susceptibility-weighted angiography (for iron deposition) and multiband diffusion kurtosis imaging (for tissue microstructure). Group differences in imaging measures in the motor cortex were tested by general linear model and relationships to clinical variables by linear regression. RESULTS: = 0.25, p = .033). A composite imaging biomarker comprising kurtosis and iron deposition measures yielded a maximal diagnostic accuracy of 83% (81% sensitivity, 85% specificity) and an area-under-the-curve of 0.86. CONCLUSION: Diffusion kurtosis is sensitive to early changes present in the motor region in ALS. We propose a composite imaging biomarker reflecting tissue microstructural changes in early ALS that may provide clinically valuable diagnostic information.

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YNICL Journal 2019 Journal Article

Gender-specific structural abnormalities in major depressive disorder revealed by fixel-based analysis

Matt Lyon
Thomas Welton
Adrina Varda
Jerome J. Maller
Kathryn Broadhouse
Mayuresh S. Korgaonkar
Stephen H. Koslow
Leanne M. Williams

BACKGROUND: Major depressive disorder (MDD) is a chronic disease with a large global impact. There are currently no clinically useful predictors of treatment outcome, and the development of biomarkers to inform clinical treatment decisions is highly desirable. METHODS: In this exploratory study we performed fixel-based analysis of diffusion MRI data from the International Study to Predict Optimized Treatment in Depression with the aim of identifying novel biomarkers at baseline that may relate to diagnosis and outcome to treatment with antidepressant medications. Analyses used MR data from individuals with MDD (n = 221) and healthy controls (n = 67). RESULTS: We show focal, gender-specific differences in the anterior limb of the internal capsule (males) and bilaterally in the genu of the corpus callosum (females) associated with diagnosis. Lower fibre cross-section in the tapetum, the conduit between the right and left hippocampi, were also associated with a decreased probability of remission. Analysis of conventional fractional anisotropy showed scattered abnormalities in the corona radiata, cerebral peduncles and mid-brain which were much lower in total volume compared to fixel-based analysis. CONCLUSIONS: Fixel-based analysis appeared to identify different underlying abnormalities than conventional tensor-based metrics, with almost no overlap between significant regions. We show that MDD is associated with gender specific abnormalities in the genu of the corpus callosum (females) and in the anterior limb of the internal capsule (males), as well as gender-independent differences in the tapetum that predict remission. Diffusion MRI may play a key role in future guidance of clinical decision-making for MDD.

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YNIMG Journal 2014 Journal Article

Thalamic volume and thalamo-cortical white matter tracts correlate with motor and verbal memory performance

David J. Philp
Mayuresh S. Korgaonkar
Stuart M. Grieve

Cognitive testing and diffusion tensor imaging data from 121 normal subjects were combined to investigate the relationship between thalamic connectivity and cognitive performance. Thalamic regions were segmented based on their cortical connectivity, and regions for both ipsilateral and contralateral thalamocortical connections were identified. White matter tracts corresponding to these regions were identified and the mean fractional anisotropy, and axial and radial diffusivities within each tract were measured. Motor task performance correlated with radial diffusivity in the dominant thalamo-precentral tract. Verbal memory corresponded with the thalamic volume connected to the left temporal lobe. These data support the use of diffusion tractography to identify functionally important regions within the thalamus. Our findings provide the first robust correlation between thalamic volumes and tract characteristics with cognitive performance data in normal subjects.

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YNICL Journal 2013 Journal Article

Widespread reductions in gray matter volume in depression

Stuart M. Grieve
Mayuresh S. Korgaonkar
Stephen H. Koslow
Evian Gordon
Leanne M. Williams

Abnormalities in functional limbic-anterior cingulate-prefrontal circuits associated with emotional reactivity, evaluation and regulation have been implicated in the pathophysiology of major depressive disorder (MDD). However, existing knowledge about structural alterations in depression is equivocal and based on cohorts of limited sample size. This study used voxel-based morphometry (VBM) and surface-based cortical thickness to investigate the structure of these circuits in a large and well-characterized patient cohort with MDD. Non-geriatric MDD outpatients (n = 102) and age- and gender-matched healthy control participants (n = 34) provided T1-weighted magnetic resonance imaging data during their baseline visit as part of the International Study to Predict Optimized Treatment for Depression. Whole-brain VBM volumetric and surface-based cortical thickness assessments were performed voxel-wise and compared (at p < 0.05 corrected for multiple comparisons) between the MDD and control groups. MDD participants had reduced gray matter volume in the anterior cingulate cortex, regions of the prefrontal circuits, including dorsolateral and dorsomedial prefrontal cortices, and lateral and medial orbitofrontal cortices, but not in limbic regions. Additional reductions were observed cortically in the posterior temporal and parieto-occipital cortices and, subcortically in the basal ganglia and cerebellum. Focal cortical thinning in the medial orbitofrontal cortex was also observed for the MDD group. These alterations in volume and cortical thickness were not associated with severity of depressive symptoms. The findings demonstrate that widespread gray matter structural abnormalities are present in a well-powered study of patients with depression. The patterns of gray matter loss correspond to the same brain functional network regions that were previously established to be abnormal in MDD, which may support an underlying structural abnormality for these circuits.

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YNIMG Journal 2011 Journal Article

Regional heterogeneity in limbic maturational changes: Evidence from integrating cortical thickness, volumetric and diffusion tensor imaging measures

Stuart M. Grieve
Mayuresh S. Korgaonkar
C. Richard Clark
Leanne M. Williams

Magnetic resonance imaging (MRI) studies of structural brain development have suggested that the limbic system is relatively preserved in comparison to other brain regions with healthy aging. The goal of this study was to systematically investigate age-related changes of the limbic system using measures of cortical thickness, volumetric and diffusion characteristics. We also investigated if the “relative preservation” concept is consistent across the individual sub-regions of the limbic system. T1 weighted structural MRI and Diffusion Tensor Imaging data from 476 healthy participants from the Brain Resource International Database was used for this study. Age-related changes in grey matter (GM)/white matter (WM) volume, cortical thickness, diffusional characteristics for the pericortical WM and for the fiber tracts associated with the limbic regions were quantified. A regional variability in the aging patterns across the limbic system was present. Four important patterns of age-related changes were highlighted for the limbic sub-regions: 1. early maturation of GM with late loss in the hippocampus and amygdala; 2. an extreme pattern of GM preservation in the entorhinal cortex; 3. a flat pattern of reduced GM loss in the anterior cingulate and the parahippocampus and; 4. accelerated GM loss in the isthmus and posterior cingulate. The GM volumetric data and cortical thickness measures proved to be internally consistent, while the diffusional measures provided complementary data that seem consistent with the GM trends identified. This heterogeneity can be hypothesized to be associated with age-related changes of cognitive function specialized for that region and direct connections to the other brain regions sub-serving these functions.

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YNIMG Journal 2010 Journal Article

COMT Val108/158Met polymorphism effects on emotional brain function and negativity bias

Leanne M. Williams
Justine M. Gatt
Stuart M. Grieve
Carol Dobson-Stone
Robert H. Paul
Evian Gordon
Peter R. Schofield

Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val108/158Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders.

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YNIMG Journal 2006 Journal Article

Progressive grey matter atrophy over the first 2–3 years of illness in first-episode schizophrenia: A tensor-based morphometry study

Thomas J. Whitford
Stuart M. Grieve
Tom F.D. Farrow
Lavier Gomes
John Brennan
Anthony W.F. Harris
Evian Gordon
Leanne M. Williams

Little is known about the structural brain changes that occur over the first few years of schizophrenia, or how these changes differ from those associated with healthy brain development in adolescence and early adulthood. In this study, we aimed to identify regional differences in grey matter (GM) volume between patients with first-episode schizophrenia (FES) and matched healthy controls, both at the time of the patients' first psychotic episode (baseline condition) and 2–3 years subsequently (follow-up condition). Forty-one patients with FES and 47 matched healthy controls underwent a T1-weighted structural MRI scan. Of these participants, 25 FES patients and 26 controls returned 2–3 years later for a follow-up scan. Voxel-based morphometry in SPM2 was used to identify the regions of GM difference between the groups in the baseline condition, while tensor-based morphometry was used to identify the longitudinal change within subject over the follow-up interval. The FES patients exhibited widespread GM reductions in the frontal, parietal, and temporal cortices and cerebellum in the baseline condition, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES subjects were observed to lose considerably more GM over the follow-up interval than the controls, especially in the parietal and temporal cortices. We argue that the progressive GM atrophy we have found to be associated with the onset of schizophrenia arises from a dysfunction in the dramatic period of healthy brain development typically associated with adolescence.

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