599 results found
He S, Yong M, Matthews PM, et al., 2016, tranSMART-XNAT Connector tranSMART-XNAT connector-image selection based on clinical phenotypes and genetic profiles., Bioinformatics, Vol: 33, Pages: 787-788, ISSN: 1367-4803
MOTIVATION: TranSMART has a wide range of functionalities for translational research and a large user community, but it does not support imaging data. In this context, imaging data typically includes 2D or 3D sets of magnitude data and metadata information. Imaging data may summarise complex feature descriptions in a less biased fashion than user defined plain texts and numeric numbers. Imaging data also is contextualised by other data sets and may be analysed jointly with other data that can explain features or their variation. RESULTS: Here we describe the tranSMART-XNAT Connector we have developed. This connector consists of components for data capture, organisation and analysis. Data capture is responsible for imaging capture either from PACS system or directly from an MRI scanner, or from raw data files. Data are organised in a similar fashion as tranSMART and are stored in a format that allows direct analysis within tranSMART. The connector enables selection and download of DICOM images and associated resources using subjects' clinical phenotypic and genotypic criteria. AVAILABILITY AND IMPLEMENTATION: tranSMART-XNAT connector is written in Java/Groovy/Grails. It is maintained and available for download at https://github.com/sh107/transmart-xnat-connector.git
Datta G, Violante IR, Scott G, et al., 2016, Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis., Multiple Sclerosis, Vol: 23, Pages: 1469-1478, ISSN: 1352-4585
BACKGROUND: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. OBJECTIVE: To explore the in vivo relationships between MRS and PET [(11)C]PBR28 in MS over a range of brain inflammatory burden. METHODS: A total of 23 patients were studied. TSPO PET imaging with [(11)C]PBR28, single voxel MRS and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC). RESULTS: [(11)C]PBR28 uptake and [ myo-inositol] were not associated. When the whole cohort was stratified by higher [(11)C]PBR28 inflammatory burden, [ myo-inositol] was positively correlated to [(11)C]PBR28 uptake (Spearman's ρ = 0.685, p = 0.014). Moderate correlations were found between [(11)C]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between other imaging or clinical measures. CONCLUSION: MRS [ myo-inositol] and PET [(11)C]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [(11)C]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.
Dichgans M, Wardlaw J, Smith E, et al., 2016, METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research, Alzheimers & Dementia, Vol: 12, Pages: 1235-1249, ISSN: 1552-5260
Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.
Newbould R, Muraro P, Bishop C, et al., 2016, Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions, NeuroImage-Clinical, Vol: 13, Pages: 9-15, ISSN: 2213-1582
Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between “younger” and “older” onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses.21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls (n = 31, 31.9 ± 3.5 years and n = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors.Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group (p < 0.001) and a strong trend in the older-onset group.These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.
Dong H, Matthews P, Guo Y, 2016, A new soft material based in-the-ear EEG recording technique, The 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’16), Publisher: IEEE
Long-term electroencephalogram (EEG) is important for seizure detection, sleep monitoring and etc. In-the- ear EEG device makes such recording robust to noise and privacy protected (invisible to other people). However, the state-of-art techniques suffer from various drawbacks such as customization for specific users, manufacturing difficulties and short life cycle. To address these issues, we proposed silvered glass silicone based in-the-ear electrode which can be manufactured using conventional compression moulding. The material and in-the-ear EEG are evaluated separately, showing that the proposed method is durable, low-cost and easy-to-make.
Russo E, Khan S, Janisch R, et al., 2016, Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn's Disease., Inflammatory Bowel Diseases, ISSN: 1536-4844
Background: 18Fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has recently attracted interest for the measurement ofdisease activity in Crohn’s disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activityand its response to treatment in patients with CD.Methods: Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used toassess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity(Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component andunderwent scanning before and 12 weeks after the initiation of anti–tumor necrosis factor alpha therapy. Patients were subcategorized on the basis ofa clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took partin the test–retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures.Results: The sensitivity and specificity of 18F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measurescorrelated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEANdemonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt .0.80 and % variability ,20%) compared with volumedependentFDG-PET measures. A proportion of the FDG signal (10%–30%) was found to originate from the lumen of diseased segments.Conclusions: 18F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD.
Paley C, Hull H, Ji Y, et al., 2016, Body fat differences by self-reported race/ethnicity in healthy term newborns., Pediatr Obes, Vol: 11, Pages: 361-368
BACKGROUND: Ethnic differences in total body fat (fat mass [FM]) have been reported in adults and children, but the timing of when these differences manifest and whether they are present at birth are unknown. OBJECTIVES: This study aimed to assess whether ethnic differences in body fat are present at birth in healthy infants born at term, where body fat is measured using air displacement plethysmography and fat distribution by skin-fold thickness. METHODS: Data were from a multiracial cross-sectional convenience sample of 332 term infants from four racial or ethnic groups based on maternal self-report (A, Asian; AA, non-Hispanic Black [African-American]; C, non-Hispanic White; and H, Hispanic). The main outcome measure was infant body fat at 1-3 days after birth, with age, birth weight, gestational age and maternal pre-pregnancy weight as covariates. RESULTS: Significant effects for race (P = 0.0011), sex (P = 0.0051) and a race by sex interaction (P = 0.0236) were found. C females had higher FM than C males (P = 0.0001), and AA females had higher FM than AA males (P = 0.0205). C males had less FM than A males (P = 0.0353) and H males (P = 0.0001). CONCLUSION: Race/ethnic and sex differences in FM are present in healthy term newborns. Although the implications of these differences are unclear, studies beginning in utero and birth set the stage for a life course approach to understanding disease later in life.
Ricotti V, Evans MR, Sinclair CD, et al., 2016, Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials., PLOS One, Vol: 11, ISSN: 1932-6203
OBJECTIVE: A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. METHODS: 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. RESULTS: Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001). A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7), accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9) and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8). CONCLUSIONS: These results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and func
Miller KL, Alfaro-Almagro F, Bangerter NK, et al., 2016, Multimodal population brain imaging in the UK Biobank prospective epidemiological study, Nature Neuroscience, Vol: 19, Pages: 1523-1536, ISSN: 1546-1726
Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, with health outcomes being tracked over the coming decades. The brain imaging includes structural, diffusion and functional modalities. Along with body and cardiac imaging, genetics, lifestyle measures, biological phenotyping and health records, this imaging is expected to enable discovery of imaging markers of a broad range of diseases at their earliest stages, as well as provide unique insight into disease mechanisms. We describe UK Biobank brain imaging and present results derived from the first 5,000 participants' data release. Although this covers just 5% of the ultimate cohort, it has already yielded a rich range of associations between brain imaging and other measures collected by UK Biobank.
James A, Joyce E, Lunn D, et al., 2016, Corrigendum to “Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning” [Eur. Psychiatry 35C (2016) 32–38], European Psychiatry, Vol: 38, Pages: 22-22, ISSN: 1778-3585
Gafson AR, Nicholas R, Giovannoni G, et al., 2016, Plasma cytokine concentration changes in multiple sclerosis patients after treatment with dimethyl fumarate, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 670-671, ISSN: 1352-4585
Matthews PM, 2016, Pharmacological applications of fMRI, Neuromethods, Pages: 817-831
© Springer Science+Business Media New York 2016. Increasing societal expectations for new drugs, lack of confidence in short-term endpoints related to long- term outcomes for chronic neurological and psychiatric diseases and rising costs of development in an increasing cost-constrained market all have created a sense of crisis in CNS drug development. New approaches are needed. For some time, the potential of clinical functional imaging for more confident progression from preclinical to clinical development stages has been recognized. Pharmacological functional MRI (fMRI), which refers specifically to applications of fMRI to questions in drug development, provides one set of these tools. With related structural MRI measures, relatively high resolution data concerning target, disease-relevant pathophysiology and effects of therapeutic interventions can be related to brain functional anatomy. In this chapter, current and potential applications of pharmacological fMRI for target validation, patient stratification and characterization of therapeutic molecule pharmacokinetics and pharmacodynamics are reviewed. Challenges to better realizing the promise of pharmacological fMRI will be discussed. The review concludes that there is a strong rationale for greater use of pharmacological fMRI particularly for early phase studies, but also outlines the need for preclinical and early clinical development to be more seamlessly integrated, for greater harmonization of clinical imaging methodologies and for sharing of data to facilitate these goals.
Datta G, Colasanti A, Kalk NJ, et al., 2016, In vivo translocator protein positron emission tomography imaging detects a heterogeneity of lesion inflammatory activity in multiple sclerosis not evident by MRI., 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 36-37, ISSN: 1352-4585
Lema A, Bishop C, Malik O, et al., 2016, A compararison of magnetization transfer methods to assess brain and cervical cord microstructure in multiple sclerosis, Journal of Neuroimaging, Vol: 27, Pages: 221-226, ISSN: 1552-6569
BACKGROUND: Demyelination is a core pathological feature of multiple sclerosis (MS) and spontaneous remyelination appears to be an important mechanism for repair in the disease. Magnetization transfer ratio imaging (MTR) has been used extensively to evaluate demyelination, although limitations to its specificity are recognized. MT saturation imaging (MTsat) removes some of the T1 dependence of MTR. We have performed a comparative evaluation of MTR and MTsat imaging in a mixed group of subjects with active MS, to explore their relative sensitivity to pathology relevant to explaining clinical outcomes. METHODS: A total of 134 subjects underwent MRI of their brain and cervical spinal cord. Isotropic 3-dimensional pre- and postcontrast T1-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) volumes were segmented into brain normal appearing white matter (NAWM), brain WM lesions (WML), normal appearing spinal cord (NASC), and spinal cord lesions. Volumes and metrics for MTR and MTsat histograms were calculated for each region. RESULTS: Significant Spearman correlations were found with the Expanded Disability Status Scale and timed 25-foot walk for the whole brain and WML MTR, but not in that from the NAWM or any cervical spinal cord region. By contrast, the MTsat was correlated with both disability metrics in all these regions in both the brain and spine. CONCLUSIONS: This study extends prior work relating atrophy and lesion load with disability, by characterization of MTsat parameters. MTsat is practical in routine clinical applications and may be more sensitive to tissue damage than MTR for both brain and cervical spinal cord.
Matthews PM, Hampshire A, 2016, Clinical concepts emerging from fMRI functional connectomics, Neuron, Vol: 91, Pages: 511-528, ISSN: 0896-6273
Recent advances in connectomics have led to a synthesis of perspectives regarding the brain's functional organization that reconciles classical concepts of localized specialization with an appreciation for properties that emerge from interactions across distributed functional networks. This provides a more comprehensive framework for understanding neural mechanisms of normal cognition and disease. Although fMRI has not become a routine clinical tool, research has already had important influences on clinical concepts guiding diagnosis and patient management. Here we review illustrative examples. Studies demonstrating the network plasticity possible in adults and the global consequences of even focal brain injuries or disease both have had substantial impact on modern concepts of disease evolution and expression. Applications of functional connectomics in studies of clinical populations are challenging traditional disease classifications and helping to clarify biological relationships between clinical syndromes (and thus also ways of extending indications for, or "re-purposing," current treatments). Large datasets from prospective, longitudinal studies promise to enable the discovery and validation of functional connectomic biomarkers with the potential to identify people at high risk of disease before clinical onset, at a time when treatments may be most effective. Studies of pain and consciousness have catalyzed reconsiderations of approaches to clinical management, but also have stimulated debate about the clinical meaningfulness of differences in internal perceptual or cognitive states inferred from functional connectomics or other physiological correlates. By way of a closing summary, we offer a personal view of immediate challenges and potential opportunities for clinically relevant applications of fMRI-based functional connectomics.
Poldrack RA, Baker CI, Durnez J, et al., 2016, Scanning the Horizon: Towards transparent and reproducible neuroimaging research, Publisher: Cold Spring Harbor Laboratory
<jats:title>Abstract</jats:title><jats:p>Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors, and lack of direct replication apply to many fields, but perhaps particularly to fMRI. Here we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful answers to neuroscientific questions.</jats:p>
Maron E, Near J, Wallis G, et al., 2016, A pilot study of the effect of short-term escitalopram treatment on brain metabolites and gamma-oscillations in healthy subjects, Journal of Psychopharmacology, Vol: 30, Pages: 579-580, ISSN: 1461-7285
Nie L, Matthews PM, Guo Y, 2016, Inferring individual-level variations in the functional parcellation of the cerebral cortex, IEEE Transactions on Biomedical Engineering, Vol: 63, Pages: 2505-2517, ISSN: 0018-9294
Objective: Functional parcellation of the cerebral cortex is variable across different subjects or between cognitive states. Ignoring individual - or state - dependent variations in the functional parcellation may lead to inaccurate representations of individual functional connectivity, limiting the precision of interpretations of differences in individual connectivity profiles. However, it is difficult to infer the individual-level variations due to the relatively low robustness of methods for parcellation of individual subjects. Methods: We propose a method called “joint K-means” to robustly parcellate the cerebral cortex using fMRI data for contrasts between two states or subjects that intended to characterize variance in individual functional parcellations. The key idea of the proposed method is to jointly infer parcellations in contrasted datasets by iterative descent, while constraining the similarity of the two pathways in searches for local minima to reduce spurious variations. Results: Parcellations of resting-state fMRI datasets from the Human Connectome Project show that the similarity of parcellations for an individual subject studied on two sessions is greater than that between different subjects. Differences in parcellations between subjects are non-uniformly distributed across the cerebral cortex, with clusters of higher variance in the prefrontal, lateral temporal and occipito-parietal cortices. This pattern is reproducible across sessions, between groups and using different numbers of parcels. Conclusion: The individual-level variations inferred by the proposed method are plausible and consistent with the previously reported functional connectivity variability. Significance: The proposed method is a promising tool for investigating relationships between the cerebral functional organization and behavioral differences.
Scott G, Gunn RN, Matthews PM, et al., 2016, Minocycline reduces microglial activation after traumatic brain injury measured using [11C]-PBR28 positron emission tomography, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 686-687, ISSN: 1362-301X
Lovestone S, Rossor M, Gallacher J, et al., 2016, Better together for better dementia research and care, Lancet Psychiatry, Vol: 3, Pages: 503-504, ISSN: 2215-0374
De Guio F, Jouvent E, Biessels GJ, et al., 2016, Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease., Journal of Cerebral Blood Flow & Metabolism, Vol: 36, Pages: 1319-1337, ISSN: 0271-678X
Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.
Tiwari AD, Wu C, Zhu J, et al., 2016, Design, Synthesis, and Evaluation of Fluorinated Radioligands for Myelin Imaging, Journal of Medicinal Chemistry, Vol: 59, Pages: 3705-3718, ISSN: 0022-2623
James A, Joyce E, Lunn D, et al., 2016, Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning, European Psychiatry, Vol: 35, Pages: 32-38, ISSN: 1778-3585
Matthews PM, Roncaroli F, Waldman A, et al., 2016, A practical review of the neuropathology and neuroimaging of multiple sclerosis, Practical Neurology, Vol: 16, Pages: 279-287, ISSN: 1474-7766
The variability in the severity and clinical course of multiple sclerosis (MS) has as its basis an extreme heterogeneity in the location, nature and extent of pathology in the brain and spinal cord. Understanding the underlying neuropathology and associated pathogenetic mechanisms of the disease helps to communicate the rationale for treatment and disease monitoring to patients. Neuroimaging is an important tool for this: it allows clinicians to relate neuropathological changes to clinical presentations and to monitor the course of their disease. Here, we review MS neuropathology and its imaging correlates to provide a practical guide for using MRI to assess disease severity and treatment responses. This provides a foundation for optimal management of patients based on the principle that they show 'no evidence of disease activity'.
Khamis RY, Woollard KJ, Hyde GD, et al., 2016, Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis, Scientific Reports, Vol: 6, ISSN: 2045-2322
We aimed to develop a quantitative antibody-based near infrared fluorescence (NIRF) approachfor the imaging of oxidized LDL in atherosclerosis. LO1, a well- characterized monoclonalautoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye toyield LO1-750. LO1-750 specifically identified necrotic core in ex vivo human coronary lesions.Injection of LO1-750 into high fat (HF) fed atherosclerotic Ldlr-/-mice led to specific focallocalization within the aortic arch and its branches, as detected by fluorescence moleculartomography (FMT) combined with micro-computed tomography (CT). Ex vivo confocalmicroscopy confirmed LO1-750 subendothelial localization of LO1-750 at sites ofatherosclerosis, in the vicinity of macrophages. When compared with a NIRF reporter of MMPactivity (MMPSense-645-FAST), both probes produced statistically significant increases inNIRF signal in the Ldlr-/- model in relation to duration of HF diet. When withdrawing the HFdiet, the reduction in oxLDL accumulation, as demonstrated with LO1-750, was less markedthan the effect seen on MMP activity. In the rabbit, in vivo injected LO1-750 localization wassuccessfully imaged ex vivo in aortic lesions with a customised intra-arterial NIRF detectioncatheter. A partially humanized chimeric LO1-Fab-Cys localized similarly to the parentantibody in murine atheroma showing promise for future translation.
Vera JH, Guo Q, Cole JH, et al., 2016, Neuroinflammation in treated HIV-positive individuals: A TSPO PET study., Neurology, Vol: 86, Pages: 1425-1432, ISSN: 1526-632X
OBJECTIVE: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). METHODS: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [(11)C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. RESULTS: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). CONCLUSIONS: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.
Scott GPT, Ramlackhansingh A, Edison P, et al., 2016, Amyloid pathology and axonal injury after brain trauma, Neurology, Vol: 86, Pages: 821-828, ISSN: 0028-3878
Objective: To image amyloid-β (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer’s disease.Methods: Patients 11 months to 17 years after moderate-severe TBI had 11C-Pittsburgh compound-B (PIB) PET, structural and diffusion MRI and neuropsychological examination. Healthy aged controls and AD patients had PET and structural MRI. Binding potential (BPND) images of 11C-PIB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy (FA), was estimated and correlated with 11C-PIB BPND.Results: 28 participants (9 TBI, 9 controls, 10 AD) were assessed. Increased 11C-PIB BPND was found in TBI versus controls in the posterior cingulate cortex (PCC) and cerebellum. Binding in the PCC increased with decreasing FA of associated white matter tracts, and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions, but increased in the cerebellum. Conclusions: Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathological features of dementia, which may relate to axonal damage produced by the injury.
Petersen SE, Matthews PM, Francis JM, et al., 2016, UK Biobank's cardiovascular magnetic resonance protocol., Journal of Cardiovascular Magnetic Resonance, Vol: 18, ISSN: 1532-429X
BACKGROUND: UK Biobank's ambitious aim is to perform cardiovascular magnetic resonance (CMR) in 100,000 people previously recruited into this prospective cohort study of half a million 40-69 year-olds. METHODS/DESIGN: We describe the CMR protocol applied in UK Biobank's pilot phase, which will be extended into the main phase with three centres using the same equipment and protocols. The CMR protocol includes white blood CMR (sagittal anatomy, coronary and transverse anatomy), cine CMR (long axis cines, short axis cines of the ventricles, coronal LVOT cine), strain CMR (tagging), flow CMR (aortic valve flow) and parametric CMR (native T1 map). DISCUSSION: This report will serve as a reference to researchers intending to use the UK Biobank resource or to replicate the UK Biobank cardiovascular magnetic resonance protocol in different settings.
Miller KL, Bangerter N, Almagro FA, et al., UK Biobank: Brain imaging protocols and first data release, ISMRM 24th Annual Meeting
Maron E, Wall M, Norbury R, et al., 2015, Effect of short-term escitalopram treatment on neural activation during emotional processing, Journal of Psychopharmacology, Vol: 30, Pages: 33-39, ISSN: 1461-7285
Recent functional magnetic resonance (fMRI) imaging studies have revealed that subchronic medication with escitalopram leads to significantreduction in both amygdala and medial frontal gyrus reactivity during processing of emotional faces, suggesting that escitalopram may have adistinguishable modulatory effect on neural activation as compared with other serotonin-selective antidepressants. In this fMRI study we aimed toexplore whether short-term medication with escitalopram in healthy volunteers is associated with reduced neural response to emotional processing,and whether this effect is predicted by drug plasma concentration. The neural response to fearful and happy faces was measured before and on day7 of treatment with escitalopram (10mg) in 15 healthy volunteers and compared with those in a control unmedicated group (n=14). Significantlyreduced activation to fearful, but not to happy facial expressions was observed in the bilateral amygdala, cingulate and right medial frontal gyrusfollowing escitalopram medication. This effect was not correlated with plasma drug concentration. In accordance with previous data, we showed thatescitalopram exerts its rapid direct effect on emotional processing via attenuation of neural activation in pathways involving medial frontal gyrus andamygdala, an effect that seems to be distinguishable from that of other SSRIs.
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