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Brain, United Kingdom

Bird J.L.E.,Clinical Pharmacology Unit | Bird J.L.E.,Wolfson Brain Imaging Center | Izquierdo-Garcia D.,Wolfson Brain Imaging Center | Davies J.R.,Addenbrookes Hospital | And 7 more authors.

Macrophage presence within atherosclerotic plaque is a feature of instability and a risk factor for plaque rupture and clinical events. Activated macrophages express high levels of the translocator protein/peripheral benzodiazepine receptor (TSPO/PBR). In this study, we investigated the potential for quantifying plaque inflammation by targeting this receptor. TSPO expression and distribution in the plaque were quantified using radioligand binding assays and autoradiography. We show that cultured human macrophages expressed 20 times more TSPO than cultured human vascular smooth muscle cells (VSMCs), the other abundant cell type in plaque. The TSPO ligands [ 3H](R)-1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([ 3H](R)-PK11195) and [ 3H]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([ 3H]-DAA1106) bound to the same sites in human carotid atherosclerotic plaques in vitro, and demonstrated significant correlation with macrophage-rich regions. In conclusion, our data indicate that radioisotope-labelled DAA1106 has the potential to quantify the macrophage content of atherosclerotic plaque. © 2009 Elsevier Ireland Ltd. Source

Mak E.,University of Cambridge | Su L.,University of Cambridge | Williams G.B.,Wolfson Brain Imaging Center | O'Brien J.T.,University of Cambridge
Alzheimer's Research and Therapy

This review summarises the findings and applications from neuroimaging studies in dementia with Lewy bodies (DLB), highlighting key differences between DLB and other subtypes of dementia. We also discuss the increasingly important role of imaging biomarkers in differential diagnosis and outline promising areas for future research in DLB. DLB shares common clinical, neuropsychological and pathological features with Parkinson's disease dementia and other dementia subtypes, such as Alzheimer's disease. Despite the development of consensus diagnostic criteria, the sensitivity for differential diagnosis of DLB in clinical practice remains low and many DLB patients will be misdiagnosed. The importance of developing accurate imaging markers in dementia is highlighted by the potential for treatments targeting specific molecular abnormalities as well as the responsiveness to cholinesterase inhibitors and marked neuroleptic sensitivity of DLB. We review various brain imaging techniques that have been applied to investigate DLB, including the characteristic nigrostriatal degeneration in DLB using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. Dopamine transporter loss has proven to reliably differentiate DLB from other dementias and has been incorporated into the revised clinical diagnostic criteria for DLB. To date, this remains the 'gold standard' for diagnostic imaging of DLB. Regional cerebral blood flow, 18 F-fluorodeoxygluclose-PET and SPECT have also identified marked deficits in the occipital regions with relative sparing of the medial temporal lobe when compared to Alzheimer's disease. In addition, structural, diffusion, and functional magnetic resonance imaging techniques have shown alterations in structure, white matter integrity, and functional activity in DLB. We argue that the multimodal identification of DLB-specific biomarkers has the potential to improve ante-mortem diagnosis and contribute to our understanding of the pathological background of DLB and its progression. © 2014 Mak et al.; licensee BioMed Central Ltd. Source

Hart M.G.,Addenbrookes Hospital | Trivedi R.A.,Addenbrookes Hospital | Hutchinson P.J.,Addenbrookes Hospital | Hutchinson P.J.,Wolfson Brain Imaging Center
British Journal of Neurosurgery

A professional boxer developed an acute subdural haematoma after boxing sparring. Despite timely surgical decompression, he had a poor overall outcome predominantly from a delayed brainstem haematoma. Magnetic resonance imaging (MRI) was used to elucidate the pathophysiology of the patients' injury and clinical condition. © 2012 The Neurosurgical Foundation. Source

Kasahara M.,University of Cambridge | Menon D.K.,University of Cambridge | Salmond C.H.,University of Cambridge | Outtrim J.G.,University of Cambridge | And 6 more authors.
Brain Injury

Primary objective: Investigation of the impact of traumatic brain injury (TBI) on the functional brain network that mediates working memory function. Research design: Functional magnetic resonance imaging (fMRI) during an n-back working memory task in nine chronic-stage patients with TBI and nine age-matched healthy controls. In addition to classical analyses investigating regional activity, the authors examined functional connectivity of the brain regions critical to working memory performance using psychophysiological interaction (PPI) analyses. Main outcomes and results: Patients with TBI made a greater percentage of errors than controls at high working memory load conditions. The fMRI data showed that the activation of the left inferior parietal gyrus (LIPG) was significantly reduced, whereas the activation of the right inferior frontal gyrus (RIFG) was significantly increased in patients compared with controls. Task performance accuracy was significantly associated with the activation of the LIPG in controls and the activation of the RIFG in patients. PPI analyses on fMRI data further suggested that the functional connectivity between the RIFG and LIPG was compromised in patients. Conclusion: The abnormal functional connectivity between LIPG and RIFG may underlie the observed working memory deficits and abnormal brain activation pattern in patients. © 2011 Informa UK Ltd All rights reserved. Source

Mak E.,University of Cambridge | Su L.,University of Cambridge | Williams G.B.,Wolfson Brain Imaging Center | Watson R.,Royal Melbourne Hospital | And 4 more authors.
NeuroImage: Clinical

Background & objective Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures. Methods 72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures. Results AD had significantly greater atrophy over 1 year (1.8%) compared to DLB (1.0%; p = 0.01) and HC (0.9%; p < 0.01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0.95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0.49, p < 0.01). Conclusions AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited. © 2015 Published by Elsevier Ltd. Source

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