A5009292765- Alzheimer's disease research and treatments
- Medical Imaging Techniques and Applications
- Dementia and Cognitive Impairment Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Acute Ischemic Stroke Management
- Advanced MRI Techniques and Applications
- Parkinson's Disease Mechanisms and Treatments
- Advanced Neuroimaging Techniques and Applications
- Functional Brain Connectivity Studies
- Cerebrovascular and Carotid Artery Diseases
- Neuroscience and Neuropharmacology Research
- S100 Proteins and Annexins
- Neurological Disease Mechanisms and Treatments
- Down syndrome and intellectual disability research
- Cardiac Imaging and Diagnostics
- Traumatic Brain Injury Research
- Tryptophan and brain disorders
- Radiopharmaceutical Chemistry and Applications
- Radiomics and Machine Learning in Medical Imaging
- Advanced Radiotherapy Techniques
- Neurotransmitter Receptor Influence on Behavior
- Cardiac Arrest and Resuscitation
- Attention Deficit Hyperactivity Disorder
- Glioma Diagnosis and Treatment
University of Cambridge
2016-2025
Cambridge University Hospitals NHS Foundation Trust
2006-2024
Imaging Center
2004-2024
Addenbrooke's Hospital
2009-2022
University College London
2015-2021
Moorfields Eye Hospital NHS Foundation Trust
2021
MRC Mitochondrial Biology Unit
2021
California State University, Northridge
2020
MRC Cognition and Brain Sciences Unit
2007-2020
University of Lethbridge
2020
Background — Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication inflammation. The glucose analogue [ 18 F]-fluorodeoxyglucose ( FDG) can be used to image non-invasively by PET. In this study we tested whether FDG-PET identify inflammation carotid artery atherosclerotic plaques. Methods and Results Eight patients with symptomatic atherosclerosis were imaged using...
Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here a form of impulsivity rats predicts high rates intravenous cocaine self-administration associated with changes dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated D2/3 receptor availability significantly reduced the nucleus accumbens impulsive were never exposed such effects independent DA...
Abstract Neurotransmitter receptors support the propagation of signals in human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, there exists no comprehensive atlas receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative 19 transporters across nine different neurotransmitter systems. We found that profiles...
The study of patients with semantic dementia, a variant frontotemporal lobar degeneration, has emerged over the last two decades as an important lesion model for studying human memory. Although it is well-known that dementia associated temporal lobe controversy remains whether deficit due to diffuse damage, damage only sub-region or even less severe elsewhere in brain. manner which right and left lobes contribute knowledge also not fully elucidated. In this we used unbiased imaging analyses...
Abstract The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested involvement mesial temporal lobe, whereas in vivo metabolic shown hypometabolism posterior cingulate cortex. Using a technique that combined anatomic precision magnetic resonance imaging with positron emission tomography, we found severe reductions metabolism throughout network limbic structures (the hippocampal complex, medial thalamus,...
Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. This study tested the efficacy gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for inflammation. We confirmed 68Ga-DOTATATE binding in macrophages excised...
The ability to assess the distribution and extent of tau pathology in Alzheimer's disease progressive supranuclear palsy vivo would help develop biomarkers for these tauopathies clinical trials disease-modifying therapies. New radioligands positron emission tomography have generated considerable interest, controversy, their potential as biomarkers. We assessed radiotracer 18F-AV-1451 with imaging compare intensity 15 patients (including amyloid-positive mild cognitive impairment), 19 palsy,...
Abstract Tau pathology, neuroinflammation, and neurodegeneration are key aspects of Alzheimer’s disease. Understanding whether these features predict cognitive decline, alone or in combination, is crucial to develop new prognostic measures enhanced stratification for clinical trials. Here, we studied how baseline assessments vivo tau pathology (measured by 18F-AV-1451 PET), neuroinflammation 11C-PK11195 PET) brain atrophy (derived from structural MRI) predicted longitudinal changes patients...
Neuroinflammation is a feature of many neurodegenerative diseases, and quantified in vivo by PET imaging with radioligands for the translocator protein (TSPO, e.g. [11C]-PK11195). TSPO radioligand binding correlates clinical severity predicts progression. However, cellular substrate altered controversial requires neuropathological validation. We used progressive supranuclear palsy (PSP) as demonstrator condition, to test hypothesis that [11C]-PK11195 reflects microglial changes. included...
To use a range of techniques to explore diffusion limitation as mechanism cellular hypoxia in the setting head injury.A prospective interventional study.A specialist neurocritical care unit.Thirteen patients within 7 days closed injury underwent imaging studies. Tissue for ultrastructural studies was obtained from cohort seven who required surgery.Cerebral tissue PO2 (PtO2) using multiple-variable sensor, and images oxygen extraction fraction (OEF), derived positron emission tomography, were...
Objective To investigate the effect of hyperventilation on cerebral blood flow in traumatic brain injury. Design A prospective interventional study. Setting specialist neurocritical care unit. Patients Fourteen healthy volunteers and 33 patients within 7 days closed head Interventions All subjects underwent positron emission tomography imaging flow. In patients, Paco2 was reduced from 36 ± 1 to 29 torr (4.8 0.1 3.9 kPa) measurements repeated. Jugular venous saturation (Sjvo2) arteriovenous...
Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours map cerebral blood flow (CBF), oxygen metabolism (CMRO2), and extraction fraction (OEF). We estimated the volume ischemic brain (IBV) used standard deviation OEF distribution estimate efficiency coupling between CMRO2. The IBV was significantly higher...
Objective: To determine whether hyperventilation exacerbates cerebral ischemia and compromises oxygen metabolism (CMRO2) following closed head injury. Design: A prospective interventional study. Setting: specialist neurocritical care unit. Patients: Ten healthy volunteers 30 patients within 10 days of Interventions: Subjects underwent oxygen-15 positron emission tomography imaging blood flow, volume, CMRO2, extraction fraction. In patients, studies, somatosensory evoked potentials, jugular...
Background and Purpose— Carotid endarterectomy is currently guided by angiographic appearance on the assumption that most stenotic lesion visible at angiography likely to be from which future embolic events will arise. However, risk of plaque rupture, common cause atherosclerosis-related thromboembolism, dictated composition plaque, in particular degree inflammation. Angiography may, therefore, an unreliable method identifying vulnerable plaques. In this study, inflammation was quantified...
Semantic dementia, in which there is progressive deterioration of semantic knowledge, associated with focal, typically asymmetric, temporal lobe degeneration. The ventrorostral most severely affected and concordance between atrophy reduced metabolic activity. In this study, we confirmed the veracity claim using 18F-fluorodeoxyglucose positron emission tomography anatomical magnetic resonance images. principal aim, however, was to understand impact on neuronal projections from cortex lesion...
Previous group studies using positron emission tomography to assess resting cerebral glucose metabolism in very early Alzheimer's disease and mild cognitive impairment have identified the posterior cingulate adjacent cingulo-parietal cortex as first isocortical area develop hypometabolism. We studied profile of individuals with whether more specific stereotyped regional hypometabolism would be evident across subjects. The study found that most consistently hypometabolic region between...
Objective: In this study we have used 15O positron emission tomography, brain tissue oxygen monitoring, and cerebral microdialysis to assess the effects of perfusion pressure augmentation on regional physiology metabolism in setting traumatic injury. Design: Prospective interventional study. Setting: Neurosciences critical care unit a university hospital. Patients: Eleven acutely head-injured patients requiring norepinephrine maintain pressure. Interventions: Using quantified response an...
Background and Purpose— Perfusion magnetic resonance imaging (pMR) is increasingly used in acute stroke, but its physiologic significance still debated. A reasonably good correlation between pMR positron emission tomography (PET) has been reported normal subjects chronic cerebrovascular disease, corresponding validation stroke lacking. Methods— We compared the cerebral blood flow (CBF), volume, mean transit time (MTT) maps generated by (deconvolution method) PET ( 15 O steady-state 5...
Background and Purpose— Microglial activation is an important component of the neuroinflammatory response to ischemic stroke. Experimental studies have outlined such patterns temporally spatially. In vivo in stroke patients relied on positron emission tomography (R)-PK11195, a ligand that binds peripheral benzodiazepine binding sites. this study we sought establish temporal spatial microglial with particular emphasis defined peri-infarct zone. Methods— Using technique, studied carotid...
Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about pathogenesis.Forty-nine adults aged 25-65 underwent positron emission tomography Pittsburgh compound-B (PIB). Regional PIB binding was assessed respect to age, clinical, and cognitive status.Abnormal became evident from 39 years, first striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal,...
<h3>Background</h3> It is unknown whether lesions in human TB are hypoxic or this influences disease pathology. Human characterised by extensive lung destruction driven host matrix metalloproteinases (MMPs), particularly collagenases such as metalloproteinase-1 (MMP-1). <h3>Methods</h3> We investigated tissue hypoxia five patients with PET imaging using the tracer [<sup>18</sup>F]-fluoromisonidazole ([<sup>18</sup>F]FMISO) and immunohistochemistry. studied regulation of MMP secretion primary...
To determine the effect of normobaric hyperoxia on cerebral metabolism in patients with severe traumatic brain injury.Prospective clinical investigation.Neurosciences critical care unit a university hospital.Eleven injury.Cerebral microdialysis, tissue oximetry (PbO2), and oxygen-15 positron emission tomography (15O-PET) were undertaken at normoxia repeated (FiO2 increase between 0.35 0.50).Established models used to image blood flow, volume, oxygen metabolism, extraction fraction....
To image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings tritium-labeled PiB ([3H]PiB) autoradiography immunocytochemistry autopsy-acquired tissue.In vivo PET at tertiary neuroscience referral center ex of tissue from a neuropathology archive. [11C]PiB was used 11 controls (median [range] age, 35 [24-60] years) 15 33 [21-50] between 1 361 days after TBI....