154 results found
Cooper N, Morrison MA, Vladescu C, et al., 2020, Identification of occult cerebral microbleeds in adults with immune thrombocytopenia, Blood, Vol: 136, Pages: 2875-2880, ISSN: 0006-4971
Management of symptoms and prevention of life-threatening hemorrhage in immune thrombocytopenia (ITP) must be balanced against adverse effects of therapies. Because current treatment guidelines based on platelet count are confounded by variable bleeding phenotypes, there is a need to identify new objective markers of disease severity for treatment stratification. In this cross-sectional prospective study of 49 patients with ITP and nadir platelet counts <30 × 109/L and 18 aged-matched healthy controls, we used susceptibility-weighted magnetic resonance imaging to detect cerebral microbleeds (CMBs) as a marker of occult hemorrhage. CMBs were detected using a semiautomated method and correlated with clinical metadata using multivariate regression analysis. No CMBs were detected in health controls. In contrast, lobar CMBs were identified in 43% (21 of 49) of patients with ITP; prevalence increased with decreasing nadir platelet count (0/4, ≥15 × 109/L; 2/9, 10-14 × 109/L; 4/11, 5-9 × 109/L; 15/25 <5 × 109/L) and was associated with longer disease duration (P = 7 × 10−6), lower nadir platelet count (P = .005), lower platelet count at time of neuroimaging (P = .029), and higher organ bleeding scores (P = .028). Mucosal and skin bleeding scores, number of previous treatments, age, and sex were not associated with CMBs. Occult cerebral microhemorrhage is common in patients with moderate to severe ITP. Strong associations with ITP duration may reflect CMB accrual over time or more refractory disease. Further longitudinal studies in children and adults will allow greater understanding of the natural history and clinical and prognostic significance of CMBs.
Orban C, McGonigle J, Flechais RSA, et al., 2020, Chronic alcohol exposure differentially modulates structural and functional properties of amygdala: A cross-sectional study, ADDICTION BIOLOGY, Vol: 26, ISSN: 1355-6215
Turton S, Myers J, Mick I, et al., 2020, Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol dependent individuals, Molecular Psychiatry, Vol: 25, Pages: 1749-1758, ISSN: 1359-4184
Addiction has been proposed as a ‘reward deficient’ state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.
Rachmadi MF, Valdes-Hernandez MDC, Li H, et al., 2020, Limited One-time Sampling Irregularity Map (LOTS-IM) for Automatic Unsupervised Assessment of White Matter Hyperintensities and Multiple Sclerosis Lesions in Structural Brain Magnetic Resonance Images, COMPUTERIZED MEDICAL IMAGING AND GRAPHICS, Vol: 79, ISSN: 0895-6111
McKeever A, Paris AF, Cullen J, et al., 2020, Hippocampal Subfield Volumes in Middle-Aged Adults at Risk of Dementia, JOURNAL OF ALZHEIMERS DISEASE, Vol: 75, Pages: 1211-1218, ISSN: 1387-2877
Grech-Sollars M, Ordidge KL, Vaqas B, et al., 2019, Imaging and tissue biomarkers of choline metabolism in diffuse adult glioma; 18F-fluoromethylcholine PET/CT, magnetic resonance spectroscopy, and choline kinase α, Cancers, Vol: 11, Pages: 1-15, ISSN: 2072-6694
The cellular and molecular basis of choline uptake on PET imaging and MRS-visible choline containing compounds is not well understood. Choline kinase alpha (ChoKa) is an enzyme that phosphorylates choline, an essential step in membrane synthesis. We investigate choline metabolism through 18F-fluoromethylcholine (18F-FMC) PET, MRS and tissue ChoKa in human glioma. 14 patients with suspected diffuse glioma underwent multimodal 3T MRI and dynamic 18FFMC PET/CT prior to surgery. Co-registered PET and MRI data were used to target biopsies to regions of high and low choline signal, and immunohistochemistry for ChoKa expression was performed. 18F-FMC/PET differentiated WHO grade IV from grade II and III tumours, whereas MRS differentiated grade III/IV from grade II tumours. Tumoural 18F-FMC/PET uptake was higher than in normal-appearing white matter across all grades and markedly elevated within regions of contrast enhancement. 18F-FMC/PET correlated weakly with MRS Cho ratios. ChoKa expression on IHC was negative or weak in all but one GBM sample, and did not correlate with tumour grade or imaging choline markers. MRS and 18F-FMC/PET provide complimentary information on glioma choline metabolism. Tracer uptake is, however, potentially confounded by blood-brain barrier permeability. ChoKa overexpression does not appear to be a common feature in diffuse glioma.
Inglese M, Katherine L O, Lesley H, et al., 2019, Reliability of dynamic contrast enhanced magnetic resonance imaging data in primary brain tumours: a comparison of Tofts and shutter speed models, Neuroradiology, Vol: 61, Pages: 1375-1386, ISSN: 0028-3940
PurposeTo investigate the robustness of pharmacokinetic modelling of DCE-MRI brain tumourdata and to ascertain reliable perfusion parameters through a model selection processand a stability test.MethodsDCE-MRI data of 14 patients with primary brain tumours were analysed using the Toftsmodel (TM), the extended Tofts model (ETM), the shutter speed model (SSM) and theextended shutter speed model (ESSM). A no-effect model (NEM) was implemented toassess overfitting of data by the other models.For each lesion, the Akaike Information Criteria (AIC) was used to build a 3D modelselection map. The variability of each pharmacokinetic parameter extracted from thismap was assessed with a noise propagation procedure, resulting in voxel-wisedistributions of the coefficient of variation (CV).ResultsThe model selection map over all patients showed NEM had the best fit in 35.5% ofvoxels, followed by ETM (32%), TM (28.2%), SSM (4.3%) and ESSM (<0.1%). Inanalysing the reliability of Ktrans, when considering regions with a CV<20%, ≈25% ofvoxels were found to be stable across all patients. The remaining 75% of voxels wereconsidered unreliable.ConclusionsThe majority of studies quantifying DCE-MRI data in brain tumours only consider asingle model and whole-tumour statistics for the output parameters. Appropriate modelselection, considering tissue biology and its effects on blood brain barrier permeabilityand exchange conditions, together with an analysis on the reliability and stability of thecalculated parameters, is critical in processing robust brain tumour DCE-MRI data.
Islam S, Morrison M, Waldman A, 2019, TO ASSESS THE UTILITY OF ADVANCED QUANTITATIVE DIFFUSION MRI DERIVED FROM MULTI B VALUE ACQUISITIONS IN THE ASSESSMENT OF TREATMENT RESPONSE, USING A SPATIALLY-INDEPENDENT APPROACH, 24th Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology (SNO) / 3rd SNO-SCIDOT Joint Conference on Therapeutic Delivery to the CNS, Publisher: OXFORD UNIV PRESS INC, Pages: 173-173, ISSN: 1522-8517
Inglese M, Honeyfield L, Aboagye E, et al., 2019, RELIABILITY OF DCE MRI DATA IN PRIMARY BRAIN TUMOURS: A COMPARISON OF TOFTS AND SHUTTER SPEED MODELS, Meeting of the British-Neuro-Oncology-Society (BNOS), Publisher: OXFORD UNIV PRESS INC, Pages: 11-11, ISSN: 1522-8517
Islam S, Morrison M, Orton M, et al., 2019, USING DWI-MRI PARAMETERS FROM MULTI- B VALUES ACQUISITION AND A HISTOGRAM APPROACH FOR ASSESSMENT OF EARLY THERAPEUTIC RESPONSE IN GLIOBLASTOMA, Meeting of the British-Neuro-Oncology-Society (BNOS), Publisher: OXFORD UNIV PRESS INC, Pages: 3-3, ISSN: 1522-8517
Nestor LJ, Paterson LM, Murphy A, et al., 2019, Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and poly-substance dependent individuals, European Journal of Neuroscience, Vol: 50, Pages: 2311-2321, ISSN: 0953-816X
Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance‐dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened “top‐down” control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no‐go (GNG) task we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent poly substance‐dependent (poly‐SUD) individuals, and controls during a randomized double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly‐SUD groups respectively. Self‐reported trait impulsivity in the poly‐SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly‐SUD groups, which are predicted by trait impulsivity in the poly‐SUD group.
Grech-Sollars M, Zhou F-L, Waldman AD, et al., 2018, Stability and reproducibility of co-electrospun brain-mimicking phantoms for quality assurance of diffusion MRI sequences, NeuroImage, Vol: 181, Pages: 395-402, ISSN: 1053-8119
Grey and white matter mimicking phantoms are important for assessing variations in diffusion MR measures at a single time point and over an extended period of time. This work investigates the stability of brain-mimicking microfibre phantoms and reproducibility of their MR derived diffusion parameters. The microfibres were produced by co-electrospinning and characterized by scanning electron microscopy (SEM). Grey matter and white matter phantoms were constructed from random and aligned microfibres, respectively. MR data were acquired from these phantoms over a period of 33 months. SEM images revealed that only small changes in fibre microstructure occurred over 30 months. The coefficient of variation in MR measurements across all time-points was between 1.6% and 3.4% for MD across all phantoms and FA in white matter phantoms. This was within the limits expected for intra-scanner variability, thereby confirming phantom stability over 33 months. These specialised diffusion phantoms may be used in a clinical environment for intra and inter-site quality assurance purposes, and for validation of quantitative diffusion biomarkers.
Islam S, Morrison M, Grech-Sollars M, et al., 2018, THE USE OF ADVANCED DIFFUSION MRI PARAMETERS IN THE ASSESSMENT OF TREATMENT RESPONSE IN GLIOBLASTOMA USING MULTI-B VALUE ACQUISITION AND A HISTOGRAM-BASED APPROACH, 23rd Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology (SNO) / 3rd CNS Anticancer Drug Discovery and Development Conference, Publisher: OXFORD UNIV PRESS INC, Pages: 20-21, ISSN: 1522-8517
Morrison M, Islam S, Waldman A, et al., 2018, A HISTOGRAM-BASED, BACK-PROJECTION METHOD FOR TREATMENT RESPONSE ASSESSMENT IN GLIOBLASTOMA USING MULTI B-VALUE ADVANCED DIFFUSION MRI, 23rd Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology (SNO) / 3rd CNS Anticancer Drug Discovery and Development Conference, Publisher: OXFORD UNIV PRESS INC, Pages: 186-187, ISSN: 1522-8517
Grech-Sollars M, Inglese M, Ordidge K, et al., 2018, ASSOCIATION BETWEEN METABOLIC PARAMETERS FROM DYNAMIC 18FMC PET, PHARMACOKINETIC DCE-MRI PARAMETERS, MRS CHOLINE TO CREATINE RATIOS AND TISSUE IMMUNOHISTOCHEMISTRY FOR CHOLINE KINASE ALPHA EXPRESSION IN HUMAN BRAIN GLIOMA, 23rd Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology (SNO) / 3rd CNS Anticancer Drug Discovery and Development Conference, Publisher: OXFORD UNIV PRESS INC, Pages: 184-184, ISSN: 1522-8517
Grech-Sollars M, Inglese M, Ordidge K, et al., 2018, ASSOCIATION BETWEEN METABOLIC PARAMETERS FROM DYNAMIC 18F-FLUOROMETHYLCHOLINE PET, PHARMACOKINETIC PARAMETERS FROM DCE-MRI, CHOLINE TO CREATINE RATIOS FROM MRS AND TISSUE IMMUNOHISTOCHEMISTRY FOR CHOLINE KINASE ALPHA EXPRESSION IN HUMAN BRAIN GLIOMA, Meeting of the British-Neuro-Oncology-Society (BNOS), Publisher: OXFORD UNIV PRESS INC, Pages: 346-346, ISSN: 1522-8517
Ritchie CW, Russ TC, Banerjee S, et al., 2018, The Edinburgh Consensus: preparing for the advent of disease-modifying therapies for Alzheimer's disease (vol 9, 85, 2017), ALZHEIMERS RESEARCH & THERAPY, Vol: 10, ISSN: 1758-9193
Inglese M, Grech-Sollars M, Ordidge K, et al., 2018, Association between pharmacokinetic parameters from DCE-MRI and metabolic parameters from dynamic 18F-fluoromethylcholine PET in human brain glioma, 27th International Society for Magnetic Resonance in Medicine
Inglese M, Honeyfield L, Aboagye E, et al., 2018, Comparison of the Tofts and the Shutter Speed Model for DCE-MRI in patients with Brain Glioma, 27th International Society for Magnetic Resonance in Medicine
Kurian KM, Jenkinson MD, Brennan PM, et al., 2018, Brain tumor research in the United Kingdom: current perspective and future challenges. A strategy document from the NCRI Brain Tumor CSG, NEURO-ONCOLOGY PRACTICE, Vol: 5, Pages: 10-17, ISSN: 2054-2577
Stefaniak JD, Su L, Mak E, et al., 2018, Cerebral small vessel disease in middle age and genetic predisposition to late-onset Alzheimer's disease, ALZHEIMERS & DEMENTIA, Vol: 14, Pages: 253-258, ISSN: 1552-5260
Rinne P, Hassan M, Fernandes C, et al., 2018, Motor dexterity and strength depend upon integrity of the attention-control system, Proceedings of the National Academy of Sciences, Vol: 115, Pages: E536-E545, ISSN: 0027-8424
Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength—by examining relationships between attention control and motor performance in healthy-aged and hemiparetic-stroke subjects (n = 93 and 167, respectively). Subjects undertook simple-tracking, precision-hold, and maximum force-generation tasks, with each hand. Performance across all tasks correlated strongly with attention control (measured as distractor resistance), independently of factors such as baseline performance, hand use, lesion size, mood, fatigue, or whether distraction was tested during motor or nonmotor cognitive tasks. Critically, asymmetric dissociations occurred in all tasks, in that severe motor impairment coexisted with normal (or impaired) attention control whereas normal motor performance was never associated with impaired attention control (below a task-dependent threshold). This implies that dexterity and force generation require intact attention control. Subsequently, we examined how motor and attention-control performance mapped to lesion location and cerebral functional connectivity. One component of motor performance (common to both arms), as well as attention control, correlated with the anatomical and functional integrity of a cingulo-opercular “salience” network. Independently of this, motor performance difference between arms correlated negatively with the integrity of the primary sensorimotor network and corticospinal tract. These results suggest that the salience network, and its attention-control function, are necessary for virtually all volitional motor acts while its damage contributes significantly to the cardinal motor deficits of stroke.
Grech-Sollars M, Ordidge K, Vaqas B, et al., 2018, 18F-METHYLCHOLINE PET/CT, IN VIVO MAGNETIC RESONANCE SPECTROSCOPY IMAGING AND TISSUE ENZYME BIOMARKERS OF CHOLINE METABOLISM IN PRIMARY BRAIN GLIOMAS., Meeting of the British-Neuro-Oncology-Society (BNOS), Publisher: OXFORD UNIV PRESS INC, Pages: 18-18, ISSN: 1522-8517
Ritchie CW, Russ TC, Banerjee S, et al., 2017, The Edinburgh Consensus: preparing for the advent of disease-modifying therapies for Alzheimer's disease, Alzheimers Research & Therapy, Vol: 9, ISSN: 1758-9193
ContextThis commentary discusses the implications of disease-modifying treatments for Alzheimer’s disease which seem likely to appear in the next few years and results from a meeting of British experts in neurodegenerative diseases in Edinburgh. The availability of such treatments would help change public and professional attitudes and accelerate engagement with the prodromal and preclinical populations who might benefit from them. However, this would require an updated understanding of Alzheimer’s disease, namely the important distinction between Alzheimer’s disease and Alzheimer’s dementia.ConsensusSince treatments are likely to be most effective in the early stages, identification of clinically relevant brain changes (for example, amyloid burden using imaging or cerebrospinal fluid biomarkers) will be crucial. While current biomarkers could be useful in identifying eligibility for new therapies, trial data are not available to aid decisions about stopping or continuing treatment in clinical practice. Therefore, effective monitoring of safety and effectiveness when these treatments are introduced into clinical practice will be necessary to inform wide-scale use. Equity of access is key but there is a tension between universal access for everyone with a diagnosis of Alzheimer’s disease and specifying an eligible population most likely to respond. We propose the resources necessary for an optimal care pathway as well as the necessary education and training for primary and secondary care.ConclusionThe majority of current services in the UK and elsewhere would not be able to accommodate the specialist investigations required to select patients and prescribe these therapies. Therefore, a stepped approach would be necessary: from innovating sentinel clinical-academic centres that already have capacity to deliver the necessary phase IV trials, through early adoption in a hub and spoke model, to nationwide adoption for true equity of access.
Carswell C, Win Z, Muckle K, et al., 2017, Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 89, Pages: 294-299, ISSN: 1468-330X
Background and objective Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer’s disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the ‘real-world’ arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic.Methods We reviewed the presenting clinical features, the pre-API and post-API investigations, diagnosis and outcomes for the first 100 patients who had API as part of their routine work-up at the Imperial Memory Centre, a tertiary referral clinic in the UK National Health Service.Results API was primarily used to investigate patients with atypical clinical features (56 cases) or those that were young at onset (42 cases). MRI features of AD did not always predict positive API (67%), and 6 of 23 patients with MRIs reported as normal were amyloid-PET positive. There were significantly more cases categorised as non-AD dementia post-API (from 11 to 23). Patients investigated when API was initially available had fewer overall investigations and all patients had significantly fewer investigations in total post-API.Conclusions API has a clear impact on the investigation of young-onset or complex dementia while reducing the overall burden of investigations. It was most useful in younger patients, atypical presentations or individuals with multiple possible causes of cognitive impairment.
Grech-Sollars M, Vaqas B, Thompson G, et al., 2017, An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems, Journal of Neurosurgery, Vol: 127, Pages: 812-818, ISSN: 0022-3085
OBJECTIVEGlioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation.METHODSA novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and 18F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling.RESULTSThe neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high 18F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization.CONCLUSIONSThese PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and 18F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods
Saleem A, Searle GE, Kenny LM, et al., 2017, Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer (vol 5, 30, 2015), EJNMMI RESEARCH, Vol: 7, ISSN: 2191-219X
Saleem A, Searle GE, Kenny LM, et al., 2017, Erratum to: Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer., EJNMMI Research, Vol: 7, Pages: 74-74, ISSN: 2191-219X
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