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Recent research has indicated that the relationship between age-related cognitive decline and falling may be mediated by the individual's capacity to quickly cancel or inhibit a motor response. This longitudinal investigation demonstrates that higher white matter fibre density in the motor inhibition network paired with low physical activity was associated with falling in elderly participants. We measured the density of white matter fibre tracts connecting key nodes in the inhibitory control network in a large sample (n = 414) of older adults. We modelled their self-reported frequency of falling over a 4-year period with white matter fibre density in pathways corresponding to the direct and hyperdirect cortical-subcortical loops implicated in the inhibitory control network. Only connectivity between right inferior frontal gyrus and right subthalamic nucleus was associated with falling as measured cross-sectionally. The connectivity was not, however, predictive of future falling when measured 2 and 4 years later. Higher white matter fibre density was associated with falling, but only in combination with low levels of physical activity. No such relationship existed for selected control brain regions that are not implicated in the inhibitory control network. Albeit statistically robust, the direction of this effect was counterintuitive (more dense connectivity associated with falling) and warrants further longitudinal investigation into whether white matter fibre density changes over time in a manner correlated with falling, and mediated by physical activity., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

This study aimed to comprehensively evaluate the current utilization and future potential of ChatGPT, an AI-based chat model, in the field of radiology. The primary focus is on its role in enhancing decision-making processes, optimizing workflow efficiency, and fostering interdisciplinary collaboration and teaching within healthcare. A systematic search was conducted in PubMed, EMBASE and Web of Science databases. Key aspects, such as its impact on complex decision-making, workflow enhancement and collaboration, were assessed. Limitations and challenges associated with ChatGPT implementation were also examined. Overall, six studies met the inclusion criteria and were included in our analysis. All studies were prospective in nature. A total of 551 chatGPT (version 3.0 to 4.0) assessment events were included in our analysis. Considering the generation of academic papers, ChatGPT was found to output data inaccuracies 80% of the time. When ChatGPT was asked questions regarding common interventional radiology procedures, it contained entirely incorrect information 45% of the time. ChatGPT was seen to better answer US board-style questions when lower order thinking was required (P = 0.002). Improvements were seen between chatGPT 3.5 and 4.0 in regard to imaging questions with accuracy rates of 61 versus 85%(P = 0.009). ChatGPT was observed to have an average translational ability score of 4.27/5 on the Likert scale regarding CT and MRI findings. ChatGPT demonstrates substantial potential to augment decision-making and optimizing workflow. While ChatGPT's promise is evident, thorough evaluation and validation are imperative before widespread adoption in the field of radiology., (© 2024 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Introduction: The management of anal cancer relies on clinical and histopathological features for treatment decisions. In recent years, the field of radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving management of pelvic cancers. The aim of this study was to evaluate the current application of radiomics in the management of anal cancer., Methods: A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Inclusion criteria encompassed randomized and non-randomized trials investigating the use of radiomics to predict post-operative recurrence in anal cancer. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools., Results: The systematic review identified a total of nine studies, with 589 patients examined. There were three main outcomes assessed in included studies: recurrence (6 studies), progression-free survival (2 studies), and prediction of human papillomavirus (HPV) status (1 study). Radiomics-based risk stratification models were found to provide valuable insights into treatment response and patient outcomes, with all developed signatures demonstrating at least modest accuracy (range: .68-1.0) in predicting their primary outcome., Conclusion: Radiomics has emerged as a promising tool in the management of anal cancer. It offers the potential for improved risk stratification, treatment planning, and response assessment, thereby guiding personalized therapeutic approaches., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Impaired recovery of blood pressure (BP) in response to standing up is a prevalent condition in older individuals. We evaluated the relationship between the early recovery of hemodynamic responses to standing and brain health in adults over 50., Methods: Participants from The Irish Longitudinal Study on Ageing (TILDA) (n=411; age 67.6 ± 7.3 years; 53.4 % women) performed an active stand challenge while blood pressure and heart rate were continuously monitored. The recovery of these parameters was determined as the slope of the BP and HR response, following the initial drop/rise after standing. We have previously reported a novel and validated measure of brain ageing using MRI data, which measures the difference between biological brain age and chronological age, providing a brain-predicted age difference (brainPAD) score., Results: Slower recovery of systolic and diastolic BP was found to be significantly associated with higher brainPAD scores (i.e., biologically older brains), where a one-year increase in brainPAD was associated with a decrease of 0.02 mmHg/s and 0.01 mmHg/s in systolic and diastolic BP recovery, respectively, after standing. Heart rate (HR) recovery was not significantly associated with brainPAD score., Conclusion: These results demonstrate that slower systolic and diastolic BP recovery in the early phase after standing is associated with accelerated brain aging in older individuals. This suggests that the BP response to standing, measured using beat-to-beat monitoring, has the potential to be used as a marker of accelerated brain aging, relying on a simple procedure and devices that are easily accessible., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Purpose: This systematic review evaluated whole-body MRI (WB-MRI) as a cancer screening tool for individuals carrying germline TP53 mutations, a population known to be at a significantly elevated risk of malignancy. The primary objective is to assess the diagnostic performance of WB-MRI in detecting cancer in this cohort., Methods: PubMed, MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials were searched until 18 August 2023. Eligible studies were selected based on predefined inclusion criteria. The data extracted included information on study characteristics, patient demographics, and the WB-MRI diagnostic performance., Results: This systematic review identified eight eligible studies, comprising 506 TP53 mutation carriers. The mean age was 34.6 ± 16.3 (range 1-74) years. In total, 321/506 (63.4%) of the patients were female and 185/506 (36.6%) were male. In addition, 267/506 (52.8%) had a previous oncological diagnosis. Thirty-six new cancers were diagnosed with WB-MRI (36/506 (7.1%)). The overall pooled proportion of cancer detected on MRI was 7% (95% confidence interval 5-10). In total, 44 new lesions were picked up, as multiple lesions were found in some patients., Conclusion: WB-MRI is an effective cancer screening tool for TP53 mutation carriers. While these findings suggest the potential for WB-MRI to contribute to early cancer detection in this high-risk population, further research and the standardisation of protocols internationally are warranted to optimise its clinical utility.

We examined the relationship between hippocampal subfield volumes and cognitive decline over a 4-year period in a healthy older adult population with the goal of identifying subjects at risk of progressive cognitive impairment which could potentially guide therapeutic interventions and monitoring. 482 subjects (68.1 years +/- 7.4; 52.9% female) from the Irish Longitudinal Study on Ageing underwent magnetic resonance brain imaging and a series of cognitive tests. Using K -means longitudinal clustering, subjects were first grouped into three separate global and domain-specific cognitive function trajectories; High-Stable, Mid-Stable and Low-Declining. Linear mixed effects models were then used to establish associations between hippocampal subfield volumes and cognitive groups. Decline in multiple hippocampal subfields was associated with global cognitive decline, specifically the presubiculum (estimate -0.20; 95% confidence interval (CI) -0.78 - -0.02; p  = 0.03), subiculum (-0.44; -0.82 - -0.06; p  = 0.02), CA1 (-0.34; -0.78 - -0.02; p  = 0.04), CA4 (-0.55; -0.93 - -0.17; p  = 0.005), molecular layer (-0.49; -0.87 - -0.11; p  = 0.01), dentate gyrus (-0.57; -0.94 - -0.19; p  = 0.003), hippocampal tail (-0.53; -0.91 - -0.15; p  = 0.006) and HATA (-0.41; -0.79 - -0.03; p  = 0.04), with smaller volumes for the Low-Declining cognition group compared to the High-Stable cognition group. In contrast to global cognitive decline, when specifically assessing the memory domain, cornu ammonis 1 subfield was not found to be associated with low declining cognition (-0.14; -0.37 - 0.10; p  = 0.26). Previously published data shows that atrophy of specific hippocampal subfields is associated with cognitive decline but our study confirms the same effect in subjects asymptomatic at time of enrolment. This strengthens the predictive value of hippocampal subfield atrophy in risk of cognitive decline and may provide a biomarker for monitoring treatment efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Doran, Carey, Knight, Meaney, Kenny and De Looze.)

Cardiovascular pathology is the leading cause of death and disability in the Western world, and current diagnostic testing usually evaluates the anatomy of the vessel to determine if the vessel contains blockages and plaques. However, there is a growing school of thought that other measures, such as wall shear stress, provide more useful information for earlier diagnosis and prediction of atherosclerotic related disease compared to pulsed-wave Doppler ultrasound, magnetic resonance angiography, or computed tomography angiography. A novel algorithm for quantifying wall shear stress (WSS) in atherosclerotic plaque using diagnostic ultrasound imaging, called Multifrequency ultrafast Doppler spectral analysis (MFUDSA), is presented. The development of this algorithm is presented, in addition to its optimisation using simulation studies and in-vitro experiments with flow phantoms approximating the early stages of cardiovascular disease. The presented algorithm is compared with commonly used WSS assessment methods, such as standard PW Doppler, Ultrafast Doppler, and Parabolic Doppler, as well as plane-wave Doppler. Compared to an equivalent processing architecture with one-dimensional Fourier analysis, the MFUDSA algorithm provided an increase in signal-to-noise ratio (SNR) by a factor of 4-8 and an increase in velocity resolution by a factor of 1.10-1.35. The results indicated that MFUDSA outperformed the others, with significant differences detected between the typical WSS values of moderate disease progression ( p = 0.003) and severe disease progression ( p = 0.001). The algorithm demonstrated an improved performance for the assessment of WSS and has potential to provide an earlier diagnosis of cardiovascular disease than current techniques allow.

Frailty in older adults is associated with greater risk of cognitive decline. Brain connectivity insights could help understand the association, but studies are lacking. We applied connectome-based predictive modeling to a 32-item self-reported Frailty Index (FI) using resting state functional MRI data from The Irish Longitudinal Study on Ageing. A total of 347 participants were included (48.9% male, mean age 68.2 years). From connectome-based predictive modeling, we obtained 204 edges that positively correlated with the FI and composed the "frailty network" characterised by connectivity of the visual network (right); and 188 edges that negatively correlated with the FI and formed the "robustness network" characterized by connectivity in the basal ganglia. Both networks' highest degree node was the caudate but with different patterns: from caudate to visual network in the frailty network; and to default mode network in the robustness network. The FI was correlated with walking speed but not with metrics of global cognition, reinforcing the matching between the FI and the brain connectivity pattern found (main predicted connectivity in basal ganglia)., Competing Interests: Disclosure statement The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate whether tooth loss was associated with regional grey matter volume (GMV) in a group of community dwelling older men and women from Ireland., Methods: A group of 380 dementia-free men and women underwent a dental examination and had a Magnetic Resonance Imaging (MRI) scan as part of The Irish Longitudinal Study of Aging (TILDA). Cortical parcellation was conducted using Freesurfer utilities to produce volumetric measures of gyral based regions of interest. Analysis included multiple linear regression to investigate the association between tooth loss and regional GMVs with adjustment for various confounders., Results: The mean age of participants was 68.1 years (SD 7.3) and 51.6% of the group were female. 50 (13.2%) of the participants were edentulous, 148 (38.9%) had 1-19 teeth, and 182 (47.9%) had ≥20 teeth. Multiple liner regression analysis with adjustment for a range of potential confounders showed associations between the number of teeth and GMVs in the paracentral lobule and the cuneus cortex. In the paracentral lobule, comparing participants with 1-19 teeth versus edentates there was an increase in GMV of β=323.0mm 3 (95% Confidence Interval [CI] 84.5, 561.6) and when comparing participants with ≥20 teeth to edentates there was an increase of β=382.3mm 3 (95% CI 126.9, 637.7). In the cuneus cortex, comparing participants with ≥20 teeth to edentates there was an increase in GMV of β=380.5mm 3 (95% CI 69.4, 691.5)., Conclusions: In this group of older men and women from Ireland, the number of teeth was associated with GMVs in the paracentral lobule and the cuneus cortex independent of various known confounders., Clinical Significance: Although not proof of causation, the finding that tooth loss was associated with regional reduced GMV in the brain may represent a potential explanatory link to the observed association between tooth loss and cognitive decline., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Iron-overload cardiomyopathy initially manifests with diastolic dysfunction and can progress to dilated cardiomyopathy if untreated. Previous studies have shown that patients with primary and secondary hemochromatosis can have subclinical left ventricle dysfunction with abnormalities on strain imaging. This study aimed to evaluate the relationship between cardiac T2* values and myocardial-wall strain in patients with hereditary hemochromatosis (HH) at the time of diagnosis and after a course of venesection treatment., Materials and Methods: Baseline cardiac magnetic resonance (CMR) at 3 T was performed in 19 patients with newly diagnosed HH with elevated serum ferritin levels and repeated after a course of treatment with venesection. Quantitative T2* mapping and strain analysis were performed offline using dedicated relaxometry fitting and feature-tracking software., Results: The majority (84%) of patients had normal baseline myocardial T2* values (mean 19.3 ms, range 8.9 to 31.2 ms), which improved significantly after venesection (mean 24.1 ms, range 11 to 38.1 ms) ( P =0.021). Mean global radial strain significantly improved from 25.0 (range: 15.6 to 32.9) to 28.3 (range: 19.8 to 35.8) ( P =0.001) and mean global circumferential strain improved, decreasing from -15.7 (range: -11.1 to -19.2) to -17.1 (range: -13.0 to -20.1) ( P =0.001)., Conclusion: Patients with HH may have normal T2* values in the presence of subclinical left ventricle dysfunction, which can be detected by abnormal radial and circumferential strain. As strain imaging improves following venesection in HH, it may serve as a useful biomarker to guide treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objectives: This study examines the cross-sectional and 2-year follow-up relationships between sleep and stress and total hippocampal volume and hippocampal subfield volumes among older adults., Methods: Four hundred seventeen adults (aged 68.8 ± 7.3; 54% women) from the Irish Longitudinal Study on Ageing completed an interview, a questionnaire, and multiparametric brain magnetic resonance imaging. The relationships between self-reported sleep duration, sleep problems, perceived stress, and total hippocampal volume were examined by using ordinary least squares regressions. Linear mixed-effects models were used to investigate the relationships between sleep duration, sleep problems, perceived stress, changes in these measures over 2-years, and hippocampal subfield volumes., Results: No cross-sectional and follow-up associations between sleep and total hippocampal volume and between stress and total hippocampal volume were found. By contrast, Long sleep (≥9-10 h/night) was associated with smaller volumes of molecular layer, hippocampal tail, presubiculum, and subiculum. The co-occurrence of Short sleep (≤6 h) and perceived stress was associated with smaller cornu ammonis 1, molecular layer, subiculum, and tail. Sleep problems independently and in conjunction with higher stress, and increase in sleep problems over 2 years were associated with smaller volumes of these same subfields., Conclusion: Our study highlights the importance of concurrently assessing suboptimal sleep and stress for phenotyping individuals at risk of hippocampal subfield atrophy., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and physical activity (PA) with gray matter cerebral blood flow (CBF GM ) in older adults. Cross-sectional data was used from the Irish Longitudinal Study on Ageing (n = 495, age 69.0 ±7.4 years, 52.1% female). Whole-brain CBF GM was quantified using arterial spin labeling MRI. Results from multivariable regression analysis revealed that an increase in BMI of 0.43 kg/m 2 , WHR of 0.01, or WC of 1.3 cm were associated with the same reduction in CBF GM as 1 year of advancing age. Participants overweight by BMI or with high WHR/WC reporting low/moderate PA had up to 3 ml/100g/min lower CBF GM (p ≤ .011); there was no significant reduction for those reporting high PA. Since PA could potentially moderate obesity/CBF associations, this may be a cost-effective and relatively easy way to help mitigate the negative impact of obesity in an older population, such as cerebral hypoperfusion, which is an early mechanism in vascular dementia and Alzheimer's disease., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF GM ) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older., Background: Quantitative assessment of CBF GM may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBF GM from pathological reduction has been hampered by the lack of reference values for cerebral perfusion., Methods: The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBF GM data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations., Results: The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBF GM for the cohort was 36.5 ± 8.2 ml/100 g/min. CBF GM decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = -0.3, -0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001)., Conclusions: This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBF GM measured at 3T using pCASL-MRI. Significant age- and sex-related differences exist in CBF GM ., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Multisensory perception might provide an important marker of brain function in aging. However, the cortical structures supporting multisensory perception in aging are poorly understood. In this study, we compared regional gray matter volume in a group of middle-aged (n = 101; 49-64 years) and older (n = 116; 71-87 years) adults from The Irish Longitudinal Study on Aging using voxel-based morphometry. Participants completed a measure of multisensory integration, the sound-induced flash illusion, and were grouped as per their illusion susceptibility. A significant interaction was observed in the right angular gyrus; in the middle-aged group, larger gray matter volume corresponded to stronger illusion perception while in older adults larger gray matter corresponded to less illusion susceptibility. This interaction remained significant even when controlling for a range of demographic, sensory, cognitive, and health variables. These findings show that multisensory integration is associated with specific structural differences in the aging brain and highlight the angular gyrus as a possible "cross-modal hub" associated with age-related change in multisensory perception., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation.We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray-Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as 'MES+ve' or 'MES-ve'. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets.Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (25 vs. 30; P  = 0.31) or between MES+ve vs. MES-ve symptomatic patients (36 vs. 25; P  = 0.09). Symptomatic patients with GSM-echodense plaques (GSM ≥25) had higher platelet counts (228 vs. 191 × 10 9 /L), neutrophil-platelet (3.3 vs. 2.7%), monocyte-platelet (6.3 vs. 4.55%) and lymphocyte-platelet complexes (2.91 vs. 2.53%) than ' asymptomatic patients with GSM-echodense plaques ' ( P ≤ 0.03).Recently, symptomatic carotid stenosis patients with 'GSM-echodense plaques' have enhanced platelet production/secretion/activation compared with their asymptomatic counterparts. Simultaneous assessment with neurovascular imaging and platelet biomarkers may aid risk-stratification in carotid stenosis.

The aim of this work was to establish the optimum acoustic characterisation approach and insonation transmit beam parameters for subharmonic signal generation with 'native' and 'altered' populations of a commonly-used microbubble contrast agent. Dynamic contrast-enhanced (DCE) ultrasound is a non-invasive method of imaging the microvasculature, typically implemented using harmonic imaging. Subharmonic imaging, in which echoes at half the fundamental frequency are detected, detects signals which are generated by the ultrasound contrast agents (UCAs) but not by tissue. However, optimal transmission parameters and furthermore, the optimum acoustic characterisation method have not been established. The subharmonic response of 'native' and 'altered' UCA, altered through decantation, was investigated at transmit centre frequencies 1.8-5 MHz and pulse lengths 1-8 cycles. The 'altered' UCA had reduced polydispersity (1-4 µm: 82% bubble volume), compared to 'native' (4-10 µm: 57% bubble volume). A custom-built narrow-band acoustic characterisation system was found to be more appropriate for acoustic characterisation compared to the commonly used broadband pulse-echo approach. Both UCA generated the highest subharmonic signal at pulse length of 3-cycles. The maximum 'native' subharmonic signal was generated at a transmit centre frequency of 1.9 MHz, corresponding to a subharmonic at 0.95 MHz. This optimal frequency increased in the 'altered' population to 2.3-2.5 MHz, bringing the subharmonic above 1 MHz and hence into a range amenable to clinical abdominal imaging transducers. The use of subharmonic signal detection coupled with a modified UCA size distribution has potential to significantly improve the quantification sensitivity and accuracy of DCE ultrasound imaging., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI.

Background: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy., Methods: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100 ® and 'low shear stress' with VerifyNow ® and Multiplate ® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve., Results: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100 ® , but not on the VerifyNow ® or Multiplate ® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100 ® (28.6%) vs. VerifyNow ® (9.5%; P = 0.049), but not Multiplate ® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup., Discussion: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100 ® , likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Purpose: To quantify the effects of DCE acquisition and pharmacokinetic modeling processing methodologies on the absolute accuracy and precision of derived pharmacokinetic (PK) parameter values using a novel anthropomorphic phantom test device in which "ground truth" values were known a priori., Methods: Ground truth arterial input function (AIF), tumor, and healthy tissue contrast agent concentration-time curves (CTCs) were established within the phantom and repeatedly measured on a 3T MRI scanner with varying temporal resolution (T res  = 1.22-30.6 s). Ground truth CTCs, K trans , v e , and k ep values were directly compared to measured values as a function of T res , with and without the application of voxel-wise flip-angle corrections applied to the data and PK modeling performed using linear and nonlinear forms of the standard Tofts model., Results: Measurement of the AIF was strongly affected by the T res used (AIF curve-shape feature errors: 3%-222% for T res : 1.22-30.6 s), which directly translated to errors in the derived K trans , v e , and k ep values of 1%-24%, 2%-5%, and 1%-26% respectively across this T res range (flip-angle correction applied). Further appreciable improvements in accuracy and precision arising from the use of flip angle corrections and nonlinear least squares fitting were quantified and used to identify optimal acquisition and analysis methodologies for which measurement errors could be constrained below threshold levels., Conclusion: This quantitative study provides insight into how errors in AIF measurement propagate to errors in PK parameter outputs. Absolute quantification of the accuracy and precision of MR-measured CTCs, and resultant PK parameter values, allowed for an optimal temporal resolution to be defined commensurate with maintaining K trans , v e , and k ep measurement errors below 5% and 10% levels. An appreciable gain in PK parameter estimation accuracy at the analysis stage was also demonstrated using flip-angle corrections and a linear approach to PK model fitting., (© 2019 American Association of Physicists in Medicine.)

Working memory-based cognitive remediation therapy (CT) for psychosis has recently been associated with broad improvements in performance on untrained tasks measuring working memory, episodic memory and IQ, and changes in associated brain regions. However, it is unclear whether these improvements transfer to the domain of social cognition and neural activity related to performance on social cognitive tasks. We examined performance on the Reading the Mind in the Eyes test (Eyes test) in a large sample of participants with psychosis who underwent working memory-based CT (N = 43) compared to a control group of participants with psychosis (N = 35). In a subset of this sample, we used functional magnetic resonance imaging (fMRI) to examine changes in neural activity during a facial emotion recognition task in participants who underwent CT (N = 15) compared to a control group (N = 15). No significant effects of CT were observed on Eyes test performance or on neural activity during facial emotion recognition, either at p < 0.05 family-wise error or at a p < 0.001 uncorrected threshold, within a priori social cognitive regions of interest. This study suggests that working memory-based CT does not significantly impact an aspect of social cognition which was measured behaviourally and neurally. It provides further evidence that deficits in the ability to decode mental state from facial expressions are dissociable from working memory deficits, and suggests that future CT programmes should target social cognition in addition to working memory for the purposes of further enhancing social function., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis., Methods: Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3-6 months post-treatment., Results: Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3-6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition., Conclusions: CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.

Background: Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainstem disease. Lesions in other regions may result in nystagmus. The identification of these other sites is enhanced by using 3-Tesla magnetic resonance imaging (3TMRI) due to increased signal-to-noise ratio., Objective: We sought to evaluate the distribution of structural lesions and disruption of tracts in patients with horizontal nystagmus secondary to MS using 3TMRI., Methods: Twenty-four patients (20 women, 4 men; age range 26-55 years) with horizontal nystagmus secondary to MS underwent 3TMRI brain scans; and 18 patients had diffusion tensor imaging (DTI) for tractography., Results: Nystagmus was bidirectional in 11, right-sided in 6 and left-sided in 7. We identified 194 lesions in 20 regions within the neural integrator circuit in 24 patients; 140 were within the cortex and 54 were within the brainstem. Only two patients had no lesions in the cortex, and 9 had no lesions in the brainstem. There was no relationship between side of lesion and direction of nystagmus. Thirteen of 18 (72 %) had tract disruption with fractional anisotropy (FA) values below 0.2. FA was significantly lower in bidirectional compared to unidirectional nystagmus (p = 0.006)., Conclusion: In MS patients with horizontal nystagmus, lesions in all cortical eye fields and their descending connections were evident. Technical improvements in tractography may help identify the specific site(s) resulting in nystagmus in MS.

A novel anthropomorphic flow phantom device has been developed, which can be used for quantitatively assessing the ability of magnetic resonance imaging (MRI) scanners to accurately measure signal/concentration time-intensity curves (CTCs) associated with dynamic contrast-enhanced (DCE) MRI. Modelling of the complex pharmacokinetics of contrast agents as they perfuse through the tumour capillary network has shown great promise for cancer diagnosis and therapy monitoring. However, clinical adoption has been hindered by methodological problems, resulting in a lack of consensus regarding the most appropriate acquisition and modelling methodology to use and a consequent wide discrepancy in published data. A heretofore overlooked source of such discrepancy may arise from measurement errors of tumour CTCs deriving from the imaging pulse sequence itself, while the effects on the fidelity of CTC measurement of using rapidly-accelerated sequences such as parallel imaging and compressed sensing remain unknown. The present work aimed to investigate these features by developing a test device in which 'ground truth' CTCs were generated and presented to the MRI scanner for measurement, thereby allowing for an assessment of the DCE-MRI protocol to accurately measure this curve shape. The device comprised a four-pump flow system wherein CTCs derived from prior patient prostate data were produced in measurement chambers placed within the imaged volume. The ground truth was determined as the mean of repeat measurements using an MRI-independent, custom-built optical imaging system. In DCE-MRI experiments, significant discrepancies between the ground truth and measured CTCs were found for both tumorous and healthy tissue-mimicking curve shapes. Pharmacokinetic modelling revealed errors in measured K trans , v e and k ep values of up to 42%, 31%, and 50% respectively, following a simple variation of the parallel imaging factor and number of signal averages in the acquisition protocol. The device allows for the quantitative assessment and standardisation of DCE-MRI protocols (both existing and emerging).

Introduction: Hypertension is a recognised risk factor for lacunar stroke. However, their association has been evaluated using static blood pressure (BP) assessment in supine or sitting position alone. We hypothesised that impaired dynamic (orthostatic) BP control may associate with lacunar strokes., Patients and Methods: Consecutive subjects with mitral regurgitation (MR) confirmed, lacunar strokes were compared with two control groups. Firstly "normal", age and sex matched, population controls (1:3 ratio) and then 'at risk' controls matched for age, sex, hypertension history and antihypertensive medication (1:2 ratio). Orthostatic BP control was assessed by active stand tests with continuous, phasic, beat-to-beat BP measurement., Findings: Thirty-six subjects (mean 69.9 years) were compared with 108 controls in group 1 and 72 in group 2. Prevalence of syncope was higher among those with lacunar stroke (cases: 44.4%, group 1: 17.6%, p  = 0.003, group 2: 12.5%, p  = 0.0004, Fisher's exact). Mean baseline systolic BP (SBP) was significantly higher in cases (cases: 150 mm Hg, group 1: 140 mm Hg, p  = 0.03, group 2: 143 mm Hg, p  = 0.1). Ten seconds after standing, SBP dropped significantly less in cases (cases: -14.1 mm Hg, group 1: -31.4 mm Hg, p  < 0.0005, group 2: -27.3 mm Hg, p  = 0.001, t test). Diastolic BP also fell significantly less in cases. Cases' SBP and DBP recovered to, then persistently overshot baseline levels., Discussion and Conclusion: Subjects with MR-defined lacunar stroke, of likely small vessel aetiology, exhibit orthostatic hypertension compared with population norms., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition associated with repetitive mild traumatic brain injury. In recent years, attention has focused on emerging evidence linking the development of CTE to concussive injuries in athletes and military personnel; however, the underlying molecular pathobiology of CTE remains unclear. Here, we provide evidence that the blood-brain barrier (BBB) is disrupted in regions of dense perivascular p-Tau accumulation in a case of CTE. Immunoreactivity patterns of the BBB-associated tight junction components claudin-5 and zonula occludens-1 were markedly discontinuous or absent in regions of perivascular p-Tau deposition; there was also immunohistochemical evidence of a BBB in these foci. Because the patient was diagnosed premortem clinically as having progressive supranuclear palsy (PSP), we also compromised that the CTE alterations appear to be distinct from those in the brain of a patient with PSP. This report represents the first description of BBB dysfunction in a pathologically proven CTE case and suggests a vascular component in the postconcussion cascade of events that may ultimately lead to development of a progressive degenerative disorder. BBB dysfunction may represent a correlate of neural dysfunction in live subjects suspected of being at risk for development of CTE., (© 2016 American Association of Neuropathologists, Inc. All rights reserved.)

Objective: The identification of "endophenotypes"-measurable variations along the pathways between genes and distal disease state-may help deconstruct focal epilepsies into more sensitive phenomena and improve future efforts to map the genetic underpinnings of the disorder. In this study, we set out to determine if diffusion tensor imaging (DTI)-inferred white matter (WM) alterations represent a suitable structural endophenotype for focal epilepsy., Methods: We recruited 25 patients with sporadic mesial temporal lobe epilepsy (MTLE) with normal magnetic resonance imaging (MRI) findings, 25 of their gender-matched, asymptomatic siblings, and 60 control subjects. Whole-brain, voxelwise statistics were conducted to identify regions of microstructural degeneration in patients with MTLE and/or their asymptomatic siblings. WM tracts exhibiting evidence of microstructural disruption were then reconstructed using deterministic tractography. Diffusion metrics including fractional anisotropy (FA) and mean diffusivity (MD) were compared across groups using a series of one-way multivariate analyses of covariance (MANCOVAs)., Results: Voxelwise statistics revealed significant FA reductions in the corpus callosum (CC), bilateral superior longitudinal fasciculi (SLF), bilateral inferior longitudinal fasciculi (ILF), and left corticospinal tract (CST) in MTLE patients only. MD increases were observed in MTLE patients and their asymptomatic siblings in the left SLF and left CST. Deterministic tractography supported the voxelwise results, revealing significant FA alterations in the left SLF and CST in patients only and significant MD alterations in MTLE patients and their unaffected siblings. The diffusion scalars of MTLE patients and their asymptomatic siblings were highly correlated in the SLF and CST ipsilateral to patients' sides of seizure onset., Significance: These findings confirm the presence of microstructural WM alterations in patients with MRI-negative MTLE and provide preliminary support for a diffusion-based endophenotype in the disorder. Further studies of narrow-sense heritability in larger cohorts of first-degree relatives of MTLE patients are required to confirm these results., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Although the visual system has been extensively investigated, an integrated account of the spatiotemporal dynamics of long-range signal propagation along the human visual pathways is not completely known or validated. In this work, we used dynamic causal modeling approach to provide insights into the underlying neural circuit dynamics of pattern reversal visual-evoked potentials extracted from concurrent EEG-fMRI data. A recurrent forward-backward connectivity model, consisting of multiple interacting brain regions identified by EEG source localization aided by fMRI spatial priors, best accounted for the data dynamics. Sources were first identified in the thalamic area, primary visual cortex, as well as higher cortical areas along the ventral and dorsal visual processing streams. Consistent with hierarchical early visual processing, the model disclosed and quantified the neural temporal dynamics across the identified activity sources. This signal propagation is dominated by a feedforward process, but we also found weaker effective feedback connectivity. Using effective connectivity analysis, the optimal dynamic causal modeling revealed enhanced connectivity along the dorsal pathway but slightly suppressed connectivity along the ventral pathway. A bias was also found in favor of the right hemisphere consistent with functional attentional asymmetry. This study validates, for the first time, the long-range signal propagation timing in the human visual pathways. A similar modeling approach can potentially be used to understand other cognitive processes and dysfunctions in signal propagation in neurological and neuropsychiatric disorders. Significance statement: An integrated account of long-range visual signal propagation in the human brain is currently incomplete. Using computational neural modeling on our acquired concurrent EEG-fMRI data under a visual evoked task, we found not only a substantial forward propagation toward "higher-order" brain regions but also a weaker backward propagation. Asymmetry in our model's long-range connectivity accounted for the various observed activity biases. Importantly, the model disclosed the timing of signal propagation across these connectivity pathways and validates, for the first time, long-range signal propagation in the human visual system. A similar modeling approach could be used to identify neural pathways for other cognitive processes and their dysfunctions in brain disorders., (Copyright © 2015 the authors 0270-6474/15/3513501-10$15.00/0.)

Aims: The prevalence of focal neurology (FN) as a consequence of syncope is unknown. The aim of the study was to determine its prevalence, risk factors and short-term consequences., Methods: A consecutive sample of syncope-unit attendees during a 9-month period had detailed diagnostic syncope evaluation as per European Cardiac Society guidelines coupled with assessment for FN present during syncope/pre-syncope by screening questionnaire, follow-up interview and neuroimaging (1.5T magnetic resonance imaging [MRI]). All participants were followed up for 24 months. Risk factors for FN were identified by comparing FN cases with syncope controls without FN (3:1 ratio)., Results: Five-hundred and forty consecutively attended for investigation of syncope (n = 401) and pre-syncope (n = 139). Thirty-one (5.7%) had FN events during hypotensive symptoms, mean age 49 years (19-85). The majority of FN cases had vasovagal syncope (VVS); 22 (71%), whereas eight had OH (25.8%) and one (3.2%) had cardiac arrhythmia. Median duration of FN was 15 min (IQR: 34.5). MRI in 28 (90%) was normal and in 3, old cerebral infarction was evident. Risk factors for FN/syncope were frequent syncope (P = 0·008), childhood syncope (P < 0.0005) and delayed diastolic recovery during active stand (P = 0·02). During 24-month follow-up and targeted intervention, no patients developed recurrence of FN., Conclusion: One in 20 patients with syncope/pre-syncope have co-extant FN, which during 24-month follow-up, does not progress to a persistent deficit (>24 h). Awareness of co-occurrence of FN and syncope is important as stroke misdiagnosis results in aggressive anti-hypertensive management and future events may ensue., (© The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: older subjects may require higher baseline blood pressures to maintain cerebral perfusion. We investigated whether episodic hypotension is associated with tissue infarction in subjects with syncopal symptoms at stroke onset., Methods: over 30 months, all acute strokes/TIAs were prospectively screened for symptoms of syncope or presyncope at stroke onset. Subjects with severe large vessel stenosis were excluded, while cases were referred for syncope unit investigation. All underwent 1.5 T MRI acutely, and suspected borderzone infarctions (BZI) were confirmed through Matlab-derived perfusion software. Case-control comparison was derived from stroke controls with no prior syncope history., Results: thirty-eight of 772 stroke patients described presyncope or syncope at stroke onset and had patent large vessels (4.9% of all strokes). Median age was 72 years (IQR 21.4). Twenty-two patients (58%) were prescribed antihypertensive agents at symptom onset. Twenty-six (68.4%) reported focal neurology <24 h in duration. 63.2% (n = 24) of cases reported prior syncope history, compared with 33% (N = 103) of controls, P < 0.001. Cases exhibited greater orthostatic BP drop than controls, P < 0.05 Twenty-four patients were diagnosed with vasovagal syncope through head-up tilt symptom reproduction, 9 with orthostatic hypotension, 4 with cardiac syncope and 1 with carotid sinus syndrome. Nineteen (50%) patients had an acute infarct on MRI, 14 of these were in the arterial borderzone (73.6%). The BZI group were significantly older than the non-BZI group, 79.2 yrs versus 63.3 yrs, P = 0.002., Conclusion: subjects reporting hypotensive symptoms at stroke onset have a higher prevalence of borderzone infarction, despite being normotensive or hypertensive at baseline., (© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Positron emission tomography and computed tomography (PET-CT) is established in the staging of esophageal cancer. In this study, an MRI protocol was designed to emulate the anatomical (T1-weighed (T1W) and T2W imaging) and functional information (diffusion-weighted imaging) provided by PET-CT., Methods: In all, 49 patients with carcinoma of the esophagus underwent PET-CT and whole-body MRI (WBMRI). WBMRI was carried out using dedicated sequences tailored to detect metastatic disease at each area corresponding to the anatomical coverage of PET-CT. Nodal status was determined from histopathology and endoscopic ultrasound biopsy (EUS)., Results: PET-CT and WBMRI identified the primary tumor in 46/49 (94%) and 48/49 (98%) patients, respectively. Nodal analysis in patients undergoing surgery (n = 18) yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 27, 100, 100, 47 and 56% for PET-CT, compared with 30, 100, 100, 53 and 61% for WBMRI. When nodal analysis included both surgical specimens and EUS criteria (n = 39), sensitivity, specificity, PPV, NPV and accuracy were 46, 91, 93, 40 and 59% for PET-CT compared with 59, 92, 94, 50 and 67% for WBMRI. Both imaging modalities identified distant metastases in 2 patients., Conclusion: WBMRI has similar accuracy to PET-CT in detecting the primary tumor, nodal deposits and for exclusion of systemic metastatic disease., (© 2015 S. Karger AG, Basel.)

Purpose: An investigation was carried out into the effect of three image registration techniques on the diagnostic image quality of contrast-enhanced magnetic resonance angiography (CE-MRA) images., Methods: Whole-body CE-MRA data from the lower legs of 27 patients recruited onto a study of asymptomatic atherosclerosis were processed using three deformable image registration algorithms. The resultant diagnostic image quality was evaluated qualitatively in a clinical evaluation by four expert observers, and quantitatively by measuring contrast-to-noise ratios and volumes of blood vessels, and assessing the techniques' ability to correct for varying degrees of motion., Results: The first registration algorithm ('AIR') introduced significant stenosis-mimicking artefacts into the blood vessels' appearance, observed both qualitatively (clinical evaluation) and quantitatively (vessel volume measurements). The two other algorithms ('Slicer' and 'SEMI'), based on the normalised mutual information (NMI) concept and designed specifically to deal with variations in signal intensity as found in contrast-enhanced image data, did not suffer from this serious issue but were rather found to significantly improve the diagnostic image quality both qualitatively and quantitatively, and demonstrated a significantly improved ability to deal with the common problem of patient motion., Conclusions: This work highlights both the significant benefits to be gained through the use of suitable registration algorithms and the deleterious effects of an inappropriate choice of algorithm for contrast-enhanced MRI data. The maximum benefit was found in the lower legs, where the small arterial vessel diameters and propensity for leg movement during image acquisitions posed considerable problems in making accurate diagnoses from the un-registered images., (Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Objectives: We aimed to 1) determine if subcortical volume deficits are common to mesial temporal lobe epilepsy (MTLE) patients and their unaffected siblings 2) assess the suitability of subcortical volumetric traits as endophenotypes for MTLE., Methods: MRI-based volume measurements of the hippocampus, amygdala, thalamus, caudate, putamen and pallidium were generated using an automated brain reconstruction method (FreeSurfer) for 101 unrelated 'sporadic' MTLE patients [70 with hippocampal sclerosis (MTLE+HS), 31 with MRI-negative TLE], 83 unaffected full siblings of patients and 86 healthy control subjects. Changes in the volume of subcortical structures in patients and their unaffected siblings were determined by comparison with healthy controls. Narrow sense heritability was estimated ipsilateral and contralateral to the side of seizure activity., Results: MTLE+HS patients displayed significant volume deficits across the hippocampus, amygdala and thalamus ipsilaterally. In addition, volume loss was detected in the putamen bilaterally. These volume deficits were not present in the unaffected siblings of MTLE+HS patients. Ipsilaterally, the heritability estimates were dramatically reduced for the volume of the hippocampus, thalamus and putamen but remained in the expected range for the amygdala. MRI-negative TLE patients and their unaffected siblings showed no significant volume changes across the same structures and heritability estimates were comparable with calculations from a healthy population., Conclusions: The findings indicate that volume deficits for many subcortical structures in 'sporadic' MTLE+HS are not heritable and likely related to acquired factors. Therefore, they do not represent suitable endophenotypes for MTLE+HS. The findings also support the view that, at a neuroanatomical level, MTLE+HS and MRI-negative TLE represent two distinct forms of MTLE.

Background and Methods: Diffusion-weighted whole-body imaging with background body signal subtraction was introduced as a qualitative approach to detecting metastases in the body. A liver-mimicking phantom with embedded tumours that could be moved to replicate respiratory motion was developed to assess its ability to accurately quantify ADC values., Results: Mean tumour ADC values were unaltered by the motion; however, a significant (p < 0.05) increase in the spread of ADC values was measured, even for relatively large tumours., Conclusions: These findings may be of significance in cancer therapy monitoring where subtle changes in ADC histograms may reveal changes in tumour heterogeneity.

Experimental studies support a neurotrophic hypothesis of major depressive disorder (MDD). The aim of this study was to determine the effect of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism on the white matter fiber tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample of patients with MDD and healthy controls. Thirty-seven patients with MDD and 42 healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61 diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was genotyped. Fiber tracts connecting the hippocampus and amygdala with the prefrontal lobe, namely uncinate fasciculus (UF), fornix, and cingulum were analyzed. A significant interaction was found in the UF between BDNF alleles and diagnosis. Patients carrying the BDNF met-allele had smaller fractional anisotropy (FA) in the UF compared to those patients homozygous for val-allele and compared to healthy subjects carrying the met-allele. A significant three-way interaction was detected between region of the cingulum (dorsal, rostral, and parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was detectable in the left rostral cingulum for met-allele carriers when compared to val/val alelle carriers. We provide evidence for the importance of the neurotrophic involvement in limbic and prefrontal connections. The met-allele of the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions associated with the UF, a tract known to be related to negative emotional-cognitive processing bias, declarative memory problems, and autonoetic self awareness., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes., Methods: Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography., Results: Twenty-one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the corpus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts., Limitations: Studying participants' strategies for coping with early-life adversity would have been helpful. Crossing fibres intracts are a general limitation of the method used., Conclusion: Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive-emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies.

Rising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants. The short- and long-term impact of donepezil was assessed using two double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiological measures (resting EEG power) that have demonstrated high-sensitivity to age-related cognitive decline. Experiment 1 tested the effects of 5 mg/per day dosage on cognitive and EEG markers at 6-hour, 2-week and 4-week follow-ups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5 mg dose. Experiment 1 found significant negative effects of donepezil on CPAL and resting Alpha and Beta band power. Experiment 2 replicated these results and found additional drug-related increases in the Delta band. EEG/fMRI analyses revealed that these oscillatory differences were associated with activity differences in the left hippocampus (Delta), right frontal-parietal network (Alpha), and default-mode network (Beta). We demonstrate the utility of simple cognitive and EEG measures in evaluating drug responses after acute and chronic donepezil administration. The presentation of previously established markers of age-related cognitive decline indicates that AChEIs can impair cognitive function in healthy older individuals. To our knowledge this is the first study to identify the precise neuroanatomical origins of EEG drug markers using simultaneous EEG/fMRI. The results of this study may be useful for evaluating novel drugs for cognitive enhancement.

Purpose: The primary purpose was to determine the prevalence of renal artery stenosis (RAS) in patients presenting with acute ("flash") pulmonary oedema (FPE), without identifiable cause using contrast-enhanced magnetic resonance angiography (CE-MRA) of renal arteries. A secondary goal was to correlate clinical parameters at presentation with the presence or absence of RAS., Materials and Methods: Patients presenting with acute pulmonary oedema without identifiable cause prospectively underwent CE-MRA. >50% renal artery stenosis was considered significant. Clinical parameters (blood pressure, serum creatinine, history of hypertension/hyperlipidaemia) were compared in patients with and without RAS using an unpaired t-test. Results expressed; mean (+/-SD)., Results: 20 patients (4 male, 16 female, age 78.5+/-11 years) underwent CE-MRA. 9 patients (45%) had significant RAS (6 (30%) bilateral, 3 (15%) unilateral). Systolic BP was higher in patients with RAS (192+/-38 mm Hg) than those without (134+/-30 mm Hg) (p<.005). Diastolic BP was higher in patients with RAS (102+/-23 mm Hg) than those without (76+/-17 mm Hg) (p<.01). All patients with RAS and 6/11(55%) patients without RAS had a history of hypertension. No significant difference in creatinine or hyperlipidaemia history was observed., Conclusion: The prevalence of RAS in patients presenting with FPE is 45%. The diagnosis should be considered in patients presenting with unexplained acute pulmonary oedema, particularly if hypertensive at presentation., (Copyright (c) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Whole-body imaging offers the promise of global disease assessment. This article reviews clinical status, and technical limitations and future prospects of this exciting technology. In particular, it describes technical aspects of magnetic resonance (MR) angiography, MR lymphography, and, in particular, total-body MR imaging., (Thieme Medical Publishers.)

Iliopsoas bursitis is a poorly recognized cause of hip pain that requires early recognition to avoid potentially serious complications caused by compression of adjacent structures. It can occur in the setting of trauma in athletes or those who engage in heavy labor and is also associated with acute or chronic arthritis. We describe the cases of 2 patients, one of whom developed a femoral neuropathy, while the other had marked venous compression of the lower limb resulting from enlargement of the iliopsoas bursa. Magnetic resonance imaging offers the most accurate information on the extent of the problem. Recalcitrant cases may require bursectomy in addition to treatment of the underlying cause.

Stroke, a major cause of death and disability in the developed world, is usually caused by atherosclerosis, most commonly an arterioocclusive lesion at the carotid bifurcation. Numerous multicentre trials have demonstrated that carotid endarterectomy can reduce the risk of stroke in these patients. However, because of the morbidity of catheter angiography coupled with the risks of surgery, the benefits outweigh the risks of surgery only for those with >70% carotid artery stenosis. The gold standard method for assessing the degree of stenosis is catheter-directed cerebral digital subtraction angiography; however, this is associated with a small but substantial stroke risk in addition to inherent risks associated with use of ionizing radiation and nephrotoxic contrast agents. The requirement for alternative imaging techniques that do not contribute to morbidity is ideally met by contrast-enhanced magnetic resonance angiography, which eliminates the need for direct catheterization and therefore eliminates stroke risk associated with a patient work-up. Advances in contrast-enhanced magnetic resonance angiography technology have led to a technique that achieves the goals of high spatial and temporal resolution required for stenosis assessment and streamlining of patients along surgical or medical lines. With the advent of a novel contrast agent, gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), which has a high relaxivity and an extended imaging time, improved diagnosis of carotid artery stenoses with magnetic resonance angiography can be expected. Gadofosveset trisodium facilitates improved first-pass imaging and also delays steady-state imaging with one injection. Although developed for vascular imaging, gadofosveset trisodium may also allow assessment of brain vascularity, blood-brain barrier breakdown and neurodegenerative disease.

Magnetic resonance angiography (MRA) provides a means of visualizing vascular structures noninvasively and is increasingly replacing conventional X-ray angiography in routine use. Contrast-enhanced MRA (CE-MRA), in which gadolinium contrast agents are used to shorten the T1 relaxation, offers increased resolution and higher signal-to-noise ratio compared with earlier flow-dependent [time-of-flight (TOF) or phase-contrast (PC)] techniques. Currently available contrast agents differ in their ability to lower T1 values, and hence the choice of contrast agent is an important consideration in the successful use of CE-MRA. Gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany) is the first of a new class of intravascular contrast agents. This agent is extensively (approximately 85%) and reversibly bound to human serum albumin and is retained within the vasculature thus allowing steady-state imaging to be perform-ed. An additional benefit is that gadofosveset offers higher relaxivity compared with other contrast agents, thus giving a lower blood T1 values which also makes it ideal for first-pass imaging. Clinical trials have consistently shown that gadofosveset enhanced MRA is more sensitive, specific and accurate than time-of-flight MRA, gives fewer uninterpretable scans and affords greater diagnostic confidence. Intravascular contrast agents such as gadofosveset, therefore, offer the potential for improved vascular imaging.

Discerning an underlying structure in the array of magnetic resonance (MR) imaging sequences and acronyms available is a bewildering task. Attempts have been made to present standard taxonomies of MR imaging sequences, primarily on the basis of their underlying physics. Despite this, it is difficult to usefully incorporate given taxonomies into routine clinical knowledge. The links, differences, and similarities among sequences are multidimensional and too complex for tabular presentation on the printed page. The authors present an interactive taxonomy of MR imaging sequences. With this graphical interface, the user can explore the changing relationships among a wide range of sequence types as they are viewed from different perspectives and through different associations, working through a natural learning process.