Resonance Imaging In Healthy Volunteers Research Articles

Evaluation of image registration algorithms for 3D phase-resolved functional lung ventilation magnetic resonance imaging in healthy volunteers and chronic obstructive pulmonary disease patients.

The purpose of the current study was to assess the influence of the registration algorithms on the repeatability of three-dimensional (3D) phase-resolved functional lung (PREFUL) ventilation magnetic resonance imaging (MRI). Twenty-three healthy volunteers and 10 patients with chronic obstructive pulmonary disease (COPD) underwent 3D PREFUL MRI during tidal breathing. The registration of dynamically acquired data to a fixed image was executed using single-step, stepwise, and group-oriented registration (GOREG) approaches. Advanced Normalization Tools (ANTs) and the Forsberg image-registration package were used for the registration. Image registration algorithms were tested for differences and evaluated by the repeatability analysis of ventilation parameters using coefficient of variation (CoV), intraclass-correlation coefficient, Bland-Altman plots, and correlation to spirometry. Also, the registration time and image quality were computed for all registration approaches. Very strong to strong correlations (r range: 0.917-0.999) were observed between ventilation parameters derived using various registration approaches. Median CoV values of the cross-correlation (CC) parameter were significantly lower (all p ≤ 0.0054) for ANTs GOREG compared with single-step and stepwise ANTs registration. The majority of comparisons between COPD patients and age-matched healthy volunteers showed agreement among the registration approaches. The repeatability of regional ventilation (RVent)-based ventilation defect percentage (VDPRVent ) and VDPCC was significantly higher (both p ≤ 0.0054) for Forsberg GOREG compared with ANTs GOREG. All 3D PREFUL-derived ventilation parameters correlated with forced expiratory volume in 1 s (FEV1 ) and the FEV1 / forced vital capacity (FVC) ratio (all |r| > 0.40, all p< 0.03). The image sharpness of RVent maps was statistically elevated (all p< 0.001) using GOREG compared with single-step and stepwise registration approaches using ANTs. The best computational performance was achieved with Forsberg GOREG. The GOREG scheme improves the repeatability and image quality of dynamic 3D PREFUL ventilation parameters. Registration time can be ~10-fold reduced to 9min using the Forsberg method with equal or even improved repeatability and comparable PREFUL ventilation results compared with the ANTs method.

The Level of Conus Medullaris in 629 Healthy Japanese Individuals.

The conus medullaris typically terminates at the L1 level; however, variations in its level and the factors associated with the conus medullaris level are unclear. We investigated the level of conus medullaris on magnetic resonance imaging in healthy volunteers. In total, 629 healthy adult volunteers (≥50 individuals of each sex and in each decade of age from 20 to 70) were enrolled. The level of the conus medullaris was assessed based on the T2-weighted sagittal magnetic resonance images, and factors affecting its level were investigated employing multivariate regression analysis including the participants’ background and radiographical parameters. L1 was the most common conus medullaris level. Participant height was significantly shorter in the caudally placed conus medullaris (p = 0.013). With respect to the radiographical parameters, pelvic incidence (p = 0.003), and pelvic tilt (p = 0.03) were significantly smaller in participants with a caudally placed conus medullaris. Multiple regression analysis showed that the pelvic incidence (p < 0.0001) and height (p < 0.0001) were significant factors affecting the conus medullaris level. These results indicated that the length of the spinal cord varies little among individuals and that skeletal differences affect the level of the conus medullaris.

Cerebrovascular effects of glibenclamide investigated using high-resolution magnetic resonance imaging in healthy volunteers

Glibenclamide inhibits sulfonylurea receptor (SUR), which regulates several ion channels including SUR1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel and ATP-sensitive potassium (KATP) channel. Stroke upregulates SURl-TRPM4 channel, which causes a rapid edema formation and brain swelling. Glibenclamide may antagonize the formation of cerebral edema during stroke. Preclinical studies showed that glibenclamide inhibits KATP channel-induced vasodilation without altering the basal vascular tone. The in vivo human cerebrovascular effects of glibenclamide have not previously been investigated. In a randomized, double-blind, placebo-controlled, three-way cross-over study, we used advanced 3 T MRI methods to investigate the effects of glibenclamide and KATP channel opener levcromakalim on mean global cerebral blood flow (CBF) and intra- and extracranial artery circumferences in 15 healthy volunteers. Glibenclamide administration did not alter the mean global CBF and the basal vascular tone. Following levcromakalim infusion, we observed a 14% increase of the mean global CBF and an 8% increase of middle cerebral artery (MCA) circumference, and glibenclamide did not attenuate levcromakalim-induced vascular changes. Collectively, the findings demonstrate the vital role of KATP channels in cerebrovascular hemodynamic and indicate that glibenclamide does not inhibit the protective effects of KATP channel activation during hypoxia and ischemia-induced brain injury.

Comparing the interobserver reproducibility of different regions of interest on multi-parametric renal magnetic resonance imaging in healthy volunteers, patients with heart failure and renal transplant recipients

ObjectiveTo assess interobserver reproducibility of different regions of interest (ROIs) on multi-parametric renal MRI using commercially available software.Materials and methodsHealthy volunteers (HV), patients with heart failure (HF) and renal transplant recipients (Tx) were recruited. Localiser scans, T1 mapping and pseudo-continuous arterial spin labelling (pCASL) were performed. HV and Tx also underwent diffusion-weighted imaging to allow calculation of apparent diffusion coefficient (ADC). For T1, pCASL and ADC, ROIs were drawn for whole kidney (WK), cortex (Cx), user-defined representative cortex (rep-Cx) and medulla. Intraclass correlation coefficient (ICC) and coefficient of variation (CoV) were assessed.ResultsForty participants were included (10 HV, 10 HF and 20 Tx). The ICC for renal volume was 0.97 and CoV 6.5%. For T1 and ADC, WK, Cx, and rep-Cx were highly reproducible with ICC ≥ 0.76 and CoV < 5%. However, cortical pCASL results were more variable (ICC > 0.86, but CoV up to 14.2%). While reproducible, WK values were derived from a wide spread of data (ROI standard deviation 17% to 55% of the mean value for ADC and pCASL, respectively). Renal volume differed between groups (p < 0.001), while mean cortical T1 values were greater in Tx compared to HV (p = 0.009) and HF (p = 0.02). Medullary T1 values were also higher in Tx than HV (p = 0.03), while medullary pCASL values were significantly lower in Tx compared to HV and HF (p = 0.03 for both).DiscussionKidney volume calculated by manually contouring a localiser scan was highly reproducible between observers and detected significant differences across patient groups. For T1, pCASL and ADC, Cx and rep-Cx ROIs are generally reproducible with advantages over WK values.

Cerebrovascular effects of endothelin-1 investigated using high-resolution magnetic resonance imaging in healthy volunteers

Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide released from vascular endothelium. ET-1 plays a major role in cerebrovascular disorders and likely worsens the outcome of acute ischaemic stroke and aneurismal subarachnoid haemorrhage through vasoconstriction and cerebral blood flow (CBF) reduction. Disorders that increase the risk of stroke, including hypertension, diabetes mellitus, and acute myocardial infarction, are associated with increased plasma levels of ET-1. The in vivo human cerebrovascular effects of systemic ET-1 infusion have not previously been investigated. In a two-way crossover, randomized, double-blind design, we used advanced 3 tesla MRI methods to investigate the effects of high-dose intravenous ET-1 on intra- and extracranial artery circumferences, global and regional CBF, and cerebral metabolic rate of oxygen (CMRO2) in 14 healthy volunteers. Following ET-1 infusion, we observed a 14% increase of mean arterial blood pressure, a 5% decrease of middle cerebral artery (MCA) circumference, but no effects on extracerebral arteries and no effects on CBF or CMRO2. Collectively, the findings indicate MCA constriction secondarily to blood pressure increase and not due to a direct vasoconstrictor effect of ET-1. We suggest that, as opposed to ET-1 in the subarachnoid space, intravascular ET-1 does not exert direct cerebrovascular effects in humans.

Tailoring Emulsions for Controlled Lipid Release: Establishing in vitro-in Vivo Correlation for Digestion of Lipids.

The use of oil-in-water emulsions for controlled lipid release is of interest to the pharmaceutical industry in the development of poorly water soluble drugs and also has gained major interest in the treatment of obesity. In this study, we focus on the relevant in vitro parameters reflecting gastric and intestinal digestion steps to reach a reliable in vitro-in vivo correlation for lipid delivery systems. We found that (i) gastric lipolysis determines early lipid release and sensing. This was mainly influenced by the emulsion stabilization mechanism. (ii) Gastric mucin influences the structure of charge-stabilized emulsion systems in the stomach, leading to destabilization or gel formation, which is supported by in vivo magnetic resonance imaging in healthy volunteers. (iii) The precursor structures of these emulsions modulate intestinal lipolysis kinetics in vitro, which is reflected in plasma triglyceride and cholecystokinin concentrations in vivo.

Measuring Cerebral Hypoperfusion Induced by Hyperventilation Challenge With Intravoxel Incoherent Motion Magnetic Resonance Imaging in Healthy Volunteers

The aim of this study was to demonstrate the feasibility to assess cerebral hypoperfusion with a hyperventilation (HV) challenge protocol using intravoxel incoherent motion (IVIM) magnetic resonance imaging. Magnetic resonance imaging experiments were performed on 10 healthy volunteers at 1.5 T, with a diffusion IVIM magnetic resonance imaging protocol using a set of b-values optimized by Cramer-Rao Lower Bound analysis. Hypoperfusion was induced by an HV maneuver. Measurements were performed in normoventilation and HV conditions. Biexponential curve fitting was used to obtain the perfusion fraction (f), pseudodiffusion coefficient (D*), and the product fD* in gray matter (GM) regions of interest (ROIs). Regional cerebral blood flow in the same ROIs was also assessed with arterial spin labeling. The HV challenge led to a diminution of IVIM perfusion-related parameters, with a decrease of f and fD* in the cerebellum (P = 0.03 for f; P = 0.01 for fD*), thalamus GM (P = 0.09 for f; P = 0.01 for fD*), and lenticular nuclei (P = 0.03 for f; P = 0.02 for fD*). Mean GM cerebral blood flow (in mL/100 g tissue/min) measured with arterial spin labeling averaged over all ROIs also decreased (normoventilation: 42.7 ± 4.1 vs HV: 33.2 ± 2.2, P = 0.004) during the HV challenge. The optimized IVIM protocol proposed in the current study allows for measurements of cerebral hypoperfusion that might be of great interest for pathologies diagnosis such as ischemic stroke.

Speech prosodic characteristics recorded by functional magnetic resonance imaging in healthy volunteers

Many mechanisms for the brain organization of speech processes remain poorly understood now. Objective : to assess the structural and functional organization of speech prosody, by applying functional magnetic resonance imaging (fMRI). This technique allows non-invasive studies of the organization of the speech system. Patients and methods. Using their proposed three paradigms, the authors evaluated speech prosody in healthy volunteers. The first paradigm was aimed to determine the intonation characteristics of a sentence; the second paradigm is to study the given accentuated and non-accentuated rhythms, and the third to recognize melodies. Results and discussion. In the first paradigm, there was bilateral activation of Wernicke's speech area (Brodmann's Area 22) that significantly prevailed in volume and intensity in the right hemisphere of the brain. Also, the right hemisphere predominantly showed activation of the supplementary motor region included in cytoarchitectonical Brodmann's Area 6. There was a significant activation Brodmann's Area 9 when a rhythm was determined in the right hemisphere and in Brodmann's Area 46 when melodies were recognized. The cerebellum, limbic system, subcortical structures, etc. were noted to be activated, which permits speech function to be regarded as a whole brain process. Conclusion. The investigation has confirmed that different regions of both hemispheres of the brain are involved in the systemic organization of speech, which enables the authors to speak about the codominance of the hemispheres in respect of this function. The presented paradigms fully meet the objectives of the study and can be used to map the prosodic characteristics of speech.

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis.

Hyperpolarized 129Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized 129Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15years, 11 boys) and 11 children with cystic fibrosis (ages 8-16years, 4 boys) underwent 129Xe MRI, receiving up to three doses of 129Xe gas prepared by either a commercially available or a homebuilt 129Xe polarizer. Subject heart rate and SpO2 were monitored for 2min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7days) post-MRI. All children tolerated multiple doses of 129Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO2 (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2min post inhalation SpO2 values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following 129Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of 129Xe MRI has been assessed in a small group of children as young as 6years. SpO2 changes were consistent with the expected physiological effects of a short anoxic breath-hold, and other mild side effects were consistent with the known anesthetic properties of xenon and with previous safety assessments of 129Xe MRI in adults. Hyperpolarized 129Xe is a safe and well-tolerated inhaled contrast agent for pulmonary MR imaging in healthy children and in children with cystic fibrosis who have mild to moderate lung disease.

Multiparametric Determination of Renal Hemodynamics and Oxygenation using Non‐Invasive Magnetic Resonance Imaging in Healthy Volunteers

PurposeDue to the risks associated with using contrast media in patients with impaired renal function there is clearly a need for non‐invasive techniques measuring renal blood flow (RBF) and oxygenation. Current techniques include arterial spin labelling (ASL), blood oxygen level‐dependent (BOLD) magnetic resonance imaging (MRI) and phase contrast (PC). In addition to needing thorough validation, it is also important to know if RBF and oxygenation are influenced by circadian rhythm. Therefore, we determined total and regional RBF and regional oxygenation in healthy volunteers as a function of time of day using these MRI.Methods and MaterialsTotal RBF was determined by PC in renal arteries, regional RBF by ASL and regional oxygenation by BOLD in 6 healthy volunteers every fourth hour for a total of 24 hours resulting in 6 repeated measurements in each individual.ResultsAverage total RBF was 898±10 ml/min and 893±27 ml/min for right and left kidney, respectively, with a drop during evening‐night but with significant individual variations. Average cortical RBF was 289±7 and 274±8 ml/min/100g for right and left kidney, respectively, with highest values during the day and lowest values during the evening‐night. Cortical oxygenation was 52±1 and 49±1 ms for right and left kidney, respectively, with minimal circadian variation.ConclusionNon‐invasive MRI is able to quantify also substile changes in RBF. Furthermore, these results demonstrate that RBF is influenced by circadian variations which should be considered when designing future studies in order to elucidate the role of deranged RBF regulation for the development of kidney disease.

Cardiac magnetic resonance imaging in healthy volunteers in normoxic and hypoxic exercise

Background Hypoxia induces pulmonary vasoconstriction leading to an increase in pulmonary vascular resistance and acute pulmonary hypertension (PH). It is known that with acute hypoxia, cardiac output (CO) is maintained with an increase in heart rate (HR) but a blunted stroke volume (SV) response. To our knowledge, the response of the healthy heart to acute pulmonary hypertension has not been studied using exercise cardiac magnetic resonance imaging (CMR). CMR is a highly reproducible and accurate method of evaluating biventricular function during exercise and can be used to measure real time physiological response to an increased cardiovascular workload. We aimed to study the ability of exercise magnetic resonance imaging to detect changes in right ventricular (RV) and left ventricular (LV) function during normoxic and hypoxic exercise.

Effect of DA-9701 on Gastric Motor Function Assessed by Magnetic Resonance Imaging in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial.

BackgroundImproving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI).MethodsForty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal.ResultsChanges in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures).ConclusionOur results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted.Trial RegistrationClinicalTrials.gov NCT02091635

OC-114 Effect of the low fodmap diet and oligofructose supplement on colonic volume, transit and fermentation: a double-blind randomised controlled trial using magnetic resonance imaging in healthy volunteers

Introduction Fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) have been shown to cause pain, bloating and flatulence in irritable bowel syndrome (IBS) which can be reduced by a low FODMAP diet. Pain and bloating could be caused by visceral distension. We have previously shown that giving a typical FODMAP, oligofructose (OF), 5 gm b.d. for one week increased fasted colonic volume (CV) by 18% when measured with magnetic resonance imaging (MRI). Our aim was to determine whether a) a low FODMAP diet reduces CV b) whether this effect could be abolished by OF but not a control, maltodextrin (MD). Method Design: A double-blind, parallel group, randomised controlled trial. 37 healthy subjects completed the study, 19 receiving OF and 18 MD. Procedures: fasting MRI and measurement of breath hydrogen (H2) and methane (CH4) at baseline and after one week of intervention. Food diaries were kept for one week before each MRI. 24 h before MRI subjects swallowed bespoke markers previously validated as a measure of GI transit. Interventions: All subjects followed the low FODMAP diet after advice from a registered dietitian. They were randomised (1:1) to supplement their diet with either MD or OF, 7 g twice daily. A standard food package (normal or low FODMAP) was provided for the 24 h preceding MRI. The study was powered to detect a 15% increase in CV on OF compared to MD. Results All results expressed as mean (95% CI). All participants complied with the diet and supplements. One subject (MD) was excluded from MRI analysis for corrupted images. Baseline CV was 673 mL (617–728). CV increased on the low FODMAP diet in both groups: OF 19.6% (6.5–32.7) and MD 15.5% (2.5–28.4). The difference between groups was not significant. Fasting breath H2rose significantly more on OF, by 16 ppm (–2–35) compared to baseline, than on MD which showed a fall of 11 ppm (3–18), p Conclusion The fall in breath H2on low FODMAP diet with MD, an effect which was reversed by OF, confirms previous studies.1,2CV increased on the low FODMAP diet, possibly because food substitutes for FODMAPs (e.g. tapioca, potato) contain substrate which can be utilised by colonic bacteria. Contrary to expectations a low FODMAP diet supplemented with MD did not cause a fall in colonic distension. The clinical benefit may be due to another mechanism, possibly related to changing microbiota. Disclosure of interest G. Major: None Declared, S. Krishnasamy: None Declared, C. Mulvenna: None Declared, S. Pritchard: None Declared, C. Hoad: None Declared, L. Marciani: None Declared, M. Lomer: None Declared, P. Gowland: None Declared, R. Spiller Grant/ Research Support from: Lesaffre, Ironwood, Norgine, Falk Pharma, Consultant for: Almirall, Astellas, Yuhan, Danone. References Ong, et al. 2010 Cani, et al. 2009

Controlled-release triple anti-inflammatory therapy based on novel gastroretentive sponges: Characterization and magnetic resonance imaging in healthy volunteers

The current work aimed to develop novel composite sponges of chitosan (CH)–chondroitin sulfate (CS) as a low-density gastroretentive delivery system for lornoxicam (LOR). This triple anti-inflammatory therapy-loaded matrices are expected to expand and float upon contact with gastric fluids for prolonged times. CH and CS solutions (3%, w/w) were prepared, mixed in different ratios, lyophilized, coated with magnesium stearate and compressed. The CH:CS interpolymer complex (IPC) was evaluated via FT-IR, DSC, and XRD. The compressed-sponges were evaluated for appearance, structure, porosity, pore diameter, density, wetting-time, floating characteristics, adhesion-retention, and LOR-release. The gastroretentivity of the best achieved magnetite-loaded sponges was monitored in healthy volunteers via MRI. The interaction between CH (protonated amino groups) and CS (anionic carboxylate/sulfate groups) proved IPC formation. DSC and XRD studies confirmed loss of LOR crystallinity. The sponges possessed interconnecting porous-network structures. The porosity, mean pore diameter, and bulk density of CH:CS (10:3) IPC sponges were 11.779%, 25.4nm, and 0.670g/mL, respectively. They showed complete wetting within seconds, gradual size-expansion within minutes and prolonged adhesion for hours. Controlled LOR-release profiles were tailored over 12h to satisfy individual patient needs. Monitoring of sponges via MRI proved their gastroretentivity for at least 5h.

Facilitation of Pain in the Human Spinal Cord by Nocebo Treatment

Nocebo hyperalgesia is an increase in subjective pain perception after a patient or subject underwent an inert treatment without any active ingredient. For example, verbal suggestion of increased pain can enhance both pain experience and responses in pain-related cortical brain areas. However, changes in cortical pain responses may be secondary to earlier amplification of incoming pain signals within the spinal cord. To test for a potential early enhancement of pain signals in the dorsal horn of the spinal cord, we combined a nocebo heat pain paradigm with spinal functional magnetic resonance imaging in healthy volunteers. We found that local application of an inert nocebo cream on the forearm increased pain ratings compared with a control cream, and also reduced pain thresholds on the nocebo-treated skin patch. On the neurobiological level, pain stimulation induced a strong activation in the spinal cord at the level of the stimulated dermatomes C5/C6. Comparing pain stimulation under nocebo to a control pain stimulation of the same physical intensity revealed enhanced pain-related activity in the ipsilateral dorsal horn of the spinal cord. Importantly, the activation of the main effect of pain and the nocebo effect spatially overlapped. The current study thus provides direct evidence for a pain-facilitating mechanism in the human spinal cord before cortical processing, which can be activated by cognitive manipulations such as nocebo treatments.

Unique Brain Areas Associated with Abstinence Control Are Damaged in Multiply Detoxified Alcoholics

BackgroundThe ability to abstain from drinking, despite incentives to imbibe, is essential to recovery from alcoholism.MethodsWe used an incentive conflict task to investigate ability to abstain from responding during presentations of incentive cues. Both alcoholic (n = 23) and healthy subjects (n = 22) were required to withhold responding during the simultaneous presentation of two visual stimuli in which the individual presentation allowed responding for monetary reward. Brain structures activated during performance of the task were studied using functional magnetic resonance imaging in healthy volunteers (n = 8), and changes in gray matter volume were studied in a separate group of patients (n = 29) compared with control subjects (n = 31) in regions of interest identified on functional magnetic resonance imaging.ResultsAbstinent alcoholic patients were severely impaired on the incentive conflict task. The impairment was greater in patients with experience of several versus a single detoxification. Healthy volunteers, during the same incentive conflict task, showed distinct patterns of brain activation (including gyrus rectus, ventromedial prefrontal cortex, and superior frontal gyrus). Reduction of gray matter volume in ventromedial prefrontal cortex and superior frontal gyrus of patients was more extensive in those with multiple detoxifications.ConclusionsPerformance deficits in alcoholics are associated with withdrawal-induced impairments in prefrontal subfields, which are exacerbated following repeated episodes of detoxification. Detoxification thus compromises functional and structural integrity of prefrontal cortex and may thus impair the ability to control future drinking. Performance in the incentive conflict task is a sensitive biomarker for such deficits.

Human amygdala reactivity is diminished by the β-noradrenergic antagonist propranolol

Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy of a β-noradrenergic receptor blockade with propranolol in the alleviation of anxiety symptoms and the secondary prevention of post traumatic stress disorder, preclinical evidence for a β-noradrenergic modulation of BLA activity in humans is missing. We combined functional magnetic resonance imaging in healthy volunteers with probabilistic mapping of intra-amygdalar responses to fearful, neutral and happy facial expressions to test the hypothesis that a β-noradrenergic receptor blockade with propranolol would inactivate the BLA. Consistent with our a priori hypothesis, propranolol diminished BLA responses to facial expressions, independent of their emotional valence. The absence of activity changes in probabilistically defined visual control regions underscores the specific action of propranolol in the BLA. Our findings provide the missing link between the anxiolytic potential of propranolol and the biological basis of β-noradrenergic activation in the human BLA as a key target for the pharmacological inhibition of anxiety neurocircuitry. Moreover, our findings add to emerging evidence that NE modulates both the reactivity (sensitivity) and the operating characteristics (specificity) of the BLA via β-noradrenergic receptors.

Whole-Body Magnetic Resonance Imaging of Healthy Volunteers: Pilot Study Results from the Population-Based SHIP Study

Approximately 4000 volunteers will undergo whole-body magnetic resonance imaging (WB-MRI) within the next 3 years in the population-based Study of Health in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the feasibility of adding a WB-MRI protocol to a large-scale population-based study, (b) to evaluate the reliability of standardized MRI interpretation, and (c) to establish an approach for handling pathological findings. The institutional review board approved the study, and oral and written informed consent was obtained from each participant. Two hundred healthy volunteers (99 women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol. The protocol was supplemented by contrast-enhanced cardiac MRI and magnetic resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography in 44 women (44.4%). MR scans were evaluated independently by two readers. Abnormalities were discussed by an advisory board and classified according to the need for further clinical work-up. One hundred ninety-four (97.0%) WB-MRI examinations were successfully completed in a mean scan time per subject of 90 minutes. There were 431 pathological findings in 176 (88%) of the participants. Of those 45 (10.4%) required further clinical work-up and 386 (89.6%) characterized as benign lesions did not. The interobserver agreement for the detection of pathological findings was excellent (kappa = 0.799). The preliminary results presented here indicate that a large prospective, population-based study using WB-MRI is feasible and that the results of image analysis are reproducible. A variety of positive findings provide valuable information regarding disease prevalence in a general adult population.

An Anatomical Study of the Parasacral Block Using Magnetic Resonance Imaging of Healthy Volunteers

The parasacral approach to sciatic blockade is reported to be easy to learn and perform, with a high success rate and few complications. Using magnetic resonance imaging, we evaluated the accuracy of a simulated needle (perpendicular to skin) in contacting the sacral plexus with this approach in 10 volunteers. Intrapelvic structures encountered during the simulated parasacral blocks were also recorded. The sacral plexus was contacted by the simulated needle in 4 of the 10 volunteers, and the sciatic nerve itself in one volunteer. The plexus was accurately located adjacent to a variety of visceral structures, including small bowel, blood vessels, and ovary. In the remaining five volunteers (in whom the plexus was not contacted on first needle pass), small bowel, rectum, blood vessels, seminal vesicles, and bony structures were encountered. Historically, when plexus is not encountered, readjustment of the needle insertion point more caudally has been recommended. We found that such an adjustment resulted in simulated perforation of intrapelvic organs or the perianal fossa. These findings question the reliability of the anatomical landmarks of the parasacral block and raise the possibility of frequent visceral puncture using this technique.

Time-resolved magnetic resonance angiography and flow-sensitive 4-dimensional magnetic resonance imaging at 3 Tesla for blood flow and wall shear stress analysis

In light of the ongoing discussion about flow-mediated arterial remodeling, it was the aim of this report to demonstrate the detailed assessment of 3-dimensional vascular hemodynamics by high-field magnetic resonance imaging in healthy volunteers and to illustrate its potential in comparison with results in a patient with stenosis. All examinations consisted of flow-sensitive 4-dimensional magnetic resonance imaging at 3 Tesla. Retrospective blood flow visualization and segmental quantification of wall shear stress and oscillatory shear index were performed. The results from 11 healthy individuals were compared with a 13-year-old patient with aortic stenosis who received a combined protocol with time-resolved 3-dimensional magnetic resonance angiography before and 5 and 9 months after intervention. Evaluation of normal blood flow characteristics demonstrated predominantly right-handed helical flow in the ascending aorta. Vortex formation was observed in 1 of 11 volunteers. Consistently high segmental wall shear stress was found along the circumference of the ascending aorta (average wall shear stress = 0.191 +/- 0.06 N/m(2)) and descending aorta (average 0.191 +/- 0.06 N/m(2)). Compared with volunteers, the patient revealed substantial flow changes proximal and distal to the stenosis. Blood flow alterations in the ascending aorta were also observed associated with changes in velocities and wall shear stress that gradually normalized after intervention. Flow-sensitive 4-dimensional magnetic resonance imaging at 3 Tesla can provide deeper insights into hemodynamic alterations in the diagnosis and follow-up of aortic pathologies. These findings indicate the potential of the methodology for the evaluation of effects of localized pathologies on the entire vascular system, which will have to be confirmed in future studies.