Design and testing of microbubble‐based MRI contrast agents for gastric pressure measurement

Purpose: This work demonstrates specifically tailored microbubble‐based preparations and their suitability as MRI contrast agents for ingestion and measuring temporal and spatial pressure variation in the human stomach. Methods: Enhanced alginate spheres were prepared by incorporating gas‐filled microbubbles into sodium alginate solution followed by the polymerization of the mixture in an aqueous calcium lactate solution. The microbubbles were prepared with a phospholipid shell and perfluorocarbon gas filling, using a mechanical cavitational agitation regime. The NMR signal changes to externally applied pressure and coming from the enhanced alginate spheres were acquired and compared with that of alginate spheres without microbubbles. In vivo investigations were also carried out on healthy volunteers to measure the pressure variation in the stomach. Results: The MR signal changes in the contrast agent exhibits a linear sensitivity of approximately 40% per bar, as opposed to no measurable signal change seen in the control gas‐free spheres. This novel contrast agent also demonstrates an excellent stability in simulated gastric conditions, including at body temperature. In vivo studies showed that the signal change exhibited in the meal within the antrum region is between 5% and 10%, but appears to come from both pressure changes and partial volume artifacts. Conclusion: This study demonstrates that alginate spheres with microbubbles can be used as an MRI contrast agent to measure pressure changes. The peristaltic movement within the stomach is seen to substantially alter the overall signal intensity of the contrast agent meal. Future work must focus on improving the contrast agent's sensitivity to pressure changes

Activation induced changes in GABA: functional MRS at 7 T with MEGA-sLASER

Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non-invasively. However, only limited information on the dynamic functional response of γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation-induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies. The Mescher-Garwood-semi-localised by adiabatic selective refocusing (MEGA-sLASER) sequence was developed at 7 T to obtain the time course of GABA concentration without macromolecular contamination. A significant decrease (−12±5%) in the GABA to total creatine ratio (GABA/tCr) was observed in the motor cortex during a period of 10 minutes of hand-clenching, compared to an initial baseline level (GABA/tCr = 0.11±0.02) at rest. An increase in the Glx (glutamate and glutamine) to tCr ratio was also found, which is in agreement with previous findings. In contrast, no significant changes in NAA/tCr and tCr were detected. With consistent and highly efficient editing performance for GABA detection and the advantage of visually identifying GABA resonances in the spectra, MEGA-sLASER is demonstrated to be an effective method for studying of dynamic changes in GABA at 7 T

Effectiveness of 0.05% oxymetazoline (Vicks Sinex Micromist) nasal spray in the treatment of objective nasal congestion demonstrated to 12h post-administration by magnetic resonance imaging

Introduction: This study aimed to assess the qualitative and quantitative utility of MRI imaging to illustrate the magnitude and duration of the effect of a standard 100 μg dose of oxymetazoline in a commercially available formulation that also contains aromatic oils. Methods: This was a randomized, open label, single dose, parallel group study in 21 adult male and female subjects who reported moderate to severe nasal congestion due to acute upper respiratory tract infection or hay fever. MRI scans were acquired using a 3T Philips Achieva scanner with a 16 channel head receive coil. High resolution MRI scans of the nasal turbinates were obtained immediately prior to dosing (baseline) and at approximately 1, 8, 10, 11, and 12 hours after dosing. The efficacy variables of primary interest were inferior turbinate total volume at 8 and 12 hours post-dosing. The secondary efficacy variables analysed were inferior turbinate total volume at 1, 10, and 11 hours post-dosing, middle turbinate total volume at 1, 8, 10, 11, and 12 hours post-dosing. Results: Changes from baseline volumes measured for the inferior and middle turbinates of subjects receiving the oxymetazoline formulation showed significant (P<0.05) decreases at all times up to and including 12 hours post-administration. No significant decreases from baseline were detected in subjects receiving a sham ‘spray’ (untreated control - spray bottles with no spray solution). Statistical ANCOVA results of inferior and middle turbinate volume indicated significant differences (P<0.05) at all measurement points up to and including 12 hours post-administration between the oxymetazoline treatment group and the untreated control with the only exception the middle turbinate volume at 10 hours (P=0.0896). The significant changes were likely to be clinically relevant though this was not measured in the study. No AEs were reported during this study and no other safety evaluations were made. Conclusions: This study showed that MRI assessment of nasal congestion in human volunteers is a robust, repeatable and viable measurement technique. The application of a 100 µg Vicks Sinex Micromist® nasal decongestant (0.05% oxymetazoline solution) delivered a highly significant reduction in inferior and middle turbinate volumes compared with the application of a control, measurable by the MRI method up to and including a 12 hour post-dose scan

A Phase I/IIA Clinical Study With A Chimeric Mouse-Human Monoclonal Antibody To The V3 Loop Of Human Immunodeficiency Virus Type 1 Gp120

A phase I/IIA clinical trial with the chimeric mouse-human monoclonal antibody CGP 47 439 to the principal neutralization determinant in the V3 region of human immunodeficiency virus type 1 (HIV-1) strain IIIB envelope protein gp 120 is reported. The trial was an uncontrolled single-center, open-label, multidose tolerability, immunogenicity, and pharmacokinetic study in homosexual men with advanced HIV disease. Patient groups were formed on the basis of the reactivity of the antibody with the gp 120 of their HIV-1 isolates. Intravenous infusions of 1, 10, and 25 mg of antibody were followed by seven escalated doses of 50, 100, and 200 mg, every 3 weeks. The antibody was well tolerated; no toxicity was observed. Some patients showed a transient but insignificant antibody response to the antibody with no apparent adverse reactions or accelerated elimination of it. Substantial serum levels of the antibody were maintained with a mean t1/2β of 8-16 days. A virus burden reduction was observed in some patient

Effect of bread gluten content on gastrointestinal function : a crossover MRI study on healthy humans

Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0\ub702). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0\ub75) compared with GFB 3 (IQR 0\ub75); P=0\ub7003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food

Relationships between cortical myeloarchitecture and electrophysiological networks

The human brain relies upon the dynamic formation and dissolution of a hierarchy of functional networks to support ongoing cognition. However, how functional connectivities underlying such networks are supported by cortical microstructure remains poorly understood. Recent animal work has demonstrated that electrical activity promotes myelination. Inspired by this, we test a hypothesis that gray-matter myelin is related to electrophysiological connectivity. Using ultra-high field MRI and the principle of structural covariance, we derive a structural network showing how myelin density differs across cortical regions and how separate regions can exhibit similar myeloarchitecture. Building upon recent evidence that neural oscillations mediate connectivity, we use magnetoencephalography to elucidate networks that represent the major electrophysiological pathways of communication in the brain. Finally, we show that a significant relationship exists between our functional and structural networks; this relationship differs as a function of neural oscillatory frequency and becomes stronger when integrating oscillations over frequency bands. Our study sheds light on the way in which cortical microstructure supports functional networks. Further, it paves the way for future investigations of the gray-matter structure/function relationship and its breakdown in pathology

Ultra-high-field arterial spin labeling MRI for non-contrast assessment of cortical lesion perfusion in multiple sclerosis

ObjectivesAssess the feasibility of using an optimised ultra-high-field high-spatial-resolution low-distortion ASL MRI acquisition to measure focal haemodynamic pathology in cortical lesions (CLs) in Multiple Sclerosis (MS).MethodsTwelve MS patients (8 female, mean age=50; range=35-64 years) gave informed consent and were scanned on a 7 Tesla Philips Achieva scanner. Perfusion data were collected at multiple post-labeling delay times using a single-slice flow-sensitive alternating inversion recovery ASL protocol with a balanced steady-state free precession readout scheme. CLs were identified using a high-resolution Phase-Sensitive Inversion Recovery (PSIR) scan. Significant differences in perfusion within CLs compared to immediately surrounding normal appearing grey matter (NAGMlocal) and total cortical normal appearing grey matter (NAGMcortical) were assessed using paired t-tests.Results40 CLs were identified in PSIR scans that overlapped with the ASL acquisition coverage. After excluding lesions due to size or intravascular contamination, 27 lesions were eligible for analysis. Mean perfusion was 40 ± 25 ml/100g/min in CLs, 53 ± 12 ml/100g/min in NAGMlocal, and 53±8 ml/100g/min in NAGMcortical. CL perfusion was significantly reduced by 23 ± 9% (mean±SE, p=0.013) and 26 ± 9% (mean±SE, p=0.006) relative to NAGMlocal and NAGMcortical perfusion, respectively.ConclusionThis is the first ASL MRI study quantifying CL perfusion in MS at 7T, demonstrating that an optimised ASL acquisition is sensitive to focal haemodynamic pathology previously observed using Dynamic Susceptibility Contrast MRI. ASL requires no exogenous contrast agent, making it a more appropriate tool to monitor longitudinal perfusion changes in MS, providing a new window to study lesion development

Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique

Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI : comparison of split vs single dose

Peer reviewe