Single subject pharmacological-MRI (phMRI) study: Modulation of brain activity of psoriatic arthritis pain by cyclooxygenase-2 inhibitor

We use fMRI to examine brain activity for pain elicited by palpating joints in a single patient suffering from psoriatic arthritis. Changes in these responses are documented when the patient ingested a single dose of a selective cyclooxygenase-2 inhibitor (COX-2i). We show that mechanical stimulation of the painful joints exhibited a cortical activity pattern similar to that reported for acute pain, with activity primarily localized to the thalamus, insular, primary and secondary somatosensory cortices and the mid anterior cingulum. COX-2i resulted in significant decreased in reported pain intensity and in brain activity after 1 hour of administration. The anterior insula and SII correlated with pain intensity, however no central activation site for the drug was detected. We demonstrate the similarity of the activation pattern for palpating painful joints to brain activity in normal subjects in response to thermal painful stimuli, by performing a spatial conjunction analysis between these maps, where overlap is observed in the insula, thalamus, secondary somatosensory cortex, and anterior cingulate. The results demonstrate that one can study effects of pharmacological manipulations in a single subject where the brain activity for a clinical condition is delineated and its modulation by COX-2i demonstrated. This approach may have diagnostic and prognostic utility

Lack of effect of citalopram on magnetic resonance spectroscopy measures of glutamate and glutamine in frontal cortex of healthy volunteers

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide localised measures of brain chemistry in vivo. We previously found that healthy volunteers receiving the selective serotonin reuptake inhibitor, citalopram, daily for 1 week showed higher levels of a combined measure of glutamate and glutamine (Glx) in occipital cortex than those receiving placebo. The aim of this study was to assess if a similar effect could be detected in the frontal brain region. Twenty-three healthy volunteers randomised to receive either citalopram 20 mg or a placebo capsule daily for 7–10 days were studied and scanned using a 3T Varian INOVA system before and at the end of treatment. Standard short-TE (echo time) PRESS (Point-resolved spectroscopy) (TE = 26 ms) and PRESS-J spectra were acquired from a single 8-cm3 voxel in a frontal region incorporating anterior cingulate cortex. Glutamate and total Glx levels were quantified both relative to creatine and as absolute levels. Relative to placebo, citalopram produced no change in Glx or glutamate alone at the end of the study. Similarly, no effect was seen on other MRS measures studied: myo-inositol, choline, N-acetylaspartate and creatine. These data suggest that the effects of serotonin reuptake to modify cortical glutamatergic MRS measures may be regionally specific. This supports the potential for MRS in assessing neuroanatomically specific serotonin-glutamate interactions in the human brain

Encapsulation and sedimentation of nanomaterials through complex coacervation

Altres ajuts: the ICN2 is funded by the CERCA programme/Generalitat de Catalunya.Hypothesis: Nanoparticles removal from seawage water is a health and environmental challenge, due to the increasing use of these materials of excellent colloidal stability. Herein we hypothesize to reach this objective through complex coacervation, a straightforward, low-cost process, normally accomplished with non-toxic and biodegradable macromolecules. Highly dense polymer-rich colloidal droplets (the coacervates) obtained from a reversible charge-driven phase separation, entrap suspended nanomaterials, allowing their settling and potential recovery. Experiments: In this work we apply this process to highly stable aqueous colloidal dispersions of different surface charge, size, type and state (solid or liquid). We systematically investigate the effects of the biopolymers excess and the nanomaterials concentration and charge on the encapsulation and sedimentation efficiency and rate. This strategy is also applied to real laboratory water-based wastes. Findings: Long-lasting colloidal suspensions are succesfully destabilized through coacervate formation, which ensures high nanomaterials encapsulation efficiencies (~85%), payloads and highly tranparent supernatants (%T ~90%), within two hours. Lower polymer excess induces faster clearance and less sediments, while preserving effective nanomaterials removal. Preliminary experiments also validate the method for the clearance of real water residuals, making complex coacervation a promising scalable, low-cost and ecofriendly alternative to concentrate, separate or recover suspended micro/nanomaterials from aqueous sludges

Motion Robust Magnetic Susceptibility and Field Inhomogeneity Estimation Using Regularized Image Restoration Techniques for fMRI

In functional MRI, head motion may cause dynamic nonlinear field-inhomogeneity changes, especially with large out-of-plane rotations. This may lead to dynamic geometric distortion or blurring in the time series, which may reduce activation detection accuracy. The use of image registration to estimate dynamic field inhomogeneity maps from a static field map is not sufficient in the presence of such rotations. This paper introduces a retrospective approach to estimate magnetic susceptibility induced field maps of an object in motion, given a static susceptibility induced field map and the associated object motion parameters. It estimates a susceptibility map from a static field map using regularized image restoration techniques, and applies rigid body motion to the former. The dynamic field map is then computed using susceptibility voxel convolution. The method addresses field map changes due to out-of-plane rotations during time series acquisition and does not involve real time field map acquisitions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85944/1/Fessler233.pd

Hemodynamic Alterations in Vertebrobasilar Large Artery Disease Assessed by Arterial Spin-Labeling MR Imaging

BACKGROUND AND PURPOSE: VB artery stenosis is associated with a high risk of recurrent ischemic events, and knowledge about the hemodynamic relevance of VB stenosis is important for clinical decision making. In this study, multiple inflow pulsed ASL MR imaging was assessed for its ability to measure CBF and ATT in patients with VB disease

A method for determining venous contribution to BOLD contrast sensory activation

While BOLD contrast reflects haemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in down-weighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with high-resolution anatomical imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type (P veins ≈ grey matter > white matter. Mean delays displayed the same ranking across tissue types (P grey matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from grey matter in the absence of independent information of macroscopic vessels (ROC=0.72). Whilst tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map

Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline

Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF), it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200 mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10 mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS). Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti