Yves Bureau

Quantification of pain-induced changes in cerebral blood flow by perfusion MRI

&NA; The purpose of this study was to assess if the functional activation caused by painful stimuli could be detected with arterial spin labeling (ASL), which is a non‐invasive magnetic resonance imaging (MRI) technique for measuring cerebral blood flow (CBF). Because ASL directly measures blood flow, it is well suited to pain conditions that are difficult to assess with current functional MRI, such as chronic pain. However, the use of ASL in neuroimaging has been hampered by its low sensitivity. Recent improvements in MRI technology, namely increased magnetic field strengths and phased array receiver coils, should enable ASL to measure the small changes in CBF associated with pain. In this study, healthy volunteers underwent two ASL imaging sessions, during which a painful thermal stimulus was applied to the left hand. The results demonstrated that the ASL technique measured changes in regional CBF in brain regions that have been previously identified with pain perception. These included bilateral CBF changes in the insula, secondary somatosensory, and cingulate cortices, as well as the supplementary motor area (SMA). Also observed were contralateral primary somatosensory and ipsilateral thalamic CBF changes. The average change in CBF for all regions of interest was 3.68 ml/100 g/min, ranging from 2.97 ml/100 g/min in ipsilateral thalamus to 4.91 ml/100 g/min in contralateral insula. The average resting global CBF was 54 ± 9.7 ml/100 g/min, and there was no change in global CBF due to the noxious thermal stimulus.

Stigma of Mental Illness-1: Clinical reflections

Although the quality and effectiveness of mental health treatments and services have improved greatly over the past 50 years, therapeutic revolutions in psychiatry have not yet been able to reduce stigma. Stigma is a risk factor leading to negative mental health outcomes. It is responsible for treatment seeking delays and reduces the likelihood that a mentally ill patient will receive adequate care. It is evident that delay due to stigma can have devastating consequences. This review will discuss the causes and consequences of stigma related to mental illness.

Redefining outcome measures in schizophrenia: integrating social and clinical parameters

Purpose of review Schizophrenia is a complex neurobehavioral disorder for which there are many promising new treatments. There is, however, a discrepancy in outcome measure reports when they are obtained from patients, relatives, caregivers, or professionals, making it difficult to determine the level of recovery. This lack of agreement may result from limitations of the measurement tools themselves, which are not comprehensive and may be measuring different aspects of outcome. Alternatively, it could be that the conceptual understanding of outcome and recovery require development. Recent findings For various reasons, patients assessed as ‘recovered’ remain excluded from mainstream society. We are of the opinion that present outcome measures do not capture real-life situations. We propose that the concept of recovery be carefully defined and the gold standard of outcome should incorporate social and clinical parameters. We attempt to redefine recovery. Patients who have shown clinical improvement do not necessarily do well in everyday situations even though there is obvious clinical improvement. Therefore, it has been repeatedly argued that a consensus of recovery should be determined and that routine clinical practice should then adapt to the agreed criteria. Summary We argue that the outcome measures should be multidimensional and consist of at least two parameters: clinical remission and social outcome.

Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction

BackgroundThe clinical application of stem cell therapy for myocardial infarction will require the development of methods to monitor treatment and pre-clinical assessment in a large animal model, to determine its effectiveness and the optimum cell population, route of delivery, timing, and flow milieu.ObjectivesTo establish a model for a) in vivo tracking to monitor cell engraftment after autologous transplantation and b) concurrent measurement of infarct evolution and remodeling.MethodsWe evaluated 22 dogs (8 sham controls, 7 treated with autologous bone marrow monocytes, and 7 with stromal cells) using both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also examined using immunohistochemistry for capillary density and presence of PKH26 labeled cells.ResultsIn vivo Indium imaging demonstrated an effective biological clearance half-life from the injection site of ~5 days. CMR demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging from 67–88% of baseline values with monocytes producing a significant treatment effect. Relative infarct shrinkage was similar through to 6 weeks in all groups, following which the treatment effect was manifest. There was a trend towards an increase in capillary density with cell treatment.ConclusionThis multi-modality approach will allow determination of the success and persistence of engraftment, and a correlation of this with infarct size shrinkage, regional function, and left ventricular remodeling. There were overall no major treatment effects with this particular model of transplantation immediately post-infarct.

Scan–rescan and intra-observer variability of magnetic resonance imaging of carotid atherosclerosis at 1.5 T and 3.0 T

Carotid atherosclerosis measurements for eight subjects at baseline and 14 +/- 2 days later were examined using 1.5 T and 3.0 T magnetic resonance imaging (MRI). A single observer blinded to field strength, subject and timepoint manually segmented carotid artery wall and lumen boundaries in randomized images in five measurement trials. Mean increases in the signal-to-noise ratios (SNR) for T1-weighted images acquired at 3.0 T compared to 1.5 T were 90% (scan) and 80% (rescan). Despite significantly improved SNR and contrast-to-noise ratios (CNR) for images acquired at 3.0 T, vessel wall volume (VWV) intra-observer variability was not significantly different using coefficients of variation (COV), and intraclass correlation coefficients (ICC). VWV interscan variability and consistency at both field strengths were not statistically different (1.5 T/3.0 T COV = 5.7%/7.8%, R(2) = 0.96 for 1.5 T and R(2) = 0.87 for 3.0 T). A two-way analysis of variance showed a VWV dependence on field strength but not scan timepoint. In addition, a paired t-test showed significant differences in VWV measured at 3.0 T as compared to 1.5 T. These results suggest that although images acquired at 1.5 T have lower SNR and CNR VWV, measurement variability was not significantly different from 3.0 T VWV and that VWV is field-strength dependent which may be an important consideration for longitudinal studies.

Liposomal-formulated curcumin [Lipocurc™] targeting HDAC (Histone Deacetylase) prevents apoptosis and improves motor deficits in Park 7 (DJ-1)-knockout rat model of Parkinson’s disease: implications for epigenetics-based nanotechnology-driven drug platform

Abstract Background: Converging evidence suggests dysregulation of epigenetics in terms of histone-mediated acetylation/deacetylation imbalance in Parkinson’s disease (PD). Targeting histone deacetylase (HDAC) in neuronal survival and neuroprotection may be beneficial in the treatment and prevention of neurodegenerative disorders. Few pharmacological studies use the transgenic model of PD to characterize the neuroprotection actions of a lead compound known to target HDAC in the brain. Methods: In our study, we investigated neuroprotective effects of liposomal-formulated curcumin: Lipocurc™ targeting HDAC inhibitor in the DJ-1(Park 7)-gene knockout rat model of PD. Group I (DJ-1-KO-Lipocurc™) received Lipocurc™ 20 mg/kg iv 3× weekly for 8 weeks; Group II: DJ-1 KO controls (DJ-1 KO-PBS) received i.v. phosphate-buffered saline (PBS). Group III: DJ-1-Wild Type (DJ-1 WT-PBS) received PBS. We monitored various components of motor behavior, rotarod, dyskinesia, and open-field behaviors, both at baseline and at regular intervals. Toward the end of the 8 weeks, we measured neuronal apoptosis and dopamine (DA) neuron-specific tyrosine hydroxylase levels by immunohistochemistry methods at post-mortem. Results: We found that DJ-KO Group I and Group II, as compared with DJ-1 WT group, exhibited moderate degree of motor impairment on the rotarod test. Lipocurc™ treatment improved the motor behavior motor impairment to a greater extent than the PBS treatment. There was marked apoptosis in the DJ-1 WT group. Lipocurc™ significantly blocked neuronal apoptosis: the apoptotic index of DJ-1-KO-Lipocurc™ group was markedly reduced compared with the DJ-KO-PBS group (3.3 vs 25.0, p<0.001). We found preliminary evidence Lipocurc™ stimulated DA neurons in the substantia nigra. The ratio of immature to mature DA neurons in substantia nigra was statistically higher in the DJ-1-KO-Lipocurc™ group (p<0.025). Conclusions: We demonstrated for the first time Lipocurc™’s anti-apoptotic and neurotrophic effects in theDJ-1-KO rat model of PD. Our promising findings warrant randomized controlled trial of Lipocurc™ in translating the novel nanotechnology-based epigenetics-driven drug discovery platform toward efficacious therapeutics in PD.

Measuring the neural response to continuous intramuscular infusion of hypertonic saline by perfusion MRI

To determine the extent to which arterial spin labeling (ASL), a functional magnetic resonance imaging technique that directly measures cerebral blood flow (CBF), is able to measure the neural activation associated with prolonged experimental muscle pain.

Prospective, randomized controlled assessment of the short‐ and long‐term efficacy of a hearing conservation education program in Canadian elementary school children

To assess the efficacy of a hearing conservation program in changing acoustic risk‐taking and hearing conservation behaviors in elementary school children.

The early postoperative course of surgical sleep apnea patients

Recent guidelines from the American Society of Anesthesiologists recommended postoperative monitoring for most patients undergoing surgery for obstructive sleep apnea (OSA). These guidelines, however, are largely based on retrospective literature and expert opinion. The appropriate level of postoperative monitoring remains controversial. Our objective was to prospectively document the early postoperative course of patients undergoing OSA surgery.

The relationship of carotid three-dimensional ultrasound vessel wall volume with age and sex: comparison to carotid intima-media thickness.

The relationship of three-dimensional ultrasound (3DUS)-derived carotid vessel wall volume (VWV) was evaluated with respect to age and sex. B-mode and 3DUS images were acquired for 316 subjects from diverse groups including obese primary prevention, diabetic nephropathy, renal transplant and rheumatoid arthritis populations. The relationship for intima-media thickness (IMT) and VWV with age and sex were determined using Pearson-product-moment correlations. Mean IMT (r = 0.18, p = 0.001) and VWV (r = 0.24, p < 0.01) correlated modestly with age. There were modest correlations in males (IMT, r = 0.19, p = 0.003; VWV, r = 0.34, p < 0.001) and in females for IMT and age (r = 0.30, p = 0.007) but not between 3DUS VWV and age in females (r = 0.10, p = 0.4). Significant associations between plaque and VWV (r = 0.36, p = 0.001) but not IMT suggest different correlations in females that may be attributed to plaque.