The z-spectrum from human blood at 7T

Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T1), which have been successfully used to study CEST effects in vivo. Full Bloch-McConnell fitting was also performed to provide an initial estimate of exchange rates and transverse relaxation rates of the various pools. CEST and NOE signals were observed at 3.5 ppm, -1.7ppm and -3.5 ppm and were found to originate primarily from the red blood cells (RBCs), although the amide proton transfer (APT) CEST effect, and NOEs showed no dependence upon oxygenation levels. Upon lysing, the APT and NOE signals fell significantly. Different pH levels in blood resulted in changes in both the APT and NOE (at -3.5ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra

Cerebrovascular and blood-brain barrier impairments in Huntington's disease: Potential implications for its pathophysiology: Vascular impairments in HD

ObjectiveAlthough the underlying cause of Huntington's disease (HD) is well established, the actual pathophysiological processes involved remain to be fully elucidated. In other proteinopathies such as Alzheimer's and Parkinson's diseases, there is evidence for impairments of the cerebral vasculature as well as the blood–brain barrier (BBB), which have been suggested to contribute to their pathophysiology. We investigated whether similar changes are also present in HD.MethodsWe used 3‐ and 7‐Tesla magnetic resonance imaging as well as postmortem tissue analyses to assess blood vessel impairments in HD patients. Our findings were further investigated in the R6/2 mouse model using in situ cerebral perfusion, histological analysis, Western blotting, as well as transmission and scanning electron microscopy.ResultsWe found mutant huntingtin protein (mHtt) aggregates to be present in all major components of the neurovascular unit of both R6/2 mice and HD patients. This was accompanied by an increase in blood vessel density, a reduction in blood vessel diameter, as well as BBB leakage in the striatum of R6/2 mice, which correlated with a reduced expression of tight junction‐associated proteins and increased numbers of transcytotic vesicles, which occasionally contained mHtt aggregates. We confirmed the existence of similar vascular and BBB changes in HD patients.InterpretationTaken together, our results provide evidence for alterations in the cerebral vasculature in HD leading to BBB leakage, both in the R6/2 mouse model and in HD patients, a phenomenon that may, in turn, have important pathophysiological implications. Ann Neurol 2015;78:160–17

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation

Meta-Analysis of Apparent Diffusion Coefficient in Pediatric Medulloblastoma, Ependymoma, and Pilocytic Astrocytoma

Background: Medulloblastoma, ependymoma, and pilocytic astrocytoma are common pediatric posterior fossa tumors. These tumors show overlapping characteristics on conventional MRI scans, making diagnosis difficult. Purpose: To investigate whether apparent diffusion coefficient (ADC) values differ between tumor types and to identify optimum cut-off values to accurately classify the tumors using different performance metrics. Study type: Systematic review and meta-analysis. Subjects: Seven studies reporting ADC in pediatric posterior fossa tumors (115 medulloblastoma, 68 ependymoma, and 86 pilocytic astrocytoma) were included following PubMed and ScienceDirect searches. Sequence and Field Strength: Diffusion weighted imaging (DWI) was performed on 1.5 and 3T across multiple institution and vendors. Assessment: The combined mean and standard deviation of ADC were calculated for each tumor type using a random-effects model, and the effect size was calculated using Hedge's g. Statistical Tests: Sensitivity/specificity, weighted classification accuracy, balanced classification accuracy. A P value 1.2 was considered to represent a large difference. Results: The mean (± standard deviation) ADCs of medulloblastoma, ependymoma, and pilocytic astrocytoma were 0.76 ± 0.16, 1.10 ± 0.10, and 1.49 ± 0.16 mm2/sec× 10−3. To maximize sensitivity and specificity using the mean ADC, the cut-off was found to be 0.96 mm2/sec× 10−3 for medulloblastoma and ependymoma and 1.26 mm2/sec× 10−3 for ependymoma and pilocytic astrocytoma. The meta-analysis showed significantly different ADC distributions for the three posterior fossa tumors. The cut-off values changed markedly (up to 7%) based on the performance metric used and the prevalence of the tumor types. Data Conclusion: There were significant differences in ADC between tumor types. However, it should be noted that only summary statistics from each study were analyzed and there were differences in how regions of interest were defined between studies. Evidence Level: 1. Technical Efficacy: Stage 3

Toward an exploration of feeling of strangeness in schizophrenia: perspectives on acousmatic and everyday listening

International audienceThe aim of this study was to investigate abnormal perceptual experiences in schizophrenia, in particular the feeling of strangeness, which is commonly found in patients' self-reports. The experimental design included auditory complex stimuli within 2 theoretical frameworks based on "sensory gating deficit" and "aberrant salience," inspired from conventional perceptual scales. A specific sound corpus was designed with environmental (meaningful) and abstract (meaningless) sounds. The authors compared sound evaluations on 3 perceptual dimensions (bizarre, familiar, and invasive) and 2 emotional dimensions (frightening and reassuring) between 20 patients with schizophrenia (SCZ) and 20 control participants (CTL). The perceptual judgment was rated on independent linear scales for each sound. In addition, the conditioning-testing P50 paradigm was conducted on 10 SCZ and 10 CTL. Both behavioral and electrophysiological data confirmed the authors' expectations according to the 2 previous theoretical frameworks and showed that abnormal perceptual experiences in SCZ consisted of perceiving meaningful sounds in a distorted manner and as flooding/inundating but also in perceiving meaningless sounds as things that become meaningful by assigning them some significance. In addition, the use of independent scales to each perceptual dimension highlighted an unexpected ambivalence on familiarity and bizarreness in SCZ compatible with the explanation of semantic process impairment. The authors further suggested that this ambivalence might be due to a conflicting coactivation of 2 types of listening, that is, every day and musical (or acousmatic) listening. (PsycINFO Database Record (c) 2011 APA, all rights reserved)

Effects of clozapine on perceptual abnormalities and sensory gating. a preliminary cross-sectional study in schizophrenia

International audienceThe aim of the present study was to investigate the effect of second-generation antipsychotics (clozapine or another second-generation antipsychotic) on perceptual abnormalities related to sensory gating deficit. Although clozapine is known to improve sensory gating assessed neuro- physiologically, we hypothesized that patients with schizophrenia treated with clozapine would report less perceptual abnormalities related to sen- sory gating deficit than patients treated with other second-generation anti- psychotics do. Forty patients with a diagnosis of schizophrenia were investigated (10 patients treated with clozapine and 30 patients treated with another second-generation antipsychotic drug). Perceptual abnor- malities were assessed with the Sensory Gating Inventory. Sensory gating was assessed through electroencephalogram with the auditory event- related potential method by measuring P50 amplitude changes in a dual click conditioning-testing procedure. Patients treated with clozapine pres- ent normal sensory gating and report less perceptual abnormalities related to sensory gating than patients treated with other second-generation anti- psychotics do. Although the cross-sectional design of this study is limited because causal inferences cannot be clearly concluded, the present study suggests clinical and neurophysiological advantages of clozapine com- pared with other second-generation antipsychotics and provides a basis for future investigations on the effect of this treatment on perceptual abnor- malities related to sensory gating deficit in patients with schizophrenia

Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)). The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively). In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress

Clinical characteristics of subjects included in lung parenchyma study.

<p>*p<0.05 between donor and spirometric GOLD 2–3 or GOLD 4 COPD,</p>#<p>p<0.05 between spirometric GOLD 2–3 and GOLD 4 COPD.</p

Expression of proteins involved in iron metabolism is altered in BAL cells obtained in subjects with COPD.

<p>Expression of proteins involved in iron metabolism in BAL cells collected in 8 non smokers without COPD, 8 smokers without COPD and 10 GOLD 1–3 COPD subjects was examined by RT-PCR.Three reference genes (GAPDH, HPRT1 and PPIA) were used for normalization. *p<0.05 (Anova analysis with a Tukey-Kramer post-hoc test), NS: non smokers.</p