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Introduction\ud There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI.\ud \ud Methods\ud In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling.\ud \ud Results\ud Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P < .001). No serious adverse events were observed.\ud \ud Discussion\ud This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.

Objective Several studies have found an increase in hippocampal volume following electroconvulsive therapy (ECT), but the effect on cortical thickness has been less investigated. We aimed to examine the effects of ECT on cortical thickness and their associations with clinical outcome. Method Using 3 Tesla MRI scanner, we obtained T1-weighted brain images of 18 severely depressed patients at three time points: before, right after and 6 months after a series of ECT. The thickness of 68 cortical regions was extracted using Free Surfer, and Linear Mixed Model was used to analyze the longitudinal changes. Results We found significant increases in cortical thickness of 26 regions right after a series of ECT, mainly within the frontal, temporal and insular cortex. The thickness returned to the baseline values at 6-month follow-up. We detected no significant decreases in cortical thickness. The increase in the thickness of the right lateral orbitofrontal cortex was associated with a greater antidepressant effect, r = 0.75, P = 0.0005. None of the cortical regions showed any associations with cognitive side effects. Conclusion The increases in cortical thickness induced by ECT are transient. Further multimodal MRI studies should examine the neural correlates of these increases and their relationship with the antidepressant effect.

The neurological disturbances of migraine aura are caused by transient cortical dysfunction due to waves of spreading depolarization that disrupt neuronal signaling. The effects of these cortical events on intrinsic brain connectivity during attacks of migraine aura have not previously been investigated. Studies of spontaneous migraine attacks are notoriously challenging due to their unpredictable nature and patient discomfort. We investigated 16 migraine patients with visual aura during attacks and in the attack-free state using resting state fMRI. We applied a hypothesis-driven seed-based approach focusing on cortical visual areas and areas involved in migraine pain, and a data-driven independent component analysis approach to detect changes in intrinsic brain signaling during attacks. In addition, we performed the analyses after mirroring the MRI data according to the side of perceived aura symptoms. We found a marked increase in connectivity during attacks between the left pons and the left primary somatosensory cortex including the head and face somatotopic areas (peak voxel: P = 0.0096, (x, y, z) = (-54, -32, 32), corresponding well with the majority of patients reporting right-sided pain. For aura-side normalized data, we found increased connectivity during attacks between visual area V5 and the lower middle frontal gyrus in the symptomatic hemisphere (peak voxel: P = 0.0194, (x, y, z) = (40, 40, 12). The present study provides evidence of altered intrinsic brain connectivity during attacks of migraine with aura, which may reflect consequences of cortical spreading depression, suggesting a link between aura and headache mechanisms. Hum Brain Mapp 38:2635-2642, 2017. © 2017 Wiley Periodicals, Inc.

Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change in hippocampal volume. We tested the hypothesis that hippocampal texture has association to early cognitive loss beyond that of volumetric changes. The texture marker was trained and evaluated using T1‐weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and subsequently applied to score independent data sets from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) and the Metropolit 1953 Danish Male Birth Cohort (Metropolit). Hippocampal texture was superior to volume reduction as predictor of MCI‐to‐AD conversion in ADNI (area under the receiver operating characteristic curve [AUC] 0.74 vs 0.67; DeLong test, p = 0.005), and provided even better prognostic results in AIBL (AUC 0.83). Hippocampal texture, but not volume, correlated with Addenbrooke's cognitive examination score (Pearson correlation, r = −0.25, p

Background Imaging studies of patients with Tourette's syndrome (TS) across different cohorts have shown alterations in gray and white matter in areas associated with the cortico-striato-thalamic-cortical (CSTC) pathways; however, no consistent findings have subsequently established a clear indication of the pathophysiology of TS. Methods This study was designed to investigate changes in gray and white matter in medication-free children with TS in the CSTC areas. With MRI, 24 children with TS and 18 healthy controls were analyzed using three complementary methods. Results and Conclusion Analyses revealed no differences between controls and patients with TS in gray or white matter. Possible discrepancies between cohorts and methods may play a role in the different findings in other studies. Further studies investigating well-defined cohorts with TS analyzing both gray and white matter in the same cohort may add additional information to the pathophysiology of TS. © 2014 International Parkinson and Movement Disorder Society

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging.

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease.

Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp 35:3578–3587, 2014. © 2013 Wiley Periodicals, Inc.

Migraine sufferers with aura often report photosensitivity and visual discomfort outside of attacks and many consider bright or flickering light an attack-precipitating factor. The nature of this visual hypersensitivity and its relation to the underlying pathophysiology of the migraine aura is unknown. Using fMRI measurements during visual stimulation we examined the visual cortical responsiveness of patients with migraine with aura. We applied a within-patient design by assessing functional interhemispheric differences in patients consistently experiencing visual aura in the same visual hemifield. We recruited 20 patients with frequent side-fixed visual aura attacks (≥90% of auras occurring in the same visual hemifield) and 20 age and sex matched healthy controls and compared the fMRI blood oxygenation level dependent (BOLD) responses to visual stimulation between symptomatic and asymptomatic hemispheres during the interictal phase and between migraine patients and controls. BOLD responses were selectively increased in the symptomatic hemispheres. This was found in the inferior parietal lobule (P = 0.002), the inferior frontal gyrus (P = 0.003), and the superior parietal lobule (P = 0.017). The affected cortical areas comprise a visually driven functional network involved in oculomotor control, guidance of movement, motion perception, visual attention, and visual spatial memory. The patients also had significantly increased response in the same cortical areas when compared to controls (P < 0.05). We discovered a lateralized alteration of a visually driven functional network in patients with side-fixed aura. These findings suggest a hyperexcitability of the visual system in the interictal phase of migraine with visual aura.

Mental speed is a common concept in theories of cognitive aging, but it is difficult to get measures of the speed of a particular psychological process that are not confounded by the speed of other processes. We used Bundesen's (1990) Theory of Visual Attention (TVA) to obtain specific estimates of processing speed in the visual system controlled for the influence of response latency and individual variations of the perception threshold. A total of 33 non-demented old people (69-87 years) were tested for the ability to recognize briefly presented letters. Performance was analyzed by the TVA model. Visual processing speed decreased approximately linearly with age and was on average halved from 70 to 85 years. Less dramatic aging effects were found for the perception threshold and the visual apprehension span. In the visual domain, cognitive aging seems to be most clearly related to reductions in processing speed.

Purpose: To investigate the within and between subject variability of quantitative cerebral blood flow (CBF) measurements in normal subjects using various MRI techniques and positron emission tomography (PET). Materials and Methods: Repeated CBF measurements were performed in 17 healthy, young subjects using three different MRI techniques: arterial spin labeling (ASL), dynamic contrast enhanced T1 weighted perfusion MRI (DCE) and phase contrast mapping (PCM). All MRI measurements were performed within the same session. In 10 of the subjects repeated CBF measurements by 15O labeled water PET had recently been performed. A mixed linear model was used to estimate between subject (CVbetw) and within subject (CVwith) coefficients of variation. Results: Mean global CBF, CVbetw and CVwith using each of the four methods were for PCM 65.2 mL/100 g/min, 17.4% and 7.4%, for ASL 37.1 mL/100 g/min, 16.2% and 4.8%, for DCE 43.0 mL/100 g/min, 20.0%, 15.1% and for PET 41.9 mL/100 g/min, 16.5% and 11.9%, respectively. Only for DCE and PCM a significant positive correlation between measurements was demonstrated. Conclusion: These findings confirm large between subject variability in CBF measurements, but suggest also that in healthy subjects a subject-method interaction is a possible source of between subject variability and of method differences. J. Magn. Reson. Imaging 2012;35:1290–1299. © 2012 Wiley Periodicals, Inc.

To compare different electroencephalography (EEG)-based regressors and their ability to predict the simultaneously recorded blood oxygenation level dependent response during blocked visual stimulation, simultaneous EEG–functional magnetic resonance imaging in 10 healthy volunteers was performed. The performance of different single-trial EEG regressors was compared in terms of predicting the measured blood oxygenation level dependent response. The EEG-based regressors were the amplitude and latency of the primary positive (P1) and negative (N2) peaks of the visual evoked potential, the combined P1–N2 amplitude, and the alpha power. Apart from peak latencies, all regressors showed significant positive or negative correlation with the blood oxygenation level dependent response in visual cortex. In addition, several EEG-based regressors were found to predict blood oxygenation level dependent variations in different occipital and extraoccipital cortical areas not explained by the boxcar regressor. The results suggest that the P1–N2 regressor is the best EEG-based regressor to model the visual paradigm, but when looking for additional effects like habituation or attention modulation that cannot be modeled by the boxcar regressor, it is better to include regressors based on individual peaks or alpha power. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.

Introduction: Patients with dystrophinopathies show low levels of neuronal nitric oxide synthase (nNOS), due to reduced or absent dystrophin expression, as nNOS is attached to the dystrophin-associated protein complex. Deficient nNOS function leads to functional ischemia during muscle activity. Dystrophin-like proteins with nNOS attached have also been identified in the brain. This suggests that a mechanism of cerebral functional ischemia with attenuation of normal activation-related vascular response may cause changes in brain function. Methods: The aim of this study was to investigate whether the brain response of patients with Becker muscular dystrophy (BMD) is dysfunctional compared to that of healthy controls. To investigate a potential change in brain activation response in patients with BMD, median nerve somatosensory evoked stimulation, with stimulation durations of 2, 4, and 10 s, was performed while recording electroencephalography and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Results: Results in 14 male patients with BMD (36.2 ± 9.9 years) were compared with those of 10 healthy controls (34.4 ± 10.9 years). Compared to controls, the patients with BMD showed sustained cortical electrical activity and a significant smaller BOLD activation in contralateral primary somatosensory cortex and bilaterally in secondary somatosensory cortex. In addition, significant activation differences were found after long duration (10 s) stimuli in thalamus. Conclusion: An altered neurovascular response in patients with BMD may increase our understanding of neurovascular coupling and the pathogenesis related to dystrophinopathy and nNOS.

Assessment of vascular properties is essential to diagnosis and follow-up and basic understanding of pathogenesis in brain tumors. In this study, a procedure is presented that allows concurrent estimation of cerebral perfusion, blood volume, and blood-brain permeability from dynamic T1-weighted imaging of a bolus of a paramagnetic contrast agent passing through the brain. The methods are applied in patients with brain tumors and in healthy subjects. Perfusion was estimated by model-free deconvolution using Tikhonov's method (gray matter/white matter/tumor: 72 ± 16/30 ± 8/56 ± 45 mL/100 g/min); blood volume (6 ± 2/4 ± 1/7 ± 6 mL/100 g) and permeability (0.9 ± 0.4/0.8 ± 0.3/3 ± 5 mL/100 g/min) were estimated by using Patlak's method and a two-compartment model. A corroboration of these results was achieved by using model simulation. In addition, it was possible to generate maps on a pixel-by-pixel basis of cerebral perfusion, cerebral blood volume, and blood-brain barrier permeability. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc.

The partial volume effect (PVE) on the arterial input function (AIF) remains a major obstacle to absolute quantification of cerebral blood flow (CBF) using MRI. This study evaluates the validity and performance of a commonly used multiplicative rescaling of the AIF to correct for the PVE. In a group of six patients, perfusion imaging was performed using a T1-weighted approach that minimizes confounding susceptibility artifacts. Various degrees of PVE were induced on the AIF and subsequently corrected using four different schemes of multiplicative AIF rescaling. Our results show that a multiplicative rescaling is not always applicable and can introduce a CBF bias. An easily measurable quantity denoted the tissue signal fraction (TSF) is proposed as a measure of the applicability of a multiplicative rescaling. For the present CBF quantification method, a TSF of

Purpose To develop a method for the measurement of brain perfusion based on dynamic contrast-enhanced T1-weighted MR imaging. Materials and Methods Dynamic imaging of the first pass of a bolus of a paramagnetic contrast agent was performed using a 3T whole-body magnet and a T1-weighted fast field echo sequence. The input function was obtained from the internal carotid artery. An initial T1 measurement was performed in order to convert the MR signal to concentration of the contrast agent. Pixelwise and region of interest (ROI)-based calculation of cerebral perfusion (CBF) was performed using Tikhonov's procedure of deconvolution. Seven patients with acute optic neuritis and two patients with acute stroke were investigated. Results The mean perfusion value for ROIs in gray matter was 62 mL/100g/min and 21 mL/100g/min in white matter in patients with acute optic neuritis. The perfusion inside the infarct core was 9 mL/100g/min in one of the stroke patients. The other stroke patient had postischemic hyperperfusion and CBF was 140 mL/100g/min. Conclusion Absolute values of brain perfusion can be obtained using dynamic contrast-enhanced MRI. These values correspond to expected values from established PET methods. Furthermore, at 3T pixelwise calculation can be performed, allowing construction of CBF maps. J. Magn. Reson. Imaging 2008;27:754–762. © 2008 Wiley-Liss, Inc.

MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only, and longitudinal studies have often been hampered by standardization and reproducibility problems. Multi-slice echo-planar spectroscopic imaging (EPSI) is presented as a promising alternative to single-voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session, measurements of metabolites in specific brain areas chosen after image acquisition (e.g., normal-appearing white matter (NAWM), gray matter (GM), and lesions) can be obtained. The identification and exclusion of regions that are inadequate for spectroscopic evaluation in global assessments can significantly improve quality and reproducibility, as demonstrated by a low within-subject variance in healthy controls. The reproducibility of the technique makes it a promising tool for future longitudinal spectroscopic studies of MS.

Objective To explore the presence of changes resembling rheumatoid arthritis erosions and synovitis in metacarpophalangeal (MCP) and wrist joints of healthy individuals on magnetic resonance imaging (MRI) and to compare the MRI findings with conventional radiographic, clinical, and biochemical findings. Methods Twenty-eight healthy individuals were studied. Contrast-enhanced MRI and conventional radiography of the dominant wrist and second through fifth MCP joints were performed, coupled with standard clinical assessments and biochemical analyses. MR images were evaluated according to the latest OMERACT (Outcome Measures in Rheumatology Clinical Trials) recommendations with respect to synovitis, erosions, and bone marrow edema. Results Conventional radiography revealed erosion-like changes in 1 of 224 MCP joint bones (0.4%) and in 1 of 420 wrist joint bones (0.2%). MRI depicted low-grade erosion-like changes in 5 of 224 MCP joint bones (2.2%) and in 7 of 420 wrist joint bones (1.7%), but postcontrast enhancement within the lesion was detected in only 8.3% of these. MRI depicted low-grade synovitis-like changes in 10 of 112 MCP joints (8.9%) and in 8 of 84 assessed wrist areas (9.5%), while only minimal early synovial enhancement was detected by dynamic MRI. Three subjects had elevated serum levels of C-reactive protein, and these subjects displayed 44.5% of the synovitis-like changes and 41.7% of the erosion-like changes. Bone marrow edema–like changes were not found in any joints. Conclusion Changes resembling mild synovitis or small bone erosions are occasionally found in the MCP and wrist joints of healthy controls. Signs of synovitis on dynamic MRI, enhancement within bone erosion–like changes, and signs of bone marrow edema appear rarely or are absent in healthy controls. These signs may thus prove to be very specific in the distinction between arthritic and normal joints.

The volume of cortical activation as detected by functional magnetic resonance imaging (fMRI) in the visual cortex has previously been shown to be reduced following optic neuritis (ON). In order to understand the cause of this change, we studied the cortical activation, both the size of the activated area and the signal change following ON, and compared the results with results of neuroophthalmological testing. We studied nine patients with previous acute ON and 10 healthy persons served as controls using fMRI with visual stimulation. In addition to a reduced activated volume, patients showed a reduced blood oxygenation level dependent (BOLD) signal increase and a greater asymmetry in the visual cortex, compared with controls. The volume of visual cortical activation was significantly correlated to the result of the contrast sensitivity test. The BOLD signal increase correlated significantly to both the results of the contrast sensitivity test and to the Snellen visual acuity. Our results indicate that fMRI is a useful method for the study of ON, even in cases where the visual acuity is severely impaired. The reduction in activated volume could be explained as a reduced neuronal input; however, the greater asymmetry might point to a cortical reorganization as a consequence of neuronal damage. Future fMRI studies in ON will add to the understanding of the neural adaptive behaviour following ON.

neurofibrillary tangles than LOAD patients. However, these findings have not been substantiated in clinical studies. Studies using Positron Emission Tomography (PET) with carbon-11-labelled Pittsburgh compound-B (PiB) were not conclusive in replicating the post-mortem findings. A previous study suggested that iron accumulation, which may reveal AD pathology and more specifically amyloid deposition, is reflected by phase information from 7T T 2*-weighted MRI sequences. The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of AD pathology, between EOAD and LOAD patients using 7T MR phase images. Methods: 12 EOAD patients, 17 LOAD patients and 17 healthy elderly controls (table 1) were scanned at 7T using a 2D transverse T 2*-weighted scan with a total imaging duration of 10 minutes. MRI scans were analyzed quantitatively by measuring lobar peak-to-peak phase shifts in the frontal, parietal, and left and right temporoparietal regions. Cortical parcellation was performed on the T 2*-weighted images using the segmented cortex and an anatomical atlas (AAL atlas) (figure 1). The regional mean gray matter (GM)/ white matter (WM) contrast was computed as the difference between the mean phase value of the GM and WM ROIs. Results: An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p1⁄40.05) (table 2). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p

Clustering functional magnetic resonance imaging (fMRI) time series has emerged in recent years as a possible alternative to parametric modeling approaches. Most of the work so far has been concerned with clustering raw time series. In this contribution we investigate the applicability of a clustering method applied to features extracted from the data. This approach is extremely versatile and encompasses previously published results [Goutte et al., 1999] as special cases. A typical application is in data reduction: as the increase in temporal resolution of fMRI experiments routinely yields fMRI sequences containing several hundreds of images, it is sometimes necessary to invoke feature extraction to reduce the dimensionality of the data space. A second interesting application is in the meta‐analysis of fMRI experiment, where features are obtained from a possibly large number of single‐voxel analyses. In particular this allows the checking of the differences and agreements between different methods of analysis. Both approaches are illustrated on a fMRI data set involving visual stimulation, and we show that the feature space clustering approach yields nontrivial results and, in particular, shows interesting differences between individual voxel analysis performed with traditional methods. Hum. Brain Mapping 13:165–183, 2001. © 2001 Wiley‐Liss, Inc.

Changes in cerebral blood flow (CBF) induced by Acetazolamide (ACZ) were measured using dynamic susceptibility contrast MRI (DSC-MRI) with both spin echo (SE) EPI and gradient echo (GE) EPI, and related to changes in internal carotid artery (ICA) flow measured by phase-mapping. Also examined was the effect of repeated bolus injections. CBF, cerebral blood volume (CBV), and mean transit time (MTT) were calculated by singular value decomposition (SVD) and by deconvolution using an exponential function as kernel. The results showed no dependency on calculation method. GE-EPI measured a significant increase in CBF and CBV in response to ACZ, while SE-EPI measured a significant increase in CBV and MTT. CBV and MTT change measured by SE-EPI was sensitive to previous bolus injections. There was a significant linear relation between change in CBF measured by GE-EPI and change in ICA flow. In conclusion, GE-EPI under the present condition was superior to SE-EPI in monitoring cerebral vascular changes.J. Magn. Reson. Imaging 2001;14:391–400. © 2001 Wiley-Liss, Inc.

Most psychiatric research has focused on the identification of etiologic and prognostic factors for specific psychiatric diagnostic categories, in particular depression and schizophrenia. A limited number of studies have examined risk factors such as composite measures of cognitive ability (IQ) or mortality across different psychiatric diseases (1–3). Furthermore, although mental disorders seem to have their roots early in life (4,5), few studies have explored the influence of early life characteristics on these disorders over the life course and potential underlying mechanisms such as systemic inflammation (6). In a cohort of Danish men, we examined the impact of social, mental and physical characteristics assessed in childhood, young adulthood and midlife on the incidence of all psychiatric admissions and of schizophrenia, depression, alcohol and drug abuse. We further explored the influence of the above psychiatric diseases on inflammatory biomarkers and survival. The information used was extracted from birth registers (birth weight and father’s socioeconomic position); a school survey in 1965 (IQ); conscript examinations (IQ, education and body mass index); a health survey in 2004 (Major Depression Inventory, body mass index and smoking) (7); and a follow-up examination in 2010 (adult socioeconomic position, IQ, Major Depression Inventory, body mass index, smoking and inflammatory biomarkers) (8). Biomarkers included high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6 and IL-18, IL-10, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). Participants were recruited from the Metropolit cohort, consisting of 11,532 men born in 1953 in the Copenhagen Metropolitan area. Data from birth certificates were available for all members of the cohort. For 11,108 men, additional information was collected from conscript board examinations at about age 20 years. Further, 7,987 cohort members participated in a school-based survey in 1965 around age 12 years, and 6,292 were followed up by mailed questionnaire in 2004 around age 51 years (7). In 2010, around age 57 years, 7,799 cohort members living in the Eastern part of Denmark were invited to The Copenhagen Ageing Midlife Biobank, and 2,486 participated in a health examination including blood sampling and psychological tests (8). Information on any admission to a psychiatric ward from 1972 to 2009 was obtained by linkage with the Danish Psychiatric Central Registry. All-cause mortality was followed from 1968 to 2009 by register linkage with the Danish civil registration system. Data were analyzed using chi-square test, t-test, linear and Cox regression analysis in STATA version 12. Psychiatric admission was entered as time-dependent variable in the survival analysis. Of the cohort members, 1,640 (14.2%) had ever been admitted to a psychiatric ward between age 19 and 56 years. The most frequent diagnosis (34.5%) was alcohol or drug abuse, while 18.2% were diagnosed with schizophrenia and 17.1% had an affective disorder. Men with any psychiatric admission had lower socioeconomic position and lower IQ from childhood to middle age. They had lower mean birth weight and lower body mass index at age 20 and in middle age, and were more often smokers. In adjusted regression analysis, low IQ at age 20 increased the likelihood of developing schizophrenia (hazard ratio, HR per SD decrease = 1.39, 95% CI: 0.79-1.61), but decreased that of developing depression (HR per SD decrease = 0.81, 95% CI: 0.68-0.96). Birth weight and low education at age 20 were associated with alcohol or drug abuse (HR per 100 g increase = 0.98, 95% CI: 0.97-1.00; and HR low versus high = 1.51, 95% CI: 1.16-1.97, respectively). Among the 2,486 men who participated in the health examination in 2010, the 242 men with a psychiatric admission had significantly higher levels of hsCRP, IL-6 and IL-18, while IL-10, TNF-alpha and IFN-gamma were not associated with psychiatric morbidity. The regression coefficients for having any psychiatric admission were β = 0.37 (95% CI: 0.16-0.57) for hsCRP; β = 0.16 (95% CI: 0.02-0.30) for IL-6; and β = 0.09 (95% CI: 0.01-0.18) for IL-18. Analyses of the relation between psychiatric diagnosis and biomarkers showed that alcohol or drug abusers (β = 0.79, 95% CI: 0.42-1.17) and those with affective disorders (β = 0.44, 95% CI: 0.00-0.89) had higher levels of hsCRP. Men with an abuse diagnosis also had higher IL-6 levels (β = 0.52, 95% CI: 0.28-0.76). During the follow-up period, 1,392 (12.7%) of the 11,532 cohort members died. Of them, 511 (37%) had a psychiatric diagnosis. Men with a psychiatric admission had higher mortality rates at age 55 years (HR = 5.43, 95% CI: 4.76-6.20), after adjustment for early life characteristics. The analyses also showed increased mortality in all four psychiatric diagnostic categories. The highest HRs were observed for alcohol or drug abuse (8.23, 95% CI: 6.98-9.68) and schizophrenia (6.43, 95% CI: 5.20-8.12). These findings suggest that low birth weight, socioeconomic position and IQ early in life increase the risk of psychiatric disease, in particular of alcohol or drug abuse, in adult men. Alcohol or drug abuse is strongly associated with inflammatory biomarkers and poor survival.

By means of proton and phosphorous magnetic resonance spectroscopy at 1.5 Tesla the human cerebral metabolism was investigated during mild and moderate hypoxaemia. Seven volunteers participated and spectra were obtained while the subjects were breathing atmospheric air, 16, 12 and 10% oxygen in N2.PaO2, PCO2 and arterial oxygen saturation were determined during the spectroscopic measurements. Haemodynamic and respiratory mechanisms compensated the hypoxic condition and no lactate production was found. There was no change in N-acetyl-aspartate. No change in intracellular pH was found. A slight but non-significant decrease in PCr/P(i)-ratio was found, indicating a decrease in the phosphorylation potential of the brain in response to hypoxaemia. The brain sustains aerobic metabolism during mild to moderate hypoxaemia.

The effect of hypoxia (inspired oxygen fraction, FiO2 of 10% and 16%) and hyperoxia (FiO2) of 100%) on gradient echo images of the brain using long echo times was investigated in six healthy volunteers (age 24-28 years). Different flip angles were used with an FiO2 of 10% to assess the importance of saturation effects. The total cerebral blood flow was measured by a phase mapping technique during normoxia as well as hypoxia (FiO2 of 10% and 16%) and hyperoxia (FiO2 of 50% and 100%). High relative signal changes were found, independently of the flip angle, with FiO2 of 10%. With a flip angle of 40 degrees the values of delta R2* for cortical grey matter, central grey matter, white matter and the sagittal sinus were 0.79, 0.41, 0.26 and 3.00/s; with a flip angle of 10 degrees the corresponding values were 0.70, 0.37, 0.24 and 3.15/s. The total cerebral blood flow increased by 41% during inhalation of 10% O2 and decreased by 27% during 100% O2; no flow changes were seen during moderate changes in FiO2. It is concluded that flow effects play a minor role for fMRI signal strength in this application since (i) they did not abolish the signal changes caused by changes in blood oxygenation during hyper- and hypoxia, (ii) the observed signal changes were closely related to the changes in arterial oxygen saturation during hypoxia and (iii) the signal changes were little affected by changing the flip angle from 40 degrees to 10 degrees.

Longitudinal microradiography has been used to determine inhibiting effects of aluminum (III), Al, and fluoride on mineral loss from slices of bovine enamel exposed to a demineralizing solution 4 h daily for 35 days. Inhibitor treatment was 5 min four times daily. For the remaining time, the samples were immersed in a neutral calcium phosphate solution which allowed neither remineralization nor demineralization. This study indicates that a 1-mM (27 ppm) solution of Al in a 0.1-M lactate solution, pH 5, has an inhibitory effect on the in vitro demineralization of bovine enamel. Application of this solution alternating with 20 mM (380 ppm) fluoride gave the same total inhibition as treatment with 20 mM fluoride alone.

Masseter muscle autopsies were obtained from six different areas of six pigs. The autopsies were stained for the demonstration of myosin ATPase activity by means of a conventional histochemical technique. As compared with human masseter, the pig masseter muscle contained more type II fibers. But, like the human masseterMasseter muscle autopsies were obtained from six different areas of six pigs. The autopsies were stained, the pig muscle had a varying distribution of fiber types in the different autopsy areas, a distribution which might be the result of an adaptation to carry out special functions such as chewing, swallowing, and jaw posture. The fiber type distribution in the pig masseter also varied among individuals, probably reflecting various levels of utilization of the muscles besides different genetic influences. Moreover, pig masseter contained fibers of intermediate staining intensity (IM fibers), a fiber type rarely seen except in human masticatory muscles. In conclusion, we consider the pig masseter to be a useful animal model to study muscular adaptations to altered function in the orofacial region.

With the aim of gaining more insight into the monoaminergic regulation of spinal motor systems in the turtle, we have studied the distribution of 5-HT (5-HTir) and tyrosine hydroxylase immunoreactivity (THir) in the brainstem and spinal cord of Pseudemys scripta elegans. 5-HTir cell bodies were located in the midline in nucleus raphe inferior, nucleus raphe superior, and laterally in nuclei reticularis superior and inferior and nucleus reticularis isthmi. THir cell bodies were located in the commissural nucleus, nucleus tractus solitarii, the locus coeruleus-subcoeruleus complex, nuclei reticularis superior and inferior, the pretectal area, and substantia nigra. 5-HTir and THir tracts were found in lateral and ventral bundles superficially in the brainstem. 5-HTir fibers in the spinal cord were located in a large dorsolateral and a smaller ventrolateral tract. In the gray matter, a high concentration of 5-HTir fibers were observed in areas I-IV and in the lateral motor column of cervical and lumbar enlargements. Areas V-VIII and area X were less intensively innervated, with the lowest fibre concentration in areas VII-VIII and area X. Throughout the spinal cord, THir nerve fibres were located in the same areas but with a lower density. Small bipolar 5-HTir and THir cell bodies were found ventromedially to the central canal especially in cervical and lumbosacral segments. Large THir cells were found in area IX in the caudal sacral and coccygeal spinal cord. THir cerebrospinal fluid-contacting cells were also found in the most caudal part of the brainstem and the upper cervical spinal cord. The well developed spinal 5-HT system and the less developed THir system provides an anatomical explanation for the monoaminergic modulation of turtle motoneuron membrane properties, which has been observed in electrophysiological experiments.

A qualitative and quantitative histological study of the initial healing response adjacent to 24 submerged and non-submerged implants placed in the lower jaws of 6 monkeys is presented. The histomorphometric analysis showed no significant differences in mineralized bone-implant contact length between submerged and non-loaded non-submerged titanium implants. The infrabony defects around some of the implants on the radiographs were significantly correlated to the histological measurements. Qualitatively, a greater number of gingival inflammation cells and a longer junctional epithelium were seen adjacent to non-submerged implants without oral hygiene than were seen adjacent to non-submerged implants with oral hygiene in the initial healing period.

Background and purpose Functional neuroimaging studies have shown hyperresponsiveness of cortical areas to visual stimuli in migraine patients with aura outside of attacks. This may be a key feature in the initiation of aura episodes and possibly also migraine headache attacks. It is unknown if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate resting-state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging. Methods Forty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine were investigated. Following advanced denoising, the data were analyzed both in a hypothesis-driven fashion, testing for abnormalities involving 27 different brain areas of potential relevance to migraine with aura including the cortical visual areas, the amygdala and peri-aqueductal grey matter, and in a data-driven exploratory fashion (dual regression) in order to reveal any possible between-group differences of resting state networks. Age, gender, attack frequency and disease duration were included as nuisance variables. Results No differences of functional connectivity were found between patients and controls. Conclusions The previously reported increased cortical hyperresponsivity in the interictal phase of migraine with aura is unlikely to be caused by abnormalities of intrinsic brain connectivity. The interictal migraine aura brain may be abnormally functioning only during exposure to external stimuli.