Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T2‐weightings

Blood–brain barrier (BBB) permeability assessment remains of ongoing interest in clinical practice and research. Transitions between intravascular (IV) and extravascular (EV) gray matter (GM) compartments may provide information regarding the microstructural status of the BBB. Due to different transverse relaxation times (T₂ ) of water protons in vessels and GM, it is possible to determine the compartment in which these protons are located. This work presents and investigates the feasibility of a simplified analytical approach for compartmentalizing the proportions of magnetically marked water protons into IV and EV GM components by biexponentially modeling T₂ ‐weighted arterial spin labeling (ASL) data. Numerous model assumptions were used to stabilize the fit and achieve in vivo applicability. Particularly, transverse relaxation times of IV and EV water protons were determined from the analysis of two supporting T₂ ‐weighted ASL measurements, utilizing a monoexponential signal model. This stabilized a two‐parameter biexponential fit of ASL data with T₂ preparation (PLD = 0.9/1.2/1.5/1.8 s, TE_T2Prep = 0/30/40/60/80/120/160 ms), which thereby robustly provided estimates of the IV and EV compartment fractions. Experiments were conducted with three healthy volunteers in a 3 T scanner. Averaged over all subjects, the labeled water protons inherit T_2,IV = 200 ± 18 ms initially and adapt T_2,EV = 91 ± 2 ms with a longer retention time in cerebral structures. Accordingly, the EVlocated ASL signal fraction rises with increasing PLD from 0.31 ± 0.11 at the shortest PLD of 0.9 s to 0.73 ± 0.02 at the longest PLD of 1.8s. These results indicate a transition of the water protons from IV to EV space. The findings support the potential of biexponential modeling for compartmentalizing ASL spin fractions between IV and EV space. The novel integration of monoexponential parameter estimates stabilizes the two‐compartment model fit, suggesting that this technique is suitable for robustly estimating the BBB permeability in vivo.     

Neutrophil functions in morbidly obese subjects

The present study aimed to determine different peripheral blood neutrophil functions in 18 morbidly obese subjects with body mass index (BMI) ranging between 35 and 69 kg/m² in parallel with age‐ and gender‐matched lean controls. Peripheral blood neutrophil functions of obese subjects and matched lean controls were determined. Neutrophils of obese subjects showed significant elevation of the release of basal superoxides (P < 0·0001), formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐stimulated superoxides (P < 0·0001) and opsonized zymosan (OZ)‐stimulated superoxides (P < 0·045) compared with lean controls. Interestingly, there were no differences in phorbol myristate acetate (PMA)‐stimulated superoxide production by neutrophils of the obese subjects and controls. There was also a significant elevation of chemotactic (P < 0·0003) and random (P < 0·0001) migration of neutrophils from obese subjects compared with lean controls. Phagocytosis, CD11b surface expression and adherence of neutrophils from obese subjects were not significantly different from those of the lean controls. The elevated superoxide production and chemotactic activity, together with the normal phagocytosis and adherence, suggest that neutrophils from obese subjects are primed and have the capability to combat infections. However, neutrophils in the priming state may participate in the pathogenesis of obesity‐related diseases.     

Relationships between plasma leptin concentrations and human brain structure: a voxel-based morphometric study

We have previously demonstrated that obese people have reduced grey matter (GM) in several brain areas, including regions implicated in the regulation of taste (i.e., inferior frontal operculum and postcentral gyrus), reward (i.e., putamen), and behavioural processing (i.e., middle frontal gyrus), compared with their lean counterparts. It is well established that the brain may serve as a direct target for adiposity signals, one of the most important being leptin. We investigated the relationships between fasting plasma leptin concentrations and brain tissue composition in a group of 32 young adult Caucasians (12M/20F, age 32+/-1 years, body fat 29+/-1%, mean+/-S.E.) with normal glucose tolerance by using voxel-based morphometry of magnetic resonance imaging scans. Fasting plasma leptin concentrations were positively correlated with GM volumes of the left cerebellum and left inferior temporal gyrus and negatively associated with GM volumes of the left inferior frontal operculum, left postcentral gyrus, and right putamen (P<0.001, uncorrected for multiple comparisons) after adjustment for sex, percent body fat, age, fasting plasma insulin concentrations (i.e., the major determinants of plasma leptin), and global GM volume (thus allowing for an assessment of regional effects only). This study showed an independent, negative correlation between fasting plasma leptin concentrations, which are increased in obesity, and the volumes of GM in brain areas where obese people have reduced GM compared to their lean counterparts. These relationships may explain some of the abnormalities in brain morphology recently found to be associated with excess body fatness.     

Time‐efficient measurement of multi‐phase arterial spin labeling MR signal in white matter

White matter (WM) perfusion has great potential as a physiological biomarker in many neurological diseases. Although it has been demonstrated previously that arterial spin labeling magnetic resonance imaging (ASL‐MRI) enables the detection of the perfusion‐weighted signal in most voxels in WM, studies of cerebral blood flow (CBF) in WM by ASL‐MRI are relatively scarce because of its particular challenges, such as significantly lower perfusion and longer arterial transit times relative to gray matter (GM). Recently, ASL with a spectroscopic readout has been proposed to enhance the sensitivity for the measurement of WM perfusion. However, this approach suffers from long acquisition times, especially when acquiring multi‐phase ASL datasets to improve CBF quantification. Furthermore, the potential increase in the signal‐to‐noise ratio (SNR) by spectroscopic readout compared with echo planar imaging (EPI) readout has not been proven experimentally. In this study, we propose the use of time‐encoded pseudo‐continuous ASL (te‐pCASL) with single‐voxel point‐resolved spectroscopy (PRESS) readout to quantify WM cerebral perfusion in a more time‐efficient manner. Results are compared with te‐pCASL with a conventional EPI readout for both WM and GM perfusion measurements. Perfusion measurements by te‐pCASL PRESS and conventional EPI showed no significant difference for quantitative WM CBF values (Student's t‐test, p = 0.19) or temporal SNR (p = 0.33 and p = 0.81 for GM and WM, respectively), whereas GM CBF values (p = 0.016) were higher using PRESS than EPI readout. WM CBF values were found to be 18.2 ± 7.6 mL/100 g/min (PRESS) and 12.5 ± 5.5 mL/100 g/min (EPI), whereas GM CBF values were found to be 77.1 ± 11.2 mL/100 g/min (PRESS) and 53.6 ± 9.6 mL/100 g/min (EPI). This study demonstrates the feasibility of te‐pCASL PRESS for the quantification of WM perfusion changes in a highly time‐efficient manner, but it does not result in improved temporal SNR, as does traditional te‐pCASL EPI, which remains the preferred option because of its flexibility in use.     

Timing dependence of peripheral pulse‐wave‐triggered pulsed arterial spin labeling

Arterial spin labeling (ASL) has been developed into a useful technique that is capable of quantifying noninvasively local cerebral blood flow (CBF) using the water molecules in arterial blood as diffusible tracers. Pulsed ASL (PASL) is more strongly affected than continuous ASL (CASL) by cardiac pulsation, because the tag bolus is shorter than the cardiac cycle in most cases. No reports have yet clarified the effects of multiple cardiac phases on the quantification of CBF in PASL when triggering is used. Fourteen subjects participated in this study. Peripheral pulse‐wave‐triggered (PPWT)‐ASL was performed at various time points at the carotid artery (delay 0 ms, second point, foot, peak and tail) and compared with nontriggered (NT)‐ASL. Regions of interest (ROIs) were applied based on the anterior, middle and posterior cerebral artery (ACA, MCA, PCA) territories, and CBFs were compared among different time points and ROIs. PPWT‐ASL strongly affects CBF values compared with NT‐ASL in ACA and MCA territories, especially when measured at the foot of the carotid artery flow phase. CBF_NT was assumed to lie approximately between the minimum and maximum CBFs, with clear statistical significance in several ROIs at several time points of PPWT‐ASL, and CBF_NT was assumed to resemble ‘randomly triggered’ PPWT‐ASL. In conclusion, PPWT‐ASL strongly affects CBF values compared with NT‐ASL, particularly at the foot of the carotid artery flow in ACA and MCA territories. Copyright © 2013 John Wiley & Sons, Ltd.     

Thalamocortical circuits: fMRI assessment of the pulvinar and medial dorsal nucleus in normal volunteers

This fMRI study investigates the activation of the thalamic nuclei in a spatial focusing-of-attention task previously shown to activate the pulvinar with FDG-PET and assesses the connectivity of the thalamic nuclei with cortical areas. Normal right-handed subjects (eight men, eight women, average age=32 years) viewed four types of stimuli positioned to the right or left of the central fixation point (left hemifield-large letter, left hemifield-small letter display with flanking letters; right hemifield-large letter, right hemifield-small letter display with flankers). BOLD responses to small letters surrounded by flankers were compared with responses to large isolated letters. To examine maximum functional regional connectivity, we modeled "subject" as a random effect and attained fixed effect parameter estimates and t-statistics for functional connectivity between each of the thalamic nuclei (pulvinar, medial dorsal, and anterior) as the seed region and each non-seed voxel. Greater BOLD activation for letters surrounded by flankers than for large letters was observed in the pulvinar as anticipated and was also marked in the medial dorsal nucleus (MDN), anterior and superior cingulate (BA24 and BA24'), dorsolateral prefrontal cortex, and frontal operculum and insula. For the MDN, maximal functional connectivity was with the dorsolateral prefrontal cortex; correlations with left superior temporal, parietal, posterior frontal, and occipital regions were also observed. For the pulvinar, maximal functional connectivity was with parietal BA39; for anterior thalamus, with anterior cingulate.     

Improved arterial spin labeling method: applications for measurements of cerebral blood flow in human brain at high magnetic field MRI

Measurements of cerebral blood flow (CBF) with arterial spin labeling (ASL) MRI are challenging primarily due to a poor signal-to-noise (SNR) ratio. Therefore, methods that improve SNR and minimize measurement errors can play a significant role for better estimations of CBF. The purpose of this work was to develop an ASL method for measurements of CBF at high magnetic field strength. In the proposed multislice ASL method, using in-plane double inversion for labeling, stationary spins are kept at equilibrium to avoid T1 relaxation effects, while blood water is labeled using a lower magnetic field gradient. Improvement for CBF measurements is demonstrated on subjects and by comparison with other multislice ASL MRI methods at 1.5 Tesla. Furthermore, echo-planar imaging (EPI) and Turbo-FLASH (TFL) at 4 T MRI are compared for mapping CBF in human brain using various postlabeling delay times. CBF maps were obtained and analyzed within region-of-interests encompassing either gray matter or white matter. Elimination of T1 dependence of stationary spins in conjunction with avoidance of magnetization transfer mismatch between labeling and control scans lead to improved CBF measurements. Although measurements of CBF in brain tissue are feasible at 4 T using either EPI or TFL, TFL reduced contaminations from an intravascular signal and susceptibility-related artifacts, providing overall more robust CBF measurements than EPI. Therefore, the proposed ASL method in combination with TFL should be used for measuring CBF of human brain at 4T.     

Reliability and precision of pseudo‐continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O‐water PET in elderly subjects at risk for Alzheimer's disease

Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer's disease (AD). In the current study, we investigated the reliability and precision of a pseudo‐continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, one with AD and two with Mild Cognitive Impairment (MCI). Six of these elderly subjects including one AD, two MCIs and three controls also received ¹⁵O‐water positron emission tomography (PET) scans 2 h before their pcASL MR scan. The instrumental reliability of pcASL was evaluated with the intraclass correlation coefficient (ICC). The ICCs were greater than 0.90 in pcASL global perfusion measurements for both the young and the elderly groups. The cross‐modality perfusion imaging comparison yielded very good global and regional agreement in global gray matter and the posterior cingulate cortex. Significant negative correlation was found between age and the gray/white matter perfusion ratio (r = –0.62, p < 0.002). The AD and MCI patients showed the lowest gray/white matter perfusion ratio among all the subjects. The data suggest that pcASL provides a reliable whole brain CBF measurement in young and elderly adults whose results converge with those obtained with the traditional ¹⁵O‐water PET perfusion imaging method. pcASL perfusion MRI offers an alternative method for non‐invasive in vivo examination of early pathophysiological changes in AD. Copyright © 2009 John Wiley & Sons, Ltd.     

Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure

(+/?)3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an abused psychostimulant that produces strong monoaminergic stimulation and whole‐body hyperthermia. MDMA‐induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP‐3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA‐induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature‐sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethyl‐1,4,7,10‐tetraacetate (DOTMA^4?)). The MDMA‐induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA‐induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA‐induced warming across brain regions. MDMA‐induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Obesity predisposes to Th17 bias

Obesity is associated with numerous inflammatory conditions including atherosclerosis, autoimmune disease and cancer. Although the precise mechanisms are unknown, obesity‐associated rises in TNF‐α, IL‐6 and TGF‐β are believed to contribute. Here we demonstrate that obesity selectively promotes an expansion of the Th17 T‐cell sublineage, a subset with prominent pro‐inflammatory roles. T‐cells from diet‐induced obese mice expand Th17 cell pools and produce progressively more IL‐17 than lean littermates in an IL‐6‐dependent process. The increased Th17 bias was associated with more pronounced autoimmune disease as confirmed in two disease models, EAE and trinitrobenzene sulfonic acid colitis. In both, diet‐induced obese mice developed more severe early disease and histopathology with increased IL‐17⁺ T‐cell pools in target tissues. The well‐described association of obesity with inflammatory and autoimmune disease is mechanistically linked to a Th17 bias.     

Changes in cerebral endothelial barrier antigen, without alteration of permeability for intravenously injected leptin in diet-induced obesity in rats

Leptin, a potent anorectic, 16-kDa, adipose tissue-derived protein, predominantly acts in hypothalamic nuclei, signaling obesity and modulating ingestive behavior. To reach this brain area, leptin, probably has to cross the blood-brain barrier (BBB). In some cases of obesity, enhanced leptin levels in the blood do not result in anorectic effects, probably due to an altered leptin transport across the BBB. Therefore, we investigated the BBB in lean and diet-induced obese Lewis rats. To obtain information about the presence of microvessels with barrier dysfunction we examined three brain areas (hypothalamus, cortex, hippocampus) using a monoclonal antibody which detects intact microvessels of the BBB (anti-endothelial barrier antigen, anti-EBA). The results showed a significantly reduced EBA staining in the brain sections of the obese animals, except the hippocampus, compared to the control group. In a second step we injected I125-labeled leptin intravenously (i.v.) in permanent i.v.-cannulated, unrestrained Lewis rats (lean and obese). We measured the radioactivity in the cerebrospinal fluid after puncture of the cisterna magna, in the blood and brain tissue 90 min after injection. The leptin content in the cerebrospinal fluid and brain was not reduced in obese compared to lean rats, thus showing a similar transport capacity of the BBB in both experimental groups. Therefore, the results of the in vivo investigations do not indicate an impairment of the BBB in diet-induced obesity, despite the immunohistological findings. Further functional and morphological studies are necessary to evaluate the specific role of other organs and distinct forms of leptin (free and protein-bound) in the pathogenesis of diet-induced obesity.     

Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo‐continuous arterial spin labeling

Arterial spin labeling (ASL)‐MRI can noninvasively map cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), potential biomarkers of cognitive impairment and dementia. Mouse models of disease are frequently used in translational MRI studies, which are commonly performed under anesthesia. Understanding the influence of the specific anesthesia protocol used on the measured parameters is important for accurate interpretation of hemodynamic studies with mice. Isoflurane is a frequently used anesthetic with vasodilative properties. Here, the influence of three distinct isoflurane protocols was studied with pseudo‐continuous ASL in two different mouse strains. The first protocol was a free‐breathing set‐up with medium concentrations, the second a free‐breathing set‐up with low induction and maintenance concentrations, and the third a set‐up with medium concentrations and mechanical ventilation. A protocol with the vasoconstrictive anesthetic medetomidine was used as a comparison. As expected, medium isoflurane anesthesia resulted in significantly higher CBF and lower CVR values than medetomidine (median whole‐brain CBF of 157.7 vs 84.4 mL/100 g/min and CVR of 0.54 vs 51.7% in C57BL/6 J mice). The other two isoflurane protocols lowered the CBF and increased the CVR values compared with medium isoflurane anesthesia, without obvious differences between them (median whole‐brain CBF of 138.9 vs 131.7 mL/100 g/min and CVR of 10.0 vs 9.6%, in C57BL/6 J mice). Furthermore, CVR was shown to be dependent on baseline CBF, regardless of the anesthesia protocol used.     

Health‐related quality of life in physically active and sedentary obese women

The aim was to assess dimensions of health‐related quality of life (HRQL) in women attending an obesity clinic, and to rate differences in HRQL in those with the highest and lowest levels of physical activity (PA). The sample included 113 sedentary and 101 physically active subjects from a total sample of 375 overweight women 16–65 years, with a body mass index (BMI) ≥27.5 kg/m² consulting at an outpatient Endocrinology Clinic, and 82 lean female volunteers who served as a reference. Weight, height, body composition, PA, physical medical conditions, depression, body image, cognitive‐behavioral conceptualization of obesity, eating behavior, functional status, walking ability, exercise capacity, social functioning, and general health and perceived quality of life were assessed cross‐sectionally. The prevalence of medical conditions and depression was not statistically different (P<0.05) in sedentary and active women. In sedentary obese women, body attitude, walking ability, and aerobic fitness were poorer; the number of people to turn to for social support was smaller; physical attributions about the basis of the subjects obesity were less pronounced; and eating was more the consequence of external triggers or diffuse emotions than in physically active obese women (P<0.05). The findings indicate that a higher level of PA in an obese female clinical population was positively associated with diverse dimensions of HRQL. However, it was not possible to determine if these favorable aspects of HRQL are the cause or the consequence of a higher PA level. Am. J. Hum. Biol. 14:777–785, 2002. © 2002 Wiley‐Liss, Inc.     

Obesity augments the age-induced increase in mitochondrial capacity for H2O2 release in Zucker fatty rats

Aim: Mitochondrial dysfunction has been suggested to play a significant role in obesity and insulin resistance. The aim of the present study was to investigate if changes in obesity and insulin resistance were related to similar changes in mitochondrial capacity for hydrogenperoxide release in Zucker diabetic fatty rats and their lean littermates. Methods: Thirty‐four rats were used in this study. Rats were either lean or obese Zucker rats killed at 5–6 (young) or 12–14 (adults) weeks of age. Mitochondria were isolated from soleus muscles; respiration and release of hydrogenperoxide were determined and related to citrate synthase activity to determine intrinsic mitochondrial function. Mitochondrial‐specific super‐oxide dismuthase (MnSOD) protein content was determined in isolated mitochondria and muscle homogenate. Catalase protein content was determined in muscle homogenate. Results: Young lean and obese rats had a higher mitochondrial respiration when using palmitoyl‐l ‐carnitine as substrate compared with adult lean and obese rats. The obese strain had higher mitochondrial hydrogenperoxide release but only in the adult animals. In both lean and obese animals, increased age was associated with increased mitochondrial hydrogenperoxide release. MnSOD tended to be higher in the obese strain in the isolated mitochondria. Regardless of age, catalase protein content was significantly lower in the obese rats. Conclusions: This study shows that the augmented increase in obesity and insulin resistance seen in Zucker diabetic fatty rats is associated with increased capacity for mitochondrial hydrogenperoxide release.     

Comparison of T1 relaxation times in adipose tissue of severely obese patients and healthy lean subjects measured by 1.5 T MRI

Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in composition, endocrine function and localization in the body. VAT is considered to play a role in the pathogenesis of insulin resistance, type 2 diabetes, fatty liver disease, and other obesity‐related disorders. It has been shown that the amount, distribution, and (cellular) composition of adipose tissue (AT) correlate well with metabolic conditions. In this study, T₁ relaxation times of AT were measured in severely obese subjects and compared with those of healthy lean controls. Here, we tested the hypothesis that T₁ relaxation times of AT differ between lean and obese individuals, but also between VAT and SAT as well as superficial (sSAT) and deep SAT (dSAT) in the same individual. Twenty severely obese subjects (BMI 41.4 ± 4.8 kg/m²) and ten healthy lean controls matched for age (BMI 21.5 ± 1.9 kg/m²) underwent MRI at 1.5 T using a single‐shot fast spin‐echo sequence (short‐tau inversion recovery) at six different inversion times (T_I range 100–1000 ms). T₁ relaxation times were computed for all subjects by fitting the T_I‐dependent MR signal intensities of user‐defined regions of interest in both SAT and VAT to a model function. T₁ times in sSAT and dSAT were only measured in obese patients. For both obese patients and controls, the T₁ times of SAT (275 ± 14 and 301 ± 12 ms) were significantly (p < 0.01) shorter than the respective values in VAT (294 ± 20 and 360 ± 35 ms). Obese subjects also showed significant (p < 0.01) T₁ differences between sSAT (268 ± 11 ms) and dSAT (281 ± 19 ms). More important, T₁ differences in both SAT and VAT were highly significant (p < 0.001) between obese patients and healthy subjects. The results of our pilot study suggest that T₁ relaxation times differ between severely obese patients and lean controls, and may potentially provide an additional means for the non‐invasive assessment of AT conditions and dysfunction. Copyright © 2014 John Wiley & Sons, Ltd.     

MR fingerprinting ASL: Sequence characterization and comparison with dynamic susceptibility contrast (DSC) MRI

MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T₁ in a single scan. However, the previous reports have only demonstrated a proof‐of‐principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic‐susceptibility‐contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF‐ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improvements. Among the TR patterns tested, a sinusoidal pattern with a period of 125 TRs provided an overall best estimation in terms of spatial consistency. These experimental observations were consistent with those of numerical simulations. In the second study (N = 8), we compared MRF‐ASL results with those of DSC MRI. It was found that MRF‐ASL and DSC MRI provided highly comparable maps of cerebral blood flow (CBF) and bolus‐arrival‐time (BAT), with spatial correlation coefficients of 0.79 and 0.91, respectively. However, in terms of quantitative values, BAT obtained with MRF‐ASL was considerably lower than that from DSC (p < 0.001), presumably because of the differences in tracer characteristics in terms of diffusible versus intravascular tracers. Test–retest assessment of MRF‐ASL MRI revealed that the spatial correlations of parametric maps were 0.997, 0.962, 0.746 and 0.863 for B₁⁺, T₁, CBF, and BAT, respectively. MRF‐ASL is a promising technique for assessing multiple perfusion parameters simultaneously without contrast agent.     

GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance?

We have recently reported a progressive decline in the expression of glucose transporter isoform 4 (GLUT4) from control subjects through obese non-diabetics to obese type 2 diabetic subjects, indicating that the reduced GLUT4 in slow twitch fibres could be secondary to obesity. In this study we investigate the association of GLUT4 expression with the intracellular triglyceride (TG) content in the same muscle fibres and with plasma lipid parameters. We used histochemistry and stereology to study the relationship between TG content and GLUT4 expression in muscle fibres from obese, obese type 2 diabetic subjects, and young lean controls. TG density was significantly higher in slow compared to fast fibres in all studied subjects (p<0.05). We found an increased TG density in slow twitch fibres of obese diabetic subjects compared to obese (p<0.05) and lean controls (p<0.008). Intracellular TG densities in slow and fast fibres did not correlate with the corresponding GLUT4 density in the same fibres in our study groups (p>0.05). Plasma TG and FFA did not correlate with GLUT4 expression in slow or fast fibres (p>0.05). In conclusion, TG content was increased in diabetic slow fibres with a reduced GLUT4 expression. The GLUT4 expression was not associated with an increased intracellular triglyceride content or with increased plasma FFA levels. Thus, intracellular TG content and circulating FFA may not influence glucose transport directly through GLUT4 expression.     

一站式多模态平扫MR动态成像在急性脑卒中的应用及对缺血半暗带的早期干预效果

目的:探讨一站式多模态平扫MR动态成像在急性脑卒中的应用及对缺血半暗带的早期干预效果。方法:回顾性分析34例急性脑卒中患者影像资料。对比患者正常区域及病变区域的脑组织血流量（CBF）、造影剂平均峰值时间等参数。结果:弥散加权成像显示所有患者均有不同程度的高信号梗死灶,其中28例成像显示存在不同程度的狭窄与闭塞。在评价缺血半暗带方面,26例动态磁敏感对比增强（DSC）与磁共振动脉自旋标记（ASL）结果高度一致。8例患者两种检测结果不一致,ASL显示高灌注,而DSC显示正常灌注,DSC与ASL显示缺血半暗带无明显差异（P>0.05）。与正常对照区域各灌注成像参数相比,半暗带及梗死区域的中枢血容量（CBV）及CBF水平更低（P<0.05）,平均通过时间（MTT）水平更高（P<0.05）;与半暗带区域相比,梗死区域的CBF及CBV水平更低（P<0.05）,MTT水平更高（P<0.05）。结论:一站式平扫MR可快速准确评价急性缺血性脑卒中,为临床个性化治疗提供客观的影像学依据。     

Association of stress and depression with regional fat distribution in healthy middle-aged men

We examined whether the association of regional fat distribution with stress, defined in terms of vital exhaustion, and depression varies according to the total amount of body fat accumulation in healthy middle-aged men (n=64). Regional fat distribution was measured using the waist-to-hip circumference ratio (WHR), and the total amount of body fat accumulation was measured using the body mass index (BMI). The results indicate that WHR in lean men was associated with characteristics contrary to those in moderately obese men. In lean men WHR tended to be associated with a high level of stress, while in moderately obese men an association was found with a low level of stress and a low level of depressive symptomatology. The present results support the suggestion that there is a difference between abdominal obesity at different degrees of generalized obesity, and they are likely to further our understanding about the differing risk for cardiovascular disorders posed by abdominal obesity in lean men compared to abdominal obesity in moderately obese men.Partial support of this research by a grant to K. R. from Emil Aaltonen's Foundation and a grant to A. H. from Signe and Ane Gyllenberg Foundation is gratefully acknowledged.