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Journal of Cerebral Blood Flow & Metabolism最新文献

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Fluctuations in intracranial pressure can be estimated non-invasively using near-infrared spectroscopy in non-human primates 在非人类灵长类动物中,可以使用近红外光谱非侵入性地估计颅内压的波动
Pub Date : 2019-11-27 DOI: 10.1177/0271678X19891359
Alexander Ruesch, Samantha E. Schmitt, Jason Yang, Matthew A. Smith, J. Kainerstorfer
Intracranial pressure (ICP) is typically measured invasively through a sensor placed inside the brain or a needle inserted into the spinal canal, limiting the patient population on which this assessment can be performed. Currently, non-invasive methods are limited due to lack of sensitivity and thus only apply to extreme cases of increased ICP, instead of use in general clinical practice. We demonstrate a novel application for near-infrared spectroscopy (NIRS) to accurately estimate ICP changes over time. Using a non-human primate (Rhesus Macaque) model, we collected optical data while we induced ICP oscillations at multiple ICP levels obtained by manipulating the height of a fluid column connected via a catheter to the lateral ventricle. Hemodynamic responses to ICP changes were measured at the occipital pole and compared to changes detected by a conventional intraparenchymal ICP probe. We demonstrate that hemoglobin concentrations are highly correlated with induced ICP oscillations and that this response is frequency dependent. We translated the NIRS data into non-invasive ICP measurements via a fitted non-parametric transfer function, demonstrating a match in both magnitude and time alignment with an invasively measured reference. Our results demonstrate that NIRS has the potential for non-invasive ICP monitoring.
颅内压(ICP)通常是通过放置在脑内的传感器或插入椎管的针头进行侵入性测量的,这限制了可以进行这种评估的患者群体。目前,由于缺乏敏感性,非侵入性方法受到限制,因此仅适用于ICP增加的极端病例,而不是在一般临床实践中使用。我们展示了一种新的应用近红外光谱(NIRS)来准确地估计ICP随时间的变化。使用非人类灵长类动物(恒河猴)模型,我们收集光学数据,同时我们通过操纵通过导管连接到侧脑室的流体柱的高度来诱导多个ICP水平的ICP振荡。在枕极测量颅内压变化的血流动力学反应,并与常规脑实质内颅内压探头检测到的变化进行比较。我们证明血红蛋白浓度与诱导ICP振荡高度相关,并且这种反应是频率依赖性的。我们通过拟合的非参数传递函数将NIRS数据转换为非侵入性ICP测量,证明了与侵入性测量参考在量级和时间上的匹配。我们的研究结果表明,近红外光谱具有非侵入性ICP监测的潜力。
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引用次数: 14
Brain–kidney interaction: Renal dysfunction following ischemic stroke 脑肾相互作用:缺血性中风后的肾功能障碍
Pub Date : 2019-11-25 DOI: 10.1177/0271678X19890931
Qiang Zhao, T. Yan, M. Chopp, P. Venkat, Jieli Chen
Stroke is a leading cause of mortality and morbidity, with long-term debilitating effects. Accumulating evidence from experimental studies as well as observational studies in patients suggests a cross talk between the brain and kidney after stroke. Stroke may lead to kidney dysfunction which can adversely impact patient outcome. In this review article, we discuss the epidemiology and mechanisms of brain–kidney interaction following ischemic stroke. Specifically, we discuss the role of the central autonomic network, autoregulation, inflammatory and immune responses, the role of extracellular vesicles and their cargo microRNA, in mediating brain–kidney interaction following stroke. Understanding the bidirectional nature of interaction between the brain and kidney after cerebral injury would have clinical implications for the treatment of stroke and overall patient outcome.
中风是死亡率和发病率的主要原因,具有长期衰弱的影响。从实验研究和对患者的观察性研究中积累的证据表明,中风后大脑和肾脏之间存在串扰。中风可能导致肾功能不全,这可能对患者的预后产生不利影响。在这篇综述文章中,我们讨论了缺血性卒中后脑肾相互作用的流行病学和机制。具体来说,我们讨论了中枢自主神经网络的作用,自我调节,炎症和免疫反应,细胞外囊泡及其货物microRNA的作用,在脑卒中后介导脑肾相互作用。了解脑损伤后脑和肾之间相互作用的双向性质将对中风的治疗和患者的总体预后具有临床意义。
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引用次数: 33
Neurovascular coupling preserved in a chronic mouse model of Alzheimer’s disease: Methodology is critical 阿尔茨海默病慢性小鼠模型中保存的神经血管耦合:方法学至关重要
Pub Date : 2019-11-23 DOI: 10.1177/0271678X19890830
P. Sharp, K. Ameen-Ali, L. Boorman, S. Harris, S. Wharton, C. Howarth, O. Shabir, P. Redgrave, J. Berwick
Impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimer’s disease (AD), which could serve as an early biomarker of cerebral pathology. We have established an anaesthetic regime to allow repeated measurements of neurovascular function over three months in the J20 mouse model of AD (J20-AD) and wild-type (WT) controls. Animals were 9–12 months old at the start of the experiment. Mice were chronically prepared with a cranial window through which 2-Dimensional optical imaging spectroscopy (2D-OIS) was used to generate functional maps of the cerebral blood volume and saturation changes evoked by whisker stimulation and vascular reactivity challenges. Unexpectedly, the hemodynamic responses were largely preserved in the J20-AD group. This result failed to confirm previous investigations using the J20-AD model. However, a final acute electrophysiology and 2D-OIS experiment was performed to measure both neural and hemodynamic responses concurrently. In this experiment, previously reported deficits in neurovascular coupling in the J20-AD model were observed. This suggests that J20-AD mice may be more susceptible to the physiologically stressing conditions of an acute experimental procedure compared to WT animals. These results therefore highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.
神经血管耦合受损已被认为是阿尔茨海默病(AD)的早期致病因素,可作为大脑病理的早期生物标志物。我们建立了一个麻醉方案,允许在三个月内重复测量J20 AD小鼠模型(J20-AD)和野生型(WT)对照的神经血管功能。实验开始时,动物为9-12个月大。小鼠长期颅窗制备,通过二维光学成像光谱(2D-OIS)生成由须刺激和血管反应性挑战引起的脑血容量和饱和度变化的功能图。出乎意料的是,J20-AD组的血流动力学反应在很大程度上得以保留。这一结果未能证实先前使用J20-AD模型进行的调查。然而,最后进行急性电生理和2D-OIS实验,同时测量神经和血液动力学反应。在本实验中,我们观察到了先前报道的J20-AD模型中神经血管偶联的缺陷。这表明,与WT动物相比,J20-AD小鼠可能更容易受到急性实验过程的生理应激条件的影响。因此,这些结果强调了在确定人类疾病动物模型的特征时实验程序的重要性。
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引用次数: 14
Longitudinal study of cerebral blood flow regulation during exercise in pregnancy 孕期运动期间脑血流调节的纵向研究
Pub Date : 2019-11-21 DOI: 10.1177/0271678X19889089
Brittany A. Matenchuk, M. James, Rachel J. Skow, Paige K Wakefield, Christina M. MacKay, C. Steinback, Margie H. Davenport
Cerebrovascular adaptation to pregnancy is poorly understood. We sought to assess cerebrovascular regulation in response to visual stimulation, hypercapnia and exercise across the three trimesters of pregnancy. Using transcranial Doppler (TCD) ultrasound, middle and posterior cerebral artery mean blood velocities (MCAvmean and PCAvmean) were measured continuously at rest and in response to (1) visual stimulation to assess neurovascular coupling (NVC); (2) a modified Duffin hyperoxic CO2 rebreathe test, and (3) an incremental cycling exercise test to volitional fatigue in non-pregnant (n = 26; NP) and pregnant women (first trimester [n = 13; TM1], second trimester [n = 21; TM2], and third trimester [n = 20; TM3]) in total 47 women. At rest, MCAvmean and PETCO2 were lower in TM2 compared to NP. PCAvmean was lower in TM2 but not TM1 or TM3 compared to NP. Cerebrovascular reactivity in MCAvmean and PCAvmean during the hypercapnic rebreathing test was not different between pregnant and non-pregnant women. MCAvmean continued to increase over the second half of the exercise test in TM2 and TM3, while it decreased in NP due to differences in ΔPETCO2 between groups. Pregnant women experienced a delayed decrease in MCAvmean in response to maximal exercise compared to non-pregnant controls which was explained by CO2 reactivity and PETCO2 level.
脑血管对妊娠的适应尚不清楚。我们试图评估脑血管对视觉刺激、高碳酸血症和运动的反应。采用经颅多普勒超声(TCD)连续测量静息状态和视觉刺激下大脑中、后动脉平均血流速度(MCAvmean和PCAvmean),评估神经血管耦合(NVC);(2)改进的Duffin高氧CO2再呼吸试验,(3)非妊娠期自发性疲劳的增量循环运动试验(n = 26;NP)和孕妇(妊娠早期[n = 13;TM1],妊娠中期[n = 21;TM2],妊娠晚期[n = 20;TM3]),总共47名女性。休息时,与NP相比,MCAvmean和PETCO2的TM2较低。与NP相比,PCAvmean的TM2较低,而TM1和TM3较低。孕妇与非孕妇在高碳酸再呼吸试验中MCAvmean和PCAvmean脑血管反应性无差异。MCAvmean在运动试验的后半部分,在TM2和TM3中继续升高,而在NP中由于ΔPETCO2在组间的差异而降低。与未怀孕的对照组相比,孕妇在最大运动后MCAvmean的延迟下降是由二氧化碳反应性和PETCO2水平解释的。
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引用次数: 5
Brain atrophy in cerebral small vessel diseases: Extent, consequences, technical limitations and perspectives: The HARNESS initiative 脑血管疾病中的脑萎缩:程度、后果、技术限制和观点:HARNESS倡议
Pub Date : 2019-11-20 DOI: 10.1177/0271678X19888967
F. De Guio, M. Duering, F. Fazekas, F. de Leeuw, S. Greenberg, L. Pantoni, Agnès Aghetti, Eric E. Smith, J. Wardlaw, E. Jouvent
Brain atrophy is increasingly evaluated in cerebral small vessel diseases. We aim at systematically reviewing the available data regarding its extent, correlates and cognitive consequences. Given that in this context, brain atrophy measures might be biased, the first part of the review focuses on technical aspects. Thereafter, data from the literature are analyzed in light of these potential limitations, to better understand the relationships between brain atrophy and other MRI markers of cerebral small vessel diseases. In the last part, we review the links between brain atrophy and cognitive alterations in patients with cerebral small vessel diseases.
脑萎缩在脑血管疾病中的评价越来越高。我们的目标是系统地审查有关其范围,相关性和认知后果的现有数据。鉴于在这种情况下,脑萎缩的测量可能是有偏见的,审查的第一部分侧重于技术方面。因此,根据这些潜在的局限性,对文献数据进行分析,以更好地了解脑萎缩与脑血管疾病的其他MRI标志物之间的关系。在最后一部分,我们回顾脑萎缩和认知改变在脑血管疾病患者之间的联系。
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引用次数: 36
Predicting 15O-Water PET cerebral blood flow maps from multi-contrast MRI using a deep convolutional neural network with evaluation of training cohort bias 利用深度卷积神经网络预测多对比MRI 15O-Water PET脑血流量图,并评估训练队列偏差
Pub Date : 2019-11-13 DOI: 10.1177/0271678X19888123
Jia Guo, E. Gong, A. Fan, M. Goubran, M. Khalighi, G. Zaharchuk
To improve the quality of MRI-based cerebral blood flow (CBF) measurements, a deep convolutional neural network (dCNN) was trained to combine single- and multi-delay arterial spin labeling (ASL) and structural images to predict gold-standard 15O-water PET CBF images obtained on a simultaneous PET/MRI scanner. The dCNN was trained and tested on 64 scans in 16 healthy controls (HC) and 16 cerebrovascular disease patients (PT) with 4-fold cross-validation. Fidelity to the PET CBF images and the effects of bias due to training on different cohorts were examined. The dCNN significantly improved CBF image quality compared with ASL alone (mean ± standard deviation): structural similarity index (0.854 ± 0.036 vs. 0.743 ± 0.045 [single-delay] and 0.732 ± 0.041 [multi-delay], P < 0.0001); normalized root mean squared error (0.209 ± 0.039 vs. 0.326 ± 0.050 [single-delay] and 0.344 ± 0.055 [multi-delay], P < 0.0001). The dCNN also yielded mean CBF with reduced estimation error in both HC and PT (P < 0.001), and demonstrated better correlation with PET. The dCNN trained with the mixed HC and PT cohort performed the best. The results also suggested that models should be trained on cases representative of the target population.
为了提高基于MRI的脑血流量(CBF)测量的质量,我们训练了一个深度卷积神经网络(dCNN),将单延迟和多延迟动脉自旋标记(ASL)和结构图像结合起来,预测同时在PET/MRI扫描仪上获得的金标准15O-water PET CBF图像。dCNN在16名健康对照(HC)和16名脑血管病患者(PT)中进行了64次扫描训练和测试,并进行了4倍交叉验证。对PET脑血流图像的保真度和训练对不同队列的偏差影响进行了检查。与单独使用ASL相比,dCNN显著改善了CBF图像质量(平均值±标准差):结构相似性指数(0.854±0.036 vs. 0.743±0.045[单延迟]和0.732±0.041[多延迟],P < 0.0001);归一化均方根误差(0.209±0.039 vs. 0.326±0.050[单延迟]和0.344±0.055[多延迟],P < 0.0001)。dCNN在HC和PT的平均CBF估计误差均降低(P < 0.001),并且与PET的相关性更好。采用HC和PT混合队列训练的dCNN表现最好。研究结果还表明,应该根据代表目标人群的案例对模型进行训练。
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引用次数: 25
Characterizing pulsatility in distal cerebral arteries using 4D flow MRI 利用4D血流MRI表征脑远端动脉搏动性
Pub Date : 2019-11-13 DOI: 10.1177/0271678X19886667
Tomas Vikner, L. Nyberg, Madelene Holmgren, J. Malm, A. Eklund, A. Wåhlin
Recent reports have suggested that age-related arterial stiffening and excessive cerebral arterial pulsatility cause blood–brain barrier breakdown, brain atrophy and cognitive decline. This has spurred interest in developing non-invasive methods to measure pulsatility in distal vessels, closer to the cerebral microcirculation. Here, we report a method based on four-dimensional (4D) flow MRI to estimate a global composite flow waveform of distal cerebral arteries. The method is based on finding and sampling arterial waveforms from thousands of cross sections in numerous small vessels of the brain, originating from cerebral cortical arteries. We demonstrate agreement with internal and external reference methods and show the ability to capture significant increases in distal cerebral arterial pulsatility as a function of age. The proposed approach can be used to advance our understanding regarding excessive arterial pulsatility as a potential trigger of cognitive decline and dementia.
最近的报道表明,与年龄相关的动脉硬化和过度的脑动脉搏动导致血脑屏障破裂、脑萎缩和认知能力下降。这激发了人们对开发非侵入性方法来测量远端血管(更接近大脑微循环)脉搏的兴趣。在这里,我们报告了一种基于四维(4D)血流MRI的方法来估计大脑远端动脉的整体复合血流波形。该方法是基于在大脑皮层动脉的众多小血管的数千个横截面上发现和采样动脉波形。我们证明了内部和外部参考方法的一致性,并显示了捕捉远端脑动脉搏动性显著增加作为年龄函数的能力。所提出的方法可以用来促进我们对过度动脉搏动作为认知能力下降和痴呆的潜在触发因素的理解。
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引用次数: 20
The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms 线粒体钙单转运体对快速皮层网络节律的产生至关重要
Pub Date : 2019-11-13 DOI: 10.1177/0271678X19887777
C. Bas-Orth, Justus Schneider, A. Lewen, Jamie McQueen, K. Hasenpusch-Theil, T. Theil, G. Hardingham, H. Bading, O. Kann
The role of the mitochondrial calcium uniporter (MCU) gene (Mcu) in cellular energy homeostasis and generation of electrical brain rhythms is widely unknown. We investigated this issue in mice and rats using Mcu-knockout and -knockdown strategies in vivo and in situ and determined the effects of these genetic manipulations on hippocampal gamma oscillations (30–70 Hz) and sharp wave-ripples. These physiological network states require precise neurotransmission between pyramidal cells and inhibitory interneurons, support spike-timing and synaptic plasticity and are associated with perception, attention and memory. Absence of the MCU resulted in (i) gamma oscillations with decreased power (by >40%) and lower synchrony, including less precise neural action potential generation (‘spiking'), (ii) sharp waves with decreased incidence (by about 22%) and decreased fast ripple frequency (by about 3%) and (iii) lack of activity-dependent pyruvate dehydrogenase dephosphorylation. However, compensatory adaptation in gene expression related to mitochondrial function and glucose metabolism was not detected. These data suggest that the neuronal MCU is crucial for the generation of network rhythms, most likely by influences on oxidative phosphorylation and perhaps by controlling cytoplasmic Ca2+ homeostasis. This work contributes to an increased understanding of mitochondrial Ca2+ uptake in cortical information processing underlying cognition and behaviour.
线粒体钙单转运基因(MCU)在细胞能量稳态和脑电节律产生中的作用尚不清楚。我们在小鼠和大鼠体内和原位使用mcu敲除和敲低策略研究了这一问题,并确定了这些基因操作对海马伽马振荡(30-70 Hz)和尖锐波纹的影响。这些生理网络状态需要锥体细胞和抑制性中间神经元之间精确的神经传递,支持峰值定时和突触可塑性,并与感知、注意和记忆有关。MCU的缺失导致(i)伽马振荡功率降低(>40%),同步性降低,包括神经动作电位产生的准确性降低(“尖峰”),(ii)尖峰波发生率降低(约22%),快速波纹频率降低(约3%),以及(iii)缺乏活性依赖性丙酮酸脱氢酶去磷酸化。然而,与线粒体功能和糖代谢相关的基因表达的代偿性适应未被检测到。这些数据表明,神经元MCU对网络节律的产生至关重要,最可能的是通过影响氧化磷酸化和控制细胞质Ca2+稳态。这项工作有助于增加对皮层信息处理中潜在认知和行为的线粒体Ca2+摄取的理解。
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引用次数: 14
Low-level carbon monoxide exposure affects BOLD fMRI response 低浓度一氧化碳暴露影响BOLD fMRI反应
Pub Date : 2019-11-11 DOI: 10.1177/0271678X19887358
Caroline Bendell, S. Moosavi, M. Herigstad
Blood oxygen level dependent (BOLD) fMRI is a common technique for measuring brain activation that could be affected by low-level carbon monoxide (CO) exposure from, e.g. smoking. This study aimed to probe the vulnerability of BOLD fMRI to CO and determine whether it may constitute a significant neuroimaging confound. Low-level (6 ppm exhaled) CO effects on BOLD response were assessed in 12 healthy never-smokers on two separate experimental days (CO and air control). fMRI tasks were breath-holds (hypercapnia), visual stimulation and fingertapping. BOLD fMRI response was lower during breath holds, visual stimulation and fingertapping in the CO protocol compared to the air control protocol. Behavioural and physiological measures remained unchanged. We conclude that BOLD fMRI might be vulnerable to changes in baseline CO, and suggest exercising caution when imaging populations exposed to elevated CO levels. Further work is required to fully elucidate the impact on CO on fMRI and its underlying mechanisms.
血氧水平依赖(BOLD)功能磁共振成像(fMRI)是一种常用的技术,用于测量可能受到低水平一氧化碳(CO)暴露(例如吸烟)影响的大脑活动。本研究旨在探讨BOLD fMRI对CO的易感性,并确定其是否可能构成重大的神经影像学混淆。在两个单独的实验天(CO和空气控制)中,对12名健康的不吸烟者进行了低水平(6 ppm) CO对BOLD反应的影响评估。fMRI任务包括屏气(高碳酸血症)、视觉刺激和手指敲击。与空气控制方案相比,在CO方案中屏气、视觉刺激和手指敲击时,BOLD fMRI反应较低。行为和生理指标保持不变。我们得出结论,BOLD fMRI可能容易受到基线CO变化的影响,并建议在对暴露于高CO水平的人群进行成像时要谨慎。需要进一步的工作来充分阐明CO对fMRI的影响及其潜在机制。
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引用次数: 2
Test–retest characteristic of [18F]MK-6240 quantitative outcomes in cognitively normal adults and subjects with Alzheimer’s disease 认知正常成人和阿尔茨海默病患者[18F]MK-6240定量结果的重测特征
Pub Date : 2019-11-11 DOI: 10.1177/0271678X19887781
C. Salinas, Talakad G. Lohith, Ajay Purohit, A. Struyk, C. Sur, I. Bennacef, J. Beaver, L. Martarello
[18F]MK-6240 is a selective, high-affinity PET radiotracer for imaging neurofibrillary tangles (NFT) in Alzheimer’s disease (AD). Herein, we report test–retest (T–RT) reproducibility of [18F]MK-6240 in AD and healthy volunteers (HV). Twelve subjects with AD and three cognitively normal HV were enrolled in the study and dynamically scanned for 150 min with [18F]MK-6240 under a T–RT protocol. Two radioactivity doses were investigated: 165 ± 3 MBq (n = 6) and 300 ± 40 MBq (n = 9). Serial arterial blood samples were taken for each scan to obtain metabolite-corrected input functions. Following intravenous administration of [18F]MK-6240, the tracer rapidly partitioned into the brain and its heterogenous distribution pattern was consistent with known NFT pathology in AD. In contrast, uptake in HV was low and uniform across the brain parenchyma. Across all subjects, average T–RT variabilities in NFT-rich regions were ∼21%, ∼14% and ∼6% for various quantitative metrics: total distribution volume (VT), binding potential (BPND), and standardized uptake ratio (SUVR90–120), respectively. No significant differences in SUVR T–RT variability were observed between the high and low injected radioactivity groups (5.6% and 6.1%, respectively). This work suggests [18F]MK-6240 has adequate SUVR T–RT characteristics supporting the use of this outcome in future studies.
[18F]MK-6240是一种选择性的、高亲和力的PET放射性示踪剂,用于成像阿尔茨海默病(AD)的神经原纤维缠结(NFT)。在此,我们报告了[18F]MK-6240在AD和健康志愿者(HV)中的重测(T-RT)可重复性。12名AD患者和3名认知正常的HV患者被纳入研究,并在T-RT协议下用[18F]MK-6240动态扫描150分钟。研究了两种放射性剂量:165±3 MBq (n = 6)和300±40 MBq (n = 9)。每次扫描都要采集一系列动脉血液样本,以获得代谢物校正的输入函数。静脉注射[18F]MK-6240后,示踪剂迅速进入大脑,其异质性分布模式与已知的AD NFT病理一致。相比之下,HV在整个脑实质中的摄取低且均匀。在所有受试者中,nft丰富区域的平均T-RT变异率在各种定量指标上分别为~ 21%、~ 14%和~ 6%:总分布体积(VT)、结合电位(BPND)和标准化摄取比(SUVR90-120)。高、低注射放射性组间SUVR T-RT变异性无显著差异(分别为5.6%和6.1%)。这项研究表明[18F]MK-6240具有足够的SUVR T-RT特征,支持在未来的研究中使用这一结果。
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引用次数: 18
期刊
Journal of Cerebral Blood Flow & Metabolism
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