Low-grade carotid artery stenosis is associated with progression of brain atrophy and cognitive decline. The SMART-MR study

Asymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease – Magnetic Resonance (SMART-MR) study without a history of cerebrovascular disease. LGCS was defined as 1–49% stenosis on baseline carotid ultrasound, whereas no LGCS (reference category) was defined as absence of carotid plaque. Brain and white matter hyperintensity (WMH) volumes and cognitive function were measured at baseline and after 4 (n = 480) and 12 years (n = 222) of follow-up. Using linear mixed-effects models, we investigated associations of LGCS with progression of brain atrophy, WMH, and cognitive decline. LGCS was associated with greater progression of global brain atrophy (estimate −0.03; 95%CI, −0.06 to −0.01; p = 0.002), and a greater decline in executive functioning (estimate −0.02; 95%CI, −0.031 to −0.01; p < 0.001) and memory (estimate −0.012; 95%CI, −0.02 to −0.001; p = 0.032), independent of demographics, cardiovascular risk factors, and incident brain infarcts on MRI. No association was observed between LGCS and progression of WMH. Our results indicate that LGCS may represent an early marker of greater future brain atrophy and cognitive decline.     

The bidirectional association between reduced cerebral blood flow and brain atrophy in the general population

The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV)=0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ⩾65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF=0.003 (95% CI −0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ⩾65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy.     

Failure of collateral blood flow is associated with infarct growth in ischemic stroke

Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion–diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion–diffusion mismatch (Spearman''s Rho 0.51, P<0.001) and smaller baseline diffusion lesion volume (Rho −0.70, P<0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute (P=0.02) and relative (P<0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho −0.68, P<0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute (P=0.003) and relative (P=0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.     

黄芪对大鼠脑缺血血脑屏障及脑血流的影响

利用大鼠局灶性脑缺血再灌流和全脑缺血再灌流损伤两种动物模型，观察黄芪注射液对脑缺血后再灌注期间血脑屏蔽及脑血流的保护作用。结果显示，与相庆对照组比较，不论是全脑缺血还是局灶性脑缺血１ｈ后再灌流３ｄ，应用黄芪的各组动物脑水肿明显减轻，血脑屏障通透性改善，大脑局部血流量显著增加。     

Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI.

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA.     

Total cerebral blood flow, white matter lesions and brain atrophy: the SMART-MR study.

We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58+/-10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0+/-10.2 mL/min per 100 mL, mean BPF was 79.2+/-2.9%, and mean VF was 2.03+/-0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.     

实验性脑出血血肿周围血流量变化的研究

目的　建立实验性脑出血的动物模型 ,探讨血肿周围的脑血流量变化。方法　采用犬脑内缓慢注入非肝素化自体血的方法建立实验性脑出血动物模型。用 1 4C- iodoantipyrine微示踪技术测定实验性脑出血 6 h、2 4 h、72 h血肿周围皮质、白质及对侧相应部位的脑血流量。结果　注血 6 h组、2 4 h组血肿周围白质的 CBF与对照组相比有所下降 ,但无统计学差异 ;而注血 72 h组血肿周围白质的 CBF较对照组降低了 19.8% (P<0 .0 5 ) ;注血 72 h组血肿对侧相应部位白质的 CBF较对照组升高了 14 .8% (P<0 .0 5 )。结论　犬脑内缓慢注入非肝素化自体血可建立可靠、重复性好的实验性 ICH动物模型 ,脑出血后 72 h,血肿周围白质的血流量下降 ,脑出血早期的脑损伤非缺血所致。     

Laser Doppler monitoring of cerebral blood flow

Abstract

The clinical management of cerebral hemodynamic status has become more important, as well as more complex, in recent years. In response", monitoring systems for neurological patients have grown increasingly sophisticated. Unfortunately the capability of monitoring cerebral blood flow is absent in commercially available monitoring systems at this time. Various investigators have demonstrated that laser Doppler systems are capable of meeting this need. We present here a summary of laser Doppler technology and also a review of the progress in application of this technology to provide meaningful input for clinical decision making. Recent clinical experience and advances in instrumentation design suggest that laser Doppler monitoring of cerebral blood flow may soon become routine in neurological intensive care settings. [Neurol Res 1996; 18: 251–255]     

Association of homocysteine with ventricular dilatation and brain atrophy in Parkinson's disease

Parkinson's disease (PD) patients are treated with levodopa (l ‐dopa) to help stabilize their impaired motor abilities; however, l ‐dopa leads to increased homocysteine (Hcy) levels, which may have a deleterious effect on brain structure and function. The purpose of this study was to examine the impact of increased Hcy concentration on global brain atrophy as determined by magnetic resonance imaging in PD patients and controls. The effect of high Hcy level on ventricular dilatation (percentage of intracranial volume [%ICV]) and total tissue volume (%ICV) was examined at baseline and longitudinally at 36 months. Age, sex, education, and l ‐dopa duration (in PD patients) were included as covariates. Elevated Hcy levels correlated positively with ventricular dilatation (%ICV) in the whole sample (P = 0.004) and in the PD group (P = 0.008). At baseline, adults with a high Hcy level (>14 μmol/L) had higher ventricular volume (%ICV) than adults with a low Hcy level (≤14 μmol/L) in the whole sample (P = 0.006) and in the PD group (P = 0.03), which persisted over 36 months in both the whole sample (P = 0.004) and the PD group (P = 0.03). PD patients with high Hcy concentrations had a greater rate of ventricular enlargement (%ICV) over time compared with those with low Hcy concentration (P = 0.02). Elevated Hcy concentration was associated with increased ventricular dilatation (%ICV) in PD patients. A larger sample with a broader age range and longer follow‐up is needed to establish the consequences of high Hcy level, including interactions with genetic and environmental risk factors, in PD. © 2014 International Parkinson and Movement Disorder Society     

Cerebral blood flow is an earlier indicator of perfusion abnormalities than cerebral blood volume in Alzheimer's disease

The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer''s disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients.     

The effect of ACTH on cerebral blood flow in children with intractable epilepsy

Cerebral blood flow was assessed by ultrasound in 12 children with intractable epilepsy who were treated with ACTH. The average maximal blood velocity (A/L) and end-diastolic blood velocity (d) of the internal carotid artery were measured, before, during and after ACTH therapy in each subject. The right and left mean A/L and d values were significantly decreased during ACTH therapy, and these values returned to the previous levels after the treatment. Cerebral function in children treated with ACTH may be affected by a decrease in cerebral blood flow.     

The relationship of resting cerebral blood flow and brain activation during a social cognition task in adolescents with chronic moderate to severe traumatic brain injury: a preliminary investigation

Alterations in cerebrovascular function are evident acutely in moderate to severe traumatic brain injury (TBI), although less is known about their chronic effects. Adolescent and adult patients with moderate to severe TBI have been reported to demonstrate diffuse activation throughout the brain during functional magnetic resonance imaging (fMRI). Because fMRI is a measure related to blood flow, it is possible that any deficits in blood flow may alter activation. An arterial spin labeling (ASL) perfusion sequence was performed on seven adolescents with chronic moderate to severe TBI and seven typically developing (TD) adolescents during the same session in which they had performed a social cognition task during fMRI. In the TD group, prefrontal CBF was positively related to prefrontal activation and negatively related to non-prefrontal, posterior, brain activation. This relationship was not seen in the TBI group, who demonstrated a greater positive relationship between prefrontal CBF and non-prefrontal activation than the TD group. An analysis of CBF data independent of fMRI showed reduced CBF in the right non-prefrontal region (p<.055) in the TBI group. To understand any role reduced CBF may play in diffuse extra-activation, we then related the right non-prefrontal CBF to activation. CBF in the right non-prefrontal region in the TD group was positively associated with prefrontal activation, suggesting an interactive role of non-prefrontal and prefrontal blood flow throughout the right hemisphere in healthy brains. However, the TBI group demonstrated a positive association with activation constrained to the right non-prefrontal region. These data suggest a relationship between impaired non-prefrontal CBF and the presence of non-prefrontal extra-activation, where the region with more limited blood flow is associated with activation limited to that region. In a secondary analysis, pathology associated with hyperintensities on T2-weighted FLAIR imaging over the whole brain was related to whole brain activation, revealing a negative relationship between lesion volume and frontal activation, and a positive relationship between lesion volume and posterior activation. These preliminary data, albeit collected with small sample sizes, suggest that reduced non-prefrontal CBF, and possibly pathological tissue associated with T2-hyperintensities, may provide contributions to the diffuse, primarily posterior extra-activation observed in adolescents following moderate to severe TBI.     

PETCO2监测过度通气水平对脑外伤患者脑血流、脑代谢和脑灌注的影响

目的 探讨呼吸末二氧化碳分压(PETCO2)监测下过度通气水平对颅脑外伤患者术中脑血流、脑代谢和脑灌注的影响.方法 选择东营鸿港医院神经外科自2009年1月至2012年6月急诊行脑外伤开颅去骨瓣减压血肿清除术的患者70例,按随机数字表法分为A、B2组,每组35例,A组患者PETCO2控制在20～25 mm Hg之间,动脉血二氧化碳分压(PaCO2)维持在22～25 mm Hg之间,B组患者PETCO2控制在25～30 mm Hg之间,PaCO2维持在30～45 mm Hg之间,比较手术开始去骨瓣前2组患者血气分析结果、平均动脉压、颅内压、脑氧分压、脑灌注压和脑氧供需平衡以及代谢产物神经元特异性稀醇化酶(NSE)、葡萄糖、乳酸的变化.结果 手术开始去骨瓣前A组患者的PaCO2水平、平均动脉压、颅内压、NSE、葡萄糖和乳酸水平显著低于B组,差异有统计学意义(P＜0.05);2组患者脑氧分压和脑灌注压、动脉血氧含量(CaO2)、静脉血氧含量(CjvO2)和脑氧摄取率(CERO2)比较差异无统计学意义(P＞0.05).结论 术中将PETCO2控制在20～25 mm Hg之间,能有效维持患者脑血流灌注和脑氧供需平衡,降低病理性代谢产物水平,值得临床重视.     

磁共振相位对比血管成像测量脑血流量的最佳速度编码

实验运用1.5-T磁共振的2D cine PC序列对10位健康志愿者C2水平感兴趣区血管进行速度编码为30~90cm/s,间隔10cm/s的7次同层扫描,探讨速度编码在磁共振相位对比血管成像中对测量脑血流量及入脑/出脑血流的影响。发现不同的速度编码对颈内动脉血流量、最大血流速度和平均血流速度影响较大,对椎动脉及颈内静脉影响不明显。当速度编码为60～80cm/s时,入脑血流量为(655±118)mL/min,出脑血流量(506±186)mL/min,入脑血流量/出脑血流量稳定在0.78～0.83,且所有血管中无混淆现象。提示在应用磁共振相位增强血管成像测量脑血流量时,应选择60～80cm/s的速度编码。     

MR correlates of cerebral atrophy in patients with multiple sclerosis

Objective To investigate the in-vivo correlates of brain atrophy in patients with multiple sclerosis (MS) by assessing the relationship between normalized measures of brain volume (NBV) and other magnetic resonance (MR) measures of tissue damage. Background Brain atrophy diffusely occurs and progressively increases in patients with MS. Nevertheless, the mechanisms leading to brain atrophy in this disease are not fully understood. Methods MR examinations were performed in 20 patients with relapsing-remitting MS. Conventional MRI was used to assess NBV and total brain T2-hyperintense and T1-hypointense lesion volumes. Proton MR spectroscopic imaging and diffusion tensor MR imaging were also performed for large portions of brain containing mainly normal-appearing tissue to provide indices of tissue damage, including N-acetylaspartate to creatine ratio (NAA/Cr) and mean diffusivity (). Results Values of NBV correlated significantly with those of average brain (r = -0.58, p = 0.007) and NAA/Cr (r = 0.67, p < 0.001). The relationship of these markers of tissue damage to NBV was also found when NAA/Cr and were computed together in a composite MR score (r = 0.70, p < 0.001). In contrast, NBV values did not correlate with measurements of average lesion , T₂ and T₁ weighted total brain MRI lesion volumes. Conclusions This study suggests that brain atrophy in MS is not simply due to axonal loss, but rather reflects a more generalized process that involves various brain tissue components. Damage to the normal-appearing tissue rather than the extent and intrinsic pathology of macroscopic lesions seems to be important in the destructive process leading to MS-related irreversible cerebral atrophy. Received: 13 September 2001 Received in revised form: 18 January 2002 Accepted: 4 March 2002     

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP ( n  = 21) and c-HSP type ( n  = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group ( P  < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes.     

橄榄脑桥小脑萎缩患者椎-基底动脉及局部脑血流的改变

目的研究橄榄脑桥小脑萎缩(OPCA)患者椎-基底动脉及局部脑血流(rCBF)的改变。方法对10例OPCA患者行数字减影血管造影(DSA)和单光子发射计算机断层扫描(SPECT)检查,并与对照组(眩晕、短暂性脑缺血发作患者)进行比较。结果OPCA组DSA表现为椎动脉细小5例(50%)、一侧缺如4例(40%)、分支稀疏9例(90%)、动脉晚期脑染色淡10例(100%);SPECT显示小脑及脑干rCBF降低8例(80%);对照组分别为3例(15%)、4例(20%)、4例(20%)、3例(15%)、7例(35%);两组差异有统计学意义(均P<0.01)。结论OPCA患者椎动脉缺如、细小的比率高,椎-基底动脉供血区rCBF减低,提示椎-基底动脉异常可能是OPCA的发病原因。     

Cerebral blood flow and oxygenation during head-up tilt in patients with multiple system atrophy and healthy control subjects

To assess cerebral hemodynamics in patients with multiple system atrophy (MSA), cerebral blood flow and oxygenation were evaluated in 7 MSA patients and 9 healthy controls during a head-up tilt test (HUT) by means of transcranial Doppler ultrasonography and near-infrared spectrophotometry. In the MSA patients examined, the perfusion pressure reduction during HUT was marked, but severe reduction in blood flow velocity was prevented because of a decrease in cerebrovascular resistance. The MSA patients showed no severe reduction in cerebral oxygenation during HUT. These findings indicate that our MSA patients exhibited a compensatory cerebral vasodilatation response to orthostatic hypotension.