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Regional resting state perfusion variability and delayed cerebrovascular uniform reactivity in subjects with chronic carotid artery stenosis
Abstract
The aim of this study was to assess regional perfusion at baseline and regional cerebrovascular resistance (CVR) to delayed acetazolamide challenge in subjects with chronic carotid artery stenosis.Sixteen patients (ten males) aged 70.94±7.71 with carotid artery stenosis ≥90% on the ipsilateral side and ≤50% on the contralateral side were enrolled into the study. In all patients, two computed tomography perfusion examinations were carried out; the first was performed before acetazolamide administration and the second 60 minutes after injection.The differences between mean values were examined by paired two-sample t-test and alternative nonparametric Wilcoxon’s test. Normality assumption was examined using W Shapiro-Wilk test.The lowest resting-state cerebral blood flow (CBF) was observed in white matter (ipsilateral side: 18.4±6.2; contralateral side: 19.3±6.6) and brainstem (ipsilateral side: 27.8±8.5; contralateral side: 29.1±10.8). Grey matter (cerebral cortex) resting state CBF was below the normal value for subjects of this age: frontal lobe – ipsilateral side: 30.4±7.0, contralateral side: 33.7±7.1; parietal lobe – ipsilateral side: 36.4±11.3, contralateral side: 42.7±9.9; temporal lobe – ipsilateral side: 32.5±8.6, contralateral side: 39.4±10.8; occipital lobe – ipsilateral side: 24.0±6.0, contralateral side: 26.4±6.6). The highest resting state CBF was observed in the insula (ipsilateral side: 49.2±17.4; contralateral side: 55.3±18.4). A relatively high resting state CBF was also recorded in the thalamus (ipsilateral side: 39.7±16.9; contralateral side: 41.7±14.1) and cerebellum (ipsilateral side: 41.4±12.2; contralateral side: 38.1±11.3). The highest CVR was observed in temporal lobe cortex (ipsilateral side: +27.1%; contralateral side: +26.1%) and cerebellum (ipsilateral side: +27.0%; contralateral side: +34.6%). The lowest CVR was recorded in brain stem (ipsilateral side: +20.2%; contralateral side: +22.2%) and white matter (ipsilateral side: +18.1%; contralateral side: +18.3%). All CBF values were provided in milliliters of blood per minute per 100 g of brain tissue [ml/100g/min]. Resting state circulation in subjects with carotid artery stenosis is low in all analysed structures with the exception of insula and cerebellum. Acetazolamide challenge yields relatively uniform response in both hemispheres in the investigated population.Grey matter is more reactive to acetazolamide challenge than white matter or brainstem.
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Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsiand contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (–9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT – 16.09%, TTP – 7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT – 14.65%, TTP – 7.46%) sides. PS decreased by almost half: ipsilateral – 48.11%, contralateral – 45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.
Cognitive decline and carotid artery atheroma are common at older ages. In community-dwelling subjects, we assessed cognition at ages 70, 73 and 76 and carotid Doppler ultrasound at age 73, to determine whether carotid stenosis was related to cognitive decline. We used latent growth curve models to examine associations between four carotid measures (internal carotid artery stenosis, velocity, pulsatility and resistivity indices) and four cognitive ability domains (memory, visuospatial function, crystallised intelligence, processing speed) adjusted for cognitive ability at age 11, current age, gender and vascular risk factors. Amongst 866 participants, carotid stenosis (median 12.96%) was not associated with cognitive abilities at age 70 or cognitive decline from age 70 to 76. Increased ICA pulsatility and resistivity indices were associated with slower processing speed (both P < 0.001) and worse visuospatial function ( P = 0.036, 0.031, respectively) at age 70, and declining crystallised intelligence from ages 70 to 76 ( P = 0.008, 0.006, respectively). The findings suggest that vascular stiffening, rather than carotid luminal narrowing, adversely influences cognitive ageing and provides a potential target for ameliorating age-related cognitive decline.
Unlabelled:
Obstructive sleep apnea syndrome (OSAS) leads to neurocognitive and autonomic deficits that are partially mediated by thalamic and putamen pathology. We examined the underlying neurochemistry of those structures using compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (JRESI), and quantified values with prior knowledge fitting. Bilaterally increased thalamic mI/Cr, putamen Glx/Cr, and Glu/Cr, and bilaterally decreased thalamic and putamen tCho/Cr and GABA/Cr occurred in OSAS vs healthy subjects (p < 0.05). Increased right thalamic Glx/Cr, Glu/Cr, Gln/Cr, Asc/Cr, and decreased GPC/Cr and decreased left thalamic tNAA/Cr, NAA/Cr were detected. The right putamen showed increased mI/Cr and decreased tCho/Cr, and the left, decreased PE/Cr ratio. ROC curve analyses demonstrated 60-100% sensitivity and specificity for the metabolite ratios in differentiating OSAS vs.
Controls:
Positive correlations were found between: left thalamus mI/Cr and baseline oxygen saturation (SaO2); right putamen tCho/Cr and apnea hypopnea index; right putamen GABA/Cr and baseline SaO2; left putamen PE/Cr and baseline SaO2; and left putamen NAA/Cr and SaO2 nadir (all p < 0.05). Negative correlations were found between left putamen PE/Cr and SaO2 nadir. These findings suggest underlying inflammation or glial activation, with greater alterations accompanying lower oxygen saturation. These metabolite levels may provide biomarkers for future neurochemical interventions by pharmacologic or other means.
Background:
The evidence accumulates that the response to acetazolamide test is delayed on the ipsilateral side to stenosis. However, the effect of acetazolamide beyond 30 minutes after acetazolamide administration remains unknown. The aim of this study was to assess the diameters of: anterior cerebral arteries (ACAs), middle cerebral arteries (MCAs) and posterior cerebral arteries (PCAs) before and 60 minutes after the acetazolamide test.
Materials and methods:
Seventeen patients with carotid artery stenosis ≥90% on the ipsilateral side and, ≤50% on the contralateral side were enrolled into the study. Diagnosis was based on ultrasonography examination and was confirmed using digital subtractive angiography. In all patients, two computed tomography angiography examinations were carried out; the first was performed before the acetazolamide administration while the second one was carried out 60 minutes after injections.
Results:
In response to the acetazolamide test: PCA diameter diminished in both ipsi- and contra- lateral side to stenosis (from 1.31 to 1.24 mm and from 1.23 to 1.15, respectively), ACA and MCA decreased in the contralateral side to the stenosis (from 1.33 to 1.26 and from 2.75 to 2.66 mm, respectively), ACA and MCA increased in the ipsilateral side to the stenosis (from 1.29 to 1.46 mm and from 2.77 to 2.96, respectively). All changes were statistically significant.
Conclusions:
There were significant differences in reactivity to acetazolamide challenge between the internal carotid artery (ICA) and vertebra-basilar circulation in patients suffering from chronic carotid artery stenosis. Within the ICA territory ACAs and MCAs responses vary in the affected and not affected side.
Inflammation of forebrain and hindbrain nuclei controlling the sympathetic nervous system (SNS) outflow from the brain to the periphery represents an emerging concept of the pathogenesis of neurogenic hypertension. Angiotensin II (Ang-II) and prorenin were shown to increase production of reactive oxygen species and pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)) while simultaneously decreasing production of interleukin-10 (IL-10) in the paraventricular nucleus of the hypothalamus and the rostral ventral lateral medulla. Peripheral chronic inflammation and Ang-II activity seem to share a common central mechanism contributing to an increase in sympathetic neurogenic vasomotor tone and entailing neurogenic hypertension. Both hypertension and obesity facilitate the penetration of peripheral immune cells in the brain parenchyma. We suggest that renin-angiotensin-driven hypertension encompasses feedback and feedforward mechanisms in the development of neurogenic hypertension while low-intensity, chronic peripheral inflammation of any origin may serve as a model of a feedforward mechanism in this condition.
Purpose:
Alzheimer's disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI).
Methods:
Nine AD subjects and ten aMCI subjects had both [(11)C]PIB and [(18)F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [(11)C]PIB or [(18)F]FDG PET scans. The [(11)C]PIB PET scans were quantified using [(11)C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis.
Results:
In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD.
Conclusion:
This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas.
Until recently, no direct comparison between [(15)O]water positron emission tomography (PET) and arterial spin labeling (ASL) for measuring cerebral blood flow (CBF) was possible. With the introduction of integrated, hybrid magnetic resonance (MR)-PET scanners, such a comparison becomes feasible. This study presents results of CBF measurements recorded simultaneously with [(15)O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [(15)O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant (P<0.05) correlation was observed between the two modalities; the whole-brain CBF values determined with PET and pCASL were 43.3±6.1 mL and 51.9±7.1 mL per 100 g per minute, respectively. The gray/white matter (GM/WM) ratio of CBF was 3.0 for PET and 3.4 for pCASL. A paired t-test revealed differences in regional CBF between ASL and PET with higher ASL-CBF than PET-CBF values in cortical areas. Using an integrated, hybrid MR-PET a direct simultaneous comparison between ASL and [(15)O]water PET became possible for the first time so that temporal, physiologic, and functional variations were avoided. Regional and individual differences were found despite the overall similarity between ASL and PET, requiring further detailed investigations.Journal of Cerebral Blood Flow & Metabolism advance online publication, 21 May 2014; doi:10.1038/jcbfm.2014.92.
Adults with obstructive sleep apnea (OSA) show significant autonomic and neuropsychologic deficits, which may derive from damage to insular regions that serve those functions. The aim was to assess glial and neuronal status from anterior insular metabolites in OSA versus controls, using proton magnetic resonance spectroscopy (PMRS), and thus to provide insights for neuroprotection against tissue changes, and to reduce injury consequences.
Cross-sectional study.
University-based medical center.
Thirty-six patients with OSA, 53 controls.
None.
We performed PMRS in bilateral anterior insulae using a 3.0-Tesla magnetic resonance imaging scanner, calculated N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), myo-inositol/creatine (MI/Cr), and MI/NAA metabolite ratios, and examined daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and neuropsychologic status (Beck Depression Inventory II [BDI-II] and Beck Anxiety Inventory [BAI]). Body mass index, BAI, BDI-II, PSQI, and ESS significantly differed between groups. NAA/ Cr ratios were significantly reduced bilaterally, and left-sided MI/Cr and MI/NAA ratios were increased in OSA over controls. Significant positive correlations emerged between left insular MI/Cr ratios and apnea-hypopnea index values, right insular Cho/Cr ratios and BDI-II and BAI scores, and negative correlations appeared between left insular NAA/Cr ratios and PSQI scores and between right-side MI/Cr ratios and baseline and nadir change in O2 saturation.
Adults with obstructive sleep apnea showed bilaterally reduced N-acetylaspartate and left-side increased myo-inositol anterior insular metabolites, indicating neuronal damage and increased glial activation, respectively, which may contribute to abnormal autonomic and neuropsychologic functions in the condition. The activated glial status likely indicates increased inflammatory action that may induce more neuronal injury, and suggests separate approaches for glial and neuronal protection.
Yadav SK, Kumar R, Macey PM, Woo MA, Yan-Go FL, Harper RM. Insular cortex metabolite changes in obstructive sleep apnea. SLEEP 2014;37(5):951-958.
Purpose
In patients with unilateral internal carotid or middle cerebral artery (ICA or MCA) occlusive disease, the degree of crossed cerebellar hypoperfusion that is evident within a few months after the onset of stroke may reflect cerebral metabolic rate of oxygen in the affected cerebral hemisphere relative to that in the contralateral cerebral hemisphere. The aim of the present study was to determine whether the ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on positron emission tomography (PET) and single photon emission computed tomography (SPECT) correlates with oxygen extraction fraction (OEF) asymmetry in the cerebral hemisphere on PET in patients with chronic unilateral ICA or MCA occlusive disease and whether this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere in such patients.
Methods
Brain blood flow and OEF were assessed using 15O-PET and N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT, respectively. All images were anatomically standardized using SPM2. A region of interest (ROI) was automatically placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres using a three-dimensional stereotaxic ROI template, and affected-to-contralateral asymmetry in the MCA territory or contralateral-to-affected asymmetry in the cerebellar hemisphere was calculated. Sixty-three patients with reduced blood flow in the affected cerebral hemisphere on 123I-IMP SPECT were enrolled in this study.
Results
A significant correlation was observed between MCA ROI asymmetry of PET OEF and the ratio of cerebellar hemisphere asymmetry of blood flow to MCA ROI asymmetry of blood flow on PET (r = 0.381, p = 0.0019) or SPECT (r = 0.459, p = 0.0001). The correlation coefficient was higher when reanalyzed in a subgroup of 43 patients undergoing a PET study within 3 months after the last ischemic event (r = 0.541, p = 0.0001 for PET; r = 0.609, p < 0.0001 for SPECT). The blood flow ratio on brain perfusion SPECT in all patients provided 100 % sensitivity and 58 % specificity, with 43 % positive and 100 % negative predictive values for detecting abnormally elevated MCA ROI asymmetry of PET OEF.
Conclusion
The ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on PET and SPECT correlates with PET OEF asymmetry in the cerebral hemisphere, and this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere.
The purpose of the study was to assess the responses of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) to acetazolamide challenge in patients with chronic carotid artery stenosis and relate these responses to changes in peak systolic velocity (PSV), cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak response (TTP).
Fifteen patients with carotid artery stenosis ≥90% on the ipsilateral side and <50% on the contralateral side were enrolled into the study. PSV was assessed using colour-coded duplex sonography, CBF, CBV, MTT and TTP with perfusion computed tomography, cc-TQ and sas-TQ with near-infrared transillumination/backscattering sounding (NIR-T/BSS).
Based on the ipsilateral/contralateral cc-TQ ratio after acetazolamide challenge two groups of patients were distinguished: the first group with a ratio ≥1 and the second with a ratio <1. In the second group increases in CBF and CBV after the acetazolamide test were significantly higher in both hemispheres (ipsilateral: +33.0%±8.1% vs. +15.3%±4.4% and +26.3%±6.6% vs. +14.3%±5.1%; contralateral: +26.8%±7.0% vs. +17.6%±5.6% and +20.0%±7.3% vs. +10.0%±3.7%, respectively), cc-TQ was significantly higher only on the ipsilateral side (+37.3%±9.3% vs. +26.6%±8.6%) and the decrease in sas-TQ was less pronounced on the ipsilateral side (-0.7%±1.5% vs. -10.2%±1.5%), in comparison with the first group. The changes in sas-TQ following the acetazolamide test were consistent with the changes in TTP.
The ipsilateral/contralateral cc-TQ ratio following acetazolamide challenge may be used to distinguish patient groups characterized by different haemodynamic parameters. Further research on a larger group of patients is warranted.
Background
Heterogeneity of arterial transit time due to cerebral artery steno-occlusive lesions hampers accurate regional cerebral blood flow measurement by arterial spin labeling (ASL).PurposeTo assess the feasibility of regional cerebral blood flow measurement by ASL with multiple-delay time sampling in patients with steno-occlusive diseases by comparing with positron emission tomography (PET), and to determine whether regional arterial transit time measured by this ASL technique is correlated with regional mean transit time, a PET index of perfusion pressure.Material and Methods
Sixteen patients with steno-occlusive diseases received both ASL and (15)O-PET. The mean regional cerebral blood flow measured by ASL and PET, regional arterial transit time by ASL, and regional mean transit time by PET were obtained by a region-of-interest analysis. Correlation between regional cerebral blood flow by ASL and that by PET, and correlation between regional arterial transit time by ASL and regional mean transit time by PET were tested using Pearson's correlation coefficient for both absolute and relative values. A multivariate regression analysis was performed to test whether regional arterial transit time by ASL was a significant contributor in modeling regional mean transit time by PET after controlling the effect of regional cerebral blood flow by ASL.ResultsA significant positive correlation was found between regional cerebral blood flow by ASL and that by PET for both absolute (r = 0.520, P < 0.0001) and relative (r = 0.691, P < 0.0001) values. A significant positive correlation was found between regional arterial transit time by ASL and regional mean transit time by PET both for absolute (r = 0.369, P = 0.0002) and relative (r = 0.443, P < 0.0001) values. The regression analysis revealed that regional arterial transit time by ASL was a significant contributor in modeling regional mean transit time by PET after controlling regional cerebral blood flow by ASL (P = 0.0011).Conclusion
The feasibility of regional cerebral blood flow measurement using ASL with multiple-delay time sampling was confirmed in patients with cerebral artery steno-occlusive diseases. Moreover, it was suggested that mapping of regional arterial transit time has the potential to detect hemodynamic impairment.
The cerebellar role in non-motor functions is supported by the clinical finding that lesions confined to cerebellum produce the cerebellar cognitive affective syndrome. Nevertheless, there is no consensus regarding the overall cerebellar contribution to cognition. Among other reasons, this deficiency might be attributed to the small sample sizes and narrow breadths of existing studies on lesions in cerebellar patients, which have focused primarily on a single cognitive domain. The aim of this study was to examine the expression of cerebellar cognitive affective syndrome with regard to lesion topography in a large group of subjects with cerebellar damage. We retrospectively analysed charts from patients in the Ataxia Lab of Santa Lucia Foundation between 1997 and 2007. Of 223 charts, 156 were included in the study, focusing on the importance of the cerebellum in cognition and the relevance of lesion topography in defining the cognitive domains that have been affected. Vascular topography and the involvement of deep cerebellar nuclei were the chief factors that determined the cognitive profile. Of the various cognitive domains, the ability to sequence was the most adversely affected in nearly all subjects, supporting the hypothesis that sequencing is a basic cerebellar operation.
Early diagnosis of cerebrovascular disease requires the accurate identification of brain regions with compromised cerebral perfusion pressure (CPP). Current clinical measures of CPP are invasive and lack regional information. Dynamic contrast-enhanced imaging provides a means of looking at regional cerebral hemodynamics. The purpose of this study was to determine if any of the parameters associated with dynamic contrast-enhanced imaging could be used as an index for CPP under graded systemic hypotension in a rabbit model. Cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT), and cerebrovascular reserve (CVR) were measured using Computed Tomography Perfusion in three groups: normotensive (n = 14), mild hypotensive (n = 9), and moderate hypotensive (n = 6). MTT demonstrated the strongest correlation with CPP (ρ = -0.642, P < 0.05). CBF was the only other parameter to demonstrate a statistically significant correlation (ρ = 0.575, P < 0.05). CVR is gaining momentum for diagnosing cerebrovascular disease; however, the technique requires patients to be given a hemodynamic challenge, which could aggravate symptoms and even trigger stroke. The results of this study suggest that the use of MTT, not requiring hemodynamic manipulation, is more sensitive to subtle changes in CPP, as would occur in the early stages of cerebrovascular disease.
Reduced cerebral blood flow and cerebrovascular reactivity to acetazolamide have been used as predictors for subsequent ischemic stroke in patients with occlusive carotid artery diseases, called type 3 ischemia. However, recent studies have shown that reduced cerebrovascular reactivity to acetazolamide does not always represent elevated oxygen extraction fraction (OEF). The aim of this study was to establish the methodology to improve the validity of an acetazolamide test identifying elevated OEF.
This study included 65 patients who developed transient ischemic attack or minor completed stroke attributable to occlusive carotid artery diseases. Hemodynamic and metabolic parameters in the bilateral middle cerebral artery territories were determined in all patients by (15)O-gas PET.
Type 3 ischemia alone had 100% sensitivity and 83.2% specificity for identifying elevated OEF, but its positive predictive value and accuracy were low, 47.2% and 0.85, respectively. However, type 3 ischemia and delayed mean transit time combined had an 83.3% positive predictive value and 0.96 accuracy.
The results strongly suggest that type 3 ischemia and delayed mean transit time together may be powerful predictors in identifying elevated OEF with high sensitivity and specificity, predictive values, and accuracy. SPECT may be able to define the patients with elevated OEF more easily and at lower costs than PET, although further study would be necessary to compare the results by using SPECT.
The aim of this study was to evaluate the effect of acetazolamide on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). CBF, arterial and jugular venous partial O2 pressure, partial CO2 pressure, pH, and O2 saturation percentage were measured in six patients before and 3 and 20 minutes after intravenous administration of 1 g of acetazolamide. CBF was measured by the intracarotid 133xenon injection technique. In addition, changes in CBF were estimated from the arteriovenous oxygen content difference. CBF increased in all patients after acetazolamide, by approximately 55 and 70% after 3 and 20 min, respectively. The CBF changes were of the same order whether calculated from the 133Xe clearance or from the arteriovenous oxygen differences (A-V)O2. CMRO2, calculated from (A-V)O2 differences and CBF, remained constant. Except for an increase in the venous oxygen saturation, the blood gases remained constant. Acetazolamide, in a dose sufficient to inhibit the erythrocyte carbonic anhydrase (EC 4.2.1.1), thus induced a rapid and marked increase in CBF, leaving CMRO2 unchanged. This effect of acetazolamide on CBF is probably explained by a decrease in brain pH rather than by brain tissue hypoxia due to inhibition of oxygen unloading in the brain capillaries.
Local cerebral perfusion pressure (CPP), a crucial parameter that should allow a better assessment of the haemodynamic compromise in cerebrovascular diseases, is not currently measurable by non-invasive means. Experimental and clinical studies have suggested that the regional ratio of cerebral blood flow to cerebral blood volume (CBF:CBV), as measured by PET, represents an index of local CPP in focal ischaemia. The present study was designed to evaluate further the reliability of the CBF:CBV ratio during manipulations of CPP by deliberately varying mean arterial pressure (MAP) in the anaesthetized baboon. Cortical CBF, CBV, cerebral metabolic rate for oxygen (CMRO2) and oxygen extraction fraction were measured by PET using the (15)O steady-state technique in 10 anaesthetized baboons. Five baboons (Group A) underwent four PET examinations at different levels of MAP: base line (101 +/- 6 mmHg) followed by moderate hypotension (58 +/- 3 mmHg) and, in a separate experiment, minor hypotension (72 +/- 3 mmHg) followed by profound hypotension (34 +/- 5 mmHg). Trimetaphan was used to lower MAP to minor and moderate levels while profound hypotension was achieved by the combined effects of trimetaphan and lower-body negative pressure. Five other baboons (Group B) were subjected to hypertension (121 +/- 2 mmHg) induced by metaraminol and were compared with their base line state (81 +/- 10 mmHg). While CBF displayed significant changes with varying MAP, i.e. decrease and increase with hypotension and hypertension, respectively (-11% from base line to moderate hypotension compared with -20%, from minor to profound hypotension and +31% from base line to hypertension), CBV was more variable and did not significantly change, except with profound hypotension when the increase was significant (+13%). The CBF:CBV ratio decreased significantly at all stages of hypotension (-21 and -31%) and was significantly increased during hypertension (+30%). Importantly, the CBF:CBV ratio demonstrated a significant correlation with MAP (rho = 0.78, Spearman's rank correlation coefficient, P < 0.01). No major changes in CMRO2 were noted during either hypotension or hypertension. Our results demonstrate that, under physiological conditions, cortical CBF:CBV is significantly correlated with CPP, itself a function of MAP. In the investigated range of MAP, the relationships between CBF:CBV and MAP appear to be linear. These findings further argue for the reliability of CBF:CBV as an index of CPP in situations where increases or decreases of MAP without superimposed changes in cerebrovascular tone are encountered, and they confirm the potential usefulness of this regional ratio for clinical investigations and management in cerebrovascular diseases.
The purpose of this study was to verify the feasibility and usefulness of a new SPECT method, called triple injection of (99m)Tc-ethylcysteinate dimer (TIE), in evaluation of the delayed or poor appearance of acetazolamide (ACZ) effects in patients with chronic cerebral ischemic disease.
Three equal-volume splits of (99m)Tc-ethylcysteinate dimer were intravenously administered, and 1,000 mg ACZ were used as a vasodilator. A middle cerebral artery territory in the lateral ventricle was used as a region of interest. The data at rest and at 7.5 and 20 min after ACZ challenge (ACZ 7.5 and ACZ 20, respectively) were obtained by dynamic SPECT, and a time response curve to ACZ was obtained through the relative ratio of regional counts to the data at rest, not through regional cerebral blood flow. Nine cases of complete occlusion of the internal carotid artery (IC) and 6 cases of severe IC stenosis were analyzed.
In 12 healthy volunteers (24 cerebral hemispheres) using a placebo (negative control), the values at rest and at rest 7.5 and rest 20 (corresponding to ACZ 7.5 and ACZ 20, respectively) were 100%, 100.4% +/- 2.8%, and 99.6% +/- 3.6%, respectively, indicating the accuracy of the TIE method. In a positive control using 24 normal cerebral hemispheres, prompt maximal vasoreactivity at ACZ 7.5 (124.5% +/- 8.0%) was confirmed, as was continuous vasoreactivity until ACZ 20 (130.1% +/- 12.8%). The values between ACZ 7.5 and ACZ 20 were not statistically different. Patients with complete IC occlusion exhibited a poor response at ACZ 7.5 despite a normal response at ACZ 20 (delayed response). Furthermore, in patients with severe IC stenosis, restoration of cerebrovascular reactivity after carotid endarterectomy was confirmed not only at ACZ 20 but also at ACZ 7.5.
The TIE method using SPECT may be a potentially useful and sensitive strategy in clinical evaluation of the delayed or poor appearance of ACZ effects in patients with chronic cerebrovascular ischemic disease.
This multi-study analysis (6 fMRI studies; 142 participants) explores the functional activation and connectivity of the cerebellum with the cerebrum during repeated behavioral information uptake informing about personality traits of different persons. The results suggest that trait repetition recruits activity in areas belonging to the mentalizing and executive control networks in the cerebrum, and the executive control areas in the cerebellum. Cerebral activation was observed in the executive control network including the posterior medial frontal cortex (pmFC), the bilateral prefrontal cortex (PFC) and bilateral inferior parietal cortex (IPC), in the mentalizing network including the bilateral middle temporal cortex (MTC) extending to the right superior temporal cortex (STC), as well as in the visual network including the left cuneus (Cun) and the left inferior occipital cortex. Moreover, cerebellar activation was found bilaterally in lobules VI and VII belonging to the executive control network. Importantly, significant patterns of functional connectivity were found linking these cerebellar executive areas with cerebral executive areas in the medial pmFC, the left PFC and the left IPC, and mentalizing areas in the left MTC. In addition, connectivity was found through links between the cerebral areas in the left hemisphere involved in the executive and mentalizing networks, as well as with their homologue areas in the right hemisphere. The discussion centers on the role of these cerebello-cerebral connections in matching internal predictions generated by the cerebellum with external information from the cerebrum, presumably involving the sequencing of behaviors.
Objectives:
The impact of coverage size on global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) parameters has not been investigated in patients with chronic carotid artery stenosis.
Materials and methods:
Sixty three patients with stenosis of more than 70% within a single internal carotid artery and neurological symptoms were randomly assigned to two well-matched groups. Differences in computed tomography perfusion scan over a 4 cm or 8 cm range of the brain were compared between the two groups.
Results:
The CBF and CBV values were higher in the 4 cm coverage size than in the 8 cm coverage size (by 14.7% and 10.7% on the ipsilateral side, and 17.2% and 7.8% on the contralateral side, respectively; all P<0.001). The MTT value was higher in the 4 cm coverage size than in the 8 cm coverage size on the ipsilateral side (9.6%; P<0.001). There was no difference between MTT values in the contralateral size. There were no differences between TTP values on the ipsilateral and contralateral sides. The relative indices rMTT and rTTP were higher in the 4 cm coverage size than in the 8 cm coverage size (8.2%; P<0.001 and 1.1%; P<0.005, respectively).
Conclusion:
Absolute CBF and CBV values and relative rMTT and rTTP indices in patients with low CBF and low CBV are highly dependent on coverage size. We recommend using a 4 cm coverage size to assess global cerebral perfusion parameters due to better accuracy and quicker post-processing.
Advances in knowledge:
To the best of our knowledge, this is the first article to compare the influence of 4 cm versus 8 cm coverage size on cerebral perfusion parameters such as CBF, CBV, MTT and TTP in subjects with chronic carotid artery stenosis.
Blood Oxygenation Level Dependent (BOLD) imaging in combination with vasoactive stimuli can be used to probe cerebrovascular reactivity (CVR). Characterizing the healthy, age-related changes in the BOLD-CVR response can provide a reference point from which to distinguish abnormal CVR from the otherwise normal effects of ageing. Using a computer controlled gas delivery system, we examine differences in BOLD-CVR response to progressive hypercapnia between 16 young (28 ± 3 years, 9 female) and 30 elderly subjects (66 ± 4 years, 13 female). Furthermore, we incorporate baseline T2* information to broaden our interpretation of the BOLD-CVR response. Significant age-related differences were observed. Grey matter CVR at 7 mm Hg above resting PetCO2 was lower amongst elderly (0.19 ± 0.06%ΔBOLD/mm Hg) as compared to young subjects (0.26 ± 0.07%ΔBOLD/mm Hg). White matter CVR at 7 mm Hg above baseline PetCO2 showed no significant difference between young (0.04 ± 0.02%ΔBOLD/mm Hg) and elderly subjects (0.05 ± 0.03%ΔBOLD/mm Hg). We saw no significant differences in the BOLD signal response to progressive hypercapnia between male and female subjects in either grey or white matter. The observed differences in the healthy BOLD-CVR response could be explained by age-related changes in vascular mechanical properties.
Purpose of review:
Inflammation of forebrain and hindbrain nuclei has recently been highlighted as an emerging factor in the pathogenesis of neurogenic hypertension. The aim of this review is to summarize the state of the art in this field and to discuss recently discovered pathophysiological mechanisms, opening new perspectives for therapeutic application.
Recent findings:
Microglia Toll-like receptor 4 causally links angiotensin II (AngII)-mediated microglia cell activation and oxidative stress within the hypothalamic paraventricular nucleus (PVN). Toll-like receptor 4 can also be activated by lipopolysaccharides. PVN infusion of nuclear factor κB inhibitor lowers the blood pressure and ameliorates cardiac hypertrophy. Ang-(1-7) exerts direct effects on microglia, causing a reduction in both baseline and prorenin-induced release of proinflammatory cytokines. A compromised blood-brain barrier (BBB) constitutes a complementary mechanism that exacerbates AngII-driven neurohumoral activation, contributing to the development of hypertension.
Summary:
PVN and BBB seem to be pivotal targets for therapeutic intervention in hypertension. Recent advances in imaging techniques enable visualization of the inflammatory state in microglia and BBB integrity in humans. AngII type I receptor blockers and AngII-converting enzyme inhibitors are the most likely candidates for controlled randomized trials in humans aimed at amelioration of brain inflammation in the forthcoming years.
Significant improvement in outcomes for patients with carotid stenosis requires liberation from the historic fixation with randomization and a procedurally based, late-stage, reactive approach to medical care. We require a multipronged and multidisciplinary approach that includes all of the following: (i) removal of overreliance on, and biased use of, randomized trial data; (ii) using accurate ways to rank evidence quality and relevance; (iii) improved research reporting standards; (iv) building quality assurance and other research capability into routine practice; (v) producing evidence-true rather than evidence-based guidelines; (vi) bringing current optimal medical treatment to the community and measuring its effectiveness; (vii) funding only interventions known to help patients when and where they are treated and use the savings to fund vital research, including quality assurance in routine practice; and (viii) recognize that making the indication for carotid procedures obsolete is a good thing.
Perfusion imaging has the potential to select patients most likely to respond to thrombolysis. We tested the correspondence of computed tomography perfusion (CTP)-derived mismatch with contemporaneous perfusion-diffusion magnetic resonance imaging (MRI).
Acute ischemic stroke patients 3 to 6 hours after onset had CTP and perfusion-diffusion MRI within 1 hour, before thrombolysis. Relative cerebral blood flow (relCBF) and time to peak of the deconvolved tissue residue function (Tmax) were calculated. The diffusion lesion (diffusion-weighted imaging) was registered to the CTP slabs and manually outlined to its maximal visual extent. Volumetric accuracy of CT-relCBF infarct core (compared with diffusion-weighted imaging) was tested. To reduce false-positive low CBF regions, relCBF core was restricted to voxels within a relative time-to-peak (relTTP) >4 seconds for lesion region of interest. The MR-Tmax >6 seconds perfusion lesion was automatically segmented and registered to CTP. Receiver-operating characteristic analysis determined the optimal CT-Tmax threshold to match MR-Tmax >6 seconds. Agreement of these CT parameters with MR perfusion-diffusion mismatch in coregistered slabs was assessed (mismatch ratio >1.2, absolute mismatch >10 mL, infarct core <70 mL).
In analysis of 49 patients (mean onset to CT, 213 minutes; mean CT to MR, 31 minutes), constraining relCBF <31% within the automated relTTP perfusion lesion region of interest reduced the median magnitude of volumetric error (vs diffusion-weighted imaging) from 47.5 mL to 15.8 mL (P<0.001). The optimal CT-Tmax threshold to match MR-Tmax >6 seconds was 6.2 seconds (95% confidence interval, 5.6-7.3 seconds; sensitivity, 91%; specificity, 70%; area under the curve, 0.87). Using CT-Tmax >6 seconds "penumbra" and relTTP-constrained relCBF "core," CT-based and MRI-based mismatch status was concordant in 90% (kappa=0.80).
Quantitative CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. The greater accessibility of CTP may facilitate generalizability of mismatch-based selection in clinical practice and trials.
Key points
Arterial CO 2 serves as a mediator of cerebral blood flow, and its relative influence on the regulation of cerebral blood flow is defined as cerebral CO 2 reactivity.
Because of methodological limitations, almost all previous studies have evaluated the response of blood flow velocity in the middle cerebral artery to changes in CO 2 as a measure of CO 2 reactivity across the whole brain.
We found that the vertebral artery has lower CO 2 reactivity than the internal carotid artery. Moreover, CO 2 reactivity in the external carotid artery was markedly lower than in the cerebral circulation.
These results demonstrate regional differences in CO 2 regulation of blood flow between the internal carotid, external carotid, and vertebro‐basilar circulation.
Abstract Arterial CO 2 serves as a mediator of cerebral blood flow (CBF), and its relative influence on the regulation of CBF is defined as cerebral CO 2 reactivity. Our previous studies have demonstrated that there are differences in CBF responses to physiological stimuli (i.e. dynamic exercise and orthostatic stress) between arteries in humans. These findings suggest that dynamic CBF regulation and cerebral CO 2 reactivity may be different in the anterior and posterior cerebral circulation. The aim of this study was to identify cerebral CO 2 reactivity by measuring blood flow and examine potential differences in CO 2 reactivity between the internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA). In 10 healthy young subjects, we evaluated the ICA, ECA, and VA blood flow responses by duplex ultrasonography (Vivid‐e, GE Healthcare), and mean blood flow velocity in middle cerebral artery (MCA) and basilar artery (BA) by transcranial Doppler (Vivid‐7, GE healthcare) during two levels of hypercapnia (3% and 6% CO 2 ), normocapnia and hypocapnia to estimate CO 2 reactivity. To characterize cerebrovascular reactivity to CO 2 , we used both exponential and linear regression analysis between CBF and estimated partial pressure of arterial CO 2 , calculated by end‐tidal partial pressure of CO 2 . CO 2 reactivity in VA was significantly lower than in ICA (coefficient of exponential regression 0.021 ± 0.008 vs . 0.030 ± 0.008; slope of linear regression 2.11 ± 0.84 vs . 3.18 ± 1.09% mmHg ⁻¹ : VA vs . ICA, P < 0.01). Lower CO 2 reactivity in the posterior cerebral circulation was persistent in distal intracranial arteries (exponent 0.023 ± 0.006 vs . 0.037 ± 0.009; linear 2.29 ± 0.56 vs . 3.31 ± 0.87% mmHg ⁻¹ : BA vs . MCA). In contrast, CO 2 reactivity in ECA was markedly lower than in the intra‐cerebral circulation (exponent 0.006 ± 0.007; linear 0.63 ± 0.64% mmHg ⁻¹ , P < 0.01). These findings indicate that vertebro‐basilar circulation has lower CO 2 reactivity than internal carotid circulation, and that CO 2 reactivity of the external carotid circulation is markedly diminished compared to that of the cerebral circulation, which may explain different CBF responses to physiological stress.
Cerebral vascular reactivity assessment is typically performed with 2 perfusion measurements before and after a vasodilatory challenge. The aim of this study was to assess the time course of the vasodilatory effect in the brain-feeding arteries after a challenge with acetazolamide in patients with a stenosis of the internal carotid artery (ICA).
Twenty-one patients with a symptomatic ICA stenosis and 18 healthy control subjects underwent 2-dimensional phase-contrast MR angiography to repeatedly measure the blood flow (mL/min) in both ICAs at baseline and in 5-minute intervals for 30 minutes after intravenous administration of acetazolamide.
At baseline, the blood flow was significantly lower in the stenosed ICAs of patients (155 ± 17 mL/min) than in the contralateral ICAs (237 ± 21 mL/min, P<0.05) and the ICAs of healthy control subjects (249 ± 15 mL/min, P<0.05) and remained lower throughout the time course. The maximum vasodilatory effect in the stenosed ICAs was observed after 15.3 ± 0.9 minutes, which was significantly later than in the contralateral ICAs (within 12.9 ± 0.7 minutes, P<0.05) and healthy ICAs (within 12.8 ± 0.8 minutes, P<0.05).
The onset of the maximum vasodilatory effect after administration of acetazolamide is delayed in patients with a symptomatic ICA stenosis.
Prior studies have demonstrated decreasing cerebral blood flow (CBF) in normal aging, but the full spatial pattern and potential mechanism of changes in CBF remain to be elucidated. Specifically, existing data have not been entirely consistent regarding the spatial distribution of such changes, potentially a result of neglecting the effect of age-related tissue atrophy in CBF measurements. In this work, we use pulsed arterial-spin labelling to quantify regional CBF in 86 cognitively and physically healthy adults, aged 23 to 88 years. Surface-based analyses were utilized to map regional decline in CBF and cortical thickness with advancing age, and to examine the spatial associations and dissociations between these metrics. Our results demonstrate regionally selective age-related reductions in cortical perfusion, involving the superior-frontal, orbito-frontal, superior-parietal, middle-inferior temporal, insular, precuneus, supramarginal, lateral-occipital and cingulate regions, while subcortical CBF was relatively preserved in aging. Regional effects of age on CBF differed from that of grey-matter atrophy. In addition, the pattern of CBF associations with age displays an interesting similarity with the default-mode network. These findings demonstrate the dissociation between regional CBF and structural alterations specific to normal aging, and augment our understanding of mechanisms of pathology in older adults.
To examine the variability in the qualitative and quantitative results of computed tomographic (CT) perfusion imaging generated from identical source data of stroke patients by using commercially available software programs provided by various CT manufacturers.
Institutional review board approval and informed consent were obtained. CT perfusion imaging data of 10 stroke patients were postprocessed by using five commercial software packages, each of which had a different algorithm: singular-value decomposition (SVD), maximum slope (MS), inverse filter (IF), box modulation transfer function (bMTF), and by using custom-made original software with standard (sSVD) and block-circulant (bSVD) SVD methods. Areas showing abnormalities in cerebral blood flow (CBF), mean transit time (MTT), and cerebral blood volume (CBV) were compared with each other and with the final infarct areas. Differences among the ratios of quantitative values in the final infarct areas and those in the unaffected side were also examined.
The areas with CBF or MTT abnormalities and the ratios of these values significantly varied among software, while those of CBV were stable. The areas with CBF or MTT abnormalities analyzed by using SVD or bMTF corresponded to those obtained with delay-sensitive sSVD, but overestimated the final infarct area. The values obtained from software by using MS or IF corresponded well with those obtained from the delay-insensitive bSVD and the final infarct area. Given the similarities between CBF and MTT, all software were separated in two groups (ie, sSVD and bSVD). The ratios of CBF or MTTs correlated well within both groups, but not across them.
CT perfusion imaging maps were significantly different among commercial software even when using identical source data, presumably because of differences in tracer-delay sensitivity.
To determine the extent of neurodegeneration of the visual association cortex, we assessed hyperphosphorylated tau-immunoreactive (HPtau-IR) neurofibrillary tangles in Brodmann Areas 18/19 in nondemented and demented subjects. At least occasional HPtau-IR neurofibrillary tangles were seen in 24% of 59 nondemented subjects with ages at death ranging from 42 to 87 years. The incidence increased to 41% in the 32 nondemented subjects who had HPtau-IR pathology in the hippocampal region. Demented subjects with Braak Stages 0 to III and corticobasal degeneration, frontotemporal lobar degeneration with TAR DNA binding protein 43, vascular cognitive impairment, or dementia with Lewy bodies also had HPtau-IR pathology in Brodmann Areas 18/19. These results support the concept that the occipital association area may have enhanced vulnerability to neurodegeneration. Neuropathologic assessment of these areas is, therefore, recommended, particularly in subjects suspected or known to have had mild cognitive impairment. Occasional HPtau-IR lesions were also seen in the medial temporal gyrus. Thus, the question as to whether scattered HPtau-IR lesions in either temporal or occipital cortex indicate a neurodegenerative disease remains unresolved. Further systematic clinicopathologic studies are needed for an understanding of regional susceptibility to neurodegeneration and the significance of scattered HPtau-IR brain lesions.
Cerebral blood flow (CBF) was measured by xenon-133 inhalation tomography in 18 patients with cerebrovascular disease before and 4 months after extracranial-intracranial bypass surgery. Only patients who showed a reduced CBF in areas that were intact on the CT scan and relevant to the clinical and angiographical findings were operated. The majority of the patients had suffered a minor stroke with or without subsequent transient ischemic attacks. They were studied at least 6 weeks following the stroke. All patients had an occlusion of the relevant internal carotid artery. To identify preoperatively the patients with a compromised collateral circulation and hence reduced CBF due to reduced perfusion pressure, a cerebral vasodilatory stress test was performed using acetazolamide (Diamox). In normal subjects, Diamox has been shown to increase tomographic CBF without change of the flow distribution. In the present series 9 patients showed a significant redistribution of flow in favor of the non-occluded side ("positive" Diamox test). Two of these 9 patients showed even a paradoxical decrease in focal CBF preoperatively, i.e., a "steal" effect. These 2 patients were the only patients who improved in focal CBF after shunting. The remaining 9 patients all showed uniform flow responses ("negative" Diamox test), and none of these increased in focal CBF postoperatively. The finding of an unchanged flow map postoperatively confirmed that the low flow areas were not due to restricted flow via collateral pathways. However, an increase in the regional vasodilatory capacity was observed postoperatively in the majority of patients.
The oxygen-15 continuous inhalation technique and PET were used to study the age-related changes in regional CBF and CMRO2. Twenty-seven patients, aged 19 to 76 years, free of any history of cerebral disease and vascular risk factors were examined in "resting state." CBF, CMRO2 and oxygen extraction fraction (OEF) values were calculated in seven different brain structures as well as in mean gray matter. Left-right ratios were also computed for all symmetrical structures analyzed. Mean gray CBF, but not mean gray CMRO2, decreased linearly with age (p less than 0.02). However, when younger subjects (less than or equal to 50 yrs) were compared to older subjects (greater than 50 yrs), an age-related matched decrease in CBF and CMRO2 was observed in mean gray matter (18% and 17%, p less than 0.05) and in all gray matter regions analyzed, particularly in frontal, temporo-sylvian and parieto-occipital cortex. White matter CBF and CMRO2 remained remarkably stable with advancing age. Although the possibility of methodological artifacts was considered, we favor progressive loss of cortical neurones and/or diminished activity of those remaining to explain our findings. In addition, age-related changes in cognitive activities might also be involved.
Local cerebral blood flow (CBF), oxygen consumption (CMRO2), and glucose utilization (CMR-Glc) have been measured in three patients by positron emission tomography (PET), together with continuous inhalation of oxygen-15-labeled gases and i.v. injection of [18F]fluoro-2-deoxy-D-glucose. In normal brain, the close local coupling between CBF and CMR-Glc, and that between CMRO2 and CMR-Glc, were well demonstrated. The coupling held for the asymptomatic areas and for parts of the affected hemispheres in two patients with cerebral ischemia. In one patient the CBF/CMR-Glc couple, but not the CMRO2/CMR-Glc couple, was disrupted in the acute ischemic core. This preliminary work demonstrates the local quantification of these important functional parameters, and indicates the potential usefulness of studying their pathophysiological interrelationship in brain disease.
The effect of hypoxaemia (mean SpO 2 78%) on cognitive function was measured in two groups of twelve normal subjects. A series of psychometric tests was administered to each subject in the same sequence and consisted of the Reitan trail-making test, a digit symbol substitution test, a visuospatial orientation test and the simple unprepared reaction-time test. Psychomotor performance was assessed in a double-blind manner while the subjects were breathing first air and then either air or a hypoxic mixture.
While there was improvement in time for the trail-making test during a repeat study breathing air, there was significant deterioration of time to completion of the test in conditions of hypoxia. A significant learning effect in the orientation test was seen in the control group but this did not occur in hypoxic subjects. Hypoxaemia was shown to cause a significant impairment of simple unprepared reaction time compared with controls. All the changes in cognitive function were small and there were no subjective differences in the air or hypoxic groups. The usefulness of the Reitan trail-making and the simple unprepared reaction-time test in the assessment of psychomotor performance deficit under conditions of hypoxaemia has been demonstrated by this study in normal subjects. It was concluded that a mean oxygen saturation of 78% caused only minor changes in cognitive function in normal subjects.
The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.
Vascular responses to changes in Paco2 are used widely to estimate cerebral perfusion reserve, and they can also be used to assess the degree of arteriosclerosis. In the present study, the effect of aging on cerebral vascular responses to both hypercapnia and hypocapnia was investigated. Cerebral blood flow was measured with positron emission tomography at rest, during hypercapnia, and during hypocapnia in 11 young men and 12 older men. The vascular response to change in Paco2 was calculated as the percent change in cerebral blood flow per absolute change in Paco2 in response to hypercapnia and hypocapnia. The total vascular response to change in Paco2 from hypocapnia to hypercapnia was also calculated. To evaluate age-related changes in regional cerebral vascular responses on a pixel-by-pixel basis, an anatomic standardization technique was also used. Although no significant differences between young and old subjects was observed for vascular responses to both hypercapnia and hypocapnia, a significant decrease in total vascular response was observed with aging, indicating progression of sclerotic changes in the cerebral perforating and medullary arteries with normal aging. According to anatomic standardization analysis, relative capacities for vasodilatation in the cerebellum and insular cortex, and relative capacity for vasoconstriction in the frontal cortex were greater in the younger subjects. Such aging effects should be considered when estimating cerebral perfusion reserve.
Blood vessels are usually conspicuous on dynamic CT perfusion images. The presence of large vessels may lead to overestimation of the quantitative value of cerebral blood flow (CBF). We evaluated the efficacy of the vascular-pixel elimination (VPE) method in quantitative CT perfusion imaging, in comparison with positron emission tomography (PET).
Five healthy volunteers underwent CT perfusion and PET studies. A four-channel multi-detector row CT scanner was used. Dynamic cine scanning was performed after bolus injection of an intravenous contrast agent. CT-CBF was calculated by the central volume principle and deconvolution method. PET was performed after infusion of (15)O-labeled water. PET-CBF was calculated by using a nonlinear least squares method. Average CBF values of the whole section, gray matter, and white matter with both CT and PET were compared after image registration. The comparison was performed with and without VPE. In the VPE method, the vascular pixels were defined by the cerebral blood volume value of the pixel. The threshold of VPE was changed from 5 to 20 mL/100 g. Pixel-by-pixel correlation between CT-CBF and PET-CBF and linear regression analysis were also performed.
Without VPE, CT-CBF was overestimated in all subjects. As the VPE threshold decreased, CT-CBF decreased and the correlation coefficient increased. The best correlation was observed at a VPE threshold of 8 mL/100 g in four of the five subjects. Average CT-CBF values, without VPE, of the whole section, gray matter, and white matter were 59.01, 66.73, and 42.53 mL/100 g/min, respectively. With VPE (threshold, 8 mL/100 g), average CT-CBF values of the whole section, gray matter, and white matter were 45.56, 52.75, and 30.38, respectively. The corresponding PET-CBF values were 46.86, 50.89, and 38.20 mL/100 g/min, respectively.
Vascular pixels should be excluded from the calculation of CT-CBF to avoid overestimation of the CBF values. If vascular pixels are excluded, CBF calculation with CT perfusion imaging is considerably accurate.
Stent-protected carotid angioplasty (SPAC) is an option for treating cervical symptomatic high-grade internal carotid artery (ICA) stenosis. So far, knowledge about hemodynamic changes in the early postinterventional phase is limited. The purpose of this study was to evaluate these changes.
Thirty-four consecutive patients with a high-grade ICA stenosis (according to European Carotid Surgery Trial criteria) and 10 healthy volunteers were enrolled. Hemodynamics of the cerebral circulation were assessed before and within 6 hours after SPAC. ICA flow volume, cerebral blood volume flow (CBVF), and collateral flow volume were sonographically assessed. The ratio of flow velocities in the middle cerebral artery (MCA) ipsilateral to the ICA stenosis was calculated and compared with that in the contralateral MCA. This ratio was designated rMCA.
Preinterventional CBVF, ICA flow volume, and rMCA were significantly reduced compared with results in healthy volunteers. After SPAC, CBVF, ICA flow volume, and rMCA increased significantly. The rMCA did not exceed 1.0. Collateral flow volume decreased in patients with posterior collateral flow only. Postinterventional CBVF and ICA flow volume in patients did not differ from values in healthy volunteers.
Cerebral hemodynamics appear to be impaired in patients with symptomatic high-grade ICA stenosis. After SPAC, hemodynamic parameters normalize within 6 hours. We did not detect hyperperfusion. However, flow volume in the contralateral ICA remains increased in patients with former anterior cross-filling.
To determine changes in cerebral perfusion parameters, based on CT perfusion imaging, in patients after unilateral transluminal angioplasty and stent placement.
74 patients with symptomatic high - grade internal carotid artery stenosis (>70%) were studied with CT perfusion imaging before and - on average - 70 hours and 172 days after carotid stent placement. There were 50 patients with unilateral carotid artery stenosis and 24 with stenosis and accompanying contralateral internal carotid artery occlusion. CT examination was performed using a multidetector helical CT scanner (Light Speed Ultra Advantage, GE Healthcare, USA). Maps showing the absolute values of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were generated.
In a group with unilateral carotid artery stenosis perfusion deficits were present in 84% of patients, ipsilaterally to stenosis. MTT elongation was noted (6.2-6.8s) together with decreased values of CBF (40-46ml/100g/min) and slightly increased CBV (3.2ml/100g). In this group, 3 days after stenting, 30% of patients had perfusion deficits, and after 6 months only 6%. In a group with carotid artery stenosis and contralateral artery occlusion severe perfusion deficits were noted in both hemispheres and they were present in 100% of patients. 6 months after stenting hypoperfusion was observed only in 17% of patients.
Brain perfusion deficits, observed in a majority of patients with carotid artery stenosis tend to improve considerably after carotid artery stenting, in long - term follow up.
To prospectively evaluate changes in brain perfusion computed tomographic (CT) parameters after revascularization of unilateral symptomatic carotid artery stenosis and to determine whether pretreatment perfusion CT parameters can be used to predict changes in cerebral hemodynamics after treatment.
This study was medical ethics committee approved, and written informed consent was obtained from all patients. Thirty-six patients (23 men, 13 women; mean age, 67 years) with unilateral symptomatic carotid artery stenosis underwent multi-detector row perfusion CT before and after revascularization. Mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were calculated, and relative values based on the comparison between symptomatic and asymptomatic hemispheres-specifically, relative CBV, relative CBF, and difference in MTT-were derived. The absolute and relative perfusion values before treatment were assessed and compared with posttreatment values. These analyses were performed for the group as a whole by using the t test and after subdividing patients into three tertiles according to the difference in MTT by using the Wilcoxon signed rank test.
Among the absolute perfusion values, only the MTT in the symptomatic hemisphere improved significantly after treatment (P < .01). All relative values (difference in MTT, relative CBV, and relative CBF) changed significantly after treatment (P < .05). When the patients were subdivided into three tertiles according to difference in MTT, no significant change in any relative perfusion value could be demonstrated in the lowest tertile, only the difference in MTT improved significantly (P = .004) in the middle tertile, and all relative perfusion values changed significantly (P = .002) in the highest tertile.
Compared with relative CT perfusion values based on interhemispheric comparison, absolute perfusion CT values are less suited for demonstrating changes in cerebral perfusion after revascularization in patients with unilateral symptomatic carotid artery stenosis.
Age-related white matter disease (leukoaraiosis) clusters in bands in the centrum semiovale, about the occipital and frontal horns of the lateral ventricles, in the corpus callosum, and internal capsule. Cerebrovascular anatomy suggests that some of these locations represent border zones between arterial supply territories. We hypothesized that there are zones of reduced cerebrovascular reserve (susceptible to selective reductions in blood flow, ie, steal phenomenon) in the white matter of young, healthy subjects, the physiological correlate of these anatomically defined border zones. Furthermore, we hypothesized that these zones spatially correspond with the regions where the elderly develop leukoaraiosis.
Twenty-eight healthy volunteers underwent functional MR mapping of the cerebrovascular response to hypercapnia. We studied 18 subjects by blood oxygen level-dependent MRI and 10 subjects by arterial spin labeling MRI. We controlled both end-tidal pCO(2) and pO(2). All functional data was registered in Montreal Neurological Institute space and generated composite blood oxygen level-dependent MR and arterial spin labeling MR maps of cerebrovascular reserve. We compared these maps with frequency maps of leukoaraiosis published previously.
Composite maps demonstrated significant (90% CI excluding the value zero) steal phenomenon in the white matter. This steal was induced by relatively small changes in end-tidal pCO(2). It occurred precisely in those locations where elderly patients develop leukoaraiosis.
This steal phenomenon likely represents the physiological correlate of the previously anatomically defined internal border zones. Spatial concordance with white matter changes in the elderly raises the possibility that this steal phenomenon may have a pathogenetic role.
Mapping of the cerebral vascular response to hypoxia and hypercapnia using quantitative perfusion MRI at 3 T
- U Nöth
- F Kotajima
- R Deichmann
- R Turner
- D R Corfield
Nöth U, Kotajima F, Deichmann R, Turner R, Corfield DR (2008)
Mapping of the cerebral vascular response to hypoxia and hypercapnia using quantitative perfusion MRI at 3 T. NMR Biomed 21:
464-472