Cerebral Arterial Compliance Research Articles

Cerebrovascular and cardiovascular autonomic regulation in sickle cell patients with white matter lesions.

White matter lesions (WMLs) are frequent in sickle cell disease (SCD), with a prevalence described to be as high as 53% by age 30. Cerebrovascular regulation and cardiovascular autonomic regulation, more specifically the sympatho-vagal balance, can be altered in SCD. In this study the association between WMLs, cerebrovascular regulation and sympatho-vagal balance was assessed in SCD patients. Sickle cell disease patients with no history of stroke were prospectively evaluated for cerebrovascular reactivity using the breath-holding test (BHT), the sympatho-vagal balance (ratio low frequency/high frequency [HF]) using heart rate variability parameters and cerebral autoregulation in the time domain using correlation index Mx, and arterial cerebral compliance based on continuous assessment of cerebral blood flow velocities using transcranial Doppler ultrasound and arterial blood pressure with photo-plethysmography. WMLs were assessed with magnetic resonance imaging using Fazekas score grading and the presence of lacunes. Forty-one patients (F/M 25/16) were included. Median age was 37.5 years (19-65). Twenty-nine (70.7%) patients had SS genotype. Eleven patients had WMLs (26.8%). Patients with WMLs were significantly older (p < 0.001), had a lower HF (p < 0.005) and an impaired cerebral arterial compliance (p < 0.014). The receiver operating curve for the regression model including age and HF showed a higher area under the curve compared to age alone (0.946 vs. 0.876). BHT and Mx did not significantly differ between the two groups. Lower parasympathetic activity and impaired cerebral arterial compliance were associated with WMLs in adults with SCD. This could potentially yield to a better understanding of pathophysiological parameters leading to premature cerebrovascular ageing in SCD.

Intracranial dynamics biomarkers at traumatic cerebral vasospasm

IntroductionPatients who suffer severe traumatic brain injury (sTBI) and cerebral vasospasm (CVS) frequently have posttraumatic cerebral ischemia (PCI). The research questionwas to study changes in cerebral microcirculatory bed parameters in sTBI patients with CVS and with or without PCI. Material and methodsA total of 136 severe TBI patients were recruited in the study. All patients underwent perfusion computed tomography, intracranial pressure monitoring, and transcranial Doppler. The levels of cerebrovascular resistance (CVR), cerebral arterial compliance (CAC), cerebrovascular time constant (CTC), and critical closing pressure (CCP) were measured using the neuromonitoring complex. Statistical analysis was performed using parametric and nonparametric methods and factor analysis. The patients were dichotomized into PCI-positive (n = 114) and PCI-negative (n = 22) groups. Data are presented as mean values (standard deviations). ResultsCVR was significantly increased, whereas CAC, CTC, and CCP were significantly decreased in sTBI patients with CVS and PCI development (p < 0.05). Factor analyses revealed that all studied microcirculatory bed parameters were significantly associated with the development of PCI (p < 0.05). Discussion and conclusionThe changes in all studied microcirculatory bed parameters in TBI patients with CVS were significantly associated with PCI development, which enables us to regard them as the biomarkers of CVS and PCI development. The causes of the described microcirculatory bed parameters changes might include complex (cytotoxic and vasogenic) brain edema development, regional microvascular spasm, and dysfunction of pericytes. A further prospective study is warranted.

Assessment of Cerebral Blood Flow Pulsatility and Cerebral Arterial Compliance With 4D Flow MRI.

BackgroundFour‐dimensional flow magnetic resonance imaging (4D flow MRI) enables efficient investigation of cerebral blood flow pulsatility in the cerebral arteries. This is important for exploring hemodynamic mechanisms behind vascular diseases associated with arterial pulsations.PurposeTo investigate the feasibility of pulsatility assessments with 4D flow MRI, its agreement with reference two‐dimensional phase‐contrast MRI (2D PC‐MRI) measurements, and to demonstrate how 4D flow MRI can be used to assess cerebral arterial compliance and cerebrovascular resistance in major cerebral arteries.Study TypeProspective.SubjectsThirty‐five subjects (20 women, 79 ± 5 years, range 70–91 years).Field Strength/Sequence4D flow MRI (PC‐VIPR) and 2D PC‐MRI acquired with a 3T scanner.AssessmentTime‐resolved flow was assessed in nine cerebral arteries. From the pulsatile flow waveform in each artery, amplitude (ΔQ), volume load (ΔV), and pulsatility index (PI) were calculated. To reduce high‐frequency noise in the 4D flow MRI data, the flow waveforms were low‐pass filtered. From the total cerebral blood flow, total PI (PItot), total volume load (ΔVtot), cerebral arterial compliance (C), and cerebrovascular resistance (R) were calculated.Statistical TestsTwo‐tailed paired t‐test, intraclass correlation (ICC).ResultsThere was no difference in ΔQ between 4D flow MRI and the reference (0.00 ± 0.022 ml/s, mean ± SEM, P = 0.97, ICC = 0.95, n = 310) with a cutoff frequency of 1.9 Hz and 15 cut plane long arterial segments. For ΔV, the difference was –0.006 ± 0.003 ml (mean ± SEM, P = 0.07, ICC = 0.93, n = 310) without filtering. Total R was 11.4 ± 2.41 mmHg/(ml/s) (mean ± SD) and C was 0.021 ± 0.009 ml/mmHg (mean ± SD). ΔVtot was 1.21 ± 0.29 ml (mean ± SD) with an ICC of 0.82 compared with the reference. PItot was 1.08 ± 0.21 (mean ± SD).Data ConclusionWe successfully assessed 4D flow MRI cerebral arterial pulsatility, cerebral arterial compliance, and cerebrovascular resistance. Averaging of multiple cut planes and low‐pass filtering was necessary to assess accurate peak‐to‐peak features in the flow rate waveforms. Level of Evidence: 2 Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2020;51:1516–1525.

Cardiorespiratory fitness is associated with increased middle cerebral arterial compliance and decreased cerebral blood flow in young healthy adults: A pulsed ASL MRI study

Cardiorespiratory fitness is thought to have beneficial effects on systemic vascular health, in part, by decreasing arterial stiffness. However, in the absence of non-invasive methods, it remains unknown whether this effect extends to the cerebrovasculature. The present study uses a novel pulsed arterial spin labelling (pASL) technique to explore the relationship between cardiorespiratory fitness and arterial compliance of the middle cerebral arteries (MCAC). Other markers of cerebrovascular health, including resting cerebral blood flow (CBF) and cerebrovascular reactivity to CO2 (CVRCO2) were also investigated. Eleven healthy males aged 21 ± 2 years with varying levels of cardiorespiratory fitness (maximal oxygen uptake (O2MAX) 38–76 ml/min/kg) underwent MRI scanning at 3 Tesla. Higher O2MAX was associated with greater MCAC (R2 = 0.64, p < 0.01) and lower resting grey matter CBF (R2 = 0.75, p < 0.01). However, O2MAX was not predictive of global grey matter BOLD-based CVR (R2 = 0.47, p = 0.17) or CBF-based CVR (R2 = 0.19, p = 0.21). The current experiment builds upon the established benefits of exercise on arterial compliance in the systemic vasculature, by showing that increased cardiorespiratory fitness is associated with greater cerebral arterial compliance in early adulthood.

Cerebral Arterial Compliance in Polytraumazed Patients with Cerebral Vasospasm.

The purpose was to determine the status of the cerebral arterial compliance (cAC) in a concomitant head injury and cerebral vasospasm (CVS) with and without the development of intracranial hematomas (ICH). In Materials and Methods, we examined 80 polytrauma patients with severe TBI and CVS. During or immediately after dynamic helical computed tomography angiography (DHCTA), the monitoring of the transcranial Doppler of the MCA was recorded bilaterally with 2-MHz probes. The cerebral blood volumes were calculated from the DHCTA data with complex mathematical procedures using the "direct flow model" algorithm. In Results, CAC was significantly decreased (p<0.001) in both the first and second group TBI and CVS (with or without ICH) in comparison with normal data (p<0.001) and TBI without CVS. The cAC was significantly decreased on the side of the former hematoma with CVS than on the contralateral side with CVS (р=0.003). In Conclusion, the cAC in TBI and CVS gets significantly lower as compared to the normal condition (p<0.001). After removal of the ICH and development of CVS, the compliance in the perifocal zone remains much lower (р=0.003) as compared to compliance of the other brain hemisphere.

Hypocapnia after traumatic brain injury: how does it affect the time constant of the cerebral circulation?

The time constant of the cerebral arterial bed (“tau”) estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor–capacitor circuit, it is expressed as the product of arterial compliance (Ca) and cerebrovascular resistance (CVR). Hypocapnia increases the time constant in healthy volunteers and decreases arterial compliance in head trauma. How the combination of hyocapnia and trauma affects this parameter has yet to be studied. We hypothesized that in TBI patients the intense vasoconstrictive action of hypocapnia would dominate over the decrease in compliance seen after hyperventilation. The predominant vasoconstrictive response would maintain an incoming blood volume in the arterial circulation, thereby lengthening tau. We retrospectively analyzed recordings of intracranial pressure (ICP), arterial blood pressure (ABP), and blood flow velocity (FV) obtained from a cohort of 27 severe TBI patients [(39/30 years (median/IQR), 5 women; admission GCS 6/5 (median/IQR)] studied during a standard clinical CO2 reactivity test. The reactivity test was performed by means of a 50-min increase in ventilation (20% increase in respiratory minute volume). CVR and Ca were estimated from these recordings, and their product calculated to find the time constant. CVR significantly increased [median CVR pre-hypocapnia/during hypocapnia: 1.05/1.35 mmHg/(cm3/s)]. Ca decreased (median Ca pre-hypocapnia/during hypocapnia: 0.130/0.124 arbitrary units) to statistical significance (p = 0.005). The product of these two parameters resulted in a significant prolongation of the time constant (median tau pre-hypocapnia/during hypocapnia: 0.136 s/0.152 s, p ˂ .001). Overall, the increase in CVR dominated over the decrease in compliance, hence tau was longer. We demonstrate a significant increase in the time constant of the cerebral circulation during hypocapnia after severe TBI, and attribute this to an increase in cerebrovascular resistance which outweighs the decrease in cerebral arterial bed compliance.

Cerebral arterial time constant calculated from the middle and posterior cerebral arteries in healthy subjects.

The cerebral arterial blood volume changes (∆CaBV) during a single cardiac cycle can be estimated using transcranial Doppler ultrasonography (TCD) by assuming pulsatile blood inflow, constant, and pulsatile flow forward from large cerebral arteries to resistive arterioles [continuous flow forward (CFF) and pulsatile flow forward (PFF)]. In this way, two alternative methods of cerebral arterial compliance (Ca) estimation are possible. Recently, we proposed a TCD-derived index, named the time constant of the cerebral arterial bed (τ), which is a product of Ca and cerebrovascular resistance and is independent of the diameter of the insonated vessel. In this study, we aim to examine whether the τ estimated by either the CFF or the PFF model differs when calculated from the middle cerebral artery (MCA) and the posterior cerebral artery (PCA). The arterial blood pressure and TCD cerebral blood flow velocity (CBFVa) in the MCA and in the PCA were non-invasively measured in 32 young, healthy volunteers (median age: 24, minimum age: 18, maximum age: 31). The τ was calculated using both the PFF and CFF models from the MCA and the PCA and compared using anon-parametric Wilcoxon signed-rank test. Results are presented as medians (25th-75th percentiles). The cerebrovascular time constant estimated in both arteries using the PFF model was shorter than when using the CFF model (ms): [64.83 (41.22-104.93) vs. 178.60 (160.40-216.70), p < 0.001 in the MCA, and 44.04 (17.15-81.17) vs. 183.50 (153.65-204.10), p < 0.001 in the PCA, respectively]. The τ obtained using the PFF model was significantly longer from the MCA than from the PCA, p = 0.004. No difference was found in the τ when calculated using the CFF model. Longer τ from the MCA might be related to the higher Ca of the MCA than that of the PCA. Our results demonstrate MCA-PCAdifferences in the τ, but only when the PFF model was applied.

OBJECTIVE-SUBJECTIVE DISPARITY IN COGNITIVE IMPAIRMENT: A CROSS-SECTIONAL INVESTIGATION IN POSTMENOPAUSAL WOMEN

Subjective memory complaint (SMC), now recognised as a prodromal phase of dementia, is linked to poor working memory and attention in perimenopausal women; whether this association remains postmenopausally is unknown. We examined the predictive value for subjective complaints of (a) objective indices of cognitive performance; (b) cardio-metabolic status, and (c) perceptions of well-being in a cross-sectional study. The following baseline measures were recorded in 142 postmenopausal women aged 65±1 years who were enrolled in a two-year resveratrol intervention trial: 10 neuropsychological tests that assess cognitive domains of processing speed, attention, language, working, verbal and episodic memory and cognitive flexibility; cardio-metabolic measures of blood pressure, systemic and cerebral arterial compliance, HOMA-IR and fasting lipids; perceptions of well-being including depressive symptoms, mood states, sleep quality, menopausal symptoms, quality-of-life (using SF-36) and osteoarthritic pain. When asked ‘Do you perceive any memory or cognitive difficulties?’, 68 women responded ‘yes’ and were grouped as SMC. Verbal and episodic memory performances were higher in the SMC group (P=0.022 and 0.011 respectively). No significant differences were seen for all other domains or in their cardio-metabolic status or age or education level. However, the SMC group reported 66% more depressive symptoms (P<0.001), twice likely to have mood disturbances (P=0.012), more menopausal symptoms (32% higher, P=0.009), lower quality-of-life (P=0.015) and 54% increase in daytime dysfunction due to sleepiness (P=0.003). Pain did not differ between groups. In our cohort, poor mood states, sleep quality and quality-of-life were associated with SMC. However, SMC did not reflect cardio-metabolic abnormalities or objective cognitive dysfunction. The link between SMC and future cognitive impairment is still unclear.

Cerebral Arterial Compliance in Traumatic Brain Injury.

The main role of the cerebral arterial compliance (cAC) is to maintain the stiffness of vessels and protect downstream vessels when changing cerebral perfusion pressure. The aim was to examine the flexibility of the cerebral arterial bed based on the assessment of the cAC in patients with traumatic brain injury (TBI) in groups with and without intracranial hematomas (IHs). We examined 80 patients with TBI (mean age, 35.7 ± 12.8 years; 42 men, 38 women). Group 1 included 41 patients without IH and group 2 included 39 polytraumatized patients with brain compression by IH. Dynamic electrocardiography (ECG)-gated computed tomography angiography (DHCTA) was performed 1-14 days after trauma in group 1 and 2-8 days after surgical evacuation of the hematoma in group 2. Amplitude of arterial blood pressure (ABP), as well as systole and diastole duration were measured noninvasively. Transcranial Doppler was measured simultaneously with DHCTA. The cAC was calculated by the formula proposed by Avezaat. The cAC was significantly decreased (p < 0.001) in both groups 1 and 2 compared with normal data. The cAC in group 2 was significantly decreased compared with group 1, both on the side of the former hematoma (р = 0.017). The cAC in TBI gets significantly lower compared with the conditional norm (p < 0.001). After removal of the intracranial hematomas, compliance in the perifocal zone remains much lower (р = 0.017) compared with compliance of the other brain hemisphere.

Mapping cerebral pulse pressure and arterial compliance over the adult lifespan with optical imaging.

Cerebrovascular health is important for maintaining a high level of cognitive performance, not only in old age, but also throughout the lifespan. Recently, it was first demonstrated that diffuse optical imaging measures of pulse amplitude and arterial compliance can provide estimates of cerebral arterial health throughout the cortex, and were associated with age, estimated cardiorespiratory fitness (eCRF), neuroanatomy and cognitive function in older adults (aged 55–87). The current study replicates and extends the original findings using a broader age range (a new adult sample aged 18–75), longer recording periods (360 s), and a more extensive optical montage (1536 channels). These methodological improvements represent a 5-fold increase in recording time and a 4-fold increase in coverage compared to the initial study. Results show that reliability for both pulse amplitude and compliance measures across recording blocks was very high (r(45) = .99 and .75, respectively). Pulse amplitude and pulse pressure were shown to correlate with age across the broader age range. We also found correlations between arterial health and both cortical and subcortical gray matter volumes. Additionally, we replicated the correlations between arterial compliance and age, eCRF, global brain atrophy, and cognitive flexibility. New regional analyses revealed that higher performance on the operation span (OSPAN) working memory task was associated with greater localized arterial compliance in frontoparietal cortex, but not with global arterial compliance. Further, greater arterial compliance in frontoparietal regions was associated with younger age and higher eCRF. These associations were not present in the visual cortex. The current study not only replicates the initial one in a sample including a much wider age range, but also provides new evidence showing that frontoparietal regions may be especially vulnerable to vascular degeneration during brain aging, with potential functional consequences in cognition.

The Cerebral Arterial Compliance in Polytraumat

Introduction and purpose. Cerebral arterial compliance (CAC) is an important parameter of a microcirculation. The main function of CAC is to maintain the stiffness of vessels and protect downstream vessels when changing perfusion pressure. The aim of the study was to assess the CAC in severe polytrauma patients with and without intracranial hematomas (IH). Materials. We examined 75 polytrauma patients with severe traumatic brain injury (mean 32.2±11.6 years, 42 men, 33 women). The first group included 34 patients without IH and the second group included 36 patients with epidural (6), subdural (26) and multiple (4) hematomas. Perfusion computed tomography (PCT) was performed in 1-14 days after trauma in the first group and in 2-8 days after surgical evacuation of the hematoma in the second group. Mean arterial pressure was measured simultaneously with PCT. CAC was calculated by the formula modified by M. Czosnyka. Results. The CAC was significantly decreased (p<0.001) in both groups in comparison with normal values. The CAC in the group 2 was significantly lower than in the groupl, both on the side of the former hematoma (p=0.017). Conclusion. The results indicate severe dysregulation of cerebral capillary blood flow in polytrauma patients, which increases in the patients with polytrauma and traumatic IH.

The major cerebral arteries proximal to the Circle of Willis contribute to cerebrovascular resistance in humans

Cerebral autoregulation ensures constant cerebral blood flow during periods of increased blood pressure by increasing cerebrovascular resistance. However, whether this increase in resistance occurs at the level of major cerebral arteries as well as at the level of smaller pial arterioles is still unknown in humans. Here, we measure cerebral arterial compliance, a measure that is inversely related to cerebrovascular resistance, with our novel non-invasive magnetic resonance imaging-based measurement, which employs short inversion time pulsed arterial spin labelling to map arterial blood volume at different phases of the cardiac cycle. We investigate the differential response of the cerebrovasculature during post exercise ischemia (a stimulus which leads to increased cerebrovascular resistance because of increases in blood pressure and sympathetic outflow). During post exercise ischemia in eight normotensive men (30.4 ± 6.4 years), cerebral arterial compliance decreased in the major cerebral arteries at the level of and below the Circle of Willis, while no changes were measured in arteries above the Circle of Willis. The reduction in arterial compliance manifested as a reduction in the arterial blood volume during systole. This study provides the first evidence that in humans the major cerebral arteries may play an important role in increasing cerebrovascular resistance.

Noninvasive assessment of arterial compliance of human cerebral arteries with short inversion time arterial spin labeling.

A noninvasive method of assessing cerebral arterial compliance (AC) is introduced in which arterial spin labeling (ASL) is used to measure changes in arterial blood volume (aBV) occurring within the cardiac cycle. Short inversion time pulsed ASL (PASL) was performed in healthy volunteers with inversion times ranging from 250 to 850 ms. A model of the arterial input function was used to obtain the cerebral aBV. Results indicate that aBV depends on the cardiac phase of the arteries in the imaging volume. Cerebral AC, estimated from aBV and brachial blood pressure measured noninvasively in systole and diastole, was assessed in the flow territories of the basal cerebral arteries originating from the circle of Willis: right and left middle cerebral arteries (RMCA and LMCA), right and left posterior cerebral arteries (RPCA and LPCA), and the anterior cerebral artery (ACA). Group average AC values calculated for the RMCA, LMCA, ACA, RPCA, and LPCA were 0.56%±0.2%, 0.50%±0.3%, 0.4%±0.2%, 1.1%±0.5%, and 1.1%±0.3% per mm Hg, respectively. The current experiment has shown the feasibility of measuring AC of cerebral arteries with short inversion time PASL.

Cerebrovascular time constant in patients suffering from hydrocephalus

Objectives: We studied possible link between cerebrospinal fluid (CSF) compensation and indices describing pulsatile inflow of cerebral arterial blood.Methods: A total of 50 infusion tests performed in patients with symptoms of normal pressure hydrocephalus (NPH) were examined retrospectively. Waveforms of CSF pressure, noninvasive arterial blood pressure (ABP), and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) were used to estimate relative changes in cerebral arterial compliance (Ca) and cerebrovascular resistance (CVR). Product of Ca and CVR, called cerebral arterial time constant (τ, unit: seconds), was calculated at the baseline and plateau phase of the test and compared with CSF compensatory parameters such as resistance to CSF outflow, elasticity, slope of amplitude–pressure line, and pulse amplitude of CSF pressure.Results: Neither of CSF compensatory parameters correlated with hemodynamic indices. However, the change in cerebral perfusion pressure (CPP) provoked change in τ (R = 0·33; P = 0·017) secondary to a change in CVR (R = 0·81; P < 0·0001). Changes in CVR and Ca had a reciprocal character (R = −0·64; P < 0·0001) with magnitude of variation in CVR (68%) prevailing over magnitude of changes in Ca (49%).Discussion: Hemodynamics of pulsatile inflow of cerebral arterial blood assessed by cerebral arterial time constant is not directly linked to dynamics of CSF circulation and pressure–volume compensation but is sensitive to changes in CPP during infusion test.

Changes in Cerebral Compartmental Compliances during Mild Hypocapnia in Patients with Traumatic Brain Injury

The benefit of induced hyperventilation for intracranial pressure (ICP) control after severe traumatic brain injury (TBI) is controversial. In this study, we investigated the impact of early and sustained hyperventilation on compliances of the cerebral arteries and of the cerebrospinal (CSF) compartment during mild hyperventilation in severe TBI patients. We included 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom an increase in ventilation (20% increase in respiratory minute volume) was performed during 50 min as part of a standard clinical CO(2) reactivity test. Using a new mathematical model, cerebral arterial compliance (Ca) and CSF compartment compliance (Ci) were calculated based on the analysis of ICP, arterial blood pressure, and cerebral blood flow velocity waveforms. Hyperventilation initially induced a reduction in ICP (17.5 ± 6.6 vs. 13.9 ± 6.2 mmHg; p < 0.001), which correlated with an increase in Ci (r(2) = 0.213; p = 0.015). Concomitantly, the reduction in cerebral blood flow velocities (CBFV, 74.6 ± 27.0 vs. 62.9 ± 22.9 cm/sec; p < 0.001) marginally correlated with the reduction in Ca (r(2) = 0.209; p = 0.017). During sustained hyperventilation, ICP increased (13.9 ± 6.2 vs. 15.3 ± 6.4 mmHg; p < 0.001), which correlated with a reduction in Ci (r(2) = 0.297; p = 0.003), but no significant changes in Ca were found during that period. The early reduction in Ca persisted irrespective of the duration of hyperventilation, which may contribute to the lack of clinical benefit of hyperventilation after TBI. Further studies are needed to determine whether monitoring of arterial and CSF compartment compliances may detect and prevent an adverse ischemic event during hyperventilation.

Effect of Hyper- and Hypocapnia on Cerebral Arterial Compliance in Normal Subjects

Changes in partial pressure of carbon dioxide (PaCO2) are associated with a decrease in cerebral blood flow (CBF) during hypocapnia and an increase in CBF during hypercapnia. However, the effects of changes in PaCO2 on cerebral arterial compliance (Ca) are unknown. We assessed the changes in Ca in 20 normal subjects using monitoring of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). Cerebral arterial blood volume (CaBV) was extracted from CBFV. Ca was defined as the ratio between the pulse amplitudes of CaBV (AMPCaBV ) and ABP (AMPABP). All parameters were recorded during normo-, hyper-, and hypocapnia. During hypocapnia, Ca was significantly lower than during normocapnia (.10±.04 vs. .17±.06; P<.001) secondary to a decrease in AMPCaBV (1.3±.4 vs. 1.9±.5; P<.001) and a concomitant increase in AMPABP (13.8±3.4 vs. 11.6±1.7 mmHg; P<.001). During hypercapnia, there was no change in Ca compared with normocapnia. Ca was inversely correlated with the cerebrovascular resistance during hypo- (R2=0.86; P<.001), and hypercapnia (R2=0.61; P<.001). Using a new mathematical model, we have described a reduction of Ca during hypocapnia. Further studies are needed to determine whether Ca may be an independent predictor of outcome in pathological conditions.

Cerebral arterial compliance in patients with internal carotid artery disease

A decrease in arterial compliance of the internal carotid artery has been associated with an increased risk in ipsilateral ischaemic stroke. However, so far, no technique has been validated to monitor the compliance of intracerebral arteries (Ca) in patients with carotid artery disease. In this study, we sought to monitor Ca in patients with unilateral symptomatic disease and to determine its variations during changes in PaCO(2). We studied 18 patients with unilateral symptomatic internal carotid artery stenosis >50% or occlusion. Patients underwent monitoring of arterial blood pressure (ABP) and middle cerebral artery cerebral blood flow velocities (CBFV) during baseline, hyperventilation and 5%CO(2) inhalation. Ca was calculated from pulsatile amplitudes of ABP and Cerebral arterial blood volume, extracted from the CBFV waveform using a new mathematical model. At baseline, the decrease in Ca on the diseased side was correlated with the degree of stenosis (r = -0.35; P = 0.01). During hypocapnia, Ca was lower compared to baseline on the normal side (P = 0.004) and on the diseased side (P = 0.04). Ca reactivity, reflecting the changes in Ca per changes in 1 mmHg PaCO(2), was lower on the diseased side between baseline and hypocapnia (3.4 vs. 2.6%; P = 0.04). During hypercapnia, no changes in Ca on the diseased (P = 0.8) nor on the normal sides (P = 0.2) were observed. The decrease in cerebral arterial compliance the side of stenosis/occlusion was correlated with the severity of the internal carotid artery disease. Further studies are needed to determine whether Ca may improve the prediction of ischaemic events in symptomatic and asymptomatic patients.

Arterial Stiffness, Fatness, and Physical Fitness

Arterial distensibility and its converse stiffness have come of age as physiological concepts1 and now as a target for intervention. The central hypothesis sustained so far is that an individual’s “arterial stiffness” measured as aortic pulse wave velocity (PWV) is a convenient, integrated index of vascular pathology over a person’s life course, more precise and reliable than other risk factors individually. For example, blood pressure (BP), whether casual or 24 hour, is more sensitive to stimuli and, therefore, more variable. Arterial distensibility is in part dependent on BP, yet its prognostic power is because of its “independence” from BP, including pulse pressure.2 It appears to indicate the general burden of atherosclerotic disease and subclinical damage from multiple risk factors over time: the “wear and tear” of constant distension and recoil (part of “aging”), effects of smoking, lipid metabolism, (hyper)glycemia, ethnicity, how family history expresses itself, etc.3 European hypertension guidelines now include PWV as a recommended but optional measure. The relationship of arterial distensibility with cardiac function and structure, known as aorto-ventricular coupling, is tantalizing because, as a bioengineering feedback loop, cause and effect are still unclear. Many other key questions remain, most critically related to the natural history of arterial stiffness but also fundamental ones of basic structural biology in the vessel wall. A clue to the natural history of arterial stiffness is published in this issue of Hypertension , an Australian study of 9- to 10-year-old, generally prepubescent schoolchildren.4 The study shows a clear relationship among degree of body fat, physical fitness, and arterial stiffness, measured by carotid-femoral PWV. The link of PWV with fitness was not independent of body fat. Why should this article be of interest, being only cross-sectional, whereby association may well …

Potential surrogate markers of cerebral microvascular angiopathy in asymptomatic subjects at risk of stroke

Cerebral microvascular angiopathy (MVA) is associated with clinical vascular risk factors and is characterised by histological changes, including thickening of the walls of arterial vessels and dilatation of the Virchow-Robin spaces (VRS). We have previously described two novel biomarkers of MVA based on magnetic resonance imaging (MRI), VRS dilatation and abnormalities in the transfer of systolic arterial pulsation to the ventricular CSF, which occur as a result of decreased cerebral arterial compliance. These are associated with vascular dementia and treatment-resistant late onset depression. We studied a group of normal subjects at risk of cerebrovascular disease to determine if these biomarkers are present in patients who have no evidence of symptomatic vascular disease. We studied 31 subjects, 16 with three or more vascular risk factors and 15 with one or less significant risk factors. We measured arterial blood flow and CSF flow in the cerebral aqueduct, white matter lesion load, and the distribution and number of VRS. There were significant differences in CSF pulsatility and in VRS in the basal ganglia between the two groups, but no differences in white matter lesion load. We conclude that asymptomatic subjects at risk of stroke have MRI evidence of MVA before white matter lesions become apparent.

Changing Concepts of Cerebrospinal Fluid Hydrodynamics: Role of Phase-Contrast Magnetic Resonance Imaging and Implications for Cerebral Microvascular Disease

Phase-contrast magnetic resonance imaging (PC-MRI) or flow-sensitive MRI can be used to noninvasively measure intracranial vascular and CSF flow. Monro-Kellie homeostasis is the complex compensatory mechanism for the increase in intracranial blood volume during systole. Through PC-MRI techniques, our understanding of Monro-Kellie homeostasis and the associated intracranial hydrodynamics has greatly improved. Failure of this homeostatic mechanism has been implicated in a wide range of cerebral disorders, including vascular and Alzheimer's dementia, late-onset depression, benign and secondary intracranial hypertension, communicating and normal pressure hydrocephalus, and age-related white matter changes. The most common mode of homeostatic failure is due to vascular disease with decreased cerebral arterial compliance. This has wide-reaching implications in the investigation of patients with cerebral vascular disease. Here we discuss the role of PC-MRI in the study of cerebral hydrodynamics and the current understanding of Monro-Kellie homeostasis in both healthy and disease states. Quantitative assessment of the changes in this homeostatic mechanism using PC-MRI has important implications in the development of biomarkers of vascular involvement in disease with application in diagnosis, treatment planning, phenotype identification, and outcome assessment in clinical trials.