An fMRI approach to assess intracranial arterial-to-venous cardiac pulse delay in aging

Previous studies have demonstrated a significant pressure gradient from carotid artery to pial or middle cerebral arteries. This pressure gradient suggests that large cerebral arteries contribute to cerebral resistance. We have tested the hypothesis that large cerebral arteries contribute to regulation of cerebral blood flow during changes in blood gases and arterial pressure. Microspheres were used to measure brain blood flow in anesthetized dogs. Resistance of large cerebral arteries was estimated by determining the pressure gradient between common carotid and wedged vertebral artery catheters. Systemic hypercapnia and hypoxia dilated large cerebral arteries, and hypocapnia constricted large cerebral arteries. Resistance of large arteries was 0.6+/-0.1 (mean +/- SE) mm Hg per ml/min per 100 g during normocapnia. During hypercapnia and hypoxia, large artery resistance decreased significantly to 0.2 +/- 0.03 and 0.3 +/- 0.05, respectively. During hypocapnia large artery resistance increased significantly to 1.0 +/- 0.1. In other experiments, we found that large cerebral arteries participate in auto-regulatory responses to hemorrhagic hypotension. When arterial pressure was reduced from 110 to 58 mm Hg, autoregulation maintained cerebral blood flow constant, and resistance of large cerebral arteries decreased significantly from 1.0 +/- 0.2 to 0.6 +/- 0.1 mm Hg per ml/min per 100 g. In absolute terms, we calculated that 20-45% of the change in total cerebral resistance during these interventions was accounted for by changes in large artery resistance. These studies indicate that large cerebral arteries, as well as arterioles, participate actively in regulation of cerebral blood flow during changes in arterial blood gases and during autoregulatory responses to hemorrhagic hypotension.

Microvascular brain injury is well recognized in neuropsychiatric systemic lupus erythematosus (SLE), but cerebral large artery involvement is being debated. Three females with SLE, aged 9 to 14years, had immunosuppressive treatment intensification because of lupus nephritis. Within the following days or weeks, they presented with intense cephalalgia - isolated or associated with neurological symptoms - and no or mild hypertension. Magnetic resonance angiography showed multiple stenoses within the circle of Willis. One patient had subsequent small subcortical cerebral infarction. Two patients were treated for neuropsychiatric SLE; one patient was treated for reversible cerebral vasoconstriction syndrome (RCVS). Angiography normalized within a few weeks in all three patients. Retrospectively, clinical and radiological features suggest that RCVS was the most likely diagnosis in all patients. Multidisciplinary analysis of clinical and angiographic features is recommended, as RCVS is rare in children and its recognition may help to adjust treatment. WHAT THIS PAPER ADDS: Reversible vasoconstriction syndrome was observed in paediatric systemic lupus erythematosus. Thorough imaging analysis was necessary to address this diagnosis in paediatric patients.

The goal of this study was to investigate factors that contribute to reductions in internal diameter of large and small cerebral arteries during chronic hypertension. We measured diameter of second- and third-order branches of the posterior cerebral artery in vitro during maximal dilation with EDTA in 6-mo-old stroke-prone spontaneously hypertensive rats (SHRSP, n = 7) and Wistar-Kyoto rats (WKY, n = 7). Cross-sectional area of the vessel wall, measured histologically, was not significantly different at 70 mmHg in SHRSP and WKY in large or small branches of posterior cerebral artery. In large branches of posterior cerebral artery, external and internal diameters were significantly less at 70 mmHg in SHRSP than in WKY, whereas external and internal diameters converged at 0 mmHg in the two groups of rats. In small branches, on the other hand, external and internal diameters were significantly less at all levels of intravascular pressure in SHRSP than in WKY. The stress-strain relation in posterior cerebral artery of SHRSP was shifted to the left in large branches and to the right in small branches, which indicates that distensibility was reduced in large cerebral arteries of SHRSP and increased in small cerebral arteries. These findings suggest that different mechanisms are responsible for impairment of maximal dilator capacity in large and small cerebral arteries of SHRSP: reduced distensibility in large arteries and remodeling with reduced external diameter in small arteries. Furthermore the findings provide additional support for the concept that hypertrophy may not be a primary factor in impaired maximal dilation.

Carbon dioxide and the cerebral circulation.

Antiretroviral drugs and the central nervous system.

Functional magnetic resonance imaging (fMRI) captures rich physiological and neuronal information that can offer insights into neurofluid dynamics, vascular health, and waste clearance function. The availability of cerebral vessel segmentation could facilitate fluid dynamics research in fMRI. However, without magnetic resonance angiography scans, cerebral vessel segmentation is challenging and time-consuming. This study leverages cardiac-induced pulsatile fMRI signal to develop a data-driven, automatic segmentation of large cerebral arteries and the superior sagittal sinus (SSS). The method was validated in a local dataset by comparing it to ground truth cerebral artery and SSS segmentations. Using the Human Connectome Project (HCP) aging dataset, the method's reproducibility was tested on 422 participants aged 36 to 100 years, each with four repeated fMRI scans. The method demonstrated high reproducibility, with an intraclass correlation coefficient > 0.7 in both cerebral artery and SSS segmentation volumes. This study demonstrates that the large cerebral arteries and SSS can be reproducibly and automatically segmented in fMRI datasets, facilitating the investigation of fluid dynamics in these regions.

Resistance of large arteries appears to be greater in the cerebral circulation than in other vascular beds. Large arteries contribute importantly to total cerebral vascular resistance and are major determinants of local microvascular pressure. Recent studies have shown that resistance of large arteries and cerebral microvascular pressure are affected by several physiological stimuli, including changes in systemic blood pressure, increases in cerebral metabolism, activity of sympathetic nerves, and humoral stimuli such as circulating vasopressin and angiotensin. Stimuli such as sympathetic stimulation and vasopressin produce selective responses of large arteries and, thereby, regulate microvascular pressure without a significant change in cerebral blood flow. These findings lead to the new hypothesis that the brain may be sensitive to changes in cerebral microvascular pressure, resulting in activation of compensatory neurohumoral mechanisms. Important changes occur in large cerebral arteries under pathophysiological conditions. Chronic hypertension increases resistance of large cerebral arteries, which protects the microcirculation against hypertension. Atherosclerosis potentiates constrictor responses of large cerebral arteries to serotonin and thromboxane, which may contribute to vasospasm and transient ischemic attacks.

The composition of intra-arterial clots might influence the efficacy of mechanical thrombectomy (MT) in ischemic stroke (IS) due to the acute occlusions within large cerebral arteries. The aims were to assess the factors associated with blood clot structure and the impact of thromboembolus structure on MT using stent-retrievers in patients with acute large artery IS in the anterior circulation. In an observational cohort study, we studied the components of intra-arterial clots retrieved from large cerebral arteries in 80 patients with acute IS treated with MT with or without i.v. thrombolysis (IVT). Histology of the clots was carried out without knowledge of the clinical findings, including the treatment methods. The components of the clots, their age, origin and semi-quantitative graded changes in the architecture of the fibrin components (e.g., "thinning") were compared via neuro-interventional, clinical and laboratory data. The most prominent changes in the architecture of the fibrin components in the thromboemboli were associated with IVT (applied in 44 patients; OR, 3.50; 95% CI: 1.21-10.10, P=0.02) and platelet count (OR, 2.94; 95% CI: 1.06-8.12, P=0.04). In patients with large artery IS treated with the MT using stent-retrievers, bridging therapy with IVT preceding MT and higher platelet count were associated with significant changes of the histological structure of blood clots.

Optic Nerve and Perioptic Sheath Diameter (ONSD), Eyeball Transverse Diameter (ETD) and ONSD/ETD Ratio on MRI in Large Middle Cerebral Artery Infarcts: A Case-Control Study

To the Editor: We read with great interest the article by Steinke and Ley and the editorial by Caplan in the June issue of Stroke .1 Among 941 patients with stroke, Steinke and Ley identified 92 patients with prevalent motor deficit; motor performances further deteriorated in 22 of these patients, and a prevalence of deep (lacunar) lesions was found on these latter patients. The conclusion, which gives the title to the article, is that lacunar stroke is the major cause of progressive motor deficits. Some observations could be made. The strict inclusion criteria of Steinke and Ley allowed selection of only a minimal number of the screened patients. Such a situation is highly “at risk” for selection biases; for example, the exclusion of patients with “minor motor or predominantly other deficits” may rule out the whole population of patients with embolic occlusion of small pial branches of the middle cerebral artery, or may overestimate relatively rare conditions such as basal ganglia infarctions as a major consequence of an embolic occlusion of the main trunk of the middle cerebral artery, with an efficient leptomeningeal collateral circulation. Moreover, the European Stroke Scale baseline is different between groups: the 22 patients with progressive courses had more limited neurological deficits and less frequent consciousness impairment, due to smaller infarctions as demonstrated on neuroimaging studies. In this setting, …

Assessing changes on large cerebral arteries in CADASIL: Preliminary insights from a case-control analysis

The goal of this study was to examine effects of arginine vasopressin and angiotensin on cerebral microvascular pressure and segmental vascular resistance. We measured pressure (servo-null) in pial arteries that were approximately 200 micron in diameter and cerebral blood flow (microspheres) in anesthetized cats, and we calculated resistance of large and small cerebral vessels. Resistance of large arteries (greater than 200 micron diam) was approximately 45% of total cerebral vascular resistance under control conditions. Vasopressin (40 mU/kg iv) decreased resistance of large arteries by 22 +/- 7%, increased pial artery pressure by 10 +/- 2 mmHg when aortic pressure was maintained at control levels, and increased small vessel resistance by 27 +/- 11%. This increase in small vessel resistance apparently was an autoregulatory response to the increase in pial pressure. Cerebral blood flow was not changed (38 +/- 4 vs. 37 +/- 3 ml.min-1.100 g-1). Intravenous infusion of angiotensin (2 micrograms.kg-1.min-1) increased large artery resistance by 32 +/- 6%, decreased pial artery pressure 6 +/- 3 mmHg with aortic pressure maintained constant, and decreased cerebral blood flow by 12 +/- 1%. Thus circulating vasopressin, at concentrations similar to those observed during hemorrhage, selectively dilates large cerebral arteries and increases microvascular pressure without changes in cerebral blood flow. In contrast to vasopressin, angiotensin selectively increases resistance of large cerebral arteries and decreases cerebral microvascular pressure. Thus vasopressin and angiotensin, at doses that have minimal effects on cerebral blood flow, may play an important role in regulation of cerebral microvascular pressure.

Arterial pulsation is crucial for promoting fluid circulation and for influencing neuronal activity. Previous studies assessed the pulsatility index based on blood flow velocity pulsatility in relatively large cerebral arteries of human. Here, we introduce a novel method to quantify the volumetric pulsatility of cerebral microvasculature across cortical layers and in white matter (WM), using high-resolution 4D vascular space occupancy (VASO) MRI with simultaneous recording of pulse signals at 7T. Microvascular volumetric pulsatility index (mvPI) and cerebral blood volume (CBV) changes across cardiac cycles are assessed through retrospective sorting of VASO signals into cardiac phases and estimating mean CBV in resting state (CBV0) by arterial spin labeling (ASL) MRI at 7T. Using data from 11 young (28.4±5.8 years) and 7 older (61.3±6.2 years) healthy participants, we investigated the aging effect on mvPI and compared microvascular pulsatility with large arterial pulsatility assessed by 4D-flow MRI. We observed the highest mvPI in the cerebrospinal fluid (CSF) on the cortical surface (0.19±0.06), which decreased towards the cortical layers as well as in larger arteries. In the deep WM, a significantly increased mvPI (p = 0.029) was observed in the older participants compared to younger ones. Additionally, mvPI in deep WM is significantly associated with the velocity pulsatility index (vePI) of large arteries (r = 0.5997, p = 0.0181). We further performed test-retest scans, non-parametric reliability test and simulations to demonstrate the reproducibility and accuracy of our method. To the best of our knowledge, our method offers the first in vivo measurement of microvascular volumetric pulsatility in human brain which has implications for cerebral microvascular health and its relationship research with glymphatic system, aging and neurodegenerative diseases.

The immune reconstitution inflammatory syndrome (IRIS) occurs frequently in patients infected with HIV and an opportunistic pathogen, usually a few weeks after the initiation of a combination antiretroviral therapy (cART) [1]. We report here two cases of HIV-infected patients who developed cerebral thrombophlebitis after the diagnosis and treatment of cryptococcal meningitidis, suggesting unusual presentation of IRIS. Case 1 A 46-year-old HIV-1-infected African man was admitted on 13 May 2005 for right hemiparesia, diplopia, left VII and bilateral VI palsies. CD4 cell counts were 10 cells/μl and plasma viral load (pVL) was 1911 copies/ml despite cART with zidovudine, lamivudine and abacavir. His cerebrospinal fluid (CSF) showed 15 lymphocytes/μl, protein and glucose levels of 0.43 g/l and 2.4 mM/l, respectively. CSF direct examination and culture found Cryptococcus neoformans. Latex agglutination test for cryptococcal polysaccharide antigen was 68 enzyme immunoassay (EIA) in serum and 597 EIA in CSF. Cerebral magnetic resonance imaging (MRI) showed left frontal hemorrhagic lacuna and ischemic arteriolar lesions in lenticular nuclei. He was treated with intravenous amphotericin B and flucytosine, and high dose steroids. On 17 June 2005, while on fluconazole, steroids were interrupted and antiretroviral therapy was switched to emtricitabine, tenofovir and boosted atazanavir. On 26 July, he was hospitalized for headache, fever and visual acuity loss. CD4 cell count was 28 cells/μl and pVL was less than 50 copies/ml. CSF showed 14 cells/μl and cryptococcal yeasts, but culture was negative. The C. neoformans antigen was 45 EIA in blood and 12 EIA in CSF. Brain MRI showed thrombophlebitis of the superior sagittal and left transverse sinuses. Efficient anticoagulation and prednisone were initiated, with improvement of brain MRI 2 months later. Case 2 On 19 November 2005, a 26-year-old African woman was hospitalized for photophobia, neck stiffness, right VI palsy revealing HIV infection and cryptococcal meningitis [20 cells/μl, 78% lymphocytes, positive cryptococcal antigen (1000 EIA) and C. neoformans in CSF]. CD4 cell count was 3 cells/μl and pVL was 200 000 copies/ml. She was treated with intravenous amphotericin B and flucytosine, then fluconazole. Eight days later, she presented a visual acuity loss. Brain MRI showed bilateral and symetric dilatation of the optical nerve sheathes and intracranial hypertension. Neurological signs disappeared after introduction of prednisone. On 17 January 2006, she started cART with emtricitabine, tenofovir and boosted atazanavir. On 6 March, she presented with blindness, confusion, neck stiffness, left VI palsy. CSF showed an opening pressure of 45 cmH2O, no cellularity, normoglycorachia, positive India ink coloration but negative culture for C. neoformans. MRI showed disappearance of venal flow in superior sagittal sinus and both transverse sinuses and intracranial hypertension. CD4 cell count was 9 cells/μl and pVL was 52 copies/ml. She received intravenous methylprednisolone, acetazolamide and curative anticoagulation. A ventriculo-peritoneal derivation was performed without subsequent visual improvement. Discussion IRIS may develop in 30% of HIV-infected patients with cryptococcal infection [2]. The most common neurological presentations are a recurrent meningitis with negative fungal culture, multiple cerebral cryptococcoma, diffuse microabscesses, marked edema, or abnormal contrast media uptake in meninges [1,3]. Cerebral venous occlusion has already been described in association with viral, bacterial or fungal infections and cancer, in HIV-infected patients [4–5] and in non-HIV patients [6–11], but never in association with cryptococcosis. In one retrospective study, risk factors of cryptococcosis-associated IRIS in HIV-infected patients were previously unknown HIV infection, CD4 cell count lower than 7 cells/μl, fungemia and cART initiation within 2 months of cryptococcosis diagnosis [1]. Median CD4 cell counts at the time of IRIS were 215 cells/μl [1]. Our two patients maintained low CD4 cell counts below 50 cells/μl at the time of IRIS, and none of them had significant increase in their CD4 count. Nevertheless, cART might have beneficial immune effects mediated by mechanisms other than CD4 cell increment, as previously suggested [12,13], and low CD4 count does not rule out diagnosis of IRIS. In our patients, the time from initial diagnosis of cryptococcosis to effective cART was 1 and 2 months and the time from initiation of an efficient cART to IRIS was 1 and 1.5 months, which were shorter than that reported in other cases [1,14]. Both had cART introduced shortly after the diagnosis of cryptococcosis (one of them switched to a new cART due to bad compliance and virological failure of his previous treatment). Both also received high dosages of corticosteroids, but thrombophlebitis developed subsequently when therapy was decreased. Optimal treatment of patients at high risk of IRIS is still under discussion, with early or delayed introduction of cART and preventive long high dosage corticosteroids with potential adverse effects. Additional studies are thus needed.

Introduction: The study aims to quantify changes in the number, size, and distribution of arachnoid granulations during the human lifespan to elucidate their role in cerebrospinal fluid physiology.Material and Methods: 3T magnetic resonance imaging of the brain was performed in 120 subjects of different ages (neonate, 2 years, 10 years, 20 years, 40 years, 60 years, and 80 years) all with the normal findings of the cerebrospinal fluid system (CSF). At each age, 10 male and 10 female subjects were analyzed. Group scanned at neonatal age was re-scanned at the age of two, while all other groups were scanned once. Arachnoid granulations were analyzed on T2 coronal and axial sections. Each arachnoid granulation was described concerning size and position relative to the superior sagittal, transverse, and sigmoid sinuses and surrounding cranial bones.Results: Our study shows that 85% of neonates and 2-year-old children do not have visible arachnoid granulations in the dural sinuses and cranial bones on magnetic resonance imaging. With age, the percentage of patients with arachnoid granulations in the superior sagittal sinus increases significantly, but there is no increase in the sigmoid and transverse sinuses. However, numerous individuals in different age groups do not have arachnoid granulations in dural sinuses. Arachnoid granulations in the cranial bones are found only around the superior sagittal sinus, for the first time at the age of 10, and over time their number increases significantly. From the age of 60 onwards, arachnoid granulations were more numerous in the cranial bones than in the dural sinuses.Conclusion: The results show that the number, size, and distribution of arachnoid granulations in the superior sagittal sinus and surrounding cranial bones change significantly over a lifetime. However, numerous individuals with a completely normal CSF system do not have arachnoid granulations in the dural sinuses, which calls into question their role in CSF physiology. It can be assumed that arachnoid granulations do not play an essential role in CSF absorption as it is generally accepted. Therefore, the lack of arachnoid granulations does not appear to cause problems in intracranial fluid homeostasis.