Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis

2019 ◽  
Vol 26 (12) ◽  
pp. 1486-1496 ◽  
Author(s):  
Dinesh K Sivakolundu ◽  
Kathryn L West ◽  
Gayathri B Maruthy ◽  
Mark Zuppichini ◽  
Monroe P Turner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blood Flow ◽  
Reaction Time ◽  
Arterial Compliance ◽  
Blood Oxygen Level Dependent ◽  
Cerebrovascular Reactivity ◽  
Healthy Controls ◽  
Vascular Compliance ◽  
Cognitive Slowing ◽  
End Tidal

Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.

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

2019 ◽  
Vol 40 (9) ◽  
pp. 1879-1889 ◽  
Author(s):  
Hannah V Furby ◽  
Esther AH Warnert ◽  
Christopher J Marley ◽  
Damian M Bailey ◽  
Richard G Wise
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cardiorespiratory Fitness ◽  
Grey Matter ◽  
Arterial Compliance ◽  
Cerebral Arteries ◽  
Early Adulthood ◽  
Cerebrovascular Reactivity ◽  
Beneficial Effects ◽  
Cerebral Arterial Compliance

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 ([Formula: see text]O2MAX) 38–76 ml/min/kg) underwent MRI scanning at 3 Tesla. Higher [Formula: see text]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, [Formula: see text]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.

Attention Network Test reveals alerting network dysfunction in multiple sclerosis

2009 ◽  
Vol 16 (1) ◽  
pp. 93-99 ◽  
Author(s):  
Carsten Urbanek ◽  
Nicholetta Weinges-Evers ◽  
Judith Bellmann-Strobl ◽  
Markus Bock ◽  
Jan Dörr ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Attention Network Test ◽  
Healthy Controls ◽  
Attention Network ◽  
Cognitive Domains ◽  
Attentional Networks ◽  
Relapsing Remitting ◽  
Cognitive Slowing ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Attention is one of the cognitive domains typically affected in multiple sclerosis. The Attention Network Test was developed to measure the function of the three distinct attentional networks, alerting, orienting, and executive control. The Attention Network Test has been performed in various neuropsychiatric conditions, but not in multiple sclerosis. Our objective was to investigate functions of attentional networks in multiple sclerosis by means of the Attention Network Test. Patients with relapsing—remitting multiple sclerosis (n = 57) and healthy controls (n = 57) matched for age, sex, and education performed the Attention Network Test. Significant differences between patients and controls were detected in the alerting network (p = 0.003), in contrast to the orienting (p = 0.696) and the conflict (p = 0.114) network of visual attention. Mean reaction time in the Attention Network Test was significantly longer in multiple sclerosis patients than in controls (p = 0.032), Multiple sclerosis patients benefited less from alerting cues for conflict resolution compared with healthy controls. The Attention Network Test revealed specific alterations of the attention network in multiple sclerosis patients which were not explained by an overall cognitive slowing.

scholarly journals The CO2 stimulus for cerebrovascular reactivity: Fixing inspired concentrations vs. targeting end-tidal partial pressures

2016 ◽  
Vol 36 (6) ◽  
pp. 1004-1011 ◽  
Author(s):  
Joseph A Fisher
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Stimulus Change ◽  
Cerebrovascular Reactivity ◽  
Main Concern ◽  
Precise Control ◽  
Trade Offs ◽  
Partial Pressures ◽  
Response Change ◽  
End Tidal

Cerebrovascular reactivity (CVR) studies have elucidated the physiology and pathophysiology of cerebral blood flow regulation. A non-invasive, high spatial resolution approach uses carbon dioxide (CO2) as the vasoactive stimulus and magnetic resonance techniques to estimate the cerebral blood flow response. CVR is assessed as the ratio response change to stimulus change. Precise control of the stimulus is sought to minimize CVR variability between tests, and show functional differences. Computerized methods targeting end-tidal CO2 partial pressures are precise, but expensive. Simpler, improvised methods that fix the inspired CO2 concentrations have been recommended as less expensive, and so more widely accessible. However, these methods have drawbacks that have not been previously presented by those that advocate their use, or those that employ them in their studies. As one of the developers of a computerized method, I provide my perspective on the trade-offs between these two methods. The main concern is that declaring the precision of fixed inspired concentration of CO2 is misleading: it does not, as implied, translate to precise control of the actual vasoactive stimulus – the arterial partial pressure of CO2. The inherent test-to-test, and therefore subject-to-subject variability, precludes clinical application of findings. Moreover, improvised methods imply widespread duplication of development, assembly time and costs, yet lack uniformity and quality control. A tabular comparison between approaches is provided.

Severely impaired cerebrovascular reserve in patients with cerebral proliferative angiopathy

2011 ◽  
Vol 8 (3) ◽  
pp. 310-315 ◽  
Author(s):  
Jorn Fierstra ◽  
Stephanie Spieth ◽  
Leanne Tran ◽  
John Conklin ◽  
Michael Tymianski ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Blood Oxygen Level Dependent ◽  
Brain Parenchyma ◽  
Cerebrovascular Reactivity ◽  
Healthy Individuals ◽  
Blood Oxygen Level ◽  
Cerebrovascular Reserve ◽  
Vascular Channels ◽  
End Tidal ◽  
Brain Avms

Object Cerebral proliferative angiopathy (CPA) has been morphologically distinguished from classically appearing brain arteriovenous malformations (AVMs) by exhibition of functional brain parenchyma that is intermingled with abnormal vascular channels. The presence of oligemia in this intralesional brain tissue may suggest ischemia, which is not detected in classic brain AVMs. The authors hypothesized that patients with CPA would exhibit a greater impairment of cerebrovascular reserve in neuronal tissue surrounding the true nidus compared with those with brain AVMs. Methods Four patients with CPA, 10 patients with brain AVMs and seizures, and 12 young healthy individuals were studied. The 4 patients with CPA underwent blood oxygen level–dependent MR imaging examinations while applying normoxic step changes in end-tidal CO2 to obtain quantitative cerebrovascular reactivity measurements. Results Patients with a CPA lesion exhibited severely impaired perilesional cerebrovascular reserve in comparison with patients with brain AVMs and seizures (0.10 ± 0.03 vs 0.16 ± 0.03, respectively; p < 0.05), and young healthy individuals (0.10 ± 0.03 vs 0.21 ± 0.06, respectively; p < 0.01) Conclusions This study demonstrated severely impaired cerebrovascular reserve in the perilesional brain tissue surrounding the abnormal vessels of patients with CPA. This finding may provide an additional means to distinguish CPA from classic brain AVMs.

A prospective study of cerebral blood flow and cerebrovascular reactivity to acetazolamide in 162 patients with idiopathic normal-pressure hydrocephalus

2009 ◽  
Vol 111 (3) ◽  
pp. 610-617 ◽  
Author(s):  
Chia-Cheng Chang ◽  
Hiroyuki Asada ◽  
Toshiro Mimura ◽  
Shinichi Suzuki
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Cerebrovascular Reactivity ◽  
Healthy Controls ◽  
Shunt Placement ◽  
Significant Difference ◽  
A Prospective Study

Object Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were investigated prospectively in 162 patients with a proposed diagnosis of idiopathic normal-pressure hydrocephalus (NPH). The aim of this study was to assess the usefulness of the measurement of CBF and CVR in determining which patients would be likely to benefit from shunt placement. Methods The mean CBF of the whole brain was measured according to the Patlak plot method by using technetium-99m hexamethylpropyleneamine oxime. The CVR value was obtained from the response to administration of 500 mg acetazolamide and calculated as the percentage change from the baseline mean CBF value. Results One hundred forty-six patients (90.1%) responded to shunt placement (“responders”), but 16 patients (9.9%) did not (“nonresponders”). No significant difference in preoperative CBF was observed between responders and nonresponders. Preoperative CVR was significantly impaired (p < 0.0025) in responders compared with healthy controls, but not in nonresponders. Responders with the incomplete triad had a significant reduction (p < 0.001) in preoperative CVR, but not in preoperative CBF, compared with healthy controls. Responders with the complete triad had significantly lower preoperative CBF and CVR than those with the incomplete triad (p < 0.01 and p < 0.05, respectively). Postoperative CBF and CVR increased significantly (p < 0.025 and p < 0.001, respectively) in responders. Conclusions Both CBF and CVR decrease with the development of NPH, suggesting that hemodynamic ischemia may be responsible for manifestation of the symptoms. Impaired CVR and reduced CBF with the development of symptoms can be proposed as diagnostic criteria for idiopathic NPH.

scholarly journals Insights Into Cerebral Tissue-Specific Response to Respiratory Challenges at 7T: Evidence for Combined Blood Flow and CO2-Mediated Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Allen A. Champagne ◽  
Alex A. Bhogal
Keyword(s):  
Blood Flow ◽  
Arrival Time ◽  
Vascular Diseases ◽  
Response Speed ◽  
Blood Oxygen Level Dependent ◽  
Cerebrovascular Reactivity ◽  
Specific Response ◽  
Vascular Networks ◽  
Blood Oxygen Level ◽  
Arterial Transit Time

Cerebrovascular reactivity (CVR) mapping is finding increasing clinical applications as a non-invasive probe for vascular health. Further analysis extracting temporal delay information from the CVR response provide additional insight that reflect arterial transit time, blood redistribution, and vascular response speed. Untangling these factors can help better understand the (patho)physiology and improve diagnosis/prognosis associated with vascular impairments. Here, we use hypercapnic (HC) and hyperoxic (HO) challenges to gather insight about factors driving temporal delays between gray-matter (GM) and white-matter (WM). Blood Oxygen Level Dependent (BOLD) datasets were acquired at 7T in nine healthy subjects throughout BLOCK- and RAMP-HC paradigms. In a subset of seven participants, a combined HC+HO block, referred as the “BOOST” protocol, was also acquired. Tissue-based differences in Rapid Interpolation at Progressive Time Delays (RIPTiDe) were compared across stimulus to explore dynamic (BLOCK-HC) versus progressive (RAMP-HC) changes in CO2, as well as the effect of bolus arrival time on CVR delays (BLOCK-HC versus BOOST). While GM delays were similar between the BLOCK- (21.80 ± 10.17 s) and RAMP-HC (24.29 ± 14.64 s), longer WM lag times were observed during the RAMP-HC (42.66 ± 17.79 s), compared to the BLOCK-HC (34.15 ± 10.72 s), suggesting that the progressive stimulus may predispose WM vasculature to longer delays due to the smaller arterial content of CO2 delivered to WM tissues, which in turn, decreases intravascular CO2 gradients modulating CO2 diffusion into WM tissues. This was supported by a maintained ∼10 s offset in GM (11.66 ± 9.54 s) versus WM (21.40 ± 11.17 s) BOOST-delays with respect to the BLOCK-HC, suggesting that the vasoactive effect of CO2 remains constant and that shortening of BOOST delays was be driven by blood arrival reflected through the non-vasodilatory HO contrast. These findings support that differences in temporal and magnitude aspects of CVR between vascular networks reflect a component of CO2 sensitivity, in addition to redistribution and steal blood flow effects. Moreover, these results emphasize that the addition of a BOOST paradigm may provide clinical insights into whether vascular diseases causing changes in CVR do so by way of severe blood flow redistribution effects, alterations in vascular properties associated with CO2 diffusion, or changes in blood arrival time.

scholarly journals Cerebral Blood Flow Reactivity to Changes in Carbon Dioxide Calculated Using End-Tidal versus Arterial Tensions

1991 ◽  
Vol 11 (6) ◽  
pp. 1031-1035 ◽  
Author(s):  
William L. Young ◽  
Isak Prohovnik ◽  
Eugene Ornstein ◽  
Noeleen Ostapkovich ◽  
Richard S. Matteo
Keyword(s):  
Carbon Dioxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebrovascular Reactivity ◽  
Noninvasive Measurement ◽  
Moderate Correlation ◽  
The Difference ◽  
Highly Correlated ◽  
End Tidal

We retrospectively examined arterial and endtidal estimations of CO2 tension used to calculate cerebrovascular reactivity in 68 anesthetized patients. CBF was measured using the intravenous 133Xe technique at mean ± SD Paco2 values of 28.2 ± 5.2 and 38.8 ± 4.8 mm Hg. The correlation between all Paco2 and end-tidal Pco2 (Petco2) values was y = 0.85 x −0.49 ( r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between Paco2 and Petco2 ( y = 0.11 x + 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g−1 min−1 mm Hg−1) was similar (p = 0.358) when calculated by using either Paco2 (1.9 ± 0.8) or Petco2 (1.8 ± 0.8) and highly correlated ( y = 0.86 x + 0.23; r = 0.91, p = 0.0001). The CBF response to changes in CO2 tension can be reliably estimated from noninvasive measurement of Petco2.

scholarly journals Cyclooxygenase inhibition abolishes age-related differences in cerebral vasodilator responses to hypercapnia

2012 ◽  
Vol 112 (11) ◽  
pp. 1884-1890 ◽  
Author(s):  
Jill N. Barnes ◽  
John E. Schmidt ◽  
Wayne T. Nicholson ◽  
Michael J. Joyner
Keyword(s):  
Blood Flow ◽  
Vascular Function ◽  
Cerebral Blood Flow Velocity ◽  
Cerebrovascular Reactivity ◽  
Cyclooxygenase Inhibition ◽  
Healthy Humans ◽  
Age Related ◽  
Before And After ◽  
End Tidal ◽  
Cerebral Vasodilator

Blood flow and vasodilatory responses are altered by age in a number of vascular beds, including the cerebral circulation. To test the role of prostaglandins as regulators of cerebral vascular function, we examined cerebral vasodilator responses to CO2 (cerebrovascular reactivity) in young (26 ± 5 yr; 6 males/6 females) and older (65 ± 6 yr, 5 males/5 females) healthy humans before and after cyclooxygenase inhibition (using indomethacin). Middle cerebral artery velocity (MCAv) responses to stepped hypercapnia were measured before and 90 min after indomethacin. Changes in MCAv during the recovery from hypercapnia (vasoconstrictor responses) were also evaluated before and after indomethacin. Cerebrovascular reactivity was calculated using linear regression between MCAv and end-tidal CO2. Young adults demonstrated greater MCAv (55 ± 6 vs. 39 ± 5 cm/s: P < 0.05) and MCAv reactivity (1.67 ± 0.20 vs. 1.09 ± 0.19 cm·s−1·mmHg−1; P < 0.05) to hypercapnia compared with older adults ( P < 0.05). In both groups MCAv and MCAv reactivity decreased between control and indomethacin. Furthermore, the age-related differences in these cerebrovascular variables were abolished by indomethacin. During the recovery from hypercapnia, there were no age-related differences in MCAv reactivity; however, indomethacin significantly reduced the MCAv reactivity in both groups. Taken together, these results suggest that cerebral blood flow velocity and cerebrovascular reactivity are attenuated in aging humans, and may be due to a loss of prostaglandin-mediated vasodilation.

scholarly journals Assessment of the optic nerve and its arterial supply by ultrasound imaging in multiple sclerosis patients

2019 ◽  
Vol 55 (1) ◽  
Author(s):  
Manal Mahmoud Al Kattan ◽  
Amira Ahmed Labib ◽  
Rania Shehata Ismail ◽  
Alshaimaa M. Aboul fotouh ◽  
Emad El Din Mostafa Mohammed
Keyword(s):  
Multiple Sclerosis ◽  
Blood Flow ◽  
Optic Nerve ◽  
Assessment Tool ◽  
Arterial Supply ◽  
Healthy Controls ◽  
Mean Velocity ◽  
Blood Flow Velocities ◽  
Multiple Sclerosis Patients ◽  
Flow Velocities

Abstract Background Transorbital sonography (TOS) has emerged as a promising assessment tool of the optic nerve and orbital arterial supply in multiple sclerosis (MS) patients. Objective To evaluate optic nerve diameter (OND), optic nerve sheath diameter (ONSD), and orbital hemodynamics using TOS in MS patients. Methods Forty MS patients and 28 matched healthy controls were included. Thirty-three eyes with previous optic neuritis (ON) and 47 eyes without previous ON of MS patients were examined. All subjects were submitted to assessment of OND, ONSD, and parameters of orbital hemodynamics using orbital ultrasound. Results OND and ONSD were smaller in MS eyes with previous ON than in controls. MS eyes with and without previous ON had statistically significant higher peak systolic and mean velocity of posterior ciliary arteries than the control eyes. Orbital blood flow velocities were negatively correlated with the duration of disease and Expanded Disability Status Scale (EDSS). A statistically significant decrease in blood flow velocities of the central retinal artery was detected in secondary progressive MS (SPMS) patients than in relapsing-remitting MS patients (RRMS). Conclusion TOS can be used as a feasible tool to detect optic atrophy in MS patients. MS patients may have abnormal retrobulbar hemodynamics compared to healthy controls.

scholarly journals Cerebral blood flow modulation insufficiency in brain networks in multiple sclerosis: A hypercapnia MRI study

2016 ◽  
Vol 36 (12) ◽  
pp. 2087-2095 ◽  
Author(s):  
Olga Marshall ◽  
Sanjeev Chawla ◽  
Hanzhang Lu ◽  
Louise Pape ◽  
Yulin Ge
Keyword(s):  
Multiple Sclerosis ◽  
Carbon Dioxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Networks ◽  
Cerebrovascular Reactivity ◽  
Functional Networks ◽  
Attention Networks ◽  
Default Mode ◽  
Multiple Sclerosis Patients

Cerebrovascular reactivity measures vascular regulation of cerebral blood flow and is responsible for maintaining healthy neurovascular coupling. Multiple sclerosis exhibits progressive neurodegeneration and global cerebrovascular reactivity deficits. This study investigates varied degrees of cerebrovascular reactivity impairment in different brain networks, which may be an underlying cause for functional changes in the brain, affecting long-distance projection integrity and cognitive function; 28 multiple sclerosis and 28 control subjects underwent pseudocontinuous arterial spin labeling perfusion MRI to measure cerebral blood flow under normocapnia (room air) and hypercapnia (5% carbon dioxide gas mixture) breathing. Cerebrovascular reactivity, measured as normocapnic to hypercapnic cerebral blood flow percent increase normalized by end-tidal carbon dioxide change, was determined from seven functional networks (default mode, frontoparietal, somatomotor, visual, limbic, dorsal, and ventral attention networks). Group analysis showed significantly decreased cerebrovascular reactivity in patients compared to controls within the default mode, frontoparietal, somatomotor, and ventral attention networks after multiple comparison correction. Regression analysis showed a significant correlation of cerebrovascular reactivity with lesion load in the default mode and ventral attention networks and with gray matter atrophy in the default mode network. Functional networks in multiple sclerosis patients exhibit varied amounts of cerebrovascular reactivity deficits. Such blood flow regulation abnormalities may contribute to functional communication disruption in multiple sclerosis.

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