Multiscale Model of Cerebral Blood Flow Control: Application to Small Vessel Disease and Cortical Spreading Depression

Cortical spreading depression (CSD) evokes a large cerebral blood flow (CBF) increase in normal rat brain. In contrast, in focal ischemic penumbra, CSD-like periinfarct depolarizations (PID) are mainly associated with hypoperfusion. Because PIDs electrophysiologically closely resemble CSD, we tested whether conditions present in ischemic penumbra, such as tissue hypoxia or reduced perfusion pressure, transform the CSD-induced CBF response in nonischemic rat cortex. Cerebral blood flow changes were recorded using laser Doppler flowmetry in rats subjected to hypoxia, hypotension, or both. Under normoxic normotensive conditions, CSD caused a characteristic transient CBF increase (74 ± 7%) occasionally preceded by a small hypoperfusion (−4 ± 2%). Both hypoxia ( pO2 45 ± 3 mm Hg) and hypotension (blood pressure 42 ± 2 mm Hg) independently augmented this initial hypoperfusion (−14 ± 2% normoxic hypotension; −16 ± 6% hypoxic normotension; −21 ± 5% hypoxic hypotension) and diminished the magnitude of hyperemia (44 ± 10% normoxic hypotension; 43 ± 9% hypoxic normotension; 27 ± 6% hypoxic hypotension). Hypotension and, to a much lesser extent, hypoxia increased the duration of hypoperfusion and the DC shift, whereas CSD amplitude remained unchanged. These results suggest that hypoxia and/or hypotension unmask a vasoconstrictive response during CSD in the rat such that, under nonphysiologic conditions (i.e., mimicking ischemic penumbra), the hyperemic response to CSD becomes attenuated resembling the blood flow response during PIDs.

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Model for Identification of the Cerebral Blood Flow Control System

Biomedical Engineering / Biomedizinische Technik ◽

10.1515/bmte.1990.35.s2.79 ◽

1990 ◽

Vol 35 (s2) ◽

pp. 79

Author(s):

I. Füzes

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Control System ◽

Flow Control ◽

Blood Flow Control ◽

Flow Control System

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Spatio-temporal cerebral blood flow perfusion patterns in cortical spreading depression

10.1117/12.2267956 ◽

2017 ◽

Author(s):

Andrey Yu. Verisokin ◽

Darya V. Verveyko ◽

Dmitry E. Postnov

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cortical Spreading Depression ◽

Spreading Depression ◽

Flow Perfusion ◽

Spatio Temporal

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Uncoupling of cerebral blood flow and metabolism after single episode of cortical spreading depression in the rat brain

Brain Research ◽

10.1016/0006-8993(86)90504-4 ◽

1986 ◽

Vol 370 (2) ◽

pp. 405-408 ◽

Cited By ~ 26

Author(s):

Martin Lauritzen ◽

Niels Henrik Diemer

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Rat Brain ◽

Cortical Spreading Depression ◽

Spreading Depression ◽

Single Episode

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Adverse effects of pre-existing cerebral small vessel disease on cognitive improvement after carotid endarterectomy

International Journal of Stroke ◽

10.1177/1747493019874732 ◽

2019 ◽

Vol 15 (6) ◽

pp. 657-665 ◽

Cited By ~ 2

Author(s):

Jun Yoshida ◽

Fumio Yamashita ◽

Makoto Sasaki ◽

Kunihiro Yoshioka ◽

Shunrou Fujiwara ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Carotid Endarterectomy ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitive Improvement ◽

Vessel Disease

Background Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. Aims The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. Methods Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. Results Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74–3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01–0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. Conclusion Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.

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Statistical Parametric Analysis of Cerebral Blood Flow in Vascular Dementia with Small-Vessel Disease Using 99mTc-HMPAO SPECT

Cerebrovascular Diseases ◽

10.1159/000160213 ◽

2008 ◽

Vol 26 (5) ◽

pp. 556-562 ◽

Cited By ~ 12

Author(s):

Hiroki Kato ◽

Takuya Yoshikawa ◽

Naohiko Oku ◽

Masao Imaizumi ◽

Masashi Takasawa ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Vascular Dementia ◽

Parametric Analysis ◽

Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Hmpao Spect

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Evaluation of Cerebral Blood Flow Measured by 3D PCASL as Biomarker of Vascular Cognitive Impairment and Dementia (VCID) in a Cohort of Elderly Latinx Subjects at Risk of Small Vessel Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.627627 ◽

2021 ◽

Vol 15 ◽

Author(s):

Kay Jann ◽

Xingfeng Shao ◽

Samantha J. Ma ◽

Steven Y. Cen ◽

Lina D’Orazio ◽

...

Keyword(s):

At Risk ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Cognitive Impairment ◽

White Matter ◽

Small Vessel Disease ◽

Vascular Cognitive Impairment ◽

Small Vessel ◽

Vessel Disease ◽

Brain White Matter

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer’s disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77–0.85, wsCV 3–9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD.

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Small vessel disease is associated with altered cerebrovascular pulsatility but not resting cerebral blood flow

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x18803956 ◽

2018 ◽

Vol 40 (1) ◽

pp. 85-99 ◽

Cited By ~ 17

Author(s):

Yulu Shi ◽

Michael J Thrippleton ◽

Gordon W Blair ◽

David A Dickie ◽

Ian Marshall ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Small Vessel Disease ◽

Superior Sagittal Sinus ◽

Small Vessel ◽

Perivascular Spaces ◽

Intracranial Volume ◽

Vessel Disease ◽

Sagittal Sinus ◽

Intracranial Pulsatility

Cerebral small vessel disease (SVD) contributes to 25% of ischemic strokes and 45% of dementias. We aimed to investigate the role of cerebral blood flow (CBF) and intracranial pulsatility in SVD. We scanned 60 patients with minor ischemic stroke, representing a range of white matter hyperintensities (WMH). We rated WMH and perivascular spaces (PVS) using semi-quantitative scales and measured WMH volume. We measured flow and pulsatility in the main cerebral vessels and cerebrospinal fluid (CSF) using phase-contrast MRI. We investigated the association between flow, pulsatility and SVD features. In 56/60 patients (40 male, 67.8±8.3 years) with complete data, median WMH volume was 10.7 mL (range 1.4–75.0 mL), representing median 0.77% (0.11–5.17%) of intracranial volume. Greater pulsatility index (PI) in venous sinuses was associated with larger WMH volume (e.g. superior sagittal sinus, β = 1.29, P < 0.01) and more basal ganglia PVS (e.g. odds ratio = 1.38, 95% confidence interval 1.06, 1.79, per 0.1 increase in superior sagittal sinus PI) independently of age, sex and blood pressure. CSF pulsatility and CBF were not associated with SVD features. Our results support a close association of SVD features with increased intracranial pulsatility rather than with low global CBF, and provide potential targets for mechanistic research, treatment and prevention of SVD.

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