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Background: Induced hypertension is used clinically to increase cerebral blood flow (CBF) in conditions such as vasospasm after subarachnoid hemorrhage. However, increased blood pressure also raises pulsatile force. Cerebrovascular compliance plays a key role in buffering flow dynamics and protecting the microcirculation, but whether it adapts to elevated pressure remains unclear. This study assessed the response of compliant cerebral arteries to induced hypertension in healthy adults using phase-contrast magnetic resonance imaging (PCMRI) and two compliance models: a two-element Windkessel (CWK) and a simplified model (CVP), representing the extremes of pulsatility transmission at the capillary level.

Methods: Eighteen healthy adults (median age: 34 years; 9 females) underwent PCMRI at baseline and after increasing mean arterial pressure by 20% using norepinephrine (NE) infusion. PCMRI quantified CBF and cardiac output, while cerebrovascular resistance and systemic vascular resistance were derived. Flow waveforms were combined with blood pressure to assess CWK and CVP in CBF, ascending/descending aorta, and external carotid arteries, while corresponding regions of interest were used to calculate cross-sectional flow areas. Data are reported as median (interquartile range).

Results: NE increased cerebrovascular compliance significantly; CWK by 110% (56% to 163%; P=0.001) and CVP by 11% (−2% to 26%; P=0.018). CWK increased in the external carotid artery by 12% (1% to 32%; P=0.037) but did not change in the ascending or descending aorta. CVP decreased in the descending aorta by 5% (-11% to 2%; P=0.028), with no changes in the ascending aorta or external carotid artery. Cross-sectional area of cerebral arteries contributing to CBF decreased by 5% (-17% to -3%; P=0.033), while the ascending and descending aorta areas increased by 7% (4% to 11%; P=0.012) and 8% (6% to 11%; P<0.001), respectively.

Conclusion: Cerebral arteries enhanced their compliance during NE-induced hypertension, unlike systemic arteries, regardless of the assumed degree of pulsatility transmission.

Background: Maintaining cerebral perfusion during anesthesia and intensive care is critical, yet the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF) remains poorly defined. In patients with aneurysmal subarachnoid hemorrhage (aSAH), pharmacologically induced hypertension is commonly applied to support cerebral perfusion, but its effects are uncertain.

Methods: This protocol describes two parallel clinical studies using identical methodology. The first study population includes adults undergoing elective general anesthesia (MAP-ANE), and the second comprises sedated intensive care patients with aSAH (MAP-SAH). In both study populations, MAP will be increased stepwise with norepinephrine (NE) infusion under continuous invasive blood pressure monitoring, and CBF measured with phase-contrast MRI (PCMRI) and arterial spin labeling (ASL), while near-infrared spectroscopy (NIRS) will be performed in parallel to evaluate its validity as a surrogate marker. The primary outcome is the change in total CBF between baseline and elevated MAP, directly testing whether induced hypertension increases CBF. Secondary outcomes include ASL perfusion changes, the slope of the MAP–CBF relationship, systemic–cerebral hemodynamic correlations, and NIRS responses.

Expected impact: These studies test the hypothesis that pharmacological MAP augmentation does not predictably increase CBF. By combining quantitative MRI with invasive monitoring, it aims to clarify MAP–CBF interactions, define the physiological basis of induced hypertension, and assess whether NIRS can serve as a clinically useful proxy. Findings are expected to inform safer and more individualized blood pressure management in perioperative and neurocritical care.

White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.

Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure.

Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta.

Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg⁻¹ · h⁻¹ (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03).

Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.

Background and aim: Current cerebrovascular imaging techniques provide important information on arterial anatomy and structural pathologies, such as stenoses and occlusions, but physicians are left to infer how the blood flow is affected. In addition, the relationship between blood pressure and cerebral blood flow is complex and poorly understood. Increased transmission of cardiac pulsatility to the cerebral microvasculature has been suggested as a causative factor of cerebral small vessel disease (CSVD) but previous research have yielded conflicting results regarding this relationship. 4D flow magnetic resonance imaging (MRI) is a novel and promising technique enabling time-resolved blood flow quantification with whole-brain coverage and relatively short scan times. However, despite its obvious potential, there is not yet an evidence-based application for the use of 4D flow MRI within stroke or CSVD. This dissertation aimed to apply 4D flow MRI to describe blood flow patterns in posterior circulation stroke and cerebral blood flow responses to common pharmacological agents used to alter arterial blood pressure as well as to examine the relationship between cerebral arterial pulsatility and CSVD.

Methods and Results: This doctoral dissertation consisted of four papers, referred to by roman numerals. 4D flow MRI and computed tomography angiography (CTA) were applied in 25 patients with acute ischemic stroke in the posterior circulation and a reference population of 15 healthy elderly (paper I). Individual flow profiles were created for each stroke patient and hemodynamic disturbances as well as collateral compensation were described. We show that hemodynamic findings were related to structural findings from CTA.

The cross-sectional relationship between cerebral arterial pulsatility (quantified using 4D flow MRI as pulsatility index [PI] and flow volume pulsatility [FVP]) and features of CSVD were examined using regression analysis in 89 patients with acute ischemic stroke (paper II) and a population-based sample of 862 elderly (paper III). Internal carotid artery FVP was associated with increasing white matter hyperintensity (WMH) volume in patients with stroke and TIA (paper II). In addition, increasing middle cerebral artery FVP and PI were associated with worse cognitive function. In the population sample, high FVP and PI were associated with increasing WMH volume, lower brain volume and the presence of lacunes, but not the composite MRI-CSVD (paper III). Among subjects with MRI-CSVD, displaying symptoms consistent with cerebral small vessel disease was associated with higher WMH volume, lower brain volume and active smoking, but not any measure of pulsatility.

Eighteen healthy volunteers were administered noradrenaline to increase mean arterial pressure by 20% above baseline, and labetalol to decrease mean arterial pressure to 15% below baseline (paper IV). Cerebral blood flow was measured using phase-contrast MRI at each blood pressure level and compared to baseline. Despite a marked increase in blood pressure, noradrenaline administration caused a reduction in cerebral blood flow and cardiac output. Meanwhile, labetalol administration caused no change in cerebral blood flow but an increased cardiac output.

Conclusions: 4D flow MRI can detect hemodynamic disturbances and discriminate between hemodynamic disturbances and normal flow in patients with structural vascular pathologies. This additional information compared to structural imaging alone could potentially be used for prognosis and selection for procedures in clinical care. Cerebral arterial pulsatility is modestly associated with several MRI and clinical features of CSVD but not all. Cerebral arterial pulsatility as the main risk factor of CSVD seems unlikely but its involvement in the pathophysiology cannot be ruled out. Raising the blood pressure with noradrenaline decreases cerebral blood flow and cardiac output without any redistribution from peripheral to cerebral flow. This highlights the pitfalls of using blood pressure as a surrogate for cerebral blood flow and questions the validity of our understanding of cerebral autoregulation. Lowering the blood pressure with labetalol does not affect cerebral blood flow, reassuring its use in clinical routine. 4D flow MRI can be integrated into an in-patient work-up in selected cases of acute ischemic stroke and into the workflow of large epidemiological studies.

Objective: A clinically feasible, non-invasive method to quantify blood flow, hemodynamics, and collateral flow in the vertebrobasilar arterial tree is missing. The objective of this study was to evaluate the feasibility of quantifying blood flow and blood flow patterns using 4D flow magnetic resonance imaging (MRI) in consecutive patients after an ischemic stroke in the posterior circulation. We also explore if 4D-flow, analyzed in conjunction with computed tomography angiography (CTA), has potential as a diagnostic tool in posterior circulation stroke.

Methods: Twenty-five patients (mean age 62 years; eight women) with acute ischemic stroke in the posterior circulation were investigated. At admission, all patients were examined with CTA followed by MRI (4D flow MRI and diffusion-weighted sequences) at median 4 days after the presenting event. Based on the classification of Caplan, patients were divided into proximal/middle (n = 16) and distal territory infarcts (n = 9). Absolute and relative blood flow rates were calculated for internal carotid arteries (ICA), vertebral arteries (VA), basilar artery (BA), posterior cerebral arteries (P1 and P2), and the posterior communicating arteries (Pcom). In a control group consisting of healthy elderly, the 90th and 10th percentiles of flow were calculated in order to define normal, increased, or decreased blood flow in each artery. “Major hemodynamic disturbance” was defined as low BA flow and either low P2 flow or high Pcom flow. Various minor hemodynamic disturbances were also defined. Blood flow rates were compared between groups. In addition, a comprehensive analysis of each patient’s blood flow profile was performed by assessing relative blood flow rates in each artery in conjunction with findings from CTA.

Results: There was no difference in total cerebral blood flow between patients and controls [604 ± 117 ml/min vs. 587 ± 169 ml/min (mean ± SD), p = 0.39] or in total inflow to the posterior circulation (i.e., the sum of total VA and Pcom flows, 159 ± 63 ml/min vs. 164 ± 52 ml/min, p = 0.98). In individual arteries, there were no significant differences between patients and controls in absolute or relative flow. However, patients had larger interindividual relative flow variance in BA, P1, and P2 (p = 0.01, <0.01, and 0.02, respectively). Out of the 16 patients that had proximal/middle territory infarcts, nine had CTA findings in VA and/or BA generating five with major hemodynamic disturbance identified with 4D flow MRI. For those without CTA findings, seven had no or minor 4D flow MRI hemodynamic disturbance. Among nine patients with distal territory infarcts, one had major hemodynamic disturbances, while the remaining had minor disturbances.

Conclusion: 4D flow MRI contributed to the identification of the patients who had major hemodynamic disturbances from the vascular pathologies revealed on CTA. We thus conclude that 4D flow MRI could add valuable hemodynamic information when used in conjunction with CTA.

Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive impairment. However, the underlying mechanisms behind SVD are still poorly understood. High cerebral arterial pulsatility has been suggested as a possible cause of SVD. In population studies, arterial pulsatility has been linked to white matter hyperintensities (WMH), cerebral atrophy, and cognitive impairment, all features of SVD. In stroke, pulsatility data are scarce and contradictory. The aim of this study was to investigate the relationship between arterial pulsatility and SVD in stroke patients. With a cross-sectional design, 89 patients with acute ischemic stroke or TIA were examined with MRI. A neuropsychological assessment was performed 1 year later. Using 4D flow MRI, pulsatile indices (PI) were calculated for the internal carotid artery (ICA) and middle cerebral artery (M1, M3). Flow volume pulsatility (FVP), a measure corresponding to the cyclic expansion of the arterial tree, was calculated for the same locations. These parameters were assessed for associations with WMH volume, brain volume and cognitive function. ICA-FVP was associated with WMH volume (β = 1.67, 95% CI: [0.1, 3.24], p = 0.037). M1-PI and M1-FVP were associated with decreasing cognitive function (β = - 4.4, 95% CI: [- 7.7, - 1.1], p = 0.009 and β = - 13.15, 95% CI: [- 24.26, - 2.04], p = 0.02 respectively). In summary, this supports an association between arterial pulsatility and SVD in stroke patients, and provides a potential target for further research and preventative treatment. FVP may become a useful biomarker for assessing pulsatile stress with PCMRI and 4D flow MRI.